Interventional

Neuroradiology
 Interventional
Neuroradiology

Edited by

Robert W. Hurst
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, USA

Robert H. Rosenwasser
Thomas Jefferson University
Philadelphia, Pennsylvania, USA
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Library of Congress Cataloging-in-Publication Data

Interventional neuroradiology / edited by Robert W. Hurst, Robert H. Rosenwasser.

p. ; cm.
Includes bibliographical references.
ISBN-13: 978-0-8493-9562-8 (hardcover: alk. paper)
ISBN-10: 0-8493-9562-3 (hardcover: alk. paper)
1. Nervous systemInterventional radiology. I. Hurst, Robert W. II. Rosenwasser, Robert H.
[DNLM: 1. Cerebrovascular Disordersradiotherapy. 2. Cardiovascular Systemanatomy & histology. 3. Central Nervous
Systemblood supply. 4. Radiology, Interventionalmethods. WL 355 I6074 2008]

RD594.15.I62 2008
616.80 04757dc22 2007023346

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To the mentors, students, and patients who have shown me how
much there is to learn and all too often, how little time in which to
accomplish it. To my wonderful wife Marilyn, and my children,
Jonathan and Katherine, who make family the greatest happiness
of my life. I must thank them for the commitment in time that has
made this endeavor possible.
Robert W. Hurst

I would like to dedicate this book to my wife Deborah August,

M.D., who has been my partner and pillar of strength and
supported me without hesitation in all my endeavors. In addition,
I wish to express my gratitude to William A. Buchheit, M.D., my
Neurosurgical Mentor and Friend, and the individual who
supported the early concept of Endovascular Therapy for disorders
of the Nervous System . . . a man way ahead of his time.
Robert H. Rosenwasser
Preface

This book is intended to provide the clinical practitioner with background

information and specific descriptions of the anatomy, techniques, disorders,
procedures, and decisions most commonly encountered in interventional neuro-
radiology. Throughout the past decade, interventional neuroradiological techni-
ques have revolutionized therapy for vascular disorders of the head, neck, and
central nervous system. These procedures now provide noninvasive treatment
for many of the most common neurological disorders and make possible treat-
ment of numerous patients for whom there were no reasonable therapeutic
options before.
With progress, however, comes the requirement for increased knowledge
and technical skill to deliver these treatments safely and effectively. Areas of
fundamental knowledge in interventional neuroradiology cross the boundaries of
classically delineated medical and surgical specialties, including neurosurgery,
neuroradiology, and neurology. Required knowledge includes familiarity with
neuroradiological imaging of vascular disease, knowledge of vascular anatomy,
and thorough understanding of cerebrovascular disorders and their endovascu-
lar treatments. Most importantly, skill in basic interventional techniques must
be coupled with good clinical judgment in patient management and decision
making.
Recent rapid advances in neuroimaging mean that practitioners of interven-
tional neuroradiology must have excellent diagnostic skills with noninvasive
neuroimaging modalities to identify the presence of cerebrovascular disease,
evaluate its effects, identify potential candidates for neurointerventional proce-
dures, and document the effects of the treatment. Separate chapters on CT, MR,
and ultrasonographic evaluation of cerebrovascular disease emphasize the cur-
rent noninvasive evaluation of disorders that are of interest to neurointervention-
alists. In addition, the authors have made every effort throughout the text to
illustrate the integration of current neuroimaging into the performance and
decision making associated with interventional neuroradiological procedures.
As in all radiological- or surgical-based specialties, thorough understanding
of pertinent anatomy is essential. For the neurointerventionalist, cerebrovascular
anatomy is the workplace. Anatomic knowledge underlies the understanding of
many, if not all, cerebrovascular disorders, provides routes of endovascular
access, and defines the scope of treatment options. Chapters covering pertinent
vascular anatomy of special importance to neurointerventional procedures have
been included. These chapters are directed at key anatomic concepts as well as
specific anatomic features of the head, neck, brain, and spine vasculature.
It is through basic neurointerventional techniques that treatment is deliv-
ered to the individual patient. No amount of theoretical understanding can
overcome poor technique in an environment as unforgiving as the cerebrovas-
cular system. Discussion of basic techniques with appropriate illustrations
should prove useful for readers at all levels of experience, from students entering
the field to experienced practitioners who may benefit from review or additional
technical options.
Coupled with anatomic and technical knowledge is the requirement for
understanding the epidemiology, pathophysiology, and clinical features of the
increasing numbers of cerebrovascular disorders that are now amenable to
endovascular treatment. Recognized experts in the field have authored clinically
oriented discussions of the most common conditions of interest to interventional
neuroradiologists. Treatment discussions are illustrated with current images to
emphasize pertinent technical and anatomic details. Extensive and current
references are included to serve as a basis for further research.
vi Preface

Perhaps most essential to successful neurointerventional practice is the

requirement for correlating the appropriate application of knowledge and tech-
nical skills to the care of patients. This book is designed to illustrate and
emphasize the importance of integrating clinical information, knowledge of
disease processes, and technical skill through the use of good clinical judgment
to formulate and perform effective neurointerventional procedures.

Robert W. Hurst
Robert H. Rosenwasser
Contents

Preface . . . . v
Contributors . . . . ix

1. Vascular Anatomy of the Head, Neck, and Skull Base . . . . . . . . . . . . . . . . . . . . . 1

Michele H. Johnson, Hjalti M. Thorisson, and Michael L. DiLuna

2. Applied Neurovascular Anatomy of the Brain and Skull . . . . . . . . . . . . . . . . . 23

Randy S. Bell, Alexander H. Vo, and Rocco A. Armonda
3. Vascular Anatomy of the Spine and Spinal Cord . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Armin K. Thron
4. Intracranial Collateral Routes and Anastomoses in
Interventional Neuroradiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
David S. Liebeskind

5. CT Imaging and Physiologic Techniques in

Interventional Neuroradiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Ronald L. Wolf

6. MR Angiography: Principles and Applications in

Interventional Neuroradiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Neerav R. Mehta and Elias R. Melhem
7. Ultrasonographic Imaging and Physiological Techniques in
Interventional Neuroradiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Jaroslaw Krejza
8. Techniques and Devices in Interventional Neuroradiology . . . . . . . . . . . . . . 161
Jeffrey M. Katz, Y. Pierre Gobin, and Howard A. Riina

9. Balloon Occlusion, Wada, and Pharmacological Testing . . . . . . . . . . . . . . . . . 183

Linda J. Bagley

10. Endovascular Management of Tumors and

Vascular Malformations of the Head and Neck . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Johnny C. Pryor, Joshua A. Hirsch, and Robert W. Hurst
11. Dissections of the Carotid and Vertebral Arteries . . . . . . . . . . . . . . . . . . . . . . . . 213
Qaisar A. Shah, Scott E. Kasner, and Robert W. Hurst
12. Direct Carotid Cavernous Fistula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
Uday S. Kanamalla, Charles A. Jungreis, and Jeffrey P. Kochan

13. Endovascular Management of Intracranial Aneurysms . . . . . . . . . . . . . . . . . . . 239

Darren Orbach, Tibor Becske, and Peter Kim Nelson
14. Endovascular Treatment of Post-Subarachnoid
Hemorrhage Vasospasm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Jonathan L. Brisman, David W. Newell, and Joseph M. Eskridge
15. Endovascular Management of Brain
Arteriovenous Malformations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
John B. Weigele, Riyadh N. Al-Okaili, and Robert W. Hurst
viii Contents

16. Endovascular Treatment of Acute Ischemic Stroke . . . . . . . . . . . . . . . . . . . . . . . 305

Mayur A. Paralkar, Alexandros L. Georgiadis, Adnan I. Qureshi, and
Qaisar A. Shah
17. Endovascular Treatment of Extracranial Carotid
Atherosclerotic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Eric Sauvageau, Robert D. Ecker, Junichi Yamamoto, Ramachandra P. Tummala,
Elad I. Levy, and L. Nelson Hopkins
18. Stenting and Angioplasty for Intracranial Atherosclerotic
Occlusive Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
Nabil M. Akkawi and Ajay K. Wakhloo
19. Endovascular Management of
Dural Arteriovenous Fistulas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
J. Marc C. van Dijk, Robert A. Willinsky

20. Inferior Petrosal Sinus Sampling in the

Diagnosis of Pituitary Adenomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
Nicholas J. Patronas and Donald L. Miller

21. Endovascular Treatment of Spinal Vascular Malformations . . . . . . . . . . . . . 363

Mayumi Oka and Kieran Murphy
22. Percutaneous Vertebroplasty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
Mary E. Jensen

Index . . . . 411
Contributors

Nabil M. Akkawi Division of Neuroimaging and Intervention, University of

Massachusetts Medical School, Worcester, Massachusetts, U.S.A.

Riyadh N. Al-Okaili Department of Radiology, King Abdulaziz Medical City,

Riyadh, Saudi Arabia.

Rocco A. Armonda Departments of Neurosurgery and Radiology, National

Naval Medical Center, and Comprehensive Neurosciences Program, Uniformed
Services University of Health Sciences, Bethesda, Maryland, U.S.A.

Linda J. Bagley Departments of Radiology and Neurosurgery, University

of Pennsylvania Medical Center, Philadelphia, Pennsylvania, U.S.A.

Tibor Becske Departments of Neurology, Neurosurgery, and Radiology, New

York University Medical Center, New York, New York, U.S.A.

Randy S. Bell Departments of Neurosurgery and Radiology, National Naval

Medical Center, and Comprehensive Neurosciences Program, Uniformed
Services University of Health Sciences, Bethesda, Maryland, U.S.A.

Jonathan L. Brisman Department of Cerebrovascular and Endovascular

Neurosurgery, Winthrop University Hospital, Mineola, Long Island,
New York, U.S.A.

Michael L. DiLuna Department of Neurosurgery, Yale University School of

Medicine, New Haven, Connecticut, U.S.A.

Robert D. Ecker Department of Neurosurgery and Toshiba Stroke Research

Center, Millard Fillmore Gates Hospital, Kaleida Health, University at Buffalo,
State University of New York, Buffalo, New York, U.S.A., and Department of
Neurological Surgery, U.S. Naval Hospital, Okinawa, Japan.

Joseph M. Eskridge Department of Interventional Neuroradiology, Seattle

Neuroscience Institute, Seattle, Washington, U.S.A.

Alexandros L. Georgiadis Department of Neurology, Zeenat Qureshi Stroke

Research Center, University of Minnesota, Minneapolis, Minnesota, U.S.A.

Y. Pierre Gobin Departments of Radiology and Neurosurgery, New York

Presbyterian Hospital, Weill Medical College of Cornell University, New York,
New York, U.S.A.

Joshua A. Hirsch Department of Interventional Neuroradiology and

Endovascular Neurosurgery, Massachusetts General Hospital, Harvard Medical
School, Boston, Massachusetts, U.S.A.

L. Nelson Hopkins Department of Neurosurgery and Toshiba Stroke Research

Center, Millard Fillmore Gates Hospital, Kaleida Health, University at Buffalo,
State University of New York, Buffalo, New York, U.S.A.

Robert W. Hurst Departments of Radiology, Neurology, and Neurosurgery,

Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Mary E. Jensen Departments of Radiology, and Neurosurgery, University of

Virginia Health Systems, Charlottesville, Virginia, U.S.A.
x Contributors

Michele H. Johnson Interventional Neuroradiology, Departments of

Diagnostic Radiology and Surgical Otolaryngology, Yale University School
of Medicine, New Haven, Connecticut, U.S.A.

Charles A. Jungreis Temple University Hospital, Temple University School of

Medicine, Philadelphia, Pennsylvania, U.S.A.

Uday S. Kanamalla Temple University Hospital, Temple University School of

Medicine, Philadelphia, Pennsylvania, U.S.A.

Scott E. Kasner Department of Neurology, Hospital of the University of

Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Jeffrey M. Katz Department of Radiology, New York Presbyterian Hospital,

Weill Medical College of Cornell University, New York, New York, U.S.A.

Jeffrey P. Kochan Temple University Hospital, Temple University School

of Medicine, Philadelphia, Pennsylvania, U.S.A.

Jaroslaw Krejza Department of Radiology, Hospital of the University

of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.; Department of Nuclear
Medicine, Medical University of Gdansk, Poland.

Elad I. Levy Department of Neurosurgery and Toshiba Stroke Research Center,

Millard Fillmore Gates Hospital, Kaleida Health, University at Buffalo, State
University of New York, Buffalo, New York, U.S.A.

David S. Liebeskind UCLA Stroke Center, University of California, Los Angeles,

California, U.S.A.

Neerav R. Mehta University of Pennsylvania Medical Center, Philadelphia,

Pennsylvania, U.S.A.

Elias R. Melhem University of Pennsylvania Medical Center, Philadelphia,

Pennsylvania, U.S.A.

Donald L. Miller Department of Radiology, National Naval Medical Center

and Department of Radiology, Uniformed Services University of Health Sciences,
Bethesda, Maryland, U.S.A.

Kieran Murphy Department of Radiology, Division of Interventional

Neuroradiology, Johns Hopkins University, Baltimore, Maryland, U.S.A.

Peter Kim Nelson Departments of Neurology, Neurosurgery, and Radiology,

New York University Medical Center, New York, New York, U.S.A.

David W. Newell Department of Neurosurgery, Seattle Neuroscience Institute,

Seattle, Washington, U.S.A.

Mayumi Oka Department of Radiology, Division of Interventional Neuro-

radiology, Johns Hopkins University, Baltimore, Maryland, U.S.A.

Darren Orbach Departments of Neurology, Neurosurgery, and Radiology,

New York University Medical Center, New York, New York, U.S.A.

Mayur A. Paralkar Department of Medicine, University of Medicine and

Dentistry of New Jersey, Newark, New Jersey, U.S.A.

Nicholas J. Patronas Department of Radiology, National Institutes of Health

Clinical Center, Bethesda, Maryland, U.S.A.

Johnny C. Pryor Department of Interventional Neuroradiology and

Endovascular Neurosurgery, Massachusetts General Hospital, Harvard
Medical School, Boston, Massachusetts, U.S.A.
 Contributors xi

Adnan I. Qureshi Department of Neurology, Zeenat Qureshi Stroke Research

Center, University of Minnesota, Minneapolis, Minnesota, U.S.A.

Howard A. Riina Departments of Radiology and Neurosurgery, New York

Presbyterian Hospital, Weill Medical College of Cornell University, New York,
New York, U.S.A.

Eric Sauvageau Department of Neurosurgery and Toshiba Stroke Research

Center, Millard Fillmore Gates Hospital, Kaleida Health, University at Buffalo,
State University of New York, Buffalo, New York, U.S.A., and Department of
Neurological Surgery, University of South Florida College of Medicine, Tampa,
Florida, U.S.A.

Qaisar A. Shah Department of Neurology, Hospital of the University of

Pennsylvania, Philadelphia, Pennsylvania, U.S.A., and Department of Neurology,
University of Minnesota, Minneapolis, Minnesota, U.S.A.

Hjalti M. Thorisson Department of Diagnostic Radiology, Yale University

School of Medicine, New Haven, Connecticut, U.S.A.

Armin K. Thron Department of Neuroradiology, University Hospital, RWTH

Aachen University, Aachen, Germany.

Ramachandra P. Tummala Department of Neurosurgery and Toshiba

Stroke Research Center, Millard Fillmore Gates Hospital, Kaleida Health,
University at Buffalo, State University of New York, Buffalo, New York, U.S.A.

J. Marc C. van Dijk Department of Neurosurgery, University Medical Center,

Groningen, Groningen, The Netherlands.

Alexander H. Vo Departments of Neurosurgery and Radiology, National Naval

Medical Center, and Comprehensive Neurosciences Program, Uniformed
Services University of Health Sciences, Bethesda, Maryland, U.S.A.

Ajay K. Wakhloo Division of Neuroimaging and Intervention, University of

Massachusetts Medical School, Worcester, Massachusetts, U.S.A.

John B. Weigele Department of Radiology, Hospital of the University of

Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Robert A. Willinsky Department of Medical Imaging, Toronto Western

Hospital, Toronto, Ontario, Canada.

Ronald L. Wolf Department of Radiology, Neuroradiology Section, University

of Pennsylvania Medical Center, Philadelphia, Pennsylvania, U.S.A.

Junichi Yamamoto Department of Neurosurgery and Toshiba Stroke Research

Center, Millard Fillmore Gates Hospital, Kaleida Health, University at Buffalo,
State University of New York, Buffalo, New York, U.S.A.
 1

Vascular Anatomy of the Head, Neck, and Skull Base

Michele H. Johnson, Hjalti M. Thorisson, and Michael L. DiLuna

Interventional Neuroradiology, Departments of Diagnostic Radiology
and Surgical Otolaryngology;, Department of Diagnostic Radiology; and
, Department of Neurosurgery, Yale University School of Medicine,
New Haven, Connecticut, U.S.A.

INTRODUCTION In rare cases, the arch is derived from the right

The emphasis of this chapter is on the anatomy and
anatomic variations of the vasculature of the head and
neck beginning in the thorax at the level of the aortic
arch and extending superiorly to the level of the skull
base (vascular entrance through the dura). Selective
catheterization is predicated on familiarity with these
anatomic features. Cross-sectional (vascular) imaging,
including CTA and MRA, has supplanted catheter
studies for the purposes of pure diagnosis. Identifica-
tion of the common and uncommon variations and
their adjacent soft tissue relationships is important to
the neurointerventionalist when assessing the cross-
sectional imaging prior to therapeutic intervention.
The anatomy of this region will be explored using a
combination of CTA, MRA, and conventional angio-
graphic images and case examples to demonstrate
features important to the neurointerventionalist (1).
EMBRYOLOGY
The embryology of the aortic arch development is
complex and beyond the scope of this chapter; how-
ever, a few relevant embryologic considerations pro-
vide a basis for understanding important normal
variants that may have an impact on catheterization
and image interpretation (26). The convexity of the
aortic arch forms from the left fourth primitive aortic
arch. The innominate or brachiocephalic artery (BCA),
the left common carotid artery (LCCA), and the left
subclavian artery (LSUB) arise sequentially from
the aortic arch (from proximal to distal) (Fig. 1A). In
the majority of cases, the LCCA arises distinctly sep-
arate from the BCA; however, in approximately 20%
of patients, the LCCA may arise in conjunction with
the BCA in a bovine configuration (Fig. 1B) (7,8). In a
small percentage of patients, the left vertebral artery
may arise as a branch of the aortic arch (Fig. 1C). Even
more rarely, the right vertebral artery may arise
directly from the aortic arch (Fig. 1D, E) (9).
primitive arch and the brachiocephalic vessels arise as
a mirror image of the normal arrangement (Fig. 1F).
More commonly, an aberrant right subclavian artery
(RSUB) is present that is characterized by the right
common carotid as the first branch from the aortic
arch, followed by the LCCA, the LSUB, and finally the
RSUB, which arises distally and proceeds toward the
right behind the esophagus to give rise to the right
vertebral artery and remaining subclavian artery
branches (Fig. 1G). A focal dilatation of the aorta
adjacent to the origin of the aberrant right subclavian
is referred to as Kommerells diverticulum and may
occasionally become aneurysmal and require surgical
repair (Fig. 1H) (10,11).
AORTIC ARCH AND BRANCHES
The aorta arises from the heart and emerges from the
pericardium in the superior mediastinum, where it
forms the ascending aortic arch (AOA) anterior to the
trachea at the level of the sternal manubrium. From
this ascending arch arise three major branches: the
BCA, the LCCA, and the LSUB (Fig. 1A). The BCA
crosses obliquely cephalad into the right anterior to
the trachea before bifurcating into the right common
carotid artery (RCCA) and RSUB behind the sterno-
clavicular joint. Fluoroscopic recognition of the head
of the clavicle as the location of the bifurcation of the
BCA can be a useful adjunct to selective catheter-
ization of the RCCA and RSUB (Fig. 2). The anterior
location of the RCCA in relationship to the RSUB can
be exploited in the selective catheterization of the
subclavian artery by turning the patients head toward
the left and extending the arm to accentuate the sep-
aration between these two vessels. The right vertebral
artery arises from the RSUB just opposite the origin of
the internal mammary (INM) artery. The left vertebral
artery can arise directly from the aorta in 5% of cases
(9). Additional subclavian branches include the
ascending cervical artery, the thyrocervical trunk,
2 Johnson et al.

Figure 1 (A) Normal LAO arch configuration. Note the typical configuration of the great vessels and the marked vertebral artery
asymmetry (right > left). (B) Bovine arch. Note the common origin of the BCA and the LCCA. The left vertebral artery is larger than the
right. (C) LAO arch injection demonstrates the origin of the left vertebral artery from the aortic arch between the origins of the LCCA and
the left SUB. Note the absence of vertebral originating from the left SUB. (D) Right vertebral artery arising from the arch demonstrated on
posterior view of 3D CTA. (E) Spontaneous aortic dissection in a patient with aberrant right subclavian and a bovine arch configuration.
The patient presented with chest and right arm pain. Note the false lumen (FL) and the dissection flap (arrows). (F) Ehlers-Danlos with
aberrant right subclavian, bovine origin, and multiple aneurysms (arrows). (G) Right aortic arch with aberrant left subclavian and tracheal
ring. Note the diverticulum of Komerell (arrows). (H) Massive oral bleeding. Aortic arch arteriogram demonstrates a normal arch
confirguration; however, there is an increased distance between the BCA and RCCA and the LCCA (arrows) secondary to mediastinal
hematoma. (I) Massive oral bleeding is associated with extravasation of contrast from this left common carotid blow-out. (J) Massive oral
bleeding is associated with extravasation of contrast from this left common carotid blow-out. Abbreviations: BCA, brachiocephalic artery;
LCCA, left common carotid artery; SUB, subclavian artery; RCCA, right common carotid artery; LAO, left anterior oblique.

Figure 2 (A,B) 3D CTA demonstrates the normal relationships of the BCA as it bifurcates into the subclavian and carotid arteries on the
right bifurcation. The BCA road-map image demonstrates the clavicle as a landmark for the bifurcation in the AP view. Abbreviation: BCA,
brachiocephalic artery.
 Chapter 1: Vascular Anatomy of the Head, Neck, and Skull Base 3

Figure 3 Proximal subclavian branches (AC) SUB injection demonstrates proximal branches supplying T2 vertebral tumor. (D) The
ascending cervical artery is a potential collateral source to the vertebral artery. Abbreviation: SUB, subclavian artery.

Figure 4 Vertebral artery cervical branches. AP view

(A) and lateral view (B) of the cervical vertebral artery
demonstrate small muscular and vertebral body
branches (arrows).

and the costocervical trunk (Fig. 3AC). These
branches are important to identify in the analysis of
pathologic processes of the lower neck as well as
vascular malformations and other pathologic lesions
involving the cervical and/or upper thoracic vertebral
bodies and spinal cord.
VERTEBRAL ARTERIES
The vertebral arteries ascend posterior to the com-
mon carotid between the longus colli and scalenus
anterior muscles, entering the transverse foramen at
C6. They traverse the transverse foramen of the cer-
vical vertebral body between C6 and C2. After exit-
ing the transverse foramen at C2, the vertebral artery
proceeds posterolaterally through the transverse
foramen of C2 and posteromedially between C1
and the occiput, before entering the foramen mag-
num (1,4,5). The cervical vertebral artery provides
small branches to supply the vertebral bodies and the
adjacent cervical musculature (Fig. 4A, B). The cer-
vical course is usually straight, although tortuosity
may limit distal microcatheterization and/or may
lead to confusion when the transverse foramen is
enlarged (Fig. 5). It is also important to recognize the
potential for luminal narrowing and/or flow
alteration within the vertebral artery as a conse-
quence of normal head turning. This normal phe-
nomenon may be accentuated by the presence of
osteophytes encroaching on the artery within the
transverse foramen (12). Provocative maneuvers dur-
ing angiography or, alternatively, during noninva-
sive vascular imaging may demonstrate these
findings, which may correlate with clinical hypoper-
fusion symptoms such as lightheadedness or vertigo
(Fig. 6A, B) (13,14).
The left vertebral artery is dominant (larger and
responsible for the majority of the posterior fossa
flow) almost half of the time, while the right vertebral
artery is dominant 25% of the time (12,1517). No size
or flow dominance is present in the remaining cases
(12,1517). Anastomoses exist at multiple levels with
the external carotid artery (ECA), the thyrocervical
trunk, and the costocervical trunk.
4 Johnson et al.
The vertebral arteries proceed through the dura
at the level of the foramen magnum and join to form
a common basilar artery. The posterior inferior cer-
ebellar artery (PICA) is the largest, though frequently
variable, branch of the vertebral artery and usually
arises proximal to origin of the basilar artery. It can
arise as a single trunk or in duplicate, and occasion-
ally the vertebral artery can terminate as the PICA
(18,19). There is a balance between distal branches of
the PICA and hemispheric branches of the anterior
inferior cerebellar artery (AICA) such that an AICA-
PICA variant may be an absent PICA, with the PICA
territory supplied by distal branches of the AICA, or
vice versa (1820). (Fig. 7A, B)
The posterior spinal artery often arises from the
vertebral artery at the level of the medulla oblongata
Figure 5 Vertebral artery tortuosity versus dissection
on CTA (A). Note the tortuosity without dissection flap
on the AP angiogram (B).
Figure 6 Syncope on head turning. (A) Left vertebral
artery: neutral position. Note the compression of the
cervical vertebral artery by uncovertebral joint degen-
erative osteophytes accentuated on moderate (B) and
maximal (C) head turning.
or may arise from the PICA, coursing posteriorly and
dividing into anterior and posterior branches to anas-
tomose with small perforators from the vertebral
artery. The ascending cervical artery, posterior inter-
costal arteries, and lumbar arteries may each contrib-
ute collateral supply to the posterior spinal arteries at
their respective levels. The anterior spinal artery arises
from the distal end of the vertebral artery and
descends anterior to the medulla oblongata, joining
with its contralateral branch to descend as a single
vessel, forming multiple anastomoses with similar
segmental perforators (as the posterior spinal artery),
to supply the anterior spinal cord to the filum termi-
nale. The posterior meningeal artery arises from the
cervical vertebral artery to supply the bone and dura
of the posterior fossa (12). Multiple small spinal
 Chapter 1: Vascular Anatomy of the Head, Neck, and Skull Base 5

Figure 7 Distal vertebral artery variations. (A) AP and (B) lateral vertebral ends in PICA. Vertebral artery fenestrations (CE);
T1-weighted sagittal MRI (F) and AP (G) and lateral (H) vertebral angiograms demonstrate an AVM fed by the ASA; AP (I) and lateral
(J) views demonstrate the origin of PICA below the foramen magnum. Abbreviations: AVM, arteriovenous malformation; ASA, anterior
spinal artery; PICA, posterior inferior cerebellar artery.

branches enter the vertebral canal through the inter- medially to enter the carotid canal at the skull base
vertebral foramina to supply the spinal cord. Muscu- (Fig. 8C, D).
lar branches at the level of the lateral mass of C1
supply the deep cervical musculature. External Carotid Artery

COMMON CAROTID ARTERIES
The common carotid arteries proceed cephalad
within the fibrous carotid sheath along with the
internal jugular vein, the vagus nerve, and the ansa
cervicalis. The common carotid arteries have no nor-
mal branches before the carotid bifurcation, although
rare variations may occur (Fig. 8A, B) (20). The ter-
minal common carotid artery dilates to form the
carotid bulb and bifurcates into the ICA and ECA.
The bifurcation is typically located between the level
of thyroid cartilage and the greater horn of the hyoid
bone, although carotid bifurcations may lie either
above or below this level (reported at the C1C2 to
the C6C7 levels) (21,22). The anatomic level of the
carotid bifurcation is more important when surgical
rather than endovascular correction of carotid
atherosclerotic disease is planned. The bifurcation is
located between C3 and C5 in approximately 80% of
patients, with the next common location at the C5C6
level (13%) (22,23). The internal carotid artery (ICA)
courses posterolateral to the ECA and then proceeds
The ECA arises at the bifurcation of the common
carotid artery in the neck and supplies the face,
scalp, and dura primarily, with potential collateral
contributions to the brain parenchyma and orbital
contents (23). The ECA branches have many varia-
tions. (Fig. 9). However, true ECA anomalies are rare,
the most common being a so-called nonbifurcated
common carotid artery, where the ECA branches
arise separately from the common carotid trunk
(24,25). Anomalous origin of the ECA from the aortic
arch is also rarely encountered (26). The ECA courses
anterolaterally from its initial position along the lat-
eral pharyngeal wall as it passes beneath the posterior
belly of the digastric and stylohyoid muscles and
pierces the parotid fascia. The deep lobe of the
parotid gland separates the ECA from the ICA (1,4, 5).
Two schemes for categorizing the ECA
branches according to cranial caudal or anterior
and posterior locations have been proposed to pre-
dict the vascular source of neovascularity or bleeding
on the basis of cross-sectional imaging prior to inter-
vention. In one scheme, the ECA branches are
6 Johnson et al.

Figure 8 Cervical carotid variations. (A) Normal bifurcation, (B) cervical loop, and (C) ascending pharyngeal artery arise from the ICA.
(D) Hypoglossal artery with ICA occlusion. (E) Hypoglossal artery CT. (F) Hypoglossal artery angiogram. (G) Fibromuscular dysplasia
(FMD). Abbreviations: ICA, internal carotid artery.

Figure 9 (A) Lateral CCA injection reveals a large facial artery (FAC) with dominant nasal supply compared with the smaller IMA
contribution. Note the prominent nasal blush in this patient with epistaxis (arrows). (B) Lateral CCA injection reveals a large IMA and
smaller FAC in another patient. Rapid visualization of collateral circulation (C) from IMA to facial territory following FAC embolization and
(D) from FAC to IMA territory demonstrated in two different patients during embolization therapy for epistaxis. Abbreviations: CCA,
common carotid artery; IMA, internal maxillary artery.
 Chapter 1: Vascular Anatomy of the Head, Neck, and Skull Base
Figure 10 Terminal ECA branching. Lateral view demonstrates
the terminal branches of the ECA, the IMA, and the STA. Note
the normal origins of the MMA and AMA from the IMA. Abbrevia-
tions: ECA, external carotid artery; IMA, internal maxillary artery;
STA, superficial temporal artery; MMA, middle meningeal
artery; AMA, accessory meningeal artery; IMA, internal maxillary
artery.
conceptually divided into three segments: (1) the
lower cervical segment, (2) the middle segment (at
the mandibular angle), and (3) the upper segment (in
the area of the parotid gland). An alternative orga-
nizational method is to consider the ECA branches as
anterior and posterior branches. The anterior
branches, listed in proximal to distal order, are the
superior thyroid, lingual, and facial arteries. The
posterior branches in proximal to distal order are
the ascending pharyngeal artery (APA), occipital,
and posterior auricular arteries. The branch order
corresponds to the associated soft tissue structures,
after which the vessels are named. The ECA termi-
nates by bifurcating into the internal maxillary and
superficial temporal arteries (Fig. 10A, B) (23).
Superior Thyroid Artery
The superior thyroid artery is usually the most prox-
imal and anterior ECA branch and can be readily
identified by the prominent thyroid blush after
contrast injection. This artery may also arise from
the carotid bifurcation or, occasionally, directly from
the cervical common carotid artery (Fig. 11) (23,27).
The superior thyroid artery arises from the anterior
surface of the ECA and courses directly inferiorly
alongside the gland to supply the superior pole of
the thyroid gland and larynx. There is extensive
collateralization with the contralateral superior
7
Figure 11 Superior thyroid artery (SUT). The normal SUT
(arrow) is the first branch of the ECA and provides a dense
arterial blush (*) to the richly vascular thyroid gland. Note the
presence of multiple branches and the incidental anterior com-
municating artery aneurysm. Abbreviation: ECA, external carotid
artery.
thyroid artery and the inferior thyroid artery, which
originates from the thyrocervical trunk. Rarely, injury
to the artery may occur at the time of tracheostomy or
laryngeal surgery, resulting in bleeding and/or pseu-
doaneurysm formation (Fig. 12A, B).
Ascending Pharyngeal Artery
The APA is the first posterior ECA branch (23).
Anteriorly directed APA branches supply the phar-
ynx and eustachian tube. Posteriorly directed
branches supply the tympanic cavity and preverte-
bral muscles (Fig. 13A, B). The main trunk of the APA
parallels the course of the ICA and can be occasionally
mistaken for the ICA on ultrasound in the setting of
internal carotid occlusion (a source of false-negative
ultrasound screening examinations) (Fig. 14A, B) (28).
The APA, in its location adjacent to the pharyngeal
mucosal space, can be eroded by tumor and become
the source of intractable bleeding (Fig. 15A, B). A
small but clinically important branch vessel is the
neuromeningeal branch, which supplies both the
dura and lower cranial nerves. There are extensive
anastomoses between the APA and the intracranial
vasculature. These include rami anastomosing with
the middle meningeal and accessory meningeal
arteries of the external carotid circulation (23,29).
There are also anastomoses with the internal carotid
system via the inferior tympanic artery, which
8 Johnson et al.

Figure 12 Superior thyroid artery (SUT) pseudoaneurysm: peritracheal bleeding nine days after radical neck surgery, layngectomy, and
tracheostomy. Oblique RCCA injection demonstrates faint blush from the distal SUT (A) better seen on microcatheter injection (B). It was
successfully embolized with acrylic (C). Abbreviation: RCCA, right common carotid artery. From Endovascular today and neurosurgical
clinics.

Figure 13 Ascending pharyngeal artery. AP (A) and lateral (B) angiograms of the normal APA that divides into an anterior (pharyngeal)
and posterior division. Collaterals exist between the posterior division and the vertebral and between the anterior division and the internal
carotid artery. (C) Note the extensive neovascular supply (arrows) from the anterior division of the APA to this JNA. Abbreviations: APA,
ascending pharyngeal artery; JNA, juvenile nasal angiofibroma.

anastomoses with the caroticotympanic artery of the
petrous internal carotid. Other variable anastomoses
may also exist between the APA and the vidian artery
and inferolateral trunk. The APA may also anasto-
mose with cervical branches of the vertebral artery via
the artery of the odontoid arch (Fig. 16). These poten-
tial pathways of collateralization are extremely
important to keep in mind during therapeutic embo-
lization of the APA territory (23,29). Careful angio-
graphic evaluation of the APA branching pattern
 Chapter 1: Vascular Anatomy of the Head, Neck, and Skull Base 9

Figure 14 Ultrasound pitfalls. (AC) High-grade carotid stenosis misdiagnosed as ICA occlusion by ultrasound. An 80-year-old female
had known bilateral carotid stenoses, which had previously been estimated at 90% on the right by ultrasound 5 months ago. Pulsed
Doppler of right ICA (A) shows increased peak systolic velocity and prominent diastolic flow. The more distal ICA could not be visualized,
and the study reported RICA occlusion. By comparison, pulsed Doppler of the left ICA (B) shows a symmetric appearance of the diastolic
flow on the left as compared with the right. A true occlusion of the RICA would demonstrate no diastolic flow in the ICA proximal to the
occlusion. (C) A CTA 3D volume-rendered image with curved reformation confirms that the right ICA is severely narrowed, but patent.
(D, E) APA mistaken for the ICA by ultrasound. Pulsed Doppler ultrasound (D) image of a patient with congenital absence of the left ICA
(same patient as shown in Fig. 32CE) demonstrates an artery in the expected location of the ICA, which has low resistance flow. This
vessel was mistaken for the ICA on initial ultrasound interpretation. A CTA 3D volume-rendered images shows the absent ICA (E). The
APA lies parallel to the carotid sheath, and the presence of APA to ICA anastomoses lead to internalization of the waveform pattern,
thus potentially causing confusion on ultrasound. Abbreviations: ICA, internal carotid artery; APA: ascending pharyngeal artery; RICA,
right internal carotid artery.

Figure 15 APA extravasation (EXTRAV). (A) Lateral CCA injection demonstrates faint extravascular contrast in the region of the APA.
(B) Microcatheter injection reveals frank extravasation. (C) Acrylic injection (CAST) resulted in cessation of bleeding. Abbreviations: APA,
ascending pharyngeal artery; CCA, common carotid artery. From Endovascular today.
10 Johnson et al.
Figure 17 Lingual artery normal. (A) AP and (B, C) lateral early- and late-phase images.
is imperative before therapeutic embolization is
performed.
Lingual Artery
The lingual artery arises from the anterior surface of the
ECA, loops upward, and proceeds anteriorly along the
hyoid and deep into the hypoglossal muscle, to supply
the ipsilateral tongue, sublingual gland, pharynx, and
hyoid musculature (1,23). It may occasionally arise from
a common trunk with the facial artery (Fig. 17). The
lingual artery has a characteristic U-shape on AP and
lateral views. Lingual artery injury, erosion, or laceration
may result in pseudoaneurysm formation and massive
bleeding (Fig. 18A, B).
Facial Artery
The facial artery is the third anteriorly oriented ECA
branch. It ascends along the superior constrictor
Figure 16 Artery of the odontoid arch. (A) Selective
APA injection before embolization of skull base giant
cell tumor (arrows) demonstrates a midline vessel filling
the vertebral artery from the APA. (B) Note the vessel
filling on the selective vertebral artery injection. Safe
embolization requires the catheter to be positioned
distal to the collateral branch. Abbreviation: APA,
ascending pharyngeal artery.
muscle, passes deep into the stylohyoid and digastric
muscles, and loops over the submandibular gland. It
crosses the anterior aspect of the mandible and
branches into the submental artery inferiorly, to supply
the floor of mouth and submandibular gland. The facial
artery and its superior branches course in an oblique
fashion from the inferolateral aspect of the face, sup-
plying the lips, face, palate, pharynx, and floor of the
nasal cavity before terminating as the angular artery
near the medial canthus of the eye (Fig. 19) (1,23).
Occipital Artery
The occipital artery is the second posteriorly oriented
ECA branch, arising opposite the facial artery. It passes
beneath the posterior belly of the digastric and
sternocleidomastoid muscles providing muscular pen-
etrating branches. It courses within the subcutaneous
tissues of the posterior scalp and supplies the posterior
 Chapter 1: Vascular Anatomy of the Head, Neck, and Skull Base 11

Figure 18 (A) Massive oral bleeding. Axial CTA dem-

onstrates radiation seeds in the tongue/floor of mouth
on the left. A rounded collection of contrast is identified
in the tongue consistent with a lingual pseudoaneurysm
(arrow). (B) CTA coronal reconstruction demonstrates
the pseudoaneurysm (arrow) and correlates with the
(C) AP external carotid arteriogram, where the pseu-
doaneurysm is identified as arising from the LIN.
(D) Lateral ECA arteriogram demonstrates the mark-
edly irregular lingual artery and the contrast extending
into the pseudoaneurysm (arrow) arising from the irreg-
ular segment. Abbreviations: ECA, external carotid
artery; LIN, lingual artery; FAC, facial artery.

Figure 19 Facial artery nasal supply. (A) AP and (B) lateral views of a FAC injection demonstrates marked vascular blush to the nasal
arcade and a focal PSA in this patient with epistaxis. Abbreviations: FAC, facial artery; PSA, pseudoaneurysm.

skin, muscle, and meninges of the posterior fossa
(1,24,30). Prominent muscular branches provide anasto-
moses between the occipital and vertebral arteries,
particularly in the setting of proximal stenosis or occlu-
sion (Fig. 20A, B). It is important to recognize that
meningeal branches pass intracranially through the
hypoglossal and mastoid canals as well as through the
jugular foramen. These branches can become enlarged
in the setting of dural arteriovenous malformation
(Fig. 21).
Posterior Auricular Artery
The posterior auricular artery arises from the poste-
rior aspect of the ECA just above the level of the
occipital artery (23). It may occasionally arise from or
as a combined trunk with the occipital artery (30).
The stylomastoid branch of the posterior auricular
artery enters the stylomastoid foramen and sends
branches to the chorda tympani within the tympanic
cavity, the mastoid, and the semicircular canals. The
12 Johnson et al.

Figure 20 Occipital artery. (A) Lateral selective occipital artery injection demonstrates scalp branches and distal meningeal branches
supplying a hypervascular meningioma (arrows). (B) Lateral common carotid injection demonstrates prompt filling of the vertebral artery
from muscular collaterals of the occipital artery. The anterior circulation fills via the posterior communicating artery in this patient with
occlusive disease of the internal carotid artery. (CE) OCC to vertebral muscular collaterals are demonstrated in this patient with left
subclavian origin occlusion. (C) Illustrates reconstitution of the intracranial vertebral artery, while later phase lateral (D) and AP (E) views
demonstrate reconstitution of the cervical vertebral artery and distal subclavian. Abbreviation: OCC, occipital.

mastoid artery anastomoses with petrosal branches

from the middle meningeal artery.

Superficial Temporal Artery

Figure 21 Enlarged dural branches with dural arteriovenous
malformation. Lateral ECA arteriogram demonstrates an
enlarged middle meningeal artery with shunting into the trans-
verse sinus and middle meningeal vein. In addition, there are
enlarged dural branches of the occipital artery shunting into the
abnormal, distally occluded transverse sinus. Abbreviation: ECA,
external carotid artery.
auricular branch supplies the scalp, the pinna, and
the external auditory canal. A prominent but normal
vascular blush is noted in the pinna after injection
of the posterior auricular artery (Fig. 22). The stylo-
The ECA terminates within the parotid gland in the
superficial temporal artery (STA) and the internal
maxillary artery. From its origin within the parotid
gland, the STA proceeds cephalad over the arch of the
zygoma and divides into frontal and parietal
branches. The STA is primarily a cutaneous artery
supplying the anterior two-thirds of the scalp, the
underlying cranium and musculature, and portions
of the parotid gland, ear, and temporomandibular
joint (1,23). Small local branches anastomose with
the maxillary and facial artery branches of the upper
portion of the face. The STA has a characteristic
hairpin turn on angiography as it courses over the
zygoma (Fig. 23). The superficial course of the STA
renders it vulnerable to direct injury with resultant
pseudoaneurysm formation. The pseudoaneurysms
commonly present as pulsatile lumps on the fore-
head or scalp following remote trauma (Fig. 24).
Internal Maxillary Artery
The internal maxillary artery courses deep to the neck
of the mandible and enters the infratemporal fossa. It
commonly passes horizontally between the heads of
the medial and lateral pterygoid muscles and through
the pterygomaxillary fissure into the pterygopalatine
fossa (1,4,5,23). Three segmental divisions of the inter-
nal maxillary artery are defined by the position of the
artery relative to the pterygoid muscle. The first seg-
ment gives rise to the inferior alveolar artery, which
extends inferiorly along with the mandibular nerve to
the mandibular foramen (Fig. 25). The middle and
accessory meningeal arteries pass through the
 Chapter 1: Vascular Anatomy of the Head, Neck, and Skull Base 13

Figure 22 PAA supplying AVM. (A) MRA 3D TOF axial source image demonstrates enlargement of the left pinna and increased signal
intensity consistent with hypervascularity. Digital AP (B) and early- and late-phase lateral (C, D) views of a selective OCC artery injection
demonstrates the PAA arising from the OCC (a normal variant) and a prominent blush with early venous drainage into the external jugular
system secondary to a high-flow AVM of the pinna. Abbreviations: AVM, arteriovenous malformation; OCC, occipital; PAA, posterior
auricular artery; TOF, time of flight.

Figure 23 Scalp AVM. (A, B) AP and lateral selective STA angiograms demonstrate the enlarged feeders from the anterior division of
the STA to an AVM of the scalp. Note the normal size of the STA posterior division and the early draining vein. Abbreviations: STA,
superficial temporal artery. Abbreviation: AVM, arteriovenous malformation.
14 Johnson et al.
foramen spinosum and ovale, respectively. The mid-
dle meningeal artery has a characteristic curve as it
exits the foramen spinosum that parallels the floor of
the sella on lateral angiogram. The meningeal
branches can be differentiated from the scalp branches
by their straight rather than tortuous course. Remem-
bering that you can wrinkle your forehead, but you
cannot wrinkle your dura is a helpful key to differ-
entiating these branches (Fig. 26). The middle menin-
geal artery may be variable in size and may
occasionally give rise to, or arise from, the ophthalmic
artery (31). The deep auricular artery that supplies the
external auditory canal and the anterior tympanic
artery that supplies the tympanic membrane both
arise from the first segment of the internal maxillary
artery. The pterygoid segment (middle) is located in
the high, deep masticator space and gives rise to
masseteric, buccal, and deep temporal arteries. These
supply the pterygoid and temporalis muscles and the
lingual and buccal nerves. The third or sphenopala-
tine segment of the internal maxillary artery lies
within the pterygopalatine fossa and sends branches
along with each nerve to the pterygopalatine ganglion
Figure 24 STA pseudoaneurysm. (A, B) Two patients
with typical STA aneurysms (arrows) following direct
trauma. Abbreviations: STA, superficial temporal artery;
MMA, middle meningeal artery.
Figure 25 Internal maxillary artery. (A, B) AP and
lateral selective IMA injections demonstrate the three
segments and the important branches. Abbreviations:
IMA, internal maxillary artery; MMA, middle meningeal
artery; ACM, accessory meningeal artery; STA, super-
ficial temporal artery.
(Fig. 27). It terminates in multiple branches to the
nasal cavity supplying both nasal wall and septum.
The posterior superior alveolar artery supplies the
palate and posterior wall of the maxilla. The infraor-
bital artery passes through the infraorbital fissure
along the orbital floor.
External Carotid Anastomotic Network
The importance of external carotid to internal carotid
collaterals and potential anastomotic pathways cannot
be overemphasized in the setting of disease and
neurointervention (23,29,30,32). These interconnec-
tions are dynamic and may change in appearance
and flow rate during the interventional procedure,
becoming most dangerous near the end of the proce-
dure. The IMA has numerous extensive anastomoses
with other ECA branches in the face. It is clinically
relevant to appreciate the extensive collateral network
between the lingual, facial, and internal maxillary
artery branches. A complex hemodynamic balance
exists between these pedicles. If a hypoplastic facial
artery is present, large buccal and masseteric branches
 Chapter 1: Vascular Anatomy of the Head, Neck, and Skull Base
will be present from the internal maxillary artery, and
vice versa. During embolization therapy for epistaxis,
it is not uncommon to appreciate anastomotic
branches restoring proximal flow to an embolized
territory (Fig. 28).
External carotid to internal carotid anastomoses
exist, and flow may proceed in either direction depend-
ing on the location and nature of the diseased vascu-
lature. The distal ethmoidal branches of the IMA
anastomose with distal ethmoidal branches of the oph-
thalmic artery. Thus the IMA, via these ethmoidal
collaterals, may provide a supply route to the supra-
clinoid ICA via reversal of flow through the ophthalmic
artery. The vidian artery anastomoses with the petrous
ICA. The artery of the foramen rotundum and the
inferolateral trunk anastomose with the cavernous
ICA. These ECA-ICA anastomoses vary to a significant
degree among patients and offer a clinically significant
15
Figure 26 Middle meningeal artery variations. The
ophthalmic artery arises from the MMA in this patient.
The reverse can also occur, posing potential problems
for embolization. Abbreviations: MMA, middle menin-
geal artery.
Figure 27 IMA nasal arcade (A) AP DSA injection into
the distal ECA demonstrates the branches of the inter-
nal maxillary artery and the nasal arcade (arrows). Note
the STA and MMA arteries. (B) Magnified superselec-
tive AP view better demonstrates the nasal arcade and
prominent mucosal blush in this patient with epistaxis.
Abbreviations: IMA, internal maxillary artery; DSA, dig-
ital subtraction angiography; ECA, external carotid
artery; STA, superficial temporal artery; MMA, middle
meningeal artery.
collateral pathway between the ECA and the ICA
systems, seen most prominently in the setting of occlu-
sive vascular disease (Fig. 29A, B) (23,29). With occlu-
sion of the ECA, ICA branches may collaterally restore
external carotid flow (Fig. 30) (23,29).
Internal Carotid Artery
The ICA enters the skull base through the carotid
canal ascending anterior to the jugular bulb and pos-
terior to the eustachian tube (1,4,5,33). The ICA pet-
rous segment courses anteromedially to the tympanic
cavity, giving rise to the caroticotympanic artery (to
the tympanic cavity), the vidian artery, and small
periosteal branches (34). The ICA courses superiorly,
extending above the foramen lacerum to pierce the
dura and enter the posterior aspect of the cavernous
sinus (Fig. 31). The ICA is occasionally congenitally
16 Johnson et al.

Figure 28 Epistaxis: the importance of ophthalmic collaterals. (A) ICA injection at the time of initial epistaxis embolization demonstrates
normal terminal ophthalmic artery branches. (BD) One month later, the patient presents with recurrent epistaxis, and sequential ICA
images demonstrate reconstitution of the nasal arcade by ophthalmic collaterals. Abbreviation: ICA, internal carotid artery.

Figure 29 Extensive collaterals to the petrous, cavernous, and supraclinoid ICA from the branches of the internal maxillary artery.
(A) IMA to OPH to ICA ethmoidal collaterals. (B) Vidian artery and inferolateral trunk to the petrous ICA. Note the occipital to vertebral
artery muscular collaterals. Abbreviations: ICA, internal carotid artery; AMA, acessory meningeal; MMA, middle meningeal artery; OPH,
ophthalmic artery.
 Chapter 1: Vascular Anatomy of the Head, Neck, and Skull Base 17

Figure 30 Restoration of ECA flow. (A) Lateral CCA

arteriogram demonstrates extravasation of contrast
from the proximal ECA at the origin from the carotid
bulb. Note the radiation seeds and the small occipital
artery identified before embolization. (B) Following par-
tial embolization of the ECA and occlusion of the right
CCA. Control arteriogram demonstrates filling of the
ipsilateral vertebral artery with filling of a large muscular
collateral with reconstitution of the occipital artery and
retrograde filling of the ECA with continued extravasa-
tion into the pharynx. Control of bleeding required
particulate embolization for occlusion and disconnec-
tion of the muscular collateral to the occipital artery.
Abbreviations: ECA, external carotid artery; CCA, com-
mon carotid artery.

Figure 31 The dural ring. The ICA enters the cavernous sinus dura, traverses the sinus and exits at the dural ring. This patient
presented with SAH and demonstrates and ICA posterior wall aneurysm. The arrow marks the location of the dural ring on the
conventional angiogram (A) and on 3D CTA (B). The trigeminal artery is a primative communication between the cavernous carotid
segment and the distal one-third of the basilar artery identified on conventional angiogram (C) and on 3D CTA (D). Abbreviation: ICA,
internal carotid artery; SAH, subarachnoid hemmorhage.
18 Johnson et al.

Figure 32 ICA anomalies. (A) CT and (B) AP angiogram demonstrate the aberrant ICA with the characteristic lateral position of the ICA
(arrow) projecting into the middle ear cavity behind the tympanic membrane. The carotid canal is incomplete and the carotid is usually
narrowed just distal to the middle ear segment. (C) CT and (D, E) CTA in agenesis of the ICA demonstrate absence (*) of the carotid canal
in addition to the absence of the ICA. Abbreviation: ICA, internal carotid artery.

absent and can be differentiated from acquired occlu-
sion by the absence of the carotid canal at the skull
base (Fig. 32A, B) (35).
Nomenclature varies, but the four-part division
of the internal carotid, designated as C1C4 and
described in the radiology and surgical literature, is
useful. The cervical segment (C1) begins proximally
at the origin of the ICA with the CCA and extends
cephalad to the external orifice of the carotid canal.
The petrous segment (C2) traverses the carotid canal
and enters the cavernous sinus (dura), where the
cavernous segment (C3) begins. The cavernous seg-
ment ends where the ICA pierces the dural roof of
the cavernous sinus. The supraclinoid segment (C4)
begins where the ICA exits the dural ring and enters
the subarachnoid space, and it ends at the internal
carotid bifurcation into anterior and middle cerebral
artery branches (34,36). The supraclinoid segment
passes medially to the anterior clinoid and below
the optic nerve. Together, the C3 and C4 segments
form the characteristic S shape seen on lateral and
oblique angiographic views of the skull base. C1 does
not normally provide any branches. C2 gives rise to
three potential branches: the caroticotympanic
branch supplying the middle and inner ear; the
vidian artery, or the artery of the pterygoid canal,
which goes through the foramen lacerum; and the
artery of the foramen rotundum (35,36). C3 gives rise
to three trunks. The posterior trunk, or the meningo-
hypophyseal trunk, branches into the tentorial artery
(of Bernasconi and Casinari) supplying the tento-
rium, the inferior hypophyseal artery supplying the
posterior pituitary capsule, and the dorsal meningeal
artery supplying the abducens nerve and the clivus
(35,36). The lateral trunk, or inferior cavernous sinus
artery, supplies the inferolateral cavernous sinus
wall and region of the foramen ovale and spinosum.
The medial trunk, or McConnels capsular artery,
supplies the anterior and inferior pituitary capsules
and is present in only 28% of the population
(33,34,36). A pituitary blush is commonly identified
on lateral internal carotid arteriograms. These small
branches become important in the analysis of skull
base tumors and provide potential anastomoses with
external carotid branches in the setting of disease
(Figs. 32 and 33) (33,34,36).
VEINS OF THE HEAD, NECK, AND SKULL BASE
The venous drainage of the face is predominantly super-
ficial and empties into the external jugular drainage
pathways (1,4,5). The supraorbital and supratrochlear
 Chapter 1: Vascular Anatomy of the Head, Neck, and Skull Base 19

Figure 33 Cervical and facial veins. (A) The proximal internal and external jugular veins are demonstrated as approached from the
femoral route. (B, C) Facial veins drain into the EJV. (D, E) Nasal and facial structures may drain superiorly into the superior and or
inferior ophthalmic veins. Abbreviations: EJV, external jugular vein; SOV, superior ophthalmic veins.

veins of the face join to become the angular vein and
proceeds as the facial vein over the angle of the man-
dible (1,4,5). The pterygopalatine venous plexus is
located around and within the lateral pterygoid muscle.
It may be recognized on CT as a focal area of irregular
enhancement adjacent to the muscle. It is often identi-
fied as a variation in the cerebral venous drainage
pattern on cerebral angiography, receiving flow from
the greater middle cerebral (sylvian) vein (Fig. 34A, C).
The pterygopalatine venous plexus drains into a pair of
maxillary veins, which lie deep in the neck of the
mandible and join with the temporalis vein draining
the temporal region of the face and scalp to form the
retromandibular vein. The inferior ophthalmic vein
travels with the infraorbital artery and drains into the
cavernous sinus intracranially and the pterygopalatine
venous plexus extracranially.
Occasionally, the facial veins will drain superi-
orly into the ophthalmic veins and into the cavernous
sinus as a normal variation in the absence of shunting
(37). The retromandibular vein passes through the
parotid gland and divides into anterior and posterior
branches that drain into the internal and external
jugular veins, respectively. The deep facial vein rep-
resents the anastomosis between the pterygopalatine
venous plexus and the facial vein. The anterior jugu-
lar veins lie in the submental region extending infe-
riorly to the suprasternal notch, where they
communicate with the external jugular vein deep to
the sternocleidomastoid muscle. The external jugular
also receives the posterior auricular vein. The external
jugular vein empties into the subclavian vein near the
midpoint of the clavicle. The internal jugular vein
originates from the jugular bulb receiving blood from
20 Johnson et al.

Figure 34 Prominent PVP (A) Axial CTA image demonstrates asymmetry of the PVP, prominent on the left (arrows)possible normal
variant versus AVM. Digital subtraction images of the venous phase after ICA injection in AP (B) and lateral (C) projections demonstrate a
prominent sylvian (greater middle cerebral) vein (arrows) draining into an unusually large PVP (arrow), which subsequently drains into the
external jugular vein. This arrangement is a normal anatomic variant. Abbreviation: PVP, pterygopalatine venous plexus; AVM,
arteriovenous malformation; ICA, internal carotid artery.

Figure 35 Veins at the skull base. (A) Late venous-phase DSA image in AP projection after arterial injection shows the normal course of
the skull base venous sinuses. (B, C) DSA images in AP and lateral projections demonstrate the course of the IPS, which is oriented
medially and anteriorly. (D) DSA image in AP projection from another patient after right IJV injection demonstrates venous communication
with contrast filling the right IPS and refluxing into the left IPS. Note the cavernous sinus filling. Abbreviations: DSA, digital subtraction
angiography; IPS, inferior petrosal sinus; SIG, sigmoid sinus; IJV, internal jugular vein.

the sigmoid sinus and its first extracranial tributary,
the inferior petrosal sinus (Fig. 35AC) (37,38). It
descends behind the ICA directly adjacent to the
arch of C1, where it joins the subclavian vein to
become the brachiocephalic vein. The left brachioce-
phalic vein joins at the right of the second costal
cartilage to become the superior vena cava.
SUMMARY
Knowledge of the normal and variant anatomy of the
head, neck, and skull base is critical to the under-
standing of its vascular pathology and to the safe
performance of diagnostic and therapeutic angiogra-
phies. Correlation with cross-sectional imaging is use-
ful in the anticipation of vascular supply and
dangerous anastomoses.
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 2
Applied Neurovascular Anatomy of the Brain and Skull
Randy S. Bell, Alexander H. Vo, and Rocco A. Armonda
Departments of Neurosurgery and Radiology,
National Naval Medical Center, and
Comprehensive Neurosciences Program, Uniformed Services
University of Health Sciences, Bethesda, Maryland, U.S.A.
INTRODUCTION
Advances in imaging and materials technology have
expanded the array of pathologies treatable through
less invasive endovascular approaches. The resultant
benefit to the patient manifested by increased inter-
ventional success rates and reduced morbidity and
mortality cannot be overstated. However, the utility of
even the most advanced biplanar machine with 3D
rotational capabilities is limited without a thorough
understanding of the craniocerebral angiographic
anatomy. This understanding must, of necessity,
include the significant arterial anastomoses and col-
lateral circulatory patterns that should be considered
during any intervention. Collateral circulation may
prevent significant neurologic deficit should parent
artery occlusion (PAO) be required. That said, known
circulatory anastomoses could result in infarct distal
to the area of embolization or PAO. The purpose of
this chapter is to provide an in-depth review of the
normal cerebrovascular angiographic anatomy as well
as the significant internal, external, and vertebrobasi-
lar anastomoses. Additionally, high-quality gross ana-
tomic specimens will be shown with the basic
angiogram to emphasize the importance of surround-
ing neurologic structures. The importance of the con-
tribution of individual anatomy in the formulation of
any treatment plan will also be emphasized. Because
thorough reviews of anatomic variants have been
provided elsewhere (15), only brief descriptions
will be highlighted where considered relevant.
INTERNAL CAROTID ARTERY
The internal carotid artery (ICA) originates from the
common carotid artery in the neck at the approximate
level of the fourth cervical vertebrae. Though several
segmental naming schemes exist, this chapter will refer
to that provided by Rhoton (5). The cervical segment
(C1) ascends to the base of the skull without producing
any branches (Fig. 1B). It enters the skull through the
carotid canal to become the horizontal petrous portion
(C2). This segment is seen as the first medial turn on a
standard anterior-posterior (AP) projection and as the
first anterior turn on a lateral projection (Fig. 1A). The
vidian and caroticotympanic branches originate from
this segment. The artery then takes a 908 superior turn
at the foramen lacerum and becomes the cavernous
portion (C3). The segment is manifested as a double
arterial density on a standard AP projection and as an
anteriorly projecting hairpin turn on a lateral projec-
tion. Branches within this segment include the menin-
gohypophyseal trunk, the inferolateral trunk, and
McConnells capsular arteries. The ophthalmic artery
may occasionally originate from this segment. The
meningohypophyseal trunk gives rise to the tentorial
artery of Bernasconi and Cassinari [important during
embolization of tentorial meningiomas or tentorial
arteriovenous malformation (AVM) (Figs. 2 and 3)],
the dorsal meningeal artery, and the inferior hypophy-
seal artery. The artery then progresses caudally and
laterally as it exits the cavernous sinus and enters the
subarachnoid space through an inner and outer dural
ring to become the supraclinoid segment (C4). The
ophthalmic, superior hypophyseal, posterior commu-
nicating, and anterior choroidal arteries arise from this
segment (Fig. 4). The internal carotid then bifurcates
into the anterior and middle cerebral arteries (MCAs).
The Ophthalmic Artery
The ophthalmic artery arises from the anterior wall of
the ICA as its first intradural branch (Fig. 4). In 8% of
cases, the artery may arise from within the cavernous
sinus (5). It then travels in an anterior direction and
enters the orbit through the optic canal along with the
optic nerve. A recurrent meningeal branch may inter-
mittently arise from the orbital portion of the ophthal-
mic artery, traveling back through the superior orbital
fissure to supply the meninges in that area. It continues
forward and gives rise to the anterior and posterior
ethmoidal arteries. The remaining terminal branches of
the ophthalmic artery are the central retinal, lacrimal,
long and short ciliary, supraorbital, medial palpebral,
infratrochlear, supratrochlear, and dorsal nasal arte-
ries (5). Significant collateral circulation exists between
the ophthalmic artery and the internal maxillary (long
sphenopalatine communication via the ethmoidal
24 Bell et al.
Figure 2 T1-weighted axial MRI through the rostral midbrain. A
tentorial AVM is shown. The black arrow (Figure 3) indicates the
location of the tentorial artery of Bernasconi and Cassinari within
the paramesencephalic cistern.
arteries), the middle meningeal (via the ethmoidal
arteries), and the superficial temporal artery (via the
lacrimal and zygomatic-orbital arteries) (1,2).
The Posterior Communicating Artery
The posterior communicating artery arises from the
posteromedial aspect of the ICA (Figs. 4, 5, and 13). It
terminates at the posterior cerebral artery (PCA) and is
the boundary between the P1 and P2 segments of that
artery. In approximately 22% of cases, the posterior
communicating artery is larger than the PCA or fails
to fuse with the PCA and becomes the dominant
Figure 1 AP (A) and lateral (B) angiogram of the ICA.
The segmental scheme of Rhoton is provided. C1
extends from the carotid bifurcation to its entrance
into the carotid canal. C2 extends from this point,
through the petrous bone, to the foramen lacerum. C3
constitutes the intracavernous segment. The supracli-
noid segment (C4) continues from the cavernous sinus
to the ICA bifurcation. Abbreviation: ICA, internal
carotid artery.
Figure 3 Lateral angiographic projection of the right ICA. The
black arrow again indicates the location of the tentorial artery.
Note the venous outflow to the superior sagittal sinus. Abbrevia-
tion: ICA, internal carotid artery.
circulation to the PCA territory (1,4,5). Anatomically,
it courses below the edge of the tentorium just superior
to the third cranial nerve (Fig. 5). There are multiple
small perforating arteries that arise from the posterior
communicating artery. The largest of these arteries is
called the premamillary artery (1,5). The perforating
arteries are divided into anterior and posterior perfo-
rating arteries. The anterior perforators supply neuro-
logic tissue within the posterior limb of the internal
capsule, the anterior thalamus, the posterior hypothal-
amus, and the anterior one-third of the optic tract,
while the posterior perforators penetrate the rostral
midbrain and supply the subthalamic nucleus (1).
 Chapter 2: Applied Neurovascular Anatomy of the Brain and Skull
Figure 4 Lateral angiogram of the C4 segment of the ICA. Note
the anterior course of the ophthalmic artery as it passes through
the optic canal with the optic nerve. The black arrow identifies the
course of the artery as it passes superior to the optic nerve.
Significant terminal branches are noted. The posterior communi-
cating and anterior choroidal arteries are also easily seen in this
view. Abbreviations: ICA, internal carotid artery; AchA, anterior
choroidal artery; pCom, posterior communicating artery; LA, lac-
rimal artery; CrA, central retinal artery; PeA, posterior ethmoidal
artery; AeA, anterior ethmoidal artery.
Figure 5 Gross anatomic specimen from Rhoton. The branches
of the ICA are viewed in an axial plane from below. Note the
location of the CN III with respect to the PCoA. and the AChA.
The cisternal segment of the AChA can be seen traveling toward
the temporal horn of the lateral ventricle and the choroid plexus
within. The M1 segment of the MCA is also shown with numerous
lenticulostriate arteries traveling superiorly through the anterior
perforated substance to supply portions of the basal ganglia.
Abbreviations: ICA, internal carotid artery; AChA, anterior cho-
roidal artery; PCoA, posterior communicating artery; CN III, third
cranial nerve; LentStrA, lenticulostriate arteries; MCA, middle
cerebral artery. Source: From Ref. 5.
The Anterior Choroidal Artery
The anterior choroidal artery is the last named branch
arising from the ICA prior to its bifurcation (Figs. 4
and 5). It travels in a posterolateral direction toward
the choroidal point and the choroid plexus of the
temporal horn of the lateral ventricle. The artery is
25
Figure 6 Lateral angiogram, arterial phase, of the ICA. The
branches and segments of the ACA are delineated. The A1
segment extends from the carotid bifurcation to the anterior
communicating artery. The A2A5 segments are then named
based on their location with respect to the corpus callosum. The
anterior and posterior internal parietal arteries are not well
visualized on this injection. Abbreviations: ACA, anterior cerebral
artery; ICA, internal carotid artery; A1, precommisural segment;
A2, infracallosal segment; A3, precallosal segment; A4, supra-
callosal segment; A5, posterocallosal segment; FpA, frontopolar
artery; AntIFA, anterior internal frontal artery; CmA, callosomar-
ginal artery; MidIFA, middle internal frontal artery; PostIFA, pos-
terior internal frontal artery; PeriA, pericallosal artery; PcA,
precentral artery.
broken into the cisternal (within the subarachnoid
cisterns) and plexal (within the lateral ventricles and
choroids plexus) segments. Small perforating vessels
arise from the cisternal segment and are not visualized
on a lateral angiogram. These arteries supply the optic
tract, the cerebral peduncle, the mesial temporal lobe,
and the lateral geniculate body.
The Anterior Cerebral Artery
The anterior cerebral artery (ACA) can be broken
down into five anatomic segments on the basis of its
location with respect to the underlying corpus cal-
losum (Figs. 6 and 7). The A1 segment, or the pre-
communicating segment, extends from the ICA
bifurcation to the anterior communicating artery.
Usually, small perforating branches feed the optic
chiasm, hypothalamus, and anterior corpus callosum,
though they are not typically visible on a normal four-
vessel cerebral angiogram. The recurrent artery of
Heubner may occasionally arise from this segment,
though it primarily originates from A2 (Fig. 13). This
artery is not commonly visualized on a basic
26 Bell et al.
diagnostic angiogram. The remaining postcommuni-
cating segments include the infracallosal (A2), the
precallosal (A3), the supracallosal (A4), and the post-
erocallosal (A5). The A2 segment typically starts at the
anterior communicating artery and extends to the
bifurcation of the pericallosal and callosomarginal
arteries. The frontopolar and orbitofrontal arteries
arise from this segment. Subserved neurologic tissue
includes the hypothalamus, septum pellucidum, ante-
rior commisure, columns of the fornix, and portions
of the basal ganglia. The A3 segment includes the
callosomarginal and pericallosal arteries. The A4 and
A5 segments involve the terminal branches of the
ACA, including the arteries that provide collateral
flow to certain areas within the MCA and PCA
distributions (Fig. 8).
The Middle Cerebral Artery
The MCA originates from the internal carotid and
travels in a course parallel to the floor of the middle
cranial fossa. The artery partitions into four anatomic
Figure 7 Gross anatomic specimen, sagittal plane
through the falx cerebri. The segments of the ACA
are shown with surrounding neurologic structures (com-
pare with Fig. 6). The ACA feeds the paracentral lobule,
which is responsible for motor control of the contralateral
leg. Abbreviation: ACA, anterior cerebral artery; Call-
MargA, callosomarginal artery. Source: From Ref. 5.
Figure 8 AP (A) and lateral (B) injection of the ICA.
The MCA segmental anatomy is shown. M1 starts at
the ICA bifurcation and ends at the LI. M2 continues
to the sharp (>908 on AP) turn at the CS. M3 travels
over the frontal, temporal, and parietal Op to terminate
as the distal, cortical M4 branches. Abbreviations: ICA,
internal carotid artery; MCA, middle cerebral artery; LI,
limen insula; CS, circular sulcus; Op, operculum.
segments, and like the other cerebral arteries organized
in this fashion, the segments are based on surrounding
cerebral anatomy rather than arterial branch points
(Fig. 8A, B). The M1 segment extends from the ICA
to the 908 turn that the artery takes at the limen insula
(Figs. 8 and 9). The MCA bifurcation may occur prior
to or after this point. The M1 segment is characterized
by multiple small perforating arteries that feed the
lentiform nuclei and the anterior limb of the internal
capsule. These lenticulostriate arteries are divided into
medial, intermediate, and lateral groups and originate
from the superior wall of the M1 segment and travel
through the anterior perforated substance to the deep
hemispheric nuclei (Figs. 12 and 13). The M2 segment
extends from the limen insula to the second turn of the
artery at the circular sulcus. Although the M2 branches
are distinguishable on a lateral angiogram, they appear
as a group of double densities on an AP view. The
gross anatomic lateral view of the insula clearly
displays the complex arterial anatomy in this region
(Fig. 11). The M3 segment specifically refers to the
course of the vessels over the frontal, parietal, and
 Chapter 2: Applied Neurovascular Anatomy of the Brain and Skull 27

Figure 9 Gross anatomic specimen, coronal view of

the brain. The MCAs are shown with surrounding anat-
omy (compare with Fig. 8A). The single white area
indicates the location of the limen insula. The double
white arrow highlights the sharp turn of the MCA at
the circular sulcus. Three white arrows approximate the
location of the operculum. Abbreviations: PCA., poste-
rior cerebral artery; LentNucl, lentiform nuclei; LentStrA,
lenticulostriate arteries; MCA, middle cerebral artery;
ACA, anterior cerebral artery. Source: From Ref. 5.

temporal opercula. The M4 segment refers to the

terminal cortical branches (Fig. 10). It is important to
remember that some of the distal MCA vessels feed
non-eloquent cortex (i.e., the temporopolar artery);
however, vessels feeding the central area bilaterally
(primary motor cortex) and the angular area on the left
could result in significant neurologic deficit should
sacrifice occur. Specifically, sacrifice of the superior
trunk of the MCA on the left could result in a Gerst-
manns syndrome (rightleft dissociation, acalculia,
agraphia without alexia, finger agnosia), while sacrifice
of the same artery on the right might result in
asomatagnosia.

Anatomic Considerations
Aneurysms and other vascular malformations of the
distal intracranial circulation present difficult treat-
ment scenarios. As a general rule, aneurysms distal
to the circle of Willis tend to rupture regardless of
size (6,7) and therefore require treatment at the time of
diagnosis. The possible exception may include the
distal aneurysms that result from the aberrant high-
flow state associated with AVMs (8,9). Although open
surgery was advocated prior to the advent of endo-
vascular treatment strategies, a combined approach is
now often necessary. The following will examine the
unique anatomic circumstances that must be consid-
ered prior to treatment of distal intracranial circula-
tion pathology. Figure 10 Late arterial phase injection, lateral view, of the ICA.
The distal MCA vessels are shown with approximate named
The Anterior Cerebral Artery locations. The dense tangle of vessels approximates the location
of the insula. Abbreviations: MCA, middle cerebral artery; Ofr,
The ACA and its branches supply the cortex within the orbitofrontal artery; PreFr, prefrontal artery; PreCen, precentral
interhemispheric fissure. Since this network includes artery; Cen, central artery; Ang, angular artery; OccTemp, tem-
the cingulate cortex and the paracentral lobule, clinical porooccipital artery; PostTemp, posterior temporal artery; Mid-
consequences from pathology in this area may manifest Temp, middle temporal artery; AntTemp, anterior temporal artery;
as lower extremity paresis or memory impairment Tp, temporopolar artery.
(Fig. 7) (8,10,11). Surgical approaches to vascular
28 Bell et al.
Figure 12 AP angiogram of the ICA, magnified view of the ICA
bifurcation. The ML, IL, and LL arteries can be seen. Note the
origin from the superior aspect of the MCA with a course through
the anterior perforated substance to supply the lentiform nuclei.
Abbreviations: ICA, internal carotid artery; MCA, middle cerebral
artery; ML, middle lenticulostriate; IL, intermediate lenticulostri-
ate; LL, lateral lenticulostriate.
pathology in this area are technically difficult and
require extensive preoperative planning (6,8). Consid-
erations include the possibility of disruption of venous
drainage to the superior sagittal sinus from surgical
exposure and retraction, the neurologic consequences
to frontal lobe retraction, and variable anatomy.
Endovascular treatments of distal ACA pathology
are technically challenging because of vessel tortuosity
and reduced distal vessel caliber. However, the possible
neuropsychiatric consequences of open surgery can be
avoided. Treatment with platinum coils of narrow-
Figure 11 Gross anatomic specimen of the arterial
anatomy of the insula (compare with Fig. 8B). The
opercular cortices have been retracted to show the
insula and vessels. Abbreviations: SupTr, superior
trunk; InfTr, inferior trunk. Source: From Ref. 5.
Figure 13 Gross anatomic specimen, anterosuperior view of
the ICA bifurcation (compare with Fig. 12). The small lenticulos-
triate arteries are indicated by white arrows. The recurrent artery
of Heubner can also be seen arising from the A2 segment of the
ACA. Abbreviations: ICA, internal carotid artery; ACA, anterior
cerebral artery; PCoA, posterior communicating artery; RecA,
recurrent artery of heubner; MCABr, middle cerebral artery
branches; FrontBr, frontal branch. Source: From Ref. 5.
necked, distal ACA saccular aneurysms alone is a rea-
sonable approach because anterograde flow through the
preserved parent artery may be possible. However, it
may be necessary at times to sacrifice the parent artery
when balloon remodeling or stent-assisted coiling of a
wide-necked or fusiform aneurysm is not feasible
(Fig. 14A, B). In this case, sufficient collateral circulation
from the PCA circulation may be seen (Fig. 23). Parent
artery occlusion (PAO) proximal to the pericallosal-
callosomarginal artery bifurcation (A2A3) may result
in some or all of the neurologic consequences previously
outlined. Occlusion distal to this vessel segment may be
clinically silent secondary to the extensive collateral
 Chapter 2: Applied Neurovascular Anatomy of the Brain and Skull
Figure 14 Magnified lateral (A) and plane lateral injection of the ICA. An irregular dilation of the A3 segment of the ACA (A, black arrow)
is noted in a patient with traversing penetrating head trauma and subarachnoid hemorrhage. The treatment strategy included PAO using
detachable platinum coils (B, black arrow). Abbreviation: ACA, anterior cerebral artery; PAO, parent artery occlusion.
circulation between the anterior and posterior cerebral
circulation through the posterior pericallosal and sple-
nial arteries. Kim et al. describe an elegant combined
open surgical and endovascular approach to an A2 ane-
urysm, where the distal artery arose from the aneurysm
dome. In this case, a side-to-side pericallosal-pericallosal
anastomosis was performed prior to unilateral endovas-
cular PAO of the A2 segment. This anastomosis resulted
in preservation of distal flow to both hemispheres and
obliteration of the complex aneurysm (12).
The Distal Middle Cerebral Artery
The MCA supplies hemispheric structures, including
the lentiform nuclei, the lateral aspect of the frontal,
parietal, and temporal cortices, and the insular cortex.
Clinical sequelae from arterial occlusion are largely
based on which segment of which MCA (right or left)
is occluded, with symptoms ranging from contrala-
teral hemiparesis or hemianesthesia to aphasia and
calculation difficulties.
MCA bifurcation aneurysms are difficult to treat
endovascularly because of the tendency toward wide-
necked morphologies or because of bifurcation
arteries distal to the aneurysm arising from the aneur-
ysm dome. Fusiform aneurysms or giant MCA bifur-
cation aneurysms may require PAO in combination
with open surgical clipping and bypass (13,14). Weill
et al. describe two cases of giant MCA trifurcation
aneurysms that were successfully treated with EC-IC
bypass and subsequent PAO. In these cases, the M1
segment was coil occluded in a patient with an intact
circle of Willis, while the supraclinoid internal carotid
was coiled in the patient with an absent anterior
communicating artery (14).
29
Mycotic aneurysms that form in the distal MCA
circulation may rupture and cause subarachnoid hem-
orrhage, or they may resolve on antibiotics (15).
Recurrent hemorrhage or interval angiographic
enlargement may push the surgeon to intervene. Sev-
eral studies have demonstrated successful obliteration
of the distal aneurysm through endovascular occlu-
sion (1620). Sodium amytal injection has been used to
determine whether parent artery occlusion (PAO) will
be tolerated. However, this procedures low sensitiv-
ity may not accurately reflect the lack of postocclusion
neurologic deficit with a negative result. In cases of
distal aneurysm formation in eloquent arterial terri-
tories, it may be necessary to accept the possibility of
neurologic deficit to reduce the risk of potentially fatal
subarachnoid hemorrhage (Fig. 15 A, B). For M4
occlusions, collateral flow from the ACA may reduce
the neurologic deficit that would occur from a central
arterial occlusion (motor strip).
PERSISTENT CAROTICOBASILAR
ANASTOMOSES
Persistent fetal circulatory patterns refer to anastomoses
between the carotid and basilar arterial systems, includ-
ing the persistent trigeminal, otic, hypoglossal, and
proatlantal arteries (Fig. 16). These structures are pres-
ent embryologically, normally recede through vessel
atresia, and are associated with other vascular malfor-
mations (2126). The trigeminal artery is the most com-
mon, occurring in 0.1% to 0.2% of the general
population. This artery typically arises from the preca-
vernous carotid and anastomoses with the distal basilar
artery (Fig. 17). The persistent otic artery arises from the
petrous portion of the carotid artery and terminates at
30 Bell et al.
Figure 16 Lateral angiographic cartoon representation of the
types of persistent caroticobasilar anastomoses. A fetal PCA (a)
is shown, though this type is common enough to be considered a
normal variant. The persistent trigeminal artery (b) originates
from the cavernous segment of the ICA and terminates at the
basilar artery. The persistent otic artery (c) originates from the
petrous portion of the ICA and terminates at the proximal basilar
artery. Both the persistent hypoglossal (d) and persistent proat-
lantal (e) arteries arise from the extracranial ICA and terminate at
the vertebral artery. C1 and C2 indicate the location of the first
and second cervical vertebrae. Abbreviation: PCA, posterior
cerebral artery; ICA, internal carotid artery.
the anterior inferior cerebellar artery (AICA) or basilar
artery (1). There are less than five reported cases of this
type in the literature. The persistent hypoglossal artery
arises from the extracranial ICA, passes through the
anterior condyloid foramen, and terminates at the distal
basilar artery. The persistent proatlantal artery is a
Figure 15 Lateral angiogram (A) and magnified lateral
angiogram of the ICA. The black arrows indicate the
focal dilation of the distal MCA consistent with the
presence of a mycotic aneurysm. Abbreviations: ICA,
internal carotid artery; MCA, middle cerebral artery.
Figure 17 Diagnostic angiogram of the ICA, lateral projection. A
persistent trigeminal artery is seen leaving the internal carotid in
the cavernous (C3) segment and entering the basilar artery Note
the filling of both the PCA and SCA circulation. Abbreviations:
ICA, internal carotid artery; PCA, posterior cerebral artery; SCA,
superior cerebellar artery.
primitive anastomosis between the ICA or ECA and
the cervical vertebral artery.
Anatomic Considerations
The presence of persistent caroticobasilar anastomoses
should be ruled in or out before certain procedures.
Wada testing is employed to localize language and
memory dominance prior to partial or complete
amygdalohippocampectomy. During this test, sodium
amobarbital is injected into the ICA on one side to
effectively anesthetize the ipsilateral hemisphere.
Should a persistent caroticobasilar anastomosis exist,
the target of the amobarbital would be the brain stem,
 Chapter 2: Applied Neurovascular Anatomy of the Brain and Skull 31

Figure 18 Lateral common carotid artery injection (A) and selective, late arterial phase injection of the ECA (B). The branches of the
ECA are identified. Note the tortuous course of the distal vessels (B) characteristic of external carotid vessels. The black arrow indicates
the sharp turn the middle meningeal artery makes just after passing through the foramen spinosum. Abbreviations: ST, superior thyroid;
L, lingual artery; F, facial artery; ECA, external carotid artery; ICA, internal carotid artery; AscP, ascending pharyngeal artery; IMax,
internal maxillary artery; MMA, middle meningeal artery; Occ, occipital artery; STA, superficial temporal artery; d, distal.

potentially resulting in respiratory arrest, stroke, or Anatomic Considerations: The Ascending

death (3). In this case, it would be necessary to select
the artery distal to the anastomosis to avoid this
complication. The same principle applies to balloon
test occlusion studies (27).
Among the list of complications for carotid
endarterectomy is the possibility of brain stem infarct
from a fractured embolus that occurs during this
procedure should a persistent hypoglossal artery be
present (28,29). Though this complication has not yet
been reported in the setting of carotid artery stenting,
it should be considered if a persistent hypoglossal
artery is present. In this case, the choice of stent length
and position would be important. A Y-stent might be
the optimal solution preserving flow routes to both
eloquent vascular distributions.
EXTERNAL CAROTID ARTERY
The external carotid artery (ECA) originates from the
common carotid artery in the neck. The named
branches in order of origin are the superior thyroid,
lingual, facial, ascending pharyngeal, occipital, poste-
rior auricular, superficial temporal, and internal max-
illary arteries (Fig. 18A). The ascending pharyngeal
artery (APA) further bifurcates into pharyngeal and
neuromeningeal trunks. The internal maxillary artery
terminates in the middle meningeal, accessory menin-
geal, and sphenopalatine arteries (Fig. 18B). Further
terminal branch description will be given later in this
text where relevant anastomoses apply.
Pharyngeal Artery
The APA is unique because it provides anastomotic
channels to the internal carotid, the vertebral artery,
and other branches within the external carotid circula-
tion (Fig. 19A) (14,30). It typically arises from the ECA,
but it can occasionally arise from the proximal ICA or
an aberrant posterior inferior cerebellar artery (PICA)
(3034). The APA starts as a common trunk and then
bifurcates into pharyngeal and neuromeningeal trunks.
The pharyngeal trunk terminates as the superior, mid-
dle, and inferior pharyngeal branch, providing rich
anastomotic connections to the internal maxillary
artery (middle pharyngeal via the descending palatine
artery and pterygovaginal artery via the accessory
meningeal artery) and the ICA (superior pharyngeal
via the inferolateral trunk and the recurrent artery of
the foramen lacerum). As the name implies, this por-
tion of the artery supplies the tissue of the oropharynx.
Although the artery is often difficult to see on an
external carotid angiogram, its clinical importance
exceeds its size in certain circumstances. Specifically,
the anastomotic channels previously described can
cloud the results of test balloon occlusion of the ICA
by providing collateral circulatory routes. These chan-
nels also become important during the embolization of
glomus jugulare, vagale, or tympanicum tumors sup-
plied predominantly by this artery.
The neuromeningeal trunk courses in a poster-
osuperior direction toward the foramen magnum. Its
32 Bell et al.

Figure 19 (A) Cartoon angiographic representation of the ascending pharyngeal artery and its anastomoses. (a) Middle pharyngeal
artery to internal maxillary artery via the descending palatine artery. (b) Pterygovaginal artery (terminal branch of the superior pharyngeal
artery) to internal maxillary artery via the accessory meningeal artery. (c) Superior pharyngeal artery to the ICA via the recurrent artery of
the foramen rotundum and the inferolateral trunk. (d) Clival branches (terminal branches of the neuromeningeal trunk) to the ICA via the
meningohypophyseal trunk. (e) inferior tympanic artery to ICA via the caroticotympanic branch. (f) Hypoglossal artery to the vertebral
artery via the odontoid arch system. (g) Neuromeningeal trunk to the vertebral artery via the odontoid arch system. (h) Neuromeningeal
trunk to the odontoid arch system. The odontoid arch then connects, at times, to the occipital artery. (B) Selective vertebral artery
injection. A direct anastomosis from the vertebral artery to the ECA via the APA is shown. Abbreviations: APA, ascending pharyngeal
artery; NmT, neuromeningeal trunk; PhB, pharyngeal branch; CCA, common carotid artery; ECA, external carotid artery; Vert, vertebral
artery; IMax, internal maxillary artery; dICA, distal internal carotid artery.

branches include the inferior tympanic, musculospi-
nal, hypoglossal, and jugular arteries, with additional
terminal branches to the internal auditory canal, the
clivus, and the odontoid arch. Clinically relevant
anastomoses occur between the hypoglossal and mus-
culospinal arteries to the vertebral artery, the inferior
tympanic branch to the ICA through the caroticotym-
panic artery, lateral clival branches directly to the ICA,
and ECA to ECA connections from the odontoid arch
system to the occipital artery (1,4,30). An example of a
direct anastomosis between the ascending pharyngeal
and vertebral artery is given in Figure 19B.
THE VERTEBROBASILAR SYSTEM
The vertebral arteries typically arise from the subcla-
vians bilaterally (V1). They proceed superiorly and
dorsally to enter the foramen transversarium at the
level of C6. The arteries subsequently travel to the
arch of C1, giving off a variable number of small
spinal muscular and segmental arteries (V2). Two
characteristic right-angle turns are noted on both AP
and lateral angiographic projections at C1 and C2 (V2)
(Figs. 20A and 22), which have been described as a
box on the AP projection. The artery then processes
dorsally to the atlanto-occipital joint and travels in an
anterosuperior direction to enter the dura (V4). Prior
to the vertebrobasilar junction, the artery gives off the
anterior spinal artery (ASA) and posterior inferior
cerebellar artery (PICA). The ASA supplies the ante-
rior spinal cord, and the PICA supplies the lower
brain stem, cerebellar tonsils, and the inferior aspect
of the cerebellar hemispheres. The basilar artery then
travels anterior to the brain stem, giving off the ante-
rior inferior cerebellar artery (AICA), multiple small
pontomesencephalic perforators, and the superior cer-
ebellar artery (SCA) (Figs. 20 and 21). There are mul-
tiple areas of collateral circulation between the SCA,
AICA, and the PICA, and distal parent artery sacrifice
in this area may be clinically silent (Fig. 23, white
arrows). The AICA and PICA may, at times, arise
from a common trunk (Fig. 22). This particular ana-
tomic variant may alter the treatment plan in certain
circumstances. The basilar artery subsequently bifur-
cates within the crural cistern into the PCA.
The Posterior Cerebral Artery
The PCAs, like the MCA and ACA, are segmentally
organized on the basis of the relevant surrounding
anatomy (Figs. 2325). The P1 segment starts at the
basilar bifurcation and extends to the insertion of the
 Chapter 2: Applied Neurovascular Anatomy of the Brain and Skull 33

Figure 20 Selective vertebral artery injection, transmaxillary projection (A) and gross anatomic specimen for comparison (B). Note the
course of the vertebral and basilar arteries with respect to the brain stem and cranial nerves. Abbreviations: Vert, vertebral artery; PICA,
posterior inferior cerebellar artery; AICA, anterior inferior cerebellar artery; B, basilar artery; SCA, superior cerebellar artery; PCA,
posterior cerebral artery; CN, cranial nerve; C1, first cervical vertebrae; C2, second cervical vertebrae. Source: From Ref. 5.

Figure 21 Lateral angiogram of the vertebral artery. Abbrevia-
tions: Vert, vertebral artery; SmB, spinomuscular branch; PICA,
posterior inferior cerebellar artery; B, basilar artery; AICA, ante-
rior inferior cerebellar artery; SCA, superior cerebellar artery;
PCA, posterior cerebral artery; C1, first cervical vertebrae; C2,
second cervical vertebrae.
Figure 22 Transmaxillary projection of the vertebral artery. Note
the bilateral absence of a true PICA, and a prominent bifurcation
of the AICA characteristic of an AICA-PICA complex. Abbrevia-
tions: PICA, posterior inferior cerebellar artery; AICA, anterior
inferior cerebellar artery.
34 Bell et al.
Figure 23 Lateral projection of the basilar artery from a verte-
bral artery injection. Collateral circulatory pathways are shown
with the segmental anatomy of the PCA. Note the filling of the
internal parietal arteries from this injection via the splenial artery.
The splenium of the corpus callosum is outlined by the splenial
artery and the lateral and medial posterior choroidal arteries. The
black arrow indicates the faint contrast blush within the posterior
thalamoperforating arteries from the basilar apex and P1. The
white arrows depict the collateral circulation of the distal cere-
bellar vessels. Abbreviations: PCA, posterior cerebral artery; B,
basilar artery; MpcA, medial posterior choroidal artery; LpcA,
lateral posterior choroidal artery; S, splenial artery; CalcA, cal-
carine artery; PoA, parietooccipital artery; IpA, internal parietal
artery; CC, corpus callosum.
Figure 24 Projection through the foramen magnum (Townes
projection), vertebral artery injection. The segmental anatomy of
the PCA is shown. P1 starts at the basilar artery and ends at the
insertion of the posterior communicating artery. P2 is divided into a
P2A within the crural cistern and P2P within the ambient wing
cistern. P3 begins at the quadrigeminal plate cistern and ends
at the origin of the calcarine and parietooccipital artery. The P4
segment includes the terminal cortical branches. The digitally
subtracted shadow of a 7.62-mm bullet is seen (FB). Abbrevia-
tions: PCA, posterior cerebral artery; AtA, anterior temporal artery;
P2A, anterior segment; P2P, posterior segment; PtA, posterior
temporal artery; PoA, parietooccipital artery; FB, foreign body.
Figure 25 Gross anatomic specimen of the medial
undersurface of cerebrum. The course and segmenta-
tion of the PCA is shown. Note the course of the
calcarine artery within primary visual cortex (Cuneus
and Lingula). The brain stem can also be seen medial
to the P2 segment. Perforating arteries from this seg-
ment supply the lateral brain stem and optic tract.
Abbreviations: PCA, posterior cerebral artery; ACA,
anterior cerebral artery; ICA, internal carotid art-
ery; CalcSulcus, calcarine sulcus; ParOccip, Sulcus-
parietooccipital sulcus. Source: From Ref. 5.
 Chapter 2: Applied Neurovascular Anatomy of the Brain and Skull 35

posterior communicating artery. The P2 segment is

divided into the anterior (P2A) and posterior (P2P) on
the basis of its cisternal location. The P2A starts at the
posterior communicating artery and travels around
the anterolateral aspect of the mesencephalon in the
crural cistern. The P2P continues posteriorly within
the paramesencephalic and ambient wing cisterns and
ends at the quadrigeminal plate cistern. Small perfo-
rating arteries, not well visualized on an angiogram,
arise from this segment and supply the cerebral
peduncles, brain stem, optic tracts, thalamus, choroids
plexus, and hippocampus. The posterior temporal
artery also emerges in this region. The P3 segment
starts at the quadrigeminal cistern (tectal plate) and
continues to the origin of the parieto-occipital and
calcarine arteries (P4).

Anatomic Considerations: The Distal

Posterior Cerebral Artery
Distal vascular anomalies in the posterior cerebral
circulation are difficult entities to treat. The surgical
approaches to the crural, paramesencephalic, ambient
wing, and quadrigeminal plate cisterns are certainly
elegant, but the associated morbidity may lend itself
to a treatment strategy that incorporates a less inva-
sive approach (7, 3538). Patients with pathology in
this region may present with hemiparesis (brain stem
perforators or compression), homonymous hemianop-
sia (compression of optic tract, infarction of calcarine
cortex), and occasionally fourth nerve compression
(Fig. 26) (7,39).
The elegant nature of the neural tissue fed by the
PCA system complicates the open surgical or endovas-
cular repair of vascular abnormalities in this region.
Surgical bypass followed by PAO is one successful
approach to complicated PCA pathology. Endovascu-
lar treatment without open surgery can reduce mor-
bidity, but the often necessary PAO can result in
additional deficit. There are diverging published opin-
ions concerning where along the PCA circulation PAO
is safe (36,40). Ciceri et al. treated 21 aneurysms in
20 patients with endovascular coil occlusion (36). The
parent artery was preserved in 14 patients, and PAO
was performed without preoperative test balloon
occlusion. Though relatively successful with proximal
PAO, the general recommendation posited by the
authors was that occlusion distal to P2 could be tol-
erated secondary to adequate distal collateral circula-
tion provided by the posterior temporal, lateral
posterior choroidal, medial posterior choroidal, and
splenial arteries. Conversely, proximal PCA occlusion
could be associated with brain stem infarct. However,
Hallacq et al. occluded the parent artery in 10 patients
with P2 segment aneurysms without postocclusion
deficit, concluding that P2 occlusion was in fact safe.
THE CEREBRAL VEINS
It is convenient to think of the cerebral venous anat-
omy as a construct of channels (sinuses) and veins
organized into a deep and superficial system. The
Figure 26 Artists rendition of the course of the distal PCA under
the surface of the tentorium cerebelli. An aneurysm in this loca-
tion could conceivably cause a fourth cranial nerve palsy sec-
ondary to its proximity to that nerve. Abbreviation: PCA, posterior
cerebral artery. Source: From Ref. 39.
sinuses receive the bulk of venous outflow from the
brain and terminate in the internal jugular veins.
The following will review the deep and superficial
venous anatomy seen on normal angiographic studies.
The Superficial Venous System
The superior sagittal sinus is the large midline vein
easily visualized on both AP and lateral angiographic
projections (Fig. 27). It receives direct inflow from the
hemispheres via the superficial frontal, parietal, and
occipital cortical veins as well as extra-axial inflow
from the diploic and meningeal veins. The superior
anastomotic vein of Trolard is the largest of the cor-
tical venous inflow tracts and is typically located in
the middle third of the sinus. The superior sagittal
sinus terminates at the torcular herophili at the con-
fluence of the sinuses. Here the straight sinus and the
superior sagittal sinus become the paired transverse
sinuses. The straight sinus receives venous inflow
from the inferior sagittal sinus, the vein of Galen,
and meningeal veins from the tentorium. The trans-
verse sinuses make a 908 turn under the asterion of the
skull to become the sigmoid sinuses. On a lateral
angiogram, the inferior anastomotic vein of Labbe
and the superior petrosal sinuses can be seen draining
into this area.
Figure 27 Lateral (A) and AP (B) projection, venous phase. Normal venous anatomy is shown. Abbreviations: IJ, internal jugular vein;
SigS, sigmoid sinus; TS, transverse sinus; SPS, superior petrosal sinus; SS, straight sinus; SSS, superior sagittal sinus; VoL, inferior
anastomotic vein of Labbe; BVoR, basal vein of Rosenthal; TsV, thalamostriate vein; VoG, vein of Galen; IcV, internal cerebral vein; AfV,
anterior frontal vein; MfV, middle frontal vein; PfV, posterior frontal vein; PrecV, precentral vein; VoT, superior anastomotic vein of Trolard;
ApV, anterior parietal vein; PpV, posterior parietal vein.

Figure 28 Representation of the main cerebral venous and sinus anatomy. Abbreviations: Ant, anterior; Post, posterior; Mid, middle;
Cent, central; Med, medial; Precent, precentral; Pericall, pericallosal; Car, Carotid; Cav, cavernous; SphenPar, sphenoparietal; Sup,
superficial; Sag, Sagittal; Inf, inferior; Paracent, paracentral; Cer, cerebral; Front, frontal; Bas, basal; Men, meningeal; Temp, temporal;
Tent, tentorial; Occip, occipital; Post, posterior; Calc, calcarine; Lat, lateral; Str, straight. Source: From Ref. 5.
 Chapter 2: Applied Neurovascular Anatomy of the Brain and Skull
Figure 29 Lateral injection of the ICA. A direct CC fistula is
shown. The cavernous sinus is best visualized during pathologic
conditions. Note the cerebellar cortical venous reflux, making this
particular CC fistula prone to causing subarachnoid hemorrhage.
Abbreviations: CC, carotid cavernous; Pp, pterygoid venous
plexus; IpS, inferior petrosal sinus; SpS, superior petrosal
sinus; CavS, cavernous sinus; RV, retinal vein.
The base of the brain contains multiple venous
sinuses that are clinically relevant. The cavernous
sinus is a paired structure composed of multiple
venous sinusoidal channels that anatomically encircle
the sella turcica (Fig. 30). This structure is not overtly
obvious on a normal angiogram, but becomes prom-
inent in the setting of direct carotid cavernous fistulas
(Fig. 29). Just posterior and inferior to this structure is
the midline basal sinus. This sinus receives inflow
from the superficial sylvian vein via the sphenopar-
ietal sinus, and outflow from the superior petrosal
sinus toward the sigmoid sinus.
The Deep Venous System
The deep venous structures are also easily visible on a
lateral angiogram. The basal veins of Rosenthal become
visible within the crural cisterns (Figs. 27A and 28).
They receive flow from the deep middle cerebral veins
and the anterior cerebral veins (Fig. 28). They subse-
quently course within the paramesencephalic and
ambient wing cisterns with the PCA to finally end at
the vein of Galen. The vein of Galen also receives
venous drainage from the internal cerebral veins. This
paired venous outflow receives predominant feeders
from the thalamostriate veins (Fig. 27A), the anterior
caudate veins, and the anterior septal veins lining the
37
Figure 30 AP projection of an ICA injection. A direct CC fistula
is shown. The cavernous sinus clearly outlines the sella turcica in
this view. Abbreviations: CC, carotid cavernous; ST, sella turcica;
CavS, cavernous sinus; Pp, pterygoid plexus.
lateral ventricles. The internal cerebral veins course
within the velum interpositum with the medial pos-
terior choroidal arteries and terminate at the vein of
Galen. The vein of Galen then empties into the
straight sinus.
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 3
Vascular Anatomy of the Spine and Spinal Cord
Armin K. Thron
Department of Neuroradiology, University Hospital,
RWTH Aachen University, Aachen, Germany
INTRODUCTION
Because of progress in microneurosurgery and inter-
ventional neuroradiology, intramedullary spinal vas-
cular lesions have become more and more accessible
and treatable. Unfortunately, a lack of knowledge
about spinal vascular anatomy is evident in many
conferences with neurologists and sometimes even
with neurosurgeons and neuroradiologists. This lack
of knowledge might be a reason for unsatisfactory
clinical results in the treatment of spinal vascular
diseases by invasive therapeutic techniques. Further-
more, magnetic resonance imaging (MRI) and mag-
netic resonance angiography (MRA) of blood vessels
in and around the spinal cord have substantially
improved. To provide a correct anatomical interpreta-
tion of the demonstrated blood vessels, knowledge of
the anatomy of spinal cord blood vessels is the first
prerequisite. At the end of the 19th century, Kadyi (1)
gave the most precise and detailed anatomical descrip-
tion of these blood vessels. His work was published in
1889, seven years after the first extensive and compre-
hensive study performed by Adamkiewicz (2).
This chapter deals with the essentials of spine
and spinal cord blood vessel anatomy (in parts
adapted from 3), outlines the possibilities of identify-
ing these vessels on tomographic images, and illus-
trates the main problems and pitfalls in the anatomical
evaluation of spinal vascular malformations.
ARTERIAL BLOOD SUPPLY
Sources of Arterial Blood Supply
to the Spine and Spinal Cord
The blood supply to the vertebral body, the paraspinal
muscles, the dura, the nerve root, and the spinal cord
is derived from segmental arteries (Fig. 1). These
vessels persist as intercostal and lumbar arteries in
the majority of the thoracolumbar region. Several
segments in the upper thoracic region have a common
feeder, which is the supreme intercostal artery.
Following intrauterine vascular rearrangements,
longitudinal arteries are established in the cervical
region. On each side, three vessels are potential
sources of spinal blood supply, namely, the vertebral
artery, the deep cervical artery, and the ascending
cervical artery.
In the sacral and lower lumbar region, sacral
arteries and the iliolumbar artery (supplying the L5
level) derived from the internal iliac arteries are the
most important supply to the caudal spine.
Generally, the segmental arteries supply all the
tissues on one side of a given metamere, with
the exception of the medulla. A spinal branch of the
posterior intercostal artery enters the vertebral canal
through the intervertebral foramen and regularly
divides into three branches: an anterior and a poste-
rior artery of the vertebral canal, which supply the
spinal column, and a radicular artery, which supplies
the dura and nerve root at every segmental level.
The hemivertebral blush, resulting from injection
of a segmental artery, may help in identifying the
artery. At the thoracic level, the artery is named
according to the number of the rib under which it
courses. The segmental arteries are connected across
the midline and between levels above and below,
through highly effective anastomoses (Figs. 2 and 7).
At certain segmental levels, this radicular artery
has persisted as a radiculomedullary artery, which
means that it follows the anterior and/or posterior
nerve roots to form and supply the superficial spinal
cord arteries (Fig. 1). The number of these radiculome-
dullary arteries is reduced during an embryonic trans-
formation process. From 2 to 14 (on average 6) anterior
radiculomedullary arteries persist as a result of this
ontogenic reduction of feeding vessels. The posterior
radiculomedullary arteries are reduced less drastically
from 11 to 16 vessels. Figure 3 demonstrates schemat-
ically the typical potential sources of arterial supply to
the anterior axis of the spinal cord.
Extra- and Intraspinal Extradural Anastomoses
1. An extraspinal system connects the neighboring
segmental arteries longitudinally. The vessels
course on the lateral aspect of the vertebra or
transverse process (Figs. 1, 2, and 7). This system
is highly developed in the cervical region where
the vertebral artery and the deep cervical and
40 Thron
ascending cervical arteries form the most effective
longitudinal anastomoses.
2. The intraspinal extradural system is mainly a
transverse anastomosis, but it also has longitudi-
nal interconnections. The retrocorporeal and
arteries are the relevant vessels for the supply of
bone and dura (Figs. 1, 2, and 7). These anasto-
moses provide an excellent collateral circulation
and therefore numerous segmental arteries can be
visualized by injection of one segmental artery
(Fig. 2).
The extra- and intraspinal anastomoses protect
the spinal cord against ischemia when pathologies,
such as arteriosclerotic disease of the aorta, cause focal
vessel occlusion.
Radicular Supply and Superficial
Spinal Cord Arteries
Several nomenclatures and classifications have been
used to describe spinal cord arteries. This variation is
an ongoing cause of misunderstanding. A recent clas-
sification proposed by Lasjaunias et al. (4) differen-
tiates three types of spinal radicular arteries: radicular,
radiculopial, and radiculomedullary.
The first type of spinal radicular artery is a small
branch present at every segmental level, which is
restricted to the supply of the nerve root. The second
type supplies the nerve root and superficial pial
plexus (e.g., posterior radicular artery). The third
type supplies the nerve root, pial plexus, and medulla.
This classification may offer some advantages to
the interventional neuroradiologist when compared
Figure 1 Blood supply of the spinal column and spinal
cord.
with classical differentiations because it stresses
the importance of the anterior supply for the gray
matter of the spinal cord parenchyma. From an ana-
tomical and linguistic point of view, however, it is not
a clear-cut differentiation because anterior and pos-
terior radicular arteries share in the blood supply of
the medulla and the posterior radicular arteries do
contribute to the supply of the central gray matter,
especially of the posterior horn.
We therefore suggest only a slight modification
of the older anatomical classification with the follow-
ing differentiation of spinal radicular arteries:
radicular arteries supplying only the nerve root and
the dura mater, but not the spinal cord;
anterior radiculomedullary arteries in which the per-
sistent medullary branch runs with the anterior
nerve root to join the longitudinal trunk, which
has been called the anterior spinal artery (Figs. 1
and 3); and
posterior radiculomedullary arteries in which the per-
sistent medullary branch accompanies the posterior
nerve root and joins the longitudinal systems of
posterolateral and/or posterior spinal arteries. The
first lies laterally and the second medially to the
posterior root entry zone. These longitudinally ori-
ented vessels are not continuous and may replace
each other (Figs. 1, 6, 7C, D, and 8C).
As has already been mentioned, the anterior
radiculomedullary supply is reduced to an average
of 6 radiculomedullary arteries (Fig. 3), whereas from
11 to 16 posterior radiculomedullary arteries persist
after embryonic life.
 Chapter 3: Vascular Anatomy of the Spine and Spinal Cord 41

Figure 2 Extra- and intraspinal extradural anastomoses. Selec-

tive injection in the first lumbar artery on the left opacifies homo-
lateral arteries as well as contralateral vessels. The typical
hexagonal configurations of the retrocorperal intraspinal anasto-
mosis (small arrows) as well as the extraspinal pretransverse and
anterolateral anastomoses (large arrows) are demonstrated. The
injected artery gives rise to an anterior radiculomedullary artery
(arrowheads), probably the Adamkiewicz artery. Note the hemi-
vertebral blush corresponding to the injected artery.
Figure 3 Sources of supply to the anterior spinal artery.

The thoracolumbar enlargement is the region

where the dominant anterior radiculomedullary
artery (arteria radicularis magna, or Adamkiewicz artery)
arises. However, in this region several posterior rad-
iculomedullary arteries may also be large-sized ves-
sels, which furnish blood supply to this area. They are
connected to the anterior spinal artery through two
anastomotic semicircles, called the arcade of the cone
(Figs. 3 and 6A).
The superficial distribution of blood to the spinal
cord is achieved by the above-mentioned anterior and
posterior longitudinal vessels, which have been
named anterior and posterior/posterolateral spinal
arteries. Both systems supply a superficial network
of smaller pial arteries that covers the spinal cord,
termed the vasocorona(Figs. 8 and 9). The anterior
spinal artery may be small or absent as a continuous
tract in the upper thoracic and upper cervical regions
of the spinal cord (Figs. 3 and 4).
The main source of arterial supply to the cord is
the anterior spinal artery (ventral axis), with a multi-
segmental distribution of blood and a distinct territory
of supply. It gives rise to the hemodynamically impor-
tant central (centrifugal) system, which supplies the
major part of the gray matter. Additionally, there are
branches to the pial system on the anterior and lateral
surface, supplying the ventral two-thirds of the vaso-
corona (Figs. 8 and 9A).
The posterior/posterolateral spinal arteries
distribute blood to the dorsal one-third of the
42 Thron
Figure 4 Anterior spinal artery in the cervical spinal cord.
The pattern of supplying vessels varies considerably, especially
in the upper spinal cord. (A) Photograph of an injected specimen.
Plexiform pattern of arterial supply in the upper cervical levels,
without formation of a midline anterior spinal artery. (B) X-ray film
in AP view. The anterior spinal artery is formed by a large
unilateral descending branch from the left vertebral artery
(arrow) and is reinforced by a large anterior radiculomedullary
artery at the C5 level on the right. The small descending branch
coming from the right vertebral artery (arrowhead) ends in this
network of small tortuous superficial arteries. Source: From
Ref. 13.
vasocorona, and in this way they share with central
artery branches in the supply of the posterior horn
and marginal parts of the central gray matter
(Fig. 9A).
The posterior/posterolateral arteries do not have
such a distinct territory of supply as the anterior
spinal artery, which means that they predominantly
reinforce the rope ladderlike network of posterior
pial arteries (Fig. 8C).
Figure 5 Demonstration of an anterior radiculomedullary feeder
to the cervical spinal cord by injecting the costocervical trunk on
the left. The ascending and descending branches (arrowheads)
are forming the anterior spinal artery at this level.
Differences in Arterial Supply of the Spinal
Cord Depending on Regions
Cervical Region
One of the ventral radicular feeders between C5 and
C8 is often distinctly larger (400600 mm) than the
others and was termed the artery of the cervical
enlargement by Lazorthes (5,6). It is more often
derived from the deep and ascending cervical arteries
than from the vertebral artery (Figs. 3 and 5). There-
fore, these vessels that originate from the thyrocer-
vical and costocervical trunks, respectively, must be
demonstrated on angiography for diagnostic and
interventional procedures. The average number of
anterior radicular feeders to the cervical medulla is
2 to 3.
The ventral feeders to the upper cervical cord,
originating from the intracranial section of the verte-
bral artery, may be very small. Their demonstration
on angiography is often impossible. If there are two
descending branches from both vertebral arteries, the
smaller or rudimentary vessel does not join the main
 Chapter 3: Vascular Anatomy of the Spine and Spinal Cord
Figure 6 X-ray film (AP view) of a contrast-injected human
spinal cord specimen with arterial filling. (A) Lumbar and (B)
thoracic regions. Note the different calibers of the anterior (large
arrowheads) and posterior radiculomedullary feeders (small
arrowheads) and of the anterior spinal artery (small arrows) at
different spinal cord levels. The important supply coming from
the artery of the lumbar enlargement is obvious as well as its
connection with the posterior arteries around the cone (arcade of
the cone) (black arrow). The system of posterior/posterolateral
arteries is discontinuous; the largest posterior radiculomedullary
feeder enters below and contralateral to the artery of Adamkie-
wicz in this specimen (oblique arrowhead). Source: From
Ref. 13.
midline trunk but ends separately as a large central
artery (Figs. 3 and 4).
Duplication of the anterior spinal artery over
some distance is frequent in this region; a pseudo-
island formation and even a net-like plexiform pattern
of arteries may be observed. Continuity of an anterior
spinal artery may not exist. All these variations have
to be regarded as a state more closely related to the
embryonic (or ontogenetic) condition (Fig. 4).
A descending branch from the vertebral artery or
posterior inferior cerebellar artery (PICA) constitutes
43
the posterior system of the upper cervical region. The
vessel may have a large caliber and originates in a
lateral position (lateral cervical artery) (7).
The number of central arteries in the cervical
enlargement is about 6/cm. They take a horizontal
course.
Thoracic Region
Occasionally, one segmental artery branches and sup-
plies two intercostal spaces. In this case, the dorsal
and spinal branch of one of the two segments may not
be seen. Therefore, a small posterior intercostal artery,
from which the spinal branch of this metamere arises,
must be looked for. This procedure may be crucial, for
example when searching for the site of a dural arterio-
venous fistula.
The upper and midthoracic regions are mostly
supplied by small radicular arteries (200400 mm), mak-
ing angiographical demonstration difficult (Fig. 3).
In addition, the ventral anastomotic tract (anterior spi-
nal artery) may be discontinuous throughout these
regions.
The pial system plays an important role in this
spinal cord region, which has relatively less gray
matter and more white matter tracts (Figs. 9A and
10A). On the posterior surface of the cord, the longi-
tudinal tracts may run in posterior/posterolateral
positions, thus indicating the functional identity of
these vessels (Figs. 6 and 8C).
The number of central arteries is only 2 to 3/cm
for this region. This fact explains the prevalence of
steeply ascending and descending central artery
branches (Fig. 10A). As pointed out earlier, the
impression of an intrinsic longitudinal anastomosis
on sagittal images was not confirmed on coronal
images of our microangiographic studies.
Thoracolumbar Region and Cauda Equina
One of the ventral feeders between T9 and L1 (excep-
tionally at L2 or L3) is always dominant (80100 mm)
and is therefore called the artery of the lumbar
enlargement (Lazorthes) or the great radicular artery
(Adamkiewicz) (Figs. 3 and 6). Below its level of
entrance, additional significant ventral feeders are
unusual.
Supply to the posterior system in this region
often includes two equally large dorsal feeders (400
500 mm) that enter the spine above or below the great
radicular artery (Fig. 6).
The ventral and dorsal systems are connected to
each other around the conus (arcade of the cone, rami
anastomotici arcuati) (1). This pattern may constitute a
significant anastomosis, comparable to the circle of
Willis.
The densest concentration of central arteries is
found in the thoracolumbar enlargement, where 6 to 8
vessels/cm can be counted on microangiograms
(Fig. 8B).
44 Thron
Intrinsic Spinal Cord Arteries
The arteries directly supplying the spinal cord are
central (or sulcal) arteries originating from the anterior
spinal artery and
perforating branches arising from the pial network
which covers the spinal cord.
The first type of perforating arteries constitutes a
centrifugal system. Each central artery (inner vessel
diameter, 100250 mm) penetrates the parenchyma to
the depth of the anterior fissure, courses to one side of
the cord, and branches mainly within the gray matter.
The second type of perforating arteries arises from the
pial covering of the cord (vasocorona) and penetrates
the white matter tracts from the periphery (centripetal
Figure 7 Angiographical demonstration and identification
of spinal cord arteries. (A, B) Selective injection of the 11th
intercostal artery with normal findings. (A) Frontal view.
Typical hairpin configuration and midline position of the
anterior radiculomedullary and anterior spinal arteries
[small ascending and larger descending branch at this
level (arrowheads)]. Note the extra- and intraspinal longitu-
dinal and transverse anatomoses (arrows) and the hemi-
vertebral blush. (B) Lateral view. Anterior location of the
artery demonstrated in (A) (arrowhead). The lateral projec-
tion is very helpful to differentiate the anterior or posterior
position of the artery with certainty, which may be difficult in
cases of scoliosis, and especially AVMs. (C, D) Injection of
the ninth intercostal artery in case of an intraspinal tumor.
(C) Frontal view. The segmental artery gives rise to an
anterior (arrowhead) and posterior (arrow) spinal cord sup-
plying artery. Note the different positions of the hairpin
curve and of the descending branches. (Displacement of
the anterior and posterior spinal arteries below the level of
the injection and the equal size of both vessels are due to
an intraspinal neurinoma.) (D) Lateral view. The anterior
(arrowhead) and posterior positions (arrow) of the anterior
and posterior spinal artery can be distinguished. Abbrevia-
tion: AVM, arteriovenous malformation.
system). These vessels are numerous, with a diameter
of up to 50 mm. Both types of intrinsic artery and
their region of supply can be appreciated on the axial
section of the microangiogram demonstrated in Fig-
ures 8, 9A, and 10A.
Superficial and Intrinsic Arterio-Arterial
Anastomoses
Arterio-arterial anastomotic interconnections are fre-
quent in the spinal cord.
The anterior spinal artery may be regarded as
the largest and most constant longitudinal anastomo-
sis (Figs. 3 and 6).
The posterior systems are not constantly devel-
oped or continuous. They include longitudinal and
 Chapter 3: Vascular Anatomy of the Spine and Spinal Cord 45

Figure 8 Anterior spinal artery, intrinsic arteries, and pial plexus demonstrated on microangiograms of the lumbar spinal cord. The spinal
cord has been cut into three coronal sections, each 2 to 3 mm thick; section length, 2.5 cm. (A) Anterior coronal section. Numerous
transverse and oblique branches from the anterior spinal artery (arrow) supply the anterior part of the superficial pial plexus called
vasocorona. (B) Middle coronal section. The central arteries, derived from the anterior spinal artery, course to one side of the cord and
branch mainly within the gray matter. From the surface of the spinal cord, perforating branches of the vasocorona penetrate and supply
the outer rim of fiber tracts and parts of the posterior horn. (C) Posterior coronal section. The larger posterolateral (arrows) and smaller
posterior spinal arteries (arrowheads) form a rope ladderlike network, supplying the posterior part of the vasocorona. The posterolateral
arteries are running laterally, the posterior arteries medially of the posterior roof entrance zone. Source: From Ref. 13.

transverse components and serve as anastomotic path-
ways and distribution channels, at least over some
segments (Figs. 6 and 8C).
The arcade of the cone has an anastomotic func-
tion, comparable to that of the circle of Willis.
Superficial interconnections between two or sev-
eral central arteries exist predominantly in the tho-
racic region. They run immediately deep and parallel
to the anterior spinal artery at the entrance of the
anterior fissure within the pial system (Fig. 10A).
Additionally, there are horizontal anastomoses
between central artery branches and the superficial
systems, especially in a centroanterolateral or centro-
posterolateral direction. However, they do not seem to
play an important role in the plasticity of blood sup-
ply to the spinal cord.
The most important observation to note is that
we could not demonstrate an intrinsic longitudinal
anastomoses between the ascending and descending
branches of the central arteries within the spinal cord
parenchyma (13), as was assumed by Adamkiewicz
(2) and Fazio and Agnoli (8).
VENOUS DRAINAGE
The pattern of venous drainage deviates substantially
from that of the arteries. Their arrangement will be
46 Thron

Figure 9 Comparison between intrinsic spinal cord arteries and veins demonstrated on microangiograms of axial sections of 2-mm
thickness. (A) Arteries at different levels of the spinal cord (anterior spinal artery, arrow; posterior/posterolateral spinal arteries at both
sides of the posterior root entry zone, small arrowheads). The central arteries (large arrowhead) are the predominant intrinsic feeders at
the level of the cervical and lumbar enlargements. They run within the anterior fissure and continue either to the right or left side of the
hemicord as a centrifugal system. The perforating branches are the predominant feeders of the thoracic spinal cord. They originate from
the superficial vasocorona as a centripetal system, and their territory of supply can very well be differentiated from the system of central
arteries. (B) Veins at different levels of the spinal cord. Radial and central veins are of almost equal size and drain to the pial covering of
the spinal cord (anterior and posterior median spinal veins, arrows). Source: From Ref. 13.

described in the direction of venous drainage from the sulcal veins (100250 mm) larger than the numerous
spinal cord parenchyma to the epidural plexus. radial veins.

Intrinsic Veins
Radial veins drain the blood of the spinal cord paren-
chyma. They show a horizontal, radial, and symmet-
rical course in most parts of the spinal cord (Fig. 9B).
Only in the lower thoracic cord, from the lower
lumbar enlargement to the conus medullaris, are the
Superficial Veins
At the level of the spinal pia mater, blood is accumu-
lated in essentially two longitudinal collectors: the an-
terior and posterior median spinal veins (Figs. 1014).
The anterior midline vein is located under the anterior
spinal artery (Fig. 11C). It has its largest caliber lumbo-
sacrally. In about 80% of cases, it runs together with the
 Chapter 3: Vascular Anatomy of the Spine and Spinal Cord
filum terminale as a sometimes very large terminal
vein to the end of the dural sac. The venous longitu-
dinal system on the anterior and posterior surfaces of
the cord is more variable in course, size, and localiza-
tion than the anterior spinal artery (Fig. 11). The lon-
gitudinal midline veins are not always continuous
tracts and may be replaced by secondary systems of
smaller caliber. The posterior median spinal vein takes
a course independent from the posterolaterally located
arteries and is especially large above the thoracolumbar
enlargement. Varicose convolutions are frequent (Figs.
11B and 14B). The posterior veins of the thoracolumbar
enlargement are undoubtedly the medullary vessels of
largest caliber (up to 1.5 mm in diameter) and are
rarely matched by superficial cervical veins. These
are the vessels most likely to be seen on MR images
(Figs. 13A and 14A). The vessels are part of a pial
47
Figure 10 Comparison between intrinsic spinal
cord arteries and veins demonstrated on micro-
angiograms of sagittal sections through the mid-
line of the spinal cord (section length, 2.5 cm;
thickness, 2 mm). (A) Arteries at a lower thoracic
level. Anterior spinal artery (large arrow) with loss
of contrast filling in small sections. The ascending
course of the central arteries with more vertical
than horizontal arborization within the gray matter
is demonstrated. The impression of an intrinsic
longitudinal anastomosis is not supported by
coronal images. Compare the small perforating
arteries of the posterior columns, originating from
the pial network of the vasocorona. (B) Veins at a
lower thoracic level. Anterior median vein (arrow)
and posterior median vein (double arrow) with
loss of contrast filling in sections. The sulcal
veins are less numerous but larger than the pos-
terior veins. Several of them join to form a com-
mon stem (arrowhead). The different pattern of
intrinsic arterial supply and venous drainage at
approximately the same spinal cord level is well
demonstrated in this comparison. Source: From
Ref. 13.
vascular network, which has been called the venous
plexus of the pia mater (9), the coronal pial plexus
(10,11), or the venous pial plexus (12).
Intraparenchymal Venous Anastomoses
These anastomoses are quite common. However, they
are not distributed uniformly over the length of a
spinal cord. They are of two types.
Anastomoses of the first type are complex and
connect central and peripheral branches (sulcal and radial
veins 100200 mm in diameter). They are very frequent
and drain to smaller veins of the superficial pial plexus.
More important are anastomoses of the second
type, which are transmedullary midline anastomoses
from 300 to 700 mm in diameter, connecting the
median veins on both sides of the cord. They do not
48 Thron

Figure 11 Superficial spinal cord veins. (A) Photograph of the dorsal aspect of a spinal cord specimen following ink injection into the
veins at cervical and thoracic levels. The posterior median vein has a variable size at different levels. Three large radiculomedullary veins
(arrows) and some smaller ones can be seen. (B) X-ray film (AP view) of a contrast-injected thoracolumbar spinal cord specimen. There
is much tortuosity mainly of the posterior spinal cord veins (posterior venous plexus). Three large radiculomedullary veins accompany
lumbar or sacral nerve roots to reach the epidural space (arrows). (C) Photograph of an injected spinal cord specimen with filling of the
ventral veins at the thoracic level. Note the hairpin configuration of the AMV, where it continues as RV. This configuration is very similar to
the arterial one. The nonfilled anterior spinal artery is running beside or over the vein (arrow). Abbreviations: AMV, anterior median vein;
RV, radicular vein.

receive tributaries from the intrinsic vessels. Because
of their size, they are not only seen on microangio-
grams (Fig. 13B) but may also be seen on angiography
or MRI (Fig. 13A). Through these large anastomoses,
blood can easily be directed from one side of the cord
to the other (13).
Differences in the Venous Drainage
Depending on Spinal Cord Region
Cervical Region
Radial symmetry of intrinsic veins is very pronounced
in the cervical spinal cord. Transmedullary midline
anastomoses are also very frequent, but they are of
smaller caliber in the upper cervical region than those
in the lower cervical and upper thoracic regions. The
anterior median vein was frequently larger than the
posterior median vein in our material. Both veins
connect to the brain stem veins and basal sinuses
around the foramen magnum. Additionally and pre-
dominantly radicular outflow to the epidural plexus
occurs at many levels (Fig. 11A).
Thoracic Region
The greatest concentration of large transmedullary
anastomic veins is found in the cervicothoracic region
(12/cm) followed by the mid- and lower thoracic
levels (Fig. 14B), where they are more widely
Chapter 3: Vascular Anatomy of the Spine and Spinal Cord 49

Figure 12 DSA of an artery of Adamkiewicz with arterial and

venous phase. (A) Typical hairpin course between the anterior
radiculomedullary artery and the descending branch of the ante-
rior spinal artery. (B) Venous phase showing the radiculomedul-
lary vein coincidentally at the same level. The configuration
between midline and radiculomedullary veins is the same. This
configuration is important to know for the interpretation of angio-
grams in case of an AVM with early venous filling or of spinal
MRAs with insufficient time resolution. Abbreviations: DSA, dig-
ital subtraction angiography; AVM, arteriovenous malformation.
Source: Courtesy of Prof. G. Schroth, Berne, Switzerland.

Figure 13 Venous midline anastomoses. (A) T1-

weighted sagittal MRI following injection of the contrast
medium. Demonstration of a large intramedullary mid-
line anastomosis between the anterior and posterior
midline veins in a normal subject (arrow). Source:
Courtesy of Prof. D. Petersen, Lubeck, Germany. (B)
Transparenchymal anastomosis near the medullary
cone with a caliber of 0.7 mm (arrows). Microangiogram
of a midsagittal cut with venous filling (same specimen
as in Fig. 10B). Note the larger caliber of the anterior
vein at the level of the cone compared with the posterior
vein. Source: From Ref. 13.
50 Thron

Figure 14 Superficial spinal cord veins in the lumbar spinal cord and cauda equina. (A) MRI of T1-subtraction image. The anterior
median vein is running together with the filum terminale to the end of the caudal sac (arrowheads), which can be an abnormal arterialized
vein or a normal variant as is shown in (B, C). (B) X-ray film of an injected specimen in lateral projection. Tortuous posterior venous
plexus at the level of the lumbar enlargement (small arrows). The anterior median vein (arrowhead) continues as a terminal vein (vein of
the filum terminale). Several transmedullary anastomoses can be assumed in this projection radiography (small arrowheads).
(C) Microangiogram of the cone with a large terminal vein (arrowhead). Source: (B) and (C) from Ref. 13.

separated. Anterior and posterior median veins are
mostly of equal size.
Lumbar Region
In this region, sulcal veins may be considerably larger
than radial veins (Fig. 9B). The posterior median spi-
nal vein is particularly large above the thoracolumbar
enlargement (Fig. 14B), frequently forming varicose
convolutions (the so-called posterior venous plexus).
The anterior median spinal vein reaches its maximum
caliber in this region, and it is important to note that
the vein of the filum terminale is the continuation of
this anterior median vein (Fig. 14). Alternatively, the
anterior vein can follow a sacral nerve root to reach
the sacral epidural space (Fig. 11B). The midline veins
of the thoracolumbar enlargement are the largest
blood vessels of the spinal cord (Figs. 13 and 14).
When demonstrated on contrast-enhanced MRI stud-
ies, or CT myelography, they should not be mistaken
for spinal cord arteries.
Radiculomedullary Veins and
the Transdural Course
The superficial venous blood collectors drain into the
epidural venous plexus through radicular veins
(Fig. 11). The transition of the midline vessel to the
radicular vein forms a hairpin course, similar to the
arterial configuration (Fig. 11). Therefore, on angio-
graphic images, the vein might be mistaken for an
 Chapter 3: Vascular Anatomy of the Spine and Spinal Cord 51

Figure 15 AVM at the level of the cone, supplied by two posterolateral feeders and the anterior spinal artery. (A) MRA showing the
malformation as a whole and the main drainage into a considerably enlarged terminal vein (arrow). (B) Unsubtracted angiogram. Typical
midline position of the anterior spinal artery. Supply from this vessel is mostly running through the arcade of the cone (arrowheads) to the
posterior surface. (CE) DSA. Note the somewhat different hairpin configurations of anterior and posterolateral feeders in AP view
(arrowheads). The largest part of the nidus is lying posteriorly (arrows). (F) Horizontal interconnections (black arrows) between the
posterolateral tracts (arrowheads) are visualized with increasing peripheral resistance during embolization.

artery (Fig. 12), particularly when an arteriovenous
malformation (AVM) with early venous filling is
present. For the same reason, it may be impossible
to distinguish an anterior spinal artery from an ante-
rior spinal vein on magnetic resonance images as long
as no sufficient time-resolved MRA is available. From
an anatomical point of view, the number of venous
outlets is high. In some studies, on average 25 rad-
icular veins were counted on the anterior and poste-
rior surfaces of the cord (14,15). However, purely
52 Thron
Figure 16 SDAVF T5 level. The AV shunt is at the level of the
dura mater (arrow) and is directed at two veins coming from
upward and downward. The mass of dilated veins resembles an
AVM, but no spinal cord artery is involved. Abbreviations: DSA,
digital subtraction angiography; SDAVF, spinal dural arterio-
venous fistula; AVM, arteriovenous malformation.
radicular veins might have been included in this
number. If smaller veins (<250 mm in diameter) are
excluded, the number of radiculomedullary veins
draining the spinal cord is from 6 to 11 for the anterior
and from 5 to 10 for the posterior systems (1,16). These
latter studies are in agreement with a study performed
by Jacobs (17). In addition, Moes and Maillot (18)
described fibrotic radicular veins at thoracic levels.
These veins may contribute to the vulnerability of the
spinal venous system, such as in the chronic impair-
ment of venous drainage in Foix and Alajouanine
disease (19) as a late complication of dural arterio-
venous fistula (AVF) (20).
The transdural course of radicular veins exhibits
special features (3). The presence of venous valves
described by Oswald (21) could not be confirmed in
later studies. Instead, an oblique and zigzag course with
considerable narrowing of the lumen was first described
by Tadie et al. (22). They concluded that this configura-
tion might act as an anti-backflow system, protecting the
spinal cord against high pressure in the extraspinal
veins. A study performed by Otto (23) is in agreement
with their findings, although this arrangement did not
always prevent reflux from the epidural plexus to the
superficial spinal cord veins when a contrast medium
was injected in the postmortem specimen (23).
Extradural Venous Spaces and
the Extraspinal Venous System
The extradural plexus, well demonstrated by spinal
contrast venography, extends as a continuous system
from the sacrum to the skull base. It drains the spinal
cord and surrounding structures.
Drainage of blood from the spine (including
spinal cord) occurs through the internal and external
venous vertebral plexus and also extends as a contin-
uous system from the sacrum to the base of the skull.
They are identifiable as anterior and posterior sys-
tems; the anterior internal vertebral plexus is larger
than the posterior internal system. The external sys-
tems run anterior to the body of the vertebrae (ante-
rior external plexus), while the posterior external
plexus lies posterolateral to the vertebral bodies.
This valveless system is connected with the
azygos and hemiazygos venous systems by intercostal
or segmental veins and in the cervical region with the
vertebral and deep cervical veins. The segmental veins
in the lumbar region are connected by the ascending
lumbar vein, joining the azygos (right side) and hemi-
azygos veins (left side) (3).
ANATOMICAL EVALUATION OF AVMs
Some important problems and pitfalls in the clinical
application of blood vessel anatomy concerning spinal
AVMs should be mentioned and explained. They are
illustrated in Figures 1519.
1. Prior to a therapeutic intervention, it is essential to
identify the feeders of a spinal AVM from both the
anterior and posterior circulation. Figure 15 illus-
trates the different configuration of the hairpin
curve in anterior and posterior radiculomedullary
arteries. Nevertheless, it is essential to have a
lateral projection for a definite identification.
2. Spinal dural arteriovenous fistulas (SDAVFs) may
look very similar to AVMs (Fig. 16). But as long as
no typical radiculomedullary artery is involved,
the arteriovenous (AV) shunt is much more likely
situated at the level of the dura mater.
3. Discrimination between a perimedullary fistula
(fistulous type of an AVM) and a SDAVF may
be difficult if the arterialized vein looks like an
anterior radiculomedullary feeder with a hairpin
curve (Fig. 17). This event is not rare in SDAVF at
lower lumbar levels when the arterialized vein
is one of the large lumbar veins shown in the
postmortem specimen of Figure 11B. To avoid
misinterpretation, careful analysis of the vessel
anatomy in the region of the intervertebral fora-
men is important as well as a look at the further
course of the vessel on the spinal cord surface on
later images (Fig. 17C). If you are unable to iden-
tify an AV shunt (fistula) on or within the spinal
cord, ask yourself whether the intradural blood
vessels as a whole could not be veins (Fig. 17).
4. Spinal cord supplying arteries and a SDAVF may
be observed at the same level and same side as
Figure 17 DSA of a SDAVF at the L3 level (arrowhead). (A) The blood vessel that is opacified first resembles a radiculomedullary artery.
It runs upward to the cone and lumbar enlargement and exhibits a narrow curve. (B) Anterior position of the blood vessel in the lateral
view. (C) Filling of typical veins on the later image in the AP view confirms that the whole of intradural vessels are veins. The configuration
of a radiculomedullary vein can be very similar to that of an artery (compare Figs. 11 and 12). Abbreviations: DSA, digital subtraction
angiography; SDAVF, spinal dural arteriovenous fistula.

Figure 18 DSA of a SDAVF with an anterior radiculo-

medullary artery entering at the same foramen. (A) AP
view. The artery (arrowheads) is partially superimposed by
the enlarged veins (arrow). (B) The lateral view demon-
strates the anterior position of the artery (arrowheads) and
the posterior position of the mass of veins (arrow). Abbre-
viations: DSA, digital subtraction angiography; SDAVF,
spinal dural arteriovenous fistula.
54 Thron
demonstrated in Figure 18. They are better dis-
criminated on lateral views.
5. If an anterior or posterior spinal artery seems to be
too large for the region to be supplied or if it
extends below the level of the cone, it should be
followed caudally. This is the only way not to miss
the small AVMs of the filum terminale (Fig. 19).
ACKNOWLEDGEMENT
Special thanks to Walter Korr, RWTH Aachen Univer-
sity, for technical assistance in the computer graphic
design of Figs. 1 and 3.
REFERENCES
1. Kadyi H. Uber die Blutgefae des menschlichen Rucken-
markes. Lemberg: Grubnowicz u Schmidt, 1889.
2. Adamkiewicz A. Die Blutgefae des menschlichen Ruck-
enmarkes. II.Teil: Die Gefae der Ruckenmarkoberflache.
Sitzungsberichte der Akademie der Wissenschaften in
Wien, Mathematisch-Naturwissenschaftliche Klasse
1882; 85:101130 (abstr 3).
3. Thron A. Vascular anatomy of the spine. In: Byrne James,
ed. Interventional Neuroradiology. Oxford: Oxford Uni-
versity Press, 2002.
4. Lasjaunias P, Berenstein A, ter Brugge K. Surgical Neuro-
angiography. Volume1: Clinical Vascular Anatomy and
Variations. 2nd ed. New York: Springer, 2002.
Figure 19 AVM of the filum terminale (DSA, AP
views). (A) The anterior spinal artery (black arrows) is
not unusually enlarged, but it continues without a
change in caliber below the level of a cone in normal
position. (B) At the L4 level, a second blood vessel is
opacified that is a little bit larger than the artery and
runs in upward direction (artery, black arrow; arterial-
ized terminal vein, arrowheads). The clinical signifi-
cance of this small AV shunt (white arrow) was
considerable. Abbreviations: AVM, arteriovenous mal-
formation; DSA, digital subtraction angiography.
5. Lazorthes G, Poulhes J, Bastide G, et al. La vascularisation
arterielle de la moelle. Recherches anatomiques et appli-
cations a la pathologie medullaire et a la pathologie
aortique. Neuro-Chirurgie 1958; 4:319.
6. Lazorthes G, Gonaze A, Djindjian R. Vascularisation et
circulation de la moelle epiniere. Paris: Masson, 1973.
7. Lasjaunias P, Vallee B, Person H, et al. The lateral spinal
artery of the upper cervical spinal cord. J Neurosurg 1985;
63:235241.
8. Fazio C, Agnoli A. The vascularization of the spinal cord.
Anatomical and pathophysiological aspects. Vasc Surg
1970; 4:245257.
9. Tveten L. Spinal cord vascularity. The venous drainage of the
spinal cord in the rat. Acta Radiol Diagn 1976; 17:653662.
10. Gillilan LA. Veins of the spinal cord. Neurology 1970;
20:860868.
11. Turnbull JM, Breig A, Hassler O. Blood supply of cervical
spinal cord in man; a microangiographic cadaver study.
J Neurosurg 1966; 24:951965.
12. Crock HV, Yoshizawa H. The blood supply of the verte-
bral column and spinal cord in man. Wien, New York:
Springer, 1977.
13. Thron AK. Vascular anatomy of the spinal cord. Wien,
New York: Springer, 1988.
14. Jellinger K. Zur Orthologie und Pathologie der Rucken-
markdurchblutung. Wien, New York: Springer, 1966.
15. von Quast H. Die Venen der Ruckenmarkoberflache.
Gegenbaurs Morphologisches Jahrbuch 1961; 102:3364.
16. Suh TH, Alexander L. Vascular system of the human
spinal cord. Arch Neurol Psychiat 1939; 41:659677.
17. Jacobs T. Venae radiculares. Anatomische Untersuchungen
zur venosen Drainage des menschlichen Ruckenmarkes.
 Chapter 3: Vascular Anatomy of the Spine and Spinal Cord
Thesis. Medizinische Fakultat der Rheinisch-Westfalischen
Technischen Hochschule Aachen, 1996.
18. Moes P, Maillot C. Les veines superficielles de la moelle
epiniere chez lhomme. Essai de systematisation. Archives
dAnatomie, dHistologie et dEmbryologie Normales et
Experimentales. Extrait du tome 64. Paris, Colmar: Edi-
tions Alsatia, 1981:5110.
19. Foix Ch, Alajouanine TH. La myelite necrotique subaigue.
Rev Neurol 1926; 33:142.
20. Thron A, Koenig E, Pfeiffer P, et al. Dural vascular anoma-
lies of the spinean important cause of progressive myel-
opathy. In: Cervos-Navarro J, Ferszt R, eds.Stroke and
Microcirculation. New York: Raven Press, 1987.
55
21. Oswald K. Untersuchungen uber das Vorkommen von
Sperrmechanismen in den Venae radiculares des Men-
schen. Thesis. Berlin, 1961.
22. Tadie M, Hemet J, Aaron C, et al. Le dispositif protecteur
anti-reflux des veines de la moelle. Neuro-Chir 1979;
25:2830.
23. Otto J. Morphologie des Sperrmechanismus am Dura-
durchtritt der Venae radiculares des Menschen. Neuro-
radiologische und histologische Befunde. Thesis.
Medizinische Fakultat der Rheinisch-Westfalischen Tech-
nischen Hochschule Aachen, 1990.
 4
Intracranial Collateral Routes and Anastomoses
in Interventional Neuroradiology
David S. Liebeskind
UCLA Stroke Center, University of California,
Los Angeles, California, U.S.A.
INTRODUCTION
Collateral circulation in the brain compensates for
obstruction to arterial inflow or venous drainage (1).
Descriptions of collateral vessels date back to the
founding of neurology. Centuries after Sir Thomas
Willis described arterial collaterals and their potential
significance in disease, angiography illustrated the
influential role of these routes. Hemodynamic studies
later emphasized the critical impact of collaterals, yet
subsequent imaging advances diverted attention
away from angiography, seeking neuroprotection
and targeting tissue ischemia. In the routine clinical
practice of interventional neuroradiology, arterial and
venous intracranial collaterals are influential factors in
the diagnosis, treatment, and prognosis of various
cerebrovascular disorders.
Knowledge of collateral anatomy and patho-
physiology may expand our understanding of numer-
ous disorders. Correlative studies of imaging features
and angiography may facilitate diagnosis and broaden
perspectives on novel treatment strategies. This chap-
ter reviews current knowledge of arterial and venous
collaterals, emphasizing the specific implications of
collaterals in various disorders.
ANATOMY
The anatomy of intracranial collaterals greatly influ-
ences the capacity of these channels to provide alter-
native blood flow routes across different regions, with
collateral capacity primarily determined by luminal
caliber. A description of arterial collateral anatomy
may be subdivided between common routes, includ-
ing Willisian collaterals at the circle of Willis or
leptomeningeal anastomoses, and atypical circuits
that may develop in response to particular lesions.
Similarly, venous collateral anatomy may be
described through the typical anastomotic routes
and the atypical, a category in which the diversity
and complexity of routes is enormous. Some connec-
tions such as the posterior communicating artery
(PCoA) represent embryonic remnants, whereas
other routes form only in response to disease. There
are also numerous collateral extracranial-intracranial
(EC-IC) routes, not discussed herein, for both arterial
and venous flow diversions. Much of the knowledge
regarding the anatomy of intracranial collaterals stems
from historical descriptions over the last few hundred
years. Only recently, with the advent of angiography
and modern imaging techniques, have the functional
correlates of these blood flow routes been established.
Prior reports have classified collateral routes as pri-
mary or secondary functional routes on the basis of
anatomical location, yet this classification may be
oversimplified, as great variability exists. The knowl-
edge of intracranial collateral anatomy in humans is
particularly important in understanding ischemic
stroke and other clinical cerebrovascular disorders,
as there are considerable differences in anatomy that
may preclude successful translation of therapeutic
approaches studied in animals (2). Species differences
in the configuration of collaterals may also be com-
pounded by differences in collateral anatomy among
various individuals or populations.
The circle of Willis provides numerous potential
routes for blood flow diversion (Fig. 1). All of the
Willisian segments, including the anterior communi-
cating artery (ACoA), the proximal anterior cerebral
artery (ACA), the PCoA, and the proximal posterior
cerebral artery (PCA), may facilitate flow diversion in
either direction depending on intraluminal pressure
gradients. All of these segments may also be atretic or
hypoplastic, yet they retain the ability to develop
significant blood flow capacity and luminal expan-
sion. These arterial segments are relatively closely
matched in size and vessel wall characteristics with
respect to their parent arteries. This configuration
allows for interhemispheric collateral flow or compen-
sation for gradients that may develop between the
anterior and the posterior circulations. Much empha-
sis has been placed on the anatomy of the PCoA (3,4).
Various terms, including persistent or fetal PCoA
anatomy, have been used to differentiate the status
of this segment on the basis of diameter measure-
ments at autopsy or on imaging studies, such as
magnetic resonance angiography (MRA), where the
status of this vessel or dominance is described in
58 Liebeskind

Figure 1 Schematic illustration of the circle of Willis and potential Willisian collaterals, including ACoA (a), proximal ACA (b), PCoA
(c), and proximal PCA (d). Abbreviations: ACoA, anterior communicating artery; ACA, anterior cerebral artery; PCoA, posterior
communicating artery; PCA, posterior cerebral artery.

relation to the proximal PCA. Descriptive terms of the

opposite situation, in which there has been involution
of the PCoAs embryonic origin from the internal
carotid artery (ICA) resulting in a hypoplastic PCoA,
have questionable validity, as even small-diameter
remnants may once again provide blood flow if the
need arises. Arterial patterns at the circle of Willis
have been categorized by citing the prevalence of
certain configurations, but such descriptive data are
also questionable, as anatomy may change with dis-
ease and age or vary among populations.
The leptomeningeal anastomoses bridging
distal reaches of the major cerebral arteries are small
(*50400 mm) arteriolar connections that allow for
retrograde perfusion of adjacent territories (Fig. 2)
(5,6). Such connections display variable configura-
tions, including end-to-end anastomoses, end-to-side
connections, and azygous variants (6). These arteriolar
anastomoses adjoin the middle cerebral artery (MCA)
with both the ACA and the PCA. Anastomoses from
the ACA potentially feed the superior or anterior
divisions of the MCA, with most of the posterior or
inferior division MCA collateral flow arising from the
PCA. Such connections are relatively sparse between Figure 2 Schematic illustration of principal supratentorial lep-
the ACA and the PCA. The seminal work of Vander tomeningeal anastomoses in the brain, including ACA-MCA
Eecken and Adams on 20 human cadavers delineated (a) and PCA-MCA (b) routes. Abbreviations: ACA, anterior cere-
the principal characteristics of leptomeningeal anasto- bral artery; MCA, middle cerebral artery; PCA, posterior cerebral
moses, illustrating considerable variability in the size, artery.
number, and location of these collaterals (6). Such
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
great variability likely influences the results of any
particular anatomical study and accounts for much
controversy in correlative studies of collateral function
with age. Anastomoses also converge over the cere-
bellar convexities, where the distal branches of the
posterior inferior cerebellar arteries (PICAs), anterior
inferior cerebellar arteries, and superior cerebellar
arteries (SCAs) meet (Fig. 3). Because of the symmetric
anatomy of posterior fossa structures, such anastomo-
ses may allow for collateral flow between cerebellar
hemispheres and from proximal to distal aspects of
the basilar distribution.
In cases in which flow demands and pressure
gradients exceed the capacity of primary arterial
routes and Willisian or leptomeningeal collaterals,
atypical routes of collateral flow may develop. Some
collateral routes may utilize the paths of normal
variants, such as azygous connections between the
ACAs. The anterior and posterior choroidal arteries
may distribute blood flow in either direction between
the anterior and posterior circulations. In cases of
moyamoya, this choroidal network is commonly
recruited. Other moyamoya arterioles pervade sub-
cortical structures, meandering around occluded
MCAs. Anastomoses may shunt flow between the
PCA and the SCA at the tentorial edge. More unusual
arterial collateral routes may also arise, commonly in
association with prominent EC-IC collaterals. Atypical
collaterals can be demonstrated in almost any config-
uration, limited to an extent solely by physical barriers
such as the falx or tentorium.
Figure 3 Schematic illustration of cerebellar anastomoses,
demonstrating potential collateral flow between SCA (a), AICA
(b), and PICA (c). Abbreviations: SCA, superior cerebellar artery;
AICA, anterior inferior cerebellar artery; PICA, posterior inferior
cerebellar artery.
59
Venous collateral anatomy is best understood in
light of typical venous flow patterns (Fig. 4) (7,8).
Venous drainage is balanced by superficial and deep
systems, with the transcerebral veins allowing for
potential shunting in either direction. The superficial
system, including the cortical veins and superior
sagittal sinus, typically empties the majority of out-
flow toward the right transverse and sigmoid sinuses
and into the jugular. The anastomotic veins of Trolard
and Labbe shunt flow across the cerebral hemisphere
to drainage pathways with lower pressures. Similarly,
cortical veins share connections, allowing for diver-
sion of flow. The deep system includes the choroid
plexuses and draining veins of the thalami, striatum,
periventricular white matter, limbic regions, and ros-
tral brain stem. Larger emissaries of this system
include the basal veins, vein of Galen, and straight
sinus. The deep system may drain via the straight
sinus and into the left transverse system or, alterna-
tively, send flow anteriorly toward the basal veins.
Numerous anastomoses abound toward the inferior
surface of the brain, allowing for drainage of the deep
system. The deep middle cerebral vein, inferior and
superior petrosal sinuses, and the basilar plexus may
shuttle flow across these regions. Because of the vari-
ability in venous outflow patterns and potential anas-
tomoses to relieve focal venous hypertension, minimal
attention has been placed on systematic characteriza-
tion of venous collateral anatomy.
Figure 4 Schematic illustration of intracranial venous anatomy
and typical collateral routes, including vein of Trolard (a), vein of
Labbe (b), deep middle cerebral vein (c), superior petrosal sinus
(d), pterygoid plexus (e), inferior petrosal sinus, and basilar
plexus (f).
60 Liebeskind
Figure 5 Right ICA injection on angiography, demonstrating Willisian and leptomeningeal collateral flow in acute stroke due to left ICA
occlusion. Abbreviation: ICA, internal carotid artery.
EPIDEMIOLOGY
The epidemiology of intracranial collaterals has occa-
sionally been broached in the literature, citing varia-
tions in Willisian anatomy or unfounded theories
related to collateral development in different cohorts,
such as the elderly. Most of these studies have used
anatomical data based on autopsy series. Unfortu-
nately, this approach of using anatomical postmortem
data to describe potential collateral function does not
make sense when one considers the dynamic changes
in collateral flow that take place during life. Studies of
Willisian configuration in normal individuals are also
limited, as collaterals are irrelevant in the absence of
disease. Functional assays such as angiographic dem-
onstration of collateral flow during particular clinical
scenarios, such as acute ischemic stroke, provide fur-
ther information (Fig. 5), yet serial changes or a reflec-
tion of collateral development may still go unresolved.
Other reports in the literature have extrapolated find-
ings on coronary or peripheral arterial collaterals to
the cerebral circulation, without validation. Much
speculation has addressed the influence of age on
collateral flow, yet considerable variability with intra-
cranial collaterals likely occurs with increasing age (9).
There is scant epidemiological data on arterial collat-
eral flow, via Willisian or leptomeningeal routes, even
within a specific disease state, and the epidemiology
of venous collaterals is unknown.
PATHOPHYSIOLOGY
The pathophysiology of collateral circulation in the
brain has largely been unexplored. Much of the
knowledge regarding arterial collaterals has been
extrapolated from studies of collateral circulation in
other vascular beds or in animal models in which vast
differences exist with respect to collateral anatomy.
Venous collateral pathophysiology remains virtually
completely unknown. Most of the very few studies of
collateral flow in humans relate to anatomical patterns
and resultant blood flow, yet very little is known
about collateral recruitment. The process of arterio-
genesis, or the recruitment and development of pre-
existing arterioles to accommodate significant flow
changes, must be distinguished from angiogenesis,
the de novo growth of vessels (10). Features of both
may be simultaneously involved with various cere-
brovascular disorders, yet the role of these processes
is quite distinct. Furthermore, although arterial collat-
erals may be emphasized in acute ischemic stroke,
there are likely changes that take place in the venous
system as well. Similarly, failure of venous collateral-
ization in cerebral venous thrombosis (CVT) may
ultimately affect arterial inflow, leading to ischemia.
As a result, the arterial and venous components must
be considered in concert. Venogenesis, the venous
counterpart of arteriogenesis, is assumed to be similar
to the pathophysiological events that accompany the
arterial process. Time is also a critical variable, as the
capacity of collaterals to adapt to blood flow derange-
ments changes with time. The particular role or influ-
ence of collaterals in specific disorders is considered
in subsequent sections of this chapter. With all of these
entities, however, it remains important to distinguish
the presence of collaterals at a specific time point
versus the development or collateralization process
itself.
The presence or extent of collaterals defined on
angiography or imaging reflects the result of an adap-
tive process responding to significant blood flow
alterations. The process of collateralization may be
best studied in cases in which collaterals are subopti-
mal or in cases with progressive ischemia or conges-
tion, allowing for investigation over a prolonged time
course. In cases of acute stroke with exuberant collat-
erals, the process may be obviated or fully realized.
The pathophysiology of arteriogenesis has been estab-
lished in the peripheral and coronary circulations
(11,12). Arteriogenesis is principally mediated by
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology 61

Figure 6 Table summary of the critical differences between arteriogenesis and angiogenesis and implications in acute cerebral
ischemia.

increased fluid shear stress due to mechanical forces retrograde fashion. Such reverse arterial flow via
that accompany pressure gradients across anastomotic selective daughter branches is extremely unusual
vessel segments. Inflammation plays a key role, (Fig. 7), unlike other blood flow routes in the systemic
incited by cytokine upregulation and macrophage circulation. This pattern of blood flow violates the
infiltration due to mechanical events at the anastomo- major hemodynamic principal of Murrays law,
ses (13). Vascular remodeling allows for potential where flow is configured in a manner that is energy
expansion of the anastomotic vessel radius, thereby efficient (18). It remains unknown whether the distal
increasing flow and alleviating fluid shear stress. This arterial tree adapts to conform to this ideal mode of
process has considerable differences with respect to blood flow by constricting adjacent daughter arteries.
angiogenesis (Fig. 6). Arteriogenesis may rapidly cul- The resulting slow flow is largely diverted toward the
minate in dramatic increases in blood flow, whereas parent occluded arterial segment. Intravascular deox-
angiogenesis is a local phenomenon that increases ygenation likely occurs because of slow flow past
permeability and relatively fragile capillary growth ischemic endothelium and neighboring ischemic
without the capacity for significant increases in blood brain parenchyma (19).
flow. Angiogenesis in the brain occurs in perilesional
areas around arteriovenous malformations, tumors,
and stroke (14). Recently, the potential for angiogen-
esis and concomitant neurogenesis has been the focus
of investigation in studies of stroke recovery or restor-
ative neurology. The potentially beneficial role of
inflammation in cerebral arteriogenesis has yet to be
established. In other arterial beds, inflammation
simultaneously promotes atherosclerosis and corre-
sponding arteriogenesis. Very recently, genetic upre-
gulation of the actin-binding Rho-activating protein
triggered by mechanical factors at anastomotic sites
has been discovered (15). Although the basic vascular
pathophysiology of arteriogenesis and collateraliza-
tion is likely to be similar, the anatomy of intracranial
collaterals and resultant pathophysiology may be
quite distinct (16).
Willisian collaterals allow for prompt flow diver-
sion across relatively small distances between arterial
territories. Pressure differentials allow for potential
circuits to open, causing flow to course toward the
ischemic vessel or territory. The diameter of these
connections may be quite variable across individuals,
likely reflecting developmental variation and subse-
quent evolving changes during life. Willisian collater-
alization and the appearance of the circle of Willis is
therefore a dynamic process (17).
Leptomeningeal anastomoses may also evolve in Figure 7 Diagram of retrograde leptomeningeal flow in the
response to environmental stressors, yet the nature of setting of MCA occlusion (a), illustrating anastomotic inflow via
leptomeningeal collateral perfusion is quite complex. isolated distal segments (b, c) and predominant flow toward the
The elongated pathways bridging arterial territories trunk of the occluded parent artery (d). Abbreviation: MCA, mid-
provide blood flow via a limited number of distal dle cerebral artery.
anastomoses that perfuse the ischemic territory in a
62 Liebeskind

In response to ischemia, the microcirculation

adapts through loss of flow heterogeneity to accommo-
date maximal oxygen extraction (20). Low-perfusion
hyperemia, the expansion of cerebral blood volume
(CBV) despite diminished blood flow due to arterial
occlusion, relies heavily on the venous system (9). The
mechanisms underlying venous engorgement remain
unclear, but progressive expansion of the venous bed
downstream from the ischemic arterial territory has
been well documented (9). A critical and potentially
influential question addresses what leads to the demise
of this compensatory mechanism. Cerebral venous
steal, reduction of the critical pressure gradient to
maintain collateral arterial inflow, and the venoarterial
reflex have been postulated as potential factors (21).
These factors may also be important in the process of
arterialization of the venous system that accompanies
other cerebrovascular disorders.
Paradoxically, much of the vascular pathophysi-
ology relating to cerebral hemodynamics and intra-
cranial collateral flow was uncovered more than
25 years ago. Although angiography was pivotal in
these investigations, it was subsequently replaced by
more noninvasive imaging modalities. The unrealized
hopes of neuroprotection and isolated focus on the Figure 8 CTV demonstrating transverse and sigmoid sinus
ischemic cascade without consideration of blood flow thromboses (arrows) with isolated headache. Abbreviation:
diverted attention away from hemodynamics and CTV, computed tomographic venography.
vascular pathophysiology that interventional neuro-
radiologists often observe in the angiography suite.

CLINICAL CORRELATES mediated by collaterals, yet imaging or angiography

The clinical features associated with collateral circu-
lation are often manifested as a dramatic minimization
of symptoms despite severe obstruction to normal
blood flow. Examples of this phenomenon include
asymptomatic acute occlusion of the MCA or clini-
cally silent occlusion of the ICA. Similar events may
occur even more frequently with venous collateraliza-
tion. For instance, CVT involving the principal dural
sinuses may go undetected (Fig. 8). Such examples of
collateral ability to ameliorate or minimize clinical
symptoms are often recognized only when dynamic
changes cause transient loss of this ability. In such
situations, wide fluctuations in symptoms or neuro-
logical deficits may be apparent. These fluctuations
are most commonly observed during the very early
stages of acute ischemia, during the first minutes and
hours after presentation. In cases of MCA ischemia
triaged in the prehospital setting as soon as 15 minutes
after symptom onset, deficits are often quite minimal,
followed by considerable changes and often devastat-
ing consequences at later time points. Certain clinical
features may also be described with specific disorders.
Collateral failure may occur during subacute stroke
despite previously sustained perfusion and no appar-
ent blood pressure or hemodynamic changes. In a
similar fashion, the limb-shaking transient ischemic
attacks (TIAs) of moyamoya may represent only tran-
sient collateral failure. Referred auditory phenomena
or bruits may indicate venous collateralization. Many
of these clinical features are often suspected to be
is often required to substantiate these claims.
IMAGING
Unlike the principal arterial and venous routes in the
brain, imaging of collaterals evades most current
techniques (22), partly because when disease alters
the normal pathways for blood flow, collaterals will
develop via numerous trajectories. Furthermore, col-
lateral anastomoses tend to be diminutive, as they are
recruited only as they are needed. As a result, the goal
of imaging collaterals often follows an indirect path
where much is inferred on the basis of vascular
distributions and the oxymoronic objective of attempt-
ing to see what cannot be seen. There is no ideal
imaging modality for demonstration of collaterals.
Although conventional angiography has been ex-
tremely influential in characterization of collaterals
and angiographic correlation is often used to substan-
tiate noninvasive markers of collateral flow, there
remain qualitative aspects of collateral perfusion that
evade angiography. As a result, imaging characteriza-
tion of intracranial collaterals is founded on integra-
tion of findings from various studies. Each modality
brings a specific advantage or limitation. For instance,
MRA may fail to demonstrate flow in a functional
ACoA if a specific threshold is not met. In contrast,
computed tomographic angiography (CTA) may dem-
onstrate fairly extensive leptomeningeal collaterals,
yet the flow in these segments may be quite minimal
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology 63

The vascular distributions of arterial or venous

Figure 9 CTA source images depicting contrast opacification of
leptomeningeal vessels (arrows) in the setting of acute left MCA
occlusion. Abbreviations: CTV, computed tomographic venogra-
phy; MCA, middle cerebral artery.
collaterals mirror normal patterns of arterial supply or
venous drainage. For instance, the borderzones of the
MCA territory are based on the normal pattern for the
periphery of blood flow in this artery. Unfortunately,
these boundaries shift on the basis of variations in
normal anatomy and with disease. In general, regions
deep within the expected primary vascular distribu-
tion are collateral poor, whereas those at the periphery
are collateral rich. The extreme variability of venous
collateral anatomy makes it quite difficult to infer
such distributions. CT or MRI parenchymal sequences
may demonstrate patterns suggestive of collateral
recruitment. Insular vulnerability in MCA occlusion
suggests collateral salvage of more peripheral cortical
regions (Fig. 10). Similarly, borderzone infarcts may
suggest collateral hemodynamic insufficiency.
Direct visualization or imaging of Willisian
routes may be feasible with most diagnostic modal-
ities. The short segmental collaterals at the circle of
Willis may be demonstrable with transcranial color-
coded Doppler ultrasonography, CTA, MRA, and
conventional angiography. In the setting of acute
ischemic stroke, Willisian flow patterns reflect
changes that took place shortly after arterial occlusion.

(Fig. 9). Differences inherent to each modality may

accentuate flow or anatomical patency to varying
degrees. For most of the clinical disorders encoun-
tered in interventional neuroradiology that are
described in this chapter, angiography remains para-
mount for definitive characterization of collateral
flow. Whereas Willisian routes are more easily
depicted with various imaging modalities, leptome-
ningeal collaterals are more difficult to delineate.
Many of the noninvasive imaging correlates beyond
definition of collaterals on conventional angiography
have been described and are based on findings in
acute ischemic stroke. Extrapolation from acute ische-
mia to other variants, such as near occlusion or
recurrent ischemia bordering on critical perfusion
thresholds, has provided insight into other clinical
scenarios where arterial collaterals are pivotal (22).
Paradoxically, the acute ischemic stroke imaging find-
ings of collateral perfusion may even have valuable
information related to venous collateral system as
well. For instance, imaging of congested venous drain-
age in low-perfusion hyperemia may be similar to the
findings noted in CVT. Imaging of collaterals is best
described by distributions, direct visualization of the
anatomical structures themselves, and functional
aspects including perfusion. The advent and increas-
ingly routine clinical application of multimodal CT
and MRI, incorporating parenchymal images, some Figure 10 CT in acute right MCA stroke with isolated hypoden-
extent of angiographic depiction of proximal lesions sity of the insular region (arrows). Abbreviations: CT, computed
and corresponding collateral circulation, as well as tomography; MCA, middle cerebral artery.
perfusion may be gleaned.
64 Liebeskind
Once flow is restored with proximal recanalization,
such diversion of flow and the pattern of Willisian
collaterals may change abruptly. Changes in Willisian
flow with apparent arterial diameter expansion may
also be evident in serial imaging of cases with chronic
hypoperfusion or ischemia (17). Leptomeningeal col-
laterals may be evident on conventional angiography
and CTA, and only in rare circumstances with MRA.
The slow flow in leptomeningeal collateral routes
precludes adequate visualization of these segments
with MRA. CTA source images may provide an indi-
cation of the extent of leptomeningeal collaterals when
viewed in axial format. The ability to depict venous
collaterals is analogous to demonstration of leptome-
ningeal arterial collaterals: conventional angiography
and CTA may illustrate these channels, yet MRA or
magnetic resonance venography (MRV) is limited. On
review of parenchymal sequences, venous collaterals
may be seen as engorged or dilated structures with
prominent flow voids. Such an appearance may
indicate the presence of a peripherally situated arte-
riovenous malformation (Fig. 11). Conventional
angiography may easily demonstrate the presence of
arterial or venous collateral routes, with some infor-
mation regarding functional capacity evident by the
temporal appearance of delayed opacification or
washout. Such images provide a link between the
Figure 11 MRI evidence of flow voids (arrows) associated with
a previously undiagnosed CAVM. Abbreviation: CAVM, cerebral
arteriovenous malformation.
anatomical information of vessel appearance and
functional aspects of resultant perfusion.
Aside from demonstrating the presence of col-
lateral routes, imaging may also provide some insight
into the functional aspects or capacity of collaterals.
Various modalities may characterize features of col-
lateral blood flow and nutrient or oxygen exchange.
The amount of flow in various Willisian collaterals
may be estimated from transcranial Doppler (TCD);
however, velocity measures alone may be deceiving,
as diameter changes may accompany collateral
recruitment. In contrast to the previous discussion
regarding direct visualization of collaterals, MRA or
MRV may have an advantage over CTA or computed
tomographic venography (CTV): MRA or MRV
accentuates flow characteristics rather than anatomy.
Therefore, standard time-of-flight (TOF) MRA may
provide very useful information regarding capacity
of specific collateral routes. Conventional MRI sequen-
ces may provide some subtle, yet very useful, findings
related to collateral flow. Fluid-attenuated inversion
recovery (FLAIR) MRI vascular hyperintensity (FVH)
may be evident in distal aspects of an occluded artery
because of slow, retrograde leptomeningeal collateral
filling of the artery (Fig. 12) (23,24). Deoxygenation in
such distal arterial segments may be evident with
gradient-recalled echo (GRE) sequences (19). Such
signal loss on GRE associated with deoxygenation
may also be observed in draining veins from the
ischemic territory in stroke or in engorged venous
Figure 12 Slow, retrograde leptomeningeal collateral filling of
the left MCA demonstrating FVH (arrows). Abbreviations: MCA,
middle cerebral artery; FVH, FLAIR MRI vascular hyperintensity.
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
Figure 13 GRE prominence of the draining basal vein (arrow)
suggesting deoxygenation in the setting of acute stroke. Abbre-
viation: GRE, gradient-recalled echo.
collaterals because of thrombosis (Fig. 13). Recent
developments in MRI have capitalized on the ability
to encode spatial or directional information with
phase-contrast (PC) MRA techniques, or selective
labeling of specific arterial inflow routes with selective
arterial spin-labeled (SASL) perfusion (25). Arterial
spin-labeled perfusion MRI may reveal delayed arte-
rial transit effects because of slow, leptomeningeal
flow supplying the periphery of an ischemic lesion.
Commonly used contrast-bolus perfusion techniques
with CT or MRI also provide important information
Figure 14 Schematic illustration of the normal tissue concentration curve (A) and the delay and dispersion associated with collateral
flow (B) in the setting of acute stroke.
65
regarding collateral flow. Both modalities demon-
strate delay and dispersion of contrast passage that
are characteristic of collateral flow (Fig. 14). CBV is
often elevated, and microcirculatory changes may be
evident if one analyzes the tissue concentration curves
in detail. When considering perfusion imaging tech-
niques, one must remember that specific patterns may
change rapidly with time and that certain perfusion
findings may have different implications in acute
versus chronic settings. During chronic phases, spe-
cific perfusion abnormalities may be better tolerated.
DISORDERS
Arterial and venous disorders affecting the brain invar-
iably involve some element of collateral circulation.
Collaterals may serve a compensatory role to sustain
oxygen and nutrient delivery scaled to metabolic
demand, or these alternative blood flow routes may
maintain homeostasis through relief of venous conges-
tion. These beneficial roles are complemented by
potentially detrimental aspects. For instance, collateral
arterial feeders and venous routes may hinder treat-
ment of arteriovenous malformations as these channels
proliferate because of humoral and mechanical influ-
ences. Although the extent of collaterals may only
marginally influence current clinical decision making,
the goals of revascularization procedures or treatments
are often synonymous with collateralization. Similar-
ities exist in the anatomy of collateral routes and
related pathophysiology, yet the role of collaterals is
best understood within the context and following dis-
cussion of specific cerebrovascular disorders.
Ischemic Stroke
Collaterals play a crucial role in acute ischemic stroke
(1,22,26). Although not all strokes are associated with
thromboembolic occlusion of an intracranial artery or
arteriole, ischemia in an arterial territory or bed is
universal. Progressive stenosis of a proximal artery
may also incite ischemia and elicit collateral recruit-
ment. The degree or extent of collateral compensation
varies, as distal cortical branch occlusions or lacunar
strokes have limited collateral routes to balance
66 Liebeskind
diminished antegrade flow. The vast knowledge re-
garding intracranial arterial collateral pathophysiol-
ogy has been garnered from clinical observations and
imaging correlates during acute or subacute cerebral
ischemia. During these dynamic early stages of collat-
eral adaptation to ischemia, patients often undergo
various imaging studies, including angiography. At
later stages, a more stable balance between residual
antegrade flow and collaterals develops. As a result,
some of the observations regarding collaterals in acute
ischemic stroke may be relatively unique, precluding
translation of these observations to other clinical set-
tings. The critical role of collaterals is accentuated by
the impressive impact of collateral perfusion on recan-
alization and the fallacy of neuroprotection without
blood flow to the penumbra beyond the occluded
vessel segment (2). Great emphasis has duly been
placed on proximal recanalization; however, such
approaches are often futile, and sustenance of the
penumbra via collaterals may be the only viable ther-
apeutic option. To capitalize on potential collateral
therapeutic interventions, attention must be focused
on integration of the wealth of clinical, imaging, and
angiographic data, which are often collected during
early stages after symptom onset (Fig. 15).
Collateral pathophysiology in acute stroke may
be ideally described in the setting of MCA occlusion.
As soon as distal intraluminal arterial pressure
beyond the clot plummets because of failure of ante-
grade flow, collaterals are recruited. Ischemia associ-
ated with a large pressure gradient, and not hypoxia,
is the principal driving force that encourages blood
flow to traverse the leptomeningeal anastomoses
between the distal reaches of the ACA and the PCA
and into the MCA field. Augmented flow in these
small anastomoses causes a dramatic rise of fluid
Figure 15 Diffusion-weighted imaging (A), time-to-peak PWI map (B), and angiogram (C) in acute left MCA occlusion. Abbreviation:
MCA, middle cerebral artery.
shear stress and resultant vascular remodeling
because of arteriogenesis. Upregulation of various
cytokines and macrophage invasion leads to perme-
ability derangements in these areas at the far periph-
ery of the ischemic field. Eventually, this process leads
to an increase in the radii of these small collateral
routes. Release of angiotensin II and neuropeptide Y
may cause systemic hypertension, yet ironically the
relatively intact vasoconstrictive capacity of these dis-
tal arterioles may offset attempted hypertension-
mediated increases in flow. Retrograde MCA flow is
highly energy inefficient, and even slight reductions in
the driving pressure gradient may cause collateral
failure. CBV elevations, principally due to venous
engorgement and loss of flow heterogeneity in the
microcirculation, allow for optimal oxygen and nutri-
ent extraction. Eventually, however, a series of detri-
mental events may ensue, where CBV drops and
collateral failure is manifest. The triggers for failure
of such beneficial early stages of CBV elevation that
has been termed low-perfusion hyperemia remain
unclear.
Unless correlative imaging or angiographic stud-
ies are acquired, the dynamic clinical fluctuations due
to collateral flow during acute ischemic stroke may go
unfounded. Rapid changes in head positioning and
dramatic increases in volume due to fluid boluses may
produce profound changes and even normalization of
the neurological examination, despite persistent arte-
rial occlusion. Unfortunately, such changes may be
transient, as sudden deterioration due to collateral
failure may also occur. This paradigm is most worri-
some when early hemodynamic improvement deters
the clinician from intravenous thrombolysis within
three hours and subsequent deterioration occurs
well beyond this limited therapeutic window.
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
Case 1
A 92-year-old woman presented with acute onset of
right hemiparesis and aphasia. Emergent MRI was
acquired, and it revealed occlusion of the left MCA
without diffusion-weighted imaging evidence of tis-
sue injury (Fig. 16). FVH illustrated slow, retrograde
collateral filling of the left MCA (Fig. 17). After
20 minutes in supine position during the MRI, her
neurological deficits completely resolved. On return
to the ER, she sat upright and her prior deficits of
aphasia and hemiparesis recrudesced. Robust lepto-
meningeal collaterals were evident on angiography
(Fig. 18), and after complete recanalization with
mechanical thrombectomy her exam normalized
again. Her transient collateral failure associated with
changes in head positioning prompted the decision to
proceed with thrombectomy. This case demonstrates
that collaterals may avert tissue injury despite abrupt
cessation of arterial flow and that vigorous collaterals
may be evidenced even with advanced age.
Almost every imaging modality provides some
information regarding collateral flow in acute ischemic
stroke. TCD ultrasonography may exhibit flow diver-
sion at the circle of Willis during acute MCA occlusion;
increased velocities in other arterial segments may
67
Figure 16 Acute left MCA occlusion on MRA (A) with
unrevealing diffusion-weighted imaging (B) despite
extensive time-to-peak abnormalities on perfusion-
weighted imaging (C). Abbreviations: MCA, middle cere-
bral artery; MRA, magnetic resonance angiography.
signify collateral flow. Transcranial color-coded ultra-
sonography may also provide direct visualization of
such Willisian correlates. Often, the most demonstrable
indirect evidence of collateral flow is loss of the insular
ribbon on noncontrast CT. This finding suggests col-
lateral preservation of the remainder of the MCA field.
Infarct growth in the setting of persistent occlusion is
also partially a reflection of collateral failure. MRI
offers several further facets of collateral flow in acute
stroke. FVH in distal segments of the MCA or occluded
vessel is due to slow, retrograde leptomeningeal col-
lateral flow (23,24). As the days from symptom onset
lapse, this finding subsides because of stabilization or
equilibration of collateral flow with infarct growth.
Correlation with conventional angiography proves
that FVH is not due to thrombosis itself. GRE MRI
sequences may depict deoxygenation in distal lepto-
meningeal collaterals, in draining veins, and in the
ischemic tissue as well. Permeability derangements at
the borderzones associated with collateral recruitment
may also be depicted as subarachnoid hyperintensity
on FLAIR (Fig. 19) or with dedicated permeability
imaging techniques. Collateral perfusion is most
readily identified on perfusion CT or MRI techniques.
The footprints of collateral perfusion are evident as
prolongation in time-to-peak contrast bolus, elevated
68 Liebeskind
Figure 17 FVH in the distal left MCA (arrow) reflecting predom-
inantly PCA to MCA collateral flow. Abbreviations: FVH, FLAIR
MRI vascular hyperintensity; MCA, middle cerebral artery; PCA,
posterior cerebral artery; MCA, middle cerebral artery.
mean transit times, augmented CBV, and microcircu-
latory measures demonstrating loss of flow heteroge-
neity. These individual parameter maps may be
generated with either CT or MRI perfusion techniques.
Other imaging techniques, such as single-photon
emission computed tomography (SPECT) or positron
emission tomography (PET), may provide additional
hemodynamic or even metabolic information related to
collateral perfusion, yet such approaches are often
cumbersome or impractical in the setting of acute
ischemic stroke. The utility of such perfusion imaging
studies to depict regions dependent on collateral flow
gave rise to the development of mismatch as an imag-
ing surrogate of salvageable penumbra. Various defi-
nitions or iterations of mismatch have been developed
to ideally select candidates for therapeutic intervention
while minimizing risk. Although in the literature much
emphasis has been placed on imaging identification of
mismatch, incredibly few have substantiated the basis
of this approach addressing the actual source of collat-
eral perfusion. Furthermore, it is often forgotten that
such imaging techniques provide only a snapshot in
time of an extremely dynamic process that may radi-
cally differ within minutes. Others have attempted to
utilize noninvasive angiographic depictions of collat-
eral flow. CTA source images may provide some indi-
cation for the extent of collateral perfusion, yet the
prolonged imaging acquisition obliterates temporal
information related to flow in order to achieve more
anatomical images. MRA may fail to demonstrate
leptomeningeal collaterals, yet ipsilateral changes in
the PCA may be indicative of PCA to MCA collateral
flow in acute stroke (Fig. 20). Such changes may
include prolongation or extension of the apparent
PCA course on MRA reconstructions, or increases in
the apparent PCA diameter (27). Ultimately, definitive
proof of collateral supply depends on conventional
angiography (28). However, correlation of angio-
graphic findings with the often subtle noninvasive
imaging findings noted above provides important
information in other cases when angiography is not
available or for ongoing imaging research related to
collateral circulation. Angiography may reveal flow
Figure 18 Retrograde leptomeningeal collateral filling
of the left MCA territory demonstrated with angiography
on a left common carotid artery injection. Abbreviation:
MCA, middle cerebral artery.
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
Figure 19 Subarachnoid hyperintensity on FLAIR due to
increased permeability and contrast leakage at the leptomenin-
geal borderzones. Abbreviation: FLAIR, Fluid-attenuated inver-
sion recovery.
Figure 20 Ipsilateral prominence of the PCA (arrows) on MRA
in the setting of acute right MCA occlusion. Abbreviations: PCA,
posterior cerebral artery; MRA, magnetic resonance angiogra-
phy; MCA, middle cerebral artery.
69
diversion via Willisian routes and leptomeningeal
sources of perfusion during the arterial phase. Adjacent
arteries such as the ACA or the PCA are initially
visualized, followed by a momentary delay during
transit through anastomoses beyond the resolution of
conventional angiography, culminating with retro-
grade filling of the MCA. Similarly, PICA to SCA
anastomoses over the cerebellar convexities may
bypass severe stenoses or occlusions of the basilar.
The extent, but also the temporal features, of such
filling patterns are important for adequate character-
ization of collateral flow. Several scales have been
developed to capture such information, incorporating
the delay of collateral perfusion that may be prolonged
well beyond the normal capillary filling and into the
late venous phases (29,30). Such prolongation of
venous perfusion may also provide important infor-
mation regarding the venous congestion associated
with elevated CBV and the low-perfusion hyperemia
of acute stroke. As most of the limited number of
angiographic scales that capture information on collat-
eral flow emphasize arterial filling, angiographic cor-
relation with perfusion mismatch may be somewhat
inaccurate. Following effective reperfusion due to
recanalization and cessation of collateral dependence,
all of these imaging or angiographic markers of collat-
eral flow disappear. In fact, persistence of such markers
of collateral flow may be indicative of incomplete
reperfusion. Many of these imaging markers of collat-
eral flow may be seen with other cerebrovascular
disorders, but multimodal correlation is often best
with the contemporaneous imaging approach unique
to acute ischemic stroke.
The reliance on angiography for validation of
collateral supply largely limits observations on collat-
eral flow in acute stroke to cases in which endovas-
cular therapy is entertained or to the decreasing
number of cases in which diagnostic conventional
angiography is pursued. Collateral flow has been
demonstrated as a strong predictor of favorable
clinical outcome in intra-arterial thrombolysis and
mechanical thrombectomy (31,32). Collateral flow
does not appear to influence the success of proximal
recanalization, yet ischemic injury may be lessened in
tissue supplied by collaterals beyond the occlusion, or
such regions may be sustained until partial restoration
of antegrade flow is established. Collateral flow
may also thereby decrease the risk of hemorrhagic
transformation. The pattern of collateral filling, such
as Willisian diversion and configuration of potential
ACA collateral flow in ICA occlusion, may have a
substantial effect on outcome. The unusual filling
pattern of retrograde arterial flow in the ischemic
field may also determine the quality or effects of
collateral perfusion (Fig. 21). Willisian collaterals
have recently been used for delivery of endovascular
therapy (33). The first endovascular device utilizing
collaterals, NeuroFloTM, is also currently being studied
in clinical trials. The device employs augmentation
of cerebral blood flow that accompanies titration of
concomitant supra- and infrarenal artery aortic bal-
loon inflation during acute stroke (Fig. 22). However,
the mechanism of this approach remains to be eluci-
dated. Once proximal recanalization or antegrade
70 Liebeskind
Figure 21 Frontal projection of a left ICA injection on angio-
graphy demonstrating retrograde filling of the MCA. Abbreviation:
ICA, internal carotid occlusion.
flow is restored, angiographic collaterals dissipate. In
clinical practice, the appearance of robust collaterals
on angiography may be deceiving in decision making.
One may be compelled to forgo relatively risky inter-
ventions to establish antegrade flow when collaterals
are excellent. Unfortunately, when left untreated,
many of these cases may be prone to collateral failure.
Alternatively, the degree of collaterals may lessen
stroke severity or clinical outcome even after failed
recanalization. Despite these ostensibly critical impli-
cations of collateral flow in acute stroke, collaterals are
often regarded as only a curious finding on angiog-
raphy in acute stroke. Most multicenter trials of endo-
vascular therapy to date have considered collaterals
only in post hoc analyses.
Ongoing investigations of collateral circulation
in acute cerebral ischemia may elucidate important
clinical features, imaging correlates, and undisclosed
pathophysiology of collateral perfusion. Such studies
may also provide relevant information for translation
to the management of other cerebrovascular disor-
ders. These findings may cease the unshakable failure
of neuroprotection related to ongoing disregard for
collateral perfusion and facilitate the development of
collateral therapeutics (2,26). Endovascular therapy
for proximal recanalization may be refined, allowing
for collateral augmentation after failed recanalization
and for prolonged windows of opportunity. The cal-
culations of time is brain assuming a linear function
may also be clarified through consideration of collat-
erals and the ability to maintain tissue for prolonged
periods of time. Revision of this concept may recog-
nize that time is brain because collaterals may fail with
time.
Intracranial Atherosclerosis
Although the intracranial arterial collateral circulation
has been well described in acute ischemic stroke and
in chronic extracranial occlusive disease, knowledge
of collaterals in chronic intracranial occlusive disor-
ders is largely limited to moyamoya. In chronic intra-
cranial atherosclerotic disease, arterial stenosis may be
isolated to a specific arterial segment, invoking a
particular pattern of collateral development. Further-
more, antegrade flow in that territory may not be
viable via shorter segmental bypasses provided by
the lenticulostriate collaterals of moyamoya. In con-
trast to acute ischemic stroke, where complete or
subtotal occlusion is common, a wide range in the
degree of stenosis may be present with intracranial
atherosclerosis. The influence of time or temporal
features may be quite distinct, as the pace of intra-
cranial atherosclerosis may allow for more consider-
able collateral compensation (Fig. 23). Collateral
flow should theoretically be inconsequential or
nonexistent if the stenosis is not hemodynamically
significant, exceeding luminal stenoses beyond
60% to 70%. Nevertheless, anecdotal descriptions
relate collateral findings with even mild to moderate
stenoses. The question remains whether such stenoses
are actually hemodynamically significant because of
factors beyond luminal stenosis. Collaterals
with intracranial occlusive disease may be far more
complex than in extracranial disease, as both lepto-
meningeal and Willisian routes are commonly uti-
lized. If one segregates focal intracranial lesions by
potential collateral routes, a different balance may
exist between leptomeningeal and Willisian collateral
influences. For instance, leptomeningeal collaterals
may be pivotal in MCA stenosis, whereas Willisian
routes may provide retrograde flow distal to a basilar
stenosis. These differences underscore the unique
aspects of intracranial collaterals in atherosclerotic
disease.
Despite these potentially important aspects of
collateral flow with intracranial atherosclerosis, the
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
Figure 22 Aortagram during placement and titration of balloons on the NeuroFlo device for potential collateral augmentation in acute stroke.
Figure 23 Frontal projection of an angiogram showing retro-
grade collateral flow in severe atherosclerotic stenosis of the left
MCA. Abbreviation: MCA, middle cerebral artery.
71
subject remains unexplored except for sporadic case
series or isolated reports that skirt the topic. Several
reasons for this lapse may exist. Intracranial athero-
sclerosis has only recently been studied in a system-
atic fashion in the Warfarin Aspirin Symptomatic
Intracranial Disease (WASID) trial (34). The study
was stopped prematurely on the basis of the futility
of detecting a significant difference in treatment
between warfarin and aspirin. A parallel investigation
of noninvasive imaging correlates, the Stroke Out-
comes and Neuroimaging of Intracranial Atheroscle-
rosis (SONIA) study, demonstrated the relatively
marginal performance of MRA and TCD for detection
of angiographic stenoses in a multicenter setting (35).
Willisian collaterals may be readily detected with such
noninvasive techniques, yet leptomeningeal collater-
als may require conventional angiography (Fig. 24).
As a result, many clinicians have deliberated the role
of imaging versus angiography and potential treat-
ments for intracranial atherosclerosis. Only very
recently has the potential impact of intracranial angio-
plasty and stenting revived the consideration of
conventional angiography and concomitant character-
ization of collaterals. Future studies will likely need to
heed the impact of collaterals on stroke risk and
stenting for a given stenosis. Such analyses of collat-
erals may reveal differences in the role of intracranial
collaterals at various stages of disease. Specific collat-
eral patterns, such as distal flow reversal in the basilar
72 Liebeskind
Figure 24 Frontal projection of a left ICA injection on angiography of concomitant ACA and distal MCA stenoses (arrows), where (A)
represents early and (B) later phases of angiogram. Abbreviations: ICA, internal carotid occlusion; ACA, anterior cerebral artery; MCA,
middle cerebral artery.
Figure 25 Angiography demonstrating retrograde leptomenin-
geal filling of the MCA beyond a proximal stenosis. Abbreviation:
MCA, middle cerebral artery.
or leptomeningeal recruitment with MCA stenosis
(Fig. 25), may be predicted on the basis of luminal
stenosis or provide critical clinical information related
to stroke risk. Similarly, the presence of beneficial
collateral flow may also be used in the future to decide
when stenting is not indicated despite severe stenoses.
Moyamoya
Moyamoya is the quintessential model of collateral
circulation in the brain. The term has been used to
describe a severe multifocal steno-occlusive intracra-
nial arterial disease that most frequently affects young
women of Asian descent. Moyamoya syndrome refers
to a similar pattern of predominantly proximal ante-
rior circulation occlusive lesions and exuberant collat-
eral formation that occurs in other cohorts or settings
(Fig. 26) (36,37). Although much debate has focused
on distinguishing this syndrome from the disease, the
late-stage pathophysiology relating to collateral flow
is same (37). The demographic and clinical features of
moyamoya cases in the United States may be strik-
ingly different than classic Asian descriptions (38). As
an example, a moyamoya pattern may be seen in older
patients with severe atherosclerotic disease because of
numerous vascular risk factors. Imaging definitions
have been used to describe a moyamoya pattern.
Specific MRI criteria have arisen from conventional
angiographic stages, delineating patterns that corre-
late with disease progression. Unfortunately, many
aspects continue to fuel debate. When unilateral or
subtle findings are noted, many question the diagno-
sis of moyamoya. Others resist usage of the term when
the pathognomonic fine network of lenticulostriate
collaterals is inapparent. Irrespective of the diverse
range of conditions that has been reported in associ-
ation with moyamoya, particular features are univer-
sal, including initial diversion of flow through
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
Figure 26 TOF MRA illustrating multifocal anterior circulation
occlusions in moyamoya syndrome. Abbreviation: TOF MRA,
time-of-flight magnetic resonance angiography.
Willisian collateral routes and crucial recruitment of
leptomeningeal collaterals to supply the vascular ter-
ritory distal to the steno-occlusive lesions. Abnormal
hemodynamics or particular flow patterns may pre-
dispose to the development of stenotic lesions, and at
later stages, further flow disturbances may lead to
aneurysm formation. Moyamoya patterns have been
described with various concomitant neurovascular
lesions, including atypical aneurysms, vascular
anomalies, and arteriovenous malformations (39,40).
The clinical features of moyamoya syndrome
have remained obscure, as these patients often present
with diverse demographic backgrounds and various
comorbidities and often have minimal clinical symp-
toms due to well-developed leptomeningeal collater-
als. Patients may present with migrainous headaches
due to leptomeningeal dilatation, seizures, or TIAs.
Sensory TIAs may be ascribed to migrainous events,
yet these brief ischemic episodes may result from
transient failure of parietal collaterals. After recover-
ing from such brief symptoms, there is often little
impetus to pursue further diagnostic studies. How-
ever, devastating strokes, including hemorrhages,
may occur. Imaging features, such as the ivy sign
(Fig. 27), may be subtle, and vascular disease may
go unsuspected unless a dedicated angiographic (non-
invasive or conventional) study is acquired (41).
Because of such poor recognition of this disorder
and the reliance on conventional angiography, angiog-
raphers such as interventional neuroradiologists often
encounter these patients. Although angiographic
descriptions have often focused on the steno-occlusive
lesions, angiography of collateral patterns is often
dramatic and may be helpful in characterization of
73
Figure 27 FLAIR depiction of the ivy sign in moyamoya,
demonstrating subtle hyperintensities of the subarachnoid
space (arrows). Abbreviation: FLAIR, Fluid-attenuated inversion
recovery.
the disorder. Aside from the fine, lenticulostriate
collaterals that bypass segmental occlusions of the
MCA or the ACA, the PCA is often markedly enlarged
or prominent, with vigorous leptomeningeal collater-
als that supply the cerebral convexities. Progressive
enlargement of the PCoA after proximal PCA stenosis
follows obliteration of normal antegrade blood flow
routes in the anterior circulation (17). Deep transcere-
bral collaterals may be evident as medullary streaks
on MRI (42,43). At later stages of the disorder, enlarge-
ment of collaterals between the anterior and posterior
choroidal arteries may herald intracerebral hemor-
rhage (44).
The lack of prospective studies of moyamoya,
especially within the United States, has lead to a
clinical quagmire where little knowledge has been
garnered regarding treatment of patients with moya-
moya. In general, once an imaging study or conven-
tional angiography confirms the diagnosis, most
patients are referred to select vascular neurosurgeons
for potential bypass or synangiosis (45). Medical treat-
ment of moyamoya remains uncharted. The specific
extent of collateral formation or perfusion derange-
ments on noninvasive studies is rarely used to select
candidates for intervention (46). Delineation of an
exhausted oxygen extraction fraction on PET may be
useful in guiding future standardized approaches (47).
Intracranial angioplasty and stent placement has only
rarely been described, perhaps because of the fear of
74 Liebeskind
dissection or perforation of the stenotic artery with
presumed inflammatory infiltrates. The decision to
proceed with EC-IC bypass or synangiosis may be
influenced by angiographic features. Following revas-
cularization of such cases, these patients may have
limited clinical follow-up by neurologists, but neuro-
radiologists may serially monitor them with multi-
modal CT, MRI, or conventional angiography.
Following revascularization, clinical symptoms of
this progressive disorder may abate because of ade-
quate collateral augmentation (48,49). Interestingly,
focal revascularization also appears to improve global
perfusion because of easing of demand on various
collateral channels (50). Future studies may focus on
moyamoya to model collateral flow in acute stroke or
to further characterize the pathophysiology of collat-
eral failure.
Extracranial Arterial Stenosis or Occlusion
Prominent pressure differentials exerted at the circle
of Willis and resultant shifts in blood flow may occur
with stenosis or occlusion of the extracranial carotid or
vertebral arteries. Although alternative EC-IC routes
of blood flow diversion are frequently noted, these
changes are accompanied by shifts in blood flow in
various Willisian segments. Unilateral carotid occlu-
sion or even vertebral occlusion with a contralateral
hypoplastic vertebral artery may elicit such changes.
Figure 28 Willisian collateralization (A, B) of the PCoA chronicled with TOF MRA. Abbreviations: PCoA, posterior communicating artery;
TOF MRA, time-of-flight magnetic resonance angiography.
Willisian segments are able to rapidly shunt flow to
the potentially ischemic region or hemisphere. Sten-
oses must exceed 60% to 70% before hemodynamic
implications are evident, yet severe stenoses or occlu-
sions are necessary to cause flow redistribution at the
circle of Willis. Moderate stenoses of the extracranial
ICA, for instance, may not be hemodynamically sig-
nificant, but embolic risk may be high. As Willisian
collaterals respond only during considerable intralu-
minal pressure shifts, even severe, ulcerated carotid
plaques may not elicit Willisian changes unless hemo-
dynamically significant. Rapid downstream pressure
changes due to plaque rupture and sudden carotid
occlusion may not be adequately predicted on the
basis of Willisian flow patterns unless the culprit
lesion is hemodynamically significant at the baseline.
More subtle changes may be evident with progressive
stenoses, allowing Willisian segments such as the
PCoA to grow with time (Fig. 28). The end-diastolic
velocity of the CCA on duplex ultrasonography of
carotid stenoses may be able to determine the hemo-
dynamic significance of such lesions as correlated
with Willisian collateral patterns (51). Once flow is
restored, these changes may be readily reversed. For
instance, rapid changes in collateral flow and cerebral
blood flow distribution may occur after endovascular
or surgical revascularization of extracranial stenoses
(52,53). Carotid revascularization of stenosis contrala-
teral to an occluded carotid may also improve ACoA
flow to the contralateral hemisphere (54).
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
A multitude of reports have described extensive
extracranial occlusive disease with good clinical out-
comes. Alternatively, in cases with rapid ICA occlu-
sion due to thromboembolic disease, failure of
Willisian segments to compensate for reduced blood
flow may lead to devastating strokes. Time appears to
be a critical factorif stenoses or occlusions develop
over a long period of time, almost any degree of
occlusive disease may be tolerated (55). Even bilateral
common carotid occlusion may be sustained with a
good clinical course (40). The configuration of Willisian
segments and metabolic demand of downstream terri-
tories may determine the size, severity, and pattern of
cerebral infarction (Fig. 29) (56,57). Presence of oph-
thalmic flow reversal and leptomeningeal recruitment
may signify relative insufficiency of Willisian segments
(58). The specific Willisian segments may also differ-
entially affect the pattern of cerebral ischemia. ACoA
flow may determine the size and occurrence of border-
zone infarction, whereas PCoA flow may be inconse-
quential (57,59). Almost every diagnostic modality
employed in prior reports has demonstrated that
collateral compensation and downstream blood
flow requirements may play a critical role in delineat-
ing asymptomatic and symptomatic carotid occlu-
sions (60).
Prediction of recurrent stroke risk with symp-
tomatic carotid occlusion has yielded conflicting
results. Some have reported high-residual flow rates
in other arterial segments and suggested that promi-
nent collateralization via PCoA flow may identify
patients at high risk for recurrent ischemia (61).
Figure 29 FLAIR demonstration of a relatively small infarct in
left ICA occlusion due to dissection and adequate collateral
capacity. Abbreviations: FLAIR, Fluid-attenuated inversion recov-
ery; ICA, internal carotid artery.
75
Improved oxygen extraction has been associated
with increased collateral flow after carotid occlusion
(62). However, after symptomatic carotid occlusion,
recurrent stroke may not be offset by improved col-
lateral flow alone (63). The size of the baseline lesion
and subsequent demand likely influences the need for
collateral blood flow via the circle of Willis. Differ-
ences in technique and patient characteristics have
likely influenced the results of numerous studies
attempting to conclusively delineate the nature of
this relationship (54,62,64). Angiographic definition
of collateral flow patterns, including Willisian diver-
sion, pial supply, and delayed venous opacification,
may provide important information regarding ische-
mic risk after symptomatic carotid occlusion. Brief
angiographic evaluation of Willisian segments alone
may not accurately predict misery perfusion on PET
(64). As much controversy persists regarding the role
of EC-IC bypass surgery, detailed evaluation of angio-
graphic, hemodynamic, and metabolic status with
PET (Fig. 30) is currently being used to identify
candidates for revascularization in the Carotid Occlu-
sion Surgery Study (COSS) (65,66).
It has also been suggested that the etiology of
proximal ICA occlusion may influence outcome. ICA
occlusion due to dissection may produce larger
infarcts compared with progressive atherosclerotic
disease due to the relative insufficiency of collaterals
with rapid occlusion following dissection (67). The
extent of Willisian collaterals after an occlusion due to
dissection may also influence the likelihood for spon-
taneous recanalization, as robust collaterals may hin-
der reestablishment of patency in the proximal
dissected segment.
Various imaging techniques and provocative
maneuvers have been used to assess not just stroke
risk, but the need for shunting or other periprocedural
interventions for carotid revascularization (25,68,69).
The absence of ACoA or PCoA flow on angiography
has been used to predict the need for shunting during
carotid revascularization (70). Phase-contrast MRA,
because of its ability to reflect not just the presence
of flow but also direction, may be useful to predict
changes that may occur with temporary carotid occlu-
sion (71). Prediction of ischemia and the need for
shunting may ideally be defined on the basis of non-
invasive studies prior to revascularization.
Cerebral Venous Thrombosis
CVT is relatively uncommon, yet it is often considered
the prototypical venous disorder. The cerebral venules
and draining sinuses account for more than 60% to 80%
of CBV; however, much of the complex physiology in
the cerebral venous system remains unexplored. The
diverse nature of CVT-associated predisposing condi-
tions or prothrombotic states has attracted much atten-
tion. In fact, most of the literature on CVT focuses on
the thrombotic aspects, without considering venous
flow patterns (Fig. 31). Several neurovascular lesions
such as arteriovenous malformations or fistulas may
have complex angioarchitecture that promote venous
thrombosis, but venous collaterals are otherwise rarely
76 Liebeskind
Figure 30 Oxygen-15 PET data showing increased oxygen extraction fraction in the right hemisphere of a patient with carotid occlusion.
Abbreviation: PET, positron emission tomography.
Figure 31 MRV illustration of prominent collateralization in
extensive CVT. Abbreviations: MRV, magnetic resonance veno-
graphy; CVT, cerebral venous thrombosis.
considered. The remarkable distensibility and ability to
compensate for pressure differentials within the cere-
bral venous system have implications for every aspect
of CVT from diagnosis to treatment.
Thrombosis of a venous sinus or draining vein is
offset by diversion of flow into neighboring channels.
Unless considerable stasis ensues, the thrombus will
remain isolated to the occluded segment until endog-
enous thrombolytic mechanisms allow for recanaliza-
tion. Venous pressure may rise in adjacent areas, but
this rise is generally well tolerated. Areas of the brain
with relative venous insufficiency may be prone to
venous hypertension, with subsequent vasogenic
edema, hemorrhage, and ultimately ischemia. Venous
hypertensive hemorrhage is more common in areas
with relatively poor venous collaterals even with
small amounts of clot, whereas extensive thrombosis
of several major dural sinuses may be inconsequential.
Because of extreme variability in venous collateral
networks, venous hemorrhage may be difficult to
recognize on the basis of location alone, as the prin-
cipal venous territories are often vague (8,72). Hem-
orrhage confined to the deep territory of the vein of
Labbe (Fig. 32) may be one of the few exceptions. The
relative dominance of right- versus left-sided drainage
of the superficial and deep venous territories
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
Figure 32 Intracerebral hemorrhage due to occlusion of the left
vein of Labbe.
influences venous hypertension and lesion location
(8,72,73). The medullary or transcerebral veins may
also divert flow in either direction between the super-
ficial and deep systems.
The clinical presentation and subsequent course
of CVT is completely determined by collaterals (74). In
fact, many CVT cases have been estimated to go
undiagnosed likely because of considerable compen-
sation by venous collaterals. Even though isolated
cortical vein thrombosis may cause neurological def-
icits in some individuals, the pursuit of this diagnosis
is often tempered because it is generally considered a
benign disorder due to collateral outflow. When
patients present with CVT, headache, seizures, and
focal neurological deficits may be noted. Sensory
complaints, transient in many cases, may occur
because of venous congestion of parietal regions
with transverse or sigmoid sinus involvement. Some
patients may describe ear fullness, bruits, or other
auditory complaints associated with shunting of
venous flow (Fig. 33). Dependent head positioning
may elicit dramatic increases in symptoms or jugular
venous distention. On occasion, a patient may present
with an intracerebral hemorrhage of unclear etiology
until venous thrombosis or prominent venous collat-
eralization is noted.
This broad spectrum of clinical manifestations
and imaging presentation with hemorrhage has
caused much confusion. Imaging correlates are
extremely variable and best defined with MRI. Any
angiographic technique (CTV, MRV, or conventional
77
Figure 33 Prominent venous collaterals on CTV causing audi-
tory phenomena in CVT. Abbreviations: CTV, computed tomo-
graphic venography; CVT, cerebral venous thrombosis.
angiography) can illustrate thrombotic occlusion and
some degree of venous collateralization. MRI offers
particular advantages, including demonstration of
isolated cortical vein thromboses, prominence or dis-
tention of medullary veins, and silent edema or dra-
matic parenchymal lesions including hemorrhage that
may easily resolve over time (56,75,76). MRI may also
show mastoid fluid collection due to venous conges-
tion and attempted outflow via collaterals (Fig. 34).
Angiography has assumed a minimal role in diagnosis
of CVT and is increasingly reserved for rescue treat-
ment when patients deteriorate.
Angiography may depict extensive venous col-
laterals in cases of dural sinus thrombosis. Following
thrombolysis or thrombectomy, such venous collater-
als may resolve, but the time course may be protracted
if thrombus is retained or stasis continues. Such resid-
ual venous collaterals may persist indefinitely, caus-
ing other clinical symptoms. Residual symptoms such
as tinnitus or nystagmus may be partially due to
collaterals. These seemingly detrimental manifesta-
tions of distended venous collaterals offset the poten-
tially high mortality rate of an otherwise relatively
benign disorder.
Dural Arteriovenous Shunts
The development of dural arteriovenous shunts or
fistulas (DAVFs) has not been elucidated, although
78 Liebeskind
Figure 34 Mastoid fluid collection on MRI in the setting of CVT.
Abbreviation: CVT, cerebral venous thrombosis.
angiogenic factors are thought to promote vascular
conduits between superficial arteries and veins. Such
shunts may be expected to produce arterial steal
syndromes, but symptoms typically result from
venous outflow disturbances (Fig. 35). Cortical venous
reflux and diversion of flow via venous collaterals
may produce focal neurological symptoms, tinnitus,
or bruits. More diffuse venous drainage patterns
Figure 35 Lateral projection of a left common carotid injection demonstrating a left transverse sinus DAVF with numerous extracranial
carotid artery feeders and prominent venous cortical reflux. Abbreviation: DAVF, dural arteriovenous fistula.
involving the sinuses may promote thrombosis or
engender cognitive deficits, including a rapidly pro-
gressive dementia (77). Abnormal flow in DAVFs may
also be associated with the development of concomi-
tant aneurysms or cerebral arteriovenous malforma-
tions (CAVMs). Because of the substantial complexity
and variable drainage patterns of these lesions, DAVF
classification standards define cases on the basis of
specific venous outflow patterns. These specific drain-
age patterns are also used to guide embolization or
surgical resection. Venous drainage of DAVFs
through collateral channels may present a far more
difficult therapeutic challenge than management of
venous congestion in CVT, as the presence and devel-
opment of a shunt increases the complexity of hemo-
dynamic factors (78).
Cerebral Arteriovenous Malformations
The complex arterial and venous angioarchitecture of
CAVMs is akin to the diverse anatomy and blood flow
derangements that accompany DAVFs. Unlike DAVFs,
however, the contribution of pial collaterals and the
influence on more proximal intracranial arterial pat-
terns are greater with CAVMs. CAVMs represent a
subset of vascular malformations in the brain. These
lesions incorporate arterial and venous segments, typ-
ically centered about a nidus, where blood flow changes
may induce angiogenesis (Fig. 36). Concomitant arterio-
genesis, or development of preexistent arterioles, may
also be accompanied by venous recruitment, or veno-
genesis. Such angioectatic elements are important cor-
relates of collateral circulation that continuously adapt
to the evolving hemodynamic disturbances within and
around a CAVM.
Collateralization is one component of a reactive
process within CAVMs in response to hemodynamic
disturbances that may diminish tissue perfusion or
exacerbate venous congestion. The presence of coex-
istent angiogenesis within the nidus and more periph-
erally situated arteriogenesis and venogenesis of
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
Figure 36 Angiographic demonstration of a complex CAVM
with multiple feeders and venous drainage pathways. Abbrevia-
tion: CAVM, cerebral arteriovenous malformation.
respective feeders and drainage routes offers an ideal
model for the study of collateralization in the brain.
Unfortunately, the complexity of these related, but
distinct, processes and the diverse anatomy of each
particular lesion limit standardized assessment of
these important pathophysiological events. As a
result, only basic accounts regarding collateral circu-
lation can be described with respect to CAVMs.
High-flow states with rapid shunting and dimin-
ished tissue perfusion adjacent to a CAVM may result
in capillary proliferation around the nidus because of
angiogenesis (79). Hypoxia triggers angiogenesis and
the formation of new capillaries. Mechanical influen-
ces, such as shear stress, drive arteriogenesis or veno-
genesis in the larger vessels that supply and drain the
CAVM. Marked hemodynamic changes due to diver-
sion of arterial flow may result in shifts or transfers of
the normal watershed or borderzone regions. Lepto-
meningeal anastomoses from adjacent arterial territo-
ries may contribute to such dramatic shifts in
perfusion. When a CAVM resides predominantly
within a specific arterial territory, such changes may
be less apparent, with only slight variations in lepto-
meningeal circulation noted distal to such lesions. As
with other cerebrovascular lesions, CAVMs may be
associated with persistent embryonic variants (e.g.,
trigeminal, hypoglossal arteries) (80). Variations in
the configuration of the circle of Willis are also fre-
quently noted with CAVMs, particularly when these
lesions are situated near borderzone regions. Arterial
stenoses that develop proximal to a CAVM may rarely
79
culminate in a moyamoya pattern or vasculopathy
(39). A combination of arteriogenic and angiogenic
factors likely leads to the proliferation of finer collat-
eral vessels in such cases. Complete occlusion of
feeding arteries to CAVMs has also been reported,
with all such patients developing exuberant pial col-
lateral supply (81). The venous outflow of CAVMs
may be exceedingly complex, with variations of nor-
mal drainage patterns in up to one-third of cases (82).
Detailed angiographic evaluation of the venous phase
may delineate or distinguish abnormal outflow tracts
with respect to normal venous drainage. The venous
collaterals associated with a CAVM may continuously
evolve in response to local changes in the CAVM and
remote or diffuse vascular events with age.
Clinical manifestations may also depend greatly
on the nature of the contributing vessels and resultant
perfusion patterns around a CAVM. Considerable
leptomeningeal supply may be associated with head-
aches or seizures. Focal neurological deficits typically
result from venous congestion. Cortical venous reflux
may result in congestion and compromised perfusion,
leading to symptoms. CAVMs situated in closer prox-
imity to the draining venous sinus are less likely to be
symptomatic. Although arterial and venous collater-
als are an important component of CAVM patho-
physiology, numerous other mechanisms are also
influential.
Case 2
A 49-year-old man underwent embolization of an
extensive CAVM of the posterior fossa. Shortly after
the procedure, he began experiencing severe retro-
orbital headaches, which exacerbated when he placed
his head in a dependent position. He also noted that
when he would rest his head with his hand on the
right side of his neck, these symptoms would become
quite severe. Serial angiography revealed marked
reduction of the nidus (Fig. 37), yet MRV showed
enlarged venous collaterals abutting the right aspect
of the tentorium (Fig. 38). His referred trigeminal pain
syndrome due to engorgement of venous collaterals
was likely exacerbated by compression of the right
internal jugular vein and abated within weeks because
of initiation of gabapentin.
Following an acute change of the hemodynamic
milieu within a CAVM, collaterals may rapidly adapt
in response to pressure changes (83,84). Such changes
may occur following rupture, embolization, surgery,
or radiation of the CAVM (85). Predicting such
changes in flow patterns may be quite difficult (86).
Therefore, care must be individualized to the specific
case on the basis of the anatomy, flow physiology,
clinical manifestations, and technical factors associ-
ated with any planned multidisciplinary intervention.
Intraoperative angiography may be used to guide
surgical management (87). Various approaches,
including combinations or staged procedures, are
utilized in clinical practice (88). After embolization
of a CAVM, serial angiography over a period of
months or one to two years may be necessary to
80 Liebeskind

Figure 37 Extensive posterior fossa CAVM on angiography before (A) and after (B) embolization with a small residual nidus.
Abbreviation: CAVM, cerebral arteriovenous malformation.

Figure 38 Gadolinium-enhanced MRV demonstrating prominent venous collateral drainage along the right tentorial surface. Abbrevia-
tion: MRV, magnetic resonance venography.
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
demonstrate adequate obliteration of the nidus.
Incomplete obstruction of the nidal-venous junction
may allow for angiogenesis and persistence or
regrowth of the vascular lesion. In general, the poten-
tial collateral supply to a given region influences the
likely success of therapeutic embolization of a CAVM
(89). Intranidal deposition of embolic material may be
necessary to avoid collateral recruitment and
regrowth of the CAVM.
Aneurysms
The relatively proximal location of most intracranial
aneurysms influences the role of collaterals with such
lesions. Aneurysms are some of the few abnormalities
that directly involve several of the potential collateral
segments at the circle of Willis. ACoA aneurysms
constitute 30% to 35% of all intracranial aneurysms,
whereas disease of this segment is otherwise uncom-
mon. PCoA aneurysms often involve only the origin
of this segment, yet other pathology of this vessel is
unusual (90). The embryonic development of these
anastomotic segments and blood flow changes that
may occur at these sites may predispose to aneurysm
formation. Abrupt hemodynamic changes may cause
rapid shifts in these communicating arterial segments
because of pressure differentials, but progressive
ischemia may also impose significant flow demands
at these junctures. Flow redistribution following
occlusion of a proximal vessel may also impart com-
plex hemodynamic changes, leading to aneurysm for-
mation that extends beyond these short diversion
segments at the circle of Willis (91). Size and location
are important variables in aneurysm management, but
also as they relate to collateral circulation. Most small
intracranial aneurysms do not invoke or affect collat-
eral flow; however, collaterals play an important role
in the context of giant cerebral aneurysms. More distal
aneurysms may spare proximal Willisian routes for
Figure 39 After initial diagnosis of a large left cavernous carotid aneurysm (A) with adequate PCoA (B) and ACoA (C) collateral supply,
parent vessel sacrifice was performed (D). Abbreviations: PCoA, posterior communicating artery; ACoA, anterior communicating artery.
81
blood flow diversion, yet these distal lesions may also
be more difficult to treat because of variability in
leptomeningeal collateral capacity (92,93). As most
current approaches for aneurysm treatment involve
surgical clipping or endovascular coil embolization
with attempted parent vessel preservation, collateral
flow may not be relevant. However, when endovas-
cular or surgical parent vessel sacrifice is entertained,
testing of collateral supply is mandatory and EC-IC
bypass surgery may even be indicated prior to defin-
itive aneurysm treatment.
Evaluation of collateral circulation with functional
studies is essential to properly gauge the risk of parent
vessel sacrifice with giant aneurysms (Fig. 39). Sources
of actual and potential collateral flow, including extrac-
ranial routes, leptomeningeal anastomoses, and Willi-
sian segments, must be carefully documented. Various
protocols have been utilized in the past, including
clinical, imaging, and specific angiographic measures.
Provocative maneuvers, including induced hypoten-
sion, have also been employed. Temporary balloon
test occlusion of the parent artery is rapidly stopped
if the patient becomes symptomatic. Other aneurysms,
when present, should be treated before tolerance test-
ing for parent artery sacrifice. Angiographic measures
of adequate collateral circulation may involve stump
pressure measurements and preserved perfusion
throughout all phases of the injection of the contrala-
teral carotid and/or vertebral arteries during balloon
inflation (94,95). To ensure adequate tolerance testing,
balloon placement may need to be moved distally in
cases in which angiography demonstrates potential
collateral channels at the skull base (96). In general,
tolerance to parent artery occlusion is greater in the
pediatric population, whereas variability in collateral
circulation with increasing age makes tolerance testing
imperative in adults.
Unruptured aneurysms may grow with subse-
quent thrombosis and occlusion of the parent artery.
Mass effect from these lesions may also precipitate
82 Liebeskind
flow diversion via collateral routes. These events may
culminate in strokes, yet adequate collateral routes
may compensate for distal hemodynamic insuffi-
ciency. In the setting of occluded or thrombosed
giant cerebral aneurysms, collateral circulation typi-
cally involves pericallosal anastomoses between the
ACA and the PCA, or lateral geniculate anastomoses
between the anterior choroidal artery and the PCA. At
more distal sites, the aneurysmal vessel and associ-
ated collateral blood flow routes may greatly influence
the risk of stroke. For instance, giant or fusiform
thrombosed aneurysms of the PCA may be offset by
efficient collateral anastomoses through the geniculate
network or via retrograde leptomeningeal supply
(94,97). Interestingly, giant or fusiform thrombosed
aneurysms of the MCA rarely recruit adequate lepto-
meningeal collaterals.
Following rupture of an intracranial aneurysm,
vasospasm may ensue. Aneurysmal subarachnoid
hemorrhage may seem radically dissimilar with
respect to ischemic stroke, yet the role of leptomenin-
geal collaterals in vasospasm may be closely related to
such influential blood flow routes in the setting of
acute cerebral ischemia. Although complete occlusion
of a proximal artery is commonly encountered in
acute ischemic stroke, vasospasm only partially
diminishes antegrade flow. Despite these differences
in the degree of patency of the proximal arteries,
retrograde leptomeningeal collaterals are influential
in both disorders. Recent studies of vasospasm sug-
gest that various medical therapies and even inves-
tigational devices, such as NeuroFlo, may be used to
augment collateral flow and improve clinical outcome
(98101). The disproportionately greater opportunity
for studying the angiographic aspects of leptomenin-
geal collateral circulation in vasospasm may provide
further insight into the influence and therapeutic
manipulation of leptomeningeal collaterals in ische-
mic stroke.
Tumors
The inherent vascular correlates in cancer or neoplasia
provide insight into the role of collaterals and arterio-
genesis in vascular disease. Much of the current knowl-
edge regarding arteriogenesis has emerged from
ongoing investigations of tumor angiogenesis, the
growth of new vessels feeding cancerous lesions
(102). In oncology, the therapeutic goal is antiangio-
genesis, or cessation of new vessel growth. This
mechanism may be important in the treatment of
arteriovenous malformations, yet the principal objec-
tive in most cerebrovascular disorders is to grow or
recruit additional compensatory blood flow routes.
Most molecular studies capitalizing on insight from
vascular correlates in tumor pathophysiology remain
at very early stages in preclinical development, yet
imaging of brain tumors has already fostered transla-
tion of dedicated imaging techniques to the vascular
realm. Perfusion CT or MRI techniques focusing on
CBV and permeability of the blood-brain barrier in
tumors provide the ability to investigate arteriogenesis
and collateral recruitment in acute stroke or chronic
ischemia.
Intracranial tumors may obliterate primary
blood flow routes causing diversion of flow through
collaterals, or such lesions may also utilize collaterals
to sustain ongoing tumor growth. This latter mecha-
nism may be used to treat tumors with intra-arterial
delivery of chemotherapeutic agents or for emboliza-
tion of nutrient vessels. As tumors generally do not
respect vascular distributions, the anatomy of collat-
eral vessels may be quite complex or even unique in a
particular case. Angiography is therefore critical for
diagnostic and therapeutic purposes (103).
Occlusion of arterial inflow due to invasion or
compression of a proximal vessel and diversion of
blood through collateral channels is most common
with rapidly growing lesions or vascular tumors
such as meningiomas (Fig. 40). Unlike the abrupt
arterial occlusion that commonly occurs in acute
ischemic stroke, tumor encroachment on a proximal
artery typically follows a prolonged course that allows
adequate collaterals to develop. Carotid occlusion due
to compression from a meningioma may therefore be
accompanied by adequate diversion of flow through
the circle of Willis. Mass effect and tumor compres-
sion may be silent or more obscure on the venous side
of the circulation. Because of marked venous disten-
sibility and often complex patterns of venous collat-
eralization, tumor compression may be clinically
inapparent. In isolated cases, diversion of blood flow
through venous collaterals may elicit headaches,
bruits, or tinnitus. During surgical resection of intra-
cranial or even extracranial tumors, knowledge of
collateral drainage patterns may be important to
Figure 40 Progressive encroachment and compression of the
torcula and proximal transverse sinuses due to a large meningi-
oma seen on MRI.
 Chapter 4: Intracranial Collateral Routes and Anastomoses in Interventional Neuroradiology
avert postoperative complications (74,104,105). Most
recently, MRI techniques have been developed to
delineate cortical venous drainage patterns prior to
resection (106).
Collateral routes may be utilized for intra-arterial
chemotherapy or embolization. Effective treatment
may depend on such collateral feeders that may
allow continued tumor growth. Prior to therapeutic
embolization, assessment of the collateral circulation is
mandatory in order to avoid resultant ischemia. Test
occlusions with demonstration of collateral compensa-
tion, including angiographic flow diversion, stump
pressure measurements, and various imaging techni-
ques, may be used for this purpose (95).
Other Considerations
A description of collateral anatomy and pathophysiol-
ogy in the most common disorders encountered within
interventional neuroradiology may be outlined on the
basis of the primary neurovascular lesion, although
systemic aspects remain quite complex. Clinical
encounters typically center on restoration or oblitera-
tion of blood flow to a focal region, but such lesions
may engender manifestations or reflect diffuse patho-
physiology within the systemic circulation. Cerebral
ischemia due to atherosclerotic disease or moyamoya
may cause systemic upregulation of various inflamma-
tory cytokines associated with arteriogenesis. Similarly,
cerebral aneurysms or arteriovenous malformations
may be associated with remote vascular lesions due
to common underlying pathophysiology. Such exam-
ples emphasize the important role of endogenous
homeostatic mechanisms and common vascular path-
ophysiology despite our focus on the cerebral circula-
tion. Even within the cerebrovasculature, concomitant
lesions may be intertwined, such as aneurysms in the
setting of moyamoya or the association of venous
thrombosis with arteriovenous malformations. Our
current knowledge of cerebrovascular anatomy and
flow physiology requires further investigation with
respect to the molecular and genetic determinants
associated with collateral recruitment.
CONCLUSIONS
The essential role of collateral circulation in cerebrovas-
cular disorders has been recognized for centuries, yet
detailed characterization of these blood flow routes
remains an elusive goal. Collaterals develop in concert
with underlying vascular lesions or disorders, compen-
sating for potential blood flow derangements but also
serving as a marker of disease with manifestations that
may be detrimental. Angiography persists as the prin-
cipal modality for defining the anatomy and associated
blood flow routes of collaterals in the cerebral arterial
and venous systems. Advanced noninvasive imaging
modalities provide additional information regarding
collateral pathophysiology, yet correlation with conven-
tional angiography is often needed. The unique features
of collateral circulation in humans limit translation of
83
animal research to the clinical realm, thereby reinforc-
ing the need to learn from correlative studies in our
patients. Diagnostic, therapeutic, and prognostic impli-
cations of intracranial collaterals underscore the impor-
tance of these blood flow routes in interventional
neuroradiology. Ongoing refinement of current thera-
peutic approaches for cerebrovascular disorders will
undoubtedly depend on further knowledge of collat-
eral perfusion.
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 5
CT Imaging and Physiologic Techniques
in Interventional Neuroradiology
Ronald L. Wolf
Department of Radiology, Neuroradiology Section, University of Pennsylvania
Medical Center, Philadelphia, Pennsylvania, U.S.A.
BACKGROUND
The first clinical CT scans of the brain were obtained
in 1972 on a prototype CT scanner developed
by Hounsfield. The first clinical scanner, EMI Mark I,
was introduced in 1973. The Nobel Prize in medicine
was awarded to Sir Godfrey Hounsfield and Alan
Cormack in 1979 for the development of computer-
assisted tomography, underscoring the impact of
this achievement on clinical medicine. Improvements
in design led to slip ring technology and thus helical
or spiral scanning, which was first introduced in
1975 at Varian and then reintroduced with a more
practical design in 1985 and 1987 by Toshiba and
Siemens, respectively. Whereas the EMI Mark I scan-
ner required approximately five minutes for the
acquisition of one imaging section, spiral scanners
could cover several centimeters in less than 60
seconds, obtaining nearly isotropic resolution over
a small field of view but at the expense of tube
heating (1).
Multidetector CT (MDCT) was first imple-
mented on the first-generation EMI Mark I scanner,
which acquired two sections at a time. Elscint intro-
duced the first helical scanner with dual detectors in
1992 and followed it by detector configurations of four
channels or more starting around 1998. Current con-
figurations have up to 64 channels, so that 30 to 40 cm
can be covered in less than 30 seconds, obtaining
nearly isotropic resolution (1). With MDCT configu-
rations, thin and thick sections are effectively acquired
simultaneously while covering a large distance along
the z axis. Data for thin sections can thus be acquired
and combined to reconstruct thicker sections for read-
ing, while retaining advantages of thin-section scan-
ning such as minimization of partial volume artifact
and resultant streaking. As long as raw data are
retained, additional thin-section reconstructions can
be obtained retrospectively for multiplanar and 3D
reformatting (2).
CT TECHNIQUES
Conventional CT and CT Myelography/
Cisternography
CT of the brain can be performed using sequential
single slice, helical multislice, or multidetector multi-
slice techniques. The American College of Radiology
guidelines suggest section thicknesses in the supra-
tentorial compartment of 10 mm or less in adults
(5 mm or less in children under age 10), and 5 mm
or less in the posterior fossa in adults or children. For
the skull base, sections of 3 mm or less are preferred. If
multiplanar reformats are required (e.g., facial and
skull base fractures in the setting of trauma) or if 3D
rendering is to be performed, sections of 2 mm or less
should be obtained. With multidetector scanners, mul-
tiple data sets (e.g., for standard CT of the brain, face,
skull base, and/or temporal bones) can be acquired
prospectively and simultaneously by selecting detector
spacing on the order of 1 mm or less, combining thin
sections for evaluation of brain and soft tissues and
reconstructing thin sections with overlap for reformat-
ting or rendering retrospectively as needed for the face,
skull base, and temporal bones (Fig. 1). The same is
true for CT of the spine after myelogram or CT of the
head and the face after cisternogram. Coronal sections
can be directly acquired by angling the gantry and
positioning the patient with the neck extended. High-
quality reformatted images from axial data are now
obtainable with newer MDCT systems, but direct coro-
nal acquisitions are still needed if reformats do not
provide sufficient detail for clinical decision-making.
Also, if the patient moves during the axial acquisition,
the reformats will of course be degraded.
CT is the primary imaging modality for emer-
gent indications such as trauma and acute changes in
neurologic status, including ischemia and intracranial
hemorrhage. For most applications concerning struc-
tural imaging of the brain, skull base, cranial vault,
88 Wolf
Figure 1 Simultaneous acquisition of standard NECT and high-resolution CT of skull base with MDCT. (A) NECT (3-mm section) shows
pneumocephalus and temporal bone fracture (arrowhead). (B) 1-mm bone reconstructions from the same raw data also reveal fracture
line through the right carotid canal (arrow), nearly invisible on standard NECT. Abbreviation: NECT, nonenhanced CT.
and spine, nonenhanced CT (NECT) is most often
adequate. The primary indications for the use of IV
contrast include infection and neoplasm, but in prac-
tice this use is relatively uncommon because CNS
infection and neoplasm will almost always prompt
an MRI, obviating the need for enhanced CT. IV
contrast is, however, preferred for routine CT of the
soft tissues of the neck and required for CT angio-
graphy (CTA). In the setting of penetrating trauma,
NECT of the neck can be useful for assessing the
trajectory of injury and proximity to vascular struc-
tures, as well as evaluating for foreign materials such
as bullets and fragments. Intrathecal contrast is of
course required for myelography or cisternography.
CT Angiography
CTA has become an attractive alternative to digital
subtraction angiography (DSA) for rapid evaluation
of the cervical and cerebral vasculature. A complete
evaluation of the brain with NECT, CTA of the head
and/or neck, and perhaps CT perfusion and contrast-
enhanced CT (CECT) of the head can be obtained in
less than 10 to 15 minutes. CTA is well tolerated and in
many cases preferred by patients compared with MR
imaging and MR angiography (3). Source images are
available immediately and provide most of the diag-
nostic information necessary for decision making. Data
for the head and the neck can be obtained during the
same imaging run (and bolus), and smaller field-of-
view reconstructions at more closely spaced intervals
(i.e., on the order of 0.5 mm) reconstructed for the circle
of Willis using the initial data set. Creation of volume-
rendered, multiplanar reformatted, and/or maximum
intensity projection (MIP) images can be performed
relatively quickly at the scan console or on a separate
workstation.
Typically, consecutive thin-axial sections (*1
2 mm) are obtained during IV contrast administration
of 75 to 100 cc iodinated contrast at 3 to 4 cc/sec,
followed by a saline chasing bolus. Reconstructing
with an overlap of about 50% improves the appear-
ance of volume-rendered and reformatted images.
Timing the bolus on the basis of contrast opacification
in the aortic arch or left ventricle allows optimal
arterial opacification and minimization of venous
interference. Timing strategies include automatic trig-
gering using specialized software or using a fraction
of the bolus administered during a cine acquisition to
obtain an enhancement profile. Alternatively, at least
for the circle of Willis, a standard delay of about
25 seconds nearly always gives good arterial opacifi-
cation, with adjustments made for patients with poor
cardiac output. A CT venogram (CTV) can be
obtained by simply adding several seconds (about
68 seconds) to the delay. Protocols vary for different
vendors and for different detector configurations and
should be optimized for each site.
There are many options for postprocessing (4),
with the most commonly used techniques including
volume rendering (VR), MIP, and oblique/orthogonal
or curved reformatting. MIP, a ray-tracing algorithm,
where the brightest pixel along a ray passed through
the volume is displayed in a projection image, is
 Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology 89

Figure 2 Stent evaluation. (A) Source and (B) curved reformatted CTA images show restenosis in a SMART1 stent (nitinol; Cordis,
New Jersey, U.S.), poorly demonstrated on (C) contrast-enhanced MRA (open arrow). (D) CTA and (E) time-of-flight MRA show patent
WALLSTENT1 (stainless steel; Boston Scientific, Massachusetts, U.S.). Ends of stent are better shown with CTA (arrows).
(F) Neuroform1 stent (nitinol, Boston Scientific, Massachusetts, U.S.) on CTA (arrowhead).

probably the most useful. VR is generated by assign- of stents (Fig. 2), while coils are better evaluated using
ing colors and opacities to ranges of attenuation so MRI techniques (Fig. 3). CTA will often be more
that vessels appear distinct from bone and soft tissues. successful than MRA in proximity to clips (Fig. 4) (8).
It is most helpful for intracranial applications in which
3D visualization is needed, especially aneurysms. VR
is less helpful in the neck, where overlapping struc- CT Perfusion
tures such as veins and the spine make postprocessing
There are essentially two imaging approaches for the
more difficult, but it can be helpful in certain situa-
measurement of cerebral blood flow (CBF) in clinical
tions such as visualizing the relationship of a high
practice: (1) intravascular or nondiffusible tracer
carotid bifurcation relative to the mandible prior to
(bolus contrast) techniques and (2) diffusible tracer
endarterectomy. Shaded surface display (SSD) meth-
(the tracer can diffuse out of the vessels and into
ods are of limited utility (5), often underestimating
surrounding tissue) techniques. Most routine clinical
degree of stenosis and now superseded by other
CT and MR perfusion-weighted imaging studies use
rendering techniques. Other useful postprocessing
an intravascular contrast agent, rapidly injecting a
techniques include automated vessel analysis techni-
bolus and analyzing the first pass. Diffusible tracer
ques for calculation of stenosis severity and for vessel
methods include stable xenon CT (XeCT) perfusion,
extraction, software for separating arteries and veins,
H215O PET, and arterial spin-labeled perfusion MRI.
and fly-through techniques. Subtraction or masking
Excellent discussions of different perfusion method-
algorithms for bone and metal exist for CTA just as
ologies are available in articles by Wintermark et al.
they do for DSA (6,7), but are not yet widely used.
(9) and Latchaw et al. (10).
Overlap between attenuation of contrast in a vessel
and adjacent bone or calcium is often present, limiting
Bolus Contrast CT Perfusion
threshold-based segmentation approaches. Associated
artifacts such as beam hardening and streaking can Bolus contrast CT perfusion (CTP) is based on the linear
limit diagnostic accuracy with or without subtraction, relationship of attenuation to concentration of iodine in
an obvious problem with routinely used aneurysm the brain. It is performed by scanning in cine mode at
clips, metallic coils in aneurysms or vessels, and between one and four imaging locations, repeatedly
stents. In general, CTA is preferable for the evaluation imaging these locations over 40 to 50 seconds at a rate
90 Wolf

Figure 3 Intracranial embolization coils. Scout topogram and axial image from NECT (A, B) demonstrate large coil mass in basilar tip
aneurysm with extensive artifact (B) limiting CTA. Conventional (C, E) and contrast-enhanced MRA (D, F) show aneurysm remnant
(arrowheads) on source (C, D) and MIP (E, F) images with minimal artifact from coils (arrows). Thrombus was seen in coiled aneurysm
inferiorly (E, block arrow). Abbreviations: NECT, nonenhanced CT; MIP, maximum intensity projection.

Figure 4 Aneurysm clips. (A, C) Axial source and

(B, D) MIP images show that CTA (top) shows the
A1 segment and ACoA complex near the clip (open
arrow, B). On MRA (top), susceptibility artifact leads to
extensive signal loss (arrows, C and D). Abbreviations:
MIP, maximum intensity projection; ACoA, anterior
communicating artery.
 Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology 91

of about one image set every 1 to 2 seconds before,
during, and after a bolus of iodinated contrast. A vol-
ume of 40 to 50 cc is infected at 5 to 8 cc/sec through a
large-bore IV. Analysis of the time series of CT images
results in a time-attenuation curve (TAC). Motion can
significantly degrade the perfusion analysis, and
although software is available that allows realignment
of motion-degraded data to an extent, care should be
taken to prepare the patient appropriately to minimize
motion, including sedation if necessary.
Hemodynamic parameters that are typically
generated include measures of the time-to-peak
(TTP, time from arrival of bolus in intracerebral
arteries to peak concentration in tissue, units of sec-
onds), cerebral blood volume (CBV, integral under the
TAC normalized to intravascular attenuation in a
large vessel such as sagittal sinus, units of cc/100 g),
mean transit time (MTT, average time for contrast to
pass from arterial to venous side, units of seconds),
and cerebral blood flow (CBF, blood flow in volume of
tissue, units of cc/100 g/min). For parameters TTP
and CBV, calculations are straightforward and rela-
tively easy to obtain. For MTT or CBF, calculations
require more sophisticated analysis, which includes
measuring and incorporating the arterial input
function (deconvolution techniques) or evaluating
the shape of the TAC (nondeconvolution techniques).
Deconvolution techniques correct for the imperfect
bolus (in theory it should be an instantaneous bolus,
but in reality it is spread out), deconvolving or remov-
ing the effect of the imperfect arterial input function
from the TAC to obtain the residue function, from
which the CBF and MTT can be generated (Fig. 5). The
central volume principle describes the relationship
between parameters as CBF = CBV/MTT (11,12).
Nondeconvolution methods use the slope of the
tissue TAC to measure the change in concentration of
iodine over time, which is proportional to CBF and to
the difference between iodine concentration in artery
and vein (12,13). A high injection rate of 6 to 8 cc/sec
is required, while deconvolution methods tolerate
lower rates of injection on the order of 5 cc/sec.
Absolute CBF quantitation is possible with deconvo-
lution methods, but there are difficulties in assuring
accuracy; for example, large vessels in the analyzed
volume can lead to overestimation of CBF. Nonde-
convolution methods tend to underestimate CBF. In
practice, relative values for perfusion parameters are
often used for interpretation, using normal-appearing
and/or contralateral brain as an internal reference.

Figure 5 Bolus contrast CTP. NECT (A) shows SAH in left basal cisterns and minimal hydrocephalus. Regions of interest (ROI) for
artery (arrowhead) and vein (arrow) are chosen (B) to generate time attenuation curves (C), from which parametric maps are generated
such as (D) CBF, (E) CBV, and (F) MTT. Abbreviations: CTP, CT perfusion; NECT, nonenhanced CT; SAH, subarachnoid hemorrhage;
CBF, cerebral blood flow; CBV, cerebral blood volume; MTT, mean transit time.
92 Wolf
Another approach, which does not rely on deconvo-
lution or analysis of the bolus itself, generates maps of
percent perfused blood volume (PBV) on the basis of a
subtraction of registered unenhanced baseline CT
images from CTA source images (14), with the change
in parenchymal attenuation linearly proportional to
the tissue concentration of iodine.
Stable Xenon Perfusion CT
Stable xenon can be used to measure absolute CBF.
Xenon is lipid soluble and thus diffusible and leads to
changes in attenuation, which can be measured on CT
images. XeCT perfusion has been applied in several
clinical settings such as cerebrovascular disorders,
traumatic brain injury, balloon test occlusion, and
subarachnoid hemorrhage (SAH) and vasospasm.
However, it is not currently FDA approved, primarily
because of reported adverse events such as apneic
episodes or increased intracranial pressure (15). These
events tend to be transient and the technique well
tolerated, particularly with the lower concentration of
inspired xenon (28%) that is now used (previously it
was 33%).
The study is performed by obtaining two base-
line scans at two to eight imaging locations without
xenon, followed by six additional scans at these loca-
tions during xenon inhalation. To determine the
change in attenuation from xenon, the baseline scans
are averaged for each location and subtracted from
that location for each of the subsequent time points.
Xenon is delivered mixed with oxygen at a concentra-
tion of 28%. End-tidal xenon concentration is mea-
sured, and end-tidal carbon dioxide is monitored, as
well as any apneic episodes. Calculation of CBF is
based on the Fick principle; that is, the amount of an
indicator in a sample of tissue is proportional to the
difference between the amount supplied in arterial
blood and the amount carried away in venous blood.
Modified Kety-Schmidt equations are used to describe
the relationship of xenon concentration in the brain
and in the arteries with the blood-brain partition
coefficient and CBF (16). The xenon concentration in
the brain is obtained from the CT measurements at
baseline and during inhalation of xenon, and the time-
dependent arterial concentration is obtained by
measuring the end-tidal xenon concentration, which
is proportional to the time-dependent arterial concen-
tration in patients without severe lung disease leading
to significant dead space. The total time of acquisition
is on the order of 5 to 6 minutes, and studies take
about 20 minutes from start to finish, including data
processing and creation of CBF maps. Repeat studies
can be obtained 20 minutes after the end of a previous
scan, allowing for washout of xenon.
CLINICAL APPLICATIONS
Nontraumatic Hemorrhage
Common causes of nontraumatic intracranial hemor-
rhage include ruptured aneurysm, arteriovenous mal-
formation (AVM), hypertension, and prematurity.
Other causes include reperfusion injury, amyloid
angiopathy, coagulopathy, drug abuse, and intracra-
nial neoplasms. Less common are entities such as
venous hypertension or occlusion, eclampsia, vascu-
litis, and infection (17). This section focuses on com-
mon clinical entities that are most relevant to
interventional neuroradiology: aneurysm, AVM, and
venous hypertension/occlusion.
Aneurysm
An aneurysm is essentially a circumscribed dilatation
of an artery. There are different types and/or causes
of aneurysms, but the most common is the berry, or
saccular, aneurysm. Other types of aneurysms include
mycotic, fusiform, dissecting, traumatic, and pseudoa-
neurysms. Aneurysms can be associated with abnor-
mal vasculature in neoplasms. Venous aneurysms also
occur, and both arterial and venous aneurysms can be
seen with AVMs. The most common locations of berry
aneurysms (ruptured or unruptured) are proximal in
the circle of Willis. About 85% to 95% involve the
anterior circulation, and 5% to 15% involve the poste-
rior circulation. The most likely locations are anterior
communicating artery (ACoA, 30%), internal carotid
artery (ICA) [including the periophthalmic and pos-
terior communicating artery (PCoA), 25%], middle
cerebral artery (MCA, 20%), basilar artery (BA, 10%),
and posterior inferior cerebellar artery (PICA, 5%).
There are multiple aneurysms in about 20% of aneur-
ysm patients (18).
CT techniques play a prominent role in the
evaluation of unruptured or ruptured aneurysms.
For unruptured aneurysms, MRA is more commonly
used as a screening modality, whereas CTA is more
often used to verify suspicion of an aneurysm (e.g.,
one suggested but not certain on MRA), to better
characterize an aneurysm detected on MRA or DSA
(e.g., giant or cavernous aneurysms), and when
patients cannot undergo MRI or MRA. Multiple stud-
ies have compared CTA with MRA, DSA, and/or
rotational angiography. Its sensitivity for detection of
aneurysms is at least as good as that of MRA but, as
with MRA, drops off below 3 mm (19). CTA is also
used to follow patients with known aneurysms.
Although aneurysm clips currently placed are largely
MR compatible, they create substantial artifact, which
often renders MRA useless. Clips can also limit CTA,
but diagnostic information is still often obtainable,
even for previously clipped aneurysms. Previously
coiled aneurysms are better evaluated with MRA.
Subarachnoid hemorrhage and saccular aneurysmal
rupture. The most common cause of nontraumatic
SAH is ruptured aneurysm (7585% of cases) (20),
with significant associated morbidity and mortality.
Other less common causes include perimesencephalic
hemorrhage, AVM or arteriovenous fistula (AVF, in
brain or spine, and possibly with associated aneur-
ysm), intracranial dissection, drugs such as am-
phetamines or cocaine, coagulation disorders,
vasculopathies such as sickle cell disease and moya-
moya, and others (21,22). NECT is almost always the
first imaging study obtained, in which blood appears
 Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology
hyperdense. NECT allows rapid evaluation for the
presence of SAH as well as immediate complications
such as hydrocephalus, is available around the clock,
and provides easy access to unstable patients. Acute
blood appears dense on CT, depending on hematocrit
and hemoglobin values (56 HU, with hematocrit of
45% compared with gray matter attenuation of just
under 40 HU or CSF at around 05 HU) (23). Coagu-
lopathies can lead to difficulty in visualizing acute
blood; for example, a low hemoglobin value of less
than 10 g/dL can be invisible. The sensitivity for
NECT in detecting SAH is approximately 95% in the
first one to two days, but decreases over time to 50%
after one week and to almost 0% after three weeks.
Negative NECT should be followed by lumbar punc-
ture to increase sensitivity for SAH detection, assess-
ing for blood and/or xanthochromia (depending on
time after initial bleed).
The pattern of SAH on NECT may suggest
the most likely location of the ruptured aneurysm, at
least for ACoA and MCA aneurysms (24). The pres-
ence of parenchymal hematoma with SAH increases
accuracy (24,25). When multiple aneurysms are pres-
ent, the pattern of hemorrhage and especially the
93
Figure 6 Aneurysm rupture and CTA. (A) NECT at
presentation shows SAH in the sylvian fissure (white
arrowhead) and a parenchymal hematoma (black
arrowheads). This pattern is suspicious for MCA aneur-
ysm rupture, confirmed on (B) MIP images from CTA
(white arrow). A second unruptured MCA aneurysm is
present (open arrow). Abbreviations: NECT, nonen-
hanced CT; SAH, subarachnoid hemorrhage; MIP,
maximum intensity projection.
location of parenchymal hematoma may provide
useful information in deciding which aneurysm is
likely to have bled, complementary to other indicators
such as aneurysm size and morphology (Fig. 6).
However, the amount and distribution of blood are
very often not predictive of the site of aneurysm
rupture (25,26).
Patterns associated with rupture of an ACoA
aneurysm include symmetric SAH, blood in the ante-
rior interhemispheric fissure, anterior pericallosal cis-
tern and/or cisterna lamina terminalis, anterior
interhemispheric clot, or inferior frontal parenchymal
hematoma (Fig. 7). Intraventricular hemorrhage may
also be associated secondary to rupture through the
lamina terminalis. Other ICA aneurysms, including
PCoA aneurysms, are more difficult to localize, often
without lateralizing signs on CT. MCA aneurysms
may demonstrate asymmetric density in the sylvian
fissure. More specific localizing presentations include
parenchymal hematoma or expansile clot in the
sylvian fissure (Fig. 8). PICA aneurysms may show
disproportionate blood in the posterior fossa and
fourth ventricle, and basilar tip aneurysms might
show SAH primarily in the interpeduncular and
Figure 7 Ruptured ACoA aneurysm pattern. (A) Axial
NECT image shows nearly symmetric SAH and a small
interhemispheric or midline parenchymal hematoma
(white arrow). (B) DSA confirms ACoA aneurysm
(black arrow), suspected for rupture. Small MCA and
ICA aneurysms were also detected (black arrowheads).
Abbreviations: ACoA, anterior communicating artery;
NECT, nonenhanced CT; SAH, subarachnoid hemor-
rhage; DSA, digital subtraction angiography; ICA, inter-
nal carotid artery.
94 Wolf
prepontine cisterns (Fig. 9). Van der Jagt et al. (25)
reported that validity of SAH distribution on CT was
inconsistent or low for ruptured aneurysm arising
from MCA, ICA, or posterior circulation aneurysms,
unless a parenchymal hematoma was in proximity.
Blood distribution was a better predictor for anterior
cerebral artery (ACA) and ACoA aneurysms. An
atypical presentation of a ruptured aneurysm is sub-
dural hematoma (SDH), often with some SAH but
rarely without any evidence of SAH. It has been
described in ICA and ACoA aneurysms (27), also
with pericallosal aneurysms (Fig. 10). Pericallosal
aneurysms might also show parenchymal hematoma
or large focal SAH above the corpus callosum.
While the most common causes of SAH are
trauma followed by intracranial aneurysm, this dis-
tinction cannot always be made clinically. Examples
include unwitnessed falls, patients found down
without overt evidence of trauma, or motor vehicle
collision or a fall where a ruptured aneurysm may
Figure 8 Ruptured MCA aneurysm. (A, B) Axial
NECT images at two locations show asymmetric SAH
and focal hematoma, expanding left sylvian fissure (see
also Fig. 9). Abbreviations: NECT, nonenhanced CT;
SAH, subarachnoid hemorrhage.
Figure 9 Ruptured posterior circulation aneurysms.
(A) NECT shows asymmetric blood in right cerebello-
pontine angle, suggesting right PICA aneurysm.
(B) NECT from a different patient with ruptured basilar
tip aneurysm shows focal blood near basilar tip. Abbre-
viations: NECT, nonenhanced CT; PICA, posterior infe-
rior cerebellar artery.
have preceded the traumatic event. Findings on NECT
favoring trauma are associated calvarial or skull base
fractures, SDH, contusions, and a relative lack of
blood in basal cisterns. On follow-up imaging, confi-
dence is increased when evolving contusions or foci
of diffuse axonal injury are clearly demonstrated.
Findings favoring aneurysm include SAH in basal
cisterns, excessive amount of SAH, and lack of obvi-
ous traumatic findings. Occasionally, the aneurysm
itself can be clearly visualized on NECT (Fig. 11). In
some cases, it is impossible on cross-sectional imaging
to accurately assess whether the source of SAH is
aneurysmal or traumatic, and conventional angiogra-
phy may be necessary.
Conventional angiography or DSA is still consid-
ered the gold standard for detection of aneurysms.
However, CTA may be preferred in some instances,
e.g., catastrophic SAH (28) (Fig. 6). In a systematic
review of noninvasive imaging studies for aneurysm,
White et al. (29) found that CTA was not as sensitive as
Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology 95

Figure 10 Atypical pattern of hemorrhage. (AC) Axial

NECT images at three locations show subdural hem-
orrhage (arrows, A and C), and relatively little SAH
(B, arrowhead ). (D) Volume-rendered image from CTA
demonstrates a pericallosal artery aneurysm. Abbrevi-
ations: NECT, nonenhanced CT; SAH, subarachnoid
hemorrhage.

Figure 11 Demonstration of aneurysm on NECT.

Axial NECT images from patients with (A) ruptured
and (B) unruptured ICA aneurysms. In each case, the
aneurysm is clearly seen without IV contrast (arrows).
Hydrocephalus is also noted in (A). Abbreviations:
NECT, nonenhanced CT; ICA, internal carotid artery.
96 Wolf
Figure 12 Giant aneurysm. (A) Sagittal T1-weighted MR image shows flow void/jet (arrowhead ) and thrombus (arrow ) in partially
thrombosed giant aneurysm. (B) MIP image from MRA fails to distinguish thrombus from patent aneurysm. (C) CTA MIP image
distinguishes patent (black asterix) from thrombosed (white plus sign) aneurysm. Abbreviation: MIP, maximum intensity projection.
DSA for small aneurysms, with an accuracy of 96% for
aneurysms larger than 3 mm but only 61% for aneur-
ysms 3 mm or less (overall accuracy of 89%). However,
studies only up to 1998 were reviewed, and higher-
quality multidetector scanners have become more
widely available from around 1998. More recently,
Chappell et al. (30) looked at 21 studies in a meta-
analysis comparing CTA and DSA (the most recent in
2002). The overall sensitivity and specificity weighted
for number of patients per study were 92.7% and
77.2%, respectively. The specificity will likely be inac-
curate, since the rate of true-negative cases is difficult
to assess in most of these studies, most of which focus
on cases in which an aneurysm was suspected clini-
cally or radiographically (30). There is increasing evi-
dence that missing a symptomatic aneurysm on CTA
would be quite rare (19,3133). Indeed, there are
reported cases in which aneurysms are detected on
CTA and not DSA, and at minimum, CTA is a valuable
adjunct study (34,35). For example, the 3D anatomy of
complicated or giant aneurysms, including those with
significant intraluminal thrombus, aneurysm relation-
ship to bony structures (e.g., paraclinoid aneurysms),
and calcifications that might interfere with clipping,
may be demonstrated more clearly (Fig. 12). Although
there are still questions regarding sensitivity for detec-
tion of very small aneurysms (<3 mm) and false
positives are also of concern (19), some centers cur-
rently use CTA for only routine aneurysmal SAH
workup and have found it safe and reliable (36,37).
SAH from aneurysmal rupture in the subacute and
chronic setting. While MRI is more sensitive and spe-
cific for evaluation of ischemia, it is not always a
viable option in a sick ICU patient. CT techniques
are preferred for following SAH patients after presen-
tation and treatment, evaluating for complications
such as rebleeding, hydrocephalus, vasospasm, and
ischemia or infarct. CTA with or without perfusion
may be helpful in vasospasm cases (Fig. 13) (38). The
addition of CTP (9,39) or XeCT perfusion studies
(9,16) may also be helpful. Effectiveness of treatment
can be tested by obtaining perfusion data before and
after changes in therapy. Other methodologies have
also been applied to this problem, including PET,
SPECT, and transcranial Doppler (TCD) (39), but
none have been established as a definitive test (10).
Imaging follow-up for the original and any additional
aneurysms depends on prior intervention. Immediate
(or intraoperative) conventional angiography is often
performed to verify clip placement, but CTA can be
used for follow-up in the subacute or chronic setting
(40,41). There are some limitations related to artifacts
from the clips (42), but at least some artifacts can be
minimized with technique (Fig. 14). Coils most often
cannot be evaluated with CTA (Fig. 3).
Nonaneurysmal subarachnoid hemorrhage. Perime-
sencephalic hemorrhage is the cause of SAH in about
10% of cases and accounts for about 70% of SAH cases
that have normal DSA (20). The typical pattern is
blood localized in cisterns around the midbrain, with-
out extension into sylvian fissures, interhemispheric
fissure, or parenchyma. Intraventricular hemorrhage
is also not typically present. Since aneurysms may be
missed initially because of spasm, compression by
hematoma, or perhaps suboptimal number or choice
of views, DSA-negative SAH should be followed in
about one week with another exam. CTA may provide
the means to forgo follow-up (or initial) DSA. Other
causes of nonaneurysmal SAH (about 5% of cases)
include intracranial dissection, AVM/AVF, coagulop-
athy, drug use (e.g., amphetamines or cocaine), and
vasculopathies such as sickle cell disease and moya-
moya (21,22).
AVM
CTA has been applied to diagnostic evaluation of
AVM, but cannot replace DSA at this time (43,44).
 Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology 97

Figure 13 CTA and vasospasm. (A) Axial source image from CTA acquisition demonstrates irregular narrowing of left M1 segment of
MCA, not present on baseline DSA and suspicious for vasospasm. (B) DSA confirms M1 vasospasm, and also shows bilateral A1 and A2
segment as well as ICA bifurcation vasospasm. Abbreviations: DSA, digital subtraction angiography; ICA, internal carotid artery.

Figure 14 Aneurysm follow-up after clipping. (A) Source image from CTA demonstrates aneurysm remnant (arrowhead ) despite artifact
from clip (block arrows). Slab MIP (B) and VR images (C) demonstrate topography of remnant (arrowheads). Abbreviation: MIP,
maximum intensity projection.

CTA can be used as a complementary examination,
primarily for depiction of 3D morphology and for
stereotactic planning, but rotational angiography can
also provide this information. AVMs and AVFs can be
detected using CTA, and it can be used for following
lesions after treatment; however, MRI and MRA prob-
ably have the edge in this regard because of superior
evaluation of parenchyma and improving temporal
resolution of MR DSA methods. In the setting of acute
intracranial hemorrhage, nearly all patients will ini-
tially undergo NECT, and in some cases a presump-
tive diagnosis can be made on NECT even without
hemorrhage (Fig. 15). Cavernomas and venous angio-
mas are commonly encountered and must be recog-
nized to avoid unnecessary testing. CTA provides a
fast evaluation of intracranial vasculature for emer-
gent intervention (Fig. 16), but the temporal resolution
of CTA is not adequate for completely evaluating AV
shunting or delineating arterial or venous aneurysms,
arterial feeders, and draining veins.
Venous Occlusive Disorders
Venous occlusive disease may be suspected on initial
NECT by demonstration of a high-attenuation clot in
one or more venous sinuses or cerebral veins. As
98 Wolf
Figure 15 Vascular malformations on NECT. (A) Cavernous malformation (open arrow). (B) Developmental venous anomaly (white
arrow). (C) AVM (arrowheads). Abbreviations: NECT, nonenhanced CT; AVM, arteriovenous malformation.
opposed to arterial ischemia, venous ischemia or
infarction more often presents with hemorrhage or
with patterns of edema atypical for arterial ischemia.
Examples include bilateral thalamic hypodensities with
deep venous occlusive disease (although this event
Figure 16 AVM with catastrophic presentation.
(A) NECT showed fourth ventricular hemorrhage
(block arrow), parenchymal hemorrhage (open arrow),
SAH, and hydrocephalus. CTA obtained en route to
surgery (B) showed left cerebellar AVM with focal
aneurysms (MIP, black arrow, arrowhead ). On postop-
erative DSA, early (C) and delayed (D) phases from
selective superior cerebellar artery injection confirmed
findings. Abbreviations: AVM, arteriovenous malforma-
tion; NECT, nonenhanced CT; SAH, subarachnoid
hemorrhage; MIP, maximum intensity projection; DSA,
digital subtraction angiography.
could be mimicked by top of the basilar syndrome)
and posterior temporal lobe hemorrhage suggestive of
vein of Labbe or transverse sinus thrombosis. High-
resolution imaging of the cerebral venous system can
be obtained with CT venography (Fig. 17) (45).
 Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology
Other Causes of Intracranial Hemorrhage
There are multiple other causes of nontraumatic intra-
cranial hemorrhage, including hypertensive hemor-
rhage, amyloid angiopathy, coagulopathy, drug
abuse, and intracranial neoplasms. Additional less
common causes are reperfusion injury, eclampsia,
vasculitis, and infection. Some of these will be dis-
cussed in the next section, since they may also present
as strokes or stroke-like syndromes, but a complete
discussion is beyond the scope of this chapter.
Ischemia
Stroke represents the third-largest cause of mortality
and a leading cause of morbidity in the United States.
The vast majority of strokes are ischemic in origin
(8085%), and the minority are hemorrhagic events.
Most ischemic infarcts are thromboembolic. Progno-
sis, risk of recurrence, and management options are
influenced by infarct subtype (Trial of ORG 10172 in
Acute Stroke Treatment or TOAST criteria) (46). Sub-
types include cardioembolic, large vessel, small ves-
sel, other (determined) causes, and cryptogenic.
Hyperacute and Acute Setting
NECT Acute imaging addresses the following
questions: (1) Is there hemorrhage or other explanation
for symptoms? (2) What is the etiology of the infarct
and status of the vessel involved, if any? (3) What is
the location and extent, and is there tissue still at risk?
(47). The first study performed is usually NECT. In the
acute setting (first 3 to 6 hours for anterior circulation
and longer for posterior circulation), this study is often
the only imaging test necessary for the stroke neurol-
ogist to decide to treat with tissue plasminogen acti-
vator (tPA). MRI with diffusion-weighted imaging
(DWI) is more sensitive and specific for detection of
acute ischemia. MRI is also sensitive to hemorrhage
(4749), though most practitioners still prefer CT.
99
Figure 17 Transverse sinus thrombosis. (A, B) NECT
shows increased density in right transverse sinus indi-
cating thrombus. (C) Posterior oblique MIP projection
confirmed absent contrast opacification of right trans-
verse sinus (arrowhead) on CTV. Abbreviations: NECT,
nonenhanced CT; MIP, maximum intensity projection;
CTV, CT venogram.
CT may show findings of ischemia within the
first 6 hours, often subtle initially but becoming obvi-
ous within 12 to 24 hours. Early signs of infarct
include the dense artery or dot sign, loss of the insular
ribbon, blurring of basal ganglia, sulcal effacement,
and loss of differentiation between gray and white
matter at the cortical margin (Fig. 18). The pattern may
provide clues to etiology. Infarcts corresponding to
one or more arterial territories with gray matter
involvement are more likely embolic, while infarcts
falling between vascular territories (borderzone or
watershed distributions) tend to reflect a more prox-
imal lesion such as large vessel stenosis or occlusion.
Overlap in pathophysiologies and patterns occurs; for
example, a high-grade carotid stenosis or occlusion
may appear identical to an ICA terminus embolus,
and large-vessel stenosis might present with associ-
ated in situ thrombosis. Small-vessel ischemic events
will most often be invisible early, appearing in sub-
acute and chronic stages as lacunar infarcts and sub-
cortical white matter lesions.
Global injuries such as those seen with cardio-
pulmonary arrests may be ischemic, hypoxic, or
anoxic. Patterns include deep gray matter injury, cor-
tical laminar necrosis, diffuse white matter injury, or a
combination. Cardiopulmonary arrest may precipitate
borderzone injuries when a preexisting large-vessel
stenosis or occlusion is present. Hypoxic-ischemic
injury or perinatal asphyxic injury in the newborn
and premature injuries such as PVL are also examples,
but beyond the scope of this chapter (50).
CTA Noninvasive imaging methods such as
CTA play an important role in the workup of cerebral
ischemia, in acute as well as subacute or chronic
settings. Multiple studies have shown good agreement
with conventional DSA (ranging from 86% to 100%)
and other imaging modalities (Fig. 18) (5155). Follow-
up studies (DSA, MRA, and brain imaging) confirm
CTA findings in approximately 80% of cases (56).
Potential for the greatest benefit from thrombolysis
has been demonstrated in a subgroup of patients
100 Wolf

Figure 18 Acute ischemic infarct. (A, B) NECT images show dense MCA sign (A, arrow) and blurred gray-white matter borders (A and
B, arrowheads). (C, D) CTA shows relative decrease in vascularity on source image (C, arrowheads) and occlusion versus high grade
stenosis (D, arrow) with distal filling MCA branches. (E, F) Follow-up NECT more clearly shows infarct, as well as hemorrhagic
transformation (F, block arrow). Abbreviation: NECT, nonenhanced CT.

with moderate or severe persisting deficit for less than
three to six hours, MCA occlusion (as opposed to other
sites such as ICA terminus), lack of extended infarct
signs, and efficient collateral circulation (55). Also
important is the ability to detect autolyzed thrombi
and spontaneous recanalization.
Perfusion imaging and comprehensive stroke evalua-
tion. Perfusion changes are immediate in the setting of
acute ischemia (i.e., evident prior to parenchymal
abnormalities, including those identified on DWI),
and information is also provided regarding tissue at
risk. Some advocate a comprehensive exam consisting
of unenhanced CT, CTA, and CTP (57,58) (Figs. 18 and
19), attractive because of more widespread availability
of CT, better access to sick patients, patient tolerance,
and speed. Others advocate a comprehensive stroke
MR protocol. In practice, combinations are often used;
for example, NECT of the brain and CTA of the head
and the neck can be performed, followed by MRI with
DWI, perfusion-weighted imaging (PWI), and gradient
echo (susceptibility- weighted) imaging sequences,
especially for subacute and chronic ischemia workup
(47). Most of the diagnostic imaging information can
thus be rapidly obtained in the hyperacute or acute
setting, with DWI improving detection and delineation
of the extent of infarcted tissue and susceptibility-
weighted imaging providing a sensitive evaluation
for subtle hemorrhage.
The goal for intervention in the acute setting is to
reestablish blood flow without causing harm. Since
use of tPA currently relies on clinical history and early
presentation of the patient (i.e., within 3 hours for
intravenous tPA and within 6 hours for intra-arterial
tPA for anterior circulation, longer for posterior
circulation), it is hoped that techniques such as perfu-
sion imaging will help establish a new starting point
for this time frame. If extent of existing infarct and
perhaps age can be established and perfusion imaging
can help assess for tissue at risk, the window of
opportunity for treatment can be extended. Normal
brain perfusion suggests that thrombolysis or other
methods for augmenting CBF are not immediately
necessary. Patients with penumbral tissue may ben-
efit from thrombolysis, but reperfusion can lead to
life-threatening hemorrhage in severely ischemic or
infarcted tissue. CTP and (5861) XeCT perfusion
(62,63) have been applied in this setting. The Council
on Cardiovascular Radiology of the American Heart
 Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology
Association recently published guidelines for perfu-
sion imaging in cerebral ischemia (10). There is evi-
dence of potential benefit and predictive value of
perfusion methodologies such as XeCT, CTP, and
slow-infusion PBV, but larger prospective studies are
required to fully establish their role.
Subacute and Chronic Setting
When thrombolysis is no longer an option, the same
questions remain. Workup of subacute and chronic
cerebrovascular disease usually involves multiple
diagnostic imaging modalities, including combina-
tions of NECT, CTA, CTP, DUS, MRI/MRA, and
PWI, DSA, and/or XeCT perfusion. CT techniques
are typically better first-line imaging strategies,
while MRI/MRA and DUS are better in the subacute
and chronic settings. MRI is the most sensitive
and specific technique for evaluation of the brain
parenchyma. After initial workup of ischemic stroke,
NECT can be used for routine follow-up in the sub-
acute setting, assessing for infarct evolution, hemor-
rhagic transformation, hydrocephalus, cerebral
edema, or mass effect. Combinations of DUS, MRA,
and/or CTA are typically used for cerebrovascular
imaging. In the neck, DUS is often the first or screen-
ing exam. Accuracy (e.g., agreement with DSA) of
101
Figure 19 Acute ischemic infarct and CTP (same
patient in Fig. 18). One time point (A) from single-
section CTP is shown. Very low CBF (B) and CBV
(C) with prolonged MTT (D) confirm right temporal lobe
infarct. Less severe decreased CBF, symmetric CBV,
and prolonged MTT in right occipital lobe (arrows)
indicate minimal penumbra. Abbreviations: CTP, CT
perfusion; CBF, cerebral blood flow; CBV, cerebral
blood volume; MTT, mean transit time.
one noninvasive test can be improved by confirm-
ing findings with a second noninvasive test, and
by adding a third if the first two are discordant
(3,64,65).
Cerebrovascular CTA
Atherosclerosis and stenotic-occlusive disease
CTA has been shown to be useful in evaluating
carotid stenosis (6467). In general, CT tends to under-
estimate the degree of stenosis compared with DSA,
while MRA tends to overestimate. However, for
severe carotid stenosis (7099%, NASCET criteria),
CTA has been shown to be fairly accurate. In a
meta-analysis of CTA studies prior to 1998 (almost
all single-detector CT acquisitions), Hollingworth
et al. (68) reported a pooled sensitivity and specificity
of 95% and 98%, respectively. CTA remained sensitive
(95%) when stenoses greater than 30% were included,
although specificity decreased to 92%. Another sys-
tematic review of CTA studies between 1990 and 2003
(69) (all single-detector CT scanners) reported pooled
sensitivity and specificity for 70% to 99% stenoses of
85% and 93%, respectively, and for occlusions they
reported sensitivity and specificity of 97% and 99%.
Accuracy for carotid stenosis (64,66) and for occlusion
(70) will likely improve with the increasing use of
MDCT. Accuracy in detection of vascular wall pathol-
ogy such as ulceration is unclear (Fig. 20), but neither
102 Wolf

Figure 20 Ulcerations. (A) DSA shows web-like focal stenosis in proximal ICA (arrow) with probable ulceration(s) more proximally
(arrowhead ). (B) MIP image from CTA also shows the focal stenosis fairly accurately, but the ulceration is not as clearly depicted.
However, ulceration can be seen on CTA source image (C) (arrowheads). Abbreviations: DSA, digital subtraction angiography; ICA,
internal carotid artery; MIP, maximum intensity projection.

is DSA considered perfectly accurate in detection of
ulcerated plaques.
For intracranial occlusive disease, CTA perfor-
mance is in general similar to that of MRA, except for
demonstration of very slow flow and collaterals, where
CTA is superior (Fig. 21) (55,71). In comparison with
MRA and DSA in a retrospective study, Bash et al. (72)
found a higher sensitivity of CTA for intracranial
stenosis, higher positive predictive value for stenosis
and occlusion, and higher interobserver reliability.
They also found cases in which a false-positive occlu-
sion on DSA may have been present that appeared
stenotic but patent on CTA. Combining noninvasive
imaging modalities likely increases confidence (73).
False-positive occlusions in the cervical carotid
also occur (66). It is often not possible to be certain of
this event, since time tends to separate the studies and
interval occlusion or recanalization could occur
between studies. DSA is considered the gold standard,
but it is a projectional technique, and limited projec-
tions are obtained. CTA has essentially infinite pro-
jections in any orientation and thus is more likely to
find the projection with the most narrowed lumen.
Rotational angiography would be a better comparison
test in this regard (66). Very slow flow in a small-
caliber artery may be easier to detect with CTA (72). In
the case of hypoplastic or atretic carotid arteries, CTA
is complementary and in some ways superior to DSA,
with the detection of a hypoplastic petrous carotid
canal establishing the diagnosis (Fig. 22). Problem
areas for CTA in the head or the neck include over-
lapping venous structures and vessels in or around

Figure 21 Intracranial stenotic-occlusive disease and CTA. (A) Oblique axial MIP image from CTA shows high-grade left M1 stenosis
(arrowhead ) with collateral filling in MCA branches (arrow). (B) Coronal MIP projection from MRA shows the abnormal M1 segment
(arrowhead ) but no convincing collaterals because of slow flow. (C) Oblique DSA projection shows the M1 stenosis (black arrowhead)
and delayed MCA filling. Abbreviations: MIP, maximum intensity projection; DSA, digital subtraction angiography.
 Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology 103

Figure 22 ICA agenesis and atresia. CTA source images show hypoplastic right petrous carotid canal (A, black arrow), absent
intracranial ICA (B, white arrow), and transsellar collateral (C, arrowhead) from left to right anterior circulation. Abbreviation: ICA, internal
carotid artery.

bony structures and heavy vascular calcifications
(64,66). CT can be used for direct evaluation of athero-
sclerotic plaque and vessel wall as well as lumen. The
extent of calcification and other components relevant
to vulnerable plaque such as ulceration and hemor-
rhage can be evaluated. MRI is likely superior in
discriminating plaque architecture, however (74).
Arterial dissection Dissections can be catego-
rized as traumatic (discussed below) or atraumatic.
Atraumatic dissections may be spontaneous or associ-
ated with a precipitating cause such as minor or trivial
trauma (e.g., a movement or position not related to an
external traumatic force). Genetic factors perhaps com-
bined with environmental factors have been implicated
in predisposition to spontaneous dissection (75).
Inherited disorders predisposing to dissection include
fibromuscular dysplasia, Marfans syndrome, Ehler-
Danlos, homocysteinuria, and others. Hypertension
and smoking may also predispose to dissection.
Dissection of the extracranial ICA is the most
common form of cerebrovascular dissection (75).
Whereas atherosclerotic disease typically involves
carotid bifurcation and bulb/ICA origin, spontaneous
dissection often originates at least 1 cm beyond the
bifurcation and involves more distal ICA. It typically
does not extend into the petrous carotid artery, but
does occur on occasion, and thrombus can also prop-
agate distally (Fig. 23). Acute ischemic infarct in a
younger patient should prompt a search for this entity,
occurring more commonly in the age range of 35 to
50 years. Vertebral artery dissections more commonly
involve the distal portions, where atherosclerotic dis-
ease is often found more proximally. Symptoms and
findings of extracranial dissection include neck pain,
headache, Horners syndrome, cranial nerve defects,
pulsatile tinnitus and bruit, and of course transient or
permanent ischemia. Compared with extracranial dis-
section, intracranial dissection is less common, is more

Figure 23 Distal cervical carotid dissection and CTA. (A) Narrowing of cervical ICA lumen (arrow) with dilatation of vessel overall
(arrowheads). (B) Intimal flap (open arrow) with true and false lumen apparent. (C) Occlusion or high-grade stenosis ICA, possibly from
propagating thrombus (black arrowhead), with distal petrous ICA filling. Abbreviation: ICA, internal carotid artery.
104 Wolf
often traumatic, and has higher morbidity and mortal-
ity. Patients are even younger than those with extrac-
ranial dissection, and the ICA is involved more
frequently than VA (76). Intracranial dissection more
often presents with sudden early infarcts or SAH,
which affects treatment decisions regarding anticoagu-
lation (Fig. 24). Mass effect from pseudoaneurysms will
be more problematic in the closed intracranial space.
The supraclinoid ICA is the most commonly affected
segment, followed by intradural and suboccipital VA
(near intradural transition).
Dissection represents a disruption of one or more
layers of the arterial wall. Intracranial arteries lack a
vasa vasorum, so an intimal tear is more likely in
intracranial dissections. Dissection of blood between
intima and media results in narrowing and potential
occlusion of the lumen, whereas collection of blood
between media and adventitia may result in expansion
of artery diameter or pseudoaneurysm. Combinations
of arterial dilation and luminal narrowing may occur.
Imaging findings include narrowing of the lumen,
especially smooth or slightly irregular tapered narrow-
ing, intimal flaps with or without double lumens,
eccentric or crescentic wall hematoma, and pseudoa-
neurysm formation (Figs. 23 and 24) (77). Intimal flaps
are specific for dissection but are seen in a minority of
cases. It is often difficult to distinguish intracranial
dissection from other pathologies such as atheroscle-
rosis or embolism causing partial or complete
occlusion. Vasospasm can also mimic dissection.
Figure 24 Intracranial dissection presenting with
SAH. (A) NECT shows SAH anterior to pontomesen-
cephalic junction. (B) Oblique coronal MIP image from
CTA shows fusiform dilatation of intradural left vertebral
artery (arrowhead ), confirmed on AP (C) and lateral (D)
DSA projections. The appearance suggests dissecting
aneurysm. Abbreviations: NECT, nonenhanced CT;
SAH, subarachnoid hemorrhage.
Noninvasive evaluation of nontraumatic dissection
has been described more extensively with MRI and
MRA, but CTA has also been applied (7881).
Perfusion imaging and evaluating long-term risk of
ischemic event. The significance of cervicocranial
stenotic-occlusive disease is modified by collaterals,
type of plaque (i.e., vulnerable plaque), autoregula-
tion and cerebrovascular reserve, oxygen extraction
fraction, cardiac status, etc. Cerebral perfusion imag-
ing can be used to evaluate the hemodynamic effect of
stenosis or occlusion, but interpretation is more com-
plicated in the subacute and chronic setting than in
hyperacute and acute settings. Symptoms may be
intermittent with embolic and/or perfusional etiolo-
gies. Because of the modifying factors noted above, a
single baseline perfusion test may not completely
address the significance of a particular lesion
(10,82). Baseline perfusion may be normal or show
only prolonged TTP or MTT, but a delay is expected
with high-grade stenosis and is difficult to translate to
stroke risk. Qualitative analysis (i.e., comparing
abnormal to contralateral side for relative measures)
may be misleading when both sides are abnormal.
Perfusion studies with a challenge can help identify
patients who may benefit from revascularization.
Hemorrhagic and Stroke-like Conditions
Hemorrhagic stroke or stroke-like entities include
reperfusion or hyperperfusion syndromes, vasculitis/
 Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology
vasculopathy, and posterior reversible encephalop-
athy syndromes (PRES). Other causes for hemorrhagic
stroke include hypertensive hemorrhage, amyloid hemorrhage. CT, CTA, and perhaps perfusion studies
angiopathy, coagulopathy, drug abuse, and intracra-
nial neoplasms. Venous hypertension and occlusion
were discussed briefly above.
Reperfusion and hyperperfusion. Attempts to estab-
lish reperfusion via medical or catheter-based throm-
bolysis are aimed at rescuing tissue at risk around an
irreversibly injured core, but early reperfusion can lead
to edema and hemorrhage, as well as neuronal injury
in the penumbra (10,83). Potential indicators for hem-
orrhagic transformation include extent of parenchymal
hypoattenuation on baseline CT, older age, and admin-
istration of aspirin prior to thrombolysis (84). Other
indicators might include those based on perfusion
studies. One retrospective study using XeCT perfusion
reported that CBF values below 10 and perhaps even
less than 15 cc/100 g/min in aggressively managed
acute MCA infarct patients could be associated with
increased risk of hemorrhage, edema, and herniation
with or without reperfusion (85).
Hyperperfusion syndrome occurs when brain tis-
sue in a vascular territory experiencing low cerebral
perfusion pressure (CPP) due to a flow-limiting vascu-
lar lesion is suddenly subjected to a normal CPP after
revascularization (86). Autoregulation is impaired or
overwhelmed, leading to development of symptoms
such as headache, seizures, and hypertension minutes
to hours after the procedure that in some cases appear
105
identical to those of infarct. Imaging may demonstrate
breakdown of the blood-brain barrier with or without
could be of use in this setting (86).
Vasculitis and vasculopathy. Vasculitides and vas-
culopathies encountered in the head and the neck
include fibromuscular dysplasia, giant cell arteritis,
Takayasu arteritis, granulomatous angiitis of the CNS,
SLE, moyamoya disease, sickle cell disease, infectious
diseases such as syphilis and herpes virus, and many
others, including PRES such as eclampsia and hyper-
tensive encephalopathy. Imaging findings include
segmental narrowing or beaded appearance, multi-
vessel or repeated dissections or pseudoaneurysms
(nontraumatic or minor trauma), occlusions, and
moyamoya pattern (Fig. 25). In some cases (e.g.,
PRES), the diagnosis can be made more effectively
on parenchymal imaging of the brain, since the vas-
cular findings on imaging may be nonspecific, subtle,
or absent. In addition to the ability to image the brain,
CT and MRI allow direct visualization of the vessel
wall, which may be helpful in making the diagnosis of
vasculitis (Fig. 26).
Trauma
The mechanisms of extracranial and intracranial trau-
matic neurovascular injury are primarily penetrating
and blunt, but all involve some form of disruption of
Figure 25 Vasculitis/vasculopathy. CTA MIP images
demonstrating (A) neurosyphilis, with nonspecific seg-
mental arterial narrowing; (B) fibromuscular dysplasia,
with beaded appearance in both ICAs; and (C, D) AIDS
vasculopathy, with fusiform arterial dilations. Abbrevia-
tions: MIP, maximum intensity projection; ICA, internal
carotid artery.
106 Wolf

Figure 26 Cross-sectional imaging in giant cell arteritis. CTA source images show circumferential smooth thickening from great vessel
origins through (arrows) common carotid arteries (A), not seen distal to carotid bifurcation in the ICA (B, arrowheads).

the vessel wall. This disruption can be subtle, as with
slight separation of intima and media with small
intramural hematoma. More severe injuries are inti-
mal disruption with formation of flap and false
lumen, pseudoaneurysm, occlusion or transection,
and AVF. Morbidity and mortality increase with
severity, primarily due to secondary CNS injury and
typically due to thromboembolic disease, drop in CPP,
and/or exsanguination. NECT of the head is often the
first exam for evaluating intracranial injury. NECT of
the face and the neck is also used in trauma, but
usually for detection of craniofacial and spinal frac-
tures as opposed to soft tissue evaluation. NECT is
suboptimal for direct visualization of vascular injury,
relying on indirect signs such as fractures predispos-
ing to vascular injury, trajectory of penetrating injury,
proximity of penetrating injuries and/or bullet frag-
ments, hematoma, or soft tissue swelling (Fig. 27).
The gold standard for neurovascular injury is
still conventional DSA. It is also considered the defin-
itive study and can be combined with endovascular
intervention. There are some advantages to using
noninvasive imaging; for example, CTA is fast, pro-
vides information regarding nonvascular structures,
and directly images vessel wall and lumen. CTA is a
3D technique, so unlimited projections are available as
opposed to limited 2D projections obtained with con-
ventional DSA. A disadvantage of CTA is low tempo-
ral resolution, making evaluation for AVF inadequate.
Artifacts from bone, heavy calcifications, and metallic
objects such as bullets can limit accuracy and render
portions of the CTA nondiagnostic. Poor arterial

Figure 27 Indirect evidence of penetrating arterial injury on NECT. (A) Bullet trajectory passed through mandible and transverse
process of C1 on right. Fracture includes transverse foramen (arrow), indicating potential vertebral artery injury. DSA confirmed occlusion.
(B) Bullet and fragment trajectories (arrow) are concerning for MCA injury, in this case directly confirmed by demonstration of right MCA
infarct (arrowheads). Abbreviations: NECT, nonenhanced CT; DSA, digital subtraction angiography.
 Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology
contrast opacification can lead to uncertainty, and
venous opacification can limit evaluation of arterial
structures. Small distal arteries such as external
carotid branches are suboptimally evaluated. CTA
interpretation begins with source images, evaluating
for caliber change, nonanatomic cross sections, intimal
flap, vessel wall abnormalities such as hematoma, and
of course extravasation (Fig. 28). Normal arterial cross
sections away from bifurcations, kinked vessels,
and dramatic turns or loops are round or oval. Most
diagnostic information is available from source data,
but some pathology is seen best on rendered or
reformatted images (Fig. 29).
107
Figure 28 Blunt carotid vertebral injury. CTA source
images show abnormal contour of bilateral ICAs (A and
B, arrowheads). (C) Left ICA caliber change on MIP
image suggests dissection/pseudoaneurysm, improved
on 12-month follow-up (D). Abbreviations: MIP, maxi-
mum intensity projection; ICA, internal carotid artery.
Penetrating Injury
There is increasing evidence supporting the use of CTA
in this setting; for example, a recent prospective study
of 175 patients with suspected arterial injury from
penetrating trauma using single-detector CTA (87)
reported a sensitivity and specificity of 100% and
98.6% and positive and negative predictive values of
92.8% and 100%, respectively. Accuracy should
improve with MDCT. A large study of CTA for intra-
cranial penetrating trauma is not yet available, and
DSA may still be required (88). Partial or complete
occlusions are the most commonly identified carotid
Figure 29 Blunt neck trauma. (A) Filling defect in the
common carotid artery proximal to bifurcation is noted
on CTA source image, but better demonstrated on MIP
(B). Abbreviation: MIP, maximum intensity projection.
108 Wolf

Figure 30 Penetrating vascular injury. (A) Source and (B) oblique MIP images from CTA show filling defects in left ICA lumen
suggesting thrombi (arrows), poorly visualized on (C) DSA. Caliber change suggesting dissection is visible on both studies. Abbrevia-
tions: MIP, maximum intensity projection; ICA, internal carotid artery; DSA, digital subtraction angiography.

injury in penetrating or blunt trauma (Fig. 30). Pseu-
doaneurysms occur in about one-third of penetrating
injuries to the ICA. Arterial extravasation or transection
is less commonly seen with noninvasive imaging, since
these patients likely require a more aggressive workup
with DSA or surgery (Fig. 31). AVFs are less commonly
seen acutely, but may become evident later on.
Blunt Injury
Blunt carotid vertebral injury (BCVI) is less common
than penetrating injury (Figs. 28,29). Aggressive
screening has been recommended on the basis of the
impression that the rate of BCVI is higher than pre-
viously recognized, that patients are often asympto-
matic for hours to days before an injury becomes
evident, and that BCVI is treatable. Lesions for blunt
carotid injury (BCI) are typically graded on a five-point
scale (89): grade I, lumen irregularity/dissection (<25%
narrowed); grade II, dissection/intimal flap or intra-
mural/intralumenal thrombus (25% narrowed);
grade III, pseudoaneurysm; grade IV, occlusion; and
grade V, transection/extravasation (Fig. 32, see also
Figs. 2831). Early reports with single-detector CT

Figure 31 Arterial transection or extravasation from penetrating injury. CTA source images demonstrate distorted true lumen of ICA
proximally (A, arrow) and faint filling of pseudoaneurysm or hematoma (B and C, arrowheads). Distal ICA was not visualized.
 Chapter 5: CT Imaging and Physiologic Techniques in Interventional Neuroradiology
technology reported suboptimal accuracy of CTA, but
accuracy will likely improve with MDCT technology.
One recent study (90) reported an incidence of 0.60%
for BCVI for all blunt trauma admissions, incidence of
BCVI of 3.7% in screened high-risk patients, and sen-
sitivity and specificity of CTA for BCVI of 100% and
94%, respectively.
Traumatic Intracranial Aneurysms
These can be caused by blunt trauma, penetrating
injuries, and/or fractures. Though the term pseudoa-
neurysm is often used to describe incomplete disrup-
tion of all layers of the vessel wall (including this
chapter), a true pseudoaneurysm or false aneurysm is
really complete disruption of all vessel wall layers,
with blood contained by perivascular clot. It is difficult
to distinguish different forms of traumatic aneurysm
on imaging, and it is unclear whether noninvasive
imaging is adequate for excluding traumatic intracra-
nial aneurysms. These aneurysms can form in the
cavernous ICA in the setting of skull base fractures or
penetrating (or iatrogenic) injuries. Peripheral vessels
can be involved as well, including MCA, ACA, and
middle meningeal arteries and less commonly smaller
branches. For example, pericallosal aneurysms can
form from shearing or compressive injuries against
the falx. They may have a delayed presentation.
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 6
MR Angiography: Principles and Applications
in Interventional Neuroradiology
Neerav R. Mehta and Elias R. Melhem
University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, U.S.A.
INTRODUCTION
Magnetic resonance imaging has revolutionized non-
invasive imaging in the late 20th century and the early
21st century. In particular, imaging of the vascular tree
has become possible with MRI technology, with
continual refinements and improvements driving it
into the future. Magnetic resonance angiography has
roots that date back to the early 1950s, when, in the
Department of Physics at the Indian Institute of
Sciences, G. Suryan, using a U tube and coils of wire,
discovered inflow effects. Singer in the late 1950s
applied Suryans discovery of inflow effects in vivo,
using a mouse and a tourniquet. From these humble
beginnings, MRI and MRA technology has progressed
to its current level of sophistication, with both neuro-
logical and nonneurological applications (1,2).
TIME-OF-FLIGHT TECHNIQUE
The vast majority of neurovascular MRA performed
today is via time-of-flight (TOF) techniques. It is widely
employed because of its ready availability as well
as the ease of acquisition of diagnostic studies. Essen-
tially, these techniques make use of blood inflow effects
to produce high intravascular signal, while signal from
background stationary tissues are minimized (36).
Let us begin with a look at a TOF sequence.
Initially, all spins are aligned along the bore of the
magnet in the positive z axis. The spins are all pre-
cessing at the same Larmor frequency (Fig. 1).
A slice select gradient is applied, and spins
within a specific slice are tipped into the xy plane
via a 908 radiofrequency (RF) pulse. If no other RF
pulses are applied, then the spins will relax back
toward the positive z axis. At time T1, approximately
63% of the magnetization has recovered to the positive
z axis (Fig. 2).
In TOF MRA, however, before the tissues can
relax back to the positive z axis, additional RF pulses
are applied. These pulses are applied at time TR, so
that TR is less than T1 of the tissues. A closer look at
this event reveals that the first RF pulse tips the spins
in the xy plane. The xy component of the signal
dephases quickly, and the z component begins to
grow, in accordance with the tissues T1 at the given
magnetic strength. Before the z component has recov-
ered, a second RF pulse is applied and the partially
recovered z component is tipped into the xy plane.
This action results in a smaller xy component, which
subsequently dephases and results in a smaller recov-
ering z component. A third, fourth, and fifth RF pulse
are applied in a similar manner, each resulting in
smaller and smaller z components and xy compo-
nents. Eventually, this process reaches a steady
state and the spins are saturated. The shorter the TR
(the time between subsequent RF pulses), the greater
the degree of saturation (Fig. 3).
The more saturated the spins become, the less is
the signal that can be measured from those spins (as
the xy components get smaller in accordance with the
RF pulse until a steady state is reached). Recall that
both z components and xy components of the satu-
rated spins are small. If fresh spins enter a slice with a
full z-axis magnetization vector, then the moment they
are tipped into the xy plane, they will produce a large
amount of signal relative to the saturated spins.
Hence, a blood vessel bringing in fresh spins will
have high intravascular signal as the fresh spins tra-
verse a slice of saturated stationary spins. This mech-
anism is the heart of TOF MRA (Fig. 4).
If the flow of blood is slow and a volume of blood
lingers in a slice for too long, then the repetitive RF
pulses that saturate the stationary tissues also begin to
saturate the blood. As mentioned previously, shorter
TR leads to greater saturation, which also applies to
blood, and a shorter TR will cause greater blood sat-
uration once it has entered into the slice. When blood
initially enters into the slice, it has its greatest magne-
tization in the z axis. This phenomenon is called entry
slice phenomenon. As blood traverses a volume that is
continuously receiving RF pulses, the blood itself gets
saturated and the signal diminishes the further it
travels into the volume of interest. In practice, a longer
TR can be chosen in order to preserve intravascular
signal over a large volume. However, this choice is
made at the cost of decreased background tissue
saturation.
In TOF MRA, 908 RF pulses are not typically
used; instead, pulses of varying flip angles are
114 Mehta and Melhem

employed. The greater the flip angle, the greater the

background saturation of stationary tissues. This
inference can be better understood by comparing the
scenario of the 908 pulse with a scenario in which the
flip angle is 18. The 18 flip angle would lead to neg-
ligible saturation of stationary tissues. A large z-axis
component would exist even after multiple RF pulses
are used. The signal obtained from inflowing blood
would be poorly differentiated from stationary
tissues. As the flip angle increases, the saturation of
stationary tissues also increases. As in the case of
shorter TR times, with larger flip angles and greater
background stationary tissue saturation, there is also
greater saturation of blood as it traverses a volume.
Hence, the same caveat that applies to shorter TR
times also applies to larger flip angles, and flip angles
can be varied to preserve intravascular signal at the
Figure 1 cost of decreased background tissue saturation.
However, 908 flip angles are typically not used in

Figure 2

Figure 3
 Chapter 6: MR Angiography: Principles and Applications in Interventional Neuroradiology
Figure 4
clinical practice. Blood flowing within the carotid and
cerebral arteries usually has laminar flow, whereas
blood along the center of the vessel moves at a faster
velocity than blood along the periphery of the vessel.
The blood along the periphery moves so slowly
that the large, 908 flip angles quickly cause blood
saturation, which is not the case for the faster moving
blood along the central part of the lumen. The net
result is the signal arising from the central portions of
the vessel and lack of signal from the periphery,
ultimately causing a perceived decrease in the caliber
of the vessel. This observation should be noted on
most MRA sequences, particularly when slow flow is
involved in scans performed with larger flip angles.
In Figure 5 (A through D), flip angles and TR were
varied on the same subject to produce MRA images that
are presented using collapsed maximum intensity pro-
jection (MIP) algorithm in the axial projection. Figure
5A serves as the reference 3D TOF MRA performed
with a typical flip angle of 258 and TR of 42 milli-
seconds. Now, compare Figure 5A with Figure 5B,
where the flip angle was decreased to 108 (TR remains
42 milliseconds). The signal within the large vessels is
decreased; however, less blood saturation results in
better visualization of the small peripheral arteries.
Compare Figure 5B, where the flip angle is 108, with
Figure 5C, where the flip angle is increased to 508 (TR
remains 42 milliseconds). Note that there is increased
signal within the large vessels; however, blood satura-
tion has resulted in poor visualization of the small
peripheral arteries. Compare Figure 5A with Figure 5D,
where the flip angle is kept at 258, but the TR has been
increased to 84 milliseconds. The increased TR leads to
less blood saturation, and hence improved visualization
of small peripheral arteries. However, the stationary
tissues are also less saturated, resulting in less contrast
between the arteries and surrounding tissues. Figure 5E
demonstrates 3D TOF MRA performed on a 3.0-tesla
magnet. The TR and the echo time (TE) are 24 and
115
3 milliseconds, respectively. The higher field magnet
theoretically doubles the signal-to-noise ratio as well as
increases vessel contrast with respect to surrounding
tissues. Shorter TE times allow for less phase dispersion
and hence higher intravascular signal within more
peripheral vessels (see below for effect of TE times on
TOF MRA). Compare Figure 5E with Figure 5A, both of
which are performed on the same subject, to get a taste
of what can be expected as routine MR imaging
migrates from 1.5 to 3.0 tesla.
2D TOF
2D TOF involves a sequential acquisition, slice by
slice. A thin slice is selected, and the spins within
the slice are saturated. The blood flowing perpendic-
ularly into the slice is bright, with high intravascular
signal. The blood flowing into the slice at an oblique
angle would have less intravascular signal, as it would
have to traverse a greater distance than within the
perpendicularly oriented vessel. As a volume of blood
traverses a greater distance within a slice, it experi-
ences a greater degree of blood saturation (Fig. 6).
If MRA images were to be acquired at this point,
the inflowing blood from both above and below the
slice would provide intravascular signal. In the case of
neck MRA, if a slice of the midneck were to be
acquired, intravascular signal from both carotid and
vertebral arteries and the jugular veins would be
acquired. If a parallel saturation band is placed
above the slice of interest, then the spins within the
jugular veins would get saturated before they enter
the slice of interest (Fig. 7). The resultant image would
only have intravascular signal from the carotid and
vertebral arteries. If a parallel saturation band is
placed below the slice of interest, then the spins
within the carotid and vertebral arteries would get
saturated before they enter the slice of interest.
116 Mehta and Melhem

Figure 5 Compare the differences between the reference MRA data set performed at 1.5 tesla and those with varying flip angles and TR
times. (A) The reference (TR 42, TE 3, flip angle 258). (B) Same TR and TE as the reference, but with a flip angle of 108. (C) Same TR and
TE as the reference, but with a flip angle of 508. (D) Same TE and flip angle as the reference, but with a TR of 848. (E) MRA of the same
subject performed at 3.0 tesla.

Figure 6
 Chapter 6: MR Angiography: Principles and Applications in Interventional Neuroradiology
Figure 8
The resulting image would only have intravascular
signal from the jugular veins (7).
After multiple slices are acquired, the resultant
data set is usually stacked and displayed using the MIP
algorithm. Postprocessing of MRA data is required in
order to display projection images reminiscent of tra-
ditional angiography. Simply stacking the data and
then viewing the summation from the side does not
work, as there is too much background tissue that
overlaps and obscures the vasculature. MIPs transgress
this limitation by displaying only the maximum pixel
value for a given projection line. Multiple projection
images can be calculated from the stacked data set to
provide images at different angles (Fig. 8). By scrolling
through a data set of MIPs, a 3D appreciation of
vasculature can be obtained. At the Hospital of the
University of Pennsylvania (HUP), projection images
are calculated at 68 increments over 1808.
Currently, 2D TOF is primarily used for imaging
carotid and vertebral arteries in the neck. These ves-
sels have an optimal orientation to acquire 2D slices as
they enter each slice with an almost perpendicular
orientation, lacking significant tortuosity. Currently,
at HUP, 2D TOF of the neck is performed with a flip
angle of 608, TR of 45 milliseconds, and TE of 6.9 milli-
seconds. The slice thickness of 1.5 mm is used with a
117
Figure 7
matrix size of 256
128 for a total of 128 slices. This
procedure is then supplemented with a 3D gadoli-
nium-enhanced sequence (see the next section).
3D TOF
3D TOF is the same concept as 2D TOF, except that a
slab or volume (38 cm) instead of a thin slice (1.5 mm)
is obtained. There is no slice selection; instead the
z axis is partitioned into 32 to 64 slices with multiple
phase-encoding steps. This partition results in very
thin slices, usually 1 mm or less in thickness. How-
ever, since blood is flowing through a large 3D vol-
ume during the acquisition, in contrast to the thin
slices of 2D acquisitions, the blood can be saturated
as it courses through the slab. This technique does
somewhat limit the evaluation of slower flow.
Modifications of the technique include making the
slabs thinner and performing multiple sequential
acquisitions of these thinner slabs. This technique
has been termed multiple overlapping thin slab acqui-
sition (MOTSA). One of the major advantages of
employing the MOTSA technique is the reduction of
saturation effects. Flip angles are also adjusted accord-
ingly, with 3D acquisition flip angles smaller than
those of 2D acquisitions. With a smaller flip angle,
118 Mehta and Melhem
blood saturation can get minimized in the 3D TOF
sequence. Flip angles for 3D TOF range from 158 to
358, whereas for 2D TOF the flip angle ranges from 408
to 908. Other methods to reduce saturation effects
within the vessels and to enhance the visualization
of the small peripheral intracranial arteries have been
developed. These include tilted optimized nonsaturat-
ing excitation (TONE) or ramped RF and magnetiza-
tion transfer imaging (MTI). The first (TONE or
ramped RF) is based on varying the flip angles across
a volumetric slab. A voxel of blood entering a slab
experiences a smaller flip angle, and as it traverses the
slab it experiences gradually increasing flip angles.
This process can help minimize saturation of blood as
it traverses the volumetric slab. The second (MTI) is
based on additional saturation of brain tissue sur-
rounding the small intracranial arteries. With magne-
tization transfer, the bound water within brain tissue
is saturated with an RF pulse targeting the bound
waters proton precession rate (which is lower than
that of free water). The bound water then interacts
with local free water to exchange a saturated proton
for an unsaturated proton. The net result is saturation,
and hence suppression, of free water in the tissues.
MTI can assist in background suppression without
having to resort to increasing flip angles or decreasing
TR (911).
One of the major advantages of 3D acquisition
over 2D acquisition is the characterization of flow in
tortuous vessels, because 2D acquisitions are much
more dependent on the angle of vessel entry into a
given slice (see above). In 3D acquisitions, blood can
flow in any direction and produce signal, as long as
blood saturation does not occur. Given the tortuosity
of the intracranial vessels, 3D TOF is much more
widely employed for intracranial vasculature evalua-
tion. At HUP, evaluation of intracranial circulation is
primarily performed with 3D TOF acquisition, with a
flip angle of 258, TR of 48 milliseconds, and TE of
5.6 milliseconds. A total of 60 slices are obtained with
a 1 mm thickness and a 512
192 matrix.
Limitations
The characteristics that limit TOF MRA include non-
laminar blood flow, slow flow, and tortuous vasculature.
Nonlaminar flow of blood leads to mixing of
blood of differing phases. If the blood of two different
phases mixes within a voxel, the resulting voxel will
have lower signal intensity. This condition takes on
particular clinical importance in the assessment of
vascular stenoses. The flow distal to a carotid stenosis
is usually nonlaminar, which will subsequently result
in phase dispersion. The image produced will then
overestimate the degree and length of stenosis. Techni-
ques to decrease the degree of phase dispersion include
minimizing TE, acquiring thinner slices, and using flow
compensation techniques (see the next section).
Slow flow is yet another source of error in MRA
sequences. Slow flow within a TOF acquisition results
in blood saturation and hence signal loss. This loss can
somewhat be compensated for by increasing TR or
decreasing flip angles; however, it is at the cost of
background suppression and vessel signal. In general,
slow flow is more of a problem for 3D techniques than
for 2D techniques, the major reason for which is
greater blood saturation within a thick slab during
the 3D acquisition compared with a thinner slice on a
2D acquisition. If a smaller, slow-flow vessel needs to
be imaged by increasing TR or decreasing flip angles,
then MTI can be used as a tool to assist in background
suppression.
Tortuous vasculature is an intrinsic concern
when evaluating the intracranial circulation, particu-
larly at the level of the cavernous carotid artery.
A tortuous vessel may lie parallel within an imaging
slice and become subject to saturation effects. Tortuos-
ity can also result in vessels entering the slice both
from above and below the slice of interest, resulting in
signal loss in patent vasculature secondary to parallel
saturation bands.
Flow Compensation
Flow compensation, also known as gradient moment
nulling, is a necessity for high-quality MRA images.
Flow compensation addresses the issue of phase dis-
persion as blood within a vessel moves at a constant
velocity. First-order flow compensation accounts for
velocity, second-order for acceleration, third-order for
change in acceleration, and so on.
During an MR acquisition, blood will flow
through a given volume of interest. As the readout
gradient is applied across a slice, the flowing blood
experiences multiple different magnetic fields and
changes phase accordingly. Assume that a voxel of
blood traverses a volume that is experiencing a mag-
netic field gradient. As the voxel travels along, it
experiences different magnetic field strengths and
hence accumulates phase as it travels through ever-
increasing local magnetic fields. The signal from the
flowing blood can either be in phase with the sur-
rounding tissues or out of phase. It so happens,
through a quadratic relationship of phase gain with
time, that during odd echoes there is dephasing, while
during even echoes there is rephasing. Hence, increased
intravascular signal is seen during even echoes. Flow
compensation techniques essentially change the shape
of the magnetic field gradient in order to reproduce the
even-echo rephasing effect during the very first echo,
resulting in increased intravascular signal. This signal
is used primarily in first-order flow compensation. The
gradient shape can be changed to account for second-
order and third-order flow compensation; however,
with each additional order of compensation, the time
of application of the gradient increases. This increased
time leads to increased TEs. In general, the shorter the
TEs, the less the effects of signal loss from nonlaminar
flow. Thus, a balance must be struck between how
complex and long a shaped gradient can be applied
and the TE times. The first-order flow compensation is
optimal, whereas the second- and third-order flow
compensation is not worth the cost of the increased
TE times (12).
 Chapter 6: MR Angiography: Principles and Applications in Interventional Neuroradiology
Echo Time
The effect of TE on MRA is also crucial to the under-
standing and production of adequate MRA images,
especially in the case of nonlaminar blood flow. Non-
laminar flow causes a loss of signal secondary to
phase dispersion. Between the RF pulse and the time
for readout of signal, i.e., TE, nonlaminar flow allows
regions of blood within a vessel of differing phases to
mix. This mixing leads to loss of intravascular signal.
If the TE is decreased, there is less time for these
regions of blood with differing phases to mix and
hence less loss of intravascular signal.
TE should also be chosen to suppress signal from
adjacent fat. Recall that fat and water precess at
slightly different frequencies. At 1.5 tesla, water pre-
cesses 220 Hz faster than fat. This difference in preces-
sional frequency allows for spins of water and fat
molecules to be either in phase or out of phase with
each other. As both molecules exist within adipose
tissue, fat can be suppressed by choosing a TE where
the spins are out of phase and hence have decreased
signal (Fig. 9; 9A is out of phase and 9B is in phase).
CONTRAST-ENHANCED MRA
The administration of contrast at first appears to be a
natural evolution of the MRA technique. The gadoli-
nium molecule itself is paramagnetic and effectively
serves to shorten the T1 of the blood around it. The
shortened T1 has the potential to provide MRA images
with high contrast-to-noise ratios and high signal-to-
noise ratios, as well as potentially shortening acquisi-
tion times secondary to shorter TR and TE times.
Gadolinium administration also reduces the saturation
effects of slow-flowing blood. The major limitation to
administering contrast is in the venous contamination.
The bolus of gadolinium must be administered and
timed accordingly to minimize both parenchymal and
venous phases. In essence, speed of imaging is one of
119
Figure 9 Comparison of out-of-phase (A) and in-
phase (B) MRA acquisitions. Note the prominence of
the orbital fat in the in-phase sequence.
the core issues with contrast- enhanced MRA. Unfortu-
nately, for intracranial circulation, venous contamina-
tion in the cavernous sinuses and basal veins severely
limits evaluation of the circle of Willis (Fig. 10). For this
reason, contrast-enhanced MRA has yet to be widely
implemented for studies targeted to the circle of Willis.
This limitation is not an issue, however, in the neck,
where gadolinium-enhanced MRA is now commonly
used in the evaluation of carotid stenosis. In perform-
ing contrast-enhanced MRA, typically 20 cc of gadoli-
nium is administered at a rate of 2 to 3 mL/sec using a
power injector. Timing the bolus of contrast is critical
and can be performed by a number of different meth-
ods. Currently, these include best guess methods,
manual timing bolus, and automated timing bolus.
Manual methods involve the administration of a
small bolus of gadolinium, typically 2 cc, followed by
a 20-cc saline flush. The volume of interest is imaged
with fast 2D gradient-recalled echo sequence, usually
at a rate less than 1 frame/sec. Once maximal contrast
appears in the target vessel, the delay can be calculated
accordingly. Automated timing bolus methods involve
the beginning of the imaging once contrast is detected
in the vessel of interest. Imaging is subsequently per-
formed using 3D SPGR technique. Early or late bolus
timing can lead to significant artifacts and venous con-
tamination, respectively (Fig. 11). As a general rule, the
acquisition of data to fill the center of k space has to
occur at the time when the maximum concentration of
contrast material is in the vessel of interest, as this
region of k space is where contrast-to-noise ratio is
maximized. The periphery of k space is used to increase
the definition of edges and borders (Fig. 12).
Contrast-enhanced MRA has become very valu-
able in neck MRA for the evaluation of carotid artery
stenosis. The faster acquisition times can result in
3D slab acquisition times of less than 20 seconds,
compared with 2D TOF methods that can last longer
than 12 minutes for the same coverage. During respi-
ration, there is motion of the neck vasculature, which
subsequently causes artifacts on the 2D TOF sequence.
120 Mehta and Melhem

Figure 10 The top image is the arterial phase of

gadolinium. The bottom image is delayed with both
arterial and venous signal. The top image demon-
strates a left posterior communicating artery aneurysm
(confirmed on CT angiography). Venous opacification
on delayed image obscures the aneurysm. The timing
on contrast-enhanced MRA is critical, particularly in
intracranial MRA, to avoid missing pathology.

Figure 11 The bolus was timed too early on

the image on the left, whereas the bolus was
too late on the image on the right.

Figure 12 Central k space provides contrast. Peripheral k space defines lines and borders.
 Chapter 6: MR Angiography: Principles and Applications in Interventional Neuroradiology
With the 3D gadolinium sequence, the entire acquisi-
tion can be performed in one breathhold. In addition,
the TE times of contrast-enhanced 3D MRA are usu-
ally three to four times shorter than those of 2D TOF
MRA. With shorter TE, the effects of intravoxel phase
dispersion get minimized. This minimization is crucial
for the accurate assessment of the degree of a carotid
stenosis. Contrast-enhanced MRA has now widely
supplanted 2D TOF sequences in the neck. 2D TOF
data are commonly used to supplement interpretation
and serve as a backup in case the bolus of gadolinium
is poorly timed. Typical TR or TE times for 3D
gadolinium-enhanced MRA are 4.4 msec/1.6 msec,
with a 258 to 308 flip angle.
Current research efforts are focused on faster
acquisitions via parallel imaging and more efficient
filling of k space (e.g., maximize the bolus of contrast
with the acquisition of central k space to maximize
contrast resolution, while acquiring spatial resolution
data at the periphery of k space before or after the
bolus). Parallel imaging with the SENSE or SMASH
technique offers the ability to reduce scan times and
improve temporal resolution. SENSE, which stands
for sensitivity encoding, uses multiple coils in combi-
nation with a reduced field of view to reduce image
acquisition times. If a reduced field of view were used
with traditional 2D or 3D Fourier transform techni-
ques, wraparound artifact would result. However,
SENSE uses multiple coils, each with different sensi-
tivity weightings determined by their orientation
around the volume to be imaged. This configuration
allows a reduced field-of-view image to be acquired.
The reduced images are extrapolated to a full field of
view, which appears folded by the wraparound
artifact. The different sensitivity weightings from
each coil are then used to unfold the image
(Fig. 13). With the time savings of SENSE, contrast
bolus can potentially be tracked into the arterial, cap-
illary, and venous phase (1318).
121
Figure 13 Reduced FOV acquisition is
unfolded to produce the final image. Abbre-
viation: FOV, field of view.
PHASE CONTRAST MRA
Phase contrast angiography (PCA) is a third major
technique that has been developed for MR. Unlike
TOF angiography, which primarily uses magnitude
data from the MR acquisition, PCA uses the phase
data. Hence, while TOF images still have signal from
surrounding anatomic structures, PCA images dem-
onstrate signal only from flowing blood (Fig. 14). One
of the major advantages of PCA over TOF imaging is
in the assessment of flow direction and velocity. A
second advantage of PCA is in the delineation of slow
flow. TOF, however, is a faster technique that requires
only one acquisition, whereas PCA requires four sep-
arate acquisitions to create one data set.
Essentially, in PCA, contrast is achieved in blood
vessels by tagging moving blood with phase changes.
Moving objects develop a phase change as opposed to
stationary objects during the acquisition. Moreover,
the velocity and direction of the motion can be deter-
mined from the data set. The concept of phase contrast
can be understood by taking the case of a blood vessel
within a slice of interest and following the effects of
the varying gradients on a voxel of blood traveling
within that vessel. The particular gradient that makes
phase contrast possible is the bipolar gradient (1921).
Take a slice of certain thickness with a blood
vessel oriented within it so that the vessel is parallel to
the x axis and perpendicular to the y axis. In practice,
such a vessel could represent the M1 segment of the
middle cerebral artery as a patient has been placed
supine within a magnet bore, with the cranial direc-
tion corresponding to the positive z axis. Initially,
prior to any RF pulse application, all spins are initially
oriented so that their net magnetization points in the
positive z direction, along the bore of the main mag-
netic field of the magnet. Spins of stationary tissue as
well as spins within the blood vessel are all initially
oriented in the same direction of the positive z axis.
122 Mehta and Melhem

Figure 14 The left image is a TOF image,

and the right is a phase contrast angiogram.
The TOF image demonstrates a saccular
structure adjacent to the left posterior cere-
bral artery with similar signal characteristics
of the surrounding vasculature, findings were
suspicious for aneurysm. The phase contrast
angiogram shows no signal in the suspected
aneurysm and no flow. The subsequent dig-
ital subtraction angiogram demonstrates no
aneursym. Abbreviation: TOF, time-of-flight.

Figure 15

Figure 16
A 908 RF pulse is applied. The spins that were point-
ing in the positive z axis are now flipped into the xy
plane (Fig. 15). Both stationary tissue spins and spins
within the blood vessel are flipped.
A gradient is applied along the x dimension
(Fig. 16). The gradient is such that spins on the left
side of the slice experience a larger field than those on
the right. The magnetic field on the left side is larger,
tapering down to a smaller magnitude on the right side.
Hence, the spins on the left side of the slice precess
faster than those on the right. When the gradient is
turned off, the spins throughout the slice once again
precess at the same frequency, although with a change
in phase. The spins on the left side of the slice have a
different phase from the spins on the right side, they
have gained phase.
A second gradient is now applied along the
x dimension. This gradient is in the opposite direction
and of reversed polarity, but equal in magnitude to
the first gradient (Fig. 17). It is such that the spins on
the left side of the slice experience a smaller magnetic Figure 17
field than those on the right. The spins on the left,
 Chapter 6: MR Angiography: Principles and Applications in Interventional Neuroradiology
therefore, precess more slowly than those on the right.
When the second gradient is turned off, the spins once
again precess at the same rate. During the gradient,
the spins on the right gained phase, canceling the
phase gain that the spins on the left had experienced
during the first gradient. For tissues that were station-
ary during the time of application of the two gra-
dients, no net change in phase was induced.
Take the case of a blood vessel with a given volume
of blood within it so that a volume of blood is initially
located on the left side of the slice and eventually ends
up located on the right. During the first gradient, the
volume of blood experiences a larger magnetic field com-
pared with spins on the right. This magnetic field
induces a larger change in phase for that volume of
blood. During the application of the first and second
gradients, the volume of blood moves from the left of the
slice (where the larger magnetic field was experienced
and a large phase change occurred) to its right. During
the second gradient, the volume of blood experiences a
larger magnetic field, as it is now located on the right of
the slice. So its phase never returns to its original phase.
The volume of blood has gained phase relative to all the
stationary spins. The blood that travels in the opposite
direction would encounter a negative phase change. The
distance that the volume of blood travels in the time the
two gradients are applied determines the degree of
phase change. If the blood has moved slowly and trav-
eled a short distance, the phase change would be small. If
the blood has moved fast, from the very edge of the slice
on the left to the very edge on the right, then the phase
change would be maximized. Hence, the change in
phase is proportional to the velocity (Fig. 18).
Figure 19
123
The initial gradient is referred to as the first
lobe of the bipolar gradient, while the second gradi-
ent is aptly referred to as the second lobe of the
bipolar gradient. So a single application of a bipolar
gradient (both lobes) results in a data set that demon-
strates phase change in tissues with motion and no
phase change in stationary tissues. In PCA, two
acquisitions are performed with two different bipolar
gradients. The first acquisition is as described above.
The second is with a reversed bipolar gradient
(Fig. 19). Once both sets of data are acquired, a
subtracted data set is calculated. The method of sub-
traction is either via a complex difference technique or
a phase difference technique.
To further clarify the purpose of the second
acquisition with reversed gradients and the subtraction
technique, take the initial case of the first acquisition as
described above. The initial bipolar gradient, per-
formed during the first acquisition, results in zero
phase change for stationary tissues. For moving blood
within our hypothetical blood vessel, the blood that
traverses the slice from the left to the right, assume that
the first gradient induces a positive phase change. A
second acquisition is subsequently performed, identi-
cal to the first acquisition but with the two lobes of the
bipolar gradient reversed. This reversal again results in
zero net change in phase for stationary tissues. How-
ever, for moving blood, the phase change is reversed
compared with the initial acquisition: it is negative. If
the phase data from the second acquisition are then
subtracted from the phase data of the first, the phase of
the stationary spins cancels out. The phase of the
moving spins, on the other hand, being in opposite
Figure 18
124 Mehta and Melhem

Figure 20

directions, results in a phase value. As can be seen from stationary spins with the same phase get subtracted
Figure 20, the x components of the phase cancel, while out, and moving spins with phase changes are dis-
the y components are additive. Notice that the result played in the resulting image. When PCA was initially
of the final calculated phase change demonstrates a introduced, two sequences were performed along each
y-component magnitude that is maximized only in axis for a total of six acquisitions. Positive and negative
certain conditions. If the phase shift of the moving bipolar gradients were applied along each of the three
protons after each bipolar gradient is 908, the shift has dimensions (x, y, and z axes), which would result in a
the greatest magnitude after subtraction, and hence full phase contrast angiogram with phase contrast data
the greatest signal intensity. This particular phase shift in the x, y, and z dimensions, including data from the
correlates with a given velocitya parameter encoded stationary tissue (Fig. 21). The number of acquisition
by the MR technologisttermed VENC. Velocities has been decreased to 4 using the Hadamard multiplex
less than this optimal encoded velocity, VENC, have flow-encoding approach, which yields the same
phase shifts less than 908 (and greater than 08) for the data set.
first acquisition and phase shifts between 08 and 908 for Given the additional time for the application of
the second acquisition. These lower velocities have the bipolar gradients, TEs can be slightly longer than
correspondingly lower signal intensities. Velocities for TOF sequences. As in TOF, shorter TEs are desired
greater than VENC have phase shifts greater than 908 to minimize artifacts from phase dispersion. Subtrac-
and less than 1808 and also have less signal intensity. tion of two data sets allows for increased vessel
Any phase shift less than, or greater than, 908 results in conspicuity. Hence, even though blood saturation
less signal, which is why the proper velocity encoding can occur with PCA, the increased conspicuity allows
is critical in PCA. For spins moving in the opposite for a shorter TR (24 milliseconds at HUP, compared
direction, the phase shift with the velocity correspond- with 48 milliseconds for TOF at HUP). In general,
ing to 908 has the greatest negative signal. The typical maximizing TOF effects will also help maximize
VENC for arterial flow is around 60 cm/sec, and for phase contrast, as phase contrast is dependent on
venous flow around 20 cm/sec. both inflow effects and phase effects.
The PCA acquisition therefore requires that phase
be utilized. In the vast majority of MR studies, magni-
tude images are primarily used. So how does one go CLINICAL APPLICATIONS
about measuring phase? With quadrature coils, signal Intracranial Aneurysms
is measured in both the positive x axis and positive
y axis. The signal in the former is the real (also An estimated 10 to 15 million people in the United
known as the in-phase or I) component, while States have intracranial aneurysms (22). Aneurysms
the signal in the latter is the imaginary (also known that have come to the attention of physicians have
as the in-quadrature or Q) component. With both primarily presented themselves in the form of
components, one can calculate either a magnitude subarachnoid hemorrhage (SAH). These ruptured
image or a phase image. The magnitude data are aneurysms tend not to be imaged by MRA, as the
commonly used in the majority of imaging sequences, presentation is acute and conventional angiography is
including the TOF sequences. The phase data are used performed expeditiously. At most institutions,
in PCA. patients have SAH detected by either unenhanced
With the acquisition of phase data encoded with a CT scan of the head or a positive lumbar puncture.
positive bipolar gradient along the x dimension sub- Typically, patients continue on to CT angiography
tracted from a second set of phase data encoded with a and finally conventional angiography. Assessment of
negative bipolar gradient along the x dimension, the aneurysm at the time of conventional angiography
 Chapter 6: MR Angiography: Principles and Applications in Interventional Neuroradiology 125

Figure 21 Phase contrast data at the level

of the A1 and M1 segments (Fig. 20A) and
the P1 segments (Fig. 20B). Note the bright
signal in the vessels flowing toward the sub-
jects left and the dark signal in the vessels
flowing toward the subjects right, corre-
sponding to the direction of flow.

most often determines whether the treatment will
proceed with coiling or clipping. As can be seen,
MRA has little role in these patients on presentation
with SAH. It is, however, within the purview of MRA
to play a role in the follow-up of patients who have
had aneurysm coiling. Typically, these patients return
for follow-up conventional digital subtraction angiog-
raphy (DSA) to assess for coil compaction, residual
neck, and parent vessel patency. Approximately 1% to
4% of patients who have had coiling may rebleed if no
follow-up is performed, making follow-up imaging
essential. 3D TOF MRA performed at 1.5 tesla has
been reported to have sensitivities of 75% to 92% in
the detection of residual aneurysm neck (Figs. 2224).
The addition of gadolinium has been reported to
increase sensitivity to 100%, with 96% specificity at
12 months postcoiling. These initial results demon-
strate considerable promise in the future of MRA,
particularly contrast-enhanced MRA, in the follow-
up of coiled aneurysms (2325).
The second arena where MRA has a particularly
important role to play is in the detection of unruptured
aneurysms. Unruptured aneurysms (Figs. 2527) can
initially be brought to attention from screening MRA.

Figure 22 Coiled anterior communicating artery aneurysm with recanalizationdiscovered on MRA and confirmed on DSA. Abbre-
viation: DSA, digital subtraction angiography. Source: DSA courtesy of Dr. Mikolaj Pawlak, Department of Neuroradiology, University of
Pennsylvania, Pennsylvania, U.S.A.
126 Mehta and Melhem
Figure 23 Coiled right supraclinoid ICA aneurysm with recanalization on 3D TOF MRA. Note the right carotid intracranial stent.
Abbreviations: ICA, internal carotid artery; TOF, time-of-flight.
There is controversy pertaining to the screening of
asymptomatic individuals with a first-degree relative
to a ruptured intracranial aneurysm (26,27). Screening
is also considered for patients with preexisting con-
ditions (e.g., adult polycystic kidney disease, fibromus-
cular dysplasia, collagen-vascular disease) that
predispose to aneurysm formation, an area where non-
invasive MRA can play an important role without the
need for invasive conventional angiography. In the
detection of aneurysms, studies have shown sensitiv-
ities for MRA ranging from 55% to 75% in comparison
with conventional DSA. The sensitivity of the MR
study can vary depending on reader experience, type
of postprocessing algorithm applied, as well as the size
of the aneurysm. Postprocessing algorithms typically
Figure 24 Recanalization in a coiled giant
aneurysm.
include MIPs; however, multiplanar reconstructions
(MPRs) have been shown to be useful, particularly in
the characterization of the aneurysm neck. MPRs are
generated by reformatting the source data in any desir-
able plane, which then allows for the evaluation of the
data set in coronal, sagittal, and oblique planes, in
addition to the traditional axial acquisition. In addition
to postprocessed data, source data must also be metic-
ulously reviewed. Aneurysms less than 5 mm tend to
be difficult to detect on MRA. One study found the
sensitivity for detection to be 55% for aneurysms of 2 to
5 mm, whereas for aneurysms greater than 5 mm,
sensitivity has been reported to be 88%. Systems of
3.0 tesla are also now coming into clinical practice
with the FDA clearance in 1999, promising increased
 Chapter 6: MR Angiography: Principles and Applications in Interventional Neuroradiology
Figure 25
signal-to-noise and contrast-to-noise ratios. Although
the detection rate of aneurysms has not yet been shown
to improve with 3.0 tesla systems compared with
1.5 tesla, increased image quality has been reported
with improved aneurysm characterization (2833).
Carotid Stenosis
Carotid stenosis is a common indication for MRA of
the neck vasculature. Traditionally, DSA has been the
gold standard for depicting carotid stenosis. Benefit
was shown in the NASCET trial for the treatment of
symptomatic carotid stenosis greater than 70%.
127
Clearly, depicting the degree of stenosis is critical in
the proper management of these patients.
The 2D and 3D TOF techniques have been com-
monly used for imaging neck vasculature. In carotid
stenosis, the blood that flows distal to the stenotic
segment tends to be turbulent. Typically, the greater
the degree of stenosis, the greater the turbulence,
which in turn leads to signal loss on TOF imaging
secondary to intravoxel dephasing. In fact, the pres-
ence of a flow void on 2D TOF MRA of the carotids
has been demonstrated to have a positive predictive
value of 84% for high-grade stenosis (greater than
70%). Unfortunately, the turbulence factor does lead
to an overestimation of the degree of stenosis. This
factor is rather critical in the case of patients who have
intermediate stenosis but whose MRA overestimates it
as greater than 70%. Hence, 2D TOF MRA has made
its role in screening for stenosis rather than in becom-
ing a substitute for DSA. The addition of gadolinium
to the imaging algorithm has held additional promise
in the characterization of stenosis. There are increased
intravascular signal, shorter acquisition times, and
TEs, as well as a high contrast-to-noise ratio compared
with TOF MRA. With the increased intravascular sig-
nal from gadolinium, which can be substituted for a
decrease in image voxel size, the effects of turbulence,
and hence intravoxel dephasing, are minimized. The
increased speed of scanning also helps with the min-
imization of motion artifacts. As in TOF MRA, gado-
linium-enhanced MRA of the carotid vessels has a
high sensitivity for the detection of high-grade steno-
sis (9397%). However, this result is similar to the
sensitivities of 3D TOF MRA without gadolinium. In
intermediate stenoses, gadolinium has not been par-
ticularly helpful, with sensitivities ranging between
14% and 68% (Fig. 28) (3340).
MRI shows considerable promise in the charac-
terization of arteriosclerotic plaque. In addition to
assessing luminal stenosis with MRA, MRI has the
ability to distinguish the various components of arte-
riosclerotic plaque and assess for high-risk lesions.
The thickness of plaques is typically on the order of
Figure 26 Pseudoaneurysm secondary to
dissection of PICA. Digital subtraction angio-
gram on the left, MRA on the right. Abbrevia-
tion: PICA, posterior inferior cerebellar artery.
128 Mehta and Melhem
millimeters; hence high-resolution MRI with phased-
array neck surface coils is necessary to achieve the
spatial resolution required to separate intraplaque
components. Important components that can be iden-
tified with MRI include the fibrous cap and the lipid
core. Vulnerable plaques are thought to have thinned
or ruptured fibrous caps and/or large lipid cores.
The lipid core is typically of intermediate signal inten-
sity on T1-weighted sequences and hypointense on
T2-weighted sequences. However, the fibrous cap is
Figure 28 Source: DSA courtesy of Dr. Mikolaj Pawlak, Department of Neuroradiology, University of Pennsylvania, Pennsylvania, U.S.A.
Figure 27
not readily identified on standard MRI sequences.
Reports have been made of a hypointense band cor-
responding to the fibrous cap on TOF sequences. This
band lies between the hyperintense arterial lumen and
the isointense lipid core. The fibrous cap on hemor-
rhagic plaque can also be seen, as the hemorrhagic
components can be T1 hyperintense (Fig. 29). One
group has proposed the following in terms of fibrous
cap characterization: thick and intact, thin and intact,
ruptured. The thick and intact fibrous cap consists of a
 Chapter 6: MR Angiography: Principles and Applications in Interventional Neuroradiology
Figure 29 Hemorrhagic atherosclerotic plaque on TOF axial
image. Between the hyperintense lumen of the internal carotid
artery and hyperintense hemorrhage within the plaque, a thin
dark fibrous cap can be seen. Source: Courtesy of Dr. Ronald
Wolf, Department of Neuroradiology, University of Pennsylvania,
Pennsylvania, U.S.A.
uniform hypointense band on TOF sequences. The
thin and intact fibrous cap consists of nonvisualization
of the hypointense band, but a smooth lumen surface
of T1- and T2-weighted sequences. The ruptured
fibrous cap consists of nonvisualization of the hypo-
intense band and an irregular lumen surface on
Figure 30 Right carotid dissection. Fat-saturated T1-weighted image on the right, 3D TOF MRA in the middle, and MIP on the right. Note
the T1 bright intramural hematoma in the fat-saturated sequence. There is high signal in the lumen and in the hematoma on the TOF
sequence (and MIP). Abbreviations: TOF, time-of-flight; MIP, maximum intensity projection.
129
T1 and T2 sequences. Utilizing these criteria, the thin
or ruptured fibrous cap was shown to have been
associated with a recent transient ischemic attack
and stroke (4144).
Dissection
Arterial dissections in the cervical carotid and verte-
bral arteries can either arise spontaneously or occur
after a traumatic event. In both situations, MRA has
supplanted conventional angiography in the initial
diagnosis. The major findings to identify on MRA
are a double lumen with an intimal flap or an
intramural hematoma within the vessel wall. The
hematoma is immediately isointense to slightly hyper-
intense to muscle during the first few days of a dis-
section (Fig. 30). Gradually, it becomes hyperintense
and can remain so for months after the dissection. A
fat-saturated T1-weighted sequence is also helpful for
identifying the hyperintense signal of the intramural
hematoma and subtract out the T1-hyperintense fat
surrounding the artery. One can also see complica-
tions of dissection, such as pseudoaneurysm forma-
tion (Figs. 26 and 31) (45).
Intracranial Vascular Malformations
Intracranial arteriovenous malformations (AVMs) are
high-flow vascular lesions characterized by dysregu-
lated angiogenesis. The lesions tend to form during
development, with the vast majority being sporadic in
occurrence and only 2% being part of a syndrome.
Pathologically, these lesions demonstrate three major
components: feeding arteries, a nidus, and draining
veins. The feeding arteries are mature vessels that
may or may not be enlarged. The arteries supply the
AVM nidus, which is composed of numerous dysplastic,
130 Mehta and Melhem
Figure 31
thin-walled vessels. These vessels are direct arteriove-
nous shunts, without intervening capillary network.
Also note that no brain parenchyma is located within
the nidus. The nidus subsequently empties into
enlarged draining veins. Occasionally, there are associ-
ated prenidal, nidal, and postnidal aneurysms.
Figure 32 AVM on 3T TOF MRA. The image on the left is a MIP collapse, the central image is a source MRA slice, and the image on the
right is FLAIR weighted showing flow voids. Abbreviations: AVM, arteriovenous malformation; MIP, maximum intensity projection; FLAIR,
fluid-attenuated inversion-recovery.
The imaging of these lesions has traditionally
been the domain of conventional DSA. A conventional
MRI demonstrates AVMs as multiple flow voids, with
variable amounts of associated hemorrhage. MRA has
been used to characterize the morphology of the AVM
(Fig. 32). The traditional 3D TOF MRA can demon-
strate high-flow feeding vessels; however, the tech-
nique is not very sensitive to slow-flowing draining
veins. Using contrast-enhanced MRA with very short
acquisition times (TR/TE 5/2 milliseconds) does
improve the visualization of draining veins as well
as feeding arteries (46).
Unfortunately, current MRA techniques do not
provide dynamic information like conventional DSA.
Magnetic resonance digital subtraction angiography
(MR DSA) is showing promise in providing this infor-
mation. The technique essentially involves obtaining
multiple fast T1-weighted acquisitions during the
administration of gadolinium. The initial, precontrast
image is used as a mask, which is then subtracted
from the contrast-enhanced sequences. When per-
formed with the 2D technique with a thick slice, on
the order of 6 to 10 cm, an image is acquired approx-
imately every 1.05 seconds to provide the necessary
temporal resolution (47,48). As this is a 2D technique,
spatial resolution is not as optimal as with the
3D technique. The recent use of keyhole imaging
and SENSE has allowed for the 3D technique with
MR DSA, acquiring an image every 1.7 seconds (49).
Indeed, recent application of 3D MR DSA technique in
the evaluation of residual AVM after radiosurgery
demonstrated a sensitivity of 81% and a specificity
 Chapter 6: MR Angiography: Principles and Applications in Interventional Neuroradiology
of 100% in the identification of a nidus or draining
vein, compared with DSA (50).
As opposed to intracranial AVMs, dural arterio-
venous fistulas (DAVFs) are thought to be acquired
later in life, not during development. Although not
completely understood, theories suggest that venous
sinus thrombosis forms and triggers angiogenesis for
recanalization. The angiogenesis then results in one of
three types of DAVFs. The three classifications are
based on venous drainage patterns, with type 1 drain-
ing anterograde into the venous sinus itself, type
2 draining reterograde into the venous sinus (2a) and
retrograde into the subarachnoid/leptomeningeal
veins (2b), and type 3 draining solely retrograde into
the subarachnoid/leptomeningeal veins (51). Detection
of DAVF by MRI is challenging, with one study finding
that a majority of DAVFs were characterized by flow
void clusters around a dural sinus (52). Type 2 and
3 lesions also tend to demonstrate dilated leptomenin-
geal and/or medullary veins. 3D TOF MRA has a 45%
sensitivity for directly demonstrating the fistulas and a
91% sensitivity for detecting flow-related enhancement
in draining veins. Dynamic MRA sequences also show
promise in characterizing these lesions (Fig. 33).
Spinal Vascular Malformations
Spinal vascular malformations are lesions that often
require an exhaustive angiographic search with
catheterization of multiple radicular arteries to help
localize the malformations. There are four types of
spinal vascular malformations, the most common
(80%) being type 1 spinal DAVFs. These are direct
arterial to venous connections located peripherally
within the dura of a nerve root sleeve. The lesions
receive supply from a dural branch of the radicular
artery, with drainage into the cord pial veins. These
type 1 lesions are best thought of as extramedullary,
intradural, peripheral AV fistulas. Type 2 lesions are
true arteriovenous malformations located within the
Figure 33 DAVF on dynamic gadolinium-enhanced MRA. From left to right: precontrast, arterial phase, delayed phase. The filling of
leptomeningeal veins and transverse sinus is immediately evident. Abbreviation: DAVF, dural arteriovenous fistula.
131
cord itself. These intramedullary lesions are supplied
by branches of the anterior or posterior spinal artery
and typically have a compact nidus, without interven-
ing parenchyma. Type 3 lesions are more complex
than type 2 lesions and have both intramedullary and
extramedullary components. Type 4 lesions are extra-
medullary arteriovenous fistulas, like type 1 lesions;
however, they are centrally located within the subar-
achnoid space. Their arterial supply arises from either
the anterior or posterior spinal arteryand there is no
niduswith direct drainage into the spinal veins.
When patients present with a suspected spinal
vascular malformation (e.g., progressive myelopathy),
they initially undergo an MRI evaluation of the spine.
Conventional MR imaging shows T2 hyperintensity
within the cord, with multiple flow voids from
engorged venous structures. Unfortunately, the site
of T2 hyperintensity in the cord, representing cord
edema from venous hypertension and resultant cord
ischemia, does not correspond to the level of a mal-
formation. Venous flow voids may or may not be seen.
As the majority of spinal vascular malformations are
type 1, intramedullary flow voids are not reliable.
Conventional angiography is then used to painstak-
ingly evaluate multiple spinal levels in the hope of
discovering the vascular lesion. Spinal MRA has
reduced this painstaking search and assisted in the
targeting of these lesions. A marked improvement has
been reported in the true-positive detection rate of
these lesions with 3D contrast-enhanced MRA, with
the true positives improving from 15% with MRI data
alone to 50% with combined MRI and MRA data (53).
Recently, 3D contrast-enhanced MRA with an elliptic
centric filling of k space was reported to have correctly
localized spinal vascular malformations in eight out of
nine patients (Fig. 34) (54). The elliptic centric algo-
rithm fills the central portion of k space in the first
one-tenth of the total scan time. The central k space
determines contrast resolution, while the peripheral
k space determines spatial resolution; hence, arterial
contrast is maximized with elliptic centric filling.
132 Mehta and Melhem
Figure 34 Spinal DAVF demonstrated at the T11 level by 3D contrast-enhanced MRA with an elliptic centric filling of k space. The level
of the arterial feeder was subsequently confirmed on DSA and embolized. Abbreviations: DAVF, dural arteriovenous fistula; DSA, digital
subtraction angiography.
Ischemic Stroke
Ischemic stroke is one of the most common causes of
morbidity and mortality. The five-year mortality rate
for carotid territory infarction is 40% (55). Imaging has
taken on an ever-increasing role in the diagnosis of
ischemic stroke. Perhaps more enticing is the prospect
of using imaging to help triage patients to proper
therapy. Intense research efforts are attempting to
better define ischemic penumbra and stratification
for thrombolytic therapies. The pathophysiology of
ischemic stroke essentially boils down to decreased
cerebral blood flow (CBF). When CBF decreases to
below 1015 mL/100 g of brain parenchyma per min-
ute, neuronal death ensues.
Conventional MRI sequences initially demon-
strate loss of flow void in the occluded vessel and
T2-hyperintense signal in regions corresponding to
ischemic tissue. These findings are analagous to the
CT findings of hyperdense arterial attenuation from
thrombus and associated hypodensity in the affected
brain parenchyma. However, the true revolution in
MRI of stroke came with the advent of diffusion-
weighted imaging (DWI) sequences. DWI sequences
essentially measure the freedom of water. If a water
molecule is within an environment where it can move
freely in all three dimensions (e.g., outside of a cell),
then it has quite a bit of freedom, and hence increased
diffusivity. With the use of diffusion gradients, MRI
can measure the diffusivity of water, creating maps of
the apparent diffusion coefficient (ADC). Areas of the
brain that have restricted diffusivity are those where
water is primarily intracellular, not extracellular.
Hypoxic neurons have failure of their sodium/potas-
sium ATP ion pumps, leading to an influx of water
into the cell, leading to restricted diffusion. DWI, in
animal models, has the capability of imaging infarc-
tion as early as five minutes on the onset of ischemia.
In humans, DWI abnormalities have been detected as
soon as 39 minutes after the onset of stroke (56).
Restricted diffusion then typically returns to normal
by day 7.
While DWI has served to image metabolic
changes occurring with a stroke, recent efforts have
focused on perfusion. One of the observations made
with DWI is that the area of restricted diffusion can
enlarge over time following the onset of ischemia. The
growth of this hypoxic region of tissue suggests an at-
risk tissue not initially identified by DWI. Perfusion-
weighted imaging (PWI) sequences came into the
picture to help identify this at-risk tissue, also
known as the ischemic penumbra (57). PWI sequences
are typically performed by administering a bolus of
gadolinium, followed by rapid sequential images
acquired as the bolus traverses the cerebral circulation
from artery to vein. As gadolinium is paramagnetic,
the T2* is shortened and is used to track the bolus and
assess its associated signal changes in the vasculature
and parenchyma. PWI sequences result in maps of
CBF, cerebral blood volume (CBV), and mean transit
time (MTT) (Fig. 35). These three variables are related
by the central volume principle, according to which
CBF CBV/MTT. Ischemic tissue has decreased CBF;
decreased, normal, or elevated CBV depending on the
degree of vascular reserve; and elevated MTT.
Infarcted tissue has decreased CBF, decreased CBV,
and elevated MTT. It is thought that elevated MTT
may be the most sensitive indicator of brain tissue at
risk for infarction. Another MR perfusion parameter,
time to peak (TTP), which is delayed in ischemic
tissue, can be used to identify the ischemic penumbra.
On the assumption that the tissue with a restricted
diffusion is infarcted, one can then subtract DWI data
from the MTT map. The final image is that of the
ischemic penumbra, the tissue that is presumably
ischemic but not yet irreversibly infarcted. This is
the tissue that is targeted for salvage with thrombo-
lytics. There is still controversy as to whether all the
tissue with decreased CBF will proceed toward infarc-
tion or not (58). There is also controversy as to
whether the tissue identified on DWI represents
infarcted tissue, as observations have shown that
thrombolytic therapy can decrease the volume of
DWI abnormality. Hence, current measurements of
 Chapter 6: MR Angiography: Principles and Applications in Interventional Neuroradiology
ischemic penumbra can be thought of as an overesti-
mate of tissue that will proceed to nonsalvageable
infarction without intervention. Also, the current
measurements of DWI abnormality can be considered
an overestimation of nonsalvageable infarcted tissue.
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 7
Ultrasonographic Imaging and Physiological Techniques
in Interventional Neuroradiology
Jaroslaw Krejza
Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia,
Pennsylvania, U.S.A., and Department of Nuclear Medicine, Medical University
of Gdansk, Poland
INTRODUCTION
Since the introduction of echoencephalography in the
early 1950s, ultrasonic techniques have evolved dra-
matically. Ultrasound (US) imaging is now considered
an integral part of the evaluation of patients with
cerebrovascular disease (CVD), because it is noninva-
sive, relatively inexpensive, accurate, and readily
accessible. This chapter provides the basics of US
and summarizes diagnostic and therapeutic applica-
tions of US in interventional neuroradiology.
TECHNICAL ASPECTS OF US IMAGING
Basics of US
In US imaging, pulsed waves emitted by a transducer
pass into the body and reflect off the boundaries
between different tissue types. These reflections, or
echoes from the reflected waves, are then assembled
into a picture on a video monitor. The frequency,
density, focus, and aperture of the US beam can vary.
Higher frequencies produce more clarity but penetrate
less deeply into the body. Lower frequencies penetrate
more deeply but produce lower resolution, or clarity.
US entering tissue may be transmitted, absorbed,
reflected, and/or scattered (1). The transmission prop-
erties of a tissue depend on its density and elasticity.
Density and speed of propagation determine a tissues
acoustic impedance. In homogeneous tissues, US
waves propagate until all their energy is dissipated
as heat. In nonhomogeneous tissues, reflection, scat-
tering, transmission, or a combination of these pro-
cesses occurs when waves encounter a layer with
different acoustic impedance. The larger the difference
in acoustic impedance, the more the waves reflected
(1,2). Reflection further depends on the angle of inso-
nation, and stronger echoes are received when the
angle of insonation is zero (2). Strongly reflective
hyperechoic interfaces, such as bone or air, prevent
imaging of weaker echoes from deeper tissue and cast
an acoustic shadow. Hypoechoic or poorly reflective
tissues, including fluids, are called sonolucent.
Bioeffects and Safety of US
Diagnostic US can produce heat that may be hazardous
to sensitive organs (3). Nonthermal effects, such as
pressure changes and mechanical disturbances, in tissue
have not been demonstrated in humans (4). US used in
therapy, however, can cause both substantial tempera-
ture increase and mechanical damage in the tissue (46).
Thermal Effects
Generally, denser tissue absorbs more heat from US.
Therefore, the fluid does not heat very much, soft
tissues heat somewhat more, and bone heats the most.
The heating rate in the bone surface can be up to
50 times faster than in soft tissues. This heating effect
is of interest, particularly in regard to the transcranial
Doppler ultrasonography (TCD) and its therapeutic
applications. Diagnostic US systems now display num-
bers that provide crude measures of a risk to patients
from the heat and/or mechanical effects. The thermal
index (TI) is an estimate of risk from heat. When the TI
is above 1, it is recommended that the risks of US be
weighed against the benefits (4). The consensus is to
minimize exposure, particularly in pulsed Doppler
applications, as a significant temperature increase can
occur at the bonesoft tissue interface. Nevertheless,
short-term continuous TCD monitoring did not increase
temperature at the temporal window in vivo (7).
Nonthermal Effects
US can also produce various mechanical effects such
as cavitation, pressure amplitude, force, torque, and
acoustic streaming (3). Cavitation occurs when US
passes through an area that contains a cavity, such
as a gas bubble. US can cause the bubble to expand
and contract rhythmically. When bubbles pulsate,
they send secondary US waves in all directions.
These secondary waves can actually improve US
imaging. If the bubbles contract toward the point of
collapsing, they can build up very high temperatures
and pressures for a few tens of nanoseconds. These
high temperatures and pressures can potentially
136 Krejza
produce free radicals and other toxic compounds that,
although considered unlikely, could theoretically
cause genetic damage (8). The rapid contraction of
bubbles can also cause microjets of liquid that can
damage cells. The safety guidelines for diagnostic US
are designed to prevent cavitations to occur (3,4).
Apart from cavitation, US produces changes in
pressure, force, torque, and streaming. These changes,
in turn, can cause audible sounds, electrical changes in
cell membranes that make them more permeable to
large molecules, movement and redistribution of cells
in liquid, and cell damage (9). In liquids, US causes a
type of stirring action called acoustic streaming. As
the acoustic pressure of US increases, the flow of
liquid speeds up. When the streaming liquid comes
near a solid object, shearing may occur, which can
damage platelets and lead to abnormal blood clotting.
Effects of US Contrast Agents
These agents usually take the form of stable gas-filled
microbubbles (MBs), which can potentially produce
cavitations and/or microstreaming, the risk of which
increases with the mechanical index (MI) value.
Diagnostic US Techniques
Gray-Scale Imaging
B-mode, or brightness mode, displays structures pro-
portionally to the intensity of returning echoes. The
US beam is swept quickly through the field of view,
and the image is continuously renewed, allowing a
real-time visualization of the underlying tissue anat-
omy. In M-mode imaging, used to evaluate the motion
of well-defined surfaces such as blood vessel walls, a
vertical time-base trace driven from left to right across
the display is simultaneously generated. The echoes
are displayed vertically as the depth of US penetration
increases.
Doppler Display Modes and Blood Velocity Measurements
The difference in frequency between emitted and
reflected ultrasonic echoes is the Doppler frequency
shift. The magnitude of the shift depends on the US
transmission velocity in the tissue (C), the relative
velocity of blood (V), and the US emitted frequency
(Fo). The observed frequency shift (DF) is expressed as
DF 2VFo/C.
The shift is measured only for the component of
motion along the axis of the US beam. Therefore,
absolute velocity measurements require that a correc-
tion be made for the angle () between the vessel and
the beam as follows: V DFC/(2Fo cos ). Doppler
modes are used to measure flow velocity. The fre-
quency shift is proportional to the velocity of moving
blood. The simplest Doppler US instrument has two
identical piezoelectric crystal transducers. One crystal
continuously emits toward the region of interest, and
the other continuously receives reflected echoes. Flow
toward the transducer produces an increase in the
received frequency, whereas flow away from the trans-
ducer causes a drop. Continuous Doppler systems can
measure a wide range of velocities but provide no
information about the depth of the reflecting tissue,
because any moving object in the beams pathway
reflects echoes. The depth or position insensitivity of
continuous-wave Doppler is overcome to a large extent
by using pulsed-wave Doppler. In this technique, a
single transducer generates US pulses and detects
returning echoes. Assuming that the speed of trans-
mission of US in tissues is a constant, the time delay
between the emitted pulse and the reflected echo
enables the sampled structures depth to be deter-
mined. However, anatomy is not displayed, and the
pulse duration and repetition frequency impose limits
on the maximum velocity that can be measured. This
technique is used for conventional TCD. Anatomy is
displayed in duplex imaging, which combines pulsed-
wave Doppler with two-dimensional real-time gray-
scale imaging. The gray-scale image of a selected vessel
is displayed, allowing precise placement of the Dop-
pler sample volume in the vessel to measure flow
velocity throughout the cardiac cycle. Optimal angle
correction for velocity calculations can be performed as
the course of the vessel in relation to the US beam is
visually depicted. Color duplex is the most commonly
used technology today for extracranial carotid imaging.
It is also used for transcranial color-coded duplex
sonography (TCCS). Color is superimposed on a con-
ventional gray-scale image to enhance the image of the
Doppler frequency shift. Red indicates flow toward the
transducer, whereas blue represents flow away from
the transducer. High flow velocities are depicted with
increasing brightness. As a result, the presence of flow,
its direction, and hemodynamic disturbances can be
quickly assessed. The color map in color Doppler US
can be displayed as the integrated power of the Dop-
pler signal, which is related to the number of red blood
cells that produce the Doppler shift. Advantages of this
power mode include independence from the angle of
insonation, absence of aliasing, and the ability to detect
very low flows.
Piezoelectric crystals are arranged into an array
inside a transducer. Linear transducers (7.516 MHz)
for carotid imaging produce rectangular fields of
view, while phased-array transducers (13.5 MHz)
used in TCCS produce wedge-shaped fields of view.
DIAGNOSTIC US IMAGING IN INTERVENTIONAL
NEURORADIOLOGY
TCD
Since the early 1980s, TCD imaging has permitted
insonation of the basal brain arteries. TCD technology
substantially evolved during the mid to late 1990s, and
TCCS is increasingly used today. Both TCD and TCCS
have specific advantages. TCD is based on pulsed-
wave Doppler measurements of blood flow velocity.
Its 2-MHz, relatively small, transducers are easy to use,
particularly when prolonged monitoring is performed.
Experience with this technology is extensive, but the
angle of insonation cannot be assessed and exact place-
ment of a sample volume in the insonated artery can-
not be controlled, leading to an error in both velocity
 Chapter 7: Ultrasonographic Imaging and Physiological Techniques in Interventional Neuroradiology 137

measurement and vessel identification. TCCS combines
two-dimensional real-time gray-scale imaging with
pulsed-wave Doppler and color-coded display of
velocity information (10). It is performed with
phased-array, 1.6- to 3.5-MHz transducers that are
slightly larger and less easy to manipulate than their
TCD counterparts. In contrast to TCD, however, TCCS
enables the sonographer to outline intracranial paren-
chymal structures, to acquire a Doppler sample at a
specific site of an insonated artery, and to image seg-
ments of the basal cerebral arteries in color (Fig. 1).
These advantages permit more rapid studies, provide

Figure 1 (A) Typical color image of the M1 segment of the right MCA superimposed on a sector-shaped conventional gray-scale image.
The sample volume is precisely placed on a green color spot related to an aliasing artifact, which indicates the site of highest flow
acceleration in the segment, and the angle between the course of the vessel in relation to the US beam is measured by an electronic
cursor. This approach allows to obtain the angle-corrected flow velocity measurements from the waveform displayed below the gray-scale
image. In this 57-year-old patient, the follow-up TCCS study, a year after clipping of MCA aneurysm, shows blood flow velocities in the
right M1 MCA (A), M2 MCA (B), A1 ACA (C), and P1 PCA (D) within normal reference range of 110 cm/sec, 48 cm/sec, 71 cm/sec, and
58 cm/sec, respectively. Angiographic study (E) performed at the same day showed normal caliber of the vessel. (F) Shows complex
spatial relationship between US beam, courses of M1 MCA and A1 ACA, and the site of temporal window. Abbreviations: MCA, middle
cerebral artery; US, ultrasound; TCCS, transcranial color-coded duplex sonography; ACA, anterior cerebral artery; PCA, posterior
cerebral artery.
138 Krejza
more information, and improve the sonographers con-
fidence as well as the tests accuracy (11). Both TCD
and TCCS are noninvasive and enable bedside testing.
Measurements are also highly reproducible. Inade-
quate ultrasonic windows, present in 10% to 20% of
patients (12), and limited accuracy constitute the major
disadvantages.
Reference Values
Reference values have been established for both TCD
and TCCS (13,14). Because of differences in correction
of insonation angles and depth of insonation, TCD
reference values cannot be used for TCCS measure-
ments. Normal reference data for TCD and TCCS
velocities have been published elsewhere, and are
presented in Table 1 for TCCS (13,14). Velocities are
highest during the first decade of life and drop during
the fifth and sixth decades. Women tend to have higher
velocity values up to the age of 60. This tendency may
be partially explained by the effect of the hormonal
fluctuations that affect the reactivity and tone of the
cerebral vasculature (15,16). Other factors that affect
flow velocities include intracranial pressure, Hct, fibri-
nogen, cardiac rhythm disorders, and medications
(17,18). Referring of blood flow velocities obtained
from a patient to the age and sex increases accuracy
of the TCCS in detecting flow abnormalities (19).
Detection of Intracranial Arterial Occlusion
For current acute ischemic stroke therapy to be effec-
tive, it must be initiated in the first few hours after
stroke (20,21). The only current proven therapy for
acute ischemic stroke is thrombolysis with tissue
plasminogen activator (tPA) within three hours of
stroke (21,22). While this treatment appears to be
effective in all major ischemic stroke subtypes, recent
trials have suggested that some therapies may offer a
benefit for one mechanism but not for others (23,24). If
the stroke mechanism could be determined in the first
few hours after stroke, then patients with specific
subtypes could be selected for specific potential thera-
pies in clinical trials and ultimately in clinical practice.
The clinical diagnosis of stroke subtype during the
Table 1 Mean and Normal Reference Limits of Vps, Vmean, and Ved Blood Flow Velocities in MCA, ACA, and PCA Cerebral Arteries
Velocities (cm/sec) N MCA
All subjects Vps
Vmean 304
Ved
Women Vps
Vmean 193
Ved
Men Vps
Vmean 111
Ved
Abbreviations: Vps, peak-systolic velocity; Vmean, mean velocity; Ved, end-diastolic velocity; MCA, middle cerebral artery; ACA, anterior
cerebral artery; PCA, posterior cerebral artery.
first 24 hours is frequently inaccurate, since clinicians
often rely only on the history, physical examination,
noncontrast CT, and ECG. Thus, for mechanism-
directed therapy to be implemented, additional diag-
nostic information is required (Fig. 2).
In the setting of acute stroke, rapid TCD testing
can be an attractive approach to early stroke subtype
diagnosis that subsequently influences patient man-
agement (25). Early diagnosis of an acute large intra-
cranial artery occlusion with TCCS is made on the
basis of the absence of Doppler signal in the artery
(26). The suitability of the acoustic window, however,
must be proven by the visualization of at least one
ipsilateral cerebral artery (26,27). Flow disturbances in
other intracranial arteries can further increase the
diagnostic accuracy of TCCS. Occlusion of the M1
MCA, for example, is frequently associated with
increased velocities in the ipsilateral ACA due to the
increased flow through leptomeningeal collaterals
(28,29). Carotid occlusion leads to the development
of collateral flow through the ophthalmic artery and
the anterior (ACoA) and posterior (PCoA) communi-
cating arteries, while basilar artery (BA) occlusion
increases the flow through PCoA (29,30). Intracranial
occlusion of the vertebral artery (VA), located proxi-
mal to the origin of the posterior inferior cerebellar
artery, may lead to reverse flow in the ipsilateral distal
VA. Occlusions of the intracranial ICA, VA, and BA
reduce upstream velocities, except in the BA, if
adequate collateral flow through cerebellar arteries is
present.
If the results of the TCCS study are inconclusive,
MR angiography (MRA) or CT angiography (CTA)
can be used for making the diagnosis of intracranial
occlusion.
Perfect sensitivity, specificity, PPV, and NPV of
TCCS in diagnosis of M1 MCA occlusion using pre-
defined criteria were found in a study of 30 patients
with ischemic stroke of less than 24 hours duration
(31). Another study has shown that MCA occlusions
located in the main stem or branches in 20 of 23
patients with acute ischemic stroke of less than five
hours duration can be rapidly (57 minutes) detected
using contrast-enhanced TCCS (32). Other authors, on
the basis of small series, also suggest high reliability of
Arteries
ACA PCA
105 (52166) 76 (34121) 69 (37103)
68 (32112) 50 (1882) 46 (2172)
45 (1777) 33 (1057) 30 (1151)
107 (48168) 77 (39124) 70 (40107)
71 (31115) 51 (2383) 47 (2474)
47 (1775) 33 (1157) 31 (1251)
100 (54158) 74 (32123) 67 (35104)
64 (31102) 48 (1682) 45 (2073)
43 (1772) 32 (857) 30 (1253)
 Chapter 7: Ultrasonographic Imaging and Physiological Techniques in Interventional Neuroradiology 139

Figure 2 Identification of arteries of the circle of Willis with TCCS enables for an operator to detect an isolated occlusion.
(A) Angiography shows not patent A1 ACA on the right side. Also TCCS shows no flow in the A1, while flow is clearly seen in the
MCA (B), ICA (C), and PCA (D). In contrast, the A1 ACA was erroneously identified in three sequential conventional TCD studies in this
patient. Abbreviations: TCCS, transcranial color-coded duplex sonography; ACA, anterior cerebral artery; MCA, middle cerebral artery;
ICA, internal carotid artery; PCA, posterior cerebral artery; TCD, transcranial Doppler ultrasonography.

contrast-enhanced TCCS in detection of M1 MCA
occlusion (33,34). Moreover, high sensitivity (94%)
and specificity (93%) of contrast-enhanced TCCS
were reported in 30 patients with ischemic stroke
within 12 hours after symptom onset (35). The accu-
racy of TCCS/TCD in detection of occlusion of
M2 MCA has not yet been studied. A TCD study,
however, has shown that occlusion of more than three
MCA branches is associated with decreased velocities
in M1 MCA (36). Another TCD study has investigated
the diagnostic accuracy of intracranial occlusion
assessment using predefined criteria (37). The corre-
sponding sensitivities were 93% for M1 MCA, 56%
for the VA, and 60% for the BA, with specificities of
9698%.
In summary, TCD/TCCS can detect angio-
graphic MCA occlusions with high (>90%) accuracy,
and ICA siphon, VA, and BA occlusions with fair to
good (7090%) accuracy. Furthermore, TCD-detected
occlusions are associated with poor neurological
recovery, disability, or death after 90 days (38,39),
whereas normal results predict early improvement
(40,41). In patients with acute ICA territory stroke,
TCD findings, stroke severity at 24 hours, and CT
lesion size were independent predictors of outcome
after 30 days (38). When combined with carotid duplex
sonography, the presence and total number of arteries
with suspected steno-occlusive lesions (especially
intracranial) by TCD in patients with transit ischemic
attack (TIA) or ischemic stroke were associated with an
increased risk of further vascular events and death
within six months (42). TCD-detected M1 MCA occlu-
sions within six hours of stroke onset may be an
independent predictor of spontaneous hemorrhagic
transformation, with a positive predictive value of
72% (43). Occluded intracranial arteries recanalize in
most cases, and TCD/TCCS provides a means to
monitor the process. Recanalization additionally con-
firms the diagnosis of a previous occlusion (44). A
multicenter TCCS study assessed M1 MCA occlusion
and recanalization in patients with acute ischemic
anterior circulation stroke who were treated with intra-
venous tPA or aspirin or heparin (45). MCA recanal-
ization rates were 50% and 78% two hours after
therapy and 24 hours after the onset of stroke in
10 cases treated with IV tPA, and 0% and 8% in
12 conservatively treated patients. A recent study
showed that delayed (>6 hours) spontaneous recanal-
ization was independently associated with hemor-
rhagic transformation (46).
The use of contrast enhancement improves
the quality of imaging and markedly increases the
140 Krejza
diagnostic confidence of TCCS, in particular in poste-
rior circulation (47,48). TCD/TCCS is probably useful
for the evaluation of patients with suspected occlu-
sion, particularly in the ICA siphon and the MCA. The
relative value of TCD/TCCS compared with MRA or
CTA remains to be determined; however, if the results
of the TCD/TCCS study are inconclusive, MRA can be
used for diagnosis.
Perfusion harmonic imaging (PHI) can detect
ischemic lesions earlier than CT and distinguish the
stroke subtype and severity of cerebral ischemia
(49,50). There is growing interest in PHI for diagnosis,
predicting recovery, differentiating stroke pathogene-
sis, and monitoring therapy. PHI is based on the
nonlinear emission of harmonics by resonant MBs
pulsating in an US field. The emission at twice the
driving frequency, termed the second harmonic, can
be detected and separated from the fundamental US
frequency. The advantage of the harmonic over the
fundamental frequency is that MBs resonate with
harmonic frequencies, whereas adjacent tissue does
so very little (51). In this way, PHI may enhance the
signal-to-noise ratio and the ability of gray-scale scan-
ners to differentiate MBs in the tissue vascular space
from the echogenic surrounding avascular tissue. PHI
is able to identify abnormal contrast enhancement in
most patients with stroke. In one study, 84% (n 21)
of stroke patients were correctly classified on the basis
of PHI (75% sensitivity and 100% specificity in pre-
dicting size and localization of the infarction). Partic-
ularly large ischemic areas affecting both the area of
the lentiform nucleus supplied by the lenticulostriate
arteries and the convex surface of the brain supplied
by the superficial MCA can be identified and differ-
entiated from isolated perforator ischemia or infarc-
tions that exclusively affect the areas supplied by the
superficial branches of the MCA. Cortical infarctions
in the territory of the superficial MCA can be identi-
fied if the adjacent white matter was affected as well.
By contrast, lacunar infarctions could not be depicted.
PHI provides a bedside tool to locate acute cere-
bral ischemia, in particular a large space occupying
and striatocapsular MCA infarctions. A normal study
may imply a minor or lacunar stroke with minimal
tissue damage. The widespread availability of TCCS
makes this technique a practical alternative to MRI,
SPECT, and PET. Larger trials are required to establish
value of PHI with respect to the extent, severity, and
short-term outcome of hemispheric stroke. Major lim-
itations of PHI are as follows: time-consuming analy-
sis of data, problems with adequate and symmetric
transparency of temporal bone windows, limited sec-
tor-shaped view of brain parenchyma, and restricted
access to cortical areas of the brain. By contrast, the
white matter is easily and reliably depicted because of
the favorable insonation depth, the median localiza-
tion in the US sector, and the marked increase in optic
intensity after echo contrast application.
Intracranial Atherosclerotic Stenosis
Ischemia related to intracranial artery stenosis is
believed to account for 6% to 10% of strokes in Whites
and up to 29% in African-Americans and Asians
(52). The most common mechanisms for ischemic
stroke from intracranial stenosis are hemodynamic
compromise of collateral blood flow and throm-
boembolism (53). The high rate of recurrent ischemia
in patients managed medically suggests that angio-
plasty and stenting can be effective when imple-
mented in a timely fashion (54,55). Thus, early
detection of the stenosis has important implications
for stroke prevention.
TCD has been studied more often than TCCS,
and available data suggest that when compared with
contrast angiography, TCD is approximately 80% to
90% sensitive and over 95% specific in detecting sten-
otic lesions of the ICA siphon and M1 MCA (5659). In
expert hands, both the sensitivity and specificity of
TCCS for the same arterial segments are more than
98% (60,61). Both techniques are less accurate when
evaluating lesions of the PCA, VA V4 segment, and
proximal BA, with the respective sensitivity and spe-
cificity of 70% and 85% for TCD (56,62) and 70% and
98% for TCCS (60). For these lesions, CT or MRA may
be more useful, particularly in patients with acute
distal basilar artery occlusion.
There is no consensus in the literature today
regarding specific criteria for the severity of stenosis.
The investigators of the Stroke Outcomes and Neuro-
imaging of Intracranial Atherosclerosis (SONIA)
study, an NIH-funded investigation assessing the
accuracy of TCD and MRA in patients with symptom-
atic intracranial stenosis, opted for a mean velocity of
100 cm/sec for the 50% narrowing of MCA, 90 cm/sec
for the carotid siphon and supraclinoid segment, and
80 cm/sec for the distal VA and proximal BA as the
minimal cutoff points for enrollment in the study (56).
Higher peak-systolic cutoff velocities for 50% narrow-
ing, ranging from 180 to 220 cm/sec, have been
proposed for TCCS (60,61). The major diagnostic prob-
lem, however, remains in patients with insufficient
temporal windows (12). The use of sonographic con-
trast agent may further improve TCCS detectability of
intracranial stenosis in these patients.
Substantial efforts have concentrated on estab-
lishing a particular threshold of flow velocity, which
can be considered as diagnostic for a specific degree
of vessel narrowing. However, flow velocity in an
artery is affected by many factors, which limit the
diagnostic reliability of any isolated threshold of
blood flow velocity. Factors decreasing the flow
velocity, such as (1) increased intracranial pressure,
(2) decreased cardiac output, (3) advanced age of a
patient, and (4) thromboembolic occlusion of periph-
eral vessels, may lead to false-negative results. False-
positive results may arise from (1) increasing velocity
in cerebral arteries supplying collateral channels in the
presence of severe narrowing or occlusion of other
cerebral arteries, or supplying arteriovenous malfor-
mations (AVMs), (2) dilation of the cerebral resistance
vessels and disturbed autoregulation in the case of
stroke, or brain trauma, and (3) systemic diseases such
as anemia (sickle-cell anemia) and hyperthyreosis,
which may raise the CBF and flow velocity in all
cerebral arteries (63).
 Chapter 7: Ultrasonographic Imaging and Physiological Techniques in Interventional Neuroradiology
The accuracy of transcranial sonography can be
improved if several Doppler parameters are taken into
account in defining the status of a vessel (64). The use
of an interhemispheric index might be helpful in
detecting the narrowing of a vessel (65). This index,
however, is not useful when dealing with multiple
lesions. High-grade MCA stenoses may also be sus-
pected because of the presence of increased velocities
in the ipsilateral ACA, which result from leptomenin-
geal collaterals (66). Intracranial arterial stenotic
lesions in the internal carotid distribution, however,
are dynamic and can evolve over time, with increasing
or decreasing flow velocities and appearance of new
collateral patterns, the latter suggesting further hemo-
dynamic compromise distal to the stenotic lesion
(67,68). In two recent studies in small, highly selected
populations using peak-systolic or mean flow veloc-
ities and variable noninvasive criteria for change in
degree of stenosis, progression of MCA stenosis was
associated with new ipsilateral stroke or TIA or major
vascular events (67,69).
In summary, TCS/TCCS can be the first-line
modality in the detection of MCA/ICA stenosis in
patients with sufficient temporal windows, though
data are insufficient to establish reliable criteria for
greater than 50% stenosis or for progression of steno-
sis in intracranial arteries. The use of sonographic
contrast agents can increase TCCS detectability of
the artery in patients with an insufficient temporal
window. MRA or CTA should be used instead of
TCCS in patients without the windows. Also, MRA
or CTA can be used to verify the results of TCD/TCCS
before referral of a patient to intra-arterial treatment.
Catheter angiography, however, remains a first-line
diagnostic modality in patients who cannot be con-
clusively studied with TCCS, CTA, or MRA.
Diagnosis and Monitoring of Cerebral Vasospasm
Symptomatic vasospasm (VSP) contributes signifi-
cantly to the morbidity and mortality of patients after
subarachnoid hemorrhage (SAH), and evidence indi-
cates that early treatment can positively influence out-
come (see chap. 14). Proper timing for intervention is
often uncertain, because the diagnosis and monitoring
of VSP are difficult when based solely on neurological
examination, because other complications common in
this patient population, such as recurrent hemorrhage,
hydrocephalus, metabolic disorders, and seizures, can
also produce similar neurological symptoms.
Digital subtraction angiography (DSA) remains
the standard criterion for defining the anatomy of
intracranial arteries to diagnose VSP, but is impracti-
cal in screening and monitoring of VSP because it
requires significant time, requires moving the patient
to the angiographic suite, is invasive, and carries a
small but definite risk of stroke, renal injury, and other
complications. Alternative vascular tests, such as
MRA and CTA, are less expensive and safer, but
they are substantially less accurate, cannot be per-
formed at the bedside, and have often limited acces-
sibility. Furthermore, the risk associated with
transport from intensive care unit and placement of
141
the patient in an environment where monitoring is
difficult at best should not be underestimated.
TCD is employed extensively for diagnosis and
monitoring of cerebral VSP, but recent systematic
meta-analysis of published reports revealed that spe-
cificity of TCD in the diagnosis of MCA spasm is high,
at the expense of low sensitivity (70,71). For the ACA,
PCA, ICA, BA, and VA, the accuracy of TCD has
either not been estimated or is known to be low.
Opinions are that some published data are of low
methodological quality, and thus bias cannot be ruled
out. It has been suggested that mean velocities less
than 120 cm/sec or greater than 200 cm/sec, a rapid
rise in flow velocities, or a higher Lindegaard ratio
(VMCA/VICA) (6  0.3) can reliably predict the absence
or presence of clinically significant angiographic MCA
VSP, although prediction of neurological deterioration
is problematic (7173). Unfortunately, almost 60% of
patients have velocities that fall between these thresh-
olds. Consequently, the accuracy of conventional TCD
in diagnosis of VSP remains questionable. A variety of
factors, such as technical issues (the specific insona-
tion site and the angle between the artery and the US
beam cannot be determined in TCD), vessel anatomy,
age, increased ICP, mean arterial pressure, Hct, arte-
rial CO 2 content, collateral flow patterns, and
response to therapeutic interventions, influence flow
velocities and must be taken into account when inter-
preting TCD results. The other problems in the diag-
nosis of VSP are related to the common presence of
impaired autoregulation and diffuse VSP. Although
corresponding data concerning the accuracy of TCCS
in the diagnosis of VSP are scarce, published reports
strongly suggest that the accuracy of the color
technique in the detection of the condition is high
(Fig. 3) (19,70,74).
TCCS is most reliable in detecting angiographic
VSP of M1 MCA. The best predictive Doppler param-
eter is peak-systolic velocity, and an average threshold
of 182 cm/sec corresponds to maximal efficiency of
discrimination between states of spasm and nonspasm
(efficiency, sensitivity, specificity, PPV, and NPV were
92%, 86%, 93%, 73%, and 97%, respectively) (70). In the
presence of VSP, the use of the VMCA/VICA ratio
[Lindegaard index (75)] might be able to identify
patients with hyperemia, especially on triple-H ther-
apy, whereas corresponding TCCS data (74) showed
that the overall accuracy of the VMCA/VICA ratio in the
diagnosis of mild and moderate-to-severe MCA nar-
rowing is better than the respective accuracy of velocity
measurements alone. Value 3.6 of the ratio is the most
efficient threshold in the diagnosis of mild (up to 25%
narrowing) M1 MCA spasm, while the threshold of 4.4
is the most efficient in the diagnosis of moderate-to-
severe spasm (more than 25% artery narrowing) (74).
The thresholds are higher than the upper normal ref-
erence limits of the VMCA/VICA ratio, calculated on the
basis of the mean velocity (76). This ratio varies in
healthy subjects from 0.86 to 3.14, for VACA/VICA from
0.54 to 2.55, and for VPCA/VVA from 0.76 to 2.90 (76).
Standardization of flow velocities with respect to age
and sex further increases the performance of TCCS
(19). Neural networks also can be employed to improve
142 Krejza

Figure 3 Fifty-six-year old women six days after SAH. Angiography shows vasospasm in M2 MCA and A1 ACA (A) on the right side and
in the distal segment of M1 MCA of the left side (B). Based on increased mean velocities in these spastic segments217 cm/s in the M2
(C) and 393 cm/s in the M1 MCA (D), and referencing these velocities to velocities in carotid arteries in the neck (E, F) (flow velocity ratios:
8.0 on the right side and 9.3 on the left side) imaging TCD study diagnosed severe VSP. Note that the aliasing artifact (blue spot ) enabled
proper placement of a sample volume to measure the highest velocity in the M1 segment. The proper identification of the artery and the
site of highest velocity acceleration is important, because in this patient conventional nonimaging TCD study, performed on the same day,
detected only slight velocity increase (90 cm/sec) in these arteries. Abbreviations: SAH, subarachnoid hemorrhage; VSP, vasospasm;
MCA, middle cerebral artery; ACA, anterior cerebral artery; TCD, transcranial Doppler ultrasonography.

the performance of TCCS, and it has been shown that
classification accuracy amounted to 92% in moderate-
to-severe spasm detection, and to 87% in the assess-
ment of VSPs of other grades (77). Thus, it could be
recommended that patients with suspicion of MCA
VSP should be investigated first with TCD, especially
with TCCS. DSA should be reserved for patients who
cannot be conclusively investigated with TCCS.
TCCS diagnosis of ACA VSP using a mean
velocity threshold of 75 cm/sec resulted in the
 Chapter 7: Ultrasonographic Imaging and Physiological Techniques in Interventional Neuroradiology
sensitivity and specificity values of 71% and 85%,
respectively (78). Visualization of the normal and
particularly the narrowed ACA is more difficult
than that of the MCA (10). False-negative results for
ACA may be explained by collateral flow through the
ACoA and by problems with angiographic differenti-
ation of frequently occurring ACA hypoplasia from
vessel narrowing. The VACA/VICA ratio can be helpful
in the differentiation of ACA spasm from the normal
status of the artery. In practice, however, diagnosis of
unilateral spasm of the ACA is not obligatory, because
its hemodynamic consequences for the downstream
flow are generally not a cause of concern. On the
contrary, bilateral ACA spasm may reduce flow to
the postcommunicating ACA segments, and TCCS
can detect increases in velocity involving at least one
artery. Very few data have been provided on TCD
diagnosis of spasm of the PCA and BA (79). A recent
study evaluating the reliability of TCD assessment of
BA VSP found a 100% sensitivity and a 95% specificity
by using a ratio of peak mean velocity in BA to the
velocity in extracranial vertebral artery (VA) over 2 as
diagnostic criterion (80). Normal reference ranges of
the velocity ratio VPCA/VVA (0.762.90) can also be
helpful in interpreting abnormal velocity results (81).
TCD is not useful for the detection of VSP
directly affecting the convexity or vertically oriented
branches of the intracranial arteries distal to the basal
cisterns (82,83), although the presence of VSP at these
sites may be inferred in some cases by indirect Dop-
pler waveform observations (e.g., decreased diastolic
flow, increased pulsatility, side-to-side differences in
pulsatility indexes). Data on TCCS in this context are
lacking.
TCD/TCCS is useful in monitoring the temporal
course of angiographic VSP after SAH. Although no
adequate study has been conducted, TCD is thought
to be valuable in the day-to-day evaluation of SAH
patients in VSP and to assess the effect and durability
of neuroradiological interventions (84,85). TCD has
been used to detect angiographic VSP following pro-
phylactic transluminal balloon angioplasty in SAH
patients at a high risk of developing VSP (86), as a
noninvasive surrogate endpoint, or to demonstrate
biological effects of treatments for vasoconstriction
or VSP in uncontrolled trials of pharmacological
therapies for eclampsia and SAH (8789). Data are
insufficient to make a recommendation regarding the
use and method(s) of autoregulation testing to predict
the risk of delayed cerebral ischemia.
The follow-up TCD/TCCS studies to assess VSP
dynamics should begin at admission, when the prob-
ability of VSP is still relatively low, in order to deter-
mine reference velocities for further comparison. In
many patients, the rate of velocity increases and the
maximal velocity can identify patients at greatest risk
of symptomatic VSP. Such patients should receive
daily TCD/TCCS studies, while those with normal
velocities and no substantial velocity rise can be moni-
tored every two to three days throughout the period of
the high risk of VSP. In interpreting Doppler results,
the global and local ICP increase and disturbed autor-
egulation should be taken into account. In every
143
patient, the velocity ratios (VMCA/VICA, VACA/VICA,
and VPCA/VICA) should also be calculated. Increased
impedance indexes may suggest the presence of local-
ized or generalized increased ICP or hydrocephalus,
necessitating appropriate diagnostic evaluation and
treatment. A patient whose neurological condition is
deteriorating and who has a normal or nondiagnostic
TCD/TCCS study should undergo angiography to
detect TCD/TCCS occult VSP if another cause for
deterioration is not identified. In addition, patients
with VSP whose condition does not improve or con-
tinues to deteriorate in spite of aggressive conservative
management should be considered for urgent endo-
vascular treatment. TCD/TCCS can demonstrate the
effectiveness of the treatment by showing a decrease in
flow velocities and velocity ratios.
TCD/TCCS can be helpful in proper timing for
aneurysm clipping or coiling, and postoperative man-
agement. If flow velocities are very high (mean veloc-
ity in MCA above 150 cm/sec) or there is evidence of
altered autoregulation and low CBF in the first or
second week after SAH, operative results may be
poor, in particular if the patient develops hypotension
during the procedure. After the procedure, transfer
from the intensive care unit or mobilization of post-
operative patients is inadvisable in the presence of
high velocities and should be postponed until flow
velocity in the affected vessel begins to decline.
Surveillance of Coiled Intracranial Aneurysms
Endovascular detachable coil treatment is being
increasingly used as an alternative to craniotomy
and clipping for many ruptured intracranial aneur-
ysms. Since the long-term risk of reopening and pos-
sibly for rebleeding after endovascular coiling is
somewhat higher than after surgical treatment, the
persistence of aneurysm occlusion after coil emboliza-
tion is of concern. A significant problem of endovas-
cular therapy is the known instability of initial coil
packing, and complete occlusion of the aneurysm is
not always possible without running a high risk of
inadvertent vessel occlusion or coil migration. Conse-
quently, an initially occluded aneurysm can recan-
alize, which may be associated with higher risks of
regrowth and rebleeding. DSA is currently used as the
primary imaging technique for the immediate and
long-term evaluation of endovascular therapy of intra-
cranial aneurysms. Diagnostic DSA is performed at
least three times: at the end of coiling procedure and
at 6 and 18 months after the procedure. If reopening
resulting in moderate-to-extensive residual flow is
seen in subsequent DSA studies, then re-embolization
therapy is usually undertaken. DSA, however, is a
costly and invasive procedure. Furthermore, the esti-
mation of aneurysm occlusion can sometimes be dif-
ficult because of X-ray attenuation of metal coils and
artifacts caused by the densely packed coils (Fig. 4).
TCCS may be more cost effective in the surveil-
lance of coiled intracranial aneurysms. TCCS can
identify large and medium-sized intracranial aneur-
ysms located in the proximal segments of the circle of
Willis (9092). Typically, an aneurysm is imaged as a
144 Krejza
Figure 4 TCCS can identify large- and medium-sized intracranial aneurysms in the proximal segments of the circle of Willis.
Angiography (A) shows large ICA aneurysm, which is depicted with power TCCS as red pulsatile color structure (B). Abbreviations:
TCCS, transcranial color-coded duplex sonography; ICA, internal carotid artery.
pulsatile colored structure adjacent to the large parent
artery. Aneurysms can display various flow patterns.
The most typical color-coded feature is the presence of
two areas with inversely directed flow: half of the
aneurysm is coded blue and the other half is coded
red. The colors correspond to the direction of inflow-
ing and outflowing blood. Between these two areas, a
black separation zone with undetectable blood flow
can be recognized. Flow velocities are usually low,
without turbulence and spontaneous velocity fluctua-
tions. Aneurysms located in the basal arterial trunks
can be recognized more easily than those situated in
the periphery. The use of sonographic contrast mate-
rial can improve the reliability of TCCS in the detec-
tion of aneurysms.
Preliminary reports suggest that TCCS with con-
trast enhancement is highly specific and sensitive in
the detection of clinically relevant residual flow within
an aneurysm after endovascular coiling. Schuknecht
et al. (93) reported that TCCS, performed immediately
after embolization, reliably confirmed complete occlu-
sion of 42 out of 43 aneurysms. In four other aneur-
ysms, a slight residual flow was recognized with
TCCS. Furthermore, in three (ophthalmic and basilar
tip and cavernous carotid aneurysm) of 26 aneurysms
reexamined 6 to 20 months after treatment, reappear-
ance of color flow signal adjacent to the coils was
detected, which was in agreement with DSA. The
persistent occlusion in the other 23 cases was demon-
strated by TCCS, which was either confirmed by
angiography in 13, or by MRA in 10. Turner et al.
(94) reported that TCCS confirmed complete occlusion
in 19 of 20 aneurysms, while minor residual flow was
detected with TCCS in 4 of 10 aneurysms. In the
detection of clinically relevant residual flow,
the results of standard TCCS were less consistent.
While moderate residual flow was detected in eight
of nine aneurysms (sensitivity 89%, specificity 97%),
more extensive residual flow was detected only in
three of seven aneurysms (sensitivity 43%, specificity
100%). The use of contrast slightly improves the sen-
sitivity of TCCS in the detection of moderate (100%)
residual flow, but substantially improves sensitivity in
aneurysms with extensive residual flow (86%) (94,95).
These studies suggest that TCCS could be used to
selectively monitor intracranial aneurysms, which
would reduce the requirement for long-term invasive
monitoring. The detection of neck refilling is improved
with contrast enhancement. In our study (unpublished
data), which is based on 107 patients with coiled
aneurysms, we found that standard TCCS can be
very specific in detecting moderate-to-severe residual
blood flow in relatively large (over 10-mm-diameter)
aneurysms located at the basilar tip, at the ICA bifur-
cation, and at the AcoA area. Thus, TCCS has great
potential to replace DSA in the surveillance of coiled
intracranial aneurysms in selected locations (Fig. 5).
Vascular Malformations
TCCS studies of AVMs show a focal accumulation of
vascular convolutions as a color mosaic with abnor-
mal Doppler waveforms (96,97). TCCS and TCD can
also detect the hemodynamic abnormalities in feeding
and draining vessels. Typically, flow velocities
in feeding vessels are high, ranging from 140 to
200 cm/sec, and impedance indexes are low, indicat-
ing a drop in distal resistance (98,99). Draining veins
are enlarged, channeling pulsatile arterialized blood
away from the AVM nidus (Fig. 6).
The diagnostic accuracy of TCD and TCCS in
detecting AVMs is not known. Large (>4 cm) and
medium-sized (24 cm) radiologically proven AVMs
are regularly detected (100). Because more than one-
third of small (<2 cm) AVMs can be missed, TCD is not
considered a reliable diagnostic tool in this setting.
Nevertheless, both TCD and TCCS are useful in mon-
itoring the effects of therapeutic procedures (101,102).
 Chapter 7: Ultrasonographic Imaging and Physiological Techniques in Interventional Neuroradiology 145

Figure 5 TCCS can detect clinically relevant residual flow within an aneurysm after endovascular coiling. In a patient with ICA
bifurcation aneurysm (A), TCCS shows coils as hyperechoic structure (BD), while TCCS in power mode identifies residual flow in the
neck and body of the aneurysm. Abbreviations: TCCS, transcranial color-coded duplex sonography; ICA, internal carotid artery.

The Intracerebral Venous System: A Neurosonological
Study with TCCS
The straight sinus, basal cerebral veins, cavernous
sinus, and superior and inferior sagittal sinuses can
be insonated with TCCS. Normal peak-systolic veloc-
ities usually range from 5 to 35 cm/sec, varying from
one sinus to the other (103). In sinus thrombosis, flow
velocities may decrease, or they may markedly
increase to above 100 cm/sec, most likely indicating
increased collateral circulation (104,105). Follow-up
studies show gradual normalization after a period of
months (105). Venous flow velocities are also affected
by ICP changes (106). Experience with cerebral vein
insonation, however, remains limited.
Current View on Microemboli Detection
The physical and technical aspects of ultrasonic detec-
tion of microembolic signals (MES) by TCD have
recently been reviewed (56,107,108). Particulate (solid,
fat) and gaseous materials in flowing blood have dif-
ferent acoustic impedance properties than surrounding
red blood cells. The Doppler US beam is both reflected
and scattered at the interface between the embolus and
blood, resulting in an increased intensity of the
received Doppler signal. MES are usually observed
within the spectral envelope, while artifacts, which
can resemble MES, extend outside the envelope and
are bidirectional. The hierarchy of backscatter of the
US, in descending order, is gaseous emboli, solid
emboli, and normal-flowing blood (including transient
red blood cell aggregates). In clinical practice, however,
it is difficult to determine whether a given MES corre-
sponds to a large platelet embolus or to a small
atheroma due to a considerable overlap between MES
characteristics. Several techniques have been proposed
to resolve these issues (Fig. 7) (109).
Technical limitations present considerable diffi-
culties. For example, using a higher-decibel threshold
improves reproducibility, but it can decrease sensitiv-
ity (110). In an attempt to establish a general consen-
sus among investigators, a committee of experts has
defined MES characteristics (107). Manual saving of
suspicious signals by the recording operator and sub-
sequent offline analysis is the standard practice today,
but it is cumbersome and time consuming. Automated
systems for embolus detection have been developed
(111,112). Their accuracy remains limited. Although
the optimal duration of insonation needed to achieve
maximum sensitivity is unknown, most centers mon-
itor for 30 minutes to 1 hour (113). Longer periods of
146 Krejza
Figure 6 TCCS shows an AVM in the base of the skull as an area of color mosaic with abnormal low-resistance Doppler waveforms
(A, B). TCCS in power mode (C) shows the arterial convolution of AVM in red color, which can help identifying the feeder and drainer
vessels. Angiography shows that the AVM is supplied from right (D) and left side (E). Abbreviations: AVM, arteriovenous malformation;
TCCS, transcranial color-coded duplex sonography.
insonation, or repeat studies, may be needed in some
instances.
MES have been detected in patients with asymp-
tomatic and symptomatic high-grade ICA stenosis,
prosthetic cardiac valves, myocardial infarction, atrial
fibrillation, aortic arch atheroma, fat embolization
syndrome, and retinal or general cerebral vascular
disease. In addition, these signals occur in coronary
catheterization, coronary angioplasty, direct current
cardioversion, cerebral angiography, carotid endarter-
ectomy (CEA), carotid angioplasty, and cardiopulmo-
nary bypass. TCD can be used to localize the embolic
source or monitor the effects of antithrombotic treat-
ment in patients with atherosclerotic CVD (114). In
patients with high-grade carotid stenosis, sources of
asymptomatic MES may include ulcerated plaques
(115) and microscopic platelet aggregates and fibrin
clots (116). Asymptomatic cerebral microembolization
was associated with an increased risk of further cere-
bral ischemia in this setting (115).
Comparison between studies on MES detection
is difficult, however, because of differences in: 1)
diagnostic criteria, 2) detection threshold, 3) instru-
ments and instrument settings, 4) nature and severity
of disease, 5) time between last symptom and detec-
tion of microembolic signals, and 6) incidence of
microembolic signals (56,107). Nevertheless, TCD is
probably useful to detect cerebral MES in a wide
variety of cardiovascular or cerebrovascular disorders.
However, current data do not support the use of TCD
for diagnosis or for monitoring response to antithrom-
botic therapy in ischemic CVD. Furthermore, data
have not shown that detection of MES leads to
improved patient outcomes.
US Monitoring of Neurointerventional Procedures
Carotid angioplasty and stenting. MES have been
associated with a higher neurological complication
rate and are a potential cause of periprocedural stroke
after CEA. MES have also been observed during
carotid angioplasty and stenting (CAS). The high fre-
quency of MES, however, is not associated with a
chronic cognitive impairment as shown by TCD mon-
itoring, although CAS is accomplished with increased
dislocation of microemboli compared with the surgi-
cal approach (117). Consequently, cerebral protection
devices are increasingly used. TCD monitoring can
help assess the efficacy of cerebral protection devices
deployed during stenting (118), though a recent study
showed that the frequency of procedure-related silent
cerebral lesions appeared to be independent of the
number of MES during the procedure (119). Also, a
systematic microscopic analysis of debris captured by
 Chapter 7: Ultrasonographic Imaging and Physiological Techniques in Interventional Neuroradiology
Figure 7 TCD can detect MES in major intracranial arteries.
The upper image shows MES during carotid angioplasty and
stenting, performed without a protective device. The MES are
also present at clam release during CEA (lower image). Also note
that flow velocities rebound substantially after the clamp release.
Abbreviations: TCD, transcranial Doppler ultrasonography; MES,
microembolic signals; CEA, carotid endarterectomy.
the filter device has no predictive value for potential
cerebral ischemia after carotid artery stent placement
(120). In CAS, TCD monitoring provides insight into
the pathogenesis of procedure-related cerebral events.
Microemboli during poststent dilation, particulate
macroembolism, massive air embolism, and angio-
plasty-induced asystole are associated with adverse
outcome, as are male gender and prior cerebral ische-
mia (121). TCD monitoring can also predict early
cerebral outcome after carotid bifurcation CAS (122).
In CAS, in addition to such obviously adverse events
as particulate macroembolism and massive air embo-
lism, multiple MES (>5 showers) at postdilation after
stent deployment and angioplasty-induced asystole
and hypotension with a significant reduction in
MCA blood flow velocities are associated with peri-
procedural cerebral deficits. In combination with the
presence of preprocedural cerebral symptoms, these
four TCD-monitoring variables reasonably differenti-
ate between patients with and without adverse cere-
bral outcome (122). Additionally, color-coded duplex
sonography of carotid arteries can demonstrate hemo-
dynamic improvement after ICA stenting (123). A
study suggests that asymptomatic MES correlate
with clinical risk (124). However, outcome studies
147
are required to determine whether MES detection
may allow prediction of stroke risk and monitoring
of the effectiveness of therapy.
Percutaneous angioplasty in posterior arteries. TCD
monitoring is also useful to detect MES during and
after percutaneous transluminal angioplasty (PTA) in
the posterior circulation (125). In the patients with
subclinical microemboli released from the dilated
vessels for three days after vertebral and subclavian
PTA, anticoagulant or antiplatelet therapies may pre-
vent embolic complications after the procedure.
Monitoring of endovascular treatment of intracranial
aneurysms. Selective occlusion of intracranial aneur-
ysms with detachable coils has an overall estimated
procedure-related permanent complication rate of
3.7% to 6.8%. Thromboembolic events with partially
or completely persisting neurological deficits are
reported in 2.4% to 5.2% of endovascular-treated
patients (126). Intraprocedural systemic administration
of heparin is widely used in several institutes to reduce
the risk of thromboembolism. Acute clotting at the
thrombogenic interventional materials is considered
the most important source of thromboembolism dur-
ing endovascular embolization of cerebral aneurysms.
Potential clinical complications can be avoided by
early recognition of thrombus at the coilparent artery
interface and by administering appropriate medical
therapy (127). TCD monitoring during and immedi-
ately after coiling can help identify patients at high risk
of thromboembolic complications. Those with high risk
can be selected for a therapy. A relatively low-dose
intra-arterial abciximab infusion can immediately dis-
solve an acute thrombus that forms during intracranial
aneurysm coil placement (128). An inhibition of the
platelet function by acetylsalicylic acid might be yet
another effective strategy to minimize the rate of
thromboembolism (129). However, even if the anti-
coagulation strategy is the most important factor to
decrease the rate of embolic events during aneurysm
treatment, the strategy has to balance the risks of
thromboembolism and bleeding (129).
Duplex Sonography of Carotid
and Vertebral Arteries
Sonographic Assessment of Vascular Pathology
The earliest atherosclerotic changes include intimal
thickening secondary to lipid deposits and lipid-
laden macrophage infiltration of the arterial wall
(130). As the process advances, atheromatous plaques
begin to protrude into the arterial lumen. Initially,
these plaques are covered with a fibrous cap that gives
them mechanical stability. Fibrous plaques are rarely
associated with neurological symptoms. On US, they
appear smooth, isoechoic, and homogenous. During
subsequent stages, increasing amounts of extracellular
lipids and cholesterol esters are deposited, calcifica-
tion occurs, and intraplaque hemorrhages develop,
giving the plaque a heterogeneous appearance on
US examination (108). When the mechanical support
of the plaque surface erodes, embolization of plaque
contents may occur. In addition, plaque surface ulcers
148 Krejza

Figure 8 Atherosclerotic plaques on US images. (A) Homogenous, soft, and fibrous plaque at the ICA origin without velocity increase. In
another patient, (B) the soft plaque in the ICA is irregular with hypoechoic area within the plaque as a potential source of
thromoembolism. In the third patient, (C, D) plaques are more complex with calcification. In the left, ICA (C) plaques cause over 70%
stenosis with subsequent peak-systolic velocity increase to 270 cm/sec, while on the left side irregular plaques cause less than 50% ICA
narrowing. Abbreviations: US, ultrasound; ICA, internal carotid artery.

may develop and serve as foci for thrombus forma-
tion. These plaques appear heterogeneous with vari-
able echodensities, calcific shadows, and surface
irregularities. Morphological and physiological fea-
tures readily assessed with US and associated with
an increased risk of cerebral infarction include intra-
plaque echolucency, surface ulceration, and most
importantly degree of stenosis (Fig. 8).
Degree of Stenosis
The North-American Symptomatic Carotid Endarter-
ectomy Trial (NASCET), the European Carotid Sur-
gery Trial (ECST), and the Asymptomatic Carotid
Artery Surgery (ACAS) trial demonstrated the benefit
of endarterectomy in symptomatic and asymptomatic
patients with moderate and severe carotid stenosis
(131133). In NASCET, however, endarterectomy was
only marginally beneficial when the degree of stenosis
was between 50% and 70%, underscoring the impor-
tance of accurately measuring the severity of stenosis.
Ultrasonography must therefore be able to distinguish
between a carotid stenosis of 50% and of 70% in
symptomatic patients and to identify 60% diameter
stenosis in asymptomatic patients.
Noninvasive evaluation of the extracranial ICA
with color duplex US and MRA is increasingly regarded
a replacement of DSA, but the role of ultrasonic
quantification of narrowing is not undisputed (134). In
a recent study comparing duplex US to DSA, duplex
ultrasonography misclassified 28% of patients consid-
ered candidates for CEA (135). Other studies suggest
that this classification can be performed more accurately
if high standards of ultrasonography are maintained
(136138).
Various diagnostic criteria have been proposed
for determining the percentage of stenosis (see
reviews of the criteria and tables) (108,138,139).
These include peak-systolic velocity, end-diastolic
velocity, and the ratio of peak-systolic velocities in
the ICA to the mid-CCA (ICA/CCA ratio). The peak-
systolic velocity has traditionally been felt to provide
the closest angiographic correlation and is easily
obtained; however, many laboratories rely also on
the end-diastolic velocity or the VICA/VCCA ratio to
obtain improved diagnostic accuracy and to correct
for factors that may alter the carotid blood flow. Such
factors include low cardiac output, valvular disease,
acute elevations in blood pressure, anemia, and abnor-
mal collateral flow. Any of these conditions may lead
to flow alterations across a carotid plaque and to
either over- or underestimation of the true degree of
stenosis. In these instances, the VICA/VCCA ratio often
helps in correcting for hemodynamic disturbances,
but it has limitations (108). The diagnostic impression
is further confirmed by B-mode and color flow
 Chapter 7: Ultrasonographic Imaging and Physiological Techniques in Interventional Neuroradiology 149

imaging, which allow visual inspection of the degree Table 3 Diagnostic Parameters for Internal Carotid Artery
of stenosis caused by the plaque. A quantitative cross- Stenosis of 60% or More
sectional analysis of plaque stenosis derived from Diagnostic Sensitivity Specificity Accuracy
color flow images was recently proposed, which fur- Reference criteria (%) (%) (%)
ther increases diagnostic accuracy (140).
150 Vps > 260 and 84 94 90
Ved > 70
Reference Values
151 ICA/CCA Vps 97 73 76
A wide range of criteria have been proposed to iden- ratio > 2
tify the clinically relevant degrees of ICA stenosis. Ved > 40 97 52 86
They are summarized in Tables 24. The diagnostic ICA/CCA Ved 100 80 88
accuracy of duplex US ranges between 85% and 95% ratio > 2.4
and varies among laboratories. A survey of diagnostic Vps > 170 98 87 92
criteria showed that at least nine different diagnostic 152 Vps > 245 and 89 92 NR
parameters are currently used to measure the severity Ved > 65
of stenosis (141). These differences among laboratories
illustrate the fact that US testing is equipment and All velocities in cm/sec.
operator dependent, and they emphasize the necessity Abbreviations: NR, not reported; Vps and Ved, peak-systolic and
for each laboratory to develop its own diagnostic end-diastolic velocities, respectively; CCA and ICA, common
criteria on the basis of DSA correlations (142,143). and internal carotid arteries, respectively.

Clinical Utility of Carotid Duplex Table 4 Diagnostic Parameters for Internal Carotid Artery
Characterization of plaque morphology and determina- Stenosis of 50% or More
tion of degree of vessel stenosis are the most common Diagnostic Sensitivity Specificity Accuracy
clinical applications of carotid US and were reviewed in Reference criteria (%) (%) (%)
many publications (108). In interventional neuroradiol- 153 Vps > 120 79 84 82
ogy, carotid US is also used in the following areas.
145 Vps > 130 97 97 97
Table 2 Diagnostic Parameters for Internal Carotid Artery 154 ICA/CCA Vps 95 92 93
Stenosis of 70% or More ratio > 1.6

Diagnostic Sensitivity Specificity Accuracy 155 Ved > 50 91 86 89

Reference criteria (%) (%) (%) Vps > 150 98 84 92
ICA/CCA Vps 96 89 93
139 Vps > 230 80 90 NR
ratio > 2
144 Vps > 325 83 100 88
149 ICA/CCA Vps 93 83 88
ICA/CCA Vps 91 87 88
ratio > 1.6
ratio > 4
Vps > 130 92 90 91
145 Ved > 100 77 85 80
Vps > 210 89 94 93 All velocities in cm/sec.
Vps > 130 and 81 98 95 Abbreviations: Vps and Ved, peak-systolic and end-diastolic
Ved > 100 velocities, respectively; CCA and ICA, common and internal
carotid arteries, respectively.
146 Vps > 270 96 86 88
Ved > 110 91 93 93
Vps > 270 and 96 91 93
Ved > 110 Monitoring after revascularization procedures. While
147 Ved > 70 92 60 77 the practice of serial follow-up examinations after
ICA/CCA Ved 100 65 79 endarterectomy is intuitively appealing, the value of
ratio > 3.3 routine postoperative surveillance is uncertain. The inci-
Vps > 210 94 77 83 dence of restenosis (defined as a reduction in diameter
ICA/CCA Vps 91 78 83 of more than 50%) varies between 2% and 20% at one to
ratio > 3 three years after surgery (156), but the incidence of
148 Vps > 130 and 87 97 95 recurrent symptoms is low (157,158). Restenosis within
Ved > 100 two years of surgery is usually secondary to intimal
hyperplasia and carries a benign prognosis, since the
149 Vps > 230 86 90 89
risk of distal embolism is low and lesions often regress
Ved > 70 82 89 87
ICA/CCA Vps 87 90 89
(158,159). Late restenosis is most likely secondary to
ratio > 3.2 recurrent atherosclerosis, and the associated risk of
ipsilateral hemispheric or retinal symptoms may not
All velocities in cm/sec. be different than that of the original primary lesion
Abbreviations: NR, not reported; Vps and Ved, peak-systolic and (159). In a small percentage of cases, postoperative
end-diastolic velocities, respectively; CCA and ICA, common testing shows evidence of thrombus formation at the
and internal carotid arteries, respectively. endarterectomy site, intimal flaps, and occlusion.
150 Krejza
Figure 9 Carotid US of common carotid artery dissection. Gray-scale image (A) shows luminal irregularities and an intimal flap. Color
image (B) confirms absence of flow beneath the flap. In the ipsilateral internal carotid artery (C), the flow pattern is abnormal with
disappearance of flow during diastole (high-resistance flow pattern). Note, compensatory high-velocity flow pattern in the VA (D).
Abbreviation: US, ultrasound; VA, vertebral artery.
Intracarotid and intravertebral stent placement is
being performed with increasing frequency. Repeat
testing after stent placement usually reveals an
improvement of the intraluminal hemodynamic pat-
tern. It is unclear, though, whether the diagnostic
criteria presented in Tables 24 are applicable in the
detection and monitoring of in-stent stenosis.
Arterial dissection. The US features of dissection
are less specific than those observed with angiography
and usually reflect flow abnormalities seen in high-
grade stenosis secondary to any etiology: high flow
velocities, high resistance flow patterns, or complete
absence of flow (108,160). Despite the advantage of US
in displaying luminal irregularities, an intimal flap is
infrequently seen, possibly because the size of the flap
lies beyond the resolution of US (Fig. 9) (161).
US is helpful in monitoring the course of natural
repair. Vertebral dissections follow a similar course.
VA flow disturbances are nonspecific and show the
same patterns as any stenotic lesion associated with
intraluminal hemodynamic change. Such patterns
include absence of a flow signal, bidirectional or
dampened flow, and elevated flow velocities with
associated turbulence (162,163).
Pitfalls of Carotid Ultrasonography
Carotid occlusion. US diagnosis of a carotid occlu-
sion remains unreliable, as a minimally patent arterial
lumen with a trickle of flow can be missed. In the case
of symptomatic atherosclerotic disease, such a differ-
entiation is vital because CEA or CAS is clearly
indicated in a patent vessel, but is generally not pos-
sible in the case of occlusion. Early reports suggested a
diagnostic accuracy of 85% for ICA occlusion, but in
more recent studies, which were based on color
duplex imaging, the accuracy was shown to exceed
96% (164,165). Difficulties arise from the presence of
calcific plaque formation and the low flow volume in
near occlusions. In addition, arterial tortuosity may
cause angle artifacts, further compromising sensitiv-
ity. Diagnostic confusion may also arise when an
external carotid artery branch overlies the ICA occlu-
sion and is incorrectly identified as a patent residual
lumen. In some patients with ICA occlusion, the
external carotid artery assumes a low-resistance
pattern as it provides collateral flow to the brain.
Tapping the fingers over the temporalis muscle and
the identification of vascular branches may help dif-
ferentiate the external from the internal carotid artery.
The ICA occlusion and high-grade stenosis also lead
to diagnostic difficulties in determining the degree of
stenosis on the contralateral side. Increased contrala-
teral flow velocities may be secondary to collateral
flow and lead the sonographer to overestimate the
degree of true stenosis. In such cases, the use of peak-
systolic velocity alone is insufficient and misleading.
The overestimation is proportional to the degree of
 Chapter 7: Ultrasonographic Imaging and Physiological Techniques in Interventional Neuroradiology 151

contralateral stenosis. Increasing the number of diag-

nostic criteria in the setting of contralateral stenosis
improves the diagnostic accuracy. The VICA/VCCA
ratio may accurately reflect the degree of stenosis in
this setting.
Calcification. Heavily calcified plaques often cast
an acoustic shadow that prevents duplex examination.
Doppler velocities can then only be measured proxi-
mal and distal to the lesion, and elevated flow veloc-
ities at the level of the stenotic plaque can be missed
(108). If the width of the acoustic shadow does not
exceed 1 cm, it may be inferred from normal distal
flow velocities that a high-grade lesion is not present.
Tortuosity. With the aging process, the ICA can
become elongated and develop loops or kinks, which
may cause increases in flow velocity, suggesting a
focal area of stenosis. Color duplex examinations are
particularly helpful in these cases.
High bifurcation. In patients with high CCA bifur-
cation, the mandible interferes with the US evaluation.
A posterior approach in these instances often allows a
better evaluation of the artery.

Extracranial VA
Atherosclerotic plaques of the extracranial VA are
usually localized at the arterys origin from the sub-
clavian artery, and they also tend to involve the
vertebrobasilar junction. In addition, the VA is also
susceptible to dissection at the V1 and V3 segments.
Intraluminal flow characteristics can be readily
assessed with extracranial US. However, velocities
are usually measured only in the V2 intravertebral
segment. Interrogation at this point allows determina-
tion of flow direction and pattern, but it gives only
indirect evidence about proximal or distal stenotic
lesions. Insonation of the VA origin is technically
difficult because of its deep intrathoracic location,
which does not always allow for optimal angle cor-
rection. Normal values range between 19 and 98 cm/
sec for peak-systolic velocity, and 6 and 30 cm/sec for
end-diastolic velocity (108,166). For the normal VA
origin, a peak-systolic velocity of 69 cm/sec and end-
diastolic velocity of 16 cm/sec have recently been
reported (167). Compared with the ICA and MCA,
flow is slower in the vertebrobasilar trunk.
There are no established US criteria for VA
stenosis. Hemodynamically significant VA disease
can be inferred when a focal flow velocity increase
of 50% or more is detected. The presence of a high-
resistance pattern suggests high-grade distal stenosis
(168). However, because the resistance pattern is
highly variable, it is an unreliable finding, which is
further confounded by the frequent presence of con-
genital variants in the vertebrobasilar circulation,
including intradural VA hypoplasia (169). Flow in a
hypoplastic vessel may be dampened, mimicking a
high-resistance pattern with almost absent diastolic
flow. This characteristic confuses the interpreter and
affects the tests accuracy. Experience with extracra-
nial VA US remains limited, and the technique is not
used as often as for ICA disease. The subclavian steal
syndrome is usually a result of high-grade stenosis or
Figure 10 The subclavian steal syndrome as a result of high-
grade stenosis of the proximal subclavian artery. The ipsilateral
VA acts as a collateral vessel, channeling blood distal to the
obstruction. Flow direction in the VA is reversed, which is shown
in red color compared with the flow direction in the common
carotid artery shown in blue color (upper image). Duplex US
shows abnormal waveform pattern (lower image). Abbreviation:
US, ultrasound.
occlusion of the proximal subclavian artery. As perfu-
sion pressure and blood flow in the arm drop, the
ipsilateral VA acts as a collateral vessel, channeling
blood distal to the obstruction. Flow direction in the
VA is reversed. The syndrome can be diagnosed with
US with high sensitivity (Fig. 10) (170,171).
THERAPEUTIC USE OF US IN ACUTE STROKE
The current treatment of acute ischemic stroke requires
intravenous delivery of a large dose of a serine pro-
tease, such as tPA, urokinase, or streptokinase, within
three hours of symptom onset. Proteases work by
converting plasminogen to the natural thrombolytic
agent, plasmin (20,21,172). Plasmin lyses thrombotic
vascular occlusions by degrading fibrinogen and fibrin
contained in a blood clot. If therapeutic recanalization
of the occluded artery is prompt, a favorable outcome
is anticipated in about 60% of those with an ischemic
152 Krejza
stroke compared with spontaneous thrombolysis,
which occurs in up to 20% of patients with variable
clinical recovery. With tPA treatment, a faster recanal-
ization results in moderate clinical improvement. Small
increments of delay in treatment decrease chances for
timely return of flow and favorable outcome, support-
ing the concept Time is brain. cavitation, the radial motion of a bubble is controlled
If a thrombolytic agent is delivered three hours
after onset of symptoms, the risk of hemorrhagic trans-
formation increases substantially; however, by using
catheter-directed arterial delivery of the thrombolytic
drug, the treatment window can be extended to six
hours with relatively low risk of hemorrhage (173175).
This procedure involves a much smaller dose of the
trombolytic agent and is directly delivered to the
thrombus in the clotted artery. After six hours, there
is no effective pharmacological thrombolytic treatment,
because if late reperfusion occurs, the area of ischemic
stroke may convert into the much more severe hemor-
rhagic stroke with worsened outcomes.
However, thrombolytic agents alone, even if given
in the desired time windows, have limited success in
recanalyzing thrombotically occluded arteries (176,177).
Major reasons for incomplete recovery include a severe
initial ischemic insult and slow and incomplete throm-
bolysis (178,179). Successful thrombolysis depends on
the delivery of tPA to the thrombus through residual
blood flow around the arterial obstruction (180,181). As
such, there is a strong need to enhance the effectiveness
of thrombolytic agents by shortening the time to reper-
fusion. Experimental and limited clinical studies sug-
gested sufficient penetration and thrombolytic effects of
either low-frequency (182,183) or diagnostic (184) US
through the skull in vitro and, hence, encouraged
empiric assessments of US for thrombolysis even with
standard US equipment (185).
Mechanism of US-Accelerated Thrombolysis
The mechanisms for US-accelerated thrombolysis in
externally applied exposures are unclear. Early studies
demonstrated that the effect was primarily nonthermal
and did not involve mechanical fragmentation (186).
Enhancement has been shown to decrease with
increasing frequency and increase as a function of on-
time as the duty cycle is varied (187). US increases the
uptake of tPA into a clot, suggesting that enzyme
transport is important (180). It also increases the bind-
ing of tPA to fibrin by maximizing access of the
enzyme to potential binding sites on the fibrin matrix
(188). Furthermore, it can reversibly increase fluid
permeation through fibrin (189), a finding shown to
depend on reversible increases in the number of fibers
per unit area and concomitant decreases in fiber diam-
eter during US exposure. Degassing reduces the effect
of US on flow through fibrin and associated structure
changes. These and other clues implicate gas concen-
tration as an important factor and suggest that acoustic
cavitation (see the section Technical Aspects of US
Imaging) may be a dominant mechanism. In stable
cavitation, the stiffness of the gas in the MBs controls
the radial pulsations of MBs driven by the US field. If a
bubble is induced to grow by US to a diameter larger
than the pore size of the fibrin lattice surrounding it,
stretching of clot fibers may occur. Microstreaming
around the MBs may cause damage to nearby cells or
fibers, or act to stir fresh fibrinolytic enzyme into
otherwise inaccessible regions in a clot. In inertial
by the inertia of the rapidly moving liquid surrounding
it. For symmetrical collapse, hot spots can form that
can produce hydroxyl free radicals capable of attacking
nearby fibers (8). For asymmetrical collapse, microjets
may form that can damage nearby fibers in the manner
of pitting on a ships propeller. If MBs collapse suffi-
ciently violently to produce broadband acoustic emis-
sions, additional inertial cavitation may produce
localized stresses, hot spots, or microjets that may
further alter the structure of clot fibers. In all cases,
US-driven MBs might exteriorize new binding sites
along fibers to allow fibrinolytic enzymes increased
access [see editorial by Polak (190)].
Besides cavitation, other effects, which depend on
the level of US energy applied, may play an important
role in vitro when the diagnostic range of US is used.
At very low energies, US promotes microstreaming of
blood close to the occluding thrombus and enhances
the mixing of tPA, effectively increasing the concentra-
tion of the agent that is in contact with the thrombus.
The pressure waves that are generated may also
increase the permeation of tPA into the interior of the
fibrin network. At slightly higher US energies, the
binding of tPA to the cross-linked fibrin and fibrin
elements within a matrix is enhanced, in vitro (191),
and the fibrin cross-links are weakened, further
increasing the binding of tPA. It is also possible that
the heat generated by US is additionally responsible for
accelerating thrombolysis (192). Experiments have con-
firmed that the temperature elevation generated by US
of sufficient power can increase the dissolution rate of
thrombi. A major limitation of TCD, however, is atten-
uation of US by the bones of the cranium; conse-
quently, diagnostic imaging and the therapeutic use
of US may not be possible in 10% to 15% of patients
(12). The US beam becomes attenuated, and 90% of
energy is deposited in the bonesoft tissue interface.
Consequently, only 10% of the maximum output inten-
sity hits the thrombus, which comes to an effective
energy of about 0.07 W/cm2. Solid data concerning
comparatively low levels of energy and their effects on
thrombolysis are lacking. In summary, the mechanism
responsible for the effect of US on thrombus dissolu-
tion is not completely known.
The excessive heat deposition at the bonesoft
tissue interface is a major limitation in applying higher
US power through the temporal window, in particular
at higher-frequency US. To overcome this problem,
several strategies were developed: first, to use endo-
vascular wires and transducers to deliver US locally;
second, to use lower-frequency and subsequently
higher-power US for transcutaneous US-enhanced
thrombolysis; third, to use US contrast to induce and
increase the number of cavitations at the site where the
US beam of a high mechanical index is targeted.
 Chapter 7: Ultrasonographic Imaging and Physiological Techniques in Interventional Neuroradiology
Endovascular Ultrasound Thrombolysis
Intravascular devices such as vibrating wires at fre-
quencies of 20 to 25 kHz delivering very high power
levels of US of up to 20 W locally have been shown to
disrupt the clots in vitro (193195). This approach has
been used to fragment, mechanically, thrombi into
small particles, resulting in reperfusion in patients
with obstructed peripheral arteries (196198). These
arteries require great angiographic skill besides of
disadvantages such as unknown effects of distal
embolization of fragments, damage or perforation of
the vessel wall, heating, and ultrasonic wire breakage.
Miniaturized transducers also have been
attached to catheters for direct endovascular use, offer-
ing the potential of localized US thrombolysis while
avoiding attenuation of intensity through the skull and
reducing insonation of the surrounding tissue. Tachi-
bana and Tachibana demonstrated enhanced clot lysis
in vitro using a microtransducer operating at 225 kHz.
Similar in vitro results were demonstrated for com-
bined application of US (170 kHz, 0.5 W/cm2) and
thrombolytic infusion (199). The specialized US throm-
bolytic infusion catheter (EKOS Corporation, Bothell,
Washington, U.S.) combines the use of a miniature US
transducer on the tip of the catheter with infusion of a
thrombolytic agent through the catheter. After a bolus
of tPA is injected, an infusion of tPA is started with
simultaneous US given for up to one hour. Human
trials showed great promise. Only large vessels can be
effectively treated with US, but tPA may lyse periph-
eral fragments in the area. The delays involved with
angiography and demands for very skilled operators,
which apply to all mechanical devices, limit the poten-
tial of endovascular use of microcatheters for acute
stroke treatment to specialized centers; thus a broader
applicability seems unrealistic.
Transcutaneous US-Enhanced Thrombolysis
Noninvasive external application of US has greater
potential for wider therapeutic application because it
requires neither angiography nor selective catheter-
ization, eliminates the risk of vessel damage by the
catheter, and can be used for vessels too small or
inaccessible for catheterization. Frequencies used
include 20 kHz (200), 40 kHz (201), 170 kHz
(202,203), 300 kHz (183), 1 MHz (186,187,196,
203,204), and 2 MHz (205), at intensities from 0.25 to
10 W/cm2.
In vitro studies have shown various levels of
moderate thrombolytic improvements averaging 30%
to 40% and required one to three hours of insonation
to get the effect (206). Several studies confirmed lytic
activity during transtemporal delivery of US using a
transducer similar to a regular TCD transducer. Lower
frequencies penetrate the skull more efficiently than
higher frequencies. Standard physical therapy devices
used a 1-MHz frequency for delivery, while TCD
devices used a 2-MHz frequency to measure flow
velocity.
153
In human clinical trials, recovery rates higher
than expected with simple tPA treatment have been
described (185,205,207,208). Better rates of recanaliza-
tion have been seen with those treated with continu-
ous US as well as tPA. Several reports showed the
bleeding rate with this technique to be similar to that
with simple tPA therapy.
The largest of these studies, the CLOTBUST
phase II study (205), used a standard TCD aimed by
a skilled sonographer at MCA thrombus in 126
randomized acute ischemic stroke patients. The flow
in the artery was observed, and intravenous tPA was
given. Continuous full-power TCD was used for two
hours, and flow was assessed intermittently. The US
beam is quite narrow; thus it requires a highly skilled
sonographer to target the occluded segment and keep
the beam on target using specially designed head
frame. The study showed that the technique is safe
and that TCD enhances recanalization.
Using lower frequencies (20 kHz to 1 MHz) than
those used for diagnostic purposes, tPA-mediated clot
degradation was shown to be as much as 50% more eff-
icient when US was applied transcranially (182,184). As
mentioned above, the CLOTBUST study using 2-MHz
transcranial probes suggested enhancement of tPA
activity with acceleration of arterial reperfusion, but so
far did not demonstrate clinical improvement. Although
encouraging, these data lack confirmation of vascular
and brain tissue effects through criterion standard imag-
ing procedures and are in contrast to experimental
studies using diagnostic US plus tPA (209).
Consequently, Transcranial Low-Frequency US-
Mediated Thrombolysis in Brain Ischemia (TRUMBI)
trial (206), a phase II, prospective, nonrandomized
study at six German university stroke centers, was
scheduled to test safety and practicability of thrombo-
lytic therapy in acute stroke patients with combined
application of tPA plus low-frequency US. A second-
ary objective was to compare clinical recovery and
rates of recanalization, reperfusion, and infarct size as
evidenced by serial MRI. Patients were alternately
allocated a standard 0.9-mg/kg tPA treatment and a
combination of tPA treatment with transcranial
insonation of low-frequency pulse-wave mode US
(NeuroFlowTM, Walnut Technologies, Andover, Mas-
sachusetts, U.S.) for 60 to 90 minutes.
The study was prematurely stopped because 5 of
12 patients from the tPA-only group, but 13 of 14
patients treated with the tPA plus US, showed signs of
bleeding in MRI. Within three days of treatment, five
symptomatic hemorrhages occurred within the tPA
plus US group (r-tPA) thrombolysis in humans using
low-frequency US (6).
Two reasons were considered to be responsible
for the increased risk of hemorrhage, the thermal
effect and disruption of the blood-brain barrier (BBB).
A study by Fatar at al. (210) showed that brain
temperature increases within two to five minutes of
insonation. The brain temperature increase and cool-
ing time, however, were in proportion to power level,
and even with the highest intensity of 7 W/cm2 for
30 minutes, the maximum elevation of mean brain
154 Krejza
temperature was 0.98C, with the highest cooling time
of 40 minutes. However, no deleterious side effects of
this treatment were found in histological examination.
Another study by Reinhard et al. (211) showed
abnormal permeability of the BBB after insonation
with low-frequency US generated by the NeuroFlow.
It indicates that the observed excessive bleeding rate
with low-frequency sonothrombolysis also involving
atypical locations (such as the intraventricular or
subarachnoid space) might in fact be attributable to
primary disruption of the BBB. In comparison with
routine 2-MHz Doppler devices, as used in the
CLOTBUST study without hemorrhagic side effects,
the applied device had a wider sonification field but
comparable power. Transient disruption of the BBB by
focused US has been described recently in animals
when it is applied in the presence of preformed gas
bubbles (9). Ultrastructural animal studies have,
among other mechanisms, proposed endothelial
injury with high power, but partial opening of tight
junctions already with low-power insonation (212).
A clue to the mechanism of BBB disruption is that
it occurs distant to the target volume: standing waves
near the bone at the borderzone of the large insonation
field may have occurred during continuous insonation
and lead to local heating or mechanical effects disrupt-
ing the BBB. Therefore, small-field insonation should
likely be preferred for sonothrombolysis in acute ische-
mic stroke.
Microbubble-Augmented US Thrombolysis
MBs are small air- or gas-filled microspheres with
specific acoustic properties that make them useful as
US contrast agents for sonographic examinations. Two
agents (Definity, Bristol-Meyers-Squibb Medical Imag-
ing, Inc., Princeton, New Jersey, U.S., and Optison,
Amersham Health, Princeton, New Jersey, U.S.) are
commercially available with FDA approval for use in
clarifying the outlines of the ventricles in cardiac US
imaging. In diagnostic US, MBs create an acoustic
impedance mismatch between fluids and body tissues,
increasing the reflection of sound. Experimental stud-
ies have shown that US-accelerated thrombolysis may
be further enhanced by administration of MBs
(202,213,214). Low-frequency US with high power has
been demonstrated to produce cavitation and fluid
motion into the thrombus (214,215). MBs, by acting as
cavitation nuclei, lower the amount of energy needed
for cavitation. Application of high-acoustic-pressure
US has been shown to induce nonlinear oscillations
of MBs, leading to a continuous absorption of energy
until the bubbles explode, releasing the absorbed
energy (216). Thus, US-mediated MBs destruction
may further accelerate the clot-dissolving effect of US.
The synergistic effect of US and MBs on sono-
thrombolysis has been demonstrated in clinical stud-
ies in patients with arteriovenous dialysis graft
thrombosis (217). Molina et al. investigated the effects
of galactose-based MBs on the beginning, degree, and
time to maximum completeness of MCA recanaliza-
tion after application of tPA intravenously plus 2-hour
continuous 2-MHz TCD monitoring plus three boluses
of 400 mg/dL of the galactose-based MBs (Levovist),
given at 2, 20, and 40 minutes after tPA administra-
tion. (218). They showed that administration of MBs
further enhances US-augmented systemic thromboly-
sis in acute ischemic stroke, leading to a more com-
plete arterial recanalization and to a trend toward
better short- and long-term outcome.
Further research is required to evaluate possible
combinations of thrombolytic drugs, MBs, and vari-
ous modes of US delivery. Once these combinations
can be assessed, some new techniques should be
ready for application in humans. Currently, human
CLOTBUST studies are progressing rapidly and
involve not only thrombolytic drugs but the addition
of MBs and of dedicated machines to make US deliv-
ery easier and more reliable.
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 8

Techniques and Devices in Interventional Neuroradiology

Jeffrey M. Katz
Department of Radiology, New York Presbyterian Hospital, Weill Medical College
of Cornell University, New York, U.S.A.
Y. Pierre Gobin and Howard A. Riina
Departments of Radiology and Neurosurgery, New York Presbyterian Hospital,
Weill Medical College of Cornell University, New York, U.S.A.

INTRODUCTION should include an assessment of vital signs, the pul-

The endovascular surgeons armamentarium is
expanding at an exponential rate. New tools and
materials are being developed and introduced into
clinical practice at a dizzying pace, while current
devices are continuously being modified for improved
safety, efficacy, and navigation in the tortuous cere-
brovascular environment. With these advancements,
standard angiographic and interventional techniques
are evolving and innovative methods and procedures
are being introduced into the endovascular arena,
enabling more effective treatment of a larger variety
of neurovascular and spinal diseases that were pre-
viously too challenging to access or complex to suc-
cessfully cure. In this chapter, we discuss techniques
commonly used in neurointerventional practice.
While a comprehensive review of all the devices
available to the endovascular surgeon is beyond the
scope of this chapter, we provide illustrative examples
of the devices used in the endovascular treatment of
intracranial, extracranial/cervical, and spinal diseases
in our clinical practice.
PREOPERATIVE EVALUATION
All endovascular procedures begin with preoperative
patient assessment and, when appropriate, educating
the patient about the intended procedure (1). The
indications for the interventional procedure should
be reviewed by comprehensive patient evaluation
and discussions with the patients referring physician.
The patients existing clinical condition, past medical
and surgical histories, medications, and allergy his-
tory, including any previous exposure to contrast dye
and whether or not the patient had any adverse effects
from that experience, need to be ascertained. If a
contrast allergy is suspected, premedication with
prednisone 50 mg orally at 24, 12, and 1 hour as
well as diphenhydramine 50 mg orally or intrave-
nously 1-hour preoperatively is the standard protocol
to prevent an allergic reaction. Physical examination
monary and cardiac status, a complete neurological
examination, documenting any preprocedural deficits,
an evaluation of the patients pulses, including the
bilateral dorsalis pedis and posterior tibial pulses for
transfemoral approaches, and Allens test for patients
and procedures requiring radial artery access. Crucial
laboratory data include platelet count, prothrombin
time, international normalized ratio, partial thrombo-
plastin times to evaluate for a bleeding diathesis, and
blood urea nitrogen and creatinine to look for renal
insufficiency or failure. For patients with renal insuf-
ficiency, prehydration with sodium bicarbonate
(130 mEq/L IV solution at 3.5 mL/kg bolus over
1 hour, then 1.2 mL/kg/hr during the procedure and
for 6 hours after the procedure) and administration of
N-acetylcysteine (600 mg orally at 24 and 12 hours
before and after the procedure) can prevent contrast-
induced nephropathy (2,3). Noninvasive imaging and
previous angiography should be reviewed for preop-
erative clinical assessment and treatment planning.
Depending on the patients age, clinical status,
and anesthesia requirements, further investigation
and testing may be required, including electro- and
echocardiography, chest X-ray, pulmonary function
tests, and referral to specialists in internal medicine,
cardiology, and pulmonology may be required for
presurgical clearance. The need for general endotra-
cheal anesthesia versus monitored sedation during
endovascular procedures depends on several factors
related to the patient (e.g., age, anxiety level), the
procedure, and operator preference. In general, embo-
lization procedures, especially of aneurysms and arte-
riovenous malformations/fistulas (AVMs/AVFs), and
intracranial angioplasty for vasospasm or atheroscler-
otic disease are performed under general endotracheal
anesthesia at our institution, whereas we perform
carotid artery stenting and tumor embolizations
under monitored sedation. Many other procedures
can be performed safely using either method, and
the choice of anesthesia relies highly on operator
preference.
162 Katz et al.
Of paramount importance in the preoperative
patient visit is a succinct but comprehensive discus-
sion of the intended procedure, as well as the risks,
benefits, and alternatives of the suggested therapy. At
this time, informed written consent should be
obtained from the patient or from the patients repre-
sentative (health care proxy or closest relative) if the
patient is incapacitated, and the discussion docu-
mented in the medical record. In certain situations,
emergency consent by two physicians is necessary to
allow the rapid institution of lifesaving therapy, as is
sometimes the case with several endovascular proce-
dures (e.g., acute stroke therapy). Particular require-
ments for consent vary between regions and
institutions and must be learned and strictly followed
during the consenting process.
VASCULAR ACCESS
Patient Monitoring
Once the patient is brought to the angiography suite
and placed in the supine position, an 18- or 20-gauge
IV line is started. Continuous electrocardiography,
pulse oximetry, and an intermittent automated blood
pressure cuff are connected to the patient during all
endovascular procedures. An arterial line is inserted
for procedures requiring strict blood pressure mon-
itoring and control, including post-subarachnoid hem-
orrhage (SAH) vasospasm therapy, ruptured
aneurysm embolization, and revascularization of crit-
ically stenosed or occluded extra- and intracranial
vessels. Intracranial pressure monitoring is typically
utilized in patients with higher-grade SAH during
aneurysm embolization or vasospasm therapy. Once
the patient is on a monitor, either light sedation or
general endotracheal anesthesia is administered.
Vascular Access Sites
Common Femoral Artery
The choice of arterial access site depends mostly on
operator preference, experience, and patient anatomy.
For common femoral artery (CFA) access, the right
CFA is the preferred access point because most inter-
ventionalists are right handed. Both groins are pre-
pared and draped in case right CFA access is
unsuccessful or bilateral arterial access is required.
The latter is sometimes necessary when numerous
devices that need to be inserted intravascularly cannot
simultaneously fit within one introducer sheath. Com-
plications of the transfemoral approach include retro-
peritoneal and groin hemorrhage, arteriovenous fistula
and pseudoaneurysm formation, femoral nerve injury,
dissection, and especially in children, arterial thrombo-
sis or embolization to the distal lower extremity.
Radial Artery
Radial artery access is becoming more popular for
endovascular procedures because it offers several
potential advantages over CFA access. The transradial
approach obviates the requirement for prolonged bed
rest and eliminates the risk of occult hematoma for-
mation, making it safer in anticoagulated patients (4),
and it is sometimes necessary when transfemoral
access of tortuous aortic arch vessels is technically
impossible or in the 2% to 10% of patients who are
incapable of undergoing transfemoral angiography
because of peripheral vascular disease, aortic occlu-
sion, or morbid obesity (5,6). Several series have
reported successful and safe utilization of this
approach for cerebral angiography (46). The trans-
radial approach requires the performance of Allens
test with pulse oximetry to demonstrate adequate
collateral circulation to the hand from the ulnar artery
and a cocktail of transintroducer sheath injections,
including verapamil (2.5 mg), cardiac lidocaine (2%,
1 mL), and nitroglycerin (0.1 mg), to prevent vaso-
spasm, as well as intravenous heparin (80 IU/kg) to
prevent thrombosis. The transbrachial approach,
offering the early ambulation and anatomical benefits
of the transradial approach, has disadvantages that
preclude its routine use, including potential median
nerve injury and brachial artery thrombosis.
Direct Puncture
In certain circumstances, alternative vascular access
sites are required. During the treatment of vascular
malformations of the head and neck, including lym-
phangiomas, capillary angiomas, venous angiomas,
and AVMs, lesion access is by direct puncture. The
latter method employs butterfly needles or long angio-
caths inserted percutaneously under fluoroscopic or
ultrasound guidance. Once intravascular position is
confirmed by contrast injection under fluoroscopy,
sclerotherapy is performed. Direct puncture of the
external carotid artery (ECA) or its branches can be
successfully performed in patients with facial AVMs
previously treated with surgical ECA ligation (7).
Arterial access is performed with a micro access set
(AngioDynamics, Inc., Queensbury, New York, U.S.;
see discussion in the next section) using fluoroscopic
guidance or cervical landmarks.
Vascular Access Technique
Standard Approach
In the transfemoral approach, the CFA is found at the
medial aspect of the femoral head, a landmark that
can be visualized under fluoroscopy and is useful in
obese patients. To prevent retroperitoneal hematoma,
the CFA should be accessed 2 to 3 cm below the
inguinal ligament (1). Once the artery is palpated,
the overlying skin is anesthetized by a 1-cm wheal
of 1% lidocaine using a long 21-gauge needle at the
skin surface. The needle is then advanced through the
wheal, and 10 mL of lidocaine is carefully infused
subcutaneously on either side of the artery and along
a track to the artery. The syringe should be aspirated
slightly before each injection to ensure extravascular
 Chapter 8: Techniques and Devices in Interventional Neuroradiology
Figure 1 Photograph of standard arterial sheath introducer set.
(A) 6-Fr introducer sheath. (B) 19-guage single-wall needle.
(C) Dilator. (D) 0.035-inch J-wire with tip straightener.
infiltration. For single-wall punctures, a 19-gauge
single-wall needle (Fig. 1) is used at a 458 angle to
the skin as the artery is fixed in position by placing the
left third, fourth, and fifth fingers above the puncture
site and the index finger just below. A small skin
incision can be made just prior to needle insertion, but
we prefer to incise the skin only when sheath intro-
duction necessitates it. With the bevel up, the needle is
advanced toward the artery, and a transmitted pulse
can commonly be felt against the right thumb posi-
tioned over the needle hub. A pulsatile efflux of bright
red blood is an indication of successful needle inser-
tion into the artery lumen. Only when this efflux is
seen should the guidewire be inserted (commonly a
0.035-inch wire with a 3-mm J tip; Fig. 1), the needle
removed with firm pressure held over the puncture
site to prevent bleeding, and the introducer sheath
with dilator advanced into the arterial lumen by the
Seldinger technique. Alternatively, double-wall arterial
puncture can be performed using a 19-gauge styleted
needle (e.g., Pulse-Vu Needle, AngioDynamics, Inc.)
over a straight 0.035-inch wire (e.g., Bentson wire,
Merit Medical Systems, Inc., South Jordan, Utah,
U.S.). If guidewire insertion meets resistance, fluoro-
scopically guided guidewire advancement should be
performed to avoid subintimal insertion and vessel
dissection. Contrast injection into the sheath can also
ensure intra-arterial (IA) catheterization. In patients
with multiple past transfemoral catheterizations,
groin fibrosis may significantly increase resistance to
sheath insertion. In these cases, progressive dilatation
with dilators (5- to 8-Fr dilator, Cook, Inc., Blooming-
ton, Indiana, U.S.) of increasing diameter over a stiffer
introducer wire (i.e., 0.035-inch Terumo glidewire,
Scimed/Boston Scientific, Fremont, California, U.S.)
may enable successful sheath insertion. Once the
sheath is in place, it should be secured with a Tega-
derm (3M Health Care, St. Paul, Minnesota, U.S.) or
suture and connected to continuous pressurized
heparin saline flush.
163
Figure 2 Photograph of 5-Fr Micro Access Kit (Angiodynamics
Inc.). (A) 21-guage echo tip needle. (B) 10-cm micro access
dilator assembly. (C) 0.018-inch stainless steel guidewire with
platinum tip (inset).
Micro Access Approach
For transradial and transbrachial approaches, patients
on anticoagulation, and children and infants, a micro
access set (AngioDynamics, Inc.; Fig. 2) is recom-
mended. This system uses a 21-gauge needle and a
0.018-inch guidewire and comes with a 4- or 5-Fr
sheath dilator. Once the micro puncture sheath is
inserted, a standard 0.035-inch J tip guidewire is intro-
duced through the sheath, which is then exchanged for
a standard length introducer sheath.
Introducer Sheaths
Standard introducer sheaths (Fig. 1) used in endovas-
cular procedures are 11 cm long and range in size
from 4 and 5 Fr, used commonly for diagnostic
catheterization, to 9 Fr, required for mechanical embo-
lectomy using the Merci Retriever (Concentric Medi-
cal, Inc., Mountain View, California, U.S.). Sheaths of
6 and 7 Fr are routinely used for most embolization
and revascularization procedures. Larger sheath sizes
(sheath size refers to the sheath inner diameter,
whereas catheter size refers to the catheter outer diam-
eter) are necessary when more devices are required for
a particular procedure. For instance, balloon-assisted
aneurysm coil embolization typically requires a 7-Fr
sheath to simultaneously introduce the balloon cathe-
ter and the embolization microcatheter rather than
using two 6-Fr guide catheters through bilateral CFA
access.
When more catheter support is needed, as in
carotid artery angioplasty and stenting (CAS) proce-
dures, a standard sheath can be exchanged over a
164 Katz et al.
guidewire for a long introducer sheath. The Vista Brite
Tip (Cordis Corp., Miami Lakes, Florida, U.S.) intro-
ducer sheath comes in 35-cm (5 and 6 Fr) and 90-cm
lengths (6-8 Fr) and provides excellent guide catheter
support. The Shuttle Select Tuohy-Borst Introducer
(Cook, Inc.) can also be used for the same purpose. It
is available in 6- to 8-Fr sizes with 90-cm length and
three different tip curves. Offers enhanced flexibility
and trackability that can be useful when navigating
tortuous vessel anatomy.
Anticoagulation
Systemic heparinization during endovascular proce-
dures should be initiated following sheath insertion
and is administered in bolus doses. An 80-IU/kg
loading dose is given to target an activated clotting
time (ACT) of two to three times baseline. The ACT
should be checked periodically during the procedure
and additional heparin boluses given to ensure tar-
geted anticoagulation to prevent embolic complica-
tions. At the end of the procedure, protamine sulfate
can be administered, slowly to avoid systemic hypo-
tension and anaphylaxis, at a dose of 0.5 to 1 mg/
100 units of heparin remaining in the patient, with a
maximum of 50 mg given over 10 minutes. Protamine
administration, however, is not always necessaryfor
instance, following embolization proceduresand in
many circumstances we allow the patients anticoagu-
lation to correct spontaneously.
CATHETERS
There are three main types of catheters: diagnostic
catheters, guide catheters, and microcatheters (balloon
catheters are discussed later in the section on bal-
loons). Safe catheter use requires that (1) the catheter
be advanced over a guidewire, especially in athero-
sclerotic patients; (2) the guidewire be withdrawn to
just within the catheter tip when turning the catheter;
(3) the catheter and guidewire tips never be out of
fluoroscopic visualization during navigation; (4) the
cause of resistance, if encountered, be investigated
and the catheter not forced; and (5) diagnostic and
guide catheters be continuously flushed with hepari-
nized saline to avoid thrombosis at the catheter tip
and inadvertent embolic complications.
Diagnostic Catheters
A wide variety of catheters are available from different
endovascular companies, and in general, catheter selec-
tion is based on personal experience and preference.
For diagnostic angiography, catheters are divided into
simple-curve and complex-curve end-hole catheters,
where simple-curve devices have only a primary (dis-
tal) curve and complex-curve devices have both pri-
mary and secondary curves that necessitate reforming
of the distal curve once the catheter is positioned in an
appropriate aortic arch vessel (typically, the left sub-
clavian artery) (1). Examples of simple-curve catheters
include the TempoVert (Cordis Corp.) and the Terumo
Glidecath Angled Taper (Scimed/Boston Scientific,
Fremont, California, U.S.) catheters that are excellent
for diagnostic angiography of uncomplicated aortic
arches.
Tortuous great vessels and bovine origin of the left
common carotid artery can be challenging to access.
When catheterizing with simple-curve catheters,
maneuvers including having the patient cough while
advancing the catheter, turning the patients head away
from the targeted vessel, and breath holding in deep
inspiration can unbend a tortuous vessel enabling cath-
eter advancement (1). The use of digital roadmap tech-
nique and the transradial approach can also be helpful
in this regard. The Simmons II catheter (Terumo
Glidecath, Scimed/Boston Scientific, Fremont, Califor-
nia, U.S., and SIM 2, Merit Medical Systems, Inc.; Fig.
3) is a complex-curve device that is useful for accessing
tortuous great vessels and bovine aortic arches. While
complex-curve catheters facilitate entry into the prox-
imal segment of a tortuous vessel, their secondary
curve may inhibit distal catheterization. In this circum-
stance, the use of an exchange length guidewire (0.035
or 0.038 inch, 260 cm; e.g., Terumo Glidewire, Scimed/
Boston Scientific, Fremont, California, U.S.) may be
used to exchange for a simple-curve catheter. For
spinal angiography, we prefer the Cobra 1 and 2
(Terumo Glidecath, Scimed/Boston Scientific, Fre-
mont, California, U.S.; Figs. 3 and 4) catheters because
their shape enables access of posterior intercostal and
lumbar arteries with relative ease and stability for
spinal embolization procedures. For lower lumbar
arteries, a Simmons 1 shape (Figs. 3 and 5) is prefer-
able. Multiholed pigtail catheters (Merit Medical Sys-
tems, Inc.; Figure 6) are used for arch aortograms when
the delineation of precise arch anatomy is required.
Guide Catheters
Guide catheters are stiffer than diagnostic catheters,
which improves support but makes navigation more
Figure 3 Photograph of several diagnostic catheters (Terumo
Glidecath, Boston Scientific, Fremont, California, U.S.). (A, B)
Complex-curve Simmons 1 and 2 diagnostic catheters, respec-
tively. (C) Simple-curve Cobra 2 diagnostic catheter.
 Chapter 8: Techniques and Devices in Interventional Neuroradiology
Figure 4 Spinal angiogram, AP view, demonstrating angio-
graphic appearance of the Cobra 2 catheter. Note the significant
tumor blush arising from branches of the right T10 posterior
intercostal artery.
Figure 5 Spinal angiogram, AP view, demonstrating the angio-
graphic appearance of the Simmons 1 catheter. Note the artery of
Adamkiewicz ( ) arising from the left T9 posterior intercostal
artery.
complex. When advancing a guide catheter through a
tortuous great vessel, certain tricks can be employed to
ease navigation. The guide catheter can be advanced
coaxially over an exchange length guidewire placed
165
Figure 6 Arch aortogram, AP view, in a patient with Takayasus
Arteritis demonstrating the angiographic appearance (inset) and
use of the pigtail diagnostic catheter. Note the absence of the
bilateral common carotid arteries and left vertebral artery and the
compensatory hypertrophied ascending and deep cervical
arteries.
distally in the targeted vessel. Delicate locations dur-
ing catheter exchange include where the initial cath-
eter is withdrawn below the origin of the tortuous
vessel, where the catheter tip leaves the sheath, and
where the guide catheter enters the tortuous vessel (1).
A long (125 cm) 4- or 5-Fr diagnostic catheter can be
placed within the larger guide catheter to facilitate
catheter navigation or exchange. In addition, as pre-
viously mentioned, a long sheath can be inserted for
added support to facilitate the insertion and stabilize
the position of a guide catheter. Our guide catheter
preference is the Envoy catheter (Cordis Corp.; Fig. 7)
for its good support balanced with sufficient naviga-
bility and smooth device exchange.
Microcatheters
Flow-Guided Microcatheters
Microcatheter selection is again based on experience
and preference rather than science. Microcatheters can
be divided into flow-guided and guidewire-directed
devices. Flow-guided microcatheters, such as the Balt
Magic (Balt/Boston Scientific, Fremont, California,
U.S.) and the Spinnaker Elite (Target Therapeutics/
Boston Scientific, Fremont, California, U.S.) micro-
catheters are manufactured with a 100- to 120-cm, 3-Fr
proximal shaft designed for support and pushability,
a supple 25- to 30-cm, 2.5-Fr mid-shaft segment
enabling navigation through tortuous vessels, and an
extra supple 10- to 30-cm, 1.2-Fr, 1.5-Fr, or 1.8-Fr
shapeable distal segment that allows for flow-guided
vessel selection. Flow-guided microcatheters are
designed for embolization of AVMs and AVFs with
liquid acrylic adhesive material and are intended for
166 Katz et al.

Figure 8 Illustration of various microcatheter shapes.

(A) Straight. (B) 458 curve. (C) 908 curve. (D) J-shaped curve.
(E) S-shaped curve. (F). C-shaped curve. Source: Courtesy of
Boston Scientific, Fremont, California, U.S.

WIRES

Guidewires
Most guidewires and catheters used in endovascular
Figure 7 Photograph of the Envoy guide catheter (6 Fr, Cordis
practice are hydrophilically coated to enhance coaxial
Corp.).
navigation of the catheter over the wire. This coating
must be prewetted with heparinized saline prior to in-
troduction into the patient by flushing the device dir-
ectly (catheter) or through an injection port on the
plastic wire container (Fig. 9). Many microwires require
navigation through the circulation by contrast injec- prewetting in a bowl of heparinized saline for 15 to
tion and flow, although microguidewire support and 30 seconds prior to shaping. Similar preparation is also
assistance may be needed. required for coils and balloon catheters. Guidewire
navigation and rotation is aided by the use of a torque
Guidewire-Directed Microcatheters device (Fig. 10) placed approximately 2 to 3 cm from
the catheter hub. Guidewires used with diagnostic and
There are multiple guidewire-directed microcatheters.
The choice depends on the main quality required, on
distal trackability or support (e.g., for aneurysm
embolization), and also on individual preferences.
Selection of a particular shape, as with adding curves
to microwires, largely depends on the vessel being
selected and the curves being traversed during the
catheterization process. Preshaped microcatheters
(Fig. 8) come with 458 or 908 angled tips, or J-, S-, or
C-shaped curves, range in distal diameter from 1.7 to
2.3 Fr, and generally have two radiopaque distal
markers. The same microcatheters are available with
straight tips, and all microcatheters can be shaped or
reshaped with steam. The angle a targeted vessel (or
aneurysm) takes from its parent artery will dictate
which curve is selected. Examples of different micro-
catheters used in our practice include the Prowler 10,
14, and Plus (Cordis Corp.) microcatheters that are
excellent for polyvinyl alcohol (PVA) particle emboli-
zation of tumors and ECA supply to dural AVF and
the Echelon 10 and 14 (Micro Therapeutics, Inc., Figure 9 Photograph of 0.038-inch Terumo Glidewire (Boston
Irvine, California, U.S.) and the Excelsior SL-10 and Scientific, Fremont, California, U.S.) with distal curve inside cir-
1018 (Target Therapeutics/Boston Scientific, Fremont, cular plastic container with Luer lock hub for flushing with hepari-
California, U.S.) microcatheters used for aneurysm nized saline before use.
coil embolization and IA infusions.
 Chapter 8: Techniques and Devices in Interventional Neuroradiology
Figure 10 Photograph of torquer device over microguidewire
(Concentric Medical, Inc.).
guide catheters are, typically, 0.035- or 0.038-inch-
diameter wires and are available in standard 150-cm
or exchange 260-cm lengths with angled or straight/
shapeable tips (e.g., Terumo Glidewire and Glidewire
LT, Scimed/Boston Scientific, Fremont, California,
U.S.). In certain situations, a stiffer wire, such as the
Ampaltz 0.038-inch 145-cm Super Stiff wire (Scimed/
Boston Scientific, Fremont, California, U.S.), may be
needed to facilitate catheter advancement into the lu-
mens of complex vessels or to increase guidecatheter/
sheath support in patients with severely tortuous great
vessel anatomy (the so-called buddy wire method).
Microguidewires
As with microcatheters, there is a panoply of micro-
guidewires available, and subtle differences as well as
operator preference dictate microguidewire selection
for different purposes. Microguidewire properties,
such as flexibility, coating, and torque ability, help
define which microguidewire is best for which situa-
tion. In general, stiffer wires are more torqueable but
are also more likely to perforate the vessel and may be
difficult to navigate past the vessel origin. Common
microguidewires used in our practice listed from stiffest
to softest include the Transend-10, -14, and EX-14
(Target Therapeutics/Boston Scientific, Fremont,
California, U.S.), the Silver- Speed-10 and -14 (Micro
Therapeutics, Inc., the Agility-14 standard (Cordis
Corp.), the Agility-10 and -14 soft (Cordis Corp.), and
the Synchro-10 and -14 (Target Therapeutics/Boston
Scientific, Fremont, California, U.S.) microguidewires.
The Mirage wire (Micro Therapeutics, Inc.) has a 0.008-
inch diameter and can be used to push a flow-guided
catheter around a tight curve and gain superselectivity
during AVM embolization. In many instances, how-
ever, it is difficult to predict which microcatheter/
microguidewire combination will be successful in nav-
igating difficult curves, and multiple attempts with
various combinations may be necessary. As with all
devices used in interventional neuroradiolgy, gaining
experience with a selected handful of microguidewires
167
can be very rewarding when complicated anatomy is
encountered.
Giving the microguidewire tip a shape is indis-
pensable for navigation, with shapes ranging from
slight to 908 angles to J-, S-, and C-shaped curves. If
the target is at a limited angle from the parent vessel,
then a limited angle or slight J-shaped curve is needed.
For acute angles, such as accessing the ophthalmic
artery, an S-shaped curve may be useful. Even with
experience, trial and error with different shapes, angles,
and microcatheters may be needed to catheterize a
challenging target.
To maintain control when navigating a micro-
catheter over a microguidewire, it is important to look
for slack and tension buildup in the guide catheter and
microcatheter. These irregularities are anticipated
when the operators movements are not being effec-
tively translated into microcatheter/microguidewire
movement. In addition, at the conclusion of a maneu-
ver, it is important to slightly direct the device in the
opposite direction to keep it in a steady position. For
instance, when a microcatheter is advanced to the
correct position within an aneurysm dome, it is neces-
sary at the end of forward motion to withdraw slightly
on the microcatheter to abolish the forward thrust that
could inadvertently move the device too distally.
ENDOVASCULAR INFUSIONS
Wada Testing
Provocative testing of the central nervous system with
IA amobarbital infusion followed by neurological and/
or neuropsychological assessment is called WADA test-
ing. During preoperative evaluations for epilepsy
surgery, the patient is connected to continuous electro-
encephalographic monitoring, and 80 to 140 mg of
amobarbital diluted to 10 mL in saline is injected
through the diagnostic catheter at 1 to 2 mL/sec into
the internal carotid artery with the patients arms
elevated to watch for intended contralateral hemiplegia.
The patient typically recovers complete neurological
function within 15 minutes, and then the contralateral
hemisphere can be tested. During AVM embolization,
25 to 50 mg of amobarbital in a 1-mL aliquot can be
injected through a microcatheter into a feeding artery
and, following neurological assessment, predict dys-
function prior to permanent vessel occlusion (8). Simi-
larly, 10 to 50 mg of 2% cardiac lidocaine can be injected
selectively into extra-axial arteries to examine the
peripheral nervous system prior to arterial embolization
of extra-axial tumors or vascular malformations, and
sequential testing with amobarbital followed by lido-
caine may be useful for testing dangerous extracranial
to intracranial anastamoses (8).
Vasodilator Infusions
Both catheter-induced vasospasm and post-SAH vaso-
spasm can be effectively managed with IA verapamil.
On selective catheterization of the targeted vessel,
5 mg of verapamil diluted to 20 mL in saline is slowly
168 Katz et al.
infused at 1 to 2 mL/min through the microcatheter at
a dose of 5 mg per injected vessel (though higher
doses may be given if needed). Slow infusion limits
cardiac side effects of hypotension and bradycardia.
The safety and efficacy (though not durability) of
chemical infusion for post-SAH vasospasm has been
demonstrated in retrospective studies for both vera-
pamil (9) and nicardipine (10). The dose used for
nicardipine is also 5 mg per injected vessel. One to
two milligrams of verapamil infused through a guid-
ing catheter is usually sufficient to treat catheter-
induced vasospasm, and pretreatment with verapamil
can provide effective prophylaxis for vasospasm sus-
ceptible vessels (e.g., ECA). The IA infusion of papa-
verine will also dilate spastic vessels; however, the
effect is short-lived and numerous side effects, includ-
ing hypotension, intracranial hypertension (occurs
with verapamil and nicardipine, but to a lesser
extent), seizures, and even increased vasospasm,
limit broad appeal (10). The advantages of chemical
infusion over angioplasty for vasospasm therapy
include decreased risk and the ability to treat distal
and small artery vasospasm not reachable by balloon.
However, balloon angioplasty is more durable.
Thrombolytic Infusions
Intra-arterial Thrombolysis
IA thrombolysis by direct thrombolytic infusion follow-
ing superselective catheterization offers treatment to
acute ischemic stroke (AIS) patients who are ineligible
for intravenous thrombolysis. Since the landmark PRO-
ACT II trial (11), both IA urokinase and recombinant
tissue plasminogen activator (r-tPA) have been increas-
ingly used for endovascular stroke therapy at many
centers. On the basis of data showing a trend toward
lower ICH complications with urokinase infusion com-
pared with IA r-tPA (12), we preferentially infuse
urokinase during IA stroke therapy at a dose of
250,000 to 750,000 IU (maximum of 1,000,000 IU)
through a microcatheter placed within the clot over
30 to 120 minutes. Prior to infusion, the microguidewire
is passed several times through the clot to increase the
surface area for thrombolysis. The use of IA glycopro-
tein (GP) IIb/IIIa inhibitors to treat intracerebral artery
occlusion refractory to IA thrombolysis also appears
effective and safe (13). Our anecdotal experience with
IA infusion of the GP IIb/IIIa inhibitor abciximab,
including for the treatment of procedure-related throm-
boembolic complications, has been superb.
Transvenous Thrombolysis
Targeted transvenous thombolytic therapy for medi-
cally refractory dural venous sinus thrombosis involves
direct thrombolytic infusion through a microcatheter
positioned in the thrombosed sinus. Sinus access is
typically from the common femoral vein, though sub-
clavian venous access may be required if the trans-
femoral route is obstructed (e.g., by femoral or inferior
vena caval clot). Complete sinus recanalization cus-
tomarily requires the microcatheter (e.g., Prowler
Select 170-cm microcatheter is needed to navigate
from the common femoral vein to the superior sagittal
sinus; Cordis Corp.) to be kept within the sinus for
continuous infusion (e.g., intrasinus r-tPA at a rate of
1 to 2 mg/hr over 24 to 48 hours, with or without a
bolus, although no standard protocol exists). Chemical
thrombolysis may be done alone, but is usually per-
formed in conjunction with mechanical thrombectomy
using the microguidewire, balloon angioplasty,
or rheolytic thrombectomy device (AngioJet, Possis
Medical, Inc., Minneapolis, Minnesota, U.S.; requires
an 8-Fr guide catheter).
BALLOONS
Balloons used in endovascular surgery may be div-
ided into high- or low-pressure devices and have four
major uses, including angioplasty for extracranial or
intracranial atherosclerotic stenosis (high-pressure
balloons), angioplasty for vasospasm, balloon-assisted
aneurysm remodeling, and balloon test occlusion
(low-pressure balloons). Endovascular balloons are
designed as balloon microcatheters to be advanced
either coaxially or in a monorail fashion over a micro-
guidewire into the desired location and are available
in numerous sizes (balloon size is shorthanded as
balloon diameter  balloon length). Careful sizing of
the balloons diameter to less than the diameter of the
target vessel is critical for minimizing the risk of artery
dissection or rupture. All balloons must be prepared
prior to patient introduction by vigilantly purging all
air from the balloon by hand suction and then training
the balloon by inflation with contrast solution. Balloon
preparation is intended to minimize the risk of air
embolism if the balloon ruptures.
High-Pressure Balloons
The Aviator (Cordis Corp.) and Viatrac 14 Plus
(Guidant Corp., Indianapolis, Indiana, U.S.) balloon
catheters are examples of high-pressure balloons used
for extracranial angioplasty. The Aviator balloon is a
3.3-Fr catheter designed for rapid monorail exchange,
is available in 4- to 5.5-mm diameters, and has a
nominal filling pressure of 10 atm with a rated burst
pressure (RBP) of 14 atm. The Viatrac 14 Plus (Figs. 11
and 12) is also a 3.3-Fr catheter allowing rapid mono-
rail exchange, is available in 4- to 7-mm diameters,
and has a nominal filling pressure of 8 atm with an
RBP of 14 atm. Both systems are efficiently used with
the RX Acculink Carotid Stent System (Guidant Corp.).
For intracranial atherosclerosic stenosis, the Maverick
(Scimed/Boston Scientific, Fremont, California, U.S.;
Fig. 13) balloon catheter (3.2 Fr) is a coaxially navigated
dual lumen high-pressure coronary angioplasty device
designed with enough flexibility and trackability to
pass through the tortuous intracranial anatomy and is
available in 1.5- to 4.0-mm balloon diameters. The
inner catheter lumen allows for microguidewire
employment (<0.014 inch), while the outer lumen is
used for inflation (with a 50:50 contrast in normal
saline solution) to nominal pressure of 6 atm and an
RBP of 12 to 14 atm (depending on the balloon size).
 Chapter 8: Techniques and Devices in Interventional Neuroradiology
Figure 11 Photograph of Viatrac 14 Plus high-pressure angio-
plasty balloons. (A) 4.5 mm  20 mm balloon and (B) 4.0 mm 
30 mm balloon (Guidant Corp.).
Figure 12 Cervical angiogram, unsubtracted lateral view, dem-
onstrating the angiographic appearance of the Viatrac 14 Plus
angioplasty balloon (Guidant Corp.) inflated in the left internal
carotid artery.
169
Figure 13 Cerebral angiogram, unsubtracted AP view, demon-
strating the angiographic appearance of the Maverick angioplasty
balloon (Boston Scientific, Fremont, California, U.S.) inflated in
the right middle cerebral artery.
During extracranial or intracranial angioplasty for
atherosclerotic stenosis, balloon diameter is selected
to approximate the vessel diameter just proximal
and distal to the stenosis. The microguidewire is
advanced past the stenosis, and the balloon is tracked
over a microguidewire and positioned with the prox-
imal and distal radiopaque markers straddling the
stenosis. Careful inflation with an insufflator device
(Fig. 14) is visualized under fluoroscopy (Fig. 15), and
then the balloon is deflated. Several inflations may be
necessary to achieve the desired lumen diameter, and
the balloon position may be readjusted proximally or
distally between inflations (once the balloon is fully
deflated). Angioplasty of an atherosclerotic plaque
creates microdissections in the nondiseased arterial
wall adjacent to the plaque (14). For concentric extrac-
ranial plaques and in-stent restenosis, a cutting balloon
(e.g., Ultra2 Monorail, Boston Scientific, Fremont,
California, U.S./Scimed) may be more useful to create
controlled dissections within the lesion.
Low-Pressure Balloons
Hyperglide and Hyperform (Micro Therapeutics Inc.;
Fig. 16) balloon catheters are examples of low-pressure
balloons designed for intracranial use. These devices
are single-lumen balloon catheters necessitating that a
0.010-inch microguidewire be positioned 10 mm
beyond the balloon catheter tip to ensure central
lumen occlusion and enable balloon inflation. The bal-
loon is inflated by 1-cc syringe hand injection of a
170 Katz et al.
Figure 14 Photograph of an insufflator device used to inflate
high-pressure angioplasty balloons. The device is filled with 10 to
20 cc of 50% contrast solution and purged of air bubbles prior to
use.
recommended 50:50 solution of 60% contrast in normal
saline and requires nominal inflation volumes of, for
example, 0.06 mL and 0.27 mL for the 4-mm and 7-mm
Hyperform balloons, respectively, to achieve full bal-
loon diameter (see individual device package insert for
specific nominal and maximal inflation volumes). The
balloon is deflated by careful retraction of the 1-cc
syringe plunger and not by microguidewire with-
drawal. The catheter can be flushed by withdrawing
the microguidewire proximal to the proximal marker.
Balloon-Assisted Aneurysm Remodeling
Balloon-assisted remodeling using these low-pressure
devices is sometimes required during coil emboliza-
tion of wide-neck aneurysms. The balloon is posi-
tioned over the neck of the aneurysm, while a
second microcatheter is positioned into the dome of
the aneurysm. The balloon is inflated during coil
placement and then slowly deflated while monitoring
coil position. If the coil mass is stable within the
aneurysm dome, the coil is detached and the balloon
reinflated for the insertion of the next coil.
Balloon Angioplasty for Vasospasm
Angioplasty for post-SAH vasospasm (Fig. 17) uses
the same technique as for intracranial atherosclerosic
angioplasty, except that a low-pressure balloon is
employed to decrease the risks of vessel dissection
and rupture. When using the smallest balloon catheter
(Hyperform 4 mm  7 mm, Micro Therapeutics, Inc.)
to perform distal angioplasty for vasospasm, we rec-
ommend using an 80% contrast solution to improve
visibility, and to further enhance inflation safety, we
use the Cadence Precision Injector (Micro Therapeu-
tics Inc.), a screw syringe that enables precise control
over balloon expansion.
Balloon Test Occlusion
Balloon test occlusion (BTO; Fig. 18) may be performed
to evaluate a patients ability to tolerate permanent
artery occlusion, for example, during the treatment of a
giant fusiform aneurysm. The balloon is advanced to
the target artery by standard technique, and the patient
Figure 15 Cerebral angiogram, AP view, left internal
carotid artery injection. (A) Before angioplasty, a critical
left middle cerebral artery stenosis is seen. (B) Unsub-
tracted AP view during Maverick balloon (Boston Sci-
entific, Fremont, California, U.S.) inflation. Note the
proximal and distal balloon markers that enable precise
balloon positioning across the stenosis. (C) After angio-
plasty and stent placement, complete recanalization
was obtained.
 Chapter 8: Techniques and Devices in Interventional Neuroradiology
Figure 16 Illustration of (A) Hyperglide and (B) Hyperform low-
pressure balloons used during balloon aneurysm remodeling.
Source: Courtesy of Micro Therapeutics Inc.
is examined preinflation, and then serially for 30 min-
utes during inflation. Any neurological deficit during
balloon inflation is a failed test and a bypass graft
procedure should be contemplated. Predictive value
can be enhanced by qualitative cerebral blood flow
(CBF) imaging during BTO by 99mTc SPECT scanning,
where the radionucleotide is injected once the patient
tolerates test occlusion for 15 minutes. Following a
successful 30-minute BTO, the balloon is deflated and
the procedure is concluded. The patient is then trans-
ferred for nuclear imaging. Quantitative CBF can be
obtained using xenon CT or CT perfusion imaging, but
is cumbersome to perform because of the requirement
for injection during balloon inflation.
Other Balloon Indications
Other balloon applications include permanent balloon
artery occlusion (e.g., detachable silicone balloon,
Target Therapeutics/Boston Scientific, Fremont,
California, U.S.), infrequently used, for mechanical
recanalization during acute stroke therapy, and
microcatheter guidance through a sharp arterial
curve. As an example of the latter, we recently
employed a 7  7-mm Hyperform balloon in the
supraophthalmic carotid artery to ease microcath-
eter/microguidewire navigation into an acutely
angled ophthalmic artery. The same technique is help-
ful when advancing into acutely angled lenticulostriate
arteries with the balloon positioned in the middle
cerebral artery.
EMBOLIC PROTECTION DEVICES
During CAS, the rate of embolic debris may be as high
as 80% to 90% with a consequent 5% to 9% neurological
event rate (15). The advent of improved pharmacolog-
ical prophylaxis and embolic protection devices has
171
Figure 17 Cerebral angiogram, AP view. (A, B) Left internal
carotid artery injection showing severe left A1 and A2 anterior
cerebral artery vasospasm before (A) and after (B) balloon
angioplasty, with significant luminal diameter improvement fol-
lowing serial balloon inflations. (C, D) Unsubtracted AP view of a
4  7-mm Hyperform balloon seen in the left A1 (C) and A2
(D) segments. Vasospasm of the left middle cerebral artery was
treated in similar fashion.
lowered this neurological event rate to 0% to 2% (15).
Various devices are under investigation, including (1)
filter protection devices composed of a 0.014-inch
microguidewire mounted with a polyurethane filter
that is advanced beyond the stenosis, deployed in a
straight vessel segment, and then retrieved by
resheathing at the conclusion of CAS and (2) balloon
occlusive devices, where a balloon is advanced past the
stenosis and inflated to block flow during CAS or an
aspiration balloon guide catheter is inflated proximal to
the stenosis followed by initiation of flow reversal from
the common carotid artery to the common femoral
vein. In the latter method, a second balloon is inflated
in the ECA to prevent reflux of debris from the ECA
into the internal carotid artery circulation through col-
lateral anastamoses. The advantage of filter devices is
that CBF is not interrupted and also angiography can
continue to be performed during the procedure.
Several embolic protection devices being investigated
172 Katz et al.

Figure 18 Cerebral angiogram during balloon test occlusion. (A) Unsubtracted AP view during Hyperglide balloon (*, dilineates balloon
margins) inflation across the vertebral basilar junction, performed to assess tolerance of bilateral vertebral artery occlusion as a treatment
option for this (B) large complex basilar artery fenestration aneurysm (PA view, 3D rotational projection, postcomputerized reconstruc-
tion). (C) Right and (D) left vertebral artery injection demonstrates no anterograde flow into the basilar artery during balloon inflation. The
patient developed vertigo at 25 minutes postinflation, thus failing the test.

include the ACCUNET (Guidant Corp., Menlo Park,
California, U.S.; Fig. 19), ANGIOGUARD (Cordis
Corp.), Emboshield (Abbott Laboratories, Abbott
Park, Illinois, U.S.), and FilterWire EZ (Boston Scien-
tific, Fremont, California, U.S.) filter systems, the Per-
cuSurge balloon (Medtronic, Inc., Santa Rosa,
California, U.S.) for distal occlusion, and the Parodi
Anti-Embolism System (AnteriA Medical Science, San
Francisco, California, U.S.) for proximal occlusion and
flow reversal (15).
STENTS
Stents are useful in varied circumstances, such as the
treatment of atherosclerotic stenosis, arterial dissec-
tion, and wide-necked aneurysms. The utilization of
all stents require pre- and postmedication with aspirin
(81325 mg/day) and clopidogrel [75 mg/day; at least
300 mg (up to 600 mg) given preoperatively, with
therapy continued for 4 to 12 weeks]. Stents may be
divided into balloon expandable (stainless steel) stents
deployed on a balloon catheter (e.g., Palmaz Genesis
Aviator-Medium Biliary Stent, Cordis Corp., as well
as drug-eluting stents and stent grafts; see below) and
over-the-wire self-expanding stents made of nitinol, a
shape-memory alloy. Self-expanding stents widen to a
preset diameter (straight or tapering), which is limited
by the vessel wall when delivered into a vessel of
smaller diameter, and enables these stents to conform
to vessels with tapering lumens typical of the neuro-
vasculature. Stent radial force implants the struts into
the vessel wall facilitating neo-endothelialization that
regenerates a smooth vessel lumen. Oversizing the
stent compared with the angiographic vessel diameter
can enhance this process (16). Typically, stents are
oversized approximately 0.5 to 1.0 mm more than the
target vessel diameter, while balloons are undersized
by approximately the same degree. Examples of niti-
nol stents used for CAS include the RX Acculink
Carotid Stent System (Guidant Corp.; Fig. 20) avail-
able in tapered (7- to 10-mm and 6- to 8-mm taper
diameters) and straight configurations that range in
size from 5- to 10-mm diameter by 20- to 40-mm
length, and the Precise stent (Cordis Corp.; designed
as a biliary stent) ranging in size from 5- to 8-mm
diameter by 20- to 40-mm length.
Intracranial stent deployment for atherosclerotic
or dissection-related stenosis requires the use of
smaller stents, of which most were designed for the
coronary arteries. Examples of these stents include the
Driver, S7, and S660 balloon expandable stents (Med-
tronic, Inc.). The benefit of these stents is sufficient
 Chapter 8: Techniques and Devices in Interventional Neuroradiology
Figure 19 (A) Photograph of Accunet distal embolic protection
device. (B) Cervical angiogram, AP view, left common carotid
artery injection demonstrating the angiographic appearance of a
deployed Accunet device. Source: (A) Courtesy of Guidant Corp.
Figure 20 Photograph of Acculink 6  30-mm to 8  30-mm
tapered stent (Guidant Corp.). Inset shows the Acculink delivery
system.
173
radial force to maintain luminal patency following
angioplasty. However, a major drawback is dimin-
ished flexibility and trackability to navigate these
stents through the tortuous intracranial anatomy.
Neointimal hyperplasia, the same problem
encountered following coronary angioplasty and
stenting, plagues intracranial (and to a lesser extent
extracranial) stenting procedures. This process can
result in restenosis as well as occlusion of small pen-
etrating arteries. To counteract this process, drug-
eluting stents, including sirolimus (CYPHER, Cordis
Corp.) and Paclitaxel (TAXUS, Boston Scientific, Fre-
mont, California, U.S.) eluting stents, are approved for
use in the coronary circulation, and coated stents, with
heparin (Hepacoat, to prevent thrombosis; Cordis
Corp.) or titanium-nitrous-oxide (TiNOX), preliminar-
ily hold promise at lowering restenosis rates. For
neuroendovascular procedures, drug-eluting stents
are currently most useful in the treatment of vertebral
artery stenosis, both because this artery has a partic-
ularly high-restenosis rate as well as because the ver-
tebral arteries have a similar diameter to the coronary
arteries (*23 mm) for which these stents have thus
far been designed.
The Neuroform stent (Boston Scientific, Fremont,
California, U.S./Target Therapeutics, Inc., Natick, Mas-
sachusetts, U.S.; Fig. 21) is a self-expanding nitinol stent
with open-cell design intended for intracranial use
during endovascular coil embolization of wide-necked
aneurysms. The Food and Drug Administration (FDA)
has approved it as a humanitarian use device for this
indication. The Neuroform Microdelivery System offers
simplified stent deployment compared with a signifi-
cantly more complex earlier iteration. During the
Figure 21 Photograph of a 3.5  10-mm Neuroform stent.
174 Katz et al.
treatment of wide-necked aneurysms, the Neuroform
stent may be deployed (1) prior to coil placement with
the microcatheter delivered through the stent struts;
(2) prior to coil placement, with the microcatheter
positioned within the aneurysm dome and wedged
between the stent and the vessel wall, the so-called
jail method; (3) alone without coil placement; or (4)
following coil occlusion performed with or without
balloon remodeling (Fig. 22). The last technique is our
preferred approach. If possible, coil embolization with
concurrent stent placement should be limited to the
treatment of unruptured aneurysms because the
required anticoagulation and antiplatelet therapy
may carry an excessively high hemorrhagic complica-
Figure 22 Illustration of aneurysm coil embolization
techniques. (A) Coils positioned through a microcatheter
in a narrow-necked aneurysm. (B, C) For wide-necked
aneurysms, coil placement with balloon remodeling fol-
lowed by stent deployment is preferred. (D) Additional
coils may be placed following stent deployment by
positioning the microcatheter through the stent struts
into the residual aneurysm neck or dome. Source: Cour-
tesy of Boston Scientific, Fremont, California, U.S.
tion risk for recently ruptured aneurysms (17). If
complete occlusion of a ruptured aneurysm following
coil embolization necessitates stent deployment, our
practice is to place a stent during a second-stage
procedure 4 to 12 weeks following the acute SAH.
The Neuroform stent is not radiopaque and instead
has four distal and four proximal radiopaque plati-
num markers (Fig. 23A). Under fluoroscopy, the deliv-
ery system has four indicators (Fig. 23B). Once the
stent is in position, the stent stabilizer (the most
proximal marker) is advanced to the proximal stent
marker and the microcatheter is then gently retracted
unsheathing the stent into position. The Neuroform
stent has a relatively low radial force compared with
Figure 23 Cerebral angiogram, unsubtracted
AP view. (A) The Neuroform stent has (1) four
distal and (2) four proximal radiopaque
markers. (B) The Neuroform3 Microdelivery
System has four radiopaque indicators repre-
senting (1) the microdelivery catheter tip, (2)
the compressed distal stent markers, (3) the
compressed proximal stent markers, and (4)
the stent stabilizer tip.
 Chapter 8: Techniques and Devices in Interventional Neuroradiology
Figure 24 (A, B) Cerebral angiogram, AP view, right vertebral
artery injection, before (A) and after (B) stent graft occlusion of a
large basilar artery fenestration aneurysm, showing complete
aneurysm occlusion following the deployment of two stent grafts
from the right vertebral artery into the left basilar fenestration arm.
(Note: same patient as in Fig. 18). (C) Photograph of an unex-
panded stent graft (JoStent, Abbott Laboratories).
coronary stents, making it impractical for the treat-
ment of intracranial atherosclerotic or dissection-
related stenosis. The new Wingspan stent (Boston
Scientific, Fremont, California, U.S.) is intended to
overcome this limitation. The FDA has recently
approved it as a humanitarian use device for the
treatment of symptomatic and greater than 50% intra-
cranial stenosis resistant to medical therapy.
Future directions for stent-assisted aneurysm
embolization involves replacing standard open-cell
stents with covered stents (also called stent grafts)
that would obviate the need for coil embolization of
some giant and wide-necked aneurysms and expand
treatment options for large fusiform aneurysms and
cavernous-carotid fistulas. Current stent grafts are
balloon expandable stents composed of a polytetra-
fluoroethylene membrane sandwiched between two
stainless steel stents (JoStent Graftmaster Coronary
Stent, Abbott Laboratories; Fig. 24). Early experience
treating intracranial vertebral and carotid artery
aneurysms has been successful (18,19). The major
limitations of covered stents are limited flexibility,
which makes navigation through the tortuous intra-
cranial vasculature difficult, and the potential for
occlusion of small penetrating arteries.
EMBOLIC MATERIAL
Microcoils
Dr. Guglielmi first introduced electrolytically detachable
platinum microcoils in 1990. Since then, advancements
have led to the availability of a plethora of coils of
175
Figure 25 Illustration of coil shapes. (A) Standard helical coil.
(B) 2D (2-diameter) coil. (C) 3D coil. Source: Courtesy of Boston
Scientific, Fremont, California, U.S.
varying sizes and shapes, degrees of stiffness, and
coatings from numerous manufacturers that have
allowed the successful treatment of more varied and
complex aneurysms. Coil size is shorthanded as coil
diameter (approximate range, 224 mm)  coil length
(approximate range, 160 cm). Coil shapes (names and
styles vary by manufacturer) include standard helical,
two-diameter, and three-dimensional (Fig. 25). Exam-
ples of some novel shapes include the Cyclone, Eight,
and Pretzel configurations available for Sapphire, NXT,
and Topaz coils (Micro Therapeutics, Inc.). Coil stiffness
availability includes ultrasoft, soft, standard, firm, and
extrafirm. Most current coils are manufactured with
stretch-resistant technology.
Coating options include bare platinum [e.g.,
Guglielmi detachable coils (GDC), Boston Scientific,
Fremont, California, U.S.], bioactive platinum coils
with polyglycolic-polylactic acid (PGLA) copolymer
covering (Matrix and Matrix2, Boston Scientific, Fre-
mont, California, U.S.; Fig. 26) or interwoven microfila-
ments (Nexus, Micro Therapeutics, Inc.), and hydrogel
coils (HydroCoil, MicroVention, Inc., Aliso Viejo, Cali-
fornia, U.S.). Tight packing of GDC coils within an
aneurysm causes impedance and stagnation of intra-
aneurysm blood flow facilitating thrombosis. The elec-
tric current applied to detach the coil augments this
prothrombotic effect. The PGLA component of Matrix
and Nexus coils incites an inflammatory cascade that
hastens the conversion of intra-aneurysmal thrombus to
mature fibrocellular scar tissue and accelerates neo-
endothelialization of the aneurysm neck. Whether this
modification actually enhances long-term aneurysm
occlusion rates over bare platinum embolization is not
known. The HydroCoil is a platinum coil coated with a
hydrogel polymer called Intelligel, which is designed to
swell over 20 minutes when the coil contacts blood (Fig.
27). The HydroCoil-10, -14, and -18 swell to volumes 5,
7, and 11 times the volume of a standard platinum coil,
176 Katz et al.
Figure 26 Illustration of coil coating. (A) Bare platinum coil
(GDC) and (B) PGLA-coated coil (Matrix). (C) Magnified view
showing the PGLA coating over the platinum base of the Matrix
coil. Abbreviations: GDC, Guglielmi detachable coils; PGLA,
polyglycolic-polylactic acid. Source: Courtesy of Boston Scien-
tific, Fremont, California, U.S.
Figure 27 (A) Photograph of a hydrated Hydrocoil and
(B) electronmicrograph of the dehydrated Intelligel coating of
the Hydrocoil. Source: Courtesy of MicroVention Inc.
respectively, which is intended to increase coil-packing
density. The coils are detached by hydrostatic pressure
rather than electrolysis. The coils must be prehydrated
with lactated Ringers solution rather than heparinized
saline. We have found these coils to be most useful
during the treatment of giant aneurysms.
The technique of aneurysm coil embolization
involves first the careful placement of a framing coil
(typically a standard 2D or 3D coil is most suitable)
into the aneurysm dome under fluoroscopic guidance
using roadmap or subtraction fluoroscopy technique.
Once coil position within the aneurysm, and without
loop herniation into the parent vessel, is confirmed by
fluoroscopy, the coil is detached. The coil pusher wire
is then carefully withdrawn under fluoroscopic guid-
ance while ensuring that the coil was fully detached. If
residual aneurysm opacification is seen, then addi-
tional coils of various shapes and successively dimin-
ishing sizes are added to the coil mass until complete
occlusion (if possible) is obtained. The first coil has to
be as large as possible in relation to the size of the
aneurysm, and the following coils are delivered in
decreasing sizes, so that the aneurysm is filled with
coils from the outside to the center. Good choice and
placement of the first coil is fundamental and some-
times will alone determinate the success of the proce-
dure. The most hazardous coils are the first (framing)
coil, which has the greatest chance of causing aneur-
ysm rupture, and the last coil at the neck, which has
the highest likelihood of herniation into the parent
vessel.
Other types of coils include fibered coils
intended for arterial and venous embolization in the
treatment of large AVF and AVM (e.g., VortX, VortX
Diamond, and fibered platinum coils, Boston Scien-
tific, Fremont, California, U.S.; Fig. 28), including vein
of Galen malformations. Fibered coils are constructed
of a platinum base coil with attached dense polyester
fibers intended to increase their thrombogenicity. Liq-
uid coils (Berenstein Liquid Coil, Boston Scientific,
Fremont, California, U.S.) are platinum microcoils
that are injected with saline instead of those delivered
with a pusher wire and are employed for artery or
vein occlusion. The supplied plunger is attached to a
3-mL saline-filled syringe and then inserted into the
hub of a microcatheter. Gentle saline infusion pushes
Figure 28 Photograph of the fibered VortX coil. Source: Cour-
tesy of Boston Scientific, Fremont, California, U.S.
 Chapter 8: Techniques and Devices in Interventional Neuroradiology 177

the coil to the tip of the microcatheter and then a small

saline bolus injects the coil into the target vessel. We
commonly use these coils during tumor embolization
to block a proximal nonfeeding artery branch to avoid
PVA particle embolization of that arterys normal
distal territory [e.g., occlusion of the anterior middle
meningeal artery (MMA) branch during PVA emboli-
zation of a posterior MMA branch feeder of a tentorial
meningioma].

Polyvinyl Alcohol Particles

Mechanical vessel occlusion is efficiently obtained
with PVA particles (Fig. 29) during the endovascular
treatment of tumors, dural AVF, and epistaxis. PVA
particles are mixed in contrast and injected selectively
through a microcatheter under subtraction fluoro-
scopic guidance. PVA particles are available in 45- to
150-mm to 1000- to 1180-mm sizes (Contour PVA par-
ticles, Boston Scientific, Fremont, California, U.S.). We
generally select 150- to 250-mm PVA particles for most
tumor embolization procedures. During PVA emboli-
zation, the microcatheter is advanced into a feeding
branch (avoiding wedge flow), and then PVA is
infused in a pulsatile fashion until particles are seen Figure 30 Photograph of PVA particles in solution demonstrat-
accumulating at the microcatheter tip. Care must be ing the rough surface and aggregation tendency typical of PVA.
taken to avoid particle accumulation in the micro-
catheter hub, and flushing the microcatheter with
heparinized saline between successive infusions
(away from other devices) is required. The particles
Embosphere Microspheres
are adherent to the endothelium, wedge in the vessels,
and accumulate within the tumor bed inciting necro- Embospheres (Biosphere Medical, Inc., Rockland, Mas-
sis. Tumor necrosis may be accompanied by signifi- sachusetts, U.S.) are an alternative particulate embolic
cantly increased surrounding edema; therefore, for agent composed of trisacryl gelatin microspheres.
large tumors with mass effect, we give a bolus dose Unlike PVA particles, which have uneven surfaces
of dexamethasone at the time of tumor embolization to and variable sizes (Fig. 30), microspheres are spherical
prevent adverse sequelae. Arterial occlusion with PVA particles of uniform size and shape. These character-
may be temporary with recanalization occurring over istics are ideal for improving distal penetration of
weeks to months as the periparticle thrombus resorbs vascular lesions and tumor vascular beds. In a direct
(20). Thus, PVA embolization is most appropriate for comparison with PVA particles, preoperative meningi-
preoperative tumor embolization, epistaxis (where the oma embolization with Embospheres resulted in sig-
etiology of the hemorrhage is temporary), and occa- nificantly less procedural blood loss (21). Following
sionally is useful for embolization of small dural tumor and vascular malformation embolization, the
feeders of dural AVF. microspheres do not degrade and cause only a mod-
erate surrounding inflammatory response (22). Embo-
spheres, unlike PVA particles, do not aggregate;
therefore, a 100-mm Embosphere bead will reliably
occlude a 100-mm vessel, whereas a 100-mm PVA par-
ticle is less predictable and may bind to a 200-mm
vessel wall causing obstruction following aggregation
with other PVA particles. This absence of aggregation
also enhances delivery because the microspheres do
not clump within the microcatheter.

Figure 29 Photograph of 500- to 710-mm PVA particles.
N-Butyl Cyanoacrylate
The liquid acrylic adhesive N-butyl cyanoacrylic acid
(NBCA) (Trufill NBCA Liquid Embolic, Cordis Corp.)
is used in the embolization of AVM and pial AVF.
NBCA preparation requires the use of clean gloves
and should be performed in a location absent of all
ionic solutions (e.g., blood, contrast, and saline). The
178 Katz et al.

adhesive is first diluted 25% to 33% with ethiodol MECHANICAL EMBOLECTOMY

(Cordis Corp.), an oily medium that increases the
polymerization time of the NBCA monomers and
enhances the character of the polymer mass as it
contacts blood (23). The solution can be further
mixed with tantalum powder (Cordis Corp.) to
increase radiopacity. Typically, a flow-guided micro-
catheter is advanced into a feeding artery until wedge
flow is obtained. The microcatheter is flushed with
3 mL of 5% dextrose in water, and then the NBCA
solution is carefully injected under subtracted fluoros-
copy into the AVM nidus or fistula, being cautious to
avoid reflux at the microcatheter tip. Anions in blood,
primarily hydroxyl anions, initiate the exothermic
polymerization of the compound, which forms an
occlusive cast in the feeding artery and nidus/fistula.
Once the adhesive is sufficiently delivered, the micro-
catheter is briskly withdrawn and discarded. Further
embolization can be performed in the same session or
in staged procedures. In our experience, however, the
majority of AVMs will require surgery or radiation
therapy for definitive cure.
Onyx
The Merci Retriever
Mechanical embolectomy devices are used in the
treatment of AIS patients who are either ineligible
for or failed IV r-tPA, and may be used in conjunction
with IA thrombolytic infusion. The Merci Retriever
(X5 and X6 Retriever, Concentric Medical) is the only
FDA-approved device available for mechanical clot
extraction during AIS treatment. Merci device safety
and efficacy in the treatment of AIS patients were
demonstrated in the MERCI Trial (29,30). The device
is a nitinol wire with five helical loops of diminishing
diameter at the distal tip (Fig. 31). The newer L-series
retrievers have cylindrical rather than tapered loops
as well as bound suture material to enhance clot
capture. The L-series retrievers are FDA approved
for endovascular foreign body retrieval and are used
off-label for mechanical embolectomy in AIS (Fig. 32).
An 8- or 9-Fr balloon guide catheter (BGC, Merci BGC,
Concentric Medical, Inc.; Fig. 31) is advanced into a
proximal vessel (proximal internal carotid artery or
subclavian artery just proximal to the vertebral artery
take-off) and inflated to cease anterograde flow

Onyx (Micro Therapeutics, Inc.) is a liquid embolic

agent composed of ethylene vinyl alcohol copolymer
dissolved in dimethyl sulfoxide (DMSO), which has
been available in Europe for the treatment of AVM
and difficult aneurysms and was recently approved
by the FDA for use in the United States for AVM
embolization. The benefit of Onyx over NBCA for
AVM embolization is that Onyx polymerizes by
desiccation and is not adhesive, which allows for con-
trolled and extensive filling of the nidus with less risk
of premature polymerization, venous occlusion, and
catheter gluing (24,25). For aneurysm treatment, a
balloon is placed over the neck of the aneurysm, and
Onyx is slowly injected at 0.1 mL/min (using the
Cadence Precision Injector, Micro Therapeutics, Inc.)
until the aneurysm is filled. With the balloon deflated,
the DMSO diffuses out over approximately 10 minutes
and the Onyx solidifies. The balloon is then re-inflated
and the microcatheter is carefully removed (26).

Absolute Ethyl Alcohol

Absolute ethyl alcohol is sometimes used in the treat-
ment of vascular malformations of the head and the
neck not amenable to surgical resection. Access is by
selective IA or transvenous approach or by direct
percutaneous puncture. Alcohol has low viscosity,
facilitating deep penetration of the nidus, and is
extremely cytotoxic, causing fibrinoid necrosis of the
endothelium and vessel thrombosis (27,28). Ethanol is
carefully infused into the lesion and requires 5 to
10 minutes for its thrombotic effect. Complete occlu- Figure 31 Photograph of the Merci mechanical embolectomy
sion typically requires a staged embolization approach system (Concentric Medical, Inc.). (A) Tapered loops of the X6
(27). General anesthesia is required because ethanol Retriever. (B) 18X microcatheter. (C) Balloon guide catheter with
embolization is painful. The main risk of intravascular balloon inflated.
ethanol infusion is acute pulmonary hypertension.
 Chapter 8: Techniques and Devices in Interventional Neuroradiology
during clot removal to prevent distal embolization of
clot fragments. The microcatheter (18X and 18L Merci
Microcatheter, Concentric Medical, Inc.) is advanced
coaxially over a microguidewire (0.014 inch) through
the clot. The microguidewire is carefully removed and
replaced with the Merci Retriever. Two to four
retriever loops are released distal to the clot, then
the device and microcatheter are withdrawn into the
clot and the device is torqued counterclockwise for
two revolutions. The microcatheter is then retracted to
unsheath the remaining loops within the clot, the BGC
is inflated, and the device is torqued clockwise for up
to five revolutions. The retriever/microcatheter unit
is then withdrawn into the BGC lumen while aspirat-
ing, the balloon is deflated, and the entire system is
removed from the patient. Alternatively, the BGC can
be kept in place if more passes with the retriever are
needed.
Other Embolectomy Devices
Additional thrombus retrieval devices include the Neu-
ronet Endovascular Snare (Guidant Corp.), composed of
a nitinol basket attached eccentrically to a microguide-
wire, and the Amplatz Goose Neck Snare (Microvena
Corp., White Bear Lake, Minnesota, U.S.), both designed
for endovascular foreign body retrieval. These devices
are under investigation for mechanical embolectomy in
AIS and are used routinely at some centers for this
indication. Other mechanical embolectomy technology
currently in development for intracranial use or being
employed investigationally for AIS therapy include
laser thrombectomy with the Endovascular Photo
Acoustic Recanalization (EPAR) Laser System (Endova-
six, Inc., San Francisco, California, U.S.) and the LaTIS
Neuro Laser Thrombolysis System (LaTIS, Inc., Coon
Rapids, Minnesota, U.S.), and obliterative thrombec-
tomy with the AngiJet Rheolytic Thrombectomy System
179
Figure 32 (A) Cerebral angiogram, unsubtracted AP
view, demonstrating the angiographic appearance of
the L-series Merci Retriever. (B) Cervical angiogram,
unsubtracted lateral view following right common carotid
artery injection with balloon inflated, demonstrates a
thrombus halo surrounding the Merci Retriever.
(Possis Medical, Inc.) (31). The latter device has been
used successfully in the endovascular treatment of dural
venous sinus thrombosis (3234). The EKOS MicroLy-
sUS infusion catheter (EKOS Corp., Bothel, Washington,
U.S.) is a novel 2.5-Fr microcatheter with a distal 2-mm,
2.1-MHz sonographic ring transducer at the tip that uses
ultrasonic pulse waves to create local cavitation at the
thrombus surface to increase the surface area for IA
thrombolysis (31).
MANAGEMENT OF COMPLICATIONS
Neuroendovascular procedures carry significant risks,
although our techniques have progressed so much in
recent years that in experienced hands the vast major-
ity of procedures are uncomplicated. Complications
include thromboembolism, vessel perforation, dissec-
tion, vasospasm, and device fracture. However, if
managed effectively, these occurrences can remain
technical in nature, avoiding patient morbidity and
mortality. Postintervention angiography is intended to
evaluate technical success and to assess for any of the
above complications.
Ischemic Complications
Intracranial thromboembolic complications, identified
by the lack of distal branch filling or the new onset of
focal neurological deficits in the absence of hemor-
rhage, may be immediate or delayed (e.g., embolic
stroke following aneurysm coil embolization may
occur days postoperatively), and if not recognized
acutely will result in cerebral infarction. Cerebral hypo-
perfusion, which may also result in new focal neuro-
logical deficits, is sometimes unavoidable, for example,
following parent artery occlusion for large fusiform
aneurysms; however, certain measures can minimize
injury and morbidity. Postoperative hypertensive and
180 Katz et al.
hypervolemic therapy to increase collateral flow to an
ischemic area may decrease infarction volume (useful
for the last example), and judicious use of aspirin
therapy may prevent delayed embolic stroke following
aneurysm coil embolization. Aspirin and clopidogrel
treatment, as already mentioned, is required following
stent placement to prevent in-stent thrombosis. Intra-
venous GP IIb/IIIa antagonists (35), IA GP IIb/IIIa
antagonists, and IA tPA are each useful alone or in
combination for treating thromboembolic complica-
tions that are recognized during angiography, and
mechanical embolectomy may be needed for larger
vessel occlusions. Extracranial embolic complications
are avoided by continuous pressurized heparin-saline
flush and by the use of proper angiographic technique.
Hemorrhagic Complications
Intracranial hemorrhage may evolve secondary to
vessel perforation, angiographically noticed as con-
trast extravasation into the subarachnoid space and
clinically by acute blood pressure elevation (Cushing
response), or may be a delayed effect of hyperperfu-
sion or reperfusion injury following revascularization
procedures (angioplasty/stenting and AIS therapy;
Fig. 33). If contrast extravasation is seen, it is important
Figure 33 Axial, noncontrast head CT scan showing a large
hyperdensity in the right basal ganglia representing massive
reperfusion intracerebral hemorrhage with midline shift following
mechanical embolectomy for an acute right middle cerebral artery
occlusion. The patient had MRI diffusion abnormality in the right
striatum prior to embolectomy. However, a large perfusion-
diffusion mismatch prompted endovascular treatment. Mechanical
recanalization was complete without the use of thrombolytic drugs.
not to withdraw the microcatheter/wire, because the
device likely plugs the perforation hole and prevents
massive hemorrhage. If a balloon is in place, as in
some aneurysm treatments, it should be inflated to
tamponade the rupture. Damage may then be mini-
mized by either NBCA infusion into the puncture hole
(infuse through the microcatheter gently into the sub-
arachnoid space), or coil embolization of the aneur-
ysm, or parent vessel. Post-revascularization injury is
best prevented by proper patient selection (especially
of AIS patients) and aggressive postoperative blood
pressure control. If a patient is at high risk for hyper-
perfusion injury, we monitor the patient in the inten-
sive care unit and keep the systolic blood pressure
between 100 and 110 mmHg. For lower-risk patients,
systolic blood pressure below 140 mmHg is usually
adequate.
Other Complications
Vessel dissections may be managed by stent place-
ment during the procedure, or more conservatively, as
most dissections heal on their own, with aspirin
or anticoagulation therapy to prevent embolization
from the intimal flap. As already discussed, verapamil
infusion is very effective for the treatment of catheter-
induced vasospasm. Device fractures (e.g., coils;
Fig. 34) may be efficiently managed by retrieval
using the Merci Retriever or Amplatz Goose Neck
Snare.
Figure 34 Cerebral angiogram, unsubtracted AP view, showing
a coil fracture during the embolization of this large left middle
cerebral artery aneurysm. The coil was successfully retrieved
with the Amplatz Goose Neck Snare (Microvena Corp.).
 Chapter 8: Techniques and Devices in Interventional Neuroradiology
GROIN CLOSURE
When the endovascular procedure is concluded, the
catheters and sheaths are removed, and hemostasis is
achieved by either manual compression or the use of a
closure device. Manual compression requires pressure
with the two fingers placed over the arterial pulse and
a third finger positioned over the puncture hole.
Pressure is gradually alleviated over 10 to 15 minutes
and the site inspected for further bleeding. Complete
hemostasis may necessitate up to 30 to 60 minutes of
compression, especially for patients on systemic anti-
coagulation and antiplatelet therapy. In children and
neonates, care must be taken not to stop arterial flow
and cause thrombosis when applying manual pres-
sure, and compression may be performed with a pulse
oximeter connected to the ipsilateral foot to monitor
extremity perfusion. Following manual compression,
the patient is maintained on strict bed rest, with the
accessed leg immobilized for the number of hours
equal to the size of the introducer sheath in French (i.e,
6 hours for a 6-Fr sheath). Hemostasis following radial
artery puncture can be aided by the use of a compres-
sion clamp. After one hour of compression, the clamp
should be slowly released while watching for contin-
ued bleeding. As already mentioned, one of the bene-
fits of the transradial approach is the lack of
postprocedure ambulation restriction.
Several closure devices are commercially avail-
able, which all carry the advantage of early ambula-
tion, enabling the patient to walk one hour after groin
closure. Examples include the Perclose Closure System
(Abbott Laboratories), which employs suture closure,
and the Angio-Seal vascular closure device (St. Jude
Medical, Inc., St. Paul, Minnesota, U.S.), which uses a
bioabsorbable anchor and collagen sponge to sandwich
and seal the arteriotomy site. Angio-Seal is available
in a 6-Fr device for sheaths less than or equal to 6 Fr
and an 8-Fr device for sheaths less than or equal to 8 Fr.
In our opinion, the Angio-Seal is simpler to use and has
fewer device failures compared with Perclose. The use
of any closure device requires placement under sterile
conditions (we typically change gloves and reprep the
groin area with rubbing alcohol). Although not recom-
mended by the manufacturer, we also administer one
dose of antibiotic (e.g., a cephalosporin for skin flora
coverage) because the device employs foreign body
implantation. Closure devices are too large and not
indicated in pediatric patients and should be cau-
tiously deployed in atherosclerotic and diabetic
patients. In addition, iliac artery angiography before
device groin closure may minimize postclosure com-
plications. Finally, in our experience, thin adult
patients often complain of persistent groin pain follow-
ing Angio-Seal closure, and we recommend that the
device be avoided in slender patients.
CONCLUSION
In recent years, the explosion of novel and enhanced
neurointerventional devices has resulted in tremen-
dous progress in endovascular techniques, making
procedures simpler, safer, and with broader indications
181
and rendering interventions that were once unimagin-
able not only possible but commonplace. One caveat is
that during this rapid evolution, insufficient outcome
analyses have been performed and many new devices
and techniques remain unproven. Our challenge in the
years to come is to demonstrate both the technical and
clinical efficacy of current and new endovascular devi-
ces and procedure through further prospective studies
and randomized clinical trials.
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 9
Balloon Occlusion, Wada, and Pharmacological Testing
Linda J. Bagley
Departments of Radiology and Neurosurgery, University of Pennsylvania
Medical Center, Philadelphia, Pennsylvania, U.S.A.
INTRODUCTION
Despite vast recent technical advances in interventional
neuroradiology, parent vessel sacrifice remains the
only viable therapeutic option for many complex intra-
cranial lesions. As such, there continues to be a role for
occlusion testing in the preprocedural management of
certain aneurysms and neoplasms with associated vas-
cular encasement or potential vascular compromise.
Functional magnetic resonance imaging (fMRI),
magnetoencephalography (MEG), and diffusion-
tensor imaging-based MR tractography in certain
cases provide noninvasive means of function and
tract localization; however, there continue to be sig-
nificant limitations of these modalities for memory
localization and when performed in the presence of
tumors or vascular malformations, which may be
associated with distorted brain architecture, altered
venous drainage patterns, and/or reorganization of
function. Selective and superselective pharmacologi-
cal tests are thus employed in the preprocedural
assessment of certain patients prior to arteriovenous
malformation (AVM) embolization, epilepsy surgery,
and select tumor resections.
This chapter discusses the indications, techniques,
and potential complications and limitations of arterial
and venous occlusion, Wada, and pharmacological
testing. Illustrative case examples are also provided.
ARTERIAL AND VENOUS OCCLUSION TESTING
Indications
Arterial and/or venous occlusion tests are appropriate
for patients scheduled for endovascular, neurosurgi-
cal, and/or otorhinolaryngological procedures in
which vascular occlusion is indicated as therapy or
in which there is a significant risk of intraprocedural
vascular occlusion (17). Such patients may include
those with aneurysms not amenable to coil emboliza-
tion, stent placement, or microsurgical repair (Fig. 1)
(2,3), those with tumors encasing or in intimate con-
tact with the carotid or vertebral arteries (Fig. 2) (4),
and those with tumors involving a dural venous sinus
or necessitating a surgical approach that could result
in sacrifice of a dural venous sinus.
Technique---Venous Occlusion Testing
A guiding catheter is typically placed within the
internal jugular vein, and a nondetachable balloon
microcatheter is advanced into the transverse or sig-
moid sinus. Arterial catheterization as well as angiog-
raphy is performed during balloon occlusion of the
transverse or sigmoid sinus that is at risk. The venous
phase of the angiogram is then assessed for drainage
of the affected hemisphere through collateral path-
ways. Larger balloon sizes (often up to 1.5 cm) are
required than those employed in arterial testing. Ana-
tomic data are obtained, but functional data are not, as
symptoms of venous ischemia are more likely to be
insidious at the onset.
Techniques---Arterial Occlusion Testing
A number of techniques have been described for
temporary arterial occlusion testing. In virtually all
cases, diagnostic angiograms are initially performed
(1, 5). This technique allows assessment of the cervical
vasculature for atherosclerotic disease and of the
intracranial circulation for integrity of the circle of
Willis and potential collateral flow. Following diag-
nostic angiography and prior to nondetachable bal-
loon inflation, patients are routinely anticoagulated,
typically with 5000 to 10,000 units of heparin with
elevation of the activated coagulation time (ACT) to
two to three times the baseline value. Heparinized
saline flush is also employed (1,5,8). Most cases are
performed with conscious sedation. Both double
lumen balloon catheters and nondetachable balloon
microcatheters (with maximal balloon diameters of
58 mm) have been used in these procedures. In
some institutions, a second catheter is utilized to per-
form diagnostic angiography during the occlusion
(confirming occlusion and assessing adequacy of col-
lateral circulation in the arterial, parenchymal, and
venous phases). During carotid occlusion testing, larger
184 Bagley

Figure 1 (A, B) Lateral views of digital sub-

traction angiogram obtained during right com-
mon carotid artery injection demonstrate a
lobulated, wide-necked approximately 2.5 
2.0-cm right internal carotid artery aneurysm,
located predominately within the cavernous
segment with extension into the supraclinoid
segment. There are multiple surgical aneur-
ysm clips about the supraclinoid internal
carotid artery.

Figure 2 (A, B) Axial gadolinium-enhanced T1-weighted images demonstrate an enhancing extra-axial posterior fossa mass
(a meningioma), encasing the right vertebral artery and compressing the brain stem. (C) Lateral projection of digital subtraction
angiogram obtained during common carotid artery injection reveals hypervascular tumor blush in the posterior fossa. (D) AP projection of
left vertebral artery angiogram demonstrates no reflux of contrast into the distal right vertebral artery. The left anterior inferior cerebellar
artery is large and supplies the posterior inferior cerebellar artery territory. (E) AP projection of right vertebral artery angiogram
demonstrates mild displacement and narrowing of the distal right vertebral artery secondary to the meningioma.
 Chapter 9: Balloon Occlusion, Wada, and Pharmacological Testing
balloon catheters are typically inflated in the proximal
internal carotid artery, while microcatheters may be
advanced to the petrous segment. Inflation times of 15
to 30 minutes have typically been reported (1,5,8).
Continuous clinical monitoring of the neurological
exam is performed, with any changes in the exam
prompting immediate deflation of the balloon and
termination of the procedure. Following deflation of
the balloon, angiography is repeated to evaluate the
internal carotid artery for injury/dissection and to
exclude emboli in the intracranial circulation. Almost
all patients failing the balloon occlusion test by clinical
criteria will develop a permanent neurological deficit if
a revascularization procedure is not performed prior to
the intended vascular occlusion (9). Of those who tol-
erate the test by clinical criteria, between 5% and 20%
have been reported to incur a permanent neurological
deficit following permanent vascular occlusion (7,10),
generally within hours to days of the permanent occlu-
sion. Deficits may result from perfusional ischemia
and/or stump emboli.
Numerous adjuvant techniques, including mea-
surement of stump pressures (11,12), induced hypo-
tension (10,13), single-photon emission tomography
(SPECT) (8,1417), transcranial Doppler examinations
(18,19), xenon CT (1,12,18,2022), cerebral blood flow
measurements (22), perfusion imaging (7,23,24), elec-
troencephalography (EEG) (2531), and monitoring of
somatosensory-evoked potentials (SSEP) (32,33) have
been employed to improve the predictive value of
occlusion testing. Unfortunately, for many of these
techniques, conflicting results have been reported in
the literature.
Measurement of Stump Pressures
Arterial pressure can be monitored distal to the occlu-
sion by the use of a double lumen catheter with
connection of the second lumen to a pressure trans-
ducer. The utility of this technique is controversial.
Some authors have reported that maintenance of a
stump pressure ratio (initial mean stump pressure/
preocclusion mean arterial pressure) of 60% or more
during test occlusion is a useful marker of adequate
collateral circulation (11). A number of studies
have found a significant correlation between stump
pressures and measures of cerebral perfusion, such as
SPECT (8), while others have failed to demonstrate
such a correlation (12).
Induced Hypotension
This technique is applied in patients who have toler-
ated 15 to 20 minutes of arterial occlusion while
normotensive (10,13). Following initial testing, systolic
blood pressure is pharmacologically lowered by
approximately 30% (typically with nitroprusside infu-
sion or intravenous labetalol), and neurological testing
is continued for an additional 15 to 20 minutes. Stan-
dard et al. (10) reported the identification of an addi-
tional 19% of patients in his series with limited
cerebrovascular reserve and a 5% false-negative rate
for patients tolerating balloon occlusion testing with
hypotensive challenge (reduced compared with
185
reported false-negative rates of conventional occlusion
testing of up to 20%). In contrast, Dare et al. (13)
reported a 15% false-negative rate for such patients.
False negatives may in part be secondary to vaso-
dilatory effects of nitroprusside. Concerns have also
been raised that induced hypotension may falsely ele-
vate the sensitivity of this test and thus inappropriately
subject these patients to revascularization procedures.
SPECT
With this technique, Tc 99m hexamethylpropylene-
amine oxime (HMPAO) is injected immediately fol-
lowing balloon inflation and vascular occlusion.
SPECT imaging is performed following balloon defla-
tion and removal of the catheter with measurement of
activity ipsilateral and contralateral to the occlusion.
Activity reflects cerebral blood flow within a few
minutes of the injection (8,15). Hemispheric asymme-
tries and reductions in tracer uptake (in comparison to
preocclusion testing when available) have been shown
to correlate with the development of clinical deficits.
MR Perfusion
MR perfusion imaging (7) may be performed with
dynamic gadolinium-enhanced imaging during bal-
loon occlusion when MR is available in the interven-
tional suite. Gadolinium is administered by bolus
injection at a dose of 0.1 mmol/kg. Cerebral blood
volume (CBV) may be calculated on the basis of signal
intensity changes in brain with and without contrast
agent. Mean transit time (MTT) of contrast through
the arterial system may also be calculated, allowing
determination of regional cerebral blood volume
(rCBV) (24). Authors have demonstrated greater per-
fusion delays in patients who have clinically failed the
test. Authors have also described alterations in con-
trast enhancement and in brain parenchymal signal
intensity in areas of hypoperfusion (7).
CT Perfusion
Perfusion CT and acetezolamide challenge have also
been employed in patients who have clinically toler-
ated test occlusion again in attempts to improve sen-
sitivity. The technique described by Jain et al. (23)
requires transport of the patient with a catheter in the
internal carotid artery and reinflation of the balloon
without fluoroscopic guidance, but on the basis of the
volume used to inflate the balloon initially. Multiple
perfusion CTs are performed with axial images
through the basal ganglia obtained during rapid
administration of intravenous contrast (4 cc/sec) ini-
tially during balloon reinflation and then following
balloon deflation. Additionally, perfusion CT is
repeated 20 minutes following administration of 1 g
of acetezolamide (Bedford Kaboratories, Bedford,
Ohio, U.S.) with balloon reinflation.
Xenon CT
This technique also attempts to measure cerebral blood
flow in patients who have clinically tolerated test
occlusion (1,12,18,2022). Again, it requires transport
186 Bagley
of the patient to the CT scanner with a catheter in the
internal carotid artery and reinflation of the balloon.
The patient inhales a gas mixture of 33% xenon and
67% oxygen. Baseline scans are obtained prior to bal-
loon inflation and are repeated during balloon infla-
tion. Xenon uptake in the middle cerebral artery
distribution is used to estimate regional cerebral
blood flow (rCBF). Regions with cerebral blood flow
of less than 30 mL/100 g/min are judged to be at risk.
Transcranial Doppler Ultrasound
Transcranial Doppler interrogation of the middle cere-
bral artery may be performed during test occlusion.
There is an imperfect correlation between cerebral
blood flow and mean velocity in the middle cerebral
artery, as velocity is also affected by vascular caliber,
hematocrit, viscosity, and insonation depth and angle
(18). However, reductions of mean blood flow velocity
and pulsatility index of less than 30% have been
shown to be predictive of clinical tolerance, whereas
reductions of more than 50% have been shown to
correlate with clinical symptoms (19).
Neurophysiological Monitoring
Many studies have documented the utility of neuro-
physiological monitoring (NPM) (EEG, SSEP, and brain
stemevoked potentials) in patients undergoing cerebro-
vascular surgery, most notably carotid endarterectomy,
performed under general anesthesia (2528). EEG
changes have been reported when rCBF is less than
10 mL/100 g/min. An rCBF of 15 mL/100 g/min ap-
pears to be a critical value below which cortical
SSEP amplitude is reduced, central conduction time is
prolonged, and cerebral infarction is likely to occur.
Liu et al. also described the use of NPM in patients
undergoing endovascular procedures and demonstrated
NPM changes in 26% of the patients in his series, with
resultant alterations in management in 14% of the
patients. Monitoring proved most beneficial in patients
who were unable to cooperate with neurological testing.
However, NPM changes were also observed in cooper-
ative patients without corresponding abnormalities
noted on physical neurological exam (33).
COMPLICATIONS
Reported complications of balloon occlusion testing
include arterial dissections, embolic infarcts, and per-
fusional ischemia. Reported rates of complications
range from less than 1% to 15% (the majority between
1% and 7%), with higher rates being reported in
earlier studies. Complication rates have decreased
with improvements in catheter and balloon technol-
ogy. Adequate anticoagulation during balloon infla-
tion has reduced the number of embolic complications
(1,5,6). However, adjuvant techniques intended to
increase the sensitivity of the test (e.g., those requiring
transport of patients with indwelling catheters, blind
reinflation of the balloon, and/or induction of hypo-
tension) have sometimes been associated with higher
complication rates (due to vascular injury and creation
of perfusional deficits) (1,10,2023).
ILLUSTRATIVE CASE
The patient is a 52-year-old woman with history of
hypertension who presented with a three-week history
of headache and right eye pain. Physical examination
was notable for a right sixth nerve palsy and mild
ptosis. Imaging studies were notable for an approxi-
mately 2-cm aneurysm of the cavernous right internal
carotid artery (Fig. 3AC). Prior to definitive treatment
and following systemic anticoagulation, a 30-minute
test occlusion of the distal cervical right internal carotid
artery was performed. No changes in the patients
neurological exam were noted during the test occlu-
sion. Subsequently, treatment of the aneurysm with
Neuroform stent placement and coil embolization was
attempted, but resulted in compromise of the parent
vessel (Fig. 3D, E). Ultimately, permanent occlusion of
the right internal carotid artery was performed without
neurological complication (Fig. 3F, G).
WADA TEST
Epilepsy
Epilepsy, the condition of spontaneously recurring
seizures, is quite common, affecting approximately
0.5% to 1% of the population (34). It is a potentially
psychosocially devastating, life-altering, and even life-
threatening disorder (due to associated increased
incidences of sudden death, traumatic injuries, and
suicide). While many advances have been made in the
medical therapy of epilepsy, many cases, between 5%
and 20%, remain medically intractable (35,36). Surgi-
cal therapies are appropriate for certain patients and
include lesional resections, temporal lobectomies, cal-
losotomies, hemispherectomies, and subpial transac-
tions (35). The most common cause of intractable
epilepsy is mesial temporal sclerosis. As such, tempo-
ral lobectomy is the most commonly performed sur-
gical procedure for the treatment of epilepsy. Patients
undergoing temporal lobectomy are at risk of devel-
oping speech/language and/or memory deficits, and
therefore commonly undergo functional preoperative
testing to minimize these risks.
Historical Background
Amobarbital is a lipid soluble substance that can cross
the blood-brain barrier and temporarily block neuro-
nal function (37).
Currently, the intracarotid amobarbital test is
performed in conjunction with neuropsychological
testing to determine lateralization of speech/language
and memory functions, most often in patients with
medically intractable epilepsy scheduled for surgical
resection of epileptogenic tissue (3840). This test is
also sometimes employed in nonepileptic patients
scheduled for resection of unilateral temporal or fron-
totemporal lesions.
Juhn A.Wada first performed the intracarotid
amobarbital procedure in the 1940s. Wada initially
injected sodium amobarbital into the left common
 Chapter 9: Balloon Occlusion, Wada, and Pharmacological Testing 187

Figure 3 (A) Axial CT scan demonstrates enlargement of the right cavernous sinus with a mildly hyperdense extra-axial mass. (B, C) AP
oblique and lateral views of digital subtraction angiogram obtained during right common carotid artery injection reveal an approximately
2 cm irregular aneurysm, without discernable neck and with possible intraluminal thrombus, of the cavernous right internal carotid artery.
(D, E) AP and lateral digital subtraction angiograms obtained following stent placement and partial coil embolization of the aneurysm are
notable for markedly decreased flow within the internal carotid artery. (F) Lateral digital subtraction angiogram demonstrates multiple
embolization coils and complete occlusion of the right internal carotid artery. (G) AP angiogram obtained during left common carotid artery
injection demonstrates extensive flow across the anterior communicating artery with contrast opacification of the right anterior and middle
cerebral arteries, without opacification of the previously demonstrated aneurysm.

carotid artery of a patient with frequent status epilep-
ticus in an attempt to arrest the convulsions. In 1949, he
first described the use of this procedure to determine
language lateralization (38) in an attempt to improve
the safety and efficacy of electroconvulsive therapy in
psychiatric patients (by placement of the electrodes
over the nonspeech dominant hemisphere). In 1960,
Wada collaborated with Rasmussen and reported the
use of the intracarotid amobarbital procedure for deter-
mination of hemispheric language dominance in epi-
lepsy surgical patients. In 1962, Milner, Branch, and
Rasmussen reported the use of this test for assessment
of memory function in the isolated hemisphere. Subse-
quent studies have examined the correlation of mem-
ory lateralization with location of the seizure focus and
prediction of surgical outcomes (4149).
Technique
The intracarotid amobarbital procedure is performed
without sedation, as sedation may confound neuro-
psychological test results. Subsequently, diagnostic
angiography is initially performed with catheter place-
ment in the cervical internal carotid artery to assess
for anatomic variation in the anterior circulation, in
particular to exclude a carotid-basilar anastomosis, but
also to assess the likely distribution of amobarbital.
The internal carotid artery supplying the presumed
abnormal hemisphere is generally the one initially
selected. Following diagnostic angiography, approxi-
mately 80 to 125 mg of sodium amobarbital are
injected into the internal carotid artery over approxi-
mately three to five seconds, while the patient counts
backward and attempts to maintain his or her arms in
an elevated position. Efficacy of amobarbital adminis-
tration may be confirmed in several ways: concurrent
unilateral EEG slowing and/or development of a neu-
rological deficit (hemiparesis and/or aphasia). Testing
of language skills and visuospatial and verbal memory
is then performed. Following a 30- to 45-minute delay
(to allow the effects of amobarbital to diminish), the
contralateral internal carotid artery is selected and the
procedure is repeated. When a carotid-basilar anasto-
mosis is present, a microcatheter can be advanced
beyond it and the procedure continued. Similarly,
when there is significant cross-flow through the
anterior communicating artery, bifrontal impairment
may result, and the neuropsychological testing may
be rendered invalid secondary to impaired patient
consciousness and inability to cooperate. In such
188 Bagley
cases, selective middle (MCA) and posterior cerebral
artery (PCA) amobarbital administration has often
been described with somewhat reduced dosages of
the agent (7580 mg). Selective MCA amobarbital
administration has been used when language lateral-
ization was of primary concern, and selective
PCA administration was performed for memory
assessment (50).
Predictive Value
The intracarotid amobarbital test has also long been
used to determine language lateralization. Multiple
studies have also investigated its validity in the pre-
diction of postoperative memory deficits (41,42,49,
5154). Cohen-Gadol et al. (52) demonstrated statisti-
cally significant correlations between Wada test scores
and hippocampal volumetry, as well as a significant
inverse correlation between the disparity of the scores
and changes in verbal (though not visuospatial) mem-
ory following temporal lobectomy. Andelman et al.
(49) demonstrated a significant correlation between
memory scores in the ipsilateral hemisphere and
postsurgical memory changes. Multiple additional
studies have also demonstrated a correlation between
Wada memory test results and seizure-free outcome,
most notably in patients with temporal lobe epilepsy.
Correct lateralization of the seizure focus (and hence,
prediction of outcome) has been reported in 75% to
85% of patients using various criteria (4548).
Alternative Agents
At times, there has been a global shortage of amobar-
bital. As such, alternative agents have been investi-
gated. Methohexital (Brevital) has been employed, but
it is quite short acting, and reinjection may be
required. Jones-Gotman et al. (55) reported successful
experience with etomidate, given by bolus followed
by infusion, which was continued during sampling of
speech measures and presentation of objects for mem-
ory testing. In the 30 hemispheres tested, contralateral
hemiplegia developed in all patients, and slowing of
EEG was observed in all injected hemispheres. Apha-
sia followed dominant hemisphere injections. All
affects reversed over approximately four minutes,
following termination of infusion. Propofol (56),
administered in doses of 10 to 20 mg (typically less
than 15 mg), has also been employed, with results
comparable to those obtained with amobarbital. How-
ever, in Mikunis study (57), adverse reactions (includ-
ing eye pain, shivering, facial contortion, confusion,
involuntary movements, increased muscle tone,
rhythmic movements, and tonic posturing) were
noted in one-third of the patients, and in some cases
precluded completion of the testing. Adverse reac-
tions were observed more frequently in patients over
55 years and when larger doses of propofol were
administered. The most severe reactions likely result
from hyperexcitic phenomena, which have been
shown to occur with sudden increases in cerebral
propofol concentrations.
Noninvasive Testing
A number of noninvasive tests have been proposed to
replace the Wada test in the presurgical evaluation of
patients with intractable epilepsy. Most notably, fMRI
has been proposed as a replacement for the Wada test
(5874); fMRI has the advantages of being less time-
consuming (typically requiring *3060 minutes), of
posing minimal risk to the patient, and of being sig-
nificantly less expensive (58). Numerous studies have
examined the validity of fMRI in language lateraliza-
tion. Binder et al. (59) found 96% concordance between
fMRI and Wada test results for language dominance.
Yetkin et al. and Lehericy et al. have reported similar
results (67,68). However, the most promising results
have been achieved in patients with left hemispheric
language dominance (the majority of patients studied)
and temporal lobe epilepsy. False categorization of
language dominance by fMRI was reported to be
approximately 9% in Woermanns series, ranging
from 3% in left-sided temporal lobe epilepsy to 25%
in left-sided extratemporal epilepsy (60). Sabbah et al.
(64) reported 95% concordance of the Wada test and
fMRI in a group of epileptic patients with suspected
atypical language lateralization.
Additional studies have examined the ability of
fMRI to predict memory following temporal lobec-
tomy (6973) and to lateralize temporal lobe epilepsy
[and hence predict surgical outcome (70)]. Rabin et al.
(69) examined fMRI activation during complex visual
scene encoding (which is believed to engage both
visuospatial and verbal memory systems) and
reported a correlation between activation asymmetries
in the mesial temporal regions on fMRI with hemi-
spheric memory dominance. Additionally, Rabin et al.
reported correlation of these activation asymmetries
with postsurgical memory as well as an inverse cor-
relation between absolute activation in the hemi-
sphere to be resected and postsurgical memory.
Jokeit et al. (70) reported 90% accuracy of lateraliza-
tion of seizure focus in patients with unilateral tem-
poral lobe epilepsy on the basis of memory-induced
mesial temporal lobe activation asymmetries on fMRI.
MEG
MEG has also been proposed as an alternative to the
Wada test (7580). MEG is based on the principle that
all electrical currents are associated with magnetic
fields. Cohen (80) developed a superconducting quan-
tum interference device to measure magnetic fields
generated by intracranial currents. Approximately
10,000 to 100,000 neurons must be simultaneously
generating current to produce a magnetic field strong
enough to be detected with present technology. Mag-
netic fields are minimally distorted by intervening
tissue, and hence MEG may provide precise localiza-
tion of the source of electrical current (e.g., seizure foci
or functional cortex). Data can then be coregistered
with conventional MRI. MEG has been used to local-
ize visual, auditory, and somatosensory cortex, and to
lateralize language (79). Papanicolaou et al. (75) dem-
onstrated a high degree of (though not absolute)
 Chapter 9: Balloon Occlusion, Wada, and Pharmacological Testing 189

concordance (87%) between MEG and Wada data for
determination of hemispheric language dominance.
MEG tended to detect more activity in the nondomi-
nant hemisphere (similar to fMRI) than predicted by
the Wada test.
ILLUSTRATIVE CASE
The patient is a 41-year-old right-handed man with
history of fall at the age of 2 associated with brief coma
with subsequent development of medically intractable
partial complex and generalized tonic-clonic epilepsy
in adulthood. EEG was suggestive of a left temporal
lobe seizure focus. MRI was notable for left mesial
temporal sclerosis (Fig. 4A) and positron emission
tomography (PET) was notable for mild left temporal
hypometabolism. A Wada test was performed as part
of the presurgical evaluation for scheduled left tempo-
ral lobectomy. Digital subtraction angiography per-
formed following selection of the left internal carotid
artery revealed a persistent left trigeminal artery
(Fig. 4B, C). A microcatheter was subsequently
advanced beyond the origin of the trigeminal artery
into the supraclinoid left internal carotid (Fig. 4D, E),
and 125 mg of sodium amobarbital was instilled. The
patient developed transient right hemiparesis and
aphasia. Neuropsychological testing revealed left
hemispheric language dominance and right hemi-
spheric memory dominance. The patient subsequently
underwent right temporal lobectomy with histological
confirmation of mesial temporal sclerosis.
PHARMACOLOGICAL TESTING
Indications
The development of permanent neurological deficits
following embolizations of cerebral and spinal AVMs
has been reported in 5% to 10% of the cases, largely
due to ischemic sequelae in eloquent tissue. Ischemic
injury to the cranial nerves, to the eye, or to cerebral
cortex (via external to internal carotid artery or external

Figure 4 (A) Coronal T2-weighted image demonstrates atrophy and hyperintensity of the left hippocampus, indicative of mesial
temporal sclerosis. (B, C) AP and lateral angiograms obtained during left internal carotid artery injection reveal a persistent trigeminal
artery. (D, E) AP and lateral angiograms obtained with a microcatheter placed in the supraclinoid left internal carotid artery beyond the
origin of the trigeminal artery.
190 Bagley
to vertebral artery anastamoses) may complicate exter-
nal carotid artery embolizations. As such, superselec-
tive angiography and provocative pharmacological
tests are often employed to predict the safety of
arterial embolization of cerebral and spinal AVMs,
dural AVMs, facial and oral vascular malformations,
and tumors (8184). Similar to Wada testing, super-
selective provocative pharmacological testing may also
be employed prior to planned surgical intervention.
Technique
Typically, provocative testing for arteries with extra-
axial destinations is performed with lidocaine and
provocative testing for arteries with intra-axial desti-
nations is performed with barbiturates, such as amo-
barbital, though both agents have also been utilized in
both situations (8186). Patients undergoing such pro-
cedures usually receive a small amount of intravenous
sedation. Neurological assessments are made imme-
diately before and after anesthetic injection and com-
pleted within a few minutes. In some cases NPM
supplements the physical exam (particularly when
the territory involved is the brain stem or thalamus),
whereas in patients under general anesthesia it may
completely replace it. Amobarbital is generally admin-
istered in doses of 30 to 75 mg, and lidocaine is
typically administered in doses ranging from 10 to
40 mg. Some authors have reported the administration
of both agents (lidocaine and amobarbital) prior to
embolization, as these agents produce anesthetic
effects via different mechanisms, and concomitant
administration may thus improve the sensitivity of
provocative testing.
Amobarbital acts at the gamma aminobutyric
acid A (GABA-A) receptor through inhibition of post-
synaptic neurons in cortical and deep gray matter and
in the hippocampus. As cerebral white matter con-
tains a paucity of GABAergic synapses, it is largely
unaffected by the drug. Lidocaine blocks voltage-
gated sodium channels, which are present on all
nerve cell membranes and thus inactivates neurons
in gray and white matter (85). Fitzsimmons et al.
reported detection of clinically significant deficits
with superselective lidocaine administration in four
patients that did not develop a deficit with super-
selective amobarbital testing (85). With high-flow
lesions, such as AVMs, hemodynamic factors may
produce false-negative and false-positive tests with
amobarbital or lidocaine. The anesthetic agent may
bypass adjacent normal tissue, but liquid embolic
agents will polymerize and may initially occlude
high-flow channels, leading to redistribution of
the embolic agent (82). Deveikis et al. (86) advocated
the use of amobarbital injections in the external
carotid circulation (to supplement lidocaine test injec-
tions) to improve the sensitivity for detection of exter-
nal carotid to internal carotid or vertebral artery
anastomoses. When a deficit is produced with phar-
macological testing, therapeutic options include
advancing the microcatheter closer to the nidus and
repeating the testing, protecting the normal territory
by placement of a coil or similar agent and repeating
the testing, utilizing a different embolic agent (such as
larger particles) or abandonment of embolization of
that particular pedicle. Complications of provocative
pharmacological testing are uncommon. Injection of
lidocaine into the external circulation often produces
some degree of discomfort in the patient . While rare,
injection of lidocaine into the cerebral circulation has
been reported to be complicated by seizures and
cardiorespiratory depression (86).
Noninvasive Alternatives
While pharmacological testing provides specific infor-
mation about the function of tissue within a vascular
territory, fMRI (87) and tractography (8891) may
noninvasively localize eloquent tissue prior to
planned surgical intervention. As above, fMRI has
been shown to localize (though imperfectly) language
and memory. It has also been utilized to localize
motor, sensory, and visual cortex. Similarly, thin-
section diffusion tensor imaging has been employed
to localize sensory, motor and visual cortex, and path-
ways (8891). As diffusion of water perpendicular to
the neural axis is limited by cell membranes and
myelin sheaths, and diffusion along the nerve axis is
less limited, the primary direction of the principal
eigenvector of the diffusion tensor at each location
can be determined and corresponds to the trajectory of
the corresponding fiber. Thus, sensory and motor
tracts may be mapped in three dimensions and in
relation to AVMs and their draining veins (88). Addi-
tionally, tractography may be fused with conventional
MRI images and utilized with neuronavigational sys-
tems (90). This technique offers advantages over phar-
macological testing as drug distribution may be
altered by arteriovenous shunting and as such testing
yields no information about displacement of cortex
and tracts or relationship of draining veins to eloquent
cortex and tracts. This technique has also been
attempted with tumors, but its utility is decreased
by the presence of vasogenic edema. The presence of
hemorrhage may also degrade images due to suscep-
tibility artifacts.
SUMMARY
Arterial and venous occlusion, Wada, and pharmaco-
logical tests provide vital information in the manage-
ment of complex aneurysms, neoplasms, AVMs, and
epilepsy. A variety of techniques have been employed
to improve the accuracy of these tests. Complications
are rare, but their incidence may be increased with
increasing complexity of the tests. A number of non-
invasive alternatives (predominantly employing MRI)
to these tests have been developed and have demon-
strated promising though imperfect results. As such,
the neurointerventionalist must be knowledgeable
of the indications, limitations, and potential compli-
cations of provocative testing and maintain expertise
in its performance.
 Chapter 9: Balloon Occlusion, Wada, and Pharmacological Testing
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193
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 10

Endovascular Management of Tumors and Vascular

Malformations of the Head and Neck

Johnny C. Pryor and Joshua A. Hirsch

Department of Interventional Neuroradiology and Endovascular Neurosurgery,
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
Robert W. Hurst
Department of Radiology, Neurology, and Neurosurgery, Hospital of the University of
Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

INTRODUCTION VASCULAR TUMORS

Vascular lesions of the head and neck are a wide-
ranging and often confusing constellation of lesions,
and diagnosis and treatment are ideally approached
through multidisciplinary cooperation. Mulliken et al.
were the first to present a rational classification of
hemangiomas and vascular malformations (15). With
modifications over time, this classification has evolved
into a clinically useful system that helps us under-
stand the etiology and pathophysiology of these
lesions and gives us a context within which to under-
stand their behavior and plan a rational treatment
strategy. This context also helps establish proper
communications between physicians and patients.
Previously, vascular lesions of the face and head
were often ubiquitously referred to as hemangiomas,
and this mistake is often still repeated even in modern
clinical practice. Mulliken et al. demonstrated that
craniofacial vascular lesions can be generally differ-
entiated into vascular tumors or malformations of
vascular structures. Craniofacial vascular malforma-
tions can involve any or all of the vascular compo-
nents, including arteries, capillaries, veins, and
lymphatic tissue. These malformations may be simple
or complex and may represent angiodysplastic syn-
dromes that are congenital and possibly have a
genetic basis. Therefore, while most craniofacial vas-
cular lesions present in childhood, many of those that
do not, have their origins or predispositions deter-
mined in utero. Certain vascular pathologies may
arise as a result of exogenous causes such as traumatic
arteriovenous fistulas or erosion of a nonvascular
tumor into a significant vascular structure; however,
even these seemingly unrelated occurrences may have
an underlying genetic predisposition. Understanding
the underlying pathophysiology allows us to predict
clinical behavior and propose rational treatment
strategies.
Vascular tumors are differentiated from vascular mal-
formations by their patterns of cellular growth.
Hemangiomas are a vascular neoplasm of endothelial
cell origin and proliferation of these cells leads to
tumor growth. Two types of hemangiomas can be
differentiated clinically: cavernous hemangiomas,
which occur in adults and are associated with throm-
bosis pathologically, and capillary hemangiomas,
which are found in children and have a propensity
to spontaneously involute.
CAPILLARY HEMANGIOMA
Capillary hemangiomas are five times more common
in girls and are usually detected in the first three
months of life. Though they are only identified at
birth in about a third of patients, hemangiomas typi-
cally display a proliferative phase in the first six
months of life that is characterized by rapid growth
of these lesions. Gradual involution is usually detected
by about the childs first birthday and is the hallmark
of capillary hemangiomas. Involution is typically com-
plete by age seven and will occur in over 95% of
patients presenting in infancy. The triggers and mech-
anisms of this spontaneous involution remain incom-
pletely understood, though an apoptotic mechanism
seems important (6). Cavernous hemangiomas prolif-
erate over a different time course and continue to
proliferate into and potentially throughout adulthood.
Since spontaneous involution can be expected in
over 95% of children presenting with capillary heman-
giomas, conservative treatment is warranted in the
vast majority cases. Nevertheless, no means is cur-
rently available to differentiate those lesions fated to
progress from the vast majority, which will go on to
complete resolution. In addition, some patients may
196 Pryor et al.
require more urgent therapeutic intervention based on
the clinical scenario. Such situations include lesions
that impinge on or compromise anatomically critical
structures and those which cause functional impair-
ment or prevent normal development of critical func-
tions. Examples of complications related to capillary
hemangioma that may mandate urgent treatment
include congestive heart failure, which may develop
as a result of high intralesional flow with arteriove-
nous shunting. In addition, compromise of airway,
feeding, or visual function are indications for immedi-
ate treatment. Moreover, hemorrhage or coagulation
abnormalities such as consumptive coagulopathy,
which in association with rapid tumor growth and
thrombocytopenia is known as Kasabach-Merritt phe-
nomenon, is well described with capillary hemangio-
mas (7). Kasabach-Merritt syndrome is also called the
hemangioma thrombocytopenia syndrome or
thrombocytopenic coagulopathy.
It should be emphasized that while Kasabach-
Merritt syndrome has rarely been associated with
capillary hemangiomas, it is most often associated
with tumors having lymphatic-like vessels such as
kaposiform hemangioendothelioma or tufted angioma
(8,9). Treatment of Kasabach-Merritt syndrome begins
with corticosteroid therapy with the possible addition
of dipyridamole (10). The efficacy of high-dose ste-
roids is a matter of debate, especially considering the
balance of positive response versus complications.
Moreover, interferon, the second line of treatment if
the platelet count does not quickly rise, is not without
complications. For example, interferon therapy for
hemangiomas has been associated with spastic diple-
gia (11). Lastly, the course of interferon treatment is
prolonged and typically extends over a year. Should
the platelet count not respond to interferon, other
treatment options include chemotherapeutic agents,
such as Vinblastine or Vincristine, radiation therapy,
or surgical resection. While radiation therapy has been
shown to be effective in selected patients, worries
about its potential long-term side effects, such as
inhibition of regional growth, scarring, and malig-
nancy, limit its application (12). Vincristine has also
been shown to be effective in treating patients with
respiratory compromise (13).
Endovascular embolization with small polyvinyl
alcohol (PVA) particles can help stabilize the situation
in selected patients and may also be used to buy time
for medical therapy to work or as an adjunct to sur-
gical resection (3). Embolization may obliterate arte-
riovenous shunting through the tumor vasculature
and thereby reverse high-output heart failure. Embo-
lization may also markedly shrink capillary heman-
giomas to relieve mass effect on the airway or
esophagus. Mass effect on the eyelid, which impairs
sight from one eye and may permanently interfere
with the development of binocular vision in the neo-
nate, represents an additional indication for endovas-
cular treatment (3).
Embolization with absolute ethanol is also
reported to quickly reverse thrombocytopenia (14).
However, one should be aware of potential complica-
tions with absolute ethanol, such as significant swelling,
necrosis of normal tissue, hemolysis, renal failure and
pulmonary hypertension. In addition, the full effect of
absolute alcohol infusion is not immediately angio-
graphically apparent and additional closure of the mal-
formation may occur within a relatively short time.
JUVENILE ANGIOFIBROMA
Although a histologically benign neoplasm, juvenile
angiofibroma (JAF) often grows aggressively, spread-
ing by local invasion throughout the nasal fossa and
anterior skull base. Nearly all patients are male and
typically present between the ages of 14 and 17.
Symptoms are determined by the tumor size and
extent, with unilateral nasal obstruction being the
most common initial symptom. Far more importantly,
epistaxis, often associated with major blood loss, is the
symptom that brings most patients to medical atten-
tion. Tumor occlusion of the sinus ostia may obstruct
drainage and cause sinusitis.
JAF originates from the posterolateral nasophar-
ynx in the region of the pterygopalatine fossa. Exten-
sion into adjacent spaces determines staging (1518).
At the time of diagnosis, JAF virtually always extends
through the sphenopalatine foramen, involving both
the pterygopalatine fossa and posterior nasal cavity.
Lateral extension into the infratemporal fossa is also
characteristic. The tumor often extends into the sphe-
noid sinus, while maxillary sinus involvement is
much less frequent. Orbital extension via the inferior
orbital fissure occurs in approximately one-third of
patients (19). Intracranial involvement, present in less
than 20%, makes complete resection difficult (20).
Imaging studies are essential prior to angio-
graphic evaluation and embolization of JAF to make
the diagnosis, delineate the extent of tumor, and differ-
entiate tumor from retained sinus secretions (21). On CT
scan, the tumor is isodense to muscle prior to contrast
administration (Fig. 1). Avid homogeneous contrast
enhancement is characteristic. Remodeling and expan-
sion of the bony walls of the pterygopalatine fossa is
most often present. This results in anterior bowing of
the posterior wall of the maxillary antrum, a charac-
terisic finding on the lateral skull film. Expansion of the
sphenopalatine foramen indicates extension between
the pterygopalatine fossa and the nasopharynx. Gener-
ally 2 to 6 cm in diameter at the time of diagnosis, JAF
also remodels and expands the nasal cavity.
MR findings include characteristic salt-and-
pepper appearance on most sequences, with punc-
tate dark regions representing flow voids from the
tumors high vascularity. Intense enhancement fol-
lows contrast administration (Fig. 2). MR imaging is
important to differentiate between enhancing tumor
and retained sinus secretions. Fat-saturated enhanced
images are often best for delineating involvement of
the skull base foramina and extension into the cav-
ernous sinus, sphenoid sinus, or intracranial cavity.
Initially, arterial supply to JAF arises from the
site of origin, with the most common feeders from
the pterygopalatine portion of the internal maxillary
artery, including the sphenopalatine, infraorbital, and
 Chapter 10: Endovascular Management of Tumors and Vascular Malformations of the Head and Neck 197

Figure 1 Juvenile angiofibroma. An 18-year-old male

with epistaxis. Axial CT scan. (A, B) Small posterior
nasal mass (arrowhead ) extends into expanded
pterygopalatine fossa (*) widening the sphenopalatine
foramen. (C, D) Higher cuts show extension anteriorly
toward infraorbital foramen and posteriorly toward
vidian canal and foramen rotundum.

Figure 2 Juvenile angiofibroma (same patient as in Figure 1). (AC) Axial T2-weighted MR images demonstrate soft tissue signal
intensity with salt-and-pepper pattern involving nasal fossa (arrowhead ) as well as pterygopalatine fossa. (DF) Axial fat-saturated
enhanced T1-weighted MR images demonstrating homogeneous, avid enhancement.
198 Pryor et al.

Figure 3 Juvenile angiofibroma (same patient as in Figure 1). (A) Lateral view of ECA injection demonstrates intense tumor blush in the
posterior nasal region. (B) Microcatheter injection illustrates nonenlarged feeding arteries, tumor blush, and lack of arteriovenous
shunting. (C) Postembolization microcatheter injection of internal maxillary arteryno residual tumor filling. (D) Postembolization CCA
injection demonstrates no residual tumor supply. Abbreviations: ECA, external carotid artery; CCA, common carotid artery.

descending palatine branches (Fig. 3). Recruitment of
adjacent vessels, including the accessory meningeal,
ascending pharyngeal, and ascending palatine
arteries, is often seen with larger tumors. Sphenoid
sinus extension results in development of blood sup-
ply from extradural branches of the internal carotid
artery (ICA) (Fig. 4). Supply from pial branches of the
ICA although uncommon, should be sought, since it
reflects intracranial extension into the anterior and
middle fossae (22). Bilateral supply is frequent, par-
ticularly with large tumors, and should also be sought
in each case.
Early, dense, persistent contrast staining charac-
terizes JAF angiographically. Unlike many other
vascular neoplasms, including paragangliomas (see
below), significant enlargement of feeding arteries
and arteriovenous shunting are uncommon.
Complete surgical removal is the therapy of
choice. Preoperative embolization of JAF has been
shown to reduce both perioperative blood loss and
the duration of surgical resection (2325). Recent expe-
rience with endoscopic resection has improved surgical
outcomes and reinforces the value of preoperative
embolization in JAF (2628). The location of JAF man-
dates particular attention to the possibility of orbital or
intracranial anastomoses from vessels that also feed
tumor. Supply to cranial nerves is also of concern, as
in all cases of embolization involving the skull base.
Presurgical embolization is usually accomplished using
PVA particles of 150 to 350 mm in diameter (2931).
 Chapter 10: Endovascular Management of Tumors and Vascular Malformations of the Head and Neck 199

Figure 4 Juvenile angiofibroma. A 17-year-old male with severe epistaxis and nasal obstruction. (A) Coronal CT and (B) MR
demonstrate avidly enhancing JAF expanding the posterior right nasal cavity with extension through the right sphenopalatine foramen
into the pterygopalatine fossa (*, normal left pterygopalatine fossa). Tumor has eroded the nasal septum to cross the midline. Sphenoid
sinus extension is present on the right, denoted by (s). (C) AP view of angiogram demonstrates vascular tumor blush involving the same
region with supply from the pterygopalatine branches of the internal maxillary artery. (D) Lateral view of angiogram demonstrates vascular
tumor blush and internal maxillary supply (internal maxillary artery, arrow). (E) Lateral view shows microcatheter route through the internal
maxillary artery (arrow) into the pterygopalatine location from which embolization was performed. (F) Postembolization, CCA injection
shows delayed ECA filling with residual tumor supply from ascending pharyngeal artery (arrowhead ) and cavernous branch of the ICA
(arrow). The latter supply angiographically indicates the sphenoid sinus extension seen on CT and MR. Abbreviations: ECA, external
carotid artery; CCA, common carotid artery; ICA, internal carotid artery.

PARAGANGLIOMAS
Paragangliomas, also known as glomus tumors, are
highly vascular neoplasms, which arise from chemo-
receptor cells of the paraganglia or glomus bodies (32).
In the head and neck, the carotid body location is most
common. Temporal bone paragangliomas are next in
frequency; glomus tympanicum tumors involve the
middle ear and glomus jugulare tumors, the jugular
fossa. Jugulotympanic paragangliomas involve both
temporal bone locations. Paragangliomas associated
with the vagus nerve (glomus vagale) and those
involving the larynx are less common (33).
The usual age of onset is in the fifth decade, but a
wide age distribution is reported with early onset in
familial cases. A female predominance of nearly 3:1 is
present in most head and neck locations, except for
carotid body tumors.
As many as 50% of all paragangliomas have been
found to be hereditary and may be associated with
familial paraganglioma, neurofibromatosis type 1, von
Hippel-Lindau disease, the Carney triad, and, rarely,
with multiple endocrine neoplasia type 2 (34). Multi-
plicity is common in hereditary forms, affecting up to
one-third of patients. Although less common in non-
familial cases, multiple tumors may occur in up to
10%, usually with vagal or carotid body locations. The
high frequency of heritability and multiple lesions
requires imaging evaluation to detect undiagnosed
lesions in any patient with a paraganglioma involving
the head and neck. Genetic counseling should be
offered to all patients with a family history of para-
ganglioma, while patients positive for paternal para-
ganglioma locus gene should undergo regular
radiological screening with MRI (35).
The typically slow, locally invasive growth of
paragangliomas causes bony destruction and infiltra-
tion of adjacent structures. Lymph node involvement
and metastases are rare, reported in less than 5% of
cases (36). Clinical manifestations related to mass
effect depend on the tumor location.
200 Pryor et al.
Symptoms associated with paragangliomas of
the temporal bone reflect the extent of tumor spread.
The Fisch classification evaluates tumors on a scale of
A through D, with A representing localized tympanic
tumor, B mastoid extension, C erosion of the carotid
canal (with subtypes), and D indicating intracranial
extension (37,38). Typical symptoms include hearing
loss, pulsatile tinnitus, and cranial nerve palsy. The
latter most often involves the lower cranial nerves or
CN VII within the temporal bone.
Carotid body tumors present as slow-growing,
painless neck masses at the bifurcation of the common
carotid artery (CCA).
While the vast majority of paragangliomas give
histological evidence of catecholamines, clinical
hypersecretion occurs in less than 5% of cases and
causes signs and symptoms identical to hyperfunc-
tioning adrenal pheochromocytoma: episodic hyper-
tension, headache, nausea, excessive perspiration, and
nausea. When a catecholamine-secreting tumor is
suspected because of paroxysmal symptoms, bio-
chemical documentation of catecholamine and fractio-
nated metanephrine hypersecretion should precede
imaging evaluation (34). Laboratory or clinical evi-
dence of hypersecretion suggests an increased risk of
blood pressure alterations during angiography, embo-
lization, or surgical resection.
Noninvasive imaging must detect and character-
ize the lesion, as well as determine multiplicity. CT
scanning can show demineralization, erosion, and
destruction of the temporal bone structures in jugulo-
tympanic paragangliomas. Features include destruc-
tion of the jugular plate, indicating involvement of
middle ear structures as well as the jugular fossa.
Encasement or displacement of the facial nerve should
also be evaluated. Anterior extension with destruction
of the vertical segment of the petrous carotid canal
may indicate ICA encasement, involvement, and vas-
cular supply.
MR is the mainstay of noninvasive imaging. Both
T1- and T2-weighted sequences typically demonstrate
the characteristic salt-and-pepper appearance of occur in tumors with anterior extension. Extradural
high-velocity flow voids within the tumor. Following
gadolinium administration, intense enhancement is
present, frequently with residual flow voids. The extent
of the tumor should be evaluated, including intralumi-
nal jugular vein growth, ICA encasement, dural
enhancement, and invasion of posterior fossa struc-
tures. MRA using 3D TOF or contrast-enhanced sequen-
ces may be useful to initially delineate arterial supply.
Angiography may also provide diagnostic infor-
mation when the diagnosis is in doubt (39). Preopera-
tive angiographic evaluation, guided by MRI, is
however necessary for all but very small tumors con-
fined to the middle ear or involving the carotid body.
Angiographic features of paraganglioma reflect the
high vascularity with enlarged feeding arteries, rapid
appearance of dense vascular tumor blush, and early
venous drainage. Paragangliomas often consist of mul-
tiple compartments, each receiving separate arterial
supply. Multiple superselective catheterizations may
therefore be necessary to opacify or embolize the entire
tumor. Evaluation of the normal intracranial venous
outflow is also necessary, should jugular vein or sig-
moid sinus sacrifice be required. The angiographic
differential diagnosis for vascular lesions of the tem-
poral bone includes other highly vascular neoplasms
including metastases from thyroid, or renal cell carci-
noma, and hemangiopericytoma. In addition, non-
neoplastic lesions, including aberrant ICA, dural
arteriovenous fistulas, and petrous or cavernous ICA
aneurysms, while easily differentiated by noninvasive
imaging, may present a highly vascular angiographic
appearance in the skull base (31,40).
Complete surgical resection, usually with preop-
erative embolization of major external carotid artery
(ECA) feeding pedicles, is the mainstay of therapy. In
very large or unresectable tumors, radiotherapy, con-
ventional or stereotactic, is a viable therapeutic option
(4143).
Preoperative embolization confined to the ECA
supply usually gives the most favorable risk/benefit
ratio (44). Occlusion testing of the ICA may also be
necessary when carotid encasement is present. Super-
selective angiography is necessary to delineate cranial
nerve supply or dangerous anastomoses with the
ICA or vertebral artery. Preoperative embolization is
usually performed using particles of PVA from 150 to
350 mm in diameter. This agent has been shown to be
both safe and effective in reducing intraoperative
blood loss in paragangliomas (45,46).
Safe and effective embolization requires knowl-
edge of vascular anatomy specific to the particular
tumor location. Jugulotympanic paragangliomas vir-
tually always receive major supply from ascending
pharyngeal artery branches to the most common areas
of origin (47). The middle ear receives supply from the
inferior tympanic branch, while the neuromeningeal
branch supplies both the jugular fossa and hypoglos-
sal canal (Fig. 5). Additional ECA supply, including
the stylomastoid branch of the occipital artery, is also
extremely common in jugulotympanic paraganglio-
mas. In addition, supply from the temporal branch
of the middle meningeal artery (MMA) may also
ICA supply from caroticotympanic or cavernous
branches may also occur, particularly with anterior
extension of temporal bone paragangliomas. Pial sup-
ply from branches of either the internal carotid or
vertebrobasilar system indicates transdural invasion
and usually a worse prognosis.
Carotid body tumors characteristically widen the
CCA bifurcation, splaying apart the proximal ICA and
ECA. Early dense tumor blush between the two ves-
sels reflects tumor vascularity, usually originating
from the proximal ECA. Ascending pharyngeal artery
supply may also be present, typically to the superior
aspect of the tumor. Multiple short feeders originating
in proximity to the CCA bifurcation mandate meticu-
lous fluoroscopic monitoring during embolization to
prevent emboli from entering the ICA.
Anterior displacement of the cervical ICA is
often seen in cases of glomus vagale tumors. The
musculospinal branch of the ascending pharyngeal
artery typically supplies vagal paragangliomas infe-
rior to the skull base (Fig. 6). Supply from deep and
Chapter 10: Endovascular Management of Tumors and Vascular Malformations of the Head and Neck 201

Figure 5 Glomus jugulare. (A) Axial CT scan demon-

strates enlargement and bony erosive changes involv-
ing right jugular fossa (arrowheads). (B) Right CCA
angiogram demonstrates highly vascular glomus jugu-
lare tumor (arrow). (C) Lateral view of microcatheter
injection of ascending pharyngeal artery demonstrates
major tumor supply. (D) Postembolization angiogram
demonstrates no residual vascularity. Abbreviation:
CCA, common carotid artery.

Figure 6 Carotid body and glomus vagale.

(A) Sagittal enhanced fat-saturated
T1-weighted MR demonstrates left-sided
carotid body tumor and glomus vagale
tumor (* ). (B) Left CCA angiogram demon-
strates intense tumor blush with characteristic
splaying of carotid bifurcation due to carotid
body tumor and anterior displacement of the
cervical ICA due to glomus vagale tumor (*).
(C) Microcatheter angiogram during emboli-
zation, demonstrates dangerous anasto-
mosis with the vertebral artery (arrow). No
embolization was performed from this site
(arrowhead, microcatheter tip). (D) Postem-
bolization left CCA angiogram demonstrates
decreased tumor blush characteristic dis-
placements of the ICA remain. Abbreviations:
CCA, common carotid artery; ICA, internal
carotid artery.
202 Pryor et al.

anterior cervical arteries as well as the inferior thyroi-
dal artery may also be present.
MENINGIOMAS
Meningiomas, the most common nonglial primary
intracranial tumor, account for approximately 15% of
primary intracranial tumors in the general population.
Believed to arise from arachnoid granulation cells,
meningiomas most often present between 20 and
60 years of age. A female predominance of nearly 3:1
is present, with meningiomas comprising more than
50% of primary intracranial tumors in women (48).
Meningiomas most often arise over the cerebral
convexities, particularly in the parasagittal area (Fig. 7).
Other common locations include the sphenoid wing,
parasellar region, olfactory groove, and tentorium.
Approximately 10% of meningiomas involve the pos-
terior fossa (49,50). Multiple meningiomas may occur
in up to 10% of cases and may rarely appear in chil-
dren, in which case initiating factors such as prior
radiation or underlying genetic abnormalities such as
neurofibromatosis type 2 must be considered (5154).
Because meningiomas arise from the dura,
meningeal arterial branches, usually originating from
the ECA, are the initial source of blood supply to the
majority of the tumors. Nevertheless, meningiomas
often recruit blood supply from adjacent meningeal
arteries or invade the dura, receiving supply from pial
vessels. However, the arterial supply to the tumors
meningeal site of origin continues and aids prediction
of primary blood supply on the basis of tumor location.
The MMA, which supplies dura of the sphenoid
wing, cerebral convexities, and much of the anterior
fossa, is the vessel most often providing arterial supply
to meningiomas. MMA supply is often bilateral in
meningiomas of the parasagittal region or those crossing
the midline. Meningiomas of the olfactory groove most
often receive supply from dural branches of the ICA,
including ethmoidal artery supply from the ophthalmic
artery. Tumors originating from the tentorium and
clivus may receive supply from cavernous ICA branches
in addition to the MMA (Fig. 8) (55). Embolization of

Figure 7 Meningioma. (A). Sagittal T1-weighted enhanced MR demonstrates parasagittal meningioma with considerable mass effect.
(B) Lateral left CCA injection demonstrates meningioma supply originating from MMA and ACA. (C) Microcatheter injection of left MMA
shows tumor supply with early venous drainage (arrow, catheter tip). No orbital communication is present. (D) Postembolization
angiogram demonstrates decrease in tumor supply. Abbreviations: CCA, common carotid artery; MMA, middle meningeal artery; ACA,
anterior cerebral artery.
 Chapter 10: Endovascular Management of Tumors and Vascular Malformations of the Head and Neck 203

Figure 8 (A) Sagittal T1-weighted enhanced MR demonstrates extra-axial mass on the superior surface of the tentorium. (B) Lateral
view of CCA angiogram shows dense contrast blush involving the mass. (C) Superselective injection of MMA demonstrates enlargement
of tentorial branch supplying the meningioma. Note spokewheel appearance of tumor vasculature (arrowhead, microcatheter tip).
(D) Postembolization angiogram demonstrates no residual tumor filling. Abbreviations: CCA, common carotid artery; MMA, middle
meningeal artery.

these ICA dural branches is often associated with
increased risk and is not commonly performed.
Posteromedially located posterior fossa meningi-
omas often receive supply from meningeal branches of
the vertebral artery. Those more laterally located in the
posterior fossa commonly receive transmastoid
branches of the occipital artery as well as contributions
from the ascending pharyngeal artery. Similar to the
case with ICA dural branches, preoperative emboliza-
tion of meningeal arteries originating directly from the
vertebral artery or of pial branches does not provide as
favorable a risk/benefit ratio as for embolization of
supply that originates from branches of the ECA (56,57).
Angiographic evaluation of meningiomas is
guided by noninvasive imaging, but provides addi-
tional information currently impossible to obtain non-
invasively. The angiogram should be designed to
acquire particular information to aid the safest and
most complete resection possible. Vascular supply to
the tumor, including dural supply, pial supply, and any
evidence of transosseous supply, must be identified.
Anatomic variants, particularly those involving the
MMA and the ophthalmic artery, may impact the abil-
ity to safely embolize and must be identified (Figs. 9
and 10). Examination of the venous phase is also
exceedingly important. In particular, depiction of large
cortical and deep-draining veins often impacts the sur-
gical approach. In addition, patency of dural venous
sinuses adjacent to or involved by the tumor, particu-
larly the sigmoid, transverse, and superior sagittal
sinuses, must be evaluated.
The angiographic appearance of meningioma
typically demonstrates a spokewheel pattern of in-
tratumoral arteries centered on the primary meningeal
204 Pryor et al.

Figure 9 (A) Axial FLAIR and (B) coronal-enhanced

T1-weighted images demonstrate an enhancing dural-
based lesion crossing the falx near the vertex. Several
areas of punctuate flow void are present within the
lesion. An enhancing dural tail is present (arrow).
Abbreviation: FLAIR, fluid-attenuated inversion-recovery.

Figure 10 (Same patient as in Figure 9). (A) AP and (B) lateral views of the right CCA angiogram demonstrate an enlarged parietal
branch of the MMA (arrows) supplying the meningioma. In addition, a frontal dural branch (open arrowheads), normally a branch of the
MMA, originates from the ophthalmic artery. (C) Lateral view of the right ECA angiogram also demonstrates the enlarged parietal branch
(arrows) of the MMA with tumor blush. Embolization of this branch was accomplished prior to surgical resection. Abbreviations: CCA,
common carotid artery; MMA, middle meningeal artery; ECA, external carotid artery.

feeding vessel. A contrast stain or blush outlining the
tumor may be present depending on the tumor vas-
cularity. Some tumors show little vascularity, while
others are highly vascular and manifest rapid prom-
inent venous drainage.
Preoperative embolization of feeding arteries to
meningiomas is usually confined to larger tumors or
those manifesting high vascularity. Designed to
decrease blood loss and engender tumor necrosis,
quantitative measurement of the success of emboliza-
tion has proved difficult. Nevertheless, evidence of
reduction in perioperative transfusion associated with
embolization has been presented (58). In addition,
there is also evidence of decreased blood loss correlat-
ing with loss of previously present enhancement on
MR and following the use of relatively small embolic
particles (59,60).
The skull base origin of the meningeal arteries
most commonly involved in meningioma supply
means that close inspection of the selective microcath-
eter angiogram for dangerous anastomotic connections
assumes paramount importance. Testing with intra-
arterial sodium amytal or lidocaine may aid in the
clinical detection of anastomoses or cranial nerve sup-
ply, which might increase risk of neurological deficit
(see chap. 9). Preoperative embolization of meningio-
mas is usually performed using particles of PVA,
although liquid embolic agents have also been used
in highly vascular tumors. Complications associated
with the procedure have been found to be low (58).
 Chapter 10: Endovascular Management of Tumors and Vascular Malformations of the Head and Neck
VASCULAR MALFORMATIONS
In contrast to neoplasms, such as hemangiomas,
vascular malformations are nonproliferative in nature
and enlarge by recruiting flow rather than increasing
the number of cells. Vascular malformations may be
comprised of any or all vessel types singly or in com-
bination, including arterial, capillary, venous, and
lymphatic malformations. Vascular malformations
are typically present at birth and often grow propor-
tionally with the patient. They do not spontaneously
regress and are usually apparent throughout life.
A spectrum of flow characterizes the lesions.
Venous, capillary, and lymphatic vascular malforma-
tions are low-flow lesions, while arteriovenous mal-
formations (AVMs) or fistulas demonstrate very high
flow. Venous malformations, composed of saccular
venous channels are the most common vascular mal-
formation of the head and neck requiring treatment.
They represent up to 50% of patients seen at centers
treating such lesions (61). Capillary malformations
such as port-wine stains involve pathological capillary
and venular-sized vessels in the dermis and may be
the most common cutaneous vascular anomaly in the
general population. Although they are often confused
with the harmless vascular birthmarks that usually
occur in the neck, eyelids, glabella, or lips of up to 40%
of newborns, stork bites typically disappear sponta-
neously within a year leaving no trace and are not
considered to be dermatopathological lesions.
AVMs are characterized by a short circuit or
nidus between the feeding arteries and draining veins
with no intervening capillaries, and their presentation
may vary from congestive heart failure at birth to
mass or hemorrhage in early adulthood.
Lymphatic malformations are composed of clusters
of channels derived from defective lymphatic vessels
within the cutaneous and subcutaneous compartments.
They are found most commonly in the cervicofacial area
and are usually microcystic in that location. Combined
malformations involving arterial, capillary, venous, and
lymphatic components also exist and are more often
found unilaterally, especially on the limbs.
Differentiation between high- and low-flow
lesions has important imaging and treatment implica-
tions. High-flow lesions (AVMs) are usually well
demonstrated on angiography and are frequently
amenable to treatment via transarterial catheter-
based embolization techniques. Low-flow lesions are
not readily demonstrable angiographically, although
occasionally angiography may be used to exclude
rapid flow indicative of an AVM and thereby confirm
the correct diagnosis. Low-flow lesions are usually
imaged noninvasively and treated via percutaneous
injections and sclerotherapy (62).
AVM
AVMs of the head and neck are far less common than
low-flow vascular anomalies. Nevertheless, these
lesions deserve attention because of their frequent
presentation with cosmetic defects or life-threatening
hemorrhage.
205
Kohout et al. reported an extensive retrospective
analysis of 81 patients with AVM of the head and neck
evaluated over a period of 20 years (63). The age of
presentation varied widely, from 2 to 66 years with a
male to female ratio of 1:1.15. A vascular anomaly was
apparent at birth in 59% of patients (82% in men, 44%
in women). Ten percent of patients noted onset in
childhood, 10% in adolescence, and 21% in adulthood.
Eight patients first noted the malformation at puberty,
and six others experienced exacerbation during
puberty. Fifteen AVMs appeared or expanded during
pregnancy.
Clinical presentation was categorized according
to the authors modification of Schobinger clinical stag-
ing: 27% in stage I (quiescence), 38% in stage II (expan-
sion), and 38% in stage III (tissue destruction). There
was a single patient with stage IV malformation (car-
diac decompensation). Stage I lesions remained stable
for long periods. Expansion (stage II) was usually
followed by pain, bleeding, and ulceration (stage III).
Once present, these symptoms and signs inevitably
progressed until the malformation was resected.
Sites of occurrence could be categorized in ana-
tomic patterns. Sixty-nine percent occurred in the mid-
face, 14% in the upper third of the face, and 17% in the
lower third. The most common sites were the cheeks
(31%), ear (16%), nose (11%), and forehead (10%) (63).
Angiographically, high-flow malformations such
as AVMs or fistulas are characterized by enlarged
arteries and veins with early filling of the draining
veins (Fig. 11). Depending on the complexity of the
lesion, the relationship of the feeding arteries and
draining veins with the nidus may be difficult to
define. Superselective angiography is often necessary
to best define the anatomy, particularly in complex
lesions.
Angiographic evaluation of head and neck
AVMs must include all vessels likely to provide
arterial supply. Persky et al. found the inferior alveo-
lar artery characteristically supplied AVMs of the
mandible (Fig. 12). Supply to regions of soft tissue
extension depended on additional sites involved (e.g.,
labial and submental arteries to the lower lip and floor
of mouth, occipital artery to the ear lobe, and the
masseteric branch of the internal maxillary artery to
the masseter muscle). AVMs isolated to the mandible
often had contralateral supply from branches of the
lingual, facial, and inferior alveolar arteries (64). They
found that supply to maxillary AVMs consisted of
distal branches of the internal maxillary artery. Max-
illary arterial vascular malformations with soft tissue
extension were supplied by their corresponding arte-
rial systems, and the ophthalmic artery was most
commonly recruited. Both the internal maxillary and
facial artery systems supplied combined maxillary/
mandibular arterial vascular malformations.
MR typically demonstrates enlarged, serpigi-
nous vessels with flow voids and phase shifts. Use
of fat-saturation technique with T2 and gadolinium-
enhanced T1 images are often beneficial in providing
enhanced detail (65). MR is often superior because CT
image quality can be compromised by dentition and
metal artifacts such as dental appliances or fillings.
206 Pryor et al.

Figure 11 Facial AVM. (A) Axial T1-weighted MR demonstrates left facial swelling with flow voids (arrowheads). (B) Lateral left ECA
injection demonstrates AVM supplied by left facial artery (arrowhead, early venous drainage). (C) Microcatheter injection of left facial
artery demonstrating AVM supply and early venous drainage (arrowhead ). (D) Postembolization angiogram demonstrates no residual
filling, patient underwent surgical resection. Abbreviations: AVM, arteriovenous malformation; ECA, external carotid artery.

Although the lesion may appear compact on cross-
sectional imaging or angiography, the appearance
may be deceptive because the surrounding tissue is
often predisposed to develop shunting. This event
may lead to recurrence or recanalization via collaterals
through the adjacent tissue.
AVM involvement of bony structures of the face
may be documented on CT, MR, and plain or Panorex
films. CT findings include radiolucencies, often hav-
ing the appearance of a honeycomb or soap bubbles,
with small rounded and irregular lacunae. Root
resorption has been observed, creating an appearance
of teeth floating in the adjacent alveolar osseous
erosion. The lesion is often well demarcated and
may mimic the appearance of odontogenic cysts (66).
Recognition of bony involvement, particularly the
roots of the teeth, is important because catastrophic
bleeding may occur when teeth become loose, are
pulled, or are lost in an uncontrolled fashion.
Kohout et al. found bony involvement in
22 patients: 11 in the nasomaxillary region and 8 in
the mandible. In 7 patients, the bone was the primary
site; in 15 other patients, the bone was involved sec-
ondarily. Nasomaxillary AVMs invariably encom-
passed the overlying soft tissues, whereas mandibular
AVMs were confined to bone in 50% of cases. In both
sites, AVM extensively permeated and expanded the
bone, crossing the midline in many patients. Persky
et al. retrospectively reviewed 26 patients with AVM
involving the mandible and/or maxilla (64). They also
found that soft tissue involvement was near universal
with maxillary lesions, while that associated with man-
dibular lesions was more limited.
MR imaging of low-flow lesions such as venous
vascular malformations are characterized by signifi-
cant enhancement, intermediate T1 signal, and heter-
ogeneous high T2 signal and may demonstrate venous
lakes and/or phleboliths, which appear as foci of low
 Chapter 10: Endovascular Management of Tumors and Vascular Malformations of the Head and Neck 207

Figure 12 Mandibular AVM. (A) Lateral CCA injection demonstrates intraosseous mandibular AVM supplied by inferior alveolar artery.
(B) Microcatheter injection of the inferior alveolar artery demonstrates AVM with intraosseous venous drainage. (C) Post-NBCA
embolization, glue cast of arterial supply, AVM nidus, and proximal venous drainage (arrowheads). (D) Postembolization angiogram
demonstrates minimal residual AVM. Abbreviations: CCA, common carotid artery; AVM, arteriovenous malformation; NBCA, N-butyl
cyanoacrylate.

signal (67). These lesions may also demonstrate sep-
tations or be associated with satellite nodules (68).
Treatment options for venous and other slow
flow malformations include surgical resection, laser
treatment of skin or mucous membranes, or percuta-
nous sclerotherapy with a variety of agents, including
ethanol, sodium tetradecyl sulfate, OK-432, bleomycin,
as well as others (69). In performing percutaneous
sclerotherapy, one must be careful to have free flow
of sclerotic agent within the vascular channels. Extrav-
asation of these agents into the soft tissue may produce
significant damage to skin or mucous membranes
manifested by blistering or deep ulceration. In addi-
tion, severe damage to adjacent structures such as the
cranial nerves or the orbital contents may result, espe-
cially with ethanol. Hematuria is a frequent sequel and
local swelling is often pronounced. Swelling can be
controlled by elevating the head of the bed and early
ambulation along with ice packs. Powdered contrast
agents such as Amipaque are no longer commercially
available to mix with ethanol and thereby allow visu-
alization, making precise delivery impossible. In our
practice, we mix sodium tetradecyl sulfate (Sotradecol
3%, Bioniche Pharma U.S.A., Inc., Bogart, Georgia,
U.S.) 2:1 with Iopamidol 76% (Isovue-370, Bracco
Diagnostics, Inc., Princeton, New Jersey, U.S.) to
make a 1% injection. This mixture can be foamed
by passing between syringes so that the material is
more stable at the site of injection. Ethanol (dehydrated
alcohol, American Regent, Inc., Shirley, New York,
U.S.) is approximately 98% pure without bacteriostatic
agents and is injected without alteration. We typically
use small (22- or 24-gauge) intravenous catheters (Jelco,
Medex, Inc., Carlsbad, California, U.S.) and approach
the lesion through adjacent normal skin. Ultrasound
guidance may be useful. When free flow of blood is
demonstrated, one may image the lesion and identify
routes of venous outflow by gently injecting contrast.
208 Pryor et al.
A piece of connecting tubing can be connected to
prevent inadvertent loss of position of the angiocath-
eter due to hand movement or torquing. Bleeding from
the puncture site may be controlled by injecting a very
thin slurry of collagen (Avitene, Davol, Inc., Cranston,
Rhode Island, U.S.) through the angiocatheter as it is
being withdrawn. One must take into consideration
that thrombosis and inflammation will continue to
occur for some period of time after the injection of
material has ceased that may lead to unwanted
tissue damage, particularly with ethanol. We believe
it prudent to stop injections while the lesion still
demonstrates filling to decrease the risk of complica-
tions, although patients should be warned that further
embolization sessions may be needed. Lymphatic
malformations also respond well to sclerotherapy,
with macrocystic lesions responding particularly
well to OK-432, which modulates the immune
response (70). Surgery and/or laser therapy may also
play a role in the treatment of lymphatic malforma-
tions. Capillary vascular malformations have shown
good results when treated with laser therapy, although
other treatment options may be considered in special
cases (71).
Treatment of high-flow lesions such as AVMs
can include surgery, laser, embolization, sclerotherapy,
or a combination of options. A multidisciplinary team
approach is required for the assessment and treatment
of these lesions, which typically involves preoperative
angiography with superselective embolization, fol-
lowed by resection of the lesion (72).
Embolization options include particles, coils,
N-butyl cyanoacrylate (NBCA; TruFill Liquid Embolic
System, Cordis Neurovascular, Inc., Miami Lakes,
Florida, U.S.), Onyx (Onyx Liquid Embolic System,
Micro Therapeutics, Inc., Irvine, California, U.S.), or
other materials. Sclerosing agents can be injected intra-
arterially or via direct percutaneous puncture using an
intravenous angiocatheter and include, primarily, etha-
nol and Sotradecol. Important considerations in selec-
tion of appropriate interventional methods include:
briskness of flow; relationship to nerves; proximity to
the surface of the skin or mucous membranes; relation
to the vermillion border of the lips, the ear, or hair-
bearing areas; and pigmentation of the skin. Platinum
coils may be placed to slow flow in extremely high-
flow lesions or to treat fistulas that are difficult to
define angiographically or are in particularly danger-
ous areas, such as in close relation to the spinal cord.
While coils are useful, Kohout et al. have emphasized
that proximal ligation of arterial feeding vessels by any
technique frequently resulted in rapid clinical progres-
sion and acquisition of diffuse collateral arterial supply
and is to be avoided if possible (63,73).
Until very recently, our preferred agents of choice
have been ethanol and NBCA; however, our recent
experience has led us to rely on Onyx for embolizing
AVMs that are not near the surface of the skin. One
should be aware that Onyx is opacified with micro-
particulate tantalum in suspension and will cause per-
manent visible staining of the skin if injected near the
surface. However, the performance characteristics of
Onyx allow excellent penetration and prolonged injec-
tions producing essentially anatomic injections of deep
malformations. Practitioners need to be aware, how-
ever, of proximity to important anatomical structures,
such as blood supply to cranial nerves and the eyes, as
well as dangerous anastomoses to vessels communicat-
ing with the internal carotid, vertebral, or other critical
arteries. We have found that penetration of embolic
material into malformations, especially large, compli-
cated ones, seems to be significantly improved with
Onyx compared with NBCA. Our recent experience
also suggests that the decrease in flow following embo-
lization with Onyx is much more consistent and pre-
dictable than with sclerosing agents such as ethanol,
which may be because ethanol does not remain in
contact with the vessel wall for a sufficient period of
time to damage the endothelium and promote complete
thrombosis and scarring. This issue can be corrected at
least partially by manually occluding the venous out-
flow, if the venous drainage is accessible. This maneu-
ver is also helpful to prevent ethanol penetrating and
damaging sensitive structures, such as the orbital veins.
Direct percutaneous attack can be used when micro-
catheters cannot be navigated distal enough in very
tortuous, normal anatomy to allow safe deposition of
material. Ultrasound may be useful in directing percu-
taneous catheter placement. Superficial bleeding can
usually be controlled by direct pressure or via percuta-
neous injection of Avitene slurry through an intrave-
nous angiocatheter, though at times these techniques
need to be augmented or supplemented with other
open endovascular or surgical procedures.
Local control of bleeding at the time of emboli-
zation may rarely be necessary but is especially diffi-
cult, particularly in bony lesions, because pressure is
difficult to apply within the tooth socket without the
presence of the tooth. Urgent control of bleeding from
AVMs with mandibular involvement by local pres-
sure may be facilitated by retaining the tooth. Using a
tea bag to tamponade bleeding may help, presumably
because of the vasoconstricting properties of tannic
acid. Avitene or materials that promote clotting may
also be useful.
Epistaxis
While a common clinical problem, the vast majority of
epistaxis is minor in magnitude, originates from the
anterior nasal septum, and is self-limited or ceases with
a short period of nasal compression. Epistaxis originat-
ing posteriorly in the nasal cavity, however, is inacces-
sible to direct pressure or cauterization and may be life
threatening. In many cases, permanent hemostasis is
achieved by the use of nasal packing to provide tam-
ponade within the nasal cavity. When nasal packing
fails, surgical ligation of the distal branches of the
internal maxillary artery supplying the nasal fossa
has been advocated. Both prolonged nasal packing
and internal maxillary ligation have been associated
with patient discomfort, complications, and recurrence
(74,75). In such cases, endovascular techniques, specif-
ically arterial embolization, may rapidly relieve most
cases of epistaxis and permit removal of packing with-
out surgical intervention.
 Chapter 10: Endovascular Management of Tumors and Vascular Malformations of the Head and Neck 209

A relatively broad differential diagnosis must be
considered in patients presenting with severe epis-
taxis. The vast majority of cases, considered idio-
pathic, arise from the effects of longstanding
hypertension and arteriosclerosis on the vessels of
the nasal mucosa. Often exacerbated by low humidity,
patients often present in the fall, when home heating
systems lacking humidifiers are turned on. Neverthe-
less, in any case of severe epistaxis, it is imperative
that a specific etiology be identified, if present, so that
the most effective treatment can be directed to the
underlying cause of the bleeding.
Conditions that should be considered in the dif-
ferential diagnosis for severe epistaxis include
1. idiopathic epistaxis, which often occurs in elderly
patients with hypertension or evidence of gener-
alized atherosclerosis;
2. tumor, e.g., JAF, nasal polyps, malignant nasal, or
sinus tumors;
3. coagulopathy, including medications, uremia, or
hepatic failure;
4. hereditary hemorrhagic telangiectasia (HHT); and
5. trauma, with damage to ECA or ICA, particularly
in the cavernous or petrous segments, including
aneurysms or pseudoaneurysms.
Pre-embolization evaluation should exclude spe-
cific etiologies, including neoplasm and traumatic
lesions. A careful medication history should be taken
with particular attention to newly added medications,
such as antiplatelet agents.
HHT, or Rendu-Osler-Weber syndrome, should
be given particular consideration in patients with
multiple episodes of epistaxis or a family history. A
number of features of the physical examination, his-
tory, and angiogram suggest the diagnosis (Fig. 13).
HHT is a common disorder that affects multiple
organ systems, the manifestations of which arise from
inherited abnormalities of vascular structure (76,77).
These genetically determined abnormalities result in
the development of arteriovenous communications of
varying sizes. The nasal mucosa, skin, lung, gastroin-
testinal tract, and central nervous system are most
frequently affected. In the nasal mucosa and skin, the
usually tiny lesions are referred to as telangiectasias.
In the central nervous system, both AVMs and direct
arteriovenous fistulas have been described, while in
the lung most lesions are direct arteriovenous fistulas.
Gastrointestinal tract lesions include telangiectasias,
AVMs, as well as angiodysplasias.
The four major diagnostic criteria for HHT
include
1. epistaxis, e.g., spontaneous, recurrent nose bleeds;
2. telangiectasias, which are usually multiple and
occur at characteristic sites, including the lips,
oral cavity, fingers, and nose;

Figure 13 Hereditary hemorrhagic telangiectasia. A 72-year-old man presented to the emergency room with severe epistaxis that had
occurred intermittently for over 24 hours. He reported a family history of epistaxis affecting his mother, brother, and several cousins.
(A, B) Physical examination revealed multiple red, slightly raised lesions on his lips, tongue, conjunctiva, fingertips, and nail beds.
Unsubtracted (C) and subtracted (D) late arterial phase RICA angiographic examination demonstrates telangiectasias as multiple
intravascular contrast collections involving the mucosa of the lips, tongue, and nasal fossa (arrows). (E) Unsubtracted and (F) subtracted
lateral right internal maxillary injection demonstrates telangiectasia (arrow) with early venous drainage (arrowhead ) indicating arterio-
venous shunting from these multiple lesions (*, microcatheter tip). (G) Lateral view of CCA injection after embolization of internal maxillary
arteries was performed bilaterally using PVA particles. Embolization was followed by removal of nasal packing with no recurrence of
epistaxis. Abbreviations: CCA, common carotid artery; PVA, polyvinyl alcohol.
210 Pryor et al.

Figure 14 Petrous carotid aneurysm.

Patient presented with severe epistaxis.
(A) Axial CT scan (bone windows) demon-
strates sharply marginated expansile skull
base lesion (arrowheads) with extension into
the middle ear (arrow) and sphenoid sinus.
(B) Right CCA angiogram identifies an aneur-
ysm of the petrous ICA as source of epistaxis.
(C) Right common carotid angiogram after
coil embolization of aneurysm with parent
vessel occlusion (arrows, coil mass). Abbre-
viation: ICA, internal carotid artery.

3. visceral lesions, including gastrointestinal telan-
giectasia (with or without bleeding), pulmonary
AVM, hepatic AVM, cerebral AVM, and spinal
AVM; and
4. family history of a first-degree relative with HHT
according to these criteria.
The diagnosis of HHT is considered definite if
three of the above criteria are present, possible if
two criteria are present, and unlikely if only one is
present (78).
Nasal telangiectasias are responsible for the most
common manifestation of HHT, epistaxis. This symp-
tom occurs in over 90% of affected patients, usually
beginning before the third decade. Severity, while
variable, tends to increase with age, often leading to
chronic anemia and requiring multiple episodes of
treatment. The lesions of the nasal fossa can be iden-
tified angiographically, suggesting the diagnosis.
Embolization has been shown to be a safe and effec-
tive treatment for prolonged epistaxis and can be
repeated if necessary (79).
Pulmonary arteriovenous fistulas have been
identified in 10% to 15% of HHT patients. Conversely,
it is estimated that over half of the patients with
pulmonary AV fistulas have HHT. The direct right-
to-left shunts may initially manifest as neurological
deficits caused by cerebral emboli. Most often diag-
nosed by CT angiography, these lesions are currently
treated with endovascular techniques.
Recent genetic studies have confirmed that HHT
is inherited as an autosomal dominant trait whose
penetrance and expressivity are variable. Mutations
involving either of two genes, endoglin or ALK-1, may
cause HHT. Two disease subtypes, HHT1 and HHT2,
result from mutations of endoglin or ALK-1, respec-
tively. The variability of disease severity in different
family members suggests, however, that other factors
in addition to the specific mutations modify the HHT
phenotype (80).
Normally most patients with epistaxis are given
a trial of nasal packing. If this treatment is unsuccess-
ful, endovascular embolization should be considered
in management of most cases. Embolization of the
arterial supply to the nasal fossa is most often
successful in idiopathic cases as well as in specific
etiologies of epistaxis directly related to disease of the
nasal fossa vessels, including uncorrectable coagulop-
athy and HHT. The procedure is associated with very
low complication rates (81).
In the angiographic evaluation of epistaxis, visu-
alization of both the ICA and ECA is necessary. ICA
evaluation excludes rare vascular lesions, such as
petrous or cavernous aneurysms, which might cause
epistaxis and whose presence would change therapy
(Fig. 14). Sources of collateral supply to the nasal fossa
should be identified, including the facial arteries and
ethmoidal branches of the ophthalmic artery. In idio-
pathic epistaxis, no significant vascular abnormalities
are normally identified.
Most cases of idiopathic epistaxis respond to
bilateral embolization of the pterygopalatine branches
of the internal maxillary arteries, which give the
majority of supply to the nasal fossa. PVA particles
(150350 mm) are usually the preferred embolic mate-
rial. In most cases, proximal blockage of the internal
maxillary arteries using coils or other devices is not
necessary, is usually ineffective in preventing col-
lateral formation, and interferes with retreatment.
Embolization of the distal facial artery may also be
necessary to block collateral vascularization, particu-
larly in patients who have undergone prior ligation of
the internal maxillary artery or its major branches.
Ethmoidal branches of the ophthalmic artery may also
provide collateral supply to the nasal fossa, particu-
larly in patients who have undergone prior surgery
for maxillary ligation. Embolization of these vessels is
not routinely performed because of the risk to vision.
Typically, patients undergo embolization with
nasal packing in place. Following initial embolization
of the internal maxillary branches, packing is removed
in the angiographic suite before removal of the
femoral sheath. If hemorrhage persists, additional
embolization of additional collaterals may then be
performed.
CONCLUSION
Vascular lesions of the face and head are a complex
group of pathologies that are undergoing explosive
growth in understanding and treatment. Diagnosis
 Chapter 10: Endovascular Management of Tumors and Vascular Malformations of the Head and Neck
and treatment are best carried out by a multidiscipli-
nary team, including specialists bringing unique inter-
ests, knowledge, and skills.
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 11

Dissections of the Carotid and Vertebral Arteries

Qaisar A. Shah
Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia,
Pennsylvania, U.S.A., and Department of Neurology, University of Minnesota,
Minneapolis, Minnesota, U.S.A.
Scott E. Kasner and Robert W. Hurst
Department of Neurology; Departments of Radiology, Neurology, and Neurosurgery,
Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

INTRODUCTION cavernous involvement representing less than 5% of

Arterial dissection occurs when intraluminal blood
penetrates the vessel wall, usually through a tear in
the intima, and extends through and between the tissue
layers of the wall. Dissections occurring in the head and
neck may involve either the internal carotid or vertebral
arteries and may affect either the extradural or intra-
dural portions of the vessels. Dissections involving the
extradural portions of the internal carotid artery (ICA)
and vertebral artery (VA) are more common than intra-
dural dissections, with extradural ICA dissection occur-
ring more commonly than that of VA. Conversely,
among intradural dissections involvement of the verte-
bral arteries is considerably more common than is
dissections of the ICA or its intracranial branches.
EPIDEMIOLOGY
Cervicocerebral arterial dissection is an uncommon
cause of stroke in the general population but accounts
for 15% to 20% of all strokes in patients under 55 years
(1). The true incidence of dissection is difficult to
ascertain because some patients may remain asympto-
matic or have minor symptoms that are never diag-
nosed. One community-based study reported the
overall incidence of cervicocerebral dissection to be
2.6/100,000/yr (2). Other estimates place the annual
incidence of ICA dissection as high as 3.5/100,000/yr
and that for VA dissection at 1 to 1.5/100,000/yr (3).
Dissections of the extradural ICA accounted for
70% to 80% of all cervical arterial dissections, exceed-
ing the extradural VA dissection by fourfold, accord-
ing to a prospective study of 200 patients (4). The
mean age of presentation for extradural ICA dissec-
tion is 44 years and there is no sex predilection, while
extradural VA dissection presents at a mean age of
39 years with a female preponderance (5).
The vast majority of extradural ICA dissections
involve the cervical portion of the ICA with petrous or
extradural ICA dissections. Sixty-five percent of VA
dissections involve the suboccipital segment (V3) with
nearly 15% of all VA dissections extending into the
intradural segment (V4). The proximal VA segment
(V1) is the second most common extradural VA loca-
tion involved. Bilateral VA dissections are also rela-
tively common and have been reported with
coexistent ICA dissections (6,7).
Intradural arterial dissections are far less com-
mon than those involving the extradural portions of
the vessels. VA dissection makes up over 80% of
intradural dissections with intradural (V4) involve-
ment often representing distal extension of a dissec-
tion involving the V3 or suboccipital segment.
Intradural VA dissection may also occur in isolation
or with extension into the basilar artery. Two-thirds of
patients with intradural VA dissection are male and
on an average are nine years older than those with
intradural ICA dissection (51.8 vs. 43.8 years) (8).
Intradural dissection of the anterior circulation
represents less than 20% of intradural dissections (9).
They may involve individual vessels (ICA, MCA, or
ACA) or extend from the intradural ICA into the MCA
or ACA (10). Isolated middle cerebral artery (MCA) or
anterior cerebral artery (ACA) dissection is rare and
usually associated with direct arterial injury or head
trauma.
PATHOGENESIS
Arterial dissections are often characterized as either
spontaneous or traumatic. Traumatic dissections occur
secondary to overt head and neck trauma, while spon-
taneous dissections occur without obvious traumatic
injury, although in some cases subclinical trauma may
be implicated. For example, dissection has been attrib-
uted to seemingly trivial traumatic events, such as nose
blowing, head turning while backing an automobile, or
prolonged telephone conversations (5).
214 Shah et al.
A number of connective tissue disorders appear
to be the risk factors for dissection, perhaps by
increasing susceptibility of the artery wall to injury
from otherwise subclinical trauma. Conditions asso-
ciated with an increased incidence of dissection
include fibromuscular dysplasia (FMD), Marfans syn-
drome, Ehlers-Danlos syndrome (type IV), osteogene-
s i s i m p e r f e c t a , c y s t i c m e d i a l n e c r o s i s , an d
pseudoxanthoma elasticum (11). Conditions other
than connective tissue disorders associated with dis-
section include recent infection, migraine, and hyper-
homocystienemia (12,13). Redundancy and loops of
the cervical ICA have also been associated with an
increased incidence of ICA dissections (14). With the
exception of FMD, potentially predisposing condi-
tions are identified in only a small minority of patients
with dissection.
Dissection of the carotid or vertebral arteries sets
in motion a sequence of events the understanding of
which is essential for proper management. Arterial
walls are composed of three layers: an internal or
endothelial layer (tunica intima), a middle or muscu-
lar layer (tunica media), and an external or connective
tissue layer (tunica adventitia). Most commonly, a tear
or disruption of the intima initiates the damage. Dis-
ruption of the intima exposes the subintimal compo-
nents of the wall, so that platelets adhere to the site of
injury, which then serves as a nidus for thrombus
formation.
The extent of injury to the wall and the hemody-
namic features of the injury site determine the subse-
quent effects of the initial injury. Penetration and
extension of blood into the vessel wall results in
an intramural hematoma. The hematoma extends
between the layers of the vessel wall and, particularly
if located between the intimal and medial layers, may
constrict the residual lumen with narrowing or com-
plete occlusion. Flow impairment may then cause
ischemia as a result of hypoperfusion of neural struc-
tures supplied by the damaged vessel. Continued flow
through the injured lumen is also potentially detri-
mental since embolization of thrombus from the
injury site may occur.
Intramural hematoma may also impair the struc-
tural integrity of the wall, resulting in aneurysmal
expansion of the vessel. Aneurysm formation is more
likely when the intramural hematoma extends
between the medial and adventitial layers of the ves-
sel wall. The term dissecting aneurysm is applied
when the walls of the dilated segment are composed
of the incomplete remaining elements of the vessel
wall. Hara and Yamamoto note that dissecting aneur-
ysm was originally a pathological term defined as a
lesion produced by penetration of the circulating
blood into the substance of the wall of a vessel, with
subsequent extension of the effused blood for varying
distances between its layers. In contrast, the term
fusiform aneurysm refers to the morphology of the
aneurysm and makes no reference to its etiology.
Consequently, some dissecting aneurysms, particu-
larly those located intradurally, are referred to as
fusiform aneurysms on the basis of their morphology
as identified on imaging or angiographic studies (15).
Other dissecting aneurysms, particularly those involv-
ing the extradural portions of the vessels, may not
have fusiform morphology and are connected to the
true lumen through a relatively narrow neck.
Complete disruption of the arterial wall permits
extravasation of blood into adjacent structures. If the
hemorrhage is into soft tissue, as is usually the case in
extradural locations, a pseudoaneurysm may form.
Unlike dissecting aneurysms, the walls of pseudo-
aneurysms are not composed of layers of the vessel wall.
The lumen of a dissecting aneurysms may retain
communication with flowing blood in the arterial
lumen. The increased diameter of the injured segment
exposes the damaged and weakened wall to increased
wall tension compared with the more normal vessel.
These factors may permit delayed growth of dissect-
ing aneurysms. In addition, slow flow within the
dilated segment combined with the absence of intimal
lining may permit intra-aneurysmal clot formation
and subsequent embolization.
The pathophysiology of dissection injury is sim-
ilar whether extracranial or intracranial locations are
involved. It is the environment surrounding the vessel
at the site of injury that is often the major determinant
of the subsequent course. Extracranially, the internal
carotid and vertebral arteries are surrounded primar-
ily by soft tissue that usually gives physical support to
the artery wall and limits, but does not always pre-
vent, delayed symptomatic hemorrhage.
Consequently, the most common symptoms
of extradural dissection are ischemic and arise from
hypoperfusion or emboli. Extradural dissection results
in symptomatic hemorrhage only rarely and in specific
locations, such as within the sphenoid sinus, middle
ear, or other cavities of the skull base (16).
Intradurally, however, the vessels and their
branches course within the subarachnoid space, sur-
rounded only by cerebrospinal fluid. There is no
external structural support for the vessel wall and
no significant restriction or confinement of hemor-
rhage if the wall is breached completely. In addition,
normal thinning of the media and adventitia as well as
defects of the internal elastic lamina characterize the
intradural segment of the VA, thus further impairing
the structural integrity of the vessel wall (17).
Consequently, the chance of aneurysmal enlarge-
ment and rupture is significantly increased in intra-
dural as compared with extradural dissections. In
addition, hemorrhage within the subarachnoid space
gives rise to the well-known sequence of events asso-
ciated with the very high morbidity and mortality of
aneurysmal subarachnoid hemorrhage (SAH).
Extradural cervical arteries are more prone to
dissection than the intradural segments because of
their greater mobility, lack of protection by the skull,
and susceptibility to mechanical damage by neighbor-
ing bony structures. Sites where a relatively mobile
segment of a vessel must traverse a fixed location,
such as skull base foramina, can also serve to concen-
trate mechanical forces. These factors determine the
characteristic locations affected by dissection.
 Chapter 11: Dissections of the Carotid and Vertebral Arteries
Extradural ICA dissection usually begins several
centimeters distal to the relatively fixed common
carotid bifurcation from where the ICA originates
(12). The dissection then involves the relatively mobile
cervical ICA, stopping at the skull base where the
artery is secured by the bony walls of the carotid canal.
The VA is mobile at both its most proximal (V1)
and distal (V3) extradural segments. The vessels loca-
tion is fixed at the origin, within the foraminal seg-
ment (V2), and at the site of dural perforation.
Extradural VA dissection often involves the V3 or
suboccipital segment, the most mobile segment of
the vessel; it may also involve the intradural (V4)
portion of the VA, often by extension from V3. In
contrast, the foraminal or V2 portion of the vessel,
because of its lack of mobility and protection by the
bony walls of the transverse foramina, is only rarely
affected. The preforaminal or V1 segment is involved
in approximately 10% of VA dissections. V1 dissec-
tions often terminate as the relatively mobile V1 seg-
ment enters the fixed transverse vertebral foramen to
become V2 (12).
CLINICAL MANIFESTATIONS
Clinical features of extradural dissections include
headache, neck pain, transient ischemic attack (TIA),
ischemic stroke, pulsatile tinnitus, or the less common
cranial nerve palsy. Intradural dissection most often
presents with either ischemic stroke or SAH.
Extradural ICA Dissection
Clinical manifestations of extradural ICA dissection
arise either from local effects at the injury site or from
distal ischemia. Although nonspecific, headache is the
most common symptom reported in at least half of the
patients. Silbert et al. reported headache, typically ante-
rior and ipsilateral to the dissection, in 68% of patients
with ICA dissection (18). Constant pain of a sharp,
aching, or pressing quality is most frequent and typi-
cally precedes other neurological signs or symptoms of
ICA dissection, with a median interval of approximately
four days. Ten percent of patients with ICA dissections
have eye, facial, or ear pain without headache (19,20).
Ophthalmological manifestations are the second
most common group of findings associated with extra-
dural ICA dissection. Ipsilateral Horners syndrome,
complete or partial, occurs in over half of the patients
(21). Ocular ischemic syndromes, such as amaurosis,
ischemic optic neuropathy, and central retinal artery
occlusion, are less frequent and may result from emboli
or distal extension of dissection (22).
Extradural ICA dissection may cause ischemia
by embolization of thrombus from the site of dissec-
tion or by hypoperfusion due to luminal compromise.
The former appears to be more common with extrac-
ranial ICA dissection. TIAs, hemispheric strokes, or
both occur in up to 49% of patients (4).
Less frequent signs or symptoms should also be
sought in suspected ICA dissection. Pulsatile tinnitus
is noted in nearly 25% of cases. Lower CN palsies (CN
215
VII to XII) have been reported in 10% of patients,
ocular motility disorders as a result of CN III, IV, or VI
dysfunction in 4% of cases, and dysgeusia, likely from
involvement of the chorda tympani has been reported
in 2% of patients (23,24). A combination of ipsilateral
cranial nerve findings and hemispheric deficits may
mimic a brain stem stroke and have been referred to as
false localizing signs (25,26).
Extradural VA Dissection
Headache and/or neck pain are the most common
clinical features of extradural VA dissection. Head-
aches posterior and ipsilateral to the dissection affect
83% of patients, while 43% present with neck pain
(4,18). Similar to the case with ICA dissection, neuro-
logical signs are often delayed, developing a median of
14.5 hours after the onset of headache. The most com-
mon neurological symptoms of VA dissection include
dizziness, vertigo, double vision, ataxia, and dysarth-
ria. As with ICA dissection, cerebral ischemia may be
caused by either thromboembolism or hypoperfusion.
Lateral medullary infarction is the most common
stroke caused by extradural VA dissection, although
cerebellar, basilar tip, or posterior cerebral artery strokes
also occur. TIAs are less common with extradural VA
dissection than with extradural ICA dissection (4).
Extradural VA dissection has been found to be
associated with cervical spine fractures, particularly
those with a rotational component. While a high index
of suspicion should be maintained in patients with
this type of injury, there is disagreement as to the
clinical significance of vertebral dissection in this set-
ting and, consequently, the need for treatment (27,28).
Intradural ICA Dissection
Stroke is far more frequent following intradural ICA
dissections than with extradural ICA dissections. In
most series, ischemia predominates, although SAH
may also result (2931). Ohkuma et al. reported that
among 49 patients with intradural ICA dissection, 63%
presented with ischemic symptoms and 36% with SAH
(9). However, Chaves et al. reported a series of spon-
taneous intradural ICA dissections where ischemia
developed in 90% of patients while SAH was present
in only 10% of cases (32). Ischemia is likely a more
common presentation than SAH in isolated dissections
of the MCA or ACA, although numbers are small and
presentation may vary between neurosurgical and neu-
rological series (3335).
Severe unilateral headache almost always her-
alds the onset of intradural ICA dissection, usually
followed by evidence of ischemia or SAH within
minutes to hours. The appearance of neurological
signs is therefore more frequent and more rapid than
in extradural dissections (29,33,35). Migraine-type
headaches have also been associated with intradural
dissection but the possibility of SAH must be thor-
oughly investigated before a diagnosis of migraine can
be accepted in this setting (32).
216 Shah et al.
Hypoperfusion due to arterial narrowing has
been suggested to be more prominent than emboli as
a mechanism of cerebral ischemia in intradural ICA
dissection than in extracranial ICA dissection (32).
Intradural VA Dissection
Intradural VA dissection is associated with headache in
approximately 55% of patients with other neurological
symptoms, including vertigo, tinnitus, nausea, and
vomiting occurring less commonly. Cerebrovascular
events include SAH or ischemia of the cerebellum and
brain stem. As is the case with extradural VA dissec-
tions, lateral medullary syndrome is the most frequent
ischemic stroke syndrome, occurring in 26% to 43% of
patients who develop infarcts (36).
However, unlike intradural ICA dissections, the
majority of intradural VA dissections are associated
with SAH (37). A nationwide study in Japan evaluated
357 patients with intracranial dissection without
reported trauma. Over 90% of cases involved the
VA. SAH was the presenting symptom in 60% of
patients. The remaining patients presented with ische-
mia or infarction due to stenosis, occlusion, or emboli
from the dissection site. In addition, recurrent symp-
toms were more frequent in patients with SAH (14%)
than in patients with no hemorrhage (4.2%) (8). Other
series have reported SAH recurrence rates of over
70%, associated with mortality exceeding 50% in the
absence of effective treatment of the dissection (38).
Correlating with the high rate of SAH, aneurys-
mal dilatation has been demonstrated in 45% to 76%
of intradural VA dissections, more than that observed
in intradural ICA dissections (39,40).
ANGIOGRAPHIC DIAGNOSIS OF DISSECTION
Dissection may be diagnosed noninvasively using
ultrasonography, computed tomography angiography
(CTA), magnetic resonance imaging (MRI), and mag-
netic resonance angiography (MRA). Each has been
proposed as a reliable method to identify arterial
dissection, but each has its limitations. In most cases
of extradural ICA dissection, MRI can provide the
pertinent information necessary for diagnosis and
medical management. However, MRI is less effective
Table 1 Angiographic Features in Extracranial ICA and VA Dissections (%)
Number of
Reference Artery arteries Normal Stenosis Aneurysm
112 spontaneous 65 76
ICA
43 ICA 78 5 41
43 VA 46 7 37
23 ICA 200 17 17
42 ICA 76 47
45 VA 26 54
Classification of features varies between reports.
Abbreviations: FMD, fibromuscular dysplasia; ICA, internal carotid artery; VA, vertebral artery.
in evaluating extradural VA dissection, which often
requires angiographic evaluation. Noninvasive imag-
ing can only suggest the diagnosis of intradural dis-
section, therefore digital subtraction angiography
remains necessary to conclusively evaluate virtually
all suspected intradural dissections. Noninvasive
imaging modalities are more fully discussed else-
where in this volume.
Angiographic evaluation of suspected ICA dis-
section begins with injection of the common carotid
artery (CCA). Imaging the CCA bifurcation depicts the
most proximal extent of ICA dissection since the CCA
bifurcation is usually spared in ICA dissection (41).
Complete angiographic evaluation of any sus-
pected dissection requires visualization of the intra-
cranial circulation. Features to be sought include
intradural extension of an extradural dissection, evi-
dence of emboli, and collateral routes of intracranial
supply. Filming into the venous phase demonstrates
slow flow or stagnation of contrast within damaged
portions of vessels, including aneurysms.
The most common angiographic findings in
extradural ICA dissection are luminal stenosis and
occlusion (Table 1). The irregular stenosis seen in dis-
section differs in both location and configuration from
that caused by atherosclerotic disease. Dissection usu-
ally spares the carotid bulb and irregularly narrows the
ICA, beginning at 4 to 6 cm distal to the origin and
stopping at the skull base where the luminal configu-
ration characteristically returns to normal. Similarly,
dissection-related occlusion of the ICA usually
spares the proximal portion of the vessel and has a
tapered distal extent in the acute phase (Fig. 1). Other
angiographic findings, which may be identified in
carotid dissection, include an intimal flap, double
lumen, intraluminal filling defects, and dissecting
aneurysms (42).
Angiographic features of conditions that predis-
pose to ICA dissection should also be sought. The
most common is FMD, a condition reported in up to
20% of ICA dissections, a higher prevalence than that
found in either the general population or in patients
with VA dissection (43) (Fig. 2).
Angiographic examination of suspected extra-
dural VA dissection may begin with injection of the
proximal subclavian artery. After excluding proximal
Features
Intimal Slow ICA-MCA Branch
flap Occlusion flow occlusion FMD
40 29 17 24 11
41 18
56 7
9 72 (occlusion or 23
stenosis > 80%)
22 1 29
42
Figure 1 Angiographic findings in extradural dissections. (A) Lateral CCA angiogram of the neck demonstrates characteristic flame-
shaped occlusion from dissection beginning several centimeters above the CCA bifurcation. (B) Lateral view of the head [of patient (A)]
shows external carotid artery collaterals reconsitituting the intracranial ICA via the ophthalmic artery. (C) Lateral and (D) AP views show
characteristic narrowing of ICA lumen beginning above the CCA bifurcation and returning to normal as the vessel enters the petrous
bone. (E) Dissection with narrowing and tell tale pouch representing mild aneurysmal dilatation. (F) AP and (G) lateral views of ICA
dissection with dissecting aneurysm (arrow shows narrowing of residual lumen). (H) Surgical specimen from different case with identical
angiographic findings as (F) and (G) demonstrates resected dissecting aneurysm. (I) Extradural VA dissection. Abbreviations: CCA,
common carotid artery; ICA, internal carotid artery; VA, vertebral artery.
218 Shah et al.

Figure 2 Angiographic findings in intradural VA dissection. (A) AP and (B) lateral views of left intradural VA dissection with intradural
dissecting aneurysm. In a patient with bilateral intradural VA dissection: (C) AP and (D) lateral views of right VA injection with string of pearls
configuration. (E) AP view of left intradural dissecting aneurysm. (F) CTA demonstrates bilateral dissection. Abbreviation: VA, vertebral artery.

VA damage, selective VA catheterization is performed vessel. An angiographic pattern of isolated stenosis

to further evaluate the vessel.
Evaluation of both VAs is important to exclude
bilateral dissection, found in 12% to 25% of cases,
which is more than that noticed in ICA dissections (43).
The most common angiographic feature of extra-
dural VA dissection is also irregular stenosis, either
with or without occlusion. Involvement usually cen-
ters at the C12 level with intradural extension in up to
15% of cases (44,45). Dissecting aneurysms are less
commonly associated with extradural VA dissection
than with either extradural ICA dissection or intra-
dural VA dissection.
Angiographic findings of intradural VA dissec-
tion include segmental narrowing, referred to as the
string sign or the pearl and string sign if nar-
rowed segments alternate with adjacent segments of
vessel dilatation. Additional angiographic findings
include aneurysms, either fusiform or saccular, double
lumen, and tapered narrowing with occlusion of the
tends to be associated with an ischemic presentation,
while aneurysms, including the pearl and string sign
are more frequently present with SAH (39) (Fig. 3).
A number of authors have reviewed the type and
frequency of angiographic findings in intradural VA
dissection (Table 2). Terminology varies, however, and
firm conclusions are difficult because of the small
numbers reported. While aneurysmal dilatation,
including the pearl and string sign, is commonly
identified in intradural VA dissections, stenosis is more
common with intradural ICA dissection. Although
rare, dissections involving the ICA branches may dem-
onstrate either stenosis or aneurysmal dilatation (46).
Suspicion for intradural VA dissection, even
without a history of trauma, must remain high when
SAH involving the posterior fossa is present without
identification of an aneurysm. In such cases, both
intradural vertebral arteries must be visualized angio-
graphically to exclude dissection as a cause of the SAH.
 Chapter 11: Dissections of the Carotid and Vertebral Arteries
Figure 3 Lateral common carotid angiogram in patient with
dissection (arrowhead ) associated with characteristic changes
of FMD (arrow). Abbreviation: FMD, fibromuscular dysplasia.
TREATMENT
Some dissections are believed to occur without pro-
ducing any symptoms and therefore may remain
completely unrecognized. Consequently, it is possible
that some dissections have a benign prognosis in the
absence of therapy. Unfortunately, at present there is
no reliable method to identify low-risk patients, and
observation without therapy cannot be recommended.
In the vast majority of dissections, medical treatment
represents the first line of therapy.
Medical Treatment of Extradural Dissection
Dissections presenting with acute ischemic stroke may
be candidates for thrombolysis with intravenous tis-
sue plasminogen activator (IV-tPA), if treated within
three hours of symptom onset, unless there are other
medical contraindications (47). Patients who develop
dissection secondary to severe trauma are usually
excluded from receiving IV-tPA, but many patients
with dissection have trivial or no trauma, thus IV-tPA
is not contraindicated.
Table 2 Angiographic Features in Intracranial VA Dissection (%)
Reference Number of arteries String sign
113 14 21
39 24 58 (or occlusion)
114 41
115 21 5 38
Classification of features varies between reports.
219
In a small case series suggesting the use of IV-
tPA in the acute setting, one patient showed symp-
tomatic intracranial hemorrhage and 36.4% of patients
showed excellent recovery with 90-day modified
Rankin score (MRS) of 01 (48,49). Between three to
six hours after symptom onset, intra-arterial (IA)-tPA
has been advocated, with efficacy supported by several
case series (5054). Some authors have recommended
IA-tPA even within three hours, though others recom-
mend IV-tPA in this context (see below) (49).
After the first few hours, antithrombotic ther-
apy is usually recommended, though there has been
no clear agreement on the optimal medical manage-
ment to prevent delayed or recurrent stroke. In the
first few days, there appears to be a relatively high
risk of ischemic symptoms, and anticoagulation is
often recommended despite the lack of controlled
trials supporting its use (55,56). A large systematic
review of 49 observational studies comprising
683 patients suggested no significant benefit for anti-
coagulation over antiplatelet therapy with regard to
the outcome of death or disability from the initial
stroke (57). Nevertheless, treatment with antiplatelet
agents was associated with a higher risk of subse-
quent stroke than treatment with anticoagulation
(4.2% vs. 0.9%), arguing in favor of anticoagulation.
Heparin or low molecular weight heparin followed
by warfarin for three months is usually the mainstay
of treatment (5861).
Follow-up imaging studies are recommended
after three months of therapy, and if there is normal
luminal configuration therapy is often discontinued. If
repeat studies show residual stenosis or irregularities,
treatment should be continued for three more months
with repeat imaging studies (62,63). The use of anti-
coagulation therapy beyond 12 months is not recom-
mended despite persistent irregularity or stenosis of
the lumen, as there is a low risk of stroke beyond the
one-year mark (49,60,64). Spontaneous recanalization
of ICAs with dissection-related occlusion occurs in
47% to 85% of cases. If warfarin is contraindicated
because of systemic trauma or other medical issues,
antiplatelet agents can be used. Patients who are
treated with medical management have uneventful
recovery in 80% to 85% of cases (65,66) (Fig. 4).
Surgical Treatment of Extradural Dissections
Surgical options for extradural dissection include
carotid ligation, aneurysm resection with carotid recon-
struction, and extracranial to intradural ICA bypass
(supraclinoid or petrous ICA) (67). However, surgical
Features
Pearl and string sign Aneurysm Double lumen Occlusion
14 7 29 21
42
68 32
14 5 33
220 Shah et al.
morbidity may be high. Perioperative stroke rates may
occur in 10% of cases, peripheral cranial nerve injury
occurs in more than half, and mortality in 2% of
patients. Recent studies suggest that extradural dissect-
ing aneurysms, if asymptomatic, generally do not war-
rant surgical intervention, as they tend to resolve
spontaneously or at least remain stable. However,
symptomatic dissecting aneurysms may be resected
followed by reconstruction of the ICA with saphenous
vein graft or primary reanastomosis (6870).
Increasing experience and evidence supports the
conclusion that in many cases in which medical treat-
ment is not appropriate or is unsuccessful, endovas-
cular procedures may be preferable to a surgical
approach for treatment of dissection-related injury.
Nevertheless, additional study is needed to more
rigorously document the indications and optimal
management of these patients.
Endovascular Treatment of Extradural
Dissections
While medical therapy is currently the mainstay and
initial management in most cases of extradural carotid
or VA dissections, recognition of the role of endo-
Figure 4 A 39-year-old female presented with left
hemiparesis two days following motor vehicle accident.
(A) T2 axial image shows deep watershed infarct on the
right. (B, C) Axial T1-weighted MRI shows hyperintense
mural hemorrhage involving the right ICA (arrow).
(D) AP right CCA angiogram shows irregular cervical
ICA narrowing characteristic of dissection. Abbrevia-
tions: ICA, internal carotid artery; CCA, common carotid
artery.
vascular treatment and its timely application have
become increasingly important. As in all neuroendo-
vascular techniques, recognition of proper indications
for intervention is an essential and a meticulous tech-
nique to ensure patient benefit (71).
In the acute period following extradural ICA or
VA dissection, symptoms arise most often from intra-
cranial emboli and may require emergent thrombol-
ysis. In cases where IV thrombolytic treatment is
ineffective or contraindicated, intra-arterial thrombol-
ysis plays a role as noted above. Less frequently, acute
symptomatic arterial stenosis or occlusion may
require revascularization of the dissected artery
using angioplasty and stenting.
The need for endovascular treatment most often
occurs with symptomatic extradural ICA dissections
(Fig. 5). Nevertheless, extradural vertebral dissections
with stenosis or occlusion may also require emergent
treatment when VA asymmetry or intracranial emboli
are present. A number of investigators have con-
firmed not only the dismal outcome of untreated
acute vertebrobasilar embolic occlusion, but also the
potential for significant benefit if thrombolysis and
reopening is accomplished prior to irreversible infarc-
tion (72,73).
 Chapter 11: Dissections of the Carotid and Vertebral Arteries
In general, indications for endovascular treat-
ment of extradural dissections include
1. patients with ischemia in whom IV thrombolysis
for ischemia is contraindicated because of sys-
temic hemorrhage, recent surgery, or trauma;
2. patients with ischemia and contralateral ICA
stenosis or occlusion;
3. patients in whom there is a need for elective
occlusion of the contralateral ICA or VA for
other pathology;
4. patients in whom there is a need to avoid flow
increase through the anterior communicating
artery because of an associated aneurysm;
5. when intradural extension of dissection occurs
with consequent risk of SAH (74,75); and
6. for treatment of dissecting aneurysms under spe-
cific circumstances (see below).
Intra-arterial thrombolysis may be needed
acutely when dissections result in symptomatic intra-
cranial emboli or arterial narrowing with super-
imposed clot causing impairment of flow. In such
cases, thorough investigation as to the etiology of cere-
bral ischemia is necessary to identify dissection, if
221
Figure 5 Simplified schematic illustration of the path-
ophysiological process of carotid artery dissection pro-
ceeding from the acute stage to either spontaneous
healing (1), formation of false lumen (2), residual steno-
sis of varying degree or complete occlusion (3), and
formation of a pseudoaneurysm (4). A stent is used in
cases not responding to medical therapy either to relieve
a hemodynamically significant stenosis, to occlude a
false lumen, or to serve as a scaffold to enable coil
embolization of a wide-necked pseudoaneurysm.
Source: From Ref. 75.
present. Identification of salvageable tissue on neuro-
imaging studies is becoming more widely available
and can assist in the selection of the most appropriate
patients for acute treatment. Intra-arterial thrombolysis
is performed using the techniques for acute stroke
(see chap. 16). Particular attention must, however, be
directed to determine the presence and extent of
dissection-related injury and consider specific treat-
ment of the dissected vessel, if necessary.
As noted, small series and case reports support
the use of intra-arterial thrombolysis in dissection,
particularly outside the conventional time constraints
of IV thrombolysis or in specific cases in which IV
thrombolysis is contraindicated (4954).
In cases of symptomatic stenosis as a result of
dissection, angioplasty using a stent can be used to
exclude a false lumen, relieve hemodynamically sig-
nificant stenosis, and restore the true lumen to more
normal size, thereby increasing flow (76,77). The tech-
nique may also be successful when the dissected ves-
sel is completely occluded. In cases of complete
occlusion, however, the potential for distal emboliza-
tion on reopening the vessel may be substantial,
depending on the clot burden within the occluded
222 Shah et al.
segment of the vessel. Careful consideration must be
given to relative risks and benefits of reopening an
occluded vessel.
The technique of stent angioplasty begins with
angiographic confirmation of the location and the
extent of the dissection-related stenosis. A microcath-
eter and microguidewire (0.0140.018 inch) are then
maneuvered through the true arterial lumen using
road mapping angiography. The microcatheter is
advanced to a position distal to the damaged segment.
An exchange length (260300 cm) microguide-
wire is used to exchange the microcatheter for the
stent catheter. The stent is then deployed within the
stenotic segment of the vessel. Because of the rela-
tively low levels of radial force needed for restoration
of lumen diameter in dissected vessels, primary
angioplasty is not normally necessary and may place
excessive stress on the already damaged arterial wall.
The stent maintains sufficient radial force on the
damaged segment of the artery wall, placing the
layers separated by the intramural hematoma in con-
tact with one another. The result is obliteration of the
false lumen, restoration of the normal luminal diam-
eter, and resolution of the stenosis.
The stent length should be chosen to cross
the entire damaged segment of the vessel when pos-
sible. In some cases of long segment dissection,
multiple overlapping stents may be required. In such
cases, the initial stent is usually placed at the proximal
margin of the dissection to eliminate the inflow zone
of the false lumen. Following initial stent placement,
additional angiography is done to confirm the need
for additional stents. Both self-expanding and balloon-
mounted stents have been found to be suitable for this
application (75). Following stent placement, patients
are maintained on an appropriate antiplatelet regimen
to prevent stent thrombosis.
In cases of dissection-associated aneurysm, stent
placement has also been found useful, both alone as
well as to provide a scaffold to permit coil emboliza-
tion (see below).
The dynamic nature of carotid and VA dissec-
tions and their ability to change over very short periods
of time has been emphasized (12). Consequently, the
need for endovascular treatment of extradural internal
carotid or vertebral dissections may also develop after
the acute phase of the injury (78). Because medical
treatment of extradural dissections is usually quite
effective, situations which merit delayed intervention,
while uncommon, usually represent failure of medical
therapy (79). They are usually manifested by new
onset, fluctuation, or recurrent neurological dysfunc-
tion of the vascular distribution of the damaged artery
(80). As is the case in the acute phase, delayed ischemic
symptoms usually result either from recurrent emboli
or development of symptomatic stenosis with poor
collateral circulation (Fig. 6).
In either situation, persistent abnormality within
the damaged segment of the artery is usually identi-
fied. Specific features include failure of the dissected
segment to heal with the development of luminal
stenosis, or persistent clot formation despite medical
treatment. In either case, angiographic evaluation
must determine whether intracranial emboli are pres-
ent, the status of the dissected vessel, and collateral
routes to the affected vascular distribution. Any areas
Figure 6 A 24-year-old male after gunshot
wound to left neck. (A) Initial lateral and
(B) AP angiograms demonstrate irregularity
(arrow) consistent with LICA dissection. Six
months later, while on anticoagulation ther-
apy, patient presented with aphasia lasting
four hours followed by complete resolution.
CT scan (C, D) shows hyperdensity within left
MCA branches (arrow) representing emboli.
(E) Angiogram demonstrated interval growth
of dissecting aneurysm. (F) Patient underwent
carotid occlusion (lateral angiogram). Abbre-
viations: LICA, left internal carotid artery;
MCA, middle cerebral artery.
 Chapter 11: Dissections of the Carotid and Vertebral Arteries
of damage not present or recognized at the time of the
initial evaluation must also be sought and identified.
When intracranial embolic occlusion occurs after
the acute phase of dissection, thrombolysis, either
intravenous or intra-arterial, may be necessary as an
initial step. Should symptoms develop in a setting of
appropriate medical therapy, additional endovascular
treatment, such as stent angioplasty, may be required
to minimize the chance of recurrence.
Extradural Dissection-Associated Aneurysms
As noted earlier, controversy often surrounds the
terminology applied to aneurysms associated with
arterial dissection. While the underlying pathology is
similar regardless of the morphology, the morpholog-
ical features of a dissecting aneurysm have major
implications for endovascular techniques that may
be useful for its treatment.
Extradural aneurysms associated with dissection
represent a radiological finding that often engenders
considerable concern and uncertainty as to manage-
ment. While extradural ICA aneurysms may arise
from other causes, including atherosclerosis and infec-
tion, a significant percentage results from prior dis-
section. Older series have recommended nearly
universal treatment of extradural carotid artery aneur-
ysms to prevent neurological deterioration (81). Sev-
eral recent studies, however, have found that
extradural dissecting aneurysms of either the ICA or
VA rarely enlarge over time. These studies have also
concluded that the vast majority of such aneurysms
remain quiescent and asymptomatic in the face of
appropriate medical management and, in most cases,
require no additional treatment (82,83).
Nevertheless, documented examples confirm
that dissection-associated aneurysms can, under cer-
tain circumstances, cause neurological deterioration as
a result of embolization or expansion with compres-
sion of cranial nerves (8487). In addition, when
located within or adjacent to the skull base, these
aneurysms may pose a significant risk of potentially
fatal bleeding (16).
In general, dissection-associated extradural
aneurysms should be seriously considered for treat-
ment when
1. they are found to be enlarging or causing symp-
toms related to mass effect,
2. their location exposes the patient to risk of hem-
orrhage into an adjacent sinus or skull base cavity
such as the middle ear, and
3. symptoms occur, which are attributable to emboli
from an extradural aneurysm in a patient on
appropriate medical management.
Therapy for dissecting extradural aneurysms is
usually feasible using endovascular techniques. Often
the simplest, safest, and most effective option may be
permanent occlusion of the involved carotid or VA.
Feasibility of vessel sacrifice is of course dependent on
collateral flow from adjacent circulations. Prior to
sacrifice of the vessel, an occlusion test is usually
performed as outlined elsewhere (see chap. 9).
223
A number of techniques have been described to
treat extradural aneurysms with preservation of the
involved vessel. Morphology of the aneurysm is the
primary feature that dictates the endovascular tech-
nique that may be successful in treating the lesion. In
cases of extradural aneurysms with relatively narrow
necks, treatment has been accomplished using coil
embolization alone. More recently, stent-assisted coil-
ing has been recommended (88). Similar to the treat-
ment of wide-necked or fusiform intracranial
aneurysms, a stent is placed across the dissected seg-
ment and neck of the aneurysm. The stent provides
support to the dissected vessel wall and also prevents
herniation of coils into the parent vessel.
Other authors have indicated that a significant
percentage of dissection-related aneurysms will
resolve after endovascular stent placement alone with-
out the necessity for additional coil embolization
(89,90). The presence of the stent across the aneurysm
neck likely impairs inflow and promotes intra-aneur-
ysmal clot formation, with subsequent thrombosis and
closure of the aneurysm (Fig. 7).
Recently, placement of covered stent grafts has
been reported to be successful in obliterating dissec-
tion-associated aneurysms in a small number of cases
(9193). The technique has shown promise at moder-
ately long-term follow-up and may be especially useful
in cases of patients symptomatic of mass effect (94).
Despite the frequent success of endovascular
treatment, a role for surgical treatment remains for
some cases of extradural aneurysms of the ICA. This
treatment is ideally accomplished for lesions located
proximally in the neck, and is adopted most often as
a result of difficulty with placement of endovascular
devices across the lesion. Difficulty in crossing the
lesion may be due to associated arterial disease such
as FMD or excessive tortuosity of the vessel. The latter
feature is encountered with some frequency and has
in fact been noted as a potentially predisposing factor
to carotid dissection (14). The use of more flexible
stents has, however, been reported to make even
relatively tortuous vessels amenable to endovascular
treatment (95).
Lastly, aggressive evaluation and consideration
of endovascular or surgical treatment should be enter-
tained in situations in which intradural extension of
extradural dissection is suspected. This situation most
often affects the region of dural penetration of the
vertebral arteries (44). As discussed below, intradural
dissection, whether primary or by extension from an
extradural injury, may represent a significant risk of
morbidity and mortality as a result of either ischemia
or SAH.
Medical Treatment of Intradural Dissection
Treatment of intradural dissection is dictated by the
initial clinical event. Patients who present with ische-
mic stroke are usually treated with antiplatelet or
anticoagulant therapy. Nevertheless, because systemic
medical therapy may present excessive risks with
intradural dissections, careful diagnosis prior to med-
ical treatment is necessary. As with extracranial
224 Shah et al.
Figure 7 Acute neck pain following motor vehicle accident.
Initial MRI (not shown) demonstrated wall hematoma. Two
months after accident, left Horners syndrome was noted after
transient right arm weakness. (A) Lateral and (B) AP views of
LICA dissecting aneurysm. (C) Unsubtracted view of stent in
place. (D) Six-month follow-up with resolution of aneurysm. No
symptom recurrence. Abbreviation: LICA, left internal carotid
artery.
dissections, surgical or endovascular approaches may
be considered in patients whose symptoms recur
despite medical therapy.
Patients with intradural dissection who present
with SAH usually require aggressive treatment with
either surgical or endovascular repair, since conserva-
tive management may result in poor outcome (38,96).
Surgical Treatment of Intradural Dissection
Surgical procedures utilized for treatment of intra-
dural dissection have included proximal occlusion of
the parent artery, trapping of the lesion, vascular
reconstruction, surgical wrapping, or clipping of the
aneurysm. Because the vast majority of intradural
dissecting aneurysms are fusiform, the role of clip-
ping, the standard surgical technique for addressing
saccular aneurysms, is limited (96).
Endovascular Treatment of Intradural
Dissections
Because of the propensity for vessel rupture and
recurrent hemorrhage, intradural dissections require
anatomic correction by either open surgical or endo-
vascular techniques at a higher rate than is the case
with extradural dissections in which the initial therapy
is most often medical. Nevertheless, indications for
treatment as well as alternatives remain controversial.
Conservative treatment or medical therapy has most
often been advocated in cases without aneurysm or
evidence of hemorrhage that present with ischemia.
In patients presenting with SAH, poor outcome
with conservative management has been emphasized
and a number of surgical and endovascular alterna-
tives have been reported (38,96).
Endovascular treatment has assumed a major role
in the management of intradural dissecting aneurysms.
Permanent endovascular occlusion using coils has been
shown to be a useful therapeutic endovascular tech-
nique for the treatment of fusiform and acute intra-
dural dissecting aneurysms of the vertebrobasilar
system (9799). Techniques vary, using combinations
of detachable balloons and coils, and are often pre-
ceded by test occlusion of the involved vessel to deter-
mine whether endovascular occlusion can be safely
accomplished. Leibowitz et al. reported long-term out-
comes for unilateral intradural VA aneurysms treated
by permanent occlusion. They found better clinical
outcomes than the patients whose aneurysms involved
the basilar artery or both vertebral arteries, where com-
plete thrombosis cannot be achieved by using perma-
nent vessel occlusion (100). The authors also reviewed
prior series supporting the usefulness of this relatively
simple endovascular occlusion technique.
Other investigators have emphasized endovascu-
lar trapping of the diseased segment proximally and
distally to ensure closure of the dissection site by the
coil mass, thereby preventing regrowth or rehemor-
rhage (Fig. 8) (101). Endovascular occlusion of the
intradural VA has also been found useful in cases in
which dissection involves isolated vertebrobasilar
branches or extends more distally into the basilar
artery (Fig. 9) (102). Nevertheless, obvious limitations
of the technique exist in more extensive dissections
where vessel preservation is essential (103).
The appearance of newer endovascular techni-
ques with the potential to preserve vessel patency has
not excluded permanent vessel occlusion from the
endovascular therapeutic armamentarium. Reports
of reformation of aneurysms following stent sup-
ported embolization designed to preserve arterial
patency have led to suggestions that parent vessel
occlusion remains the first option for treatment in
patients who will tolerate sacrifice of the parent vessel
along with its diseased segment (104).
Nevertheless, techniques that promise to treat
intradural dissections while preserving vessel patency
are of increasing clinical importance and interest.
Advantages include maintaining maximum intracra-
nial flow, a particular advantage in older patients who
might have coexisting vascular disease, but also
 Chapter 11: Dissections of the Carotid and Vertebral Arteries 225

Figure 8 A 36-year-old female with acute onset of headache, no SAH. (A) AP view of left VA angiogram at presentation demonstrates
mild irregular fusiform dissection of intradural VA (arrow). (BD) MRI at time of presentation shows minimal enlargement of intradural left
VA (arrow). (EG) CT scan 10 years after initial presentation, when patient developed progressive left hemiparesis, shows hyperdense
mass in the region of previous abnormality. (H) Angiography of right VA (J, K) demonstrates growth of thrombus filled fusiform aneurysm.
(I) AP plain film following coil embolization with packing of aneurysmal segment and left VA occlusion. Abbreviations: SAH, subarachnoid
hemorrhage; VA, vertebral artery.

potentially beneficial in younger patients who would
be expected to live longer with the results of treat-
ment. In addition, vessel-preserving treatment
extends the advantages of endovascular therapy to
patients who will not tolerate vessel occlusion includ-
ing those with more extensive lesions.
The usually fusiform morphology and structur-
ally incompetent wall of intradural dissecting aneur-
ysms eliminates any major role for selective aneurysm
embolization using coils alone. The use of stents,
either alone or more often followed by coil placement
through the interstices of the stent, has emerged as a
significant advance in managing intradural dissec-
tions while preserving the affected vessel (105). The
technique is identical to that utilized in stent-
supported coil embolization of saccular aneurysms.
It has shown high rates of success in the limited num-
ber of reported cases with low incidence of delayed
vessel occlusion or ischemic stroke (Fig. 10) (88).
Stent-supported coiling of intradural dissecting
aneurysms extends endovascular options to portions
of vessels where sacrifice of a dissected segment is not
possible without neurological deficit. This observation
is particularly true when intradural vertebral dis-
sections extend to involve the basilar artery (106).
The usefulness of stenting has been demonstrated in
226 Shah et al.

Figure 9 (A) Lateral right VA angiogram showing dissection of right PICA (arrow) in patient who presented with SAH. (B) Unsubtracted
and subtracted (C) images following coil occlusion of right PICA. Abbreviations: VA, vertebral artery; PICA, posterior inferior cerebellar
artery; SAH, subarachnoid hemorrhage.

Figure 10 Enlarged intradural VA-dissecting aneurysm in a patient who had already undergone left VA occlusion for an enlarged
intradural VA aneurysm ( , coil mass within occluded left VAdissecting aneurysm). (A) Subtracted AP view after placement of two
overlapping stents across the aneurysm neck (arrowheads, markers at the ends of the overlapping stents). (B) Microcatheter (arrows)
crosses the interstices of the stent to deploy coils within the aneurysm. (C) Aneurysm coiled, follow-up confirmed aneurysm occlusion
with normal flow through the parent vessel.

both aneurysmal and occlusive basilar dissection
(107). In addition, an increasing number of reports
document the effectiveness of the technique in intra-
dural dissections of the anterior circulation (108).
Recent reports indicate that intradural fusiform
aneurysm treatment may also be accomplished using
covered stent grafts (94,109). Long-term outcome and
specific indications for this technique await additional
experience.
PROGNOSIS AND OUTCOME
Most patients with stroke due to extradural ICA or VA
dissection sustain relatively mild deficits with ulti-
mate resolution of their symptoms, though a signifi-
cant minority (510%) suffer disabling stroke. The
recurrence rate of thromboembolic episodes after dis-
section is 0.6% to 10.4% (79). There may be a tendency
for VA dissections to cause more severe strokes than
ICA dissections. Traumatic dissections appear to have
a worse prognosis than spontaneous dissections in
terms of persistent neurological symptoms (110).
Patients with intradural dissection have poor
outcome as compared to those with extracranial dis-
section. Intradural dissection associated with dissect-
ing aneurysm and associated SAH carries high risk of
morbidity and mortality (2050%), exposes the patient
to the risk of recurrent hemorrhage, and thus requires
urgent medical, endovascular, or surgical intervention
as discussed earlier (99).
In general, the rate of recurrent arterial dissec-
tion is low. Recurrence in the same vessel is rare,
though may possibly occur as a result of a vascular
defect created by scar tissue formation. The recurrence
rate may also be higher in patients with a family
history of arterial dissection (111).
 Chapter 11: Dissections of the Carotid and Vertebral Arteries
Patients who have had cervicocerebral arterial
dissections should be advised to avoid activities that
may cause sudden rotation or extension of the neck.
However, no substantial data exist to define the limits
of activity for these patients. There is no apparent
reason to manage physical therapy differently
during rehabilitation following stroke resulting from
dissection.
Dissection of the carotid and vertebral arteries
represents a significant etiology of stroke in young
patients. The understanding, recognition, and diagno-
sis of this disorder have rapidly advanced in recent
years and the development of endovascular techni-
ques has made a major contribution to patients for
whom medical treatment is not suitable.
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 12

Direct Carotid Cavernous Fistula

Uday S. Kanamalla, Charles A. Jungreis,

and Jeffrey P. Kochan
Temple University Hospital, Temple University School of Medicine,
Philadelphia, Pennsylvania, U.S.A.

INTRODUCTION CLINICAL FEATURES

Carotid cavernous fistula (CCF) is an abnormal com-
munication between the internal carotid artery (ICA)
and the cavernous sinus. Direct CCF represents one
specific form of CCF with high-pressure arterial blood
entering the low-pressure venous cavernous sinus,
most commonly via a single hole in the cavernous
segment of the ICA (Fig. 1). In contrast, the other
variety of CCF has been coined an indirect CCF
and is characterized by a nidus of dural arterioles
(13). Indirect CCF is described more fully in another
chapter.
ETIOLOGY
While most indirect CCFs are of spontaneous origin
and uncertain etiology, direct CCFs most often occur
as the result of closed head injury associated with a
basal skull fracture (13). The ICA is fixed between the
foramen lacerum and the anterior clinoid process by
dural attachments. Shearing forces from head trauma,
sometimes with accompanying penetrating injury
from bony spicules, can cause the ICA to be torn
between its points of dural attachment. In most
cases, the laceration is single and unilateral. Some-
times the holes in the ICA are multiple, and some-
times bilateral CCFs occur. Direct CCF can also result
from penetrating trauma, including iatrogenic trauma,
such as during transsphenoidal surgery (4). Collagen
deficiency diseases, such as Ehlers-Danlos syndrome,
ruptured cavernous aneurysms, dissections, osteogen-
esis imperfecta, and fibromuscular dysplasia, have
also been associated with the development of a CCF
(5,7). The etiology of spontaneous direct CCF remains
speculative and has most commonly been attributed
to rupture of a preexisting cavernous aneurysm (2,3)
(Fig. 2).
Direct CCF is more common in the younger
population as opposed to indirect CCF, which tends
to occur in the older population. However, trauma at
any age remains the most common etiology of direct
CCF.
The onset of symptoms and signs of a direct CCF is
usually acute and most commonly occurs within a few
days of the instigating trauma. The length of time
between the onset of the first symptoms and radio-
graphic diagnosis of a CCF, however, has been
reported to be variable and ranges up to 18 months
(1,8). The severity and acuity of clinical features do not
directly correlate to the size of the fistula, but are
affected by the venous drainage.
The most common symptoms and signs are
orbital (Table 1) and include pulsatile tinnitus with
a periorbital bruit, proptosis, chemosis, and injec-
tion (13,9,10). Less common presentations include
intracranial hemorrhage (11). Cerebral ischemia,
related to vascular steal, appears to be an exceed-
ingly rare phenomenon, though it may occur in
patients with an incomplete circle of Willis. The orbital
symptoms and signs appear to relate not only to the
degree of shunt but also to the pattern of venous
drainage. The symptoms of CCF may be present in
the contralateral eye secondary to drainage of the
fistula through the intercavernous veins to the oppo-
site side.
Improvement or resolution of orbital symptoms
following successful occlusion of the fistula tends to
occur in about 80% of patients (12). The symptoms
typically tend to resolve significantly in hours or days,
though total resolution could take weeks or months,
if it occurs at all. Duration of symptoms is also an
important prognostic factor, with prolonged symp-
toms resolving more slowly.
A relatively common, though dangerous, clinical
scenario occurs in the setting of major trauma. Several
days or a week after the trauma, an acute onset of
severe proptosis, chemosis, injection, and pain asso-
ciated with a pulsatile bruit over the orbit develops.
Intraocular pressures elevate dramatically, and the
patient becomes ophthalmoplegic in the affected eye.
Despite the severe signs and symptoms, intervention
within the next day or two typically results in rapid
improvement (Fig. 3).
232 Kanamalla et al.

Figure 1 Direct CCF embolized with detachable coils. (A) Axial MR shows large varices especially in relation to the left cavernous sinus.
(B) Axial MR shows dilated superior ophthalmic veins bilaterally. (C) Lateral angiographic view during a selective ICA injection shows rapid flow
into the varices. The posterior venous drainage is poor, and most of the flow is anterior into the superior ophthalmic vein. (D) Postembolization
with detachable coils shows a minimal remnant. No arteriovenous shunting persists and the ICA is preserved. (E) Unsubtracted angiographic
view showing coil nest postemobilization. Abbreviations: MR, magnetic resonance; ICA, internal carotid artery.

Figure 2 Direct CCF secondary to rupture of a cav-

ernous ICA aneurysm embolized with a detachable
balloon. (A) Lateral angiographic view during a selec-
tive ICA injection shows rapid flow into the varices. The
venous drainage is mainly posterior into the IPS.
(B) Postembolization. The cavernous aneurysm is
now apparent. The fistula is closed. Abbreviations:
CCF, carotid cavernous fistula; ICA, internal carotid
artery; IPS, inferior petrosal sinus.

Table 1 Symptoms and Signs Associated with Direct CCF (1) ANATOMY AND PATHOPHYSIOLOGY
Number of cases The cavernous sinus has been regarded as a contig-
Symptoms uous network of anatomically separated sinusoids
Diplopia 14 rather than actual veins (13). A rent in the wall of the
Eye redness 13 intracavernous carotid artery, or rupture of one of its
Proptosis 10 branches that traverses and is surrounded on all
Headache 9
sides by the sinus cavity, produces an arteriovenous
Bruit 8
Diminished vision 7
fistula without concomitant venous injury in contra-
Facial numbness 6 distinction to fistulas elsewhere in the body.
Ocular pain 5 The superior and inferior ophthalmic veins
Signs provide normal venous drainage from the orbit to
Dilated episcleral veins 14 the cavernous sinus. The superficial middle cerebral
Diminished vision 12 veins drain the brain through the sphenoparietal sinus
Elevated intraocular pressure 10 to the cavernous sinus. The cavernous sinus, in turn,
Sixth nerve paresis 10 normally drains through the superior and inferior
Chemosis 10 petrosal sinuses (IPSs) to the jugular bulb and via
Third nerve paresis 4
emissary veins to the pterygoid venous plexus.
Papilledema 4
When a fistula develops between the ICA and
Total number of cases 14. the cavernous sinus, the high flow and pressure

Figure 3 64-year-old female before and after embolization of a
CCF. (Top) Photograph before treatment. Note the bilateral prop-
tosis, chemosis, and injection. The pupils are dilated. (Bottom)
Photograph 10 days after treatment. It shows significant resolution.
Abbreviation: CCF, carotid cavernous fistula.
within the venous drainage pathways increase and
there is reversal of flow within the normal tributaries
to the cavernous sinus. Furthermore, the venous
drainage pathways dilate to accommodate the
increased flow. It is this abnormal venous diversion
of flow that results in the characteristic signs and
symptoms associated with direct CCF.
The reversed and increased flow into the supe-
rior and inferior ophthalmic veins causes orbital
venous hypertension. Visual deterioration results
from a combination of reduced arterial perfusion
and venous hypertension with accompanying glau-
coma. Retinal perfusion suffers. Intraocular pressures
rise as a result of venous hypertension. Rubeosis irdis,
a neovascularity of the iris induced by prolonged
ischemia, may also contribute to overall ocular necro-
sis (10). Obtrusive diplopia and ophthalmoplegia
occur as a result of cranial nerve compression second-
ary to mass effect in the cavernous sinus from dis-
tended vessels. Edema of extraocular contents,
including the muscles, can also contribute to diplopia
and appears to be related to vascular engorgement
and enlargement of the extraocular muscles. The
symptoms and signs vary depending on which veins
drain the fistula and how distended they become. For
example, posterior drainage via the superior and IPSs
can result in pulsatile tinnitus.
Intracranial hemorrhage is a dreaded complica-
tion. This is due to reversal of venous drainage into
the sphenoparietal sinus, with resultant cerebral cor-
tical venous hypertension.
Chapter 12: Direct Carotid Cavernous Fistula 233
Additionally, during treatment, one should
always remember the possibility of redirection of
flow into dangerous venous channels by the treatment
itself. This kind of acute venous diversion into the
remaining venous pathways following selective occlu-
sion of one venous channel can result in aggravation
of symptoms and increase the morbidity and mortal-
ity associated with the disease. For example, if the IPS
is occluded during treatment, diversion of flow into
the superior ophthalmic vein may increase proptosis
and may also increase cortical venous drainage with
associated increased risk of intracerebral or subarach-
noid hemorrhage (11,14).
CLASSIFICATION
CCFs can be classified according to three criteria:
(1) pathogenically into spontaneous or traumatic fis-
tulas, (2) hemodynamically into high-flow or low-
flow fistulas, and (3) angiographically into direct or
indirect (dural) fistulas. Some CCFs are hybrids of
the above. An angiographic classification provides an
objective method for grouping CCF, determining
prognosis, and planning the therapeutic manage-
ment. All CCFs can be placed into one of four angio-
graphic categories based on whether the CCF is
direct and on the anatomical origin of the arteries
supplying the fistula (Fig. 1) (2,3). Type A fistulas are
direct shunts between the ICA and cavernous sinus.
Types B, C, and D are indirect or dural shunts. Type
B is a fistula between meningeal branches of the ICA
and the cavernous sinus. Type C is a dural shunt
between meningeal branches of the external carotid
artery (ECA) and the cavernous sinus. Type D, the
most common type, is a dural shunt between menin-
geal branches of both the ICA and ECA and the
cavernous sinus. Bilateral CCFs represent a special
case of the above.
The angiographic criteria for differentiating a
fistula into high-flow or low-flow categories are
quite subjective. High-flow fistulas fill the cavernous
sinus and efferent veins within a fraction of a second,
and the intracranial branches of the ICA fill partially
or are not visualized at all. In contrast, an angiogram
of a low-flow fistula will reveal slower drainage into
the venous system and filling of the intracranial
branches of the ICA. Note that the terms high
flow and low flow are relative to each other.
Both are high flow compared with normal.
INDICATIONS FOR TREATMENT
The indications for treatment are not absolute and
depend on the general physical condition of the
patient, the severity of the symptoms, and the
anatomy of the fistula, which, in turn, determines
the treatment modality. Type A direct fistulas will
rarely resolve spontaneously and almost always
require treatment. Progressive visual loss, uncontrol-
lable elevations of intraocular pressure, an intolerable
bruit or headache, or enlargement of traumatic
234 Kanamalla et al.

aneurysm beyond the cavernous sinus are all strong
indications for treatment. Additionally, treatment is
also appropriate because of corneal exposure, obtru-
sive diplopia, or cosmetically offensive proptosis.
Finally, the presence of cortical venous drainage,
where there is concern for intracranial hemorrhage,
constitutes an indication for therapy (28).
Halbach et al. have identified certain high-risk
features that represent indications for urgent treat-
ment. These include development of intracranial hem-
orrhage, epistaxis, increased intraocular pressures,
decreased visual acuity, rapidly progressive proptosis,
and cerebral ischemia (11).
IMAGING STUDIES
Conventional catheter angiography is usually
required. It helps confirm the diagnosis, helps deter-
mine the type of fistula, and provides the therapeutic
capability.
CT or MRI can establish the diagnosis of CCF.
Their primary role, though, is to evaluate the brain
parenchyma for associated injuries in the setting of
trauma and to detect possible ischemic changes. Addi-
tionally, thin-section CT with coronal reconstructions
can help evaluate skull base fractures. The findings of
CCF on cross-sectional imaging include proptosis,
swelling of extraocular muscles, and dilation of the
superior ophthalmic vein with distention of the ipsi-
lateral cavernous sinus (Fig. 4). However, CT or MRI
will not typically help with differentiation of direct
from the indirect types.
Orbital ultrasound can also be performed to
demonstrate findings of thickened extraocular
muscles as well as dilated superior ophthalmic
veins. In the right clinical setting, this procedure can
also help confirm the clinical diagnosis.
Other tests that are often performed include com-
plete ophthalmologic workup inclusive of visual acuity,
pupillary function, intraocular pressure measurement,
fundoscopy (direct and indirect), and gonioscopy.
For optimal angiography, high-resolution digital
subtraction is essential. The goals of the diagnostic
angiogram are to evaluate the location and size of the
fistula and the venous drainage pathways. Addition-
ally, associated traumatic vascular injuries, ICA pseu-
doaneurysms, and cavernous sinus varices need to be
excluded. To help differentiate a direct from an indi-
rect fistula, an angiographic search should be carried
out for an ECA supply to the fistula. The angiographic
evaluation of CCF should, therefore, include selective
catheterization and angiography of the ICAs and
ECAs bilaterally.
Because of the very high flow, it may not be
possible to identify the morphology of the fistula in
terms of exact location or size on selective angiograms
without specific maneuvers to slow the flow across
the fistula. The maneuvers could consist of ipsilateral
ICA compression while injecting into the artery to
slow the flow. Alternatively, the contralateral ICA or
vertebral artery (so-called Allcock maneuver) can be

Figure 4 Direct CCF embolized with a detachable balloon. (A) Axial CT showing dilated left superior ophthalmic vein. (B) PA
angiographic view during a right ICA injection shows arteriovenous shunting with cross-filling to the opposite side, including the left
cavernous sinus and left superior ophthalmic vein. (C) Lateral angiographic view during a right ICA injection again demonstrates rapid
arteriovenous shunting. (D) Lateral angiographic view with balloon in position closing the fistula with preservation of the ICA.
(E) Unsubtracted view showing balloon postembolization. Abbreviations: CCF, carotid cavernous fistula; CT, computed tomography;
PA, posteroanterior; ICA, internal carotid artery.

injected while providing ipsilateral ICA compression
(Dr. Allan Fox, personal communication). Often,
because of the high flow, injection of the contralateral
ICA or the vertebral artery will opacify the CCF even
without compression.
The venous drainage from the cavernous sinus of
a direct CCF can extend anteriorly into the ophthalmic
veins, inferiorly into the pterygoid venous plexus,
posteriorly into the petrosal sinuses, superiorly into
the cortical veins via the sphenoparietal sinus, and
finally into the contralateral cavernous sinus. The
pattern of venous drainage dictates the predominant
symptom or sign seen in the patient. Most often a
pattern of mixed venous drainage will be seen.
TREATMENT OPTIONS AND CONSIDERATIONS
While there are reasons to intervene very early, in
general the treatment of CCF is rarely an emergent
procedure, but it is often urgent. That is, treatment can
usually be undertaken semielectively when the patient
is otherwise stable.
The treatment of CCF has evolved over the past
40 years. The earliest surgical treatments of proximal
occlusion of the ICA or trapping have largely been
abandoned because of the high risk of stroke and
blindness, often without obliterating the fistula (10).
Today, the primary treatment modality is endovascu-
lar therapy. Approaches to occlude CCFs have been
described, with an increased focus on preserving ICA
flow. Maintained patency of the ICA after treatment
of traumatic CCF is increasing largely because of
improvements in the technology (better devices), but
will probably never reach 100% (3,1517).
The goal of treatment is to obliterate the fistula,
which can be accomplished with a wide variety of
techniques and agents, each with its advantages and
disadvantages. The treatment of CCF takes into con-
sideration the speed of flow through the fistula, its
arterial supply, and the routes of venous drainage.
Equally important is to take into consideration the
patients general physical condition prior to formulat-
ing a therapeutic plan. For example, in the setting of
acute CCF in a multitrauma patient, the more critical
injuries of the patient must be addressed first.
Medical Therapy
In the acute setting of vision loss and/or paralysis of
cranial nerves, glucocorticosteroids (e.g., dexame-
thasone) may be used while waiting for definitive
diagnostic studies and treatments. Similarly, in
patients with elevated intraocular pressures, pharma-
cologic management with topical -adrenergic block-
ers and oral acetazolamide (Diamox) is performed as
adjunctive therapy, until definitive therapy for the
fistula is undertaken.
Surgical Therapy
Surgical therapy is presently considered only as a last
resort. The earlier treatments in the form of proximal
Chapter 12: Direct Carotid Cavernous Fistula 235
ICA occlusion or ICA trapping have largely been
abandoned. Surgical therapy is only considered in
cases where there has been a failure of endovascular
therapy or is used in conjunction with endovascular
therapy.
One form of surgical therapy is assistance in
endovascular access to the superior ophthalmic vein.
In patients without arterial or venous access to the
fistula, direct access to the superior ophthalmic vein
following surgical exposure of the vein in the orbit has
been used with successful transvenous embolization
of the fistula (18). Direct surgical exposure of the
cavernous sinus via craniotomy followed by direct
puncture for embolization and closure of the fistula
remains an alternative when all other routes are
exhausted (19).
There are also reports in the literature of using a
superficial temporal artery to middle cerebral artery
bypass prior to sacrifice of the ipsilateral ICA in
patients who are unable to tolerate ICA occlusion (2).
Adjunctive surgical procedures in the form of a
lateral canthotomy have been performed as a tempo-
rizing measure for orbital symptoms such as severe
proptosis, markedly elevated intraocular pressures,
and rapidly declining visual acuity.
Endovascular Therapy
This therapy is performed transarterially and/or
transvenously. Large series have shown the effective-
ness of transarterial balloon embolization, which had
emerged as the treatment of choice for this disease
(3,1517). In the United States, however, detachable
silicone balloons have been withdrawn from the mar-
ket, which has led to the use of various alternative
embolization agents, including platinum microcoils
and acrylic (N-butyl cyanoacrylate, or NBCA) (2026).
More recently, closure of fistula via stent graft and
stent/balloon assist has been reported (2634). Cur-
rently, our initial treatment attempt is with endovas-
cular coils via the transarterial approach.
Transarterial Approach
Conceptually, the ideal goal of treatment is to occlude
the fistula on the venous side, thereby preserving the
ICA. However, sometimes this treatment proves to
be impossible, and sacrifice of the ICA is required to
close the fistula. If the ICA requires sacrifice, then it
must be occluded both above and below the fistula or
flow to the fistula will persist (Fig. 5). This metho-
dology of occluding the ICA is called trapping and
can be done surgically, endovascularly or by a com-
bination thereof. In treating 54 traumatic CCFs with
detachable balloons, Debrun et al. had to sacrifice the
ICA close to the fistula in 20 (37%) of their cases. ICA
occlusion at the level of the fistula can be performed
with detachable balloons or with platinum coils. Inter-
estingly, since the ICA flow above the level of the
fistula is usually reversed into the fistula, test occlu-
sion of the ICA is not usually required. However, in a
patient in whom some distal ICA flow above the
fistula remains antegrade, tolerance to ICA occlusion
236 Kanamalla et al.

Figure 5 Direct CCF secondary to a gunshot wound. The right ICA required sacrifice to close the fistula completely. Endovascular coils
were utilized to trap the fistula. (A) Lateral view after embolization. The detachable coils are in the right ICA and trap the fistula.
Detachable coils are both above and below the fistula. Note also that some larger free coils are in the proximal ICA to provide additional
stability to the coil nest. (B) Frontal angiographic view after right carotid sacrifice during left ICA angiogram showing excellent cross-filling
without flow into the fistula. (C) Lateral angiographic view after embolization during a vertebral artery angiogram. The distal right ICA is
filled via the posterior communicating artery, but the coils prevent retrograde flow to the fistula. Abbreviations: CCF, carotid cavernous
fistula; ICA, internal carotid artery.

using the balloon occlusion test prior to occlusion of
the ICA may be required. In the uncommon event
of failure to tolerate the occlusion, alternate methods
of therapy will need to be strongly considered.
Selective embolization of the fistula via the trans-
arterial approach with detachable balloons or coils is
presently considered the method of choice for the
treatment of most single-hole CCFs. When using
balloons, the procedure involves the detachment of
single or multiple silicone balloons into the cavernous
sinus (venous side) close to the fistula to occlude the
abnormal fistulous communication. Thromboembolic
complications from the procedure, though rare, are
well described in the literature and could be the result
of catheter or balloon manipulation causing endothe-
lial damage or the result of inadvertent balloon
detachment or balloon migration. Transarterial bal-
loon embolization fails in at least 5% to 10% of cases
(20,26,35). Failure occurs because the fistula orifice
may be too small to allow entry of the balloon cath-
eter, the venous compartment of the fistulous com-
munication may be too small to allow balloon
inflation, or sharp margins of the adjacent bony frag-
ments or foreign bodies may rupture the balloon
during inflation (36). Also, in some patients who
have subtotal occlusion after initial balloon emboliza-
tion, navigation of additional balloons into the fistula
may be unsuccessful owing to the presence of balloons
partially blocking the fistula orifice. Lastly, the ability
to microcatheterize and hold position within the
fistula may also be limited depending on the position
of the fistula ostium. Typically, it is more difficult to
catheterize when the fistula orifice is just beyond the
posterior genu along the inferior wall of the C4 seg-
ment of the cavernous carotid artery because the angle
of entry from the ICA is very acute.
The development of steerable microcatheters
and microguidewires has allowed successful use of
other embolic agents such as platinum coils or liquid
embolic material. It is technically easier to guide a
microcatheter/microguidewire combination through
a small fistula than it is to guide a detachable balloon,
and the former also allows for more precise placement
of embolic agents within the cavernous sinus close to
the fistula orifice. Care must be taken to ensure that
these embolic agents are not deposited within the
carotid artery. An intracavernous venogram should
always be obtained to verify that the microcatheter is
positioned properly and to accurately delineate the
cavernous sinus prior to deposition of coils. The
occluding coils should be placed as close to the fistula
orifice as possible. Also, fewer coils are needed if the
fistula can be blocked at its orifice.
The use of standard nondetachable or free
platinum coils in the successful treatment of CCF
has been described in the literature (20). Since the
development of detachable platinum coils, though,
embolization using free coils by themselves is rarely
performed. Technical pitfalls associated with emboli-
zation using free platinum coils, including difficulty in
retrieval, the relative stiffness of the coils, the risk of
perforation, and the difficulty of packing them tightly,
have encouraged the use of the newer-generation
detachable coils. With detachable coils, if the micro-
catheter recoils during placement of the coil, the coil
can be repositioned. Nondetachable balloon assistance
during coil insertion can also be helpful.
The development of detachable or retrievable
platinum coils has significantly reduced the risks
associated with standard free platinum coils (2026).
The advantage of using detachable platinum coils is
the ability to control their placement and to easily
retrieve, reposition, or exchange them if necessary.
Technical pitfalls are possible with detachable plati-
num coils also. The soft platinum coils exert little force
on the surrounding structures and might be more
easily displaced in a high-flow fistula. Again, use of
stent- or balloon-assisted placement of the detachable
platinum coils may allow for tighter packing and
more complete closure of the fistula.
Liquid adhesives such as NBCA or IBCA have also
been used in conjunction with balloons or coils (26).

Initial placement of detachable balloons or coils within
the fistula helps significantly reduce the flow, allowing
for a safer use of liquid adhesives to complete the
occlusion of the fistula. When liquid adhesives are
used, reflux into the carotid artery and devastating
strokes can occur. This risk increases when closure of
the fistula is nearly complete and the pressure gradient
between the carotid artery and cavernous sinus is
lowered. Real-time digital subtraction and careful
slow injections of small volumes of embolic material
can avert this potential complication. Newer liquid
agents such as Onyx (Onyx Liquid Embolic System,
Micro Therapeutics, Inc., Irvine, California, U.S.) hold
interesting promise but remain unproven.
In younger patients and in those with a
straighter course of the vessel, it is possible to deliver
covered stents to bridge the site of fistula and, thereby,
close the fistula with preservation of the ICA (33,34).
Delivery of stents to the small-caliber, tortuous intra-
cranial arteries requires low-profile, flexible stents
with high elasticity as well as good pushability prop-
erties for the delivery catheter. Stent designs are con-
tinually being improved in order to overcome
problems in delivery, deployment, and prevention of
stent thrombosis. The Jomed covered stent (JoMed
International AB, Helsingborg, Sweden) is a surgical
steel endoprosthesis with an expandable PTFE graft,
and this device is manually compressed over a con-
ventional angioplasty balloon. The highly stretchable,
ultrathin graft material allows radial expansion, and
its surface and edges are very smooth. Once com-
pressed on an angioplasty balloon, the device is still
relatively stiff and its introduction into an intracranial
artery is problematic. The use of a stiff guidewire and
distally advanced guiding catheter with firm backup
are mandatory. Stent thrombosis after successful
deployment constitutes an important complication,
especially in covered stents. Adequate anticoagulant
and antiplatelet treatment before and after the proce-
dure are essential to prevent thromboembolic compli-
cations, therapeutic requirements that might not be
desirable in the multitrauma patient.
Transvenous Approach
When transarterial routes are unsuccessful, or if the
venous anatomy is opportune, transvenous emboliza-
tion can be performed (15,26,35,37). Access to the
cavernous sinus through the ipsilateral jugular vein
and IPS is the most common transvenous approach.
Other venous routes that have been used on occasion
to access the cavernous sinus include the contralateral
IPS, pterygoid plexus of veins, superior ophthalmic
vein, and also cortical veins via the sphenoparietal
sinus. These alternate venous routes were used
because of nonvisualization of the IPS or inability to
adequately gain access to the cavernous sinus via
the ipsilateral IPS. Following transvenous access to
the cavernous sinus, detachable balloons, detachable
platinum coils, or liquid embolic agents have been
used successfully. In transvenous cases, an arterial
catheter (4-5 French) typically has to be placed into
the ipsilateral common carotid artery or ICA for
Chapter 12: Direct Carotid Cavernous Fistula 237
angiographic localization of the fistula site and con-
firmation of fistula closure.
While the transvenous approach may be effec-
tive, it is not without risk. The most common compli-
cation associated with the procedure is perforation of
intracranial veins during catheterization. Although
arterialization of venous structures can occur in
long-standing shunts, the draining veins and dural
sinuses in CCFs are often still thin-walled and can be
perforated by a catheter or guidewire. With the
increased pressure and flow of the arterialized blood
in these structures, small perforations can result in
rapidly fatal subarachnoid hemorrhage. Alternatively,
venous thrombosis may occur following injury to the
veins. This could be significant if the venous drainage
is altered but the fistula remains open. For example, if
the posterior drainage (IPS) is occluded without clo-
sure of the fistula, aggravation of ocular symptoms
(superior ophthalmic vein) or hemorrhage (cortical
drainage) may occur. Similarly, if the superior oph-
thalmic vein is occluded, fistula flow may be diverted
into cortical veins, increasing the risk of hemorrhagic
complications. In our experience, closure of the distal
superior ophthalmic vein is often associate with
severe aggravation of ocular symptoms if persistent
fistula exists. As a technical note, therefore, care must
be taken not to occlude the access vein before the other
venous channels and fistula are closed. If cortical
venous drainage is noted, occlusion of the cavernous
sinus at the origin of the vein or, alternatively, direct
placement of coils into the sphenoparietal sinus
should be performed as a first step. Also, if a vein is
occluded, drainage of the pons and brain stem may be
impaired. Debrun et al. (15), in his report of trans-
femoral venous occlusion of CCF with detachable
balloons, noted that the percentage of success was
low because partitions within the cavernous sinus
precluded placement of a balloon near the fistula
orifice. With the development of softer and smaller
catheters and steerable guidewires, the risks of these
complications have been reduced.
Transorbital Approach
As the technology has improved, the success rate for
treatment using other approaches has increased. The
transorbital approach entails direct cut-down under
ultrasound guidance into the superior ophthalmic
vein with catheterization and embolization of the fis-
tula. We found this approach more difficult and cum-
bersome than the others and have abandoned it.
FOLLOW-UP
Angiographic residual flow through the fistula is not a
definite indication for further treatment. Subtotal
occlusion of a fistula may not indicate failure. On
the contrary, the goals of treatment are to alleviate
the clinical symptoms, to control the intraocular pres-
sures, and to eliminate cortical venous drainage. We
use a follow-up angiogram at three to six months after
treatment for evaluation in conjunction with a thor-
ough ophthalmologic exam.
238 Kanamalla et al.
SUMMARY
Direct CCF results from a tear in the cavernous ICA.
Endovascular occlusion of the fistula is the preferred
method of treatment. With improvement in catheter
techniques as well as embolic agents and stents, the
treatment of these complex lesions is generally safe
and effective.
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 13
Endovascular Management of Intracranial Aneurysms
Darren Orbach, Tibor Becske, and Peter Kim Nelson
Departments of Neurology, Neurosurgery, and Radiology, New York University
Medical Center, New York, New York, U.S.A.
DEFINITIONS AND EPIDEMIOLOGY
Intracranial arterial aneurysms historically have been
thought to result from a developmental abnormality
in vasculogenesis or angiogenesis, resulting in an
error in the normal cycle of cell birth, apoptosis, and
maintenance of the normal extracellular matrix (1) and
ultimately leading to fatigue of the viscoelastic ele-
ments of the vessel wall and outward ballooning of
the affected vascular segment with an increasing pro-
pensity to rupture as they enlarge. Although com-
puter models have recently been used to elucidate the
growth and rupture mechanism of aneurysms (2,3), it
remains an area of active investigation.
Arterial dissections, pseudoaneurysms, mycotic
aneurysms, and flow-related aneurysms associated
with arteriovenous malformations (AVMs) are specif-
ically excluded from this discussion in that these
lesions result from postnatal insults to a biologically
and morphologically normal cerebral artery. While
the techniques brought to bear in treating these con-
ditions can be similar to those used for congenital
aneurysms, the etiology and overall management of
these entities are sufficiently disparate that these latter
conditions merit their own attention.
Intracranial aneurysms constitute a common cer-
ebrovascular abnormality resulting in a significant
health problem worldwide. The estimated adult prev-
alence varies from 0.2% to 9% (4,5), with the incidence
of those discovered angiographically ranging from
0.5% to 1% of the population (6). A recent 30-year
retrospective study found the incidence of intracranial
aneurysms to be nearly equal to that of primary brain
tumors in the same population (7). While patients
with intracranial aneurysms may present with neuro-
logic deficit secondary to mass effect or thromboemb-
olism, the most common clinical presentation is
subarachnoid hemorrhage (SAH). This condition,
which commonly afflicts young and middle-aged
adults, has an annual U.S. incidence of over 25,000
cases, leaving over 18,000 of these patients (i.e., 72%)
dead or severely disabled, and generating a cost of
greater than $1.75 billion/yr (8). Comparing the high
prevalence of cerebral aneurysms with the relatively
low incidence of SAH, it should be apparent that only
a small fraction of aneurysms ever rupture. However,
the neurologic devastation wrought by a rupture is
sufficient enough for the treatment of asymptomatic
aneurysms to be often advocated.
DECISION MATRIX---TO TREAT
OR NOT TO TREAT
Ruptured intracranial aneurysms are almost always
treated urgently because of the high risk of rebleed.
Moreover, there is evidence that unruptured aneur-
ysms in a patient with a history of SAH are at
increased risk of rupture, and elective treatment for
these patients is widely advocated. However, the
decision to treat an unruptured intracranial aneurysm
in a patient with no prior history of SAH must be
based on consideration of the patients clinical pre-
sentation, within the context of what is known of the
natural history of aneurysms and the risk/benefit
ratio associated with a specific treatment. These latter
two considerations are themselves complex, involving
such factors as location and size of the aneurysm,
presence of a connective tissue disorder such as poly-
cystic kidney disease, the presence of hypertension,
the patients age, the case volume of the treating
institution and operator, etc. (912).
The 1998 International Study of Unruptured
Intracranial Aneurysms (ISUIA) investigated both
the natural history of previously unruptured intra-
cranial aneurysms as a function of different patient
characteristics (in its retrospective arm) and the mor-
bidity and mortality of surgical treatment (in its pro-
spective arm) (13). The investigators initially
concluded that for patients with aneurysms measur-
ing less than 10 mm in diameter, if there was no prior
history of SAH in the patient, the risk of rupture was
less than 0.05% per year, and such aneurysms are
referred to as incidental. In the setting of previous
SAH (from another aneurysm), the risk was 11 times
higher, and such aneurysms are referred to as addi-
tional. For aneurysms of 10-mm or greater diameter,
the annual risk of rupture approached 1%, whether or
not there was a prior history of SAH. Thus, in asymp-
tomatic patients with small aneurysms, the adverse
effects associated with surgical treatment exceeded
the morbidity and mortality of the condition.
240 Orbach et al.
Several neurosurgical groups criticized the
ISUIA soon after its publication (14), stressing that
the retrospective arm of the study was biased toward
aneurysm locations that were less likely to rupture.
Moreover, by dint of the study subjects having been
specifically chosen as a group in which not to inter-
vene, these aneurysms were thought to possibly be
more stable than randomly selected aneurysms from
the community would be. In fact, a long-term study of
unselected unoperated patients from Finland, pub-
lished after ISUIA (15), reported a significantly higher
rupture rate. Others (16) pointed out that the annual
incidence of 16,000 cases of SAH in the United States
could not be explained by a rupture rate of 0.05% for
aneurysms smaller than 10 mm; the prevalence of
unruptured aneurysms would have to be orders of
magnitude higher than it actually is. Along these lines,
a biophysical model of aneurysm rupture (17) pre-
dicted that, rather than a sharp threshold of increasing
risk at 10 mm as suggested by ISUIA, there was
actually a continuously increasing risk of rupture,
scaling with the diameter (18).
Nevertheless, the ISUIA and other studies (19)
led to the issuance, in 2000, of a set of formal Recom-
mendations for the Management of Patients with Unrup-
tured Intracranial Aneurysms by the American Heart
Association (20), which recommended no treatment
for small, incidental aneurysms in asymptomatic
patients. Treatment was recommended for those
with large aneurysms, those with worrying morphol-
ogy, and those with a history of SAH.
In 2003, the full report from the prospective arm
of ISUIA was published (13), comparing the natural
history of unruptured aneurysms and the morbidity
and mortality of neurosurgical clipping and endovas-
cular coiling in various groups of patients. As in the
1998 report, the investigators found that the size of the
aneurysm was an important determinant of its natural
history, with aneurysms smaller than 7 mm in patients
without prior SAH having an approximately 0.1%
annual risk. Interestingly, a family history of rupture
seemed to pose no additional hazard. The investiga-
tors pointed out that this cohort was nearly asympto-
matic, and the presence of symptoms may be
indicative of a more dangerous aneurysm. Larger
aneurysm size was a definite risk factor for rupture
in previously unruptured patients, but less clearly so
for patients with prior SAH, in whom even small
aneurysms had a relatively high rupture rate. Multi-
variate analysis showed that relative to those with
aneurysms smaller than 7 mm, those with 7- to
12-mm aneurysms had a relative risk (RR) of rupture
of 3.3 and those with larger than 12 mm had an RR
of 17. Three locations were associated with altered risks
of rupture relative to the internal carotid artery: the
basilar tip (RR 2.3), the cavernous carotid (RR 0.15), and
the posterior communicating artery (RR 2.1). Patient
age was not predictive of rupture likelihood. However,
surgical morbidity and mortality were closely tied to
age; endovascular morbidity appeared to be less so.
Other factors linked to poor postsurgical outcome
included aneurysms larger than 12 mm, posterior cir-
culation location, previous cerebral ischemic disease,
and aneurysmal symptoms other than rupture (such as
mass effect). Conversely, only location in the posterior
circulation and sizes greater than 12 mm were linked to
postcoiling outcome. This second report, too, was
criticized (21) on the basis that the mechanism for
stratification of patients into untreated, surgically
clipped, and coiled cohorts was not elucidated, and
thus selection bias may have contributed to the dispa-
rate results between cohorts.
A 2005 meta-analysis examining the risk of
aneurysmal rupture as a function of location (22)
found that, excluding the ISUIA data, across all sizes
of aneurysm, the annualized risk of rupture was 1.3%
for all anterior circulation aneurysms and 3.4% for the
posterior circulation. There was no statistical differ-
ence among different locations within the anterior
circulation, including the posterior communicat-
ing artery. When the ISUIA data was included, the
annualized risk was 0.5% for the anterior circulation
and 1.8 for the posterior circulation, lending credence
to the notion that ISUIA rates of rupture were mark-
edly lower than those published in other studies. The
authors conclude that the ISUIA inclusion of posterior
communicating segment aneurysms with those of the
posterior circulation as possessing higher risk of rup-
ture is misguided.
A recent study using three-dimensional CTA to
follow the natural history of unruptured cerebral
aneurysms (23), with a mean follow-up of 17.7 months,
found that aneurysmal growth or new bleb formation,
thought to be precursors to rupture, were likelier the
larger the initial size of the aneurysm. Thus, 2.4% of
2- to 4-mm aneurysms, 9.1% of 5- to 9-mm aneurysms,
and 50% of 10- to 20-mm aneurysms grew . Location
was an important factor as well, with 2 out of 5 basilar
tip aneurysms and 0 of 43 middle cerebral artery
aneurysms growing.
Giant intracranial aneurysms (>2.5 cm) may
become clinically apparent through progressive focal
neurologic deficit secondary to mass effect, SAH, or
thromboembolic events resulting from dislodgment of
intraluminal thrombus contained within the aneur-
ysm fundus. These aneurysms are disproportionately
represented in most endovascular treatment serie-
sand, as discussed below, are often associated with
increased treatment failure as defined by degree and
persistence of occlusion. However, when successful,
endovascular treatment may be beneficial not just in
reducing the risk of rupture and thromboembolism,
but also in ameliorating symptoms of mass effect. In a
review of 26 patients with neurologic deficits related
to aneurysmal mass effect treated by neurointerven-
tional management, Halbach et al. (24) observed clin-
ical improvement in 9 of 11 patients harboring giant
aneurysms despite incomplete occlusion of seven
aneurysms.
As is the case for intradural aneurysms, for
patients with intracavernous aneurysms, the decision
to treat depends to a large extent on the clinical pre-
sentation. Signs and symptoms usually relate to cranial
neuropathy secondary to the mass effect of the aneur-
ysm. Kupersmith et al. (25) concluded that aneurysms
of the cavernous carotid artery are rarely associated
 Chapter 13: Endovascular Management of Intracranial Aneurysms
with life-threatening symptoms. In this and other stud-
ies (2527), spontaneous clinical improvement in symp-
tomatic cavernous carotid aneurysms has been
observed following conservative management. Thera-
peutic intervention is usually reserved for patients with
acute incapacitating cranial neuropathy or significant
neuropathy failing to resolve with conservative
management, intractable pain, signs of transient ische-
mic attack, SAH, or potential for life-threatening epis-
taxis as a result of bony erosion into the sphenoid
sinus. In addition, cavernous aneurysms arising from
the anterior genu of the carotid siphon (ring aneur-
ysms), with MR characteristics suggestive of extension
into the subarachnoid space, are usually treated aggres-
sively because of the risk of SAH (26).
ENDOVASCULAR STRATEGIES
Although microsurgical clipping has been historically
advocated in the treatment of aneurysmal SAH and
incidentally discovered aneurysms, endovascular ther-
apy has evolved over the past decade and can now be
offered as a viable alternative to direct open surgical
treatment in many cases. Endovascular methods typi-
cally promote occlusive thrombosis of the aneurysm
and may be broadly classified into two essential strat-
egies: deconstructive and reconstructive approaches.
Deconstructive procedures involve sacrifice of the par-
ent vessel from which the aneurysm arises, while
reconstructive approaches involve selective occlusion
of an aneurysm with preservation of the parent artery
(i.e., reconstruction of an aneurysm-free lumen).
DECONSTRUCTIVE APPROACH
Most surgical series of carotid ligation for treatment of
intracranial aneurysms were characterized by high
morbidity and mortality related to ischemic stroke
(28). In a survey of the surgical literature for carotid
occlusion therapy, Scott et al. (29) reported a morbid-
ity rate of 33% among 909 patients retrospectively
reviewed. By comparison, most neurointerventional
series of balloon occlusion therapy have reported
transient neurologic deficits ranging from 7% to
10%, with permanent deficit seen in 1.5% to 5% of
patients (3032). These results have led to wider
acceptance of endovascular occlusion in the treatment
of symptomatic giant, fusiform or wide-necked aneur-
ysms of the proximal carotid artery and vertebrobasi-
lar circulation (31,3335).
Endovascular occlusion of the ICA offers several
advantages to surgical clamping or ligation. Occlusion
may be performed easily on an awake patient permit-
ting continuous neurologic assessment during balloon
test occlusion (BTO) prior to permanent vessel sacri-
fice. The collateral support to the compromised vas-
cular territory may be evaluated angiographically at
the time of BTO, providing an anatomic basis
for confidence in the occlusion test (Figs. 1D, E and
2C,F). The possibility of residual flow within the
aneurysm may be evaluated for each potential site of
parent vessel occlusion. This is particularly important
241
in aneurysms of the supraclinoid segment of the ICA
and those affecting the vertebrobasilar circulation,
which may be reconstituted by collateral vessels
after occlusion therapy (36).
SAFETY AND EFFICACY
Deconstructive procedures have been demonstrated to
be highly effective and safe in the treatment of properly
selected patients. Higashida et al. (32) reported results
in 127 patients treated with detachable balloons and
found the incidence of permanent morbidity to be
5.5%, with a mortality rate of 3.9%. Importantly, in
this and other studies, following carotid occlusion, the
size of the aneurysm often decreased (27), usually
accompanied by resolution of the patients symptoms.
Fox et al. (30) reported complete thrombosis in 50 of
65 cases of large and giant surgically incurable aneur-
ysms of the anterior circulation treated by parent artery
occlusion. Morbidity due to cerebral ischemia was seen
in 12.3% of patients, with only one case progressing to
permanent stroke and no deaths.
While it is often assumed that post-occlusion
stroke in patients previously passing BTO is related
to cerebrovascular insufficiency, other mechanisms
may account for the observed ischemic events. Anon
et al. (37) have reported an angiographically docu-
mented middle cerebral embolus in one of two patients
suffering from permanent neurologic complications
after ICA occlusion, among 32 patients treated for
cavernous carotid aneurysms who successfully passed
BTO. Their data, as well as that of others (38), suggest
the possibility that mechanisms other than insufficient
collateral support may explain the development of
neurologic deficits in patients after ICA sacrifice.
While deconstructive approaches to aneurysms
involving the supraclinoid ICA may be effective, prox-
imal parent vessel occlusion is less reliable at inducing
complete aneurysm thrombosis because of the possi-
bility of persistent aneurysm filling through collaterals
at the ophthalmic segment and circle of Willis. In the
series of Fox et al. (30), 37 patients with cavernous
aneurysms were found to have complete obliteration
of the aneurysm as a result of proximal artery occlu-
sion. However, among 21 supraclinoid aneurysms in
their series, complete thrombosis occurred in only 10.
Similar results have been observed for aneurysms
arising within the vertebrobasilar circulation. Aymard
et al. (39) reported complete thrombosis in only 13 of
21 inoperable posterior circulation aneurysms by
endovascular occlusion of the vertebral arteries. Com-
plications in these procedures were typically because
of thromboembolic phenomena or inadequate collat-
eral blood flow resulting in transient or permanent
cerebral ischemic events.
THERAPEUTIC VESSEL OCCLUSION:
TECHNIQUES
Deconstructive procedures commonly employed in
the management of intracranial aneurysms involve
parent vessel occlusion with balloons (Fig. 1) or coils
242 Orbach et al.

Figure 1 (A) Axial T2-weighted and (B) lateral arterial phase angiographic images illustrating a giant cavernous segment aneurysm of
the LICA. BTO of the LICA was performed prior to sacrifice of the parent vessel. (C) Lateral arterial phase image of the right common
carotid artery after inflation of the test balloon confirming flow arrest in the LICA. (D) Frontal arterial phase image of the intracranial RICA
runoff, and (E) lateral arterial phase image of a left vertebral/basilar runoff performed during BTO of the LICA, demonstrating collateral
support of the left hemispheric circulation through the circle of Willis. The patient tolerated test occlusion of the LICA and the aneurysm
was subsequently treated deconstructively by permanent occlusion of the parent LICA with detachable balloons (F). A second diagnostic
catheter is useful in angiographically assessing potential collateral support to a compromised circulation during BTO. Abbreviations:
LICA, left internal carotid artery; BTO, balloon test occlusion.

(Fig. 3). Refinements in this technique have included
the deposition of coils within the aneurysm proper to
further secure occlusion of the aneurysm fundus,
particularly in situations where the aneurysm may
be reconstituted by collateral circulation. The protocol
often includes BTO in the initial angiographic assess-
ment of potential collateral supply to the cerebral
vascular territory placed at ischemic risk by the parent
vessel occlusion. Such collateral supply may be
derived through (1) the circle of Willis, (2) external-
to-internal carotid artery anastomoses, at the ophthal-
mic, cavernous, and petrous ICA segments (Fig. 4), or
(3) leptomeningeal collateral support over the convex-
ities, depending on the proposed level of occlusion.
The uninvolved cervical and cerebral vasculature
should also be evaluated for signs of disease, i.e.,
additional aneurysms, vessel dissection, fibromuscu-
lar dysplasia, or other conditions that might mitigate
against occlusion therapy.
Patients in whom the collateral circulation, as
demonstrated angiographically, appears adequate,
tolerance testing is performed by temporary balloon
occlusion of the parent vessel at or near the site of
proposed permanent vessel sacrifice (36). In cases of
aneurysms arising from the ICA, a double lumen
occlusion balloon catheter may be introduced alone
or via a coaxial system through a larger guiding
catheter positioned within the common carotid artery.
The balloon occlusion catheter is introduced into the
cervical segment of the ICA and then inflated under
digital subtraction fluoroscopy, employing a road-
mapped image of the ICA. In addition to systemic
heparinization, local perfusion of the occluded seg-
ment proximal to the balloon is established through
the guide catheter component of the coaxial system,
while the segment distal to the occlusive balloon is
perfused with heparinized saline through the distal
lumen of the occlusion catheter. Following balloon
inflation, vessel occlusion is verified either by admin-
istration of contrast through the distal lumen of the
balloon occlusion catheter (resulting in a stagnant
column of contrast within the occluded segment distal
 Chapter 13: Endovascular Management of Intracranial Aneurysms 243

Figure 2 Angiographically failed BTO of the LICA. (A) Frontal arterial phase DSA image of the LICA demonstrating a recurrent wide-
necked aneurysm previously treated by surgical clipping. (B) A balloon was subsequently inflated within the LICA for test occlusion.
Cerebral angiography of the RICA, performed during BTO of the LICA (CF), was notable for angiographically inadequate collateral
support across the anterior communicating artery characterized by poor cross opacification of the left hemispheric circulation and delayed
angiographic progression. Note the increasing discrepancy in angiographic phase between right and left hemispheres evident from (C) to
(F) suggesting reduced flow within the left anterior and middle cerebral territories. The left posterior communicating artery was atretic.
Abbreviations: LICA, left internal carotid artery; BTO, balloon test occlusion; RICA, right internal carotid artery.

to the inflated balloon) or by angiographic assessment
of ipsilateral common carotid runoff from the proxi-
mal guiding catheter. While the potential for collateral
reconstitution of the compromised cerebrovascular
territory may be inferred from dilution of the stagnant
contrast column by wash-in of unopacified blood, this
determination is better made using a second diagnos-
tic catheter to angiographically assess collateral sup-
port during test occlusion of the index vessel.
If carotid occlusion is not tolerated, sensorimotor
dysfunction usually develops within a short time.
While not universally accepted, a variety of semiquan-
titative measures of cerebral blood flow (PET, SPECT,
and XeCT) have been used to increase the rigor of
occlusion testing (38,4042). Hypotensive challenge
(29) with or without transcranial Doppler ultrasound
monitoring has been advocated for assessment of mar-
ginal cases, although its power in predicting delayed
ischemic complications has been questioned (43). In
recent years, the use of hexamethylpropyleneamine
oxide (42) has made it technically simpler, easier, and
safer to perform cerebral blood flow measurement
during test occlusion by eliminating the need for
blind inflation of the occlusion balloon and transfer
of the patient with indwelling catheters for imaging
purposes. Unfortunately, no method offers perfect
specificity and sensitivity in predicting the outcome
of permanent parent vessel occlusion, and all may be
associated with complications. With experience, how-
ever, a false positive predictive morbidity rate of less
than 5% should be achievable.
Following uneventful test occlusion, the balloon
is deflated, and permanent vessel sacrifice performed
with detachable balloons or coils. The advantages of
balloon occlusion include the immediacy of flow
arrest and an overall reduction in procedure time.
The primary disadvantage is the possibility of prema-
ture balloon deflation during placement of the initial
244 Orbach et al.

Figure 3 Reformatted CT angiogram demonstrating a mostly thrombosed giant fusiform aneurysm involving the distal left vertebral, VB
junction, and proximal basilar arteries. Both posterior communicating arteries were atretic, so (A) surgical bypass from the right external
carotid to posterior artery was performed (B) prior to deconstructive coil occlusion of the aneurysm and parent left vertebral and basilar
arteries (CF). (C) Unsubtracted image of the skull illustrating the coil mass. (D) Frontal arterial phase image of the bypass (white
arrowhead ) runoff demonstrating retrograde opacification of the upper basilar artery to the level of the AICA segment (white arrow).
(E) Frontal arterial phase DSA image of the right vertebral artery confirming occlusion of the aneurysm and VB segment with preservation
of the right posterior inferior cerebellar artery (notched black arrowhead ) and radiculomedullary contribution to the anterior spinal artery
(black arrow). (F) DSA left vertebral artery confirming occlusion of the distal left vertebral artery and aneurysm. Abbreviations: VB,
vertebrobasilar; AICA, anterior inferior cerebellar artery.

balloon prior to secured flow arrest, which may lead
to embolization of the deflated balloon. The likelihood
of unintended balloon embolization can be reduced by
timely placement of tandem balloons, or deployment
of the initial balloon under conditions of flow arrest,
employing a balloon occlusion guide catheter to arrest
flow more proximally while the target vessel is per-
manently occluded.
The risks of coil occlusion include increased
time of the procedure, the possibility of coil emboli-
zation into the distal intracranial circulation, and the
potential for thromboembolic events during the pro-
cedure prior to the full arrest of antegrade flow in the
sacrificed vessel. These difficulties can in part be
addressed by using an occlusion balloon guide cath-
eter to arrest flow in the parent vessel proximal to the
site of coil deposition during the procedure. It should
be pointed out that permanent occlusion of major
vessels such as the ICA or vertebral arteries may
require a large number of coils, increasing the
expense of the procedure.
For balloon occlusion of the ICA, a detachable
balloon is usually advanced to the site of proposed
deployment (36). In treating cavernous segment
aneurysms, a common strategy is to use a trapping
method, in which the first balloon is advanced, often
with the aid of a microguidewire, to the segment of
ICA just distal to the aneurysm neck. A second bal-
loon is then placed either across the aneurysm neck or
just proximal to the aneurysm, effectively trapping the
lesion between the two inflated balloons. In cases
complicated by cavernous aneurysm rupture (with
accompanying carotid-cavernous fistula), proximal
occlusion may result in cerebral ischemia or stroke
as a result of vascular steal unless the accompany-
ing fistula is first occluded (44).
 Chapter 13: Endovascular Management of Intracranial Aneurysms 245

Figure 4 Skull base collaterals potentially confounding adequate BTO of the internal carotid artery. (A) Midarterial phase DSA image
from a left common carotid runoff (lateral projection) after inflation of a balloon (black arrow ) within the midcervical segment of the left ICA
during BTO. Injection of contrast at the left common carotid artery bifurcation reveals collateral reconstitution of the ICA beyond the
occlusion balloon (notched black arrowhead ) through the vidian artery (partially obscured by the petrous bone, white arrowhead ) and the
ophthalmic artery (white arrow ) through a meningoophthalmic branch (black arrowhead ). (B) DSA image of the left ICA (lateral projection)
demonstrating angiographically identifiable meningohypophyseal (arrow) and vidian (notched arrowhead ) arteries. (C) Midarterial DSA
image (frontal projection) during super-selective microcatheter angiography of the neuromeningeal trunk of the left ascending pharyngeal
artery (microcatheter tip labeled with solid arrowhead ). Distal branches of the right ascending pharyngeal artery (notched arrowhead ) are
retrogradely opacified across the midline through collaterals of the retroclival arcade (small double arrows). The left internal carotid artery
(large single arrow) is opacified through collaterals between the neuromeningeal trunk and branches of the MHA. This ECA/ICA collateral
route could provide a hemodynamically significant conduit for reconstituting the intracranial ICA circulation during BTO, unless the balloon
was inflated over or distal to the MHA. Abbreviations: ICA, internal carotid artery; ECA, external carotid artery; BTO, balloon test
occlusion; MHA meningohypophyseal artery.

After detachment of the initial balloon, addi-
tional balloons are usually deployed within the cervi-
cal segment of the ICA, with the most proximal
occlusion balloon usually detached at the internal
carotid origin effectively creating a stumpectomy.
The need for placement of a stumpectomy balloon is
somewhat controversial. At issue is the relative risk of
thromboembolic events arising from turbulent flow
and thrombosis at the unsecured internal carotid bulb,
which may occur through external-to-internal carotid
collaterals (45), versus cardiodynamic instability
attributed to mechanical overdistension of barorecep-
tors with deployment of a balloon at this location.
For giant aneurysms involving the supraclinoid
segment of the ICA or the vertebrobasilar circulation,
an understanding of the potential pathways for col-
lateral reconstitution of the lesion (through the oph-
thalmic or posterior communicating arteries in
supraclinoid ICA aneurysms or through collaterals
at the cervical interspaces in distal vertebral artery
aneurysms) will determine the level of parent vessel
occlusion required.
Deconstructive treatment of aneurysms arising
from distal cerebral vessels is more complex and
technically more challenging. Positioning the balloon
microcatheter for temporary occlusion of the distal
circulation is associated with increased risk of vessel
rupture and relies far more on anatomic studies in the
evaluation of the leptomeningeal circulation at the cor-
tical level to assess potential reconstitution of the distal
vascular territory occluded by the balloon. The risk of
future deficit may be assessed by superselective injec-
tion of sodium amytal, which will usually disclose a
potential neurologic deficit related to the entire territory
of the occluded vessel. This deficit generally provides an
overestimation of the potential neurologic dysfunction,
but it may nevertheless prompt a more conservative
approach, depending on the degree of eloquence of the
territory at risk.
As opposed to balloon or macrocoil (0.035 inch)
occlusion of larger proximal vessels, it is often pref-
erential to use microcoils for distal occlusive proce-
dures. In this context, refinements in microcoil
technology, reflected in part by the development of
the Guglielmi detachable coil (GDC) system (see
below), have improved the accuracy of coil position-
ing and retrieval, dramatically increasing the safety of
this approach.
Deconstructive endovascular approaches can
also be used in concert with surgical exploration in
treating giant aneurysms associated with critical mass
effect. Mounayer et al. (46) report on a giant anterior
communicating aneurysm that presented with symp-
toms of bifrontal mass effect, whose treatment con-
sisted of endovascular occlusion of both anterior
cerebral arteries using a Trispan device and several
coils (with leptomeningeal MCA collaterals supplying
the affected territories), followed several days later by
surgical aneurysmectomy. Others have reported sim-
ilarly on the utility of temporary intraoperative
246 Orbach et al.
endovascular flow arrest in providing for a better-
controlled surgical approach to large paraclinoid
aneurysms (47).
RECONSTRUCTIVE APPROACH
Reconstructive repair of aneurysms, i.e., approaches
that aim to exclude the aneurysm sac from the arterial
circulation while preserving the parent vessel, can take
one of two general forms: (1) endosaccular, where the
strategy is aimed at filling the aneurysm sac with
embolic materials thereby promoting aneurysmal
thrombosis, and (2) endoluminal, where the goal is not
merely to treat the aneurysm sac, but rather to restore
the vessel wall deficiency to its preaneurysmal state.
Early endovascular reconstructive approaches
were exclusively endosaccular. It quickly became
apparent that selective occlusion of an aneurysm
with preservation of the parent artery (i.e., recon-
struction of an aneurysm-free lumen) could be per-
formed by direct deposition of occlusion balloons
within the aneurysm lumen. Despite several early
reports of success using reconstructive balloon occlu-
sion therapy (24,4850), this technique as well as those
employing pushable microcoils and liquid embolic
agents (51) for intracranial aneurysm occlusion have
been eclipsed by the safety and efficacy of detachable
coil systems, exemplified by the GDC (5254).
The GDC was introduced for clinical trial to a
limited number of centers in 1991 and received the
U.S. FDA approval for treatment of patients with
surgically unmanageable aneurysms in 1995. The rec-
ommended indications were subsequently liberalized
in 2003, following publication of results from the
International Subarachnoid Aneurysm Trial (ISAT)
(55), to permit its use more broadly in select patients
with ruptured cerebral aneurysms. In this study, clin-
ical, neuropsychological, and angiographic follow-up
was obtained, on a cohort of patients with ruptured
aneurysms thought to be equally suitable for clipping
or coiling, and randomly assigned to one or the other.
Enrollment was prematurely terminated after deter-
mination of a demonstrably lower risk of death or
dependency in the coiled subgroup (absolute risk
reduction of 6.9%). The rebleeding rate was 2.6% in
the coiled group versus 1% in the clipped group, but
the morbidity was nevertheless lower. The publication
of ISAT led to the release of a position statement by
the American Society of Interventional and Therapeu-
tic Neuroradiology (ASITN) (56), endorsing a neuro-
interventional consultation, wherever feasible, for
every case of SAH.
A follow-up of the ISAT cohort, published in
2005 (57), reported that the relative risk reduction of
coiling versus clipping had in the interim increased to
7.4% and was maintained out to seven years of follow-
up. The risk of epilepsy was significantly lower in the
coiled group as well (RR 0.52). Despite the fact that
the risk of rebleeding in the coiled group was higher
(7 vs. 2 patients), as was the percentage of incom-
pletely occluded aneurysms on follow-up angiograms
(34% vs. 18%), the investigators concluded that the
follow-up study bolstered the initial ISAT conclusions
regarding the potential superiority of endovascular
treatment of acutely ruptured cerebral aneurysms, in
cases where either treatment is a valid option.
The advantage of detachable coils in treating
cerebral aneurysms is related to four distinct proper-
ties: (1) the method of its delivery, attached to a
delivery mandrel, enables the operator to determine
and to change the placement of the coil prior to final
deployment, thereby increasing the number of possi-
ble strategies for achieving ideal occlusion, (2) the
intrinsic compliance of the coil helix permits adapta-
tion to a relatively wide range of aneurysm morphol-
ogies, (3) the low thrombogenicity of the platinum coil
strand allows coil retrieval and repositioning of sub-
optimally deployed coils, without undue concern for
shearing of clot matter from the manipulated coil, and
(4) availability in a wide selection of sizes and shapes
from several manufacturers.
There are in general two size classes of aneurysm
coils, one employing platinum wire of 0.015-inch
gauge for delivery through a 1.9- to 2.5-French (Fr)
microcatheter and a second constructed of 0.010-inch
gauge platinum coils, which may be delivered
through 1.7-Fr microcatheters. The original platinum
coils were available in various lengths ranging from
2 to 30 cm and were constructed to assume a helical
configuration of 2- to 20-mm diameter in the uncon-
strained state, depending on the specific type of coil.
Since their release in 1991, more sophisticated coil
designs have become available, varying in their con-
formability, configurational complexity (2D, 3D, 360),
and resistance to stretching during manipulation or
retrieval. Later generations have included hybrid coils
incorporating various bioactive substances and volu-
metrically expansile coatings (hydrogels).
In most designs, the coil proper is attached prox-
imally to a delivery mandrel (measuring *175 cm in
length) through an intermediate coupling represent-
ing the potential detachment zone. By convention, the
detachment zone for all coil makes is 3 cm distal to a
radiopaque marker located on the delivery mandrel,
which, when aligned with the proximal marker of the
aneurysm microcatheter, serves to ensure proper loca-
tion of the detachment zone outside the tip of the
microcatheter. Once acceptably placed within the
aneurysm, coils may be separated from the delivery
stylette by electrolysis or temperature-dependent dis-
solution of a polymeric linkage, employing direct cur-
rent (DC) of 1 to 2 mA, or by one of several hydraulic
systems.
ANEURYSM COIL PROTOCOL
At most neurointerventional centers, reconstructive
treatment of cerebral aneurysms with aneurysm coils
is performed under general anesthesia, which insures
more controlled patient management and better
imaging quality, particularly important for navigating
difficult vascular anatomy and the superselective cath-
eterization of small and complex aneurysms. A radial
artery line is placed for continuous monitoring of
 Chapter 13: Endovascular Management of Intracranial Aneurysms
arterial blood pressure and the activated coagulation
time (ACT). In those patients with compromised car-
diopulmonary function, or in patients presenting with
acute SAH, central venous access may be helpful. This
enables both monitoring of central venous pressure
and placement of a Swan-Ganz catheter for monitoring
of pulmonary wedge pressure in patients requiring
subsequent triple-H (hypertensive, hypervolemic,
hemodilutional) therapy. In the setting of acute SAH,
it has been shown that the morbidity and mortality rate
(40%) secondary to medical complications in the after-
math approaches that due to the primary neurologic
event (58), and scrupulous attention to peri- and post-
procedural neurocritical care is mandatory.
After patient preparation, cerebral angiography
is performed to obtain the anatomic information
required for optimal planning of endovascular treat-
ment. The angiographic assessment, which is fre-
quently aided by 3D volumetric rendering of a
rotational angiographic data set, includes (1) the
size, shape, and orientation of the aneurysm, includ-
ing correlation with transaxial imaging to assess the
presence of intra-aneurysmal thrombus; (2) the size of
the aneurysm neck in relation to that of the aneurysm
fundus and parent vessel; (3) the size and morphology
of the parent vessel from which the aneurysm arises;
(4) potential collateral blood supply to the vascular
territory supplied by the affected artery, including the
presence of any anatomic variations; and (5) angio-
graphic evidence of vasospasm or other vascular
anomalies or disease states often associated with
247
intracranial aneurysms (AVMs, fibromuscular dyspla-
sia, vasculitis, additional aneurysms, etc.).
After obtaining the best working position, a
road-map image of the parent vessel and aneurysm
is obtained, and the aneurysm fundus selectively
catheterized with a coaxially introduced 2-marker
microcatheter (Fig. 5). The tip of the catheter may be
shaped to conform to the anatomic configuration of
the aneurysmparent vessel complex or may be intro-
duced unshaped, depending on the strategy employed
by the operator. Regardless of approach, however, care
must be taken to ensure that neither the microcatheter
tip nor the guidewire forcibly interact with the wall of
the aneurysm.
The first coil selected should be the largest coil
deployed and serves to frame the theoretical bound-
ary of the aneurysm. Appropriately sized smaller coils
are subsequently delivered to fill the interstices of
the aneurysm fundus, and any coil inadvertently
herniating into the parent vessel, or suboptimally
positioned within the aneurysm, may be withdrawn
and repositioned into a more optimal configuration
prior to its detachment. As successive coils are
deployed within the aneurysm, it may become
increasingly difficult to visualize each new coil fluo-
roscopically as it is positioned within the deposited
coil mass. Precise placement of additional coils, how-
ever, may continue through alignment of the delivery
mandrels radiopaque marker, with the proximal plat-
inum marker on the microcatheter (outside the aneur-
ysm), 3 cm from its tip.
Figure 5 (A) Reformatted rotational angio-
graphic image of the intracranial LICA circula-
tion demonstrating a large left middle cerebral
artery aneurysm (white arrow) (other aneur-
ysms have been clipped). (B, C) Successive
real-time road-mapped images of the intracra-
nial LICA circulation (frontal projection) during
deployment of the first platinum coil. In (C), the
coil has been fully delivered into the aneurysm
as indicated by the alignment of the delivery
mandrel marker with the proximal microcath-
eter marker band (notched arrow). (D) Post-
treatment rotational angiographic image
confirming near complete coil occlusion of
the aneurysm. Abbreviation: LICA, left internal
carotid artery.
248 Orbach et al.
Using live digital subtraction techniques, the
deployment of each new coil can be individually
followed. After the desired coil position has been
achieved, DC is applied to the proximal end of the
delivery wire, resulting in separation of the coil from
its guidewire over an interval of 2 to 60 seconds,
depending primarily on the specific manufacturers
design. The delivery mandrel is then removed, and if
required, additional coils are deployed through the
indwelling microcatheter, usually until a dense coil
mesh within the aneurysm has been achieved. The
deposited coil mass results in stagnation of flow
within the aneurysm fundus, promoting thrombosis
and isolation of the aneurysm wall from the arterial
circulation.
The extent to which DC-induced electrothrom-
bosis participates in the formation of the aneurysmal
clot during coil deployment has not been delineated in
vivo. Initial evidence from in vitro models and animal
experiments suggested that to some degree thrombus
does form around the activated platinum anode in
proportion to the current magnitude (54), and further,
that aneurysmal thrombosis is followed by growth
of a neo-endothelium over the base of the aneurysm
(59). However, subsequent findings in humans (60)
and bifurcation aneurysm models in experimental
animals (61) have raised questions regarding the sta-
bility of the coil-thrombus complex and its histologic
evolution.
Given that thromboembolic complications con-
stitute the major risk to patients undergoing coil-
endovascular occlusion of intracranial aneurysms,
anticoagulation during treatment is employed at
most centers. Although the precise regimen varies
across institutions, generally anticoagulation with
intravenous heparin or heparinization combined with
antiplatelet therapy is begun during the endovascular
procedure and is continued for 12 to 48 hours. How-
ever, a controlled study examining the efficacy of
anticoagulation and/or antiplatelet therapy in this
setting has not been done.
FOLLOW-UP AFTER TREATMENT
Radiographic follow-up of treated aneurysms usually
involves plain-film assessment of the coil pack con-
figuration in conjunction with serial angiograms, usu-
ally at yearly intervals during the first years,
supplemented by MRA (62,63) for long-term assess-
ment of treatment stability. In most cases, 3D time-of-
flight images are adequate, with the addition of a
saturation band in cases of high perianeurysmal signal
allowing the distinction between slow flow and blood
products. Contrast-enhanced MRA is further useful
(64), increasing signal-to-noise ratio and helping dis-
tinguish slow flow at the coiled aneurysm base, par-
ticularly in the setting of giant aneurysms.
The application of MRA in the evaluation of
aneurysm recanalization was reported to have a sen-
sitivity of 97%, a specificity of 100%, a positive pre-
dictive value of 100%, and a negative predictive value
of 94.7%.
CLINICAL RESULTS: RECONSTRUCTIVE
APPROACH WITH ANEURYSM COILS
It must be borne in mind that most series that appear
in the literature describing outcome after endovascu-
lar aneurysm treatment include patients unsuitable
for surgical clipping, and are thus biased by inclusion
of a higher proportion of posterior circulation aneur-
ysms and of patients with higher Hunt and Hess
grade than are comparable surgical series.
A 2004 study (65) reviewed the clinical outcome
among patients who presented with Hunt and Hess
grade IV or V SAH and who were coiled between days
one and seven from their ictus. Patients with large
intracranial hematomas, with evidence of large vol-
ume infarcts, with extensive midline shift, or with
evidence of brain stem damage were excluded. No
balloons or stents were used. Outcome was assessed
at six months and was favorable (i.e., at most moder-
ate disability) in 48% of the cohort, a figure that is
comparable to results from early neurosurgical clip-
ping and significantly improved over the natural
course of such patients (66).
A retrospective 1998 study (67), comparing the
frequency of vasospasm after SAH of similar severity
treated either with surgical clipping (19 patients) or
endovascularly (18 patients), showed a notably higher
tendency toward vasospasm in the surgical group,
with 14 of the 19 patients requiring triple-H therapy
and three requiring mechanical angioplasty and intra-
arterial pharmacologic treatment of vasospasm.
Among the endovascular group, four patients devel-
oped clinical signs of vasospasm, all of whom
responded to elevation of blood pressure.
Koivisto et al. (68) prospectively examined the
question of endovascular versus surgical treatment of
acutely ruptured aneurysms (i.e., within 72 hours of
ictus) by randomly assigning 109 consecutive patients
to either modality. Clinical and neuropsychological
follow-up was performed at 3 and 12 months postpro-
cedure, MRI of the brain at 12 months, and follow-up
angiography after clipping for the surgical group and
at 3 and 12 months for the endovascular group. The
following conclusions emerged: (1) outcome was over-
whelmingly dependent on the severity of the clinical
presentation of the initial SAH, regardless of treatment
modality; (2) there were no significant differences in
outcome between the two groups on clinical or neuro-
psychological grounds, with no important clinical
improvement between months 3 and 12, but with
meaningful neuropsychological improvement during
that time; and (3) while there were no significant
differences in the rate of clinical vasospasm between
the groups, MRI showed more frequent ischemic
lesions in the territory of the ruptured aneurysm for
the surgical group than for the endovascular group.
A retrospective study of 327 patients who pre-
sented with SAH and who were treated with GDCs
(69) found no statistical difference in outcome when
patients were stratified according to time lag between
the ictus and the procedure. The authors thus recom-
mended treatment as early as possible to circumvent
rebleeding.
 Chapter 13: Endovascular Management of Intracranial Aneurysms
Cloft and Kallmes (70), in a meta-analysis, dem-
onstrated that the risk of endovascular intraproce-
dural aneurysmal perforation was significantly
higher in the setting of acutely ruptured aneurysms
(4.1%) than in cases of elective coiling (0.5%). The
associated risk of permanent neurologic morbidity or
death was significantly higher as well (38% vs. 29%,
respectively). Interestingly, the morbidity and mortal-
ity rate for perforations caused by coils (39%) was
similar to those caused by microcatheters (33%), while
perforations caused by microguidewires had no asso-
ciated morbidity or mortality. There was a tendency
toward higher morbidity and mortality among
patients receiving intraprocedural IV heparin than
among those not receiving heparin, but this did not
achieve statistical significance. However, in cases of
perforation, the investigators recommend reversal
of anticoagulation, placement of a ventriculostomy
(if not already in place), and use of an additional
microcatheter to complete the embolization, leaving
the perforating device in place in the interim.
Needless to say, in cases where the aneurysm
location makes surgical approach difficult or impossi-
ble, endovascular therapy may be the only viable
option. A retrospective study (71) of 150 basilar tip
aneurysms treated with GDCs revealed, after a mean
angiographic follow-up period of 9.8 months for
unruptured aneurysms and 13.7 months in cases of
rupture, a rebleed rate of 3.3% for the ruptured group
and 4.1% for the unruptured group, with permanent
deficits secondary to stroke of 5% and 9%, respectively,
and a periprocedural mortality rate of 2.7%. These rates
contrast with mortality rates of 23% in conservatively
managed ruptured basilar tip aneurysms and 12% in
unruptured cases over similar lengths of follow-up.
The authors conclude that endovascular therapy is
certainly warranted in cases of rupture, while appro-
priate management of cases of unruptured basilar tip
aneurysms still needs clarification.
Similarly, Tateshima et al. (72) reported their
single-center experience with 75 basilar tip aneurysms
treated with GDCs and found that immediately post-
procedure, 85.3% of the aneurysms were completely
occluded, 9.3% partially occluded, and 5.3% could not
be treated because of technical anatomic difficulties.
The procedure-related morbidity and mortality were
4.1% and 1.4%, respectively, and 91.3% of the patients
treated remained either neurologically intact or
unchanged from their state at presentation.
Johnston et al. (73) calculated total costs, in both
morbidity and financial terms, in comparing endovasc-
ularly treated versus surgically clipped aneurysms at
academic medical centers. They followed the rate of
adverse outcomes (defined as in-hospital deaths and
discharge from the hospital to a nursing home or
rehabilitation center), length of stay, and cost of hospi-
talization. They took into account the fact that the
endovascular patients occasionally required recathete-
rization and repeated treatment because of incomplete
aneurysm occlusion, while the surgical patients rarely
required follow-up treatment. The cost of endovascular
treatment was calculated as the sum of the costs for all
admissions for a given patient required to treat a given
249
aneurysm, and adverse outcomes for the endovascular
patients were tallied as the worst outcome associated
with any one of the endovascular procedures per-
formed to treat that aneurysm. Even so, the results
significantly favored endovascular therapy: the rates of
adverse outcomes were 18.5% for the surgical group
and 10.6% for the endovascular group, the rates of in-
house deaths were 2.3% and 0.4%, the lengths of stay
were 9.6 and 4.6 days, and the mean charges were
$43,000 and $30,000, respectively. These results are all
the more remarkable in that this was a cohort rather
than a randomized study and, as pointed out above,
during this era, patients directed to endovascular ther-
apy tend to be poor surgical candidates, either because
of concomitant systemic medical conditions or because
of surgically inaccessible aneurysms.
A similar, more recent comparison of neurologic
outcome (measured as change in Rankin scale) was
performed by Johnston et al. (74) for aneurysms that
were retrospectively judged by blinded neuroradiolo-
gists and neurosurgeons to be approachable via either
technique. Twenty-five percent of the surgically
treated group had a change in Rankin scale of 2 or
more (signifying significant disability), while only 8%
of the endovascular group did so, and again, total
length of stay and hospital charges were greater for
the surgical group (7.7 vs. 5 days, and $38,000 vs.
$33,400, respectively). Most importantly, at a mean
follow-up of 3.9 years postprocedure, 34% of the sur-
gically treated patients reported a persistent new def-
icit since treatment, while only 8% of the endovascular
group did so. Importantly, it was only after one year
that 50% of the surgical cohort reported returning to
their baseline condition, while for the endovascular
group the comparable elapsed time was 27 days.
RECURRENCE IN WIDE-NECKED ANEURYSMS:
TESTING THE ENDOSACCULAR APPROACH
Despite the encouraging results from ISAT and other
case series (75), the surprisingly low reported frequen-
cies of up-front aneurysm occlusion (7679) and the
prevalence of posttreatment recurrences (7681) among
coil-treated aneurysms have become serious obstacles
to the widespread acceptance of endovascular treat-
ment as definitive therapy. This is particularly (and
paradoxically) true in the case of large, complex aneur-
ysms for which the treatment was initially indicated.
Aneurysm recurrence following coiling has gen-
erally been thought to proceed through two mecha-
nisms: (1) recanalization (acute or delayed) of the
coiled aneurysm fundus, resulting from an underlying
instability of the intra-aneurysmal coil-thrombus com-
plex, and/or (2) progressive absolute aneurysm growth
from either an unsecured niche of an incompletely
coiled aneurysm or an intrinsic (initially occult) defi-
ciency in the wall of the perianeurysmal parent artery.
Such features as completeness of aneurysm lumen
obliteration, tightness of packing of the coils, aneurys-
mal geometry and location (e.g., dome-to-neck ratio of
at least 2 and location of the aneurysm away from high-
flow arterial bifurcation sites) are thought to be strongly
250 Orbach et al.
prognostic of long-term success (82). Nevertheless, there
have been reports of recurrent aneurysm with SAH; in a
notable example, 18 months posttreatment, at the site of
an unruptured aneurysm that was angiographically
occluded after coiling and that remained occluded at
six-month angiographic follow-up (83).
The extent of the problem, first suggested in
early reports (76), has since been elucidated in multi-
ple studies. Raymond et al. (81), in a retrospective
analysis of data collected from 466 patients with 501
aneurysms, observed a strong correlation between
aneurysm dimensions and neck size and the preva-
lence of posttreatment recurrence. Among 383 patients
with follow-up angiograms, recurrence, defined as
major by the authors, was found in 20.7% (at a mean
angiographic follow-up of 17 months). When analyzed
by aneurysm morphology, recurrence (of all degrees)
was observed in 50.6% of large aneurysms as opposed
to 21.3% of small aneurysms (<10 mm), and 52.3% of
wide-necked aneurysms (>4 mm) versus 23.7% of
aneurysms with small neck size.
More recently, a 2005 study reviewing long-term
follow-up (mean 36 months) on 705 patients with
ruptured aneurysms treated with GDCs (84) reported
a technical feasibility rate of 96.9%, with failures
related either to vessel tortuosity or to coil herniation
outside the aneurysm neck. Complete occlusion
(>99% of the volume) was achieved in 72% of cases,
subtotal (9599% embolization) in 25%, and incom-
plete (<95%) in 2.4%. For completely embolized
aneurysms, 72.4% remained stable, 10.5% showed a
small recurrence and were followed with MRA and effectiveness of the coil mass in promoting maturation
DSA, and 2.8% showed significant coil compaction
and recanalization and were retreated. For cases with
subtotal occlusion, 42.1% showed no change, 29.2%
had spontaneous thrombosis resulting in complete
occlusion, and 7.6% had significant recanalization
and were retreated. For patients with incomplete ini-
tial occlusion, 37.5% had repeat coiling to attempt
improvement, 31.3% had spontaneous improvement
from thrombosis, and 25% died. The only parameter
examined that was predictive of occlusion outcome
was the initial size of the aneurysm, with total occlusion
achieved in 74% of aneurysms smaller than 10 mm, and
50% in aneurysms larger than 15 mm.
In terms of the proximate postcoiling outcome,
Kole et al. (78) found 27% of aneurysms with large
remnants immediately after coiling. The same authors
further reported an increased remnant size in 19.1%
of patients with a mean angiographic follow-up of
18.2 months, 14.5% requiring aneurysm recoiling. This
last statistic is of interest because two deaths occurred
among the patients undergoing retreatment, illustrat-
ing an often-ignored source of risk to which patients
with unresolved aneurysms are exposed.
Ironically, our perception of incomplete treat-
ment or aneurysm recurrence after endosaccular coil
therapy has been partly obfuscated by the rapid
evolution and assimilation of new coil technologies
(3D coils, polymer- and hydrogel-coated coils, and
ultrasoft coils) (8588), liquid embolic agents (8992),
and adjunctive techniques (balloon remodeling) (9395),
each purported to improve treatment efficacy, whether
or not these new innovations actually contribute to a
more secure endovascular outcome. In a provocative
study examining the impact of endovascular advance-
ments during the decade following introduction of the
GDC, Murayama et al. (79) reported results from
11 years experience in 818 patients treated at Univer-
sity of California Los Angeles (UCLA). Analyses of
treatment outcomes were stratified by aneurysm mor-
phology and date of treatment. Angiographic results
from those who were treated in the first half of the
decade (19901995) were compared with those from
the second half (19962002), after modified specialty
coils and newer adjunctive techniques became avail-
able. The early group comprised 230 patients harbor-
ing 251 aneurysms, while the more recently treated
group represented 588 patients harboring 665 aneu-
rysms: 49.4% of the patients presented with acute SAH,
while 41.8% had unruptured aneurysms. Angio-
graphic follow-up ranged from three months to eight
years (mean 11 months). Ironically, despite the inter-
vening improvements in devices and technique, recur-
rence rates among the larger aneurysm subgroups
treated since 1996 [37.7% (large) to 52.9% (giant)]
were not statistically different from those in the first
half-decade [33.3% (large) to 63% (giant)]. Further-
more, recurrences were also found in 18.2% of small
wide-necked aneurysms for the years 1996 to 2002. These
results, unfortunately, did not capture the effects of
more recent innovations designed to improve volu-
metric packing of the aneurysm sac (with hydrogel-
coated coils or liquid embolic agents) or to increase the
of the intra-aneurysmal thrombus (with bioactive coat-
ings). However, subsequently publicized, unpublished
results from the Microvention-sponsored HEAL
(AANS-CNS Joint Section-ASITN 2005 Annual Meeting,
New Orleans, Louisiana, U.S.) and Boston Scientific
sponsored MATRIX-ACTIVE (American Society of
Neuroradiology, 2004 Annual Meeting, Seattle,
Washington, U.S.) trials, in addition to early published
reports of clinical experience with polyglycolic acid
lactide copolymer (PGLA)-coated coils (87), have been
less than wholly reassuring, implicating a potential
deficiency in coil-dependent endosaccular approaches
to the treatment of these aneurysm subtypes, at least in
terms of achieving a stable anatomic result. Addition-
ally, early experience in the MATRIX Registry seemed
to confirm the fundamental importance of the aneu-
rysmal coil mass (the density and completeness of coil
packing), and by implication its effect on intra-
aneurysmal blood flow to the ultimate recanalization
outcome, supporting the importance of a stable hemo-
static environment in enabling the bioinducible poten-
tial of the PGLA jacket.
CONDITIONS FAVORING SUCCESSFUL
ENDOVASCULAR ANEURYSM TREATMENT
Three conditions seem necessary for durable endosacc-
ular occlusion of cerebral aneurysms with coils.
(1) Effective hemostasis must be established through-
out the aneurysm and sustained over some critical
 Chapter 13: Endovascular Management of Intracranial Aneurysms
interval. (2) The thrombus formed within the aneurysm
as a result of coil-induced intra-aneurysmal hemostasis
must mature during this critical interval (ideally under-
going organization into a fibrointimal scar). (3) The
uniformity and stability of the coil-thrombus complex
at the aneurysm base must be biomechanically suffi-
cient to support neointimal overgrowth of the aneur-
ysm neck defect.
While these requirements are usually satisfied
during endosaccular coiling of the idealized small-
necked aneurysm (favorable neck/fundus ratio),
reconstruction of the larger aneurysm neck (which in
certain dysplastic aneurysms encompass >1808 of the
cross-sectional vessel circumference) (Fig. 1) is techni-
cally more challenging and frequently confounded by
inadequate coiling of the aneurysm base. This situa-
tion has led to the adoption of adjunctive methods
such as balloon remodeling and the complimentary
use of endoluminal devices for more robust reconstruc-
tion of the neck defect in such aneurysms (94101).
The long-term consequences of subtotal aneur-
ysm coiling have not been studied scientifically; how-
ever, they may be inferred from several single-center
(81) and multicenter (55,102) series, which suggest that
incomplete coiling of the aneurysm neck increases the
likelihood of recurrence and may be a factor in delayed
(Sluzewski, 2005) posttreatment rehemorrhage
estimated to range between 0.2% and 0.3% per year
for previously ruptured aneurysms treated with coils.
The collective factors responsible for recurrence
(103106), theoretically, can be divided into factors
operational in incompletely occluded aneurysms and
factors responsible for recanalization of aneurysms
initially occluded at the time of coil treatment. For
complex-neck, large, and giant aneurysms, recanaliza-
tions frequently result from unintentional or deliberate
undercoiling of the neck region and involve a sequence
of events leading to lysis and remodeling of incom-
pletely organized intra-aneurysmal thrombus and coil
compaction, with or without true continued growth of
the aneurysm. Once formed, the fate of the intra-
aneurysmal coil-thrombus complex depends on a num-
ber of factors, including the coagulative disposition of
the specific patient, the coil composition (i.e., surface
texture, coatings, and charge density), the complete-
ness of aneurysm packing, and, importantly, the
degree of sustained aneurysmal hemostasis. Although
coil packing density has been correlated anecdotally to
stable aneurysm occlusion, with bare metallic- or
polymer-coated coils, coil packing densities of treated
aneurysms usually are significantly less than 40% by
volume, even in ideally packed aneurysms (85). It is
therefore likely that the effectiveness of coils in treating
aneurysms is dependent in large part on the degree by
which intra-aneurysmal flow is reduced, and, corre-
spondingly, to the inherent stability of the intra-
aneurysmal coil-thrombus complex.
BALLOON REMODELING
In an effort to facilitate coil treatment of wide-necked
aneurysms, Moret et al. (18,94,107,108) developed a
method whereby a small balloon occlusion microcatheter
251
is intermittently inflated within the parent artery across
the aneurysm neck to provide structural support against
which to deploy coils within the aneurysm through a
second microcatheter positioned within the aneurysm
fundus. In providing this barrier at the aneurysm neck,
the inflated balloon allows successively deployed coils to
assume an increasingly stable conformation within the
aneurysm, while preventing their herniation into the
parent vessel. Flow is reestablished in the parent artery
after each balloon deflation (Fig. 6).
In a review of their experience, Moret et al. (94)
reported stable angiographic occlusion in 20 of 21
completely occluded broad-necked aneurysms (ante-
rior and posterior circulations) among patients with
at least four-month angiographic follow-up (mean,
13 months). These results approach those obtained
with small-necked aneurysms coiled directly. Further-
more, when analyzing common complications related
to the GDC technique (thromboembolic events, etc.),
these authors concluded that their complication rate
employing balloon-assisted coiling was no greater than
that experienced with primary (unassisted) GDC treat-
ment. Similar results have been reported by Malek et
al. (109), Lefkowitz et al. (93), and Nelson and Levy
(95), who demonstrated angiographic aneurysmal
occlusion at a mean follow-up of 19 months, in 17 of
20 patients who had undergone balloon-assisted embo-
lization of wide-necked aneurysms.
Although promising, several technical concerns
have arisen. The procedure may be performed via a
single groin site, employing a 6-Fr sheath (Shuttle,
Cook Inc., Bloomington, Indiana, U.S.) or a single 7- or
8-Fr guide catheter, or using two guide catheters
introduced through separate groin sites. This may
lead to increased frequency of groin complications,
particularly in centers employing a regimen of 24 to
48 hours of anticoagulation after coil treatment. While
groin sheaths may safely be left in place over the 24 to
48 hour posttreatment period that the patient is anti-
coagulated, several hemostatic devices are available to
facilitate early groin sheath removal and may be use-
ful to avoid complications of the groin puncture site in
patients who are anticoagulated or who are uncooper-
ative following the procedure and in whom it is
desirable to remove the sheath prior to normalization
of the partial thromboplastin time to avoid iliofemoral
vessel injury or extensive hemorrhage.
Additionally, the increased number of guide-
wires and microcatheters necessary for balloon-
assisted coiling potentially complicate the technique,
making vessel dissection, rupture, and thromboem-
bolic complication likelier. While intracranial balloon
angioplasty has been used extensively in the treatment
of vasospasm with acceptable complication rates
(110), inflation of the microballoon in the vicinity of
an aneurysm neck is known to be associated with
increased risk of vessel or aneurysm rupture. Precise
control of balloon placement and inflation is therefore
paramount in using this technique safely.
The duration of balloon inflation must be
matched with the distal collateral supply to the
occluded vascular territory to avoid the development
of cerebral ischemia during treatment of the aneurysm.
252 Orbach et al.

Figure 6 (A) Lateral DSA image of the LICA illustrating a large wide-necked ophthalmic segment aneurysm. (B, C) Unsubtracted
images during coiling of the aneurysm with balloon assistance, which facilitates curvilinear reconstruction of the anterosuperior vessel
wall across the neck deficiency, evident after balloon deflation (D); usually not possible in the absence of an assist balloon. (E)
Posttreatment angiography of the LICA confirms occlusion of the aneurysm. Abbreviation: LICA, left internal carotid artery.

In a retrospective review of 49 patients undergoing otherwise inaccessible aneurysms, such as retrograde

temporary occlusion of the MCA during aneurysm
surgery, Lavine et al. (111) concluded that temporary
occlusion times of 10 minutes or less were safely
tolerated in the majority of patients.
Additionally, the risk of delayed coil herniation
into the parent artery must be considered, particularly
in those cases in which coils placed subsequent to the
framing coil are deployed without further balloon
protection.
Finally, the risk of thromboembolism associated
either with temporary flow arrest in the parent artery
or with the increased exposed coil surface at the
aneurysm neck may require more aggressive antico-
agulation during and after the procedure.
ACHIEVING DENSE ANEURYSM PACKING:
ALTERNATIVES TO BALLOON REMODELING
Refinement and improvement of the armamentarium
for endovascular treatment of aneurysms proceed at a
rapid clip: bridging devices other than balloons have
found use in improving the effectiveness and safety of
aneurysm coil packing (112) and biologically active
materials are being incorporated into the surface of
the coils to promote healing and degree of occlusion
(68,85,88,113). Novel microcatheter approaches to
via a major communicating vessel (114) and the incor-
poration of 3D digital subtraction angiography in
the assessment of aneurysmal conformation (115),
have broadened the range of aneurysms that are
amenable to endovascular treatment.
Three-dimensional coil shapes may be useful in
this regard as well. A 2004 study (116) on the use of 3D
coils in the treatment of wide-necked (>4 mm) aneur-
ysms (excluding giant aneurysms) showed similar
success in achieving complete occlusion of narrow-
necked (72%) and wide-necked (68%) aneurysms, so
long as one or more 3D coil was used in first framing
the aneurysm. Moreover, of the 160 aneurysms coiled
using this technique, balloon remodeling was needed
in only two cases.
In terms of bioactive agents, Kallmes et al. (117),
in a murine model, showed increased fibroblast pro-
liferation and collagen formation in coils that had
been coated with fibroblasts containing multiple cop-
ies of the gene-encoding fibroblast growth factor
(FGF), as compared with control coils (at 14 and
35 days). Others (118) have pointed out that coated
coils may be an excellent means by which to deliver
targeted gene therapy aimed at preventing aneurysm
rupture, either by way of antibody-tethered viruses
expressing gene products that promote vascular
 Chapter 13: Endovascular Management of Intracranial Aneurysms
healing or by way of radiation-inducible promoters,
injected intravenously, being activated by radioactive
coils. Moreover, it has been demonstrated in a canine
model (119) that the implantation of radioactive (86)
P ions onto standard platinum coils inhibits recanal-
ization of coiled aneurysms, and clinical feasibility of
the technique has been suggested by a small clinical
trial (120). Clearly, questions about long-term stability
and potential adverse effects of such treatment remain
to be clarified.
A drastically different approach toward endo-
saccular aneurysm obliteration relies on the use of
liquid embolic agents (8992). Biophysical models
have demonstrated that coils fill only 30% to 40% of
the volume of aneurysms (121,122) [possibly increased
to as high as 73% with hydrogel-coated coils (85)],
and there may be residual flow even within tightly
packed aneurysms. Moreover, in recurrent aneur-
ysms, coils have been demonstrated to compact over
time, occupying less volume than when originally
placed. Liquid embolic agents theoretically permit
more efficient and complete endosaccular aneurysm
filling than is possible with coils. Several are under
active development, such as calcium alginate (123), a
nontoxic emulsifier and Onyx.
Onyx is a liquid embolic agent originally devel-
oped for use in AVMs. The authors of the CAMEO
study (90) reported that with Onyx they achieved a
higher-occlusion rate, better clinical outcome, and rate
of adverse effects comparable to more traditional endo-
vascular techniques in treating large or giant aneur-
ysms. This was corroborated in a 2005 study of Onyx in
wide-necked large or giant carotid aneurysms (124),
where total occlusion was achieved in 81% of aneur-
ysms and was maintained at follow-up angiography in
91%. Complications included two stenoses and one
occlusion of the involved parent internal carotid artery.
Four cases had presented with cranial neuropathy sec-
ondary to mass effect, and two of these patients
improved following treatment. Of the initially asymp-
tomatic patients, 14/15 remained so at follow-up, while
one experienced a transient ischemic attack.
A recent report (125) of chemical meningitis in
two patients following placement of both hydrogel
and Matrix coils raises the specter of an exuberant
inflammatory response to this particular combination.
Both patients responded well to immunomodulation
with steroids.
SURGERY FOLLOWING PARTIAL
EMBOLIZATION AND VICE VERSA
Although technically challenging, it is possible to
surgically clip aneurysms that have been partially
coiled. In a recent study (126), patients with SAH had
initially undergone endovascular embolization after
presentation with Hunt and Hess grade III and IV
hemorrhages or medical comorbidities that precluded
surgery. The average time interval between emboliza-
tion and surgery was 11 months. Patients had intra-
operative angiography, and all were followed with
serial contrast-enhanced MRA. All aneurysms were
found at surgery to have some coils extruded through
253
the aneurysm wall into the extravascular space, and all
were associated with a translucent membrane that
made removal impossible; as a result, the coils were
left in place. Eighteen patients underwent attempted
clipping, in 15 of whom complete aneurysm exclusion
was successful, while 3 patients required aneurysm
wrapping as an alternative. The authors recommend
a dome-to-neck ratio of at least 2 to make postemboli-
zation clipping feasible. Others have reported similar
results (127,128).
However, balloon remodeling and/or stenting
as a second treatment after coil embolization is pref-
erable to surgery, if possible. A report (129) on the
morbidity and success rate of repeat coiling for aneur-
ysms found to be incompletely embolized at six-
month follow-up showed no complications, and com-
plete occlusion was achieved in 76% of cases.
Conversely, others (130132) have reported on
the feasibility of endovascular treatment of an aneur-
ysm remnant after partial surgical clipping. Repeat
surgery is often technically difficult and poses signif-
icant morbidity and mortality risk because of peria-
neurysmal scarring (133). In this setting, endovascular
occlusion may represent a potentially valuable option.
ENDOLUMINAL RECONSTRUCTION: THE
EMERGENCE OF ADJUNCTIVE STENT-
SUPPORTED COIL EMBOLIZATION OF
CEREBRAL ANEURYSMS
The feasibility of a combined endoluminal-endosaccular
aneurysm treatment was first established in a dog
aneurysm model (100) and, subsequently, confirmed
by several case reports (99,101) and small clinical series
(96,97), documenting results initially with balloon-
expandable stainless steel stents and following the intro-
duction of Neuroform (Boston Scientific-Target Thera-
peutics, Fremont, CA) and Leo (Balt, Montmorency,
France), with self-expanding microstents. A mathemat-
ical model (134) demonstrated the drastic change in
intra-aneurysmal flow pattern that followed placement
of an asymmetric stent, with inflow dramatically
reduced in comparison to the pattern seen following
coil embolization.
The rationale for adjunctive stenting in the treat-
ment of wide-necked cerebral aneurysms relies on
three effects.
(1) The uncoupling of momentum exchange between the
parent artery and aneurysm. This effect enhances the
flow disruptive influence of the intra-aneurysmal
coil mass, diminishing intra-aneurysmal flow and
increasing the mean circulation time through the
aneurysm fundus (135138). The net effect is
the induction of more profound hemostasis within
the aneurysm, contributing hypothetically to
intra-aneurysmal conditions in which recanaliza-
tion is less likely.
(2) The subintimal incorporation of the stent into the
parent vessel wall. The mural integration of the
stent into the parent artery (Fig. 2) modifies
the viscoelastic properties of the perianeurysmal
vascular segment, reinforcing the parent artery at
254 Orbach et al.
the neck margins and potentially reducing the
likelihood of recurrent aneurysm growth from
the neck region.
(3) Neck-bridging barrier effects. These effects create a
structural boundary across the aneurysm neck.
The stent-imposed scaffolding facilitates more
complete endosaccular treatment, together with
neck region coils, provides a more organized
substrate to support neointimal growth over the
aneurysm neck.
Many groups deploy a stent over the aneurysm
neck and then introduce the microcatheter through the
stent interstices into the aneurysm sac to place coils,
which is in accordance with advantage 3 listed above.
However, it should be noted that advantages 1 and 2
above can be achieved even if the stent is deployed
after aneurysm packing by coils. This approach may be
particularly valuable in the setting of SAH, where
pretreatment with antiplatelet agents is not desirable.
The strategy in these cases, therefore, is to secure the
aneurysm acutely and, subsequently, deploy a stent
several weeks later, following adequate premedication.
NEUROFORM: CLINICAL RESULTS
While early experience with stent-supported coil
endosaccular treatment of wide-necked aneurysms
has been promising (96,97,139), long-term angio-
graphic evaluation of the synergy expected from
such combined endovascular therapy is lacking.
Examination of the existing literature on the topic
reveals significant variation in the reporting of out-
come milestones and imaging follow-up in addition to
the wide variety of cardiac stents used prior to the
introduction of the flexible self-expanding Neuroform
(Boston Scientific) and Leo (Balt) devices.
In a review of 50 patients with wide-necked cere-
bral aneurysms undergoing attempted Neuroform-
supported coiling, Lylyk et al. (140) reported immediate
occlusion rates between 84.6% and 87.5%, depending on
whether the stent preceded coiling or was placed after
aneurysm coiling, respectively. Their results are partic-
ularly encouraging when compared to the immediate
occlusion rate of 40.4% for large aneurysms reported by
Murayama et al. (79), and in line with initial occlusion
rates reported for balloon remodeling techniques in
other series of broad-necked aneurysms (94,95).
Fiorella et al. (97) reported, in their 20-month
prospective study of 61 aneurysms undergoing
stent-supported coiling with Neuroform, complete or
near complete aneurysm occlusion in 28 (45.9%) and
partial (presumably analogous to subtotal) occlusion in
33 (54%) of patients. Follow-up angiography or MRA
was available at a median reevaluation period of
four months. This series included a higher percentage
of smaller aneurysms with small necks but unfavorable
neck/fundus ratios and a larger number of ruptured
aneurysms for which they advocated a conservative,
staged approach in which the aneurysm is deliberately
undercoiled during the initial therapeutic setting.
Nelson et al. (141) recently reported their expe-
rience with Neuroform-supported endosaccular
treatment of select complex wide-necked aneurysms
and assessed the anatomic stability of this combined
endoluminal-endosaccular treatment over medium-
term clinical and angiographic follow-up in 16 patients.
The cohort included one giant aneurysm (>25 mm
diameter) and 15 large aneurysms (ranging in size
from 11 to 22 mm), all of which exhibited neck sizes
equaling or exceeding 7 mm in linear dimension along
the parent vessel (ranging from 7 to 14 mm). There
were no treatment-related deaths or clinically evident
neurologic complications. A single technical complica-
tion occurred involving transient nonocclusive stent-
associated thrombus, which resolved without clinical
sequelae after the administration of intra-arterial abcix-
imab. Follow-up angiography was between 11 and
24 months posttreatment. With the exception of three
patients, all treated aneurysms were occluded at angio-
graphic reevaluation. Clinical follow-up averaged
29 months. All patients had excellent clinical outcomes
with the exception of two patients. The first experi-
enced recurrence of third and sixth nerve palsies, while
the second had minor residual short-term memory
deficit related to an index SAH, which prevented full-
time return to work. There was one suicide-related
death 22 months after treatment.
ADVANCED STENT TECHNIQUES
For complex aneurysms, where the parent vessel
aneurysm interface cannot be sufficiently resolved
by 2D fluoroscopy/angiography, staged approaches
using balloon remodeling to coil the aneurysm prior
to stent placement may provide more confidence in
coiling neck domains overlapping the parent vessel
(Fig. 7). Balloon remodeling will likely continue to be
useful in facilitating more complete initial occlusion in
complex ruptured aneurysms, permitting later staged
stent placement once antiplatelet agents can be given
safely.
Overlapping stents may be useful to increase
metallic coverage over the aneurysmparent vessel
interface. By constraining full expansion of the inter-
nal stent through oversizing, one further increases the
mesh coverage throughout the region of stent overlap
beyond that anticipated because of the summation of
struts from like-sized stents. The additional stent cov-
erage further enhances the hemodynamic modifica-
tion of the intra-aneurysmal circulation.
A technique being adopted in bifurcation aneur-
ysms is the use of the Y-stent configuration (142),
whereby a Neuroform stent is first placed across one
arm of the bifurcation and then a second stent is
telescoped through the interstices of the first stent,
into the second arm of the bifurcation. The aneurysm
is then coiled through the interstices of the double-
stent scaffold.
STENT COMPLICATIONS
Use of stents and other adjuncts to coiling has been
reported to increase the risk of complications. A recent
large study examining follow-up from 1811
 Chapter 13: Endovascular Management of Intracranial Aneurysms 255

Figure 7 (A) Images from an intracranial CT angiogram demonstrating a fusiform mid-basilar artery aneurysm (patient #1). (B) Frontal
and lateral oblique angiographic images depicting the aneurysm. (C) The aneurysm was treated with GDC under balloon remodeling
conditions (4 mm  20 mm balloon), following which (D) overlapping 4.0 mm  20 mm (outside) and 4.5 mm  20 mm (inside) Neuroform
stents were deployed across the aneurysm neck. (E) Immediate post-treatment angiography (lateral oblique projection) disclosed minor
persistent contrast opacification throughout the intra-aneurismal coil interstices (white arrow) which is not apparent on the 12 month
(F) follow-up angiogram (frontal and lateral views). (G) Sequential source images through the aneurismal segment from an MRA obtained
25 months after treatment, illustrating cylindrical reconstruction of the parent basilar artery (small white arrows: susceptibility artifact
related to the intra-aneurismal coil mass).

aneurysms coiled at a single center, including both
ruptured and unruptured aneurysms (143), reported
an overall complication rate of 17.7%. Large aneurysm
diameter and neck-to-dome ratio were associated with
a higher complication rate than was the case for small,
narrow-necked aneurysms. Use of modified tech-
nique (balloon remodeling or stenting) resulted in an
increase in the complication rate from 15.7% to 20%.
Of course, it would be expected that aneurysms
requiring the use of the modified technique were
larger and more complex than others, perhaps
explaining some of the increases in complications.
The Barrow group (144), in their initial report of
their Neuroform experience, described several
types of complications. In two cases, the stent
migrated away from its intended location after micro-
catheter manipulations, in one case migrating into the
aneurysm lumen. In one case, GDC coil stretching
occurred followed by coil fracture, as the coils were
deployed through the stent interstices, likely because
of friction between the coil and the stent matrix. In all
cases in which stenting and coiling were at the same
sitting, the coils were successfully passed through the
stent interstices. In a single case in which two over-
lapping stents were placed, in which transstent coiling
was attempted two weeks after stent deployment,
only the microwire and not the microcatheter could
be passed through the interstices. This group had
256 Orbach et al.
reported (144) technical problems involving the stent
stabilizer that have been resolved in later-generation
Neuroforms.
Additional concerns arising when stents are
placed within the intracranial circulation include the
potential for perforator occlusion [Lopes, 2003 (41)]
and delayed in-stent stenosis (145). Fiorella (Congress
of Neurological Surgeons 2005 Annual Meeting, Bos-
ton, Massachusetts, U.S.) and Woo (WFITN 2005
Annual Meeting, Venice, Italy) have reported, from
the combined experiences at the Barrow Neurologic
Institute and Cleveland Clinic, several isolated cases
of Neuroform-associated delayed in-stent stenosis
found on follow-up angiography to have resolved
spontaneously. These findings implicate a dynamic
series of local histovascular events set in motion
by stent implantation and its subsequent subintimal
integration into the vessel wall (some of which may be
important in mediating aneurysm healing).
THROMBOEMBOLISM
Thromboembolic complications of endovascular aneur-
ysm treatments may be attributed to multiple factors,
which deserve particular consideration when selecting
patients for stent-supported coil treatment. Attention
should be given to (1) the inherent thrombogenicity of
the devices; (2) specific patient factors such as comor-
bidities (age, diabetes, etc.), coagulopathic states, and
resistance to antiplatelet drugs; (3) procedure-related
factors, such as the duration and complexity of the
procedure, timing and dosing of the antiplatelet-
anticoagulant regimen, mechanical compromise of the
parent vessel lumen (either from encroachment of the
coil mass or malapposition of the stent), dislodgement
of existing intra-aneurysmal thrombus, or perianeur-
ysmal injury of the parent vessel (by balloon remodel-
ing or stent deployment); and (4) attributes of the lesion
and its microenvironment contributing to thromboemb-
olism, such as the vessel size, aneurysm morphology,
local platelet activation, and the hemodynamic charac-
teristics in the vicinity of the aneurysm.
The prevalence of thrombotic events in coil-
treated aneurysms has been estimated to range from
2.5% to 61% depending on the individual case series
cited and the method of surveillance employed,
with permanent deficits ranging from 2.5% to 5.5%
(146148). Soeda et al. (148), using diffusion MR sur-
veillance, noted that in 73% of cases in which balloon
remodeling was used, there was a diffusion-positive
lesion, although most were clinically silent; the inci-
dence of diffusion-positive lesions was similarly high
in cases of aneurysms with wide necks. Interestingly,
78% of the diffusion-positive lesions in the posterior
fossa were in brain parenchyma whose arterial supply
lay proximal to the aneurysms, potentially implicating
catheter and wire manipulation rather than aneurys-
mal thrombus as the etiology.
Four stent-related thrombotic events (2 clinically
consequential) were reported by Fiorella et al. (144) in
their series of 21 Neuroform-treated aneurysms in
19 patients. Three of their four events occurred during
treatment of acutely ruptured aneurysms without
antiplatelet pretreatment, further emphasizing the
inherent thrombogenic hazard of primary stenting.
The investigators felt that overlapping stents were
significantly more thrombogenic than single stents,
and as a result, they add treatment with aspirin for
24 hours following stent placement to their normal
antiplatelet regimen with clopidogrel in cases of stent
overlap. Benitez et al. (96) described 4 thrombotic
events (3 stent related) among their Neuroform series
of 49 aneurysms in 48 patients. Nelson et al. (141)
reported on a patient harboring a large basilar apex
aneurysm requiring Y-stent reconstruction of the neck
prior to aneurysm coiling, who developed nonocclu-
sive in-stent thrombus within the left P1 segment
despite what was felt to be adequate antiplatelet
coverage.
CONCLUSIONS
Early experience with stent-supported coil emboliza-
tion of cerebral aneurysms has engendered signifi-
cant interest in endoluminal solutions for cerebral
aneurysms. Available devices have primarily been
used within the context of increasing the effective-
ness of existing coil-based endosaccular approaches.
For how long this complementary therapeutic
approach will evolve before being supplanted by
more sophisticated combined or stand-alone endo-
saccular and endoluminal devices is uncertain. How-
ever, it is clear that stent-supported endosaccular
approaches represent potentially promising endovas-
cular solutions to that set of complex aneurysms for
which it was hoped the GDC would provide safe
definitive therapy.
Combined surgical and endovascular approaches
to very complex aneurysms have been successfully
reported (149152), and this multipronged approach
will likely yield results in complex cases superior to
that which might have been achievable through the use
of either technique in isolation.
A promising potential avenue for endovascular
treatment of aneurysms is the use of covered stents or
stent grafts, which perhaps best encapsulates the con-
cept of luminal reconstruction. Several case reports
and one series of patients (153) with internal carotid
aneurysms proximal to the level of the supraclinoid
segment have been published, with excellent results
and low morbidity. Significant technical hurdles
remain, chiefly involving the rigidity of the coronary-
covered stents now in use and the inability to navigate
them distally into the tortuous cerebral vasculature.
Additionally, long-term patency rates remain to be
determined, with the potential development of long-
term delayed stenosis, a known complication of coro-
nary use.
A recent study detailing the first rigorous very
long-term follow-up on a cohort of patients with
intracranial aneurysms that were treated surgically
(154) makes clear that the presence of cerebral aneur-
ysms is not an isolated phenomenon but rather rep-
resents a manifestation of a widespread vasculopathy.
 Chapter 13: Endovascular Management of Intracranial Aneurysms
At follow-up angiography of 140 aneurysms in
112 patients at an average of 9.3 years postoperatively,
2.9% of the clipped aneurysms were found to have
regrown (with an annual risk of regrowth of 0.26%),
while formation of de novo aneurysms was seen in 8%
of patients (with an annual risk of de novo formation
of 0.89%). The majority of patients who developed
SAH did so over nine years after surgery, and the
cumulative rate of aneurysm recurrence was approx-
imately 10% at nine years. Patients with multiple
aneurysms were no more likely than those with single
aneurysms to have recurrences or de novo aneurysms,
nor was gender a factor. The authors thus propose
that even in the setting of aneurysms considered to be
fully treatable, where technically unassailable surgical
clipping has taken place, repeat angiography 9 to
10 years postoperatively might be a reasonable diag-
nostic procedure.
Other studies (155) have shown that patients
with completely clipped, unruptured asymptomatic
aneurysms continue to have a higher mortality rate
than age-matched cohorts from the general popula-
tion, for up to 10 years of follow-up; for a 52-year-old
cohort, survival at 10 years was 91% in the general
population and 76% in the clipped cohort. Thus,
patients with aneurysms remain vulnerable, perhaps
throughout their lives, to the development of other
aneurysms, and lifelong surveillance is necessary.
Clearly, much work remains in elucidating the
biological mechanisms underlying aneurysm forma-
tion. This would allow us to aim our treatment at
these foundational causes rather than coping with treat-
ments aimed largely at improving vascular morphol-
ogy, as we do today.
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 14

Endovascular Treatment of Post-Subarachnoid

Hemorrhage Vasospasm

Jonathan L. Brisman
Department of Cerebrovascular and Endovascular Neurosurgery,
Winthrop University Hospital, Mineola, Long Island, New York, U.S.A.
David W. Newell and Joseph M. Eskridge
Department of Neurosurgery; Department of Interventional Neuroradiology,
Seattle Neuroscience Institute, Seattle, Washington, U.S.A.

INTRODUCTION DINDs in some patients. Some patients, however,

Endovascular therapy to treat symptomatic vaso-
spasm after aneurysmal subarachnoid hemorrhage
(aSAH) has become a mainstay in many centers. Cere-
bral vasospasm, defined as reversible vasoconstriction
of the intracranial vasculature, is found in approxi-
mately 30% to 70% of patients after aSAH, although
perhaps only one-third to one-half of these patients
will develop symptoms and/or delayed ischemic
neurologic deficits (DINDs). DINDs remain the lead-
ing cause of stroke, morbidity, and mortality after
aSAH (1). The Fisher grade (Table 1) (2), scoring the
amount of blood seen on the initial head computed
tomography (CT) scan, remains a good predictor of
the severity of vasospasm to be anticipated and the
incidence of CT demonstrable infarction and associ-
ated morbidity and mortality. Whether patients pre-
senting with aSAH are more likely to develop
vasospasm, if treated by endovascular coiling versus
craniotomy and clipping, is a matter of recent debate
with evidence supporting both claims (35) and no
prospective study as of yet performed.
Medical therapy, including the administration of
nimodipine for 21 days post bleed, regardless of the
presence of vasospasm, and triple-H (hypervole- gered by the coating of the vessels with the break-
mia, hypertension, and hemodilution) therapy once
vasospasm has been identified have improved out-
comes after aSAH and averted vasospasm-induced
Table 1 Fishers Grade
Grade 1 No detectable blood on CT
Grade 2 Diffuse think SAH on CT with vertical layers <1-mm
thick
Grade 3 Local clot or thick SAH with vertical layers >1-mm
thick
Grade 4 Intracerebral or intraventricular blood without
findings of a grade 3
Abbreviations: CT, computed tomography; SAH, subarachnoid
hemorrhage.
will suffer devastating cerebral ischemia despite
these efforts. Neurointerventional techniques, includ-
ing intra-arterial administration of vasodilators such
as papaverine and transluminal balloon angioplasty
(TBA), have gained good results and have emerged as
a more aggressive approach for such patients (6).
These endovascular techniques (intra-arterial infusion
of medication and angioplasty) have their own asso-
ciated risks and benefits, and controversy exists over
the best method (7). At what point to intervene with
endovascular treatment has also been controversial
with some waiting until aggressive maximal medical
therapy has failed and others advocating prophylactic
balloon angioplasty in patients at high risk of devel-
oping symptomatic vasospasm (8,9).
PATHOPHYSIOLOGY
Critical to an understanding of the endovascular
approach to vasospasm is a working knowledge of
the proposed mechanism leading to vasoconstriction.
The exact etiology remains unknown. Causation is
likely multifactorial, with the process somehow trig-
down products of blood, such as oxyhemoglobin, and
the release of factors including serotonin, angiotensin,
prostaglandins, and thromboxane. Free radicals gen-
erated in the blood vessel wall are also believed to
play a major role in causing vasospasm.
Both vascular smooth muscle cells and endothe-
lium mediate cerebral vascular autoregulation, a pro-
cess whereby the brain attempts to maintain adequate
blood flow despite varying alterations in blood pres-
sure. Vasoconstriction is the result of smooth muscle
cell contractility, which is a calcium-dependent func-
tion. The counterpart to vasoconstriction is vasodila-
tation, a process influenced by the endothelium and
its production of substances such as nitric oxide. In
essence, vasospasm seems to be the result of both a
264 Brisman et al.
heightened vasoconstriction by the smooth muscle
cells and a decreased vasodilatation, which is perhaps
the result of diminished nitric oxide activity and
increased endothelin activity. Histologic response of
the blood vessels to a prolonged exposure to blood
components has been documented and includes thick-
ening of the media, intimal edema, subintimal cellular
proliferation with muscle cells and fibroblasts, throm-
bus formation, and ultimately necrosis and fibrosis.
HISTORICAL ASPECTS
In 1984, Zubkov et al. published the first report of
balloon angioplasty to reverse angiographic vasospasm
caused by aSAH with resultant clinical improvement
(10). Although, earlier reports had described the endo-
vascular infusion of vasodilators for vasospasm, these
techniques had not been incorporated into routine clin-
ical usage. As endovascular technology developed,
softer silicone balloons and newer microcatheters per-
mitted the more widespread use of these devices by
interventional neuroradiologists who were already
employing such devices to treat aneurysms and intra-
cranial vascular malformations. In 1989, two groups in
North America fueled the mainstream application of
these techniques with promising results by treating
vasospasm via the endovascular route (11,12). Other
reports followed and the instillation of intra-arterial
papaverine (IAP) locally at the site of intracranial vaso-
spasm gained popularity for some time. IAP, however,
was found to be associated with multiple side effects
and its action was found to be short-lived. This dissat-
isfaction led to the experimental use of other selectively
infused vasodilators, such as nicardipine, verapamil,
and milrinone, and paved the way for the growth of
transluminal angioplasty as a first-line therapy for
refractory vasospasm (13,14).
DIAGNOSIS AND MEDICAL MANAGEMENT
Cerebral vasospasm generally occurs between days 3
and 12 after aSAH, with a peak incidence on days 6 to
8 (1,15). The condition is marked by blood vessel
narrowing at the base of the brain in the large vessels
of and near the circle of Willis. Distal vasospasm may
also be seen, but less commonly so. The diagnosis of
cerebral vasospasm is made based on the clinical
condition of the patient in concert with a series of
ancillary tests. The importance of distinguishing
between angiographic or radiologic vasospasm and
clinically symptomatic vasospasm cannot be under-
scored enough, as the latter is treated much more
aggressively and the risks of endovascular therapy
are usually higher than with medical therapy alone.
An estimated one-third to one-half of all patients who
develop angiographic vasospasm will not develop
symptoms (15,16). When cerebral blood flow (CBF) is
greatly reduced and compensatory mechanisms, such
as autoregulation, collateral flow, and increased oxygen
extraction, are exhausted, clinically symptomatic ische-
mia and infarction may develop (15).
The Fisher four point grading scale (Table 1) has
been shown to be a good prognostic indicator for the
development of vasospasm, but the correlation is not
exact and all patients with aSAH should be monitored
carefully for the development of vasospasm (2,17).
Any patient who has suffered aSAH and who devel-
ops a new focal neurologic deficit or decrease in level
of arousal should be strongly considered to have
vasospasm, particularly once other causes such as
metabolic derangements, aneurysmal rebleeding,
and hydrocephalus have been ruled out. Frequently,
these conditions may coexist or such symptoms may
be difficult to detect in patients who present in poor
clinical grade, and it may therefore be wise to assume
that symptomatic vasospasm is present until proven
contrary.
We use transcranial Doppler (TCD) velocities,
obtained daily in all patients with aSAH, to detect and
monitor the progress of vasospasm (Fig. 1). Mean
velocities are recorded in all vascular territories and
measured in cm/sec. Mild vasospasm as detected by
TCDs is responded to with permissive hypertension
(allowing the patients blood pressure to rise on its
own and withdrawing the patients usual antihyper-
tensive regimen, if one exists) initially and artificial
hypertensive therapy if the TCD velocities rise into the
moderate to severe range (1,15,17,18). The second
component of triple-H therapy, hypervolemia, is
important in that it facilitates the use of pressor agents
to maintain the blood pressure within the desired
range. Therefore, patients experiencing incremental
rise in TCD velocities are hydrated with saline and
albumin to achieve a central venous pressure of 8 to 12
mm Hg. Swan-Ganz catheters are routinely used in
patients with significant cardiac histories; a cardiology
consult is prudent to assist with the fluid management
at this point.
If the patient remains neurologically stable, TCD
velocity alterations are treated with medical therapy
alone and then gradually tapered in response to
decreasing TCD velocities. A baseline single-photon
emission computerized tomography (SPECT) is
obtained on admission, and may be repeated in
patients who deteriorate, to decipher between cerebral
ischemia and other causes for the clinical decline.
When the significance of the TCD results are in ques-
tion, computed tomographic angiography and at
times diagnostic angiography are often employed,
particularly if the confirmation or repudiation of vaso-
spasm would change the degree or duration of the
therapy employed (15).
ENDOVASCULAR THERAPY
Intra-arterial Antispasmodics
Papaverine
Papaverine, a benzylisoquinoline alkaloid and a
potent smooth muscle relaxant, is believed to act by
the inhibition of phosphodiesterase activity in smooth
muscle cells (15). First used to treat cerebral vaso-
spasm in 1992, papaverine has been demonstrated
to reproducibly result in vasodilatation in both
 Chapter 14: Endovascular Treatment of Post-Subarachnoid Hemorrhage Vasospasm 265

Figure 1 TCD velocities accurately predict angiographic vasospasm. Anteroposterior left ICA angiograms on admission (left ) and
several days after aSAH shows A1 and M1 segment severe stenosis (long arrows) on day 5, which correlates with markedly elevated
TCD velocities (in the severe vasospasm range). Abbreviations: TCD, transcranial Doppler; ICA, internal carotid artery; aSAH,
aneurysmal subarachnoid hemorrhage.

experimental animal models (19,20) and clinical prac-
tice (2123). Perhaps the largest experience in endo-
vascular management of aSAH-induced vasospasm
has been with this agent (21,2326).
Administration of IAP is technically straightfor-
ward. Once angiography documents the degree and
location of vasospasm, a microcatheter is navigated
into the spastic vessels for the anterior circulation
and just proximal to the area of spasm in the posterior
circulation. Although dosage recommendations vary
and should be based somewhat on the degree of vaso-
spasm encountered, administration of 100 to 300 mg of
the drug diluted in normal saline over 30 to 60 minutes
is standard. This procedure and dosage may be repeated
if different territories are involved (22,26). Because of its
short duration of action, repeat procedures are often
necessary (14.842% in three reports) (7,25,27).
Reported clinical success with papaverine has,
like the other endovascular approaches to vasospasm,
been variable. Reported angiographic response is
quite high with success in various studies seen any-
where from 57% to 90% of the time (2123). In one
study that tried to quantify blood vessel responsive-
ness on the basis of angiography, the authors found an
average increase in vessel diameter of 26.5% in
34 patients undergoing 81 treatments (21).
The success of papaverine has also been docu-
mented using indirect methods quantifying the
increase in vessel diameter and CBF. Studies using
TCD ultrasound, Xenon 133, and SPECT have each
lent supporting evidence that intra-arterially admin-
istered papaverine relieves vasospasm with resultant
augmentation of blood flow (7,23). Polin et al. studied
the effect of intra-arterially administered papaverine
using TCD examinations on the day before and after
treatment. They found that 41% of patients displayed
greater than 20 cm/sec improvement in vasospasm
parameters, with six individuals showing more than
50 cm/sec change (24). In a study comparing IAP to
TBA, we showed that TCD velocities measured in the
internal carotid artery (ICA) and middle cerebral
arteries (MCAs) reliably showed vasodilatation after
IAP (7). SPECT scanning in the same study showed
increased perfusion in 31% of 37 patients in whom this
test was performed after IAP (7). Oskouian et al. used
TCD velocities to compare the vasodilatation seen
after IAP versus that observed with a combination of
TBA and IAP (28).
Fandino et al., after studying jugular bulb
venous oxygen saturation (SvjO2) and arteriovenous
differences in lactate in 10 patients before and after
IAP, demonstrated that IAP improved global perfu-
sion. All 10 patients had an early improvement in
neurologic function, nine of whom had improvement
in the SvjO2; interestingly, no significant difference in
the lactate was observed (29). In another study,
researchers implanted thermal diffusion microprobes
into the white matter of affected vascular territories in
266 Brisman et al.
eight patients with vasospasm. IAP resulted in a sig-
nificant improvement in the CBF, with the increase
being proportional to the degree of vasospasm and
hypoperfusion prior to treatment (30). Hoh et al.
conducted a literature review looking at the improve-
ment in CBF after IAP and found an increase in CBF in
60% of patients and in 31% of vascular territories
treated (16).
Despite the success of IAP at reversing vaso-
spasm, its use has been significantly hampered by the
fact that the results appear to be temporary in most
cases (7,21). Recurrent vasospasm with persistent
neurologic deficits prompts repeat endovascular
instillations. In one study reviewing the collective
literature on 401 patients undergoing IAP for vaso-
spasm, Hoh and Ogilvy found a total of 663 treat-
ments or an average of 1.7 intra-arterial sessions per
patient (16). This result is similar to the observations
of TCD velocities before and after IAP (7). While we
detected an average improvement in TCD velocity of
20% after papaverine infusion, these levels returned to
baseline one day later (7). These findings correlate
well with the study by Vajkoczy et al. in which CBF
was found to return to pretreatment levels after just
three hours (30). And although angiographic reversal
of vasospasm is often accompanied by clinical
improvement, this is not necessarily the result. In
one study, angiographic success was demonstrated
in 78% of patients while neurologic improvement
was evident in only 26% of cases (31). Clinical
improvement was found in 148 out of 348 patients
(43%) in one systematic review of the literature on IAP
(16). Timing of IAP relative to development of symp-
toms appears to be important, with patients in whom
symptoms have been present for a longer time appear-
ing less likely to respond (15).
Numerous complications related to IAP have
been described, with systemic hypotension and
increased intracranial pressure (ICP) being the most
common and the most serious. Fortunately, both of
these adverse side effects seem to be related to the rate
of infusion and therefore can be minimized with care-
ful attention to how quickly the drug is administered
(32). Frequent communication with the anesthesiolo-
gist and a heightened attention to the blood pressure
and ICP (when such monitoring is present) can avoid
serious complications. Systemic hypotension and/or
increased ICP can be devastating to a patient with
aSAH, in whom compromised cerebral perfusion
because of vasospasm or increased ICP from hydro-
cephalus or brain swelling make even small fluctua-
tions in the cerebral perfusion pressure dangerous.
Additional, but less commonly reported side effects
of IAP include pupillary dilatation (33), aneurysm
perforation (33), tachycardia, respiratory depression
(34), exacerbation of vasospasm (35,36), seizures (37),
and severe neurologic deterioration associated with
gray-matter destruction seen on MRI (15,16,38).
Given the lack of sustained effect of papaverine and
the host of potential side effects, many have moved
away from IAP as a first-line therapy for medically
refractory vasospasm. Its use remains paramount for
patients with small vessel vasospasm not amenable to
balloon angioplasty and to temporarily open blood
vessels to allow microcatheter navigation beyond the
area of stricture to permit more definitive therapies
(i.e., balloon angioplasty or aneurysm coiling) (15,31).
Nicardipine, Verapamil, and Milrinone
Because of the myriad of side effects of IAP and its
short-acting nature, some have explored the intra-
arterial administration of two additional calcium
channel blockers (verapamil and nicardipine) and
one phosphodiesterase inhibitor (milrinone) to treat
medically refractory vasospasm (13,14,39,40). Intra-
arterial nicardipine (0.56 mg/vessel) resulted in sig-
nificant improvement in angiographic vessel caliber
and TCD velocities in 18 patients (44 vessels) thus
treated. These radiographic results were accompanied
by clinical improvement in eight patients (42%), with
only one instance of transient elevation of ICP and no
other adverse events (13). In another study, intra-
arterial verapamil was administered to treat vasospasm
after SAH in 29 patients. Intra-arterial verapamil was
successfully and safely employed in one study in
which 10 patients were evaluated angiographically
and clinically. An average dose of 3 mg/patient
resulted in successful angiographic response in all
10 patients with an average vessel dilatation of 44
9%;
only 6 of these 10 patients, however, had intra-arterial
verapamil as the sole endovascular therapy. When intra-
arterial verapamil was used as the sole antispasmodic,
5 out of 17 (29.4%) patients showed clinical improvement
treated with intra-arterial verapamil alone (14). There
were no adverse sequelae related to the treatment.
Milrinone, a potent inotrope, was given intra-arterially
(dosage: 2.515 mg) and then continued intravenously
(0.50.75 (mg/kg/min) for up to two weeks in seven
patients presenting with cerebral vasospasm (40).
Vasodilatation was demonstrated in all patients, with
increased CBF in six of six patients in which it was
measured and with no adverse effects. On the basis of
these studies, it seems that further validation of the safety
and efficacy of both these agents for this usage are
warranted.
Balloon Angioplasty
Overview
Currently, we use TBA of cerebral vessels as the
preferred technique for the treatment of medically
refractory vasospasm (7,15,31), reserving papaverine
for vasospasm in the distal segments of the intra-
cranial vasculature not suitable for TBA or to dilate
proximal blood vessels sufficiently to allow passage of
the balloon. TBA, pioneered in 1984 by Zubkov,
carries somewhat higher risks of a major complication
such as vessel rupture compared with intra-arterial
infusion of vasodilators (7,9,41). In distinction with
intra-arterial instillation of antispasmodics such as
papaverine, however, the vasodilatation achieved
with TBA is usually more sustained. When performed
by experienced operators, side effects are less frequent
(7), and the procedure can safely and reproducibly
 Chapter 14: Endovascular Treatment of Post-Subarachnoid Hemorrhage Vasospasm
lead to vasodilatation of vessels in spasm with angio-
graphic and clinical improvement in a large propor-
tion of patients (6,7,15,28,31,42,43).
Numerous pathophysiologic mechanisms under-
lying the successful effects of balloon angioplasty have
been hypothesized and supported clinically as well as
in experimental animal models (4448). Using electron
microscopy to study intracranial blood vessels of two
patients who underwent TBA treatment for aSAH and
subsequently died, Honma et al. found stretching and
disruption of fibers throughout the vessel wall,
including nonmuscular as well as muscular elements.
These changes resulted in a persistent luminal dilata-
tion seen at autopsy that was similar in both patients
and concentrated in the medial layer. In a single case
report, Zubkov documented their findings at postmor-
tem analysis using both light microscopy and electron
microscopy. Similar findings included stretching of the
internal elastic lamina and muscular layer as well as
proliferation of connective tissue. The subendothelial
layer was thicker than that seen in non-angioplastied
vessels and the internal elastic lamina displayed a
corrugated pattern.
Such findings have been replicated in animal
studies. The ICA in 12 dogs was evaluated histologi-
cally after TBA and a loss of endothelial cells associ-
ated with flattening of the intima and internal elastic
lamina was observed (48). Electron microscopy
showed thinning of the internal elastic lamina with
occasional areas of rupture and crowding of the
smooth muscle cells in the tunica media. The increase
in vessel lumen diameter (documented by both
angiography and histologic analysis) persisted to
seven days despite efforts to induce vasospasm by
bathing the vessels in clotted blood. Using electron
microscopy to study autopsied MCAs in which TBA
was performed, Yamamoto et al. documented torn
and stretched collagen fibers and postulated that
disrupted connective tissue within blood vessels was
responsible for the sustained effect of TBA (47). In the
same study, a very similar disruption in the normal
structure of collagen fibers was seen in two segments
of MCA harvested from human autopsy studies and
subjected to balloon angioplasty postmortem. Mac-
donald et al. found that in a rabbit model of vaso-
spasm, TBA led to endothelial proliferation and
smooth muscle cell layer thinning, which persisted
at three to four weeks post-angioplasty. They postu-
lated that this long-lasting histologic finding
explained the durability seen with TBA (45).
Since Zubkovs initial description of the use of
balloon angioplasty to treat 105 vessels in 33 patients,
numerous other reports have surfaced documenting
its angiographic and clinical success for the treatment
of vasospasm after aSAH (612,28,4143,4953). 69%, 80%, and 58%, respectively, after TBA.
Improvements in endovascular technology, such as
newer softer balloons and better catheters, and
increased operator experience have led to increased
popularity of TBA and its use as a primary modality
to treat medically refractory vasospasm in many cen-
ters. Properly executed TBA can be expected to result
in clinical improvement, usually immediately notice-
able, in 60% to 80% of patients, sustained angiographic
267
dilatation in nearly all accessible vessels, and impro-
vements in CBF as evidenced by SPECT and TCD
studies (7,15).
Clinical and Radiographic Results
Numerous studies have been published documenting
the clinical success associated with TBA. Although the
results of each study must be interpreted based on
patient selection, timing of intervention, and outcome
measures, immediate neurologic improvement was
noticed in upwards of 60% of patients. In one litera-
ture review on this topic, Hoh and Ogilvy collected all
the patients treated with TBA for vasospasm; clinical
improvement was noted in 328 out of 530 patients
treated (16). In 1992, we reported a 72% clinical
improvement rate for 41 patients treated with TBA,
where success was defined by increase in Glasgow
Coma Score by two points or significant improvement
in speech or motor deficit (6). That clinical efficacy rate
remained fairly constant (61% and 74% from two
additional studies from our group) despite additional
operator experience, suggesting a plateau after which
increased operator experience plays less of a role,
patient specific factors become more germane (7,41).
Reports on TBA from other groups have not been as
optimistic. One recent study reviewed the results of
TBA for the patients forming the cohort evaluating the
benefit of tirilizad in aSAH and found no benefit of
TBA when compared with controls. The methodolog-
ical flaws of this study can explain the discrepancy
between this report and the majority of other reports
documenting the utility of TBA. CT scan results of
postplasty were assessed without the benefit of pre-
plasty scans. This assessment is unacceptable given
the finding that 22 out of 29 CT scans post-angioplasty
revealed infarcts. Additionally, there was variable
assessment of the severity of vasospasm and incon-
sistent technique related to the multicenter nature of
the study (15 different centers participating) (42).
Clinical success of TBA, however, does not nec-
essarily accompany angiographic success. Our group
and others have found a nearly 100% angiographic
response to TBA (6,11,12,54). Patient specific factors
such as pre-angioplasty clinical condition and the met-
abolic status of the brain that may be beyond the scope
of basic imaging may help explain this discrepancy.
It is therefore not surprising that the rate of
clinical success with TBA more closely parallels suc-
cessful increase in CBF as quantified by TCD
(6,7,12,29,42), Xenon CT, Xenon clearance, and
SPECT. Reports using TCD (16), regional blood flow
as measured by SPECT (6), and CBF measured by
Xenon clearance (28) have found improvements of
Major complications associated with TBA have
been recorded and include vessel rupture (41,55),
vessel occlusion (12), hemorrhagic infarction of the
vascular territory undergoing angioplasty (11), arterial
dissection, and hemorrhage from unsecured aneur-
ysms (12). In a literature review on this topic, a 5.0%
major complication rate with a 1.1% vessel rupture
rate was noted (16). Vessel rupture, the most serious
268 Brisman et al.
complication, is often lethal. Large series in the modern
era, however, have now shown that using soft compli-
ant balloons with gentle inflation techniques (as
described below) can minimize, if not eliminate, this
complication. Two recent reports at high-volume treat-
ment centers have experienced no neurologic compli-
cations associated with TBA in a total of 115 patients
treated (8,43).
On the basis of the above data and on our own
study in which we compared TBA to IAP, we have
adopted the practice of using TBA as the first-line
endovascular therapy for those with symptomatic
vasospasm failing medical treatment. In our study,
we noticed marked and more sustained improve-
ments in TCD velocities using TBA compared with
IAP (7). To our knowledge, no prospectively con-
trolled randomized trial has been performed compar-
ing the two modalities. We still make use of IAP in
patients in whom we find angiographic distal spasm
in which TBA would not be safe or as an adjunct to
facilitate TBA to open severely stenotic proximal
vessels to permit passage of the balloon. A compari-
son of the two major techniques (IAP and TBA) for
endovascular treatment of medically refractory post-
SAH vasospasm appears in Table 2.
Technique
Our technique for performing TBA for refractory
vasospasm has undergone changes that reflect our
increased experience with treating this entity, an
increased understanding of the pathophysiology of
this disease process, and the newer-endovascular
devices available (15,31). We perform TBA under
general anesthesia with full paralysis once a CT scan
of the head documents that there is no obvious cause
for the neurologic decline other than vasospasm,
such as hydrocephalus or aneurysmal rebleeding,
and there is no large territorial infarction. Completed
infarction, depending on the size, is a relative contra-
indication to TBA, particularly if it is associated with
a fixed neurologic deficit present for several hours or
more. Such conditions markedly increase the chance
that TBA will result in a reperfusion hemorrhage.
With the currently available technology, TBA can
Table 2 Comparison of TBA and IAP for Medically Refractory Vasospasm after SAH
Angiographic Clinical
Technique Mechanism of action success (%) success (%) Complications
TBAa Intravascular balloon 83100 62b
inflation, disruption
of IEL and smooth
muscle of media
IAP Slow intra-arterial 5790 43b
infusion, inhibits
phosphodiesterase in
smooth muscle cells
a
Preferred primary modality for refractory vasospasm.
b
From Ref. 16.
Abbreviations: TBA, transluminal balloon angioplasty; IAP, intra-arterial papaverine; SAH, subarachnoid hemorrhage; IEL, internal elastic
lamina; Rx., treat.
only be performed on the accessible large vessels at
the base of the brain and is not effective for distal
small-vessel vasospasm, which usually means any
second order branch of an intracranial arterial tree
(A2, M2, P2 segments). Once the decision is made to
proceed with angioplasty, all areas of vasospasm
visualized angiographically are treated, not just
those yielding clinical symptoms. We treat the ante-
rior circulation first.
Angioplasty is performed with the patient sys-
temically heparinized, achieved by giving an intrave-
nous bolus of heparin of 5000 to 7000 units, once the
vascular sheath is placed, followed by additional
boluses of 1000 to 2000 units to maintain an activated
coagulation time above 300 seconds. A 6-French (Fr)
guide catheter is typically used with a 6-Fr vascular
sheath placed within the common femoral artery. A
rotating hemostatic valve attached to the guiding
catheter prevents untoward movements of the balloon
microcatheter. Using biplane fluoroscopy and careful
guidewire manipulation, the guide catheter is
advanced so that the tip sits within the distal cervical
ICA or distal dominant vertebral artery, depending
on which part of the circulation is being treated. The
chosen balloon is preloaded with a microguide-
wire and introduced into the rotating valve. Through
the use of fluoroscopic road-mapping technique in the
anteroposterior and lateral projections, the balloon
microcatheter is advanced to the vessel in vasospasm.
It is important to maintain a high-quality road-map
image throughout the procedure as well as to advance
the guide catheter distally enough such that the tip is
visible at all times.
The most important factor about the choice of
balloon is that it is soft and pliable, which usually is
associated with balloons made of silicone or poly-
ethylene as opposed to latex. Such balloons, referred
to as compliant balloons, in distinction to balloons
used for angioplasty of atheromatous disease, are less
likely to result in vessel rupture. Currently, we prefer
the Endeavor or Sentry balloon (Target Therapeutics/
Boston Scientific, Fremont, California, U.S.) (Fig. 2),
although the Hyperglide balloon (Microtherapeutics,
Inc., Irvine, California, U.S.) has been used with equal
success.
Advantages Disadvantages
Major: 5% High angiographic More serious
Rupture: 1.1%b and clinical success, complications for
sustained effect inexperienced
operators, cannot Rx.
distal vasospasm
spasm, cannot Rx. distal
Major: 9.9% Moderate angiographic Effect often transient,
and clinical success, more frequent, albeit,
easy technique, can less serious
Rx.distal vasospasm complications.
 Chapter 14: Endovascular Treatment of Post-Subarachnoid Hemorrhage Vasospasm
The Sentry balloon (usually 3.5 mm  10 mm,
though other sizes exist) is a single-lumen balloon-
tipped microcatheter with an end hole that accepts
0.010- to 0.014-inch guidewires, allowing the balloon
microcatheter to be steered to the desired vessel of
interest. The balloon is prepared by flushing with
contrast material prior to preloading with the micro-
guidewire. Once the balloon has been placed in the
most distal region of the vessel to be treated, the
wire is removed. With the microguidewire removed,
the balloon can be gently inflated and then permitted
to spontaneously deflate. Although the Sentry balloon
is designed to undergo controlled inflation up to
4 atmospheres with the microguidewire inside, we
have found this technique useful to avoid untoward
overinflation for durations longer than desired.
Through the use of biplane fluoroscopy and mag-
nification road map, the Sentry balloon is navigated
using a microguidewire. The microguidewire is then
removed and a 3 cc syringe filled with contrast is
attached to the end of the balloon microcatheter. Angio-
plasty is performed as a four-step process, successively
increasing the diameter of the balloon inflation. We
start with the anterior circulation and begin by placing
269
Figure 2 (A) The soft compliant nature of
the Sentry balloon (3.5 mm  10 mm pictured)
allows for safe angioplastic dilatation of
vasospastic vessels. (B) We prefer using a
3-cc syringe for inflation, with the microguide-
wire removed, as shown here.
the balloon in the M1 segment and slowly inflate the
balloon under fluoroscopic guidance. Gentle inflation
of the balloon to approximately 25% of the maximal
balloon volume and diameter is followed by successive
inflations to 50%, 75%, and ultimately 100% (15). Par-
ticular care is given to avoid either overinflation or too
rapid inflation, especially with the first inflation, as
these maneuvers are most likely to result in vessel
injury and/or rupture. To achieve an effect, however,
we have found it necessary to hold the inflation for at
least one to two seconds. TBA is started distally (gen-
erally speaking slightly beyond the M1 segment) and
then moved proximally, with attempts made to overlap
areas of inflation so as to smooth out the angio-
graphic result and avoid leaving areas of residual
stenosis. It is critical not to inflate the balloon to a
diameter that exceeds the diameter of the native vessel;
the importance of careful evaluation, when possible, of
the original angiogram cannot be underscored.
Once the MCA segment angioplasty has been
satisfactorily performed, we move the catheter prox-
imally toward the supraclinoid ICA and repeat the
process (Fig. 3). Of note, we have found that it is
sometimes easy to maintain partial inflation of the
Figure 3 (A) Vasospasm of the right supraclinoid ICA
and M1 segment of the MCA is evident on this oblique
projection of a right ICA injection angiogram. (B) Follow-
ing balloon angioplasty of both segments (right internal
carotid angiogram, same obliquity), markedly increased
vessel diameters are achieved. Abbreviations: ICA,
internal carotid artery; MCA, middle cerebral artery.
270 Brisman et al.
balloon as it is navigated into the supraclinoid ICA,
as there is a tendency for the completely inflated
balloon to slide past a focal area of stenosis. This
phenomenon is believed to result from the pooling of
subarachnoid blood in dural folds in the vicinity of
the supraclinoid ICA. TBA of the A1 segment
is technically feasible (56), but should only be under-
taken by experienced operators in situations where
there is reason to believe that the resultant vaso-
spasm is truly symptomatic. Once study of the initial
angiogram confirms that the A1 segment of interest is
truly spastic and not simply congenitally aplastic or
hypoplastic, TBA is performed in the same stepwise
sequence as outlined for the MCA above. Most likely,
augmenting flow by dilating the supraclinoid ICA
will improve flow into the anterior cerebral artery
territory, and therefore if any question exists, it is
best to avoid A1 dilatation. We limit angioplasty to
the MCA prior to its bifurcation into the M2 seg-
ments, ICA, and A1 segments.
For the posterior circulation, the general tech-
nique is identical. The guide catheter is placed in the
cervical segment of the vertebral artery and the bal-
loon microcatheter is navigated into the basilar artery
using road-mapping technique. It is here that we
initiate TBA of the vertebrobasilar system. As with
the A1 segments, careful attention must be given to
the size of the P1 segments on the original angiogram to
rule out congenital hypoplasia. Angioplasty proceeds
from distal to proximal in a stepwise fashion, ending
just proximal to the takeoff of the posterior inferior
cerebellar artery. We generally do not dilate both the
vertebral arteries.
Timing
On the basis of the results of treatment for other forms
of neurologic deficit, such as subdural hematomas,
spinal cord compression, and cerebral ischemia of all
varieties, it would seem intuitive that the sooner one
treats a patient with symptomatic vasospasm, the more
likely there will be a good outcome. Multiple authors
have documented the applicability of this phenome-
non to TBA (8,41,43). TBA and IAP cannot return
function to infarcted brain and may even lead to
reperfusion hemorrhage. In fact some authors support
TBA, pointing out that some series with low clinical
responses to TBA may have included patients in
whom significant completed infarction had already
developed (8,51). Optimal timing for endovascular
intervention remains controversial. Whereas some are
evaluating the utility of prophylactic angioplasty for
those deemed highly likely to develop vasospasm (9),
most await failure of medical (triple-H) therapy.
Two studies looking at the issue of timing of
endovascular therapy and its effect on benefit in
patients with symptomatic vasospasm were published
in 1998. Bejjani et al. described their results with TBA in
31 patients with refractory symptomatic vasospasm
and found an increased likelihood of good recovery
in patients treated within 24 hours of symptom onset
(43). We found similar results in our early experience
with TBA, but noted a 12-hour cutoff after the
development of symptoms beyond which outcomes
appeared worse (41). Currently, we proceed to TBA if
a patient demonstrates neurologic deficits despite two
hours of maximal triple-H therapy. This management
schema is derived from the results of Rosenwassers
study in which he analyzed the effect of timing of TBA
after aSAH in 84 patients. In that study, patients treated
within two hours of symptom onset (n 51) had a 70%
rate of early favorable outcome compared with those
patients (n 33) treated after two hours (8).
Given the fact that TBA is ineffective once infarc-
tion has developed and that the time window between
development of symptoms and permanent ischemia is
still not well defined, a study was designed to test the
appropriateness of prophylactic angioplasty in select
patients. In a pilot study, Muizelaar et al. studied the
effectiveness and safety of performing prophylactic
angioplasty in the patients most susceptible to vaso-
spasm, those suffering Fisher grade 3 aSAH. Out of
13 patients enrolled in this study and treated with
prophylactic TBA, none suffered symptomatic vaso-
spasm and none developed severe vasospasm by TCD
criteria (9). There was one procedural-related death
associated with arterial rupture during TBA, prompt-
ing concern over the risk/benefit profile associated
with prophylactic TBA. Because of the small series
size, statistically powered recommendations cannot
be made and a larger prospective randomized study
is therefore underway to further define the role of
prophylactic angioplasty in such patients.
Endovascular Treatment of Vasospasm
in the Face of a Ruptured Unsecured
Aneurysm: A Special Case
On occasion, a patient who suffers aSAH may not be
brought to medical attention until several days after
the ictus. Some of these patients will be found to have
significant vasospasm at the time of initial angio-
graphic evaluation. This complication poses a unique
management dilemma. If the patient is salvageable,
aggressive treatment of both the aneurysm and vaso-
spasm is indicated.
In 1994, we reported on five patients who pre-
sented with severe vasospasm and ruptured aneur-
ysms (57). All five were treated with craniotomy and
clip ligation and then brought immediately thereafter
to the angiography suite for balloon angioplasty of the
narrowed vessels. This treatment resulted in
improved TCD velocities and SPECT compared with
pretreatment with good clinical outcome in four out of
five patients (57). As endovascular coiling has become
more popular and accepted as a primary modality to
secure ruptured aneurysms, the idea that the aneur-
ysm could be secured and the vasospasm treated in
the same sitting came to the fore. In one report,
12 patients presenting with symptomatic vasospasm
and ruptured aneurysms were treated with aneurysm
coiling and simultaneous TBA (6 patients), IAP
(2 patients), or both modalities (4 patients) (58).
Recently, we reported on intentional endosaccular par-
tial dome-coiling of two MCA aneurysms presenting
with severe vasospasm followed by delayed clipping
 Chapter 14: Endovascular Treatment of Post-Subarachnoid Hemorrhage Vasospasm 271

Figure 4 (A) Axial noncontrast CT scan revealing a small SAH in the left sylvian fissure. (B) Anteroposterior left internal carotid
angiogram showing a bilobed MCA bifurcation aneurysm with significant M1 vasospasm. (C) Angiogram, similar view, immediately
after partial dome-coiling and balloon angioplasty of the M1 segment. (D) Angiogram, similar view, six days later shows a normal M1
lumen diameter. (E, F) Postclipping angiogram digitally subtracted (E) and unsubtracted (F), similar views, shows successful
obliteration of the aneurysm. Abbreviations: CT, computed tomography; SAH, subarachnoid hemorrhage; MCA, middle carotid artery.
Source: From Ref. 59.

(Fig. 4) (59). Because of the morphology of the aneur-
ysm, it was felt that clipping would ultimately provide
the most definitive long-term cure of the lesion, but
partial dome-coiling was deemed safer than craniot-
omy and clipping to prevent an early rehemorrhage in
these patients who presented in the heat of vasospasm.
Predicting Outcome after Endovascular Therapy
for Vasospasm and Long-term Effects
Although both IAP and TBA appear to have a well-
documented radiographic and clinical success, it is not
known why some patients respond and others do not.
Why does one patient proceed to infarction and poor
outcome despite good angiographic success? Rabin-
stein et al. sought to determine predictors of outcome
after endovascular treatment of symptomatic vaso-
spasm by studying 81 consecutive patients undergo-
ing IAP, TBA, or both after aSAH (60). Using a logistic
regression analysis they found that advanced age and
poor clinical grade on admission were associated with
poor outcome in patients undergoing endovascular
therapy for vasospasm.
Perhaps because of the known temporary angio-
graphic and clinical effect of IAP, the long-term effects
of the intra-arterial administration of papaverine on the
cerebral vasculature have not been studied. Long-term
effects of TBA, however, have been studied in both
animal models and humans. Using a canine model of
vasospasm, Megyesi et al. demonstrated that the vas-
cular response to TBA, both functionally and morpho-
logically, was almost completely resolved by three
weeks after angioplasty (61). We reported on our
analysis of 28 consecutively treated patients with TBA
for vasospasm after aSAH and evaluated using TCDs
an average of 44 months after this procedure. No new
neurologic events were noted in 21 patients with clin-
ical follow-up. Normal TCD velocities were recorded in
all patients as were dynamic autoregulatory studies,
suggesting unimpaired vasomotor functioning (62).
272 Brisman et al.
CONCLUSIONS
Endovascular therapy has proven to be an important
adjunct in the treatment of medically refractory vaso-
spasm. Although both intra-arterial administration of
vasodilators and balloon angioplasty have been used as
primary interventional modalities, most centers now
favor the use of balloon angioplasty as a first-line agent
because of its reproducible angiographic and clinical
results, sustained effect, and decreased neurotoxicity.
Low complication rates are now the norm for TBA when
performed by experienced operators using modern day
compliant balloons. Intra-arterial vasodilators continue
to play an adjunct role in special circumstances and
future studies on newer intra-arterially administered
agents may increase their use. The results of the ongoing
trial on the prophylactic use of balloon angioplasty for
Fisher grade 3 aSAH as well as the continued refine-
ments in balloon and catheter technology should further
define and advance the role of interventional procedures
in the treatment of this condition.
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 15

Endovascular Management of Brain

Arteriovenous Malformations

John B. Weigele and Robert W. Hurst

Department of Radiology; Department of Radiology, Neurology, and Neurosurgery,
Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
Riyadh N. Al-Okaili
Department of Radiology, King Abdulaziz Medical City, Riyadh, Saudi Arabia

INTRODUCTION hamartomas rather than neoplasms. Vascular malfor-

Brain arteriovenous malformations (AVMs) are rela-
tively rare central nervous system lesions that are the
cause of significant long-term morbidity and mortal-
ity. Current therapeutic options include microvascular
neurosurgery, stereotactic radiation (radiosurgery),
and endovascular embolization. Embolization is an
important, well-established modality for brain AVM
treatment that is usually combined with surgery or
stereotactic radiosurgery. Embolization is, however,
associated with significant risks that must be carefully
balanced against the potential benefits in each patient.
Embolization performed by experienced interven-
tional neuroradiologists in appropriately selected
cases improves the overall safety and efficacy of
brain AVM treatment.
CLASSIFICATION AND PATHOGENESIS OF
CEREBRAL VASCULAR MALFORMATIONS
Cerebral vascular malformations have been studied
since the 18th century. Nonetheless, clinically useful
classification schemes have only been developed
recently. Initially, vascular malformations were cate-
gorized by their gross pathological appearance, result-
ing in confusing and contradictory nomenclature that
created a barrier to understanding their etiology, nat-
ural history, and clinical management (1).
A new biological classification for vascular
lesions was proposed in 1982 (2). Two major catego-
ries were identified: hemangiomas and vascular mal-
formations. Lesions with growth potential shown by
proliferation of endothelial cells with active DNA
synthesis were defined as hemangiomas and were
considered vascular neoplasms. Lesions without
endothelial cell proliferation or active DNA synthesis
and displaying proportionate growth were named
vascular malformations and were thought to be
mations were subdivided into arterial, capillary,
venous, lymphatic, and combined types (2).
Four categories of intracranial vascular malfor-
mations have been defined on the basis of gross and
microscopic pathological data: AVM, capillary telan-
giectasia, cavernous malformation, and venous mal-
formation (35). A mixed malformation also has been
described (6). These have been considered congenital
lesions, present from birth without the potential for
significant cellular proliferation or de novo postnatal
development.
Brain AVMs have cerebral arterial feeders directly
connected to the venous system without an intervening
capillary bed, resulting in high-flow arteriovenous
(AV) shunts. The nidus (Latin for nest) contains the
direct AV connections. The vessels in the nidus vary in
size and histology from relatively well-differentiated
arteries and veins to thick- and thin-walled, hyalinized,
malformed vessels that are neither. Dilated segments of
vessels commonly occur. There is gliotic brain paren-
chyma within and around the nidus. Gross or micro-
scopic calcification may be present with the vascular
walls or in the gliotic parenchyma. Hemosiderin is
commonly present, indicative of some degree of prior
hemorrhage. The gross pathological appearance has
been aptly described as a bag of worms (5).
Most brain AVMs occur sporadically; however,
they also are associated with a number of congenital
or hereditary syndromes, including: Rendu-Osler-
Weber syndrome (hereditary hemorrhagic telangiec-
tasia), Klippel-Trenaunay syndrome, Parks-Weber
syndrome, Wyburn-Mason syndrome, and Sturge-
Weber disease (7). Rare familial cases not associated
with syndromes also have been described (8).
There is recent evidence that not all brain AVMs
are congenital in origin (7). Although the large major-
ity probably occurs congenitally because of the failure
of capillary formation during early embryogenesis (9),
some brain AVMs appear to form in response to a
postnatal stimulus of angiogenesis, particularly in
276 Weigele et al.
younger patients. The de novo development of brain
AVMs in a child (10) and in an adult (11) has been
reported. Also, brain AVMs have reoccurred in chil-
dren after complete surgical resection (12).
EPIDEMIOLOGY OF BRAIN AVMs
Most of the estimates of the prevalence of brain AVMs
are flawed and potentially inaccurate. The widely
quoted prevalence estimates of 500 to 600/100,000
were based on biased autopsy data. Another erroneous
estimate of 140/100,000 was based on an inappropriate
analysis of the Cooperative Study of Intracranial
Aneurysm and Subarachnoid Hemorrhage data.
These estimates may represent greater than 10-fold
overestimates of the true prevalence (13).
A comprehensive review of the published litera-
ture performed in 2001 identified only three population-
based studies of the incidence and/or prevalence of
brain AVMs, all retrospective in nature (14). The Mayo
Clinics identified a total of 48 intracranial vascular
malformations in the population of Olmstead County,
Minnesota, over a period of 27 years, from 1965 to 1992.
The brain AVM detection rate was 1.11 (95% CI, 0.71.5)
per 100,000 person-years (15). The incidence of
symptomatic brain AVMs was 1.1 (95% CI, 0.61.8)
per 100,000 patient-years in the Leeward Islands of the
Netherlands Antilles between 1980 and 1990 (16). A
retrospective study in the Lothian region of Scotland
found a minimum point prevalence of 15 symptomatic
brain AVMs per 100,000 in unselected living adults
(17,18).
In 2003, an ongoing, prospective population-
based study of brain AVMs in the New York Islands
(Manhattan, Staten Island, and Long Island) with
9.4 million residents reported an AVM detection rate
of 1.34 (95% CI, 1.181.49) per 100,000 person-years.
The estimated prevalence of brain AVM hemorrhage
within the detected cases was 0.68 (95% CI, 0.570.79)
per 100,000 (19). The currently available data do not
suggest that there is a large reservoir of asymptomatic
brain AVMs in the general population, but that most
brain AVMs become symptomatic during life (20).
NATURAL HISTORY OF BRAIN AVMs
The risks of treating a brain AVM must be weighed
against the natural history of the disease, in particular
the possibility that a brain AVM will hemorrhage or
rehemorrhage if it is not treated and the associated
potential clinical consequences. Unfortunately, little
unbiased natural history data are available, in part,
because brain AVMs are relatively rare and quite
heterogeneous and also because most undergo some
form of treatment. No level I or level II natural history
studies have been published (21). Data on specific
predictors for the clinical course of a specific brain
AVM are even more limited. In many natural history
studies there is a selection bias toward untreatable
AVMs. In addition, natural history outcomes usually
have not been correlated with the type of presentation,
the analyses have differed and follow-up periods have
been short (14).
Despite these limitations, some general observa-
tions can be made about the natural history of brain
AVMs. Clinical presentation can occur at any age, with
the mean age of presentation in the fourth decade of
life. There is an essentially equal distribution between
sexes (14). Brain AVMs most commonly present with
intracranial hemorrhage, epilepsy, headache, or a focal
neurological deficit, although they are occasionally
found incidentally (14).
Intracranial hemorrhage is the most common
form of clinical presentation (21). In a prospective
population-based study published in 1996, 65% of
patients newly diagnosed with a brain AVM presented
with intracranial hemorrhage (22). Intraparenchymal
hemorrhage occurred in 41% of these cases, subarach-
noid hemorrhage in 24%, intraventricular hemorrhage
in 12%, and a combination of these types in 23% of
cases. The more recent prospective population-based
study of brain AVMs in the New York Islands reported
that 38% of patients with newly found AVMs pre-
sented with intracranial hemorrhage (19).
Hospital-based case series have been retrospec-
tively analyzed to identify risk factors for brain AVM
hemorrhage (14). These findings have not been con-
firmed by prospective population-based studies. The
features most consistently associated with an
increased risk of hemorrhage include deep venous
drainage, a single draining vein, venous stenoses,
and high-feeding mean arterial pressure (14). These
may share the common hemodynamic mechanism of
associated high intranidal pressures (23). Less consis-
tent risk factors for hemorrhage are a small AVM size,
feeding artery and intranidal aneurysms, and deep or
posterior fossa locations (14). Sex and pregnancy do
not appear to increase the risk of hemorrhage (24).
Features that may be associated with a decreased risk
of hemorrhage include a large AVM size (25), arterial
stenosis and ectasia (26), dural arterial supply (27),
venous recruitment (28), and angiogenesis (29).
The second most common form of clinical
presentation is epilepsy. In one retrospective popula-
tion-based study, 19% of newly discovered AVMs
presented with seizures (22). In two retrospective
hospital-based studies, 18% and 27% of AVMs pre-
sented with seizures, respectively (30,31).
Other less common brain AVM presentations
include headache (1% and 11% in two hospital-based
series) (30,31), focal neurological deficit (7% and 5% in
two hospital-based series) (30,31), and as an incidental
finding in an asymptomatic individual (15% in one
population-based study, 0% and 3% in two hospital-
based series) (22,30,31).
There are extremely limited data on the natural
history of brain AVMs following the initial diagnosis.
An annual 2% to 4% risk of first-ever hemorrhage
from a brain AVM is widely quoted on the basis of a
few hospital-based series (30,3235). No prospective,
population-based study of the clinical course of
unruptured brain AVMs has been published (14).
After an initial bleed, the risk for recurrent hemor-
rhage may be as high as 18% in the first year (31). This
appears to subsequently decrease to the baseline 2% to
4% annual risk of hemorrhage over time (36).
Fatality rates from brain AVM hemorrhage range
from 0% to 18% during the first year (22,30,31,35,37).
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations
The reported long-term annual fatality rates are 1% to
1.5% (30,35). Ondra et al. prospectively evaluated 166
untreated symptomatic brain AVM patients over a
mean follow-up period of 23.7 years. There was a
4.0% annual rate of hemorrhage and a 1.0% annual
mortality rate. The combined rate of mortality and
major morbidity was 2.7% per year. Over the follow-
up period, 23% of the patients died from hemorrhage.
The incidence of bleeding and death were the same
whether the AVM initially presented with hemor-
rhage (35). Recurrent hemorrhage appears to cause a
morbidity rate similar to the initial bleed (36). In
another hospital-based study, 47% of patients with a
first-ever hemorrhage sustained no neurological
defect and 37% experienced no significant disability
despite symptoms (Rankin 1) (37). Parenchymal hem-
orrhage had a greater likelihood (52%) of producing a
neurological defect.
ANGIOGRAPHY AND ANGIOARCHITECTURE
OF BRAIN AVMs
Selective and Superselective
Cerebral Angiography
Brain AVMs demonstrate AV shunting on angiogra-
phy, resulting in early opacification of the draining
veins and a decrease in the AV transit time (38). This
shunting is the result of a direct connection between
the arterial and venous sides of the cerebral circula-
Figure 1 Large, fistulous AVM (large arrows in A and B). Note
proximal arterial aneurysms (small arrows, A), venous ectasia
(arrowheads, B), and venous aneurysms (small arrows in C
and D). Also note nonvisualization of normal anterior and middle
cerebral arterial territories due to vascular steal. (A) AP
angiogram-arterial phase, (B) lateral angiogram-arterial phase,
(C) AP angiogram-venous phase, and (D) lateral angiogram-
venous phase. Abbreviation: AVM, arteriovenous malformation.
277
tion without an intervening capillary bed. There are
two types of AV connections: fistulous and plexiform
(39). A fistulous nidus contains large-caliber direct AV
connections (Fig. 1). A plexiform nidus consists of a
conglomerate of multiple smaller and more numerous
vascular channels supplied by one or more arterial
feeders (Fig. 2). These are collected into one or more
draining veins. A plexiform nidus can contain one or
more direct fistulas (mixed plexiform-fistulous nidus;
Fig. 3) (39,40).
The complete angiographic evaluation of a brain
AVM consists of (1) the selective evaluation of the
AVM and the entire cerebral circulation using 4- or
5-French (Fr) diagnostic catheters and (2) the super-
selective angiographic evaluation of the feeding arte-
rial pedicles, the nidus, and the venous drainage using
microcatheters advanced into distal aspects of the
arterial feeders (38).
The goals of the selective angiographic evaluation
are listed in Table 1. This provides an important
assessment of the arterial supply to the AVM, the
general characteristics of the nidus, the venous drain-
age of the AVM, and the rest of the intracranial circu-
lation. Selective angiography, however, has significant
limitations. Rapid AV shunting often superimposes the
arterial feeders, the nidus, and the draining veins
obscuring important features, such as small arterial
feeders, distal feeding pedicles, nidal aneurysms, direct
AV fistulas, and small accessory draining veins (38).
The goals of superselective angiography are
listed in Table 2. Such detailed anatomic information
from superselective angiography concerning the distal
Figure 2 Plexiform AVM (arrowheads in A, B, and C). (A) AP
angiogram, (B) lateral angiogram, (C) superselective angiogram
(microcatheter tip, arrow), and (D) lateral postembolization angio-
gram (arrow, residual nidus). Abbreviation: AVM, arteriovenous
malformation.
278 Weigele et al.

Figure 3 Mixed plexiform (A, arrowheads) and fistulous Figure 4 Sulcal AVM. (A) Triangular nidus (arrow) on lateral
(B, arrow) nidus in an 11-month old. (A) Selective lateral angio- angiogram. (B) NBCA in nidus (arrow) on unenhanced axial CT
gram and (B) superselective lateral angiogram. image. Abbreviation: NBCA, N-butyl cyanoacrylate.

arterial feeders, the nidus, and the proximal draining A sulcal AVM nidus occupies the subpial space
veins is critical for planning and performing endovas- of the sulcus. The nidus may remain contained within
cular embolizations (38). the sulcus or variably extend through the sulcus into
the cerebral cortex, into the subcortical white matter,
Classification of Brain AVMs and into the deep white matter to the ventricular wall.
Sulcal AVMs assume a conical or pyramidal shape
Brain AVMs are categorized into superficial (cortical) conforming to the sulcal space (Fig. 4). Their most
or deep types. Cortical AVMs are subcategorized into superficial aspect is covered by the meninges, not by
sulcal, gyral, and mixed (sulcogyral) types. Deep parenchyma. Because of this, meningeal arterial supply
AVMs are subdivided into subarachnoid, deep paren- to their superficial aspect is common. Pial arteries are
chymal, plexal, and mixed types (38). their primary supply. These end in the nidus after
providing cortical and medullary branches to adjacent
gyri (terminal feeders). This terminal supply is usually
Table 1 Goals of Selective Angiographic Evaluation of Brain AVMs
amenable to safe embolization. Larger sulcal AVMs
also receive supply from basal perforating arteries (38).
1. Arterial territories supplying the AVM Gyral AVMs are covered by cortex and are typ-
2. Feeding pedicles ically spherical (Fig. 5). The gyrus usually is enlarged
3. High-flow arteriopathy (stenoses, ectasias, flow-related
aneurysms)
4. Nidus (size, shape, location, flow, fistulas, ectasias,
aneurysms)
5. Venous drainage (territories, deep, superficial)
6. Individual draining veins
7. High-flow venous angiopathy (dural sinuses, venous
stenoses, occlusions, and varices)
8. Venous drainage of normal brain parenchyma
Abbreviation: AVM, arteriovenous malformation.
Source: From Ref. 114.

Table 2 Goals of Superselective Angiographic Evaluation of

Brain AVMs
1. Distal feeding pedicles (anatomy, aneurysms, geometry,
hemodynamics)
2. Arterionidal junction
3. Nidus (compartments, direct AV fistulas, plexiform regions,
intranidal ectasias, and aneurysms)
4. Venonidal junction
5. Proximal aspects of the draining veins Figure 5 Gyral AVM. Axial T2-weighted MRI (A) and lateral
angiogram (B) demonstrate a small gyral AVM (arrow). Abbre-
Abbreviations: AVM, arteriovenous malformation; AV, arterio-
viation: AVM, arteriovenous malformation.
venous.
Source: From Ref. 114.
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations
Figure 6 Deep AVM (large arrow in A and B) on lateral angio-
gram (A) and axial T2-weighted MRI (B). Note venous ectasia
(arrowhead, A) and venous aneurysm (small arrow, A). Abbre-
viation: AVM, arteriovenous malformation.
and adjacent sulci are compressed. A large gyral AVM
may extend into the subcortical white matter toward
the ventricular wall. The arterial supply is primarily
from pial branches that continue beyond the AVM to
supply normal parenchyma (indirect feeders). Menin-
geal supply typically is absent because the overlying
cortex is positioned between the nidus and the
meninges. Basal perforating arteries may supply the
deeper extension of a large gyral AVM (38).
Mixed (sulcogyral) types usually are large AVMs
that combine both sulcal and gyral features. The AVM
typically involves gyri and sulci, extending into the
subcortical white matter to the ventricular wall. The
arterial supply combines meningeal arteries and ter-
minal pial branches from the sulcal component, non-
terminal pial branches from the gyral component, and
basal perforating arteries (38).
Deep AVMs are relatively rare. They can be
subdivided into subarachnoid, deep parenchymal,
plexal, and mixed types. Subarachnoid AVMs are
found in the basal cisterns and fissures, supplied by
the subarachnoid portions of the choroidal and perfo-
rating arteries. Deep parenchymal AVMs are located in
deep gray and white matter such as the thalamus, basal
ganglia, and corpus callosum (Fig. 6). Basal perforators,
choroidal arteries, basal circumferential arteries, and
medullary pial branches supply them. Plexal AVMs are
intraventricular, primarily supplied by the choroidal
arteries. Mixed deep AVMs are typically larger, com-
bining subarachnoid, deep parenchymal, and plexal
features. Venous drainage is predominately into the
deep venous system; however, transmedullary cortical
venous drainage also is seen (38).
Angioarchitecture of Brain AVMs
The routine use of superselective angiography in addi-
tion to conventional selective cerebral angiography in
279
recent years has added considerably to the under-
standing of brain AVM angioarchitecture.
Feeding Arteries
The classification of the arterial feeders to a brain
AVM using anatomic, geometric, and hemodynamic
criteria is essential for planning and performing
endovascular embolization. Pial supply may be pro-
vided by extracortical (subpial), cortical, medullary,
and/or corticomedullary branches. Meningeal supply
may be direct or through transdural pial anastamoses
(Fig. 7). Collateral supply can occur through leptome-
ningeal and subependymal anastamoses. Choroidal
artery supply can arise from the extraventricular
(fissural, parenchymal) or intraventricular portions
(39,40).
Geometric classification of arterial feeders
defines the relationship of the distal feeder with the
nidus and normal parenchyma. Three types are
defined on superselective angiography: terminal,
pseudoterminal, and indirect (39,40). The terminal
feeder ends within the nidus distal to branches sup-
plying normal brain. Terminal feeders are usually
large, facilitating their superselective catheterization.
Embolization is relatively safe if the catheter tip is
positioned distal to branches to normal parenchyma
(39,40). The pseudoterminal feeder appears to end in
the nidus, but actually continues beyond to supply
normal brain. The distal segment is not angiographi-
cally visible because of the high flow (sump effect)
into the nidus. Its presence must be inferred on an
anatomic basis. A wedged catheter position during
superselective angiography can contribute to the
nonvisualization of the distal portion. Changing
hemodynamic conditions during embolization of a
pseudoterminal feeder can cause the embolic material
to occlude the distal portion to normal brain, resulting
in an ischemic complication (39,40). The indirect
feeder (feeder en passage) is a branch to the nidus
Figure 7 External carotid supply to AVM from middle meningeal
(arrow, B) and occipital (arrowheads, B) branches. (A) AP angio-
gram and (B) lateral angiogram. Abbreviation: AVM, arteriove-
nous malformation.
280 Weigele et al.

Figure 8 En passage supply during embolization of a

plexiform AVM. (A) AP angiogram shows superficial
(arrow, A) and deep (arrowhead, A) venous drainage.
(B) Lateral angiogram shows venous ectasia (arrow-
head, B) and venous aneurysm (arrow, B). (C) Lateral
superselective angiogram shows en passage supply
(arrowheads, C) to nidus (large arrow, C) and microcath-
eter tip (small arrow, C). (D) Lateral angiogram shows
residual nidus after embolization (arrowheads, D). Abbre-
viation: AVM, arteriovenous malformation.

arising from an artery that passes in proximity to the AVM Nidus

nidus while continuing on to supply normal brain
(Fig. 8). Indirect feeders are typically smaller and The nidus is considered the region between very distal
shorter, usually originating at an acute or right angle aspects of the readily identifiable arterial feeders and
from the parent vessel. Superselective catheterization the proximal aspects of the draining veins. AV shunt-
is often feasible, but more difficult. The parent vessel ing occurs at this site and represents the primary
may be enlarged up to the origin of the indirect target of embolization. Complete obliteration of the
feeders and smaller beyond (39,40). nidus results in a cure (39,40).
Most brain AVMs have a compact, well-defined
Feeding arteries may be characterized hemody-
nidus with well-demarcated borders, discrete feeding
namically into dominant or supplementary feeders
arteries, and draining veins. A minority has diffused
according to the amount of flow. Dominant feeders
and ill-defined margins. Angiogenesis associated with
supply a large portion of the nidus, are larger, and
watershed transfer may mimic a diffused nidus. Nidal
carry more flow than supplementary feeders. Dominant
sizes vary tremendously. Their shapes tend to con-
and supplementary feeders can arise from the same or
form to their anatomic environments. Sulcal AVMs
different vascular territories. Most cerebral AVMs con-
are usually conical (Fig. 4), gyral and subcortical white
tain a combination of both types of feeders (38).
matter AVMs tend to be spherical (Fig. 5), and deep
High-flow angiopathy results in stenoses in the
AVM shapes vary with location (callosal, cisternal,
feeding arteries in up to 20% of brain AVMs. These
etc.) (Fig. 6). Larger AVMs have more complex shapes
may be isolated, proximal stenoses intrinsic to the
reflecting their involvement with multiple anatomic
vessel wall or rarely caused by extrinsic compression.
structures (38).
Diffuse stenoses with a moyamoya appearance are
Superselective angiography has led to the con-
occasionally seen in younger patients (40). Arterial
cept of the nidal vascular compartment, referring to an
stenoses associated with decreased distal tissue per-
intranidal vascular unit consisting of one or more
fusion may result in a shift in the watershed zone
feeding arteries supplying the region of AV shunting
toward the nidus (watershed transfer), occurring in
with a unique draining vein. A nidus may be com-
up to 30% of superficial (cortical) AVMs. Cortical
posed of one or multiple vascular compartments of
arteries and leptomeningeal collaterals are recruited
varying sizes and flow patterns. The AV connections
to supply more of the territory distal to the AVM. This
within a given compartment may be plexiform, fistu-
shift in arterial supply may perfuse just the normal
lous, or mixed. These compartments are often hemo-
parenchyma or also include the distal aspect of the
dynamically interconnected, so occlusion of the
AVM nidus. Angiogenesis can occur with watershed
compartmental feeders without occlusion of the com-
transfer in response to chronic parenchymal ischemia.
partmental zone of AV shunting may allow the com-
It may be mistaken for part of the nidus; however,
partment to continue to fill from neighboring units.
angiogenesis has no AV shunting and is not a true
Compartmental vein occlusion can increase the risk of
AVM component (40).
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations
nidal rupture. Hence, careful characterization of the
compartmental angioarchitecture is essential for plan-
ning an embolization (38).
Histological studies have described the nidus as
a complex system of coiling and intercommunicating
vascular channels emptying into tortuous thin-walled
collecting veins. Three zones have been described
within the nidus: arterial, intermediate, and venous.
The arterial zone consists of a plexus of interconnect-
ing thick-walled vessels. The intermediate zone is
very heterogeneous, containing four types of coiled,
interconnected channels ranging from 0.15 to 1.0 mm
in diameter. The venous zone consists of 1- to 3-mm
thin-walled vessels converging into the draining
veins. AV shunting is thought to occur between the
arterial and intermediate zones (41).
Draining Veins
The location of a brain AVM usually predicts the
pattern of venous drainage; however, there are fre-
quent variations. Cortical AVMs (sulcal and gyral)
typically drain through cortical veins into the nearby
dural sinuses. Those with subcortical or ventricular
extension often have both superficial (cortical) and
deep (subependymal) venous drainage. Central
AVMs usually drain into the deep venous system.
However, unexpected patterns, such as transcerebral
cortical venous drainage of a deep AVM or deep
venous drainage of a cortical AVM, may be seen
approximately 30% of the time. These variants may
represent venous collaterals that developed after
occlusion of the original venous drainage system (40).
Important aspects of the nidal venous drainage
include venous anatomic variations, collateral venous
drainage, and high-flow angiopathy (Fig. 9). Anatomic
variations in venous drainage develop in response to
hemodynamic effects, such as persistence of embry-
onic veins and variations in the cerebral veins and
dural sinuses. Collateral venous drainage is acquired
as a response to obstruction including ipsilateral,
contralateral, and transcerebral rerouting of venous
Figure 9 Large, high-flow AVM with left transverse sinus occlu-
sion (A, arrow) and right sigmoid sinus stenosis (B, arrow)
causing venous hypertension and cognitive impairment. (A) AP
angiogram-venous phase and (B) lateral angiogram-venous
phase. Abbreviation: AVM, arteriovenous malformation.
281
drainage. This may be due to mechanical venous
compression or intrinsic venous stenoses or thrombo-
ses due to high-flow angiopathy. Insufficiently devel-
oped collateral venous drainage may result in venous
hypertension, venous aneurysms, and venous ectasia
(varix) proximal to the obstruction, especially in high-
flow AVMs (Fig. 1). Clinical symptoms may result
from direct compression of the brain or cranial nerves
by the varix, seizures or neurological deficits from
venous hypertension (Fig. 9), and hemorrhage from
AVM rupture (38,40).
Aneurysms Associated with Brain AVMs
Introduction. The association of aneurysms with
brain AVMs has been reported for many years
although until recently little was known regarding
the frequency or clinical implications of their concom-
itant occurrence. The publication of relatively large
series has enabled study and understanding of some
aspects of the association between these two cerebro-
vascular lesions. Although much remains to be under-
stood, it is clear that significant clinical and
therapeutic implications may arise from the relatively
common association of these two cerebrovascular
lesions.
Classification. Classification of aneurysms asso-
ciated with AVMs was first proposed by Hayashi et al.
in 1981 (42). These authors included only aneurysms
external to the AVM nidus in their classification. They
divided extranidal aneurysms into three groups
depending on whether they were located proximally
or distally on vessels giving supply to the AVM or
were located on vessels unrelated to the AVM supply.
In 1994, the Tews classification (Table 3) divided
AVM-associated aneurysms into four groups based on
their relationship to the AVM nidus and feeding arteries
(43). This classification also includes intranidal aneu-
rysms (Type IV). This comprehensive and relatively
straightforward classification has the advantage of sug-
gesting potential mechanisms for aneurysm formation
based on location. In addition, it has proven useful in
attempts to relate aneurysm types to clinical behavior.
Differences in definitions are often seen, how-
ever, with some series simplifying the classification
into three or even two groups of aneurysms. These
often overlap and have included aneurysms unrelated
to the AVM supply; flow-related aneurysms, which
have been subdivided into those located either prox-
imally or distally on arteries supplying the AVM; and
intranidal aneurysms (4446).
Nevertheless, definitions of AVM-associated
aneurysms similar to those outlined in the Tews
Table 3 Tews Classification of AVM-Associated Aneurysms
Type I Dysplastic or remote, not related to AVM supply
Type II Proximal, arising from the circle of Willis or origin of a
vessel supplying the AVM
Type III Pedicular, arising from the midcourse of a feeding
pedicle
Type IV Intranidal, within the AVM nidus
Abbreviation: AVM, arteriovenous malformation.
Source: From Ref. 43.
282 Weigele et al.
Figure 10 (A) Distal flow-related aneurysm, (B) additional
example of distal flow-related aneurysm, (C) intranidal aneurysm,
(D) proximal flow-related aneurysm, and (E) non-flow-related
aneurysm. Source: From Ref. 47.
classification have become relatively standardized with
publication of Reporting Terminology for Brain Arte-
riovenous Malformation Clinical and Radiographic
Features for use in Clinical Trials (Fig. 10) (47).
Epidemiology. The reported prevalence of
aneurysms associated with AVMs varies widely
among series (Table 4). In an early examination of
the subject, the First Cooperative Study of Intracranial
Aneurysms and Subarachnoid Hemorrhage found
intracranial aneurysms associated with 6.2% of 545
AVMs (48). Similarly, in a large series of 600 AVMs,
Thompson et al. identified 7.5% patients whose AVMs
were associated with extranidal aneurysms (49). Other
series have noted prevalence of extranidal aneurysms
as high as 17.6% (Figs. 11 and 12) (50).
In 1994, Turjman et al., using superselective
angiography, demonstrated a considerably higher prev-
alence, which included a group of aneurysms located
within the angiographic boundaries of the AVM nidus
and which filled prior to filling of significant portions of
the nidus. These intranidal aneurysms were identified
Figure 11 Proximally located aneurysms: (A) M1-2 junction and
(B) basilar tip.
Figure 12 Distal feeding artery aneurysm on anterior choroidal
artery.
in 58% of 100 consecutive AVMs (51). Meisel et al.
evaluated 662 AVM patients and identified 46% with
associated aneurysms. Among 305 patients having both
aneurysms and AVMs, 372 of the aneurysms were
identified as intranidal, with 313 located on vessels
supplying the AVM (46).
Halim et al. evaluated 336 AVM patients, 82 from
University of California at San Francisco (UCSF) and
254 from Columbia Presbyterian Medical Center
(CPMC). Their evaluation also included intranidal as
well as extranidal aneurysm types. They found similar
overall aneurysm prevalence at both institutions with
34% in the UCSF patients and 29% from patients
evaluated at CPMC (45). Redekop et al., however,
found a somewhat lower frequency and identified
aneurysms in association with 16.7% of 632 AVMs of
which 5.5% were intranidal aneurysms (52).
Overall, the reported prevalence of AVM-
associated aneurysms falls generally into the range
of 15% to 25%. Nevertheless, prevalence in individual
series varies 10-fold, from 5.8% to 58% in different
series. This variability in reported aneurysm preva-
lence may arise from a number of factors. These
include poor interobserver agreement as to what
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations 283

Table 4 Reports of AVM-Associated Aneurysms

Multiple On feeding
Reference Year AVMs Aneurysms (Pts) aneurysms vessel Intranidal Unrelated
48 1966 490 37 (7.6%) 15/34 (37%) NE 18/34 (43%)
39 1987 414 45 (11%) 42/45 (93%) NE 3/45 (7%)
50 1990 91 16 (17.6%) 25 NE
63 1992 400 39 (9.8%) 63/64 (98%) NE 1/64 (2%)
51 1994 100 58 (58%) 34/58 (58.6%)
52 1998 632 97/632 (15.3%) 71 pts (11.2%) 35 (5.5%) 5/632 (0.8%)
had 123
flow-related
aneurysms
49 1998 600 45 (7.5%) 51% 30/45 (66%) NE 15/45 (33%)
46 2000 662 (450 305 (46.1%) 205/305 (67.2%) 138/450 181/450
Rxd) (30.7%) (40%)
67 2000 222: 198 Total: 13/222 (5.8%); 1/222 (0.045%) All by definition NE 1/222
supra, 24 Supratent 3.5%; (0.045%)
infratent infratent 20.8%
53 2000 172 25 (14.5%) 18/25 (72%)
65 2001 270 30 (11%) 14/30 (47%) All NE
44 2002 463 117 (25.3%) 24/117 (20.5%) 77/463 (17%); 35/463 AVMs 32/463 (7%);
54/117 (46%) (8%); (21/117 18/117
(17.9%) (15.3%)
45 2002 Total of 336- 28 (34%) (UCSF)/74 16/82 (23%); 11/82 (17%); 2/82 (4%);
82/254 (29%)(CPMC) 35/254 (16%) 23/254 (11%) 10/254 (5%)

Total 4852 929/4852 (19.1%)

Abbreviation: AVM, arteriovenous malformation; NE, not evaluated.

constitutes an AVM-associated aneurysm, particularly
aneurysms within or in proximity to the AVM nidus.
In addition, differing definitions, data collection meth-
odology, and inclusion criteria, all impact on the
diagnosis and classification of AVM-associated aneu-
rysms. For example, whether aneurysms located
within the AVM nidus are included can be expected
to impact the overall numbers of aneurysms identi-
fied. Lastly, heterogeneity of study populations,
including referral bias, contributes to the variable
prevalence reported in the literature.
Most series indicate that AVM-associated aneur-
ysm prevalence is similar in men and women. The
frequency of AVM-associated aneurysms has been
noted, however, to increase with patient age, as well
as flow rate and size of the AVM nidus.
Reported multiplicity of AVM-associated aneur-
ysms is common but also quite variable. Ezura et al.,
for example, found multiple aneurysms in 18 of the
25 patients (72%) to be AVM-associated aneurysms in
their series, while Meisel et al. found 67% of their
AVM-associated aneurysm cases to have multiple
aneurysms (46,53,54). Data suggest that close to half
of patients with AVM-associated aneurysms will have
more than one aneurysm, and a significant proportion
will have more than two aneurysms.
Pathogenesis of AVM-associated aneurysms. Three
major theories have addressed the association of
AVMs and aneurysms. These include coincidental
occurrence, an underlying congenital vascular defect
responsible for both lesions, and the flow-related or
hyperdynamic theory.
Early suggestions were that the relationship
between the two lesions was one of simple chance
occurrence. For adults without specific risk factors, the
prevalence of intracranial aneurysms alone has been
estimated at approximately 2.3% (54). Coincidental
occurrence may explain some AVM-associated aneu-
rysms, particularly those located on vessels unrelated
to the AVM. As noted above, however, most studies
report a considerably higher frequency of aneurysms
occurring in association with AVMs than would be
expected by chance, and this theory is currently given
little credence.
To date, no underlying congenital defect has
been identified to explain an association between
aneurysms and AVMs. While a number of genes
have been found to be differentially expressed in
AVM-feeding pedicles compared with normal cere-
bral vessels, current information suggests that this
differential expression is likely a consequence of
increased flow dynamics rather than an underlying
cause of the AVM (55).
Although AVMs are considered congenital
lesions, only a very limited number are associated
with, and perhaps arise from, inherited genetic
defects. An increased prevalence of brain AVMs has
been most closely associated with hereditary hemor-
rhagic telangiectasia (HHT), an autosomal dominant
disorder characterized by AV shunts involving many
organ systems. MRI evaluation of a population of
184 HHT patients demonstrated brain AVMs in 5.6%
of these patients (56). While reports of aneurysms in
HHT exist, there is no indication that an increased
frequency of arterial aneurysms characterizes patients
with this disorder.
Conversely, a large number of inherited or con-
genital conditions have been associated with an
284 Weigele et al.
increased prevalence of intracranial aneurysms. Adult
polycystic kidney disease and coarctation of the aorta
may engender aneurysm formation, likely through the
mechanism of systemic hypertension. A number of
other heritable disorders, many of which involve
defects in connective tissue, have also been associated
with an increased prevalence of intracranial aneur-
ysms (57). No convincing evidence has been presented
to suggest an increase in brain AVMs associated with
any of these conditions.
Flow phenomena associated with the AVM pro-
vide a logical mechanism to explain the greater than
expected prevalence of aneurysms on AVM feeding
vessels. This theory, initially articulated by McKissock
over 50 years ago, bases the development of aneur-
ysms on the hyperdynamic flow resulting from AV
shunt through the AVM (58). The low resistance
through the AVM and consequent increased velocity
in feeding arteries places increased shear stress on the
vessel walls. While aneurysm formation is undoubt-
edly multifactorial, abnormal shear stress acting on
the arterial wall has been found to play a role in
formation, growth, and rupture of all types of arterial
aneurysms (5961). Indeed, no histological or imaging
features have been found to distinguish flow-related
aneurysms occurring in association with AVMs from
those aneurysms occurring in the absence of AVMs.
Support for a hyperdynamic flow mechanism
comes from the observed tendency of aneurysms to
arise far more commonly on vessels providing arterial
supply to the AVM, than on unrelated vessels. An
analysis of 78 reported cases of AVM-associated aneur-
ysms, by Okamoto et al., showed a significant correla-
tion of aneurysm location to vessels supplying the
AVMs (62). This was reinforced by the results reported
by Cunha e Sa et al. who found 98% of AVM-associated
extranidal aneurysms on vessels directly supplying the
AVMs (63). In addition, Redekop et al. identified flow-
related aneurysms in 11.2% of 632 AVMs, while aneur-
ysms on vessels unrelated to the AVM were found in
only 0.8% (52). These authors also found a tendency for
aneurysms to occur more often on arteries feeding
larger AVMs, and therefore associated with higher
flow, than on arteries supplying smaller AVMs.
Additional support for a hyperdynamic flow
mechanism underlying many AVM-related aneur-
ysms arises from frequently observed changes in
aneurysm size following treatment of the AVM and
consequent decrease in the AV shunt. Examination of
23 proximal aneurysms following complete AVM
obliteration revealed disappearance of one (4.3%)
and a decrease in size of four (17.4%) aneurysms. In
the same patient population, four (80%) of five distally
located aneurysms regressed completely and one was
unchanged (52). These data emphasize the effect of
AVM flow on changes in aneurysms located along
feeding arteries. They also suggest that more distally
located aneurysms are more sensitive to alterations in
flow than those located more proximally.
Attribution of aneurysm formation to flow phe-
nomena helps to explain the formation and clinical
behavior of a large proportion of AVM-associated
aneurysms. In addition, this explanation aids classifi-
cation of AVM-associated aneurysms and may sug-
gest guidelines for management as noted below.
Nevertheless, hemodynamic mechanisms do not
fully explain the incidence of all AVM-associated
aneurysms, even those confined to direct feeding
vessels. That other, perhaps individual features, are
involved is evidenced by the fact that most AVMs are
not associated with aneurysms.
Additional controversy surrounds the etiology
of intranidal aneurysms. Many believe that these
lesions represent true aneurysms located in the most
distal arterial branches adjacent to the AVM nidus.
Other authors have suggested, however, that some of
these lesions represent early filling of dilated venous
pouches rather than true arterial aneurysms, while
others may represent pseudoaneurysms arising as
residua of prior hemorrhages (64).
Clinical implications. The natural history of
AVMs associated with aneurysms has been the subject
of considerable controversy and little firm agreement.
In large part, this uncertainty is due to the heteroge-
neity of AVM-associated aneurysms as well as to the
heterogeneity of AVMs themselves.
Some data suggest that increased rates of both
initial and recurrent hemorrhage occur in patients who
have AVMs with concomitant aneurysms. Piotin et al.
found that 50% of their patients with AVM-associated
aneurysm presented with intracranial hemorrhage. Of
these, 80% had bled from their aneurysms (65). Simi-
larly, Batjer et al. found that for patients who harbored
both lesions and presented with intracranial hemor-
rhage, 78% had bled from the associated aneurysms
(66). Cunha e Sa et al. identified the source of intra-
cranial hemorrhage in patients with AVM-associated
aneurysms as the aneurysm in 46% of their series (63).
Brown et al. emphasized the long-term risk of harbor-
ing an aneurysm in association with an AVM. They
found that patients with AVM-associated aneurysms
had an annual hemorrhage risk of 7% at five years
following diagnosis. This was significantly higher than
the 1.7% annual hemorrhage rate for those AVM
patients without coexisting aneurysms (50).
Studies of clinical behavior also suggest that
important differences may characterize different
types of AVM-associated aneurysms. Intranidal
aneurysms have been associated with a higher inci-
dence of initial hemorrhage as well as with multiple
episodes of recurrent bleeding. For example, Redekop
et al. noted intracranial hemorrhage associated with
38% of their series of 632 AVMs. Presentation with
intracranial hemorrhage occurred in 72% of patients
with intranidal aneurysm; 36% without aneurysm;
and 40% with flow-related or unrelated aneurysms.
These authors also found an annual hemorrhage rate
of nearly 10% among patients with intranidal aneu-
rysms who were not treated (52).
In contrast, Meisel did not find initial hemor-
rhage to be correlated with any type of aneurysm. In
their experience, however, intranidal aneurysms dem-
onstrated a significantly higher rebleeding rate before
treatment (46). Similarly, Thompson et al. were unable
to attribute any increased risk of an initial hemor-
rhagic presentation to the existence of aneurysm (49).
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations
Figure 13 Distal feeding artery aneurysm on superior cerebellar
artery, (A) AP and (B) lateral view.
The difficulty in evaluating risks of AVM-
associated aneurysms is emphasized by Halim et al.
These investigators studied the association between
AVM-associated aneurysms and presentation with
intracranial hemorrhage in 336 patients from two refer-
ral populations, at CPMC and UCSF. While aneurysm
prevalence was similar at both institutions, they found
that initial presentation with hemorrhage was associ-
ated with a coexisting aneurysm at CPMC, while the
opposite trend was seen in the UCSF population (45).
Despite the difficulty in formulating risk profiles
associated with AVM-associated aneurysms in gen-
eral, aneurysms seem to present more of a risk of
hemorrhage when located closer to or within the AVM
nidus. In addition, intriguing data from small number
of patients suggest that AVM-associated aneurysms
may behave in an especially aggressive fashion when
occurring in certain locations. Westphals series of
285
222 patients with AVMs included 198 supratentorial
AVMs and 24 located infratentorially (67). They iden-
tified aneurysms associated with 5 out of 24 (20.8%) of
infratentorial AVMs, a considerably larger proportion
than the 3.5% associated with their AVMs in a supra-
tentorial location. Their findings also suggested more
aggressive behavior associated with aneurysms in the
infratentorial group. Of the five aneurysms associated
with infratentorial AVMs, four were located distally
and 75% of these were responsible for intracranial
hemorrhage (Figs. 13 and 14).
Data suggesting a relatively aggressive course of
cerebellar feeding pedicle aneurysms are supported
by Kaptains evaluation of 27 cerebellar AVMs, all of
which were associated with aneurysms (68). Eighty-
nine percent of this population presented with symp-
toms of aneurysm rupture. The vast majority of
aneurysms, i.e. 29 out of 36 (81%), was located distally
on arteries supplying the AVM. These authors also
concluded that aneurysms associated with cerebellar
AVMs frequently present with rupture. In addition,
the usually distal location made the aneurysms treat-
able in a large proportion of cases without significant
risk to the brain stem. Finally, Khaw et al. reported a
higher prevalence of aneurysms associated with infra-
tentorial AVMs in comparison to those in a supra-
tentorial location. Infratentorial AVMs with associated
aneurysms were also significantly more likely to pres-
ent with intracranial hemorrhage than those without
associated aneurysms (69).
It is not clear to what extent aneurysms increase
the risk of intracranial hemorrhage when they occur in
association with AVMs. In part, the difficulty arises
from identifying the incremental risk associated with
the aneurysm in the face of an already high risk of
hemorrhage presented by the AVM. Sufficient data
Figure 14 (A). Intranidal aneurysm responsible for
AVM hemorrhage (arrow). (B) Unsubtracted and (C)
subtracted microcatheter injection of feeding pedicle
(arrow: aneurysm; arrowhead: catheter tip). (D) Post-
embolization, no filling of pedicle (arrow) or aneurysm.
Residual AVM treated with radiosurgery. Abbreviation:
AVM, arteriovenous malformation.
286 Weigele et al.

exist, however, to indicate that patients with AVM-
associated aneurysms are likely at higher risk of hem-
orrhage than are patients with an AVM alone. While
this seems particularly true for infratentorial AVMs, it
apparently holds as well for AVMs in all locations
associated with intranidal aneurysms, and to a lesser
extent for extranidal aneurysms. Given this informa-
tion, a number of management approaches to patients
identified as having AVM-associated aneurysms have
been suggested.
Treatment approaches. Specific management rec-
ommendations for patients having both aneurysm(s)
and an AVM are difficult to formulate because of the
relatively sparse and often conflicting data. General
guidelines have been suggested, however (Table 5).
For patients presenting with hemorrhage, the first step
is to determine which lesion was responsible for the
hemorrhage. It is that lesion toward which the initial
treatment should be directed. As noted, in posterior
fossa AVMs, higher proportions of hemorrhage may
result from feeding artery aneurysms than is the case
in supratentorial locations (Fig. 15). When no deter-
mination can be made as to the source of hemorrhage,
the greater morbidity and higher chance of repeat
hemorrhage from an aneurysm dictates that the
aneurysm be addressed as a first priority.
In cases where the AVM is identified as the source
of hemorrhage, initial treatment is directed at that
lesion. Most data indicate that intranidal aneurysms
associated with AVMs presenting with hemorrhage
should be strongly considered to be the source of
hemorrhage and treatment initially directed at this
feature of the AVM (46). While detailed imaging and
identification of the aneurysm adjacent to the hematoma
may often confirm the source of the hemorrhage, this
may not be possible in all cases.
The specific treatment depends on the overall
treatment plan for the AVM. If surgically treatable,
intranidal aneurysms may be addressed by surgical
resection of the entire AVM, possibly preceded by
presurgical embolization. If performed, endovascular
treatment should be targeted to close the feeding
pedicle from which the aneurysm originates first in
order to minimize the chance of subsequent hemor-
rhage. If the AVM is to be treated with radiosurgery,
preradiosurgery embolization directed at the intra-
nidal aneurysm may also be a reasonable plan to
decrease the risk of hemorrhage during the period
required for obliteration of the AVM.
While the AVM should be addressed initially
when identified as the source of hemorrhage, the
effect of closure of the AV shunt on associated aneur-
ysms must also be considered, regardless of which
lesion is responsible for the initial presentation. Differ-
ing recommendations have been made with respect to
prophylactic treatment of feeding artery aneurysms in
conjunction with AVM hemorrhage.
Thompson et al. found that of 45 aneurysms
identified in their 600 patients (7.5%), five bled prior
to treatment while two bled within three weeks

Table 5 Management of AVM-Associated Aneurysm Patients with Hemorrhage

Aneurysm hemorrhage Aneurysm location Rx
AVM resectable Intranidal aneurysm Both lesions simultaneously
Distal pedicle aneurysm Aneurysm firstconsider AVM resection at same time
Proximal aneurysm Aneurysm firstconsider AVM resection at same time
Unrelated aneurysm Aneurysm first
AVM unresectable Intranidal aneurysm Embolization of aneurysm & pedicle
Distal pedicle aneurysm Aneurysm
Proximal aneurysm Aneurysm
Unrelated aneurysm Aneurysm

AVM hemorrhage Aneurysm location Rx

AVM resectable Any Rx AVM firstconsider distal pedicle aneurysm treatment if low risk
AVM unresectable Intranidal aneurysm Embolization of intranidal aneurysm feeder first
Radiosurgery, consider embolization of intranidal feeder first
Distal pedicle aneurysm Consider aneurysm Rx first (controversial)
Proximal aneurysm AVM first
Unrelated aneurysm AVM first

Unknown hemorrhage source Aneurysm location Rx

AVM resectable Intranidal aneurysm Rx AVM and aneurysm
Distal pedicle aneurysm Rx AVM and aneurysm
Proximal aneurysm Rx aneurysm first
Unrelated aneurysm Rx aneurysm first
AVM unresectable Intranidal aneurysm Embolization of intranidal feeder first
Distal pedicle aneurysm Rx aneurysm
Proximal aneurysm Rx aneurysm
Unrelated aneurysm Rx aneurysm
Abbreviation: AVM, arteriovenous malformation.
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations
following AVM treatment. Their experience led them
to recommend treatment of aneurysms on feeding
vessels prior to definitive treatment of the AVM (49).
Similarly, Ezura et al. treated feeding artery aneur-
ysms endovascularly prior to treating the AVM with
either resection or radiosurgery (53).
However, others suggest that decreasing flow
through the AVM results in frequent regression of
extranidal aneurysms without the need for direct
treatment. For example, Redekop et al. reported com-
plete spontaneous regression of aneurysms on distal
feeding arteries in 80% of cases after curative therapy
of the AVM (52). These authors also noted shrinkage
of proximally located aneurysms in 18% of cases with
complete disappearance in 4%. The effect on aneur-
ysms appeared to be less in cases of incomplete AVM
treatment. Of 16 patients with less than 50% reduction
in the AVM, no aneurysms regressed, although two
enlarged and bled. In cases with greater than 50%
reduction in the AVM, two of three distal aneurysms
disappeared and five proximal aneurysms were
unchanged.
Meisel et al. also reported significant regression
of feeding artery aneurysms after treatment of the
AVM (46). In 83 treated patients with 149 proximally
located aneurysms, they found complete regression in
8% and more than 50% shrinkage in 22%. The shrink-
age of proximally located aneurysms was influenced
by the degree of AVM occlusion and occurred faster
for those aneurysms on midline vessels, such as the
anterior cerebral artery and the circle of Willis. Their
287
Figure 15 Embolization of an ectatic distal arterial
feeder and aneurysm supplying a cerebellar AVM
presenting with hemorrhage. (A) Selective and
(B) superselective lateral vertebral angiograms show
a cerebellar AVM supplied by an ectatic distal feeder
(arrowhead ) containing an aneurysm (arrow). (C) Post-
embolization with NBCA, no filling of pedicle or aneur-
ysm. (D) Unenhanced CT image shows an NBCA-filled
aneurysm (arrow) surrounded by hyperdense hemor-
rhage (arrowheads ). Abbreviations: AVM, arteriove-
nous malformation; NBCA, N-butyl cyanoacrylate.
finding that no hemorrhage from untreated proxi-
mally located aneurysms occurred after partial treat-
ment of AVMs led them to conclude that proximally
located aneurysms should not be treated primarily in
cases where the AVM is the source of hemorrhage.
Summary. Aneurysms are found in association
with a significant proportion of AVMs. They may
occur within the AVM nidus, on routes of flow to
the AVM, or on vessels unrelated to the AVM supply.
Those on vessels providing supply to the AVM likely
arise from the high flow resulting from the AVM.
AVM-associated aneurysms present an increased risk
of hemorrhage, particularly those that are intranidal
or distally located on feeding pedicles. They may
regress spontaneously following AVM treatment,
with those more distally located being more affected
by flow and pressure changes associated with AVM
obliteration. In any case, AVM-associated aneurysms
represent an additional source of potential morbidity
that must be considered in formulating treatment of
the AVM patient.
GRADING SYSTEMS FOR BRAIN AVMs
Because of the tremendous variability of brain AVMs
with respect to their anatomy and biological behavior,
a number of studies have attempted to correlate spe-
cific criteria of AVM characteristics with therapeutic
outcomes to guide clinical decision-making. Most
of these grading systems have focused on surgical
management.
288 Weigele et al.
Luessenhop and Gennarelli were the first to
assign a grade to a brain AVM in an effort to predict
operability and outcome. Grading was based on the
number of arteries feeding the AVM and the vascular
territory that was involved. Other criteria such as size,
anatomic location, degree of vascular steal, and
venous drainage were not included, limiting the sys-
tems utility (70).
In 1986, two new grading systems were pro-
posed. Shi and Chen categorized AVMs on the basis
of four criteria: (1) size, (2) location and depth, (3) com-
plexity of the arterial supply, and (4) complexity of the
venous drainage. Each criterion was attributed a
grade of I to IV on the basis of a detailed analysis
that was related to the operative risk. A composite
grade was assigned on the basis of the grades for the
individual criteria. This complex system did not gain
widespread usage (71).
Spetzler and Martin also proposed a grading
system for brain AVMs in 1986 that has become the
most widely utilized. The authors sought a system
that was simple and applicable to all brain AVMs
providing a reasonable estimate of operative morbid-
ity and mortality. They considered a number of
parameters, including the AVM size, the number of
feeding arteries, the anatomic location, the operative
accessibility, the amount of flow, degree of vascular
steal, the eloquence of nearby brain parenchyma, and
the venous drainage pattern (72).
Recognizing that a grading system that attempted
to incorporate all of the potential parameters would be
too complex to be practical, and that many of those
variables were interrelated, they proposed a simplified
grading system based on three criteria: the AVM size,
the venous drainage pattern, and the eloquence of the
adjacent brain parenchyma. The AVM size was div-
ided into three categories: small (<3 cm), medium (3 to
6 cm), and large (>6 cm). The venous drainage was
designated as superficial only if all of the venous
drainage emptied into the cortical venous system. If
any or all of the venous drainage egressed through
deep veins (internal cerebral, basal veins, precentral
cerebellar vein) it was categorized as deep. An AVM
was considered to be adjacent to eloquent brain paren-
chyma if it was next to the sensorimotor cortex, lan-
guage areas, visual cortex, hypothalamus, thalamus,
internal capsule, brain stem, cerebellar peduncles, or
deep cerebellar nuclei (72).
When using the Spetzler-Martin grading system,
points are assigned for the AVM size, the venous
drainage pattern, and the location relative to eloquent
brain (Table 6). The points for each parameter are
added for the total score (15) that corresponds to the
Spetzler-Martin grade (IV). For example, a 2-cm
anterior frontal lobe AVM with cortical venous drain-
age (1 point for size, 0 points for venous drainage,
0 points for eloquence) is a Spetzler-Martin grade I
AVM, whereas a 4-cm thalamic AVM with deep
venous drainage (2 points for size, 1 point for venous
drainage, 1 point for eloquence) is a Spetzler-Martin
grade IV AVM. AVMs with no possibility of surgical
resection (e.g., diffuse brain stem or holohemispheric
involvement) are assigned a grade of VI (72).
Table 6 Spetzler-Martin grading system for brain AVMs
AVM Feature Points
Size of nidus
<3 cm (small) 1
36 cm (medium) 2
>6 cm (large) 3
Eloquence of adjacent brain
Noneloquent 0
Eloquent 1
Venous drainage
Superficial 0
Deep 1
The assigned grade equals the sum of the points for all the three
features.
Abbreviation: AVM, arteriovenous malformation.
Source: From Ref. 72.
Following resection of Spetzler-Martin grade I
and II AVMs, the authors retrospective evaluation of
their personal surgical experience found a low inci-
dence of minor deficits (0%, 5% in grade I AND II,
respectively) and no major neurological deficits; grade
IV and V AVM resections were associated with signif-
icant incidences of both minor deficits (20%, 19% in
grade IV and grade V, respectively) and major deficits
(7%, 12% in grade IV and grade V, respectively) (72).
A subsequent prospective evaluation confirmed the
accuracy of the Spetzler-Martin grading system for
predicting both new-temporary and new-permanent
neurological deficits (73). A recent analysis demon-
strated interobserver variability between a neuroradi-
ologist and a neurosurgeon performing Spetzler-
Martin grading in 27.7% of patients; however, this
variability did not diminish the predictive value of
the Spetzler-Martin scale (74).
EMBOLIZATION OF BRAIN AVMs
Historical Background
In a landmark publication in 1960, Luessenhop and
Spence reported the first therapeutic embolization of a
brain AVM (75). Because this report predated the
development of selective cerebral angiography, the
authors injected Silastic spheres directly into a surgi-
cally accessed cervical internal carotid artery. Their
technique relied on the much greater rate of blood
flow to the AVM to direct the spheres into the nidus
rather than into normal cerebral branches; however,
this flow-dependent embolization was unreliable and
was associated with a significant risk of causing an
ischemic infarct. Another problem was that the rela-
tively large spheres lodged in the proximal feeders
and did not penetrate into the nidus. The nidus
remained unoccluded and could recruit deep perfo-
rating arteries that were much more difficult to control
during surgery (7679).
In 1974, Serbinenko was the first to report super-
selective cerebral artery catheterization and emboliza-
tion using a detachable balloon attached to a flexible,
flow-directed catheter (80). Superselective catheteriza-
tion of the target vessel with the balloon catheter was
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations
not always technically feasible because it depended
on the arterial geometry and hemodynamics. Similar
to the problem with the flow-directed Silastic spheres,
the detachable balloons occluded the proximal arterial
feeders inducing the nidus to recruit new blood sup-
ply from other branches that were often more difficult
to control during surgery. This early experience sug-
gested the AVM nidus should be the target of thera-
peutic embolization.
In 1976, Kerber set the stage for the development
of modern therapeutic brain AVM embolization tech-
niques. He reported the use of a microcatheter with a
calibrated-leak balloon to superselectively catheterize
cerebral arteries and to deliver a liquid embolic agent
[isobutyl-2-cyanoacrylate (IBCA)] into the AVM nidus
(81). However, both the catheter and the embolic
agent had serious limitations. Calibrated-leak balloon
catheters were difficult to use and were associated
with multiple complications including vascular inju-
ries. The catheters also could be permanently glued
into the AVM (82). In addition, the IBCA transformed
the AVM into a hard, incompressible mass with ill-
defined borders and containing embolized vessels that
were difficult to surgically cut or coagulate (82,83).
IBCA also was reported to be carcinogenic and asso-
ciated with toxic reactions (84,85).
These pioneering efforts provided the founda-
tion and stimulus for the development of the micro-
catheters, guidewires, and embolic agents that are
currently used for AVM embolization. This early
experience also established the concept of targeting
the nidus for embolic occlusion, and defined the risks
of embolizing too proximally (the arterial feeders) and
too distally (the venous outflow).
Embolization Indications
Current therapeutic options for brain AVMs include
embolization, microvascular surgery, stereotactic radi-
ation (radiosurgery), and various combinations. The
goal of any combined therapy is to decrease the over-
all morbidity and mortality of AVM treatment. In
many centers, brain AVM embolization is most com-
monly performed before microsurgical resection.
Embolization is also performed prior to radiosurgery.
In this setting, the goal is to permanently occlude
enough of the nidus so that stereotactic radiation can
target the rest with a higher dose and a better chance
for cure. Less frequently, embolization is used as a
stand-alone curative technique, especially for small,
surgically difficult lesions. Occasionally, embolization
is employed for the palliation of symptoms from an
otherwise untreatable AVM. Ideally, a multidiscipli-
nary team consisting of a microvascular neurosur-
geon, an interventional neuroradiologist, and a
radiation therapist collectively evaluates and formu-
lates an individualized plan for each patient.
Presurgical Embolization
Microvascular surgery is the principle method to treat
brain AVMs at many centers. Neurosurgical outcomes
have improved with advances in stereotactic guid-
ance, electrophysiological monitoring, barbiturate
289
anesthesia, intraoperative angiography, and aggres-
sive perioperative blood pressure control. Many small,
superficial brain AVMs can be surgically resected
without preoperative embolization with minimal mor-
bidity and mortality (73). Nonetheless, preoperative
embolization results in improvements in overall treat-
ment outcomes for many brain AVMs.
Brain AVM embolization can improve surgical
outcomes through several mechanisms. Often, the
most valuable contribution is the elimination of deep
or surgically inaccessible feeders. The deep arterial
supply is approached through the nidus toward the
end of the surgical resection, and gaining surgical
control can be treacherous. Preoperative embolization
of the deep arterial supply can allow an otherwise
inoperable AVM to be successfully resected (86). Also,
embolization can decrease the size of the nidus and
the amount of blood flow through the AVM resulting
in shorter surgical times and less blood loss. Embolized
vessels also are easily identified during surgery. This
provides a road map for the resection of the arterial
feeders and nidus while preserving en passage arteries
to nearby eloquent parenchyma (Fig. 8). In addition,
the staged embolization of a large, high-flow AVM can
decrease the incidence of potentially catastrophic
hemorrhage caused by rapidly changing hemodynam-
ics (e.g., normal perfusion pressure breakthrough).
Finally, preoperative embolization of feeding vessel
and nidal aneurysms can eliminate those angioarchi-
tectural risk factors for perioperative hemorrhage.
Proximal feeding artery aneurysms are at risk for rup-
ture after AVM resection because elimination of the AV
shunt causes a sudden increase in arterial pressure.
These proximal aneurysms may be impossible to access
through the craniotomy for the AVM resection, and
preoperative embolization eliminates the need for a
second craniotomy (86,87).
There is a general consensus that many superfi-
cial Spetzler-Martin grade I and II AVMs can be
surgically resected with minimal morbidity and mor-
tality without preoperative embolization. In these
cases, the additional risks of embolization may not
be justified. There are, however, exceptions such as a
grade I or II AVM with a deep feeder that is difficult to
access surgically (88,89). Also, some experts advocate
embolizing an intranidal aneurysm in a Spetzler-
Martin grade I or II AVM presenting with acute
hemorrhage to stabilize the nidus until surgery (89).
Embolization is used frequently for Spetzler-Martin
grade III AVMs, particularly for those in central and
eloquent locations and those with deep feeders. Pre-
operative embolization (often staged) is commonly
employed for those Spetzler-Martin grades IV and V
AVMs considered for resection.
Preradiosurgical Embolization
There is a wide variability at different institutions in
the use of combined embolization and radiosurgery.
Stereotactic radiosurgery primarily is employed
at some centers for small brain AVMs that have
a high surgical risk because they are deep-seated or
are located in the eloquent cortex. Other centers
290 Weigele et al.
frequently use embolization to render large brain
AVMs amenable to stereotactic radiosurgery. In this
setting, embolization is used to reduce the size of the
AVM to increase the probability of a radiosurgical cure
(90). The rate of cure after stereotactic radiosurgery
significantly decreases as the volume of AVM being
treated increases (9193). Radiosurgical cure is more
likely after embolization has reduced the residual
AVM volume to less than 10 cc (90,94). The goal of
embolization is to shrink the nidus into a smaller single
target; however, this is not always possible. Alterna-
tively, two or more discrete areas of residual nidus can
be treated with a volume-staged approach (95). Embo-
lization is also performed prior to radiosurgery to
occlude nidal aneurysms that represent a risk for hem-
orrhage until the radiosurgically induced obliteration
occurs and also to occlude high-flow fistulas that may
be refractory to radiosurgery (90). Repeat embolization
or surgery also can be used to treat residual AVM
persisting after radiosurgery (96,97).
Curative Embolization
There is currently a limited role for curative emboli-
zation of brain AVMs (Fig. 16). Although embolization
can successfully obliterate some small AVMs that
have limited feeders, it rarely cures large, complex
AVMs. Most of the AVMs that have a relatively high
probability of cure with embolization are amenable to
complete surgical removal with negligible morbidity
and mortality. Therefore, justifying the risks of an
attempted curative embolization is often questionable
(73,98). Small deep central AVMs with limited feeders
are exceptions where curative embolization can play
an important role (99).
Palliative Embolization
Palliative embolization does not appear to improve on
conservative medical management of most patients
with incurable AVMs and may even worsen the sub-
sequent clinical course (100). There are, however,
appropriate goal-directed roles for palliative emboli-
zation in select circumstances. Palliative embolization
can alleviate symptoms due to vascular steal and
mechanical compression and obliterate specific aneur-
ysms responsible for repeated hemorrhages. Emboli-
zation of meningeal supply can improve intractable
headaches (101103).
Embolization Tools and Technique
Microcatheters and Guidewires
The flow-directed microcatheters currently used for
embolization with liquid agents are designed for safe
and reliable navigation into the very distal aspects of
the intracranial circulation. They have several seg-
ments of progressive softness. The proximal segments
are relatively stiff and thick-walled to transmit longi-
tudinal motion and torque efficiently. The transitional
middle segments have thinner walls and progres-
sively increase in flexibility but remain pushable.
The distal segments are small (1.3- to 1.8-Fr outer
diameter), thin walled, and extremely soft and supple.
They provide no intrinsic transmission of longitudinal
Figure 16 Curative AVM embolization. (A) Lateral
angiogram shows occipital AVM nidus (arrow).
(B) Superselective angiogram (arrow, microcatheter
tip). (C, D) AP and lateral postembolization angiogram
shows complete obliteration of the nidus. Abbreviation:
AVM, arteriovenous malformation.
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations
force. The catheter tips are slightly bulbous so blood
flow will pull them forward. The microcatheters have
hydrophilic surface coatings to decrease thromboge-
nicity, facilitate movement through small tortuous
vessels, and prevent adhesion of embolic agents.
Guidewires designed for use in the cerebral arteries
(0.0080.014 inch) have very flexible distal segments
and soft, shapeable platinum tips. They also are
covered with a hydrophilic coating to reduce friction
between the catheter and guidewire. They remain
torquable even after they have gone through sev-
eral curves. Only the smallest guidewires, such as the
0.008-inch Mirage (EV3, Plymouth, Minnesota, U.S.),
will pass through the flow-directed microcatheters
commonly used with liquid embolic agents (104).
Vessel Selection
Current techniques for brain AVM embolization
require advancing a suitable microcatheter into the
very distal aspect of an arterial feeder supplying the
nidus. A guide catheter (e.g., Envoy, Cordis Endovas-
cular, Miami Lakes, Florida, U.S.) first is placed in the
distal cervical aspect of the appropriate internal carotid
or vertebral artery. A 6-Fr guide catheter is preferred
for easier contrast injections while the microcatheter is
inserted; however, a 5-Fr guide catheter may be
safer in a small vertebral artery. A rotating hemostatic
valve is used for coaxial placement of a microcatheter
and to continuously flush the guide catheter with
heparinized saline. Intravenous heparin is adminis-
tered on an individual basis to prevent thromboemboli
if there are small feeders or there is slow flow. A
microcatheter (1.5- or 1.8-Fr Spinnaker Elite, Boston
Scientific Corporation, Natick, Massachusetts, U.S.;
Marathon or Ultraflow, EV3) with a small steam-
shaped distal curve (e.g., 1-mm radius distal J
shape) is navigated through the cerebral arteries
under continuous subtracted fluoroscopic (road-map)
imaging. There are two primary techniques for intra-
cranial navigation: flow directed and guidewire
assisted. Flow-directed navigation uses arterial blood
flow to drag the very flexible distal catheter segment
and slightly bulbous catheter tip forward. The tip will
preferentially tend to advance into the vessel with the
highest flow, which is usually the desired feeder to the
AVM. Directional control also is facilitated by gentle
injections of contrast (puffing) to redirect the curved
tip into the desired branch. For guidewire-assisted
navigation, a 0.008-inch Mirage (EV3) guidewire is
advanced into the distal segment of the microcatheter
to augment its pushability and to change shape of
the catheter tip. Advancing and withdrawing the
guidewire in the distal segment also changes its elas-
ticity often prompting the catheter tip to spring for-
ward. When necessary, the Mirage guidewire can be
extended beyond the microcatheter tip to navigate
difficult anatomy; however, this must be done with
caution to avoid arterial perforation or dissection.
Blood pressure augmentation with neosynephrine or
vasodilatation with papaverine or hypercapnia also
can be used to facilitate distal catheter advancements
(104106).
291
Provocative Testing (Superselective Wada Test)
Approximately 10% of brain AVM embolizations
cause a permanent neurological deficit (107). Many
of these deficits are caused by embolization of
branches arising from an AVM feeder that supply
normal brain parenchyma (108). These branches may
not be seen during superselective angiography prior
to embolization because of the high blood flow (sump
effect) into the nidus. They can be occluded during
subsequent embolization because of changing hemo-
dynamic conditions, resulting in an infarct. Provoca-
tive testing (the superselective Wada test) is intended
to prevent this complication by identifying any angio-
graphically occult blood supply to eloquent brain
parenchyma from the feeder proposed for emboliza-
tion. Although some experts are strong proponents for
the use of this provocative testing, others argue it is
not necessary (109).
A short-acting barbiturate (amobarbital) is
injected intra-arterially with the microcatheter posi-
tioned at the site of intended embolization and appro-
priate neurological testing is carried out. Provocative
testing usually is performed with the patient awake to
facilitate neurological examinations after the amobar-
bital is injected. If a transient neurological deficit
occurs, embolization is contraindicated from that cath-
eter position. The addition of electroencephalographic
monitoring to the clinical exam has been reported to
increase the tests sensitivity (110).
Amobarbital principally affects the gray matter
through the gamma-amino butryic acid A (GABAA)
receptor. The white matter is not affected. A recent
report advocates additional provocative testing with
lidocaine. This inhibits both gray and white matter by
blocking the voltage-dependent sodium channel and
has been suggested to be able to detect deficits that
might not be detected by amobarbital alone (111).
Several case series have reported provocative
testing that can identify situations where embolization
will cause a neurological deficit; however, they are all
relatively small and uncontrolled (110113). The value
of provocative testing is vigorously debated. Those
who opposed to provocative testing argue that if
contrast does not flow into normal branches during
superselective angiography because of the sump
effect, then even the provocative agent will not flow,
thus yielding a false negative test result. Also, the
changing hemodynamics that occur during emboliza-
tion are not simulated during the provocative test. In
addition, the potential effect of proximal reflux during
embolization is not evaluated. Finally, the use of gen-
eral anesthesia is precluded by the need for neu-
rological testing. Some believe general anesthesia
significantly enhances the safety of embolization by
preventing dangerous patient motion during critical
moments of the procedure. Opponents of provocative
testing conclude that careful evaluation of the AVM
anatomy (location with respect to eloquent brain
and the angioarchitecture), as well as the use of an
intranidal microcatheter position for embolization
may be more reliable than provocative testing to
avoid ischemic complications (109,114). Proponents
292 Weigele et al.
for provocative testing argue that superselective amo-
barbital testing compliments the analysis of the vas-
cular anatomy to minimize ischemic complications
and do not believe general anesthesia is essential to
perform safe embolizations (110). Provocative testing
also may be important from a medicolegal perspective
if there is a serious complication (109).
Embolic Agents
There are three general categories of currently avail-
able embolic agents: solid occlusive devices (coils, silk
threads, balloons), particulates [polyvinyl alcohol
(PVA) particles], and liquids (cyanoacrylates, Onyx,
ethanol) (115). Solid occlusive devices primarily are
used to occlude large direct AV fistulas. Particulate
embolization using PVA particles has been replaced
by liquid embolization with N-butyl cyanoacrylate
(NBCA) at most centers (109). Onyx is a promising
liquid embolic agent recently approved by the Food
and Drug Administration (FDA) (116). Although abso-
lute ethanol and silk threads have been used to
embolize brain AVMs, limited results have been pub-
lished (117,118).
Polyvinyl alcohol particles. PVA particles were
commonly used for brain AVM embolization before
liquid agents such as NBCA and Onyx became more
widely used. PVA particles are supplied in various
size ranges from 50 to 1000 mm. They are nonradio-
paque and are mixed with iodinated contrast for
delivery. PVA particles are often used in combination
with coils or silk threads to facilitate their retention,
especially in larger AV shunts (119). Typically, larger
(e.g., 3-Fr) over-the-wire microcatheters have been
required for larger PVA particles (>500 mm) resulting
in more proximal embolizations of the arterial feeders
rather than the nidus, although recently more distal
PVA embolizations have been made possible with
hybrid flow-guided or over-the-wire catheters and
liquid coils (89).
PVA particles have several disadvantages as
compared to liquid embolic agents. They can occlude
the small, flow-directed microcatheters that can be
most reliably advanced into the distal feeder. Also,
since the particles are radiolucent, it is not possible to
identify where they deposit. There is evidence they
often aggregate and frequently occlude the arterial
feeder rather than the nidus. The nidus can then
recruit collateral blood supply and regrow. This may
explain why Sorimachi et al. found 43% of brain
AVMs partially embolized with PVA particles dem-
onstrated an increase in the size of the nidus on
follow-up angiograms (119). In addition, a histopatho-
logical analysis revealed PVA-embolized vessel
lumens contained clumps of particles intermixed with
thrombus rather than solid luminal packing with PVA.
Eighteen percent of the embolized vessels were par-
tially recanalized (120). This may explain why AVMs
that appear completely obliterated on angiography
after PVA embolization can reappear on follow-up
exams (119).
For these reasons, a permanent occlusion of
some or all of an AVM nidus seems less likely with
PVA than with liquid embolic agents. This lack of
permanency is undesirable for an embolization per-
formed as an adjunct for radiosurgery where the
embolized portion of the AVM is excluded from the
radiation field or for an embolization performed for
cure. This conclusion is supported by the observation
that 15% to 20% of AVM patients undergoing PVA
embolization prior to radiosurgery had recanalization
two to three years later on follow-up angiography
(92,94). This lack of a durable occlusion, however,
may not be a significant disadvantage for presurgical
embolizations with PVA particles. A prospective,
randomized, multicenter trial concluded PVA and
NBCA were similar in safety and effectiveness for
preoperative brain AVM embolization (89).
N-Butyl cyanoacrylate. Cyanoacrylates have been
used for brain AVM embolization for more than
20 years. Early problems with cyanoacrylate emboliza-
tion (see historical background) that prevented wide-
spread use have been solved with the replacement of
previous formulations with NBCA and with advances
in microcatheter and guidewire technology (109). The
FDA approved NBCA (Trufill, Cordis Endovascular)
for brain AVM embolization in 2000. NBCA has
become the most commonly used embolic agent for
this purpose in the United States. The Cordis NBCA kit
contains NBCA, ethiodol, and tantalum powder. Ethio-
dol is mixed with NBCA to prolong the polymerization
time and also to make the solution radiopaque. Tanta-
lum power can be added to the NBCA/ethiodol mix-
ture to further increase its radiopacity.
The liquid NBCA monomer undergoes a rapid
exothermic polymerization catalyzed by nucleophiles
found in blood and on the vascular endothelium to
form an adhesive, nonbiodegradable solid. The vessel
is permanently occluded when the polymer com-
pletely fills the lumen. NBCA provokes an inflam-
matory response in the wall of the vessel and
surrounding tissue leading to vessel necrosis and
fibrous ingrowth. These histological responses also
may contribute to the permanency of NBCA occlu-
sions (121,122).
NBCA has a number of useful properties for
brain AVM embolization. The liquid monomer can
be injected through small (1.5- and 1.8-Fr) flow-
directed microcatheters such as the Spinnaker Elite
(Boston Scientific) and the Ultraflow (EV3) that can be
reliably and safely positioned in the distal arterial
feeder or within the nidus. This distal catheter posi-
tioning maximizes the likelihood of adequate nidal
penetration to achieve a permanent occlusion and
minimizes the risk of inadvertent embolization of
normal branches (109).
The NBCA polymerization rate can be adjusted
to satisfy specific requirements. The goal of the embo-
lization is to form a solid intranidal NBCA cast,
avoiding early polymerization in the arterial feeder
or late polymerization in the venous outflow. Pure
NBCA polymerizes almost instantaneously at the
catheter tip. Although this may be necessary to
occlude a direct high-flow fistula, immediate poly-
merization will not allow the NBCA to penetrate
optimally into a plexiform nidus (109). The addition
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations
of ethiodol slows the polymerization rate, allowing
better nidal penetration. The polymerization rate pro-
gressively decreases as more ethiodol is added. The
objective is to use an ethiodol/NBCA mixture with a
polymerization time optimally matched to the indi-
vidual AVMs angioarchitecture and hemodynamics.
The AV transit time on superselective angiography is
subjectively evaluated as a guide to formulating the
mixture. This is far from an exact science and is highly
dependent on experience. The concept of a wedged transform inoperable AVMs into surgically resectable
catheter position, where forward flow is controlled by
the rate of injection, theoretically allows slower, more
controlled injections of a more dilute NBCA/ethiodol
mixture with a longer polymerization time (109).
The use of ethiodol has limitations. A high
ethiodol concentration also increases the viscosity of
the mixture, which can conversely decrease the nidal
penetration. Dilute NBCA mixtures also tend to dis-
perse in small droplets that can incompletely cast the
vessels, possibly allowing recanalization (122). Glacial
acetic acid can be added as an alternative method to
slow the rate of polymerization, without causing the
increased viscosity of higher ethiodol/NBCA concen-
trations. This may result in better nidal penetration
and more solid casting (123).
293
Many experts believe portions of the AVM nidus
that are well cast with NBCA can be considered
permanently obliterated (109). Wikholm followed
12 brain AVMs totally occluded with NBCA for 4 to
78 months and found no angiographic evidence of
recanalization (124). In a recent study, six patients with
complete obliteration of the AVM nidus had no angio-
graphic evidence of recurrence at 17 to 32 months (125).
NBCA embolization therefore has the potential to
lesions and to reduce the size of an AVM nidus
sufficiently to make radiosurgery possible. Some
small AVMs can be cured by embolization alone.
A solid NBCA cast in the nidus is essential to
assure permanent obliteration of the AVM (109).
Debrun described the single-column flow-controlled
technique for optimal nidal filling using a microcath-
eter that is wedged intranidally and the use of a
relatively dilute NBCA mixture (Fig. 17) (109). Solid
casting is important since brain AVMs that were
incompletely embolized with NBCA demonstrated
histological evidence of capillary regrowth in the
lumen of embolized vessels after three months (121).
Brain AVMs embolized with NBCA have favor-
able properties for surgical resection. The vessels are
Figure 17 Wedged catheter embolization of nidal
pseudoaneurysm presenting with hemorrhage. (A, B)
AP and lateral angiograms show plexiform cerebellar
AVM. (C) Superselective superior cerebellar angiogram
shows large nidal pseudoaneurysm (arrow ) and small
nidal aneurysm (arrowhead ). (D) Wedged catheter
injection visualizing pseudoaneurysm and superior
nidus (arrow, microcatheter tip). (E) NBCA cast in
pseudoaneurysm (arrow) and superior nidus (arrow-
heads). (F) Lateral postembolization angiogram. Abbre-
viations: AVM, arteriovenous malformation; NBCA,
N-butyl cyanoacrylate.
294 Weigele et al.
easily compressible and transected. The embolized
feeders can be readily identified and differentiated
from nonembolized en passage branches to normal
brain (Fig. 8). In addition, the embolization of the
AVM nidus provides a distinct boundary zone
between the AVM and normal brain (126).
NBCA Technique The following is a general
description of the brain AVM embolization protocol
using NBCA at our institution. Procedures are usually
performed under conscious sedation rather than gen-
eral anesthesia to allow provocative testing. An appro-
priate microcatheter is negotiated through the cerebral
vasculature into the desired AVM feeder using a
combination of flow and guidewire guidance (see
vessel selection). The microcatheter tip is advanced
into the distal aspect of the desired feeder. Operator
preference and the nidal anatomy determine whether
a free or wedged catheter tip position is used. Excess
slack (redundant loops) in the microcatheter is
removed to facilitate its removal after the emboliza-
tion. A superselective angiogram is performed with a
1-cc syringe and a gentle hand injection. The
angioarchitecture is analyzed. If no normal branches
are visible, provocative testing is performed with
amobarbital.
The NBCA/ethiodol/tantalum mixture (Trufill,
Cordis Endovascular) is prepared using clean gloves
on a separate sterile table to prevent contamination
with ionic catalysts. For a wedged injection (109), a
relatively dilute concentration of NBCA (2533%) is
made by mixing 1 cc of NBCA with 2 or 3 cc of
ethiodol in a shot glass. The vial of tantalum powder
included in the Trufill kit is added to increase the
radiopacity of the mixture. Relative hypotension is
induced (2030% decrease in mean arterial pressure).
Test injections are made with a subtracted fluoro-
scopic image to confirm the catheter position and to
gauge the optimal injection rate. The microcatheter is
irrigated with 5% dextrose to flush all of the ionic
catalysts from the lumen. The dilute NBCA solution is
then injected slowly into the nidus over 15 to 60
seconds during continuous subtracted fluoroscopic
observation. The injection rate is modified to obtain
a solid nidal cast without causing proximal reflux. If a
drop of NBCA enters a draining vein, the injection is
paused several seconds. The injection is then restarted
and continued if additional nidal filling is observed. If
another drop enters a vein, the injection is terminated.
The injection is also terminated if proximal reflux
occurs. The microcatheter is aspirated and briskly
removed. The guide catheter is aspirated and its tip
is examined fluoroscopically. A postembolization
angiogram is then obtained.
A nonwedged injection is performed in a sim-
ilar fashion; however, a more concentrated NBCA
solution is used because of the more rapid flow and
the shorter arterial-venous transit time through the
nidus. The injection rate is faster and the injection
time is much shorter (one to three seconds). If a large
direct fistula is present, maximal induced hypotension
and a very high NBCA concentration are used. In this
setting, coils (Liquid Coils, Target/Boston Scientific,
Natick, Massachusetts, U.S.) can be injected first into
the fistula to slow the rate of flow and to form a
framework for the NBCA to adhere to.
At our institution, NBCA is most commonly
used for preoperative embolization of large, complex
AVMs. We typically occlude a maximum of 33% of the
nidus during one session to minimize the risk of
normal perfusion pressure breakthroughinduced
hemorrhage (127). Embolization is also terminated if
venous stagnation occurs to minimize the risk of
postprocedural hemorrhage caused by venous out-
flow compromise (128).
Onyx. Onyx (EV3) is a premixed, liquid
embolic agent consisting of ethylene-vinyl alcohol
copolymer (EVOH) and tantalum powder (for radio-
pacity) dissolved in dimethyl sulfoxide (DMSO).
EVOH contains 48-mol/L ethylene and 52-mol/L
vinyl alcohol (129). Taki et al. were the first to describe
the use of EVOH, mixed with metrizimide powder
(for radiopacity), dissolved in DMSO to embolize
brain AVMs in 1990 (130). Subsequent studies led to
a multicenter randomized trial that demonstrated
noninferiority of Onyx compared to NBCA in achiev-
ing greater than or equal to 50% volume reduction for
presurgical brain AVM embolization, resulting in
FDA approval of Onyx for presurgical brain AVM
embolization in 2005 (116,131,132).
Onyx is a cohesive, nonadhesive liquid embolic
agent. The copolymer holds together as it is injected,
but it does not adhere to the endothelium or to
the microcatheter tip. When the mixture contacts an
aqueous solution such as saline or blood, the DMSO
diffuses away rapidly, causing the copolymer to
precipitate into a soft, spongy solid. The precipitation
progresses from the outer surface inward, forming a
skin with a liquid center that continues to flow as the
solidification continues. During the injection, the col-
umn of Onyx advances into the path of least resis-
tance. The rate of precipitation of the copolymer is
proportional to the concentration of EVOH in the
solution. There are currently two commercially avail-
able concentrations of EVOH for brain AVM embo-
lization: Onyx 18 (6% EVOH) and Onyx 34 (8%
EVOH). Onyx 18 travels farther distally and pene-
trates more deeply into the nidus because of its lower
viscosity and slower precipitation rate. Onyx 18 is
used for distal feeding pedicle injections into a plexi-
form nidus, whereas Onyx 34 is recommended for
embolizing high-flow fistulas. Complete solidi-
fication of both formulations occurs within five
minutes.
DMSO was chosen as the solvent because it
rapidly diffuses in aqueous solution and its physio-
logical properties in humans are well known (130).
DMSO is angiotoxic, however, with adverse effects
that include vasospasm, angionecrosis, arterial throm-
bosis, and vascular rupture (133). These undesirable
consequences are related to the volume of DMSO
infused and the endothelial contact time (131). Severe
angiotoxic effects do not occur when the DMSO infu-
sion rate does not exceed 0.25 mL/90 sec (116,131).
Only specifically approved microcatheters (Ultraflow,
Marathon, Echelon; EV3) can be used with Onyx
because the DMSO will dissolve incompatible
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations
catheters. Patients may notice a garlic-like taste for
several hours, and their skin and breath may have a
characteristic odor due to the DMSO for one to two
days after an embolization with Onyx.
The cohesive and nonadhesive properties of
Onyx provide several advantages compared to
NBCA. Because Onyx is nonadhesive and it solidifies
more slowly than NBCA, typical injections are per-
formed over much longer time intervals (minutes) and
are easier to control. This procedure results in a much
more leisurely embolization, providing time to ana-
lyze progress with interval angiography, if desired,
and involving less risk of refluxing the embolic agent
too proximally in the arterial feeders or extending too
distally into the venous outflow (Fig. 18). It is also
possible that a more complete and solid casting of the
nidus may be obtained with Onyx compared to
NBCA. This may result in an increased rate of cure,
but this remains to be proven. In addition, the catheter
also can be repositioned into a second pedicle and
another embolization can be performed, a maneuver
that is not possible with NBCA. Finally, Onyx does
not cause inadvertent gluing of the catheter tip to the
vessel (116).
Although Onyx is a very promising embolic
agent, only limited data on its use for brain AVM
have been published. Jahan et al. embolized 23 brain
AVMs achieving an average 63% reduction in AVM
volume with 4% permanent morbidity and no mor-
tality. Histopathological examination of the resected
specimens showed mild inflammation one day after
embolization and chronic inflammatory changes after
four days. Angionecrosis was seen in two patients, but
the vessel wall integrity was maintained in all speci-
mens (116). In another study, the surgical handling
characteristics of Onyx were compared with NBCA in
embolized swine rete mirabile (132). Onyx was softer
and handled better than NBCA during surgical
resection. The permanency of Onyx embolization is
as yet unknown. Short-term angiographic follow-up
(1100 days) did not reveal recanalization (116);
Figure 18 Angiogram obtained during embolization with Onyx.
(A) Onyx cast (arrowheads) and microcatheter tip (arrow) on
lateral radiograph. (B) Lateral angiogram obtained through guide
catheter during embolization.
295
however, no long follow-up studies have been pub-
lished. Therefore, the role for Onyx as an adjunct to
stereotactic radiosurgery or for curative embolization
has not been definitively established.
Onyx Technique Patients can experience pain
during embolization with Onyx; therefore, general
anesthesia is used more frequently than with NBCA.
Some perform provocative testing at the planned
embolization sites prior to inducing general anesthe-
sia. An Onyx-compatible microcatheter is positioned
in the desired location using flow-directed and guide-
wire-assisted navigation as described above. Better
nidal penetration is usually obtained in a larger
feeder. A wedged intra-nidal position is optimal.
After positioning of the microcatheter, a superselec-
tive angiogram is obtained.
The Onyx solution must be vigorously shaken
for 20 minutes to fully suspend the micronized tanta-
lum powder. Mixing is continued until just before
the embolization. Failure to do this may result in
inadequate radiopacity (129). The manufacturer pro-
vides an adapted Vortex-Genie (Scientific Industries,
Inc., Bohemia, New York, U.S.) to mix the Onyx. The
catheter is flushed with normal saline and the dead
space is loaded with pure DMSO solvent. The Onyx
mixture is drawn into a DMSO-compatible 1-cc
syringe, the syringe is connected to the microcatheter
and a slow, steady injection is begun at a rate of
0.25 mL/90 sec to displace the DMSO in the dead
space with Onyx. Subtracted fluoroscopy is begun just
before the dead space volume has been replaced by
the injection. The injection is continued at 0.1 mL/min
as the Onyx begins to deliver out of the microcatheter.
A slow, steady injection usually results in optimal
nidal penetration. Changes in the injection rate tend
to cause proximal reflux. The injection rate is not
allowed to exceed 0.25 mL/90 sec to prevent angio-
toxicity.
If proximal reflux occurs, the injection is paused
30 seconds and restarted. This allows a plug to solidify
around the catheter tip that prevents further reflux
and promotes forward flow. This plug and push
technique can be repeated multiple times as required.
Proximal reflux around the catheter tip should be
limited to 1 cm to avoid causing difficulty with the
catheter retrieval. As a circumferential plug forms
around the catheter tip, the injection can be paused
for as long as two minutes to allow the plug to solid-
ify. This will establish proximal flow arrest when the
injection is restarted so that the subsequent flow will
move distally. Similarly, if Onyx begins to fill a drain-
ing vein, a pause in the injection will allow that
material to solidify, and when the injection is restarted
the additional Onyx usually fills new areas of the
nidus. The injection should never be paused for
more than two minutes to prevent Onyx from precip-
itating in the catheter lumen. If there is resistance, the
injection should be discontinued to avoid rupturing
the catheter.
There are two catheter retrieval techniques. The
slow traction method uses incremental catheter
withdrawal (cm by cm) with sustained moderate
tension on the catheter. The quick wrist-snap
296 Weigele et al.
technique is to withdraw the catheter enough (35 cm)
to create slight tension and then quickly snapping the
wrist (not the entire arm) 10 to 20 cm left to right.
Pulling too far or hard runs the risk of causing a
catheter separation.
Postprocedural Care
Patients are observed in the neurointensive care unit
for 24 hours and usually discharged to home on the
second postembolization day. Mild hypotension
(mean arterial pressure ~90% of normal) may be
induced for 24 hours if a large, high-flow AVM has
been embolized. Additional embolization sessions for
large, high-flow AVMs are staged every three to four
weeks.
Results
The literature on outcomes for brain AVM treatments
primarily consists of uncontrolled, single institution
case series. Many of these have demonstrated an
important role for brain AVM embolization in selected
patient populations. Nonetheless, they have relatively
small sample sizes, and tremendous variability in
selection criteria, techniques, patient evaluation, and
follow-up. Multicenter, randomized, controlled out-
come trials are needed to form a scientific basis for the
selection of optimal therapeutic plans. Since brain
AVM embolization is used mostly as an adjunct to
surgery or radiosurgery, these trials will need to
compare the natural history with the overall results
of individual and combined treatment strategies.
Presurgical Embolization
A number of case series comparing groups undergo-
ing surgical resection of brain AVMs with and with-
out preoperative embolization have demonstrated
that selective preoperative embolization improves
overall outcomes (126,134,135). Preoperative emboli-
zation and surgery is also cost-effective compared to
surgery without embolization, with cost per quality-
adjusted life-year savings as high as 34% (136).
Pasqualin et al. demonstrated that preoperative
embolization of large, high-flow AVMs was associated
with less intraoperative bleeding, and there were
fewer postoperative neurological deficits, seizures,
and deaths in the group that underwent preoperative
embolization. The frequency of major new deficits was
31% in the surgery only group versus 5% in the
combined embolization and surgery group. However,
the incidence of postoperative hyperemic complica-
tions did not differ between the embolized and non-
embolized groups (134).
Demeritt et al. compared 30 patients who under-
went preoperative AVM embolization with NBCA
followed by surgery with 41 patients who had surgery
without preoperative embolization. The combined
embolization and surgery group had a higher average
Spetzler-Martin score compared to the surgery only
group (89% vs. 68% in grade III and IV, respectively)
and a larger average nidal maximal diameter (4.2

1.5 cm vs. 3.4
1.8 cm); however, two-week and long-
term Glasgow Outcome Scale scores were better in the
combined embolization and surgery group than the
surgery only group (70% vs. 41%, respectively, had a
two-week Glasgow Outcome Scale score of 5; 86% vs.
66%, respectively, had a long-term Glasgow Outcome
Scale score of 5) (135).
Similarly, Jafar et al. compared 20 patients who
underwent preoperative AVM embolization with
NBCA followed by surgery with 13 patients who
had surgery alone. The combined group had a larger
average AVM diameter (3.9 cm vs. 2.3 cm) and a
higher average Spetzler-Martin grade (3.2 vs. 2.5)
compared to the nonembolized group. Embolization
complications included immediate and delayed hem-
orrhage (15%) and transient ischemia (5%). There was
no embolization-related death. No difference in sur-
gical complications was found between the embolized
and nonembolized groups. The large majority of
patients (91%) in both groups had good to excellent
long-term neurological outcome. The authors con-
cluded that preoperative NBCA embolization of
AVMs makes lesions of larger size and higher grade
the surgical equivalent of lesions of smaller size and
lower grade (126).
Martin found that embolization was only effec-
tive to decrease blood loss and shorten operative time
when the nidal size was decreased more than 66%.
Less reduction in the size of the nidus and a reduction
in the rate of AV shunting were not effective (86).
Preradiosurgical Embolization
Gobin et al. reported the results in treatment of
125 patients with embolization and radiosurgery.
Approximately half of the AVMs had diameters
greater than 4 cm and most were Spetzler-Martin
grade III or greater. Embolization cured 11% and
made 77% suitable for radiosurgery. Greater than
50% of the AVMs with diameters greater than 6 cm
and more than 10% with diameters between 4 and
6 cm did not have sufficient nidal size reduction for
subsequent radiosurgery. Overall cure rates were 76%
to 78% for AVMs less than 4 cm in diameter, 59% for
those 4 to 6 cm, and 7% for those over 6 cm. Therefore,
adjunctive embolization was most effective for AVMs
of 4 to 6 cm in diameter. There was no convincing
advantage for combined embolization and radiosur-
gery compared to radiosurgery alone for AVMs
smaller than 4 cm. Embolization and radiosurgery
did not result in a significant cure rate for lesions
larger than 6 cm. Preradiosurgical embolization did
not provide protection from hemorrhage during the
latent period until radiosurgical obliteration. There
was approximately a 3% annual rate of hemorrhage
during the one- to three-year follow-up period, similar
to the natural history brain AVM hemorrhage rate.
The absence of residual AVM nidus or AV
shunting after radiosurgery does not equate with
definitive evidence of permanent obliteration of the
AVM. Although a negative angiogram had been
considered the practical endpoint defining suc-
cessful treatment, a recent retrospective review of
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations 297

236 fradiosurgery-treated AVMs followed for a

Table 7 AVM Embolization Morbidity and Permanent Mortality
median of 6.4 years after angiographic evidence of
obliteration found four cases of subsequent hemor- Number of Mortality Permanent
rhage in the previous AVM site. The two cases that Reference Year patients rate (%) morbidity rate (%)
were resected had small regions containing tiny 140 1995 1246 1.0 8.0
patent AVM vessels. In each case, there was enhance- 109 1997 54 3.7 5.6
ment in the treated site on postgadolinium MRI scans 139 1998 387 1.3 5.1
despite normal posttreatment angiograms. The annual 144 2002 233 1.0 14.0
risk of hemorrhage was 0.3% (137). 153 2002 450 1.1 3.8
Embolization can also be used to treat an AVM 89 2002 54 1.9 13.0
persisting after radiosurgery. Marks et al. reported six 145 2004 201 2.0 9.0
143 2006 306 2.6 4.9
patients with brain AVMs remaining 24 to 55 months
(mean 34 months) after radiosurgery. Embolization Abbreviation: AVM, arteriovenous malformation.
resulted in one cure, facilitated surgical resection in Source: From Ref. 143.
three, and caused sufficient volume reduction in two
patients in whom repeat radiosurgery could be per- venous embolization (101). Embolization of dural sup-
formed. There were no complications (96). ply can alleviate intractable headaches. In patients
Curative Embolization
with repeated hemorrhages, targeted embolization of
angioarchitectural risk factors such as proximal and
Published embolization cure rates vary considerably nidal aneurysms can limit additional bleeds (103).
because of selection bias, differing therapeutic goals
and techniques. Small AVMs with few feeders have Complications
the highest probability of endovascular cure. Case
series performed without specific selection of those Incidence The reported incidence of overall
AVMs that are most likely to be cured by embolization complications from brain AVM embolization varies
alone, have reported an overall durable embolization from 3% to 25% (88,108,134,138,142). The rates of
cure in 5% to 40% of patients (90,138140). Valavanis permanent morbidity and mortality in large series
and Yasargil had a 74% rate of curative embolization range from 3.8% to 14% and 1.0% to 3.7%, respectively
in a subgroup of patients with favorable angiographic (Table 7) (143). Most are caused by hemorrhagic and
features such as one or few dominant feeders, no ischemic events (103). Since complications are related
perinidal angiogenesis, and a fistulous nidus versus to a number of technical and hemodynamic factors,
a 40% rate of curative embolization for their entire this wide range in reported rates probably reflects at
series of 387 patients (139). least, in part, differences in case selection, emboliza-
tion techniques, and management strategies.
Palliative Embolization
In 1995, Frizel and Fisher reported a review of
32 case series of brain AVM embolizations in a total
In general, palliative embolization does not appear to of 1246 patients over 35 years from 1969 to 1993.
improve on conservative medical management and Overall temporary and permanent morbidity were
may even worsen the subsequent clinical course. 10% and 8%, respectively. Overall mortality was 1%.
Kwon et al. obtained long-term follow-up in a group There was no significant difference in permanent
of 27 patients with inoperable brain AVMs. Out of morbidity and mortality in the patients treated before
these patients, 16 were treated medically and 11 were and after 1990 (140).
partially embolized. There was no significant differ- In 2002, Hartmann et al. prospectively evaluated
ence between the two groups with respect to clinical 233 patients undergoing 545 embolizations. Thirty-
improvement, lack of change, and deterioration. In three patients (14%) had treatment-related neurologi-
addition, 46% of the partially embolized group expe- cal deficits; however, they were persistent and
rienced hemorrhage in the follow-up period versus disabling in only five patients (2%). There were two
25% in the nonembolized group (p 0.27) (100). deaths (1%). Factors statistically associated with new
Miyamoto et al. obtained 49-month (mean) deficits were increasing patient age, absence of a
follow-up of 46 patients with unresectable AVMs pretreatment deficit, and the number of embolization
treated with various palliative techniques (partial sessions (144).
embolization, radiosurgery, subtotal resection, and In 2004, Taylor et al. reviewed 339 AVM embo-
feeder ligation). There was a 14.6% annual rate of lizations performed in 201 patients over an 11-year
hemorrhage, 23% incidence of new major neurological period. There was a 7.7% rate of major complications
deficits, and a 9% mortality rate (141). per procedure. Nine percent of the patients had a
Nonetheless, palliative embolization can be ben- permanent neurological deficit and 2% died from the
eficial in selected circumstances. Ischemic neurologi- embolizations (145).
cal deficits caused by vascular steal and venous In 2006, Haw et al. reported the results of 513
hypertension in a high-flow, inoperable AVM were attempted embolizations in 306 patients performed
improved following partial embolization (102). In between 1984 and 2002. There were eight (2.6%)
another patient, hemifacial spasm caused by a dilated deaths, six caused by hemorrhage and two caused
lateral mesencephalic vein draining an inoperable by ischemic strokes. The rate of death and permanent
temporo-occipital AVM was cured by selective trans- disabling morbidity was 3.9%. Three factors were
298 Weigele et al.
statistically associated with complications: an elo-
quent AVM location, a AV fistula, and venous depo-
sition of the embolic agent (cyanoacrylates). Passage
of the embolic agent into the draining veins caused 8
of the 12 (67%) deaths or disabling deficits. There was
a reduction in complications producing death or per-
manent disability in the second half of the study. The
authors suggest this was due to advances in equip-
ment and techniques, as well as greater expertise and
clinical judgment gained through experience (143).
Types of complications
Periprocedural hemorrhage There are a num-
ber of causes of periprocedural hemorrhage from
brain AVM embolizations. Technical factors include
catheter or guidewire-induced arterial perforations,
dissections, rupture of aneurysms, vascular injuries
during catheter retrieval, and accidental emboliza-
tions of venous outflow (109,143).
Physiological factors include venous outflow
thrombosis, hemodynamic changes in the setting of
impaired cerebrovascular reactivity, and hemodynamic
stresses on angioarchitectural weak sites such as feeder,
nidal, and venous aneurysms. Embolization can mark-
edly reduce flow through a fistulous nidus causing
stagnation in the draining veins (Fig. 19). This can
result in venous outflow thrombosis, nidal congestion,
and a delayed hemorrhage or a venous ischemic infarct
(128,143,146). Normal perfusion pressure breakthrough
is another important physiological cause of hemor-
rhage following AVM treatment. The sump effect
of a large shunt causes low pressure in the arterial
feeders and nearby parenchymal branches. The high
flow through the nidus elevates venous pressures. The
result is a chronically low cerebral perfusion pressure
that can impair cerebrovascular autoregulation. If the
shunt is suddenly therapeutically disrupted, there is an
immediate increase in arterial pressure and a decrease
in venous pressure, with a resulting dramatic increase
in the cerebral perfusion pressure. If cerebrovascular
autoregulation is impaired, resulting parenchymal
hyperperfusion can cause cerebral edema or hemor-
rhage. Spetzler et al. called this normal perfusion pres-
sure breakthrough and found it was associated with
large, high-flow AVMs, poor angiographic filling of
normal cerebral arteries, extensive collateral flow (steal)
(Fig. 1), external carotid supply, and progressive or
fluctuating neurological deficits (103,127). The risk of
normal perfusion pressure breakthroughinduced
hemorrhage can be minimized by stepwise reduction
in the degree of shunting in large, high-flow AVMs
through multiple embolizations staged every three to
four weeks, facilitating the gradual recovery of normal
vascular reactivity (103).
Prompt surgical evacuation of an embolization-
induced cerebral hematoma results in a good outcome
in most cases. Jafar and Rezai reported the emergent
surgical evacuation of acute intracerebral hematomas
from brain AVMs in 10 patients experiencing acute
neurological deterioration, including eight cases
occurring after embolization. They employed imme-
diate intubation, hyperventilation, osmotic diuresis,
barbiturate anesthesia, and surgery. The hematoma
was evacuated and the AVM was totally resected if
possible (8 out of 10). Postoperative cerebral perfusion
pressure was maintained above 55-mm Hg with man-
nitol and barbiturates. Nine of the 10 patients had
good to excellent outcomes (147).
Ischemic stroke Technical causes of acute
stroke during embolization include the showering of
NBCA droplets from the catheter tip as it is removed,
catheter- or guidewire-related arterial dissections and
thromboemboli, the embolization of en passage or
pseudoterminal supply to normal brain parenchyma
distal to the nidal supply, and the inadvertent reflux
of embolic material into normal branches proximal to
the catheter tip. Ischemic stroke can result from retro-
grade thrombosis in stagnant feeding arteries propa-
gating into branches to normal brain (Fig. 20) (148).
Delayed venous thrombosis can cause a venous infarct
(146). Careful attention to the angioarchitecture on
superselective angiography and to an optimal embo-
lization technique will minimize these events (143).
Other complications Embolization with cya-
noacrylates has caused permanent adhesion of the
microcatheter tip to the embolized vessel in a small
percentage of cases. This incidence has decreased
significantly in recent years with the use of NBCA
rather than isobutyl cyanoacrylate, a wedged micro-
catheter position to prevent proximal reflux, more
dilute NBCA/ethiodol mixtures with slower polymer-
ization rates, and more durable microcatheters with
hydrophilic coatings. Careful technique also is impor-
tant. Redundant loops should be removed before
Figure 19 Partially embolized AVM nidus with venous
stagnation (C, arrowheads). Note venous stenosis (B,
large arrow) and venous aneurysm (B, small arrow).
(A) Lateral angiogram-arterial phase, (B) lateral angio-
gram-venous phase, and (C) lateral angiogram-late
venous phase. Abbreviation: AVM, arteriovenous mal-
formation.
 Chapter 15: Endovascular Management of Brain Arteriovenous Malformations
Figure 20 Partially embolized AVM with arterial stagnation
(arrowheads, B). (A) Lateral angiogram-arterial phase and
(B) lateral angiogram-venous phase. Abbreviation: AVM, arterio-
venous malformation.
embolization, and the microcatheter should be aspi-
rated and pulled briskly during removal (109).
Retained catheters usually can be transected and
buried in the femoral arteriotomy without adverse
sequelae; however, brain and lower extremity ische-
mic complications have been reported (143,149).
Pulmonary emboli (PE) have been reported with
both particulate and liquid embolic agents (Fig. 21).
Most are asymptomatic, although respiratory distress
Figure 21 NBCA pulmonary embolus (A, arrow) on chest CT
scan causing pulmonary infarct (B, arrow). Abbreviation: NBCA,
N-butyl cyanoacrylate.
299
and death have occurred. The risk of PE using NBCA
is increased with high-flow fistulas, with the use of
ethiodol or glacial acetic acid to slow the polymerization
time and by not using flow-arrest techniques. PE were
found in 12 (35%) of a series of 47 pediatric patients after
brain AVM embolization. The large majority (45) were
asymptomatic and found incidentally on chest X rays.
The most common agent was cyanoacrylate (10 out of
12), causing respiratory distress in two (150). A retro-
spective review of 182 patients embolized with cyanoa-
crylates found three cases of symptomatic PE,
associated with the embolization high-flow AVMs with-
out the use of flow-arrest techniques (151).
Multistage angiographic and embolization pro-
cedures result in significant radiation doses. Tempo-
rary alopecia has been reported, which typically occurs
after a short-term radiation dose of 3 to 6 Gy (152).
CONCLUSIONS
Brain AVMs are very heterogeneous, rare central ner-
vous system vascular malformations associated with
significant long-term morbidity and mortality. Embo-
lization has become an increasingly important thera-
peutic option, usually in combination with surgery or
stereotactic radiosurgery. It is, however, associated
with risks that must be considered in the context of
the overall treatment plan. A multispecialty team
comprised of experts in vascular neurosurgery,
interventional neuroradiology, and radiosurgery opti-
mally manages brain AVMs.
Rapid advances in technology have had a pro-
found impact on brain AVM embolization, and the
innovations promise to continue. Dramatic improve-
ments in microcatheter and guidewire technology
have led to the superselective catheterization of distal
cerebral arteries. This has led to a better understand-
ing of AVM angioarchitecture and has enabled the
intranidal embolization of AVMs with liquid embolic
agents. Nonetheless, further work is required to
improve the safety and efficacy of embolization, and
more rigorous data on the natural history of brain
AVMs and treatment outcomes are needed.
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 16

Endovascular Treatment of Acute Ischemic Stroke

Mayur A. Paralkar
Department of Medicine, University of Medicine and Dentistry
of New Jersey, Newark, New Jersey, U.S.A.
Alexandros L. Georgiadis and Adnan I. Qureshi
Department of Neurology, Zeenat Qureshi Stroke Research Center,
University of Minnesota, Minneapolis, Minnesota, U.S.A.
Qaisar A. Shah
Department of Neurology, Hospital of the University of Pennsylvania,
Philadelphia, Pennsylvania, U.S.A., and Department of Neurology,
University of Minnesota, Minneapolis, Minnesota, U.S.A.

INTRODUCTION: THE EVOLUTION
OF STROKE TREATMENT
It is well known that stroke is one of the leading causes
of death and disability in Western societies (1). How-
ever, progress in the treatment of stroke has been slow.
For many years, neurologists could only localize
lesions and describe the resulting syndromes, i.e.,
establish clinicopathological correlations. Little was
known about the etiology of stroke, and the prevailing
presumption was that in situ thrombosis of the intra-
cranial vasculature was the most common culprit (2).
The observation that thrombotic material could emb-
olize from the carotid artery to the intracranial vessels
(3) and the description of lacunar syndromes and their
underlying pathophysiology (4) were pivotal in help-
ing neurologists advance to the next stage, which was
to assess the etiology of stroke. Thus, strategies for
secondary prevention could emerge, but there was still
no acute treatment available.
Initial attempts to use systemic thrombolysis in
stroke were hampered by the propensity of cerebral
tissue to bleed. It was not clear how to dose thrombolytic
medications, what the therapeutic time window was,
and which patients were at highest risk of complications.
The first three trials of intravenous thrombolysis for
acute stroke used streptokinase and were all terminated
because of excessive rates of intracerebral hemorrhage
(ICH) in the treated patients (57). They were followed
by one more negative trial, the European Cooperative
Acute Stroke Study (ECASS), which used recombinant
tissue plasminogen activator (r-tPA) at a dose of 1.1 mg/
kg within six hours from symptom onset (8). The
National Institute of Neurological Diseases and Stroke
(NINDS) study, using a smaller r-tPA dose of 0.9 mg/kg
only within three hours from symptom onset, demon-
strated significant clinical benefit for the treated patients
with an acceptable risk of ICH (9). On the basis of the
results of this study, r-tPA was approved for intrave-
nous use in acute stroke within three hours from
symptom onset by the Food and Drug Administration
(FDA). The three-hour window for the administration
of intravenous r-tPA was later confirmed by the
Alteplase Thrombolysis for Acute Noninterventional
Therapy in Ischemic Stroke (ATLANTIS) trial, which
demonstrated no benefit for patients treated at three to
five hours after symptom onset (10). To this day,
intravenous thrombolysis with r-tPA remains the
only FDA-approved treatment for acute stroke.
Intra-arterial thrombolysis, first reported in 1982
(11), offers several advantages. These include visual-
ization of the actual vascular lesion, a therapeutic
window that extends to six hours, administration of
smaller doses of thrombolytic medication, and the pos-
sibility of combining pharmacological thrombolysis
with mechanical disruption of the clot (mechanical
thrombolysis). The smaller dose of thrombolytic medi-
cation makes it possible to intra-arterially treat patients
who do not qualify for intravenous thrombolysis, such
as those in the immediate postoperative period (12). In
some cases, intra-arterial thrombolysis is performed six
hours after stroke onset, such as in posterior circulation
strokes associated with basilar artery thrombosis (13). In
those cases, the high mortality of the untreated patients
justifies intra-arterial thrombolysis at even 12 hours or
more after stroke onset.
INTRA-ARTERIAL THROMBOLYSIS
Intra-arterial Thrombolysis as Sole Treatment
There were some early promising reports of patients
treated with intra-arterial thrombolysis (14), but the
306 Paralkar et al.

first randomized trial (Prolyse in Acute Cerebral
Thromboembolism, or PROACT) was not published
before 1998 (15). This trial showed better recanaliza-
tion rates for patients randomized to intra-arterial
recombinant prourokinase, but no clinical benefit. In
PROACT II, 110 patients were randomized to intra-
arterial recombinant prourokinase and intravenous
heparin versus heparin alone (16). The patients who
were treated with thrombolytic medications had a
higher likelihood of partial or complete recanalization
(67% vs. 18%) and of living independently at three
months (40% vs. 25%). The rate of symptomatic ICH
was 11% in the patients treated with thrombolytic
medications versus 3% in the untreated patients.
A series of 54 patients treated with intra-arterial
urokinase published by Suarez et al. also showed
significant clinical benefit, but with a higher rate of
symptomatic ICH (17).
These data indicate that intra-arterial thrombol-
ysis is an effective treatment for patients who present
at three to six hours after symptom onset. The
reported rates of symptomatic ICH are consistently
higher than with intravenous r-tPA given within three
hours, but very similar to that shown in ATLANTIS,
in which r-tPA was given at three to five hours after
onset. All these studies used intravenous heparin in
varying doses, a practice that is now outdated and
certainly increases the risk of ICH. Moreover, those
patients were treated with first (urokinase) or second-
generation (prourokinase) thrombolytic agents. Third-
generation thrombolytic agents available today, such
as reteplase, offer higher clot specificity and promise
less hemorrhagic complications.
Intra-arterial Thrombolysis and Intravenous
Antiplatelet Drugs
Clot formation and lysis is a dynamic process. Throm-
bolytic medications lead to clot lysis but at the same
time activate thrombin and platelets, thus promoting
rethrombosis. Platelet glycoprotein IIb/IIIa receptor
activation is an integral part of the cascade that leads
to clot formation; hence the idea of combining throm-
bolysis with glycoprotein IIb/IIIa inhibitors. Several
studies have reported promising results, but so far
only on small numbers of patients who were treated
with a variety of different protocols and medications
(2326). Some recent retrospective data have shown
that the combined use of thrombolytic agents and
glycoprotein IIb/IIIa inhibitors is an independent pos-
itive predictor of recanalization (27).
Multimodal Thrombolysis
In case of failure of pharmacological thrombolysis and
simple microcatheter maneuvers for clot disruption,
more advanced methods of mechanical thrombolysis
can be employed, as deemed most appropriate for the
given patient (multimodal thrombolysis) (24,25). A
multimodal thrombolysis treatment is illustrated in
Figures 19. The various methods that can be used are
discussed below.
Acute Angioplasty and Stenting
Acute angioplasty, combined, if needed, with intra-
arterial r-tPA, has been recently shown to be superior
to intra-arterial r-tPA alone in a retrospective analysis
of 70 patients (28). Superiority was demonstrated in

Combined Intravenous and Intra-arterial

Thrombolysis
An alternative treatment algorithm for patients pre-
senting within three hours from symptom onset is to
administer intravenous r-tPA at a lower dose, so as to
quasi reserve some r-tPA for intra-arterial adminis-
tration. This algorithm is usually applied to patients
with large deficits and is based on the observation that
patients with a National Institutes of Health Stroke
Scale (NIHSS) score of greater than 10 often do not
benefit from intravenous thrombolysis (18).
Commonly, two-third of the recommended dose
is given intravenously (i.e., 0.6 mg/kg), and then a
maximal dose of 0.3 mg/kg is administered intra-
arterially if an occlusion is visualized on angiography
(1922). Some centers have recommended screening
patients with diffusion- and perfusion-weighted
magnetic resonance imaging (MRI) after the intrave-
nous thrombolytic medication is given and proceed-
ing with angiography only in selected cases (22).
Available studies have not evaluated efficacy of the
combined intravenous and intra-arterial approach
when compared with intravenous thrombolysis alone. Figure 1 Angiographic perfusion image. A 20 cranial AP pro-
One new concept currently under preliminary jection taken after injection, with the guide catheter placed in the
study is to administer the full dose of intravenous proximal aortic arch. There is no filling of the intracranial right
r-tPA followed by small doses of intra-arterial rete- carotid artery.
plase combined with mechanical thrombolysis.
 Chapter 16: Endovascular Treatment of Acute Ischemic Stroke
Figure 3 The microcatheter is passed through the guide cath-
eter into the right middle cerebral artery. The arrow points at the
tip of the microcatheter.
Figure 5 Reteplase is administered inside and at the edges of
the clot following clot manipulation with the microcatheter.
307
Figure 2 AP view of right internal carotid artery injec-
tion. (A) Early arterial phase. There is no filling of the
right middle cerebral artery. (B) Late arterial-early
venous phase. There is filling of the distal M1-middle
cerebral artery and of one of its segments. The flow is
through pial collaterals from the anterior cerebral artery.
The arrows indicate the direction of flow.
Figure 4 Double injection, AP view: a simultaneous injection
through the guide catheter and the microcatheter. The middle
cerebral artery fills from the microcatheter injection. The proximal
middle cerebral artery is thrombosed and does not fill (circle). The
arrow points at another clot located in the area of the trifurcation.
Figure 6 Following the administration of reteplase, a snare device
is introduced into the middle cerebral artery to help capture and
extract the clot.
308 Paralkar et al.
Figure 7 Right internal carotid artery injection (AP view) after
reteplase administration and snare maneuvers. There is good
filling of the middle cerebral artery.
Figure 8 Follow-up angiography 24 hours later. The patient had
been maintained on a continuous infusion of intravenous Integ-
rilin. Right common carotid artery injection, AP view. Patency of
the middle cerebral artery is maintained. There is some proximal
irregularity representing residual thrombosis (arrow).
terms of incidence of favorable clinical outcome,
recanalization rates, and rate of hemorrhage.
In select cases of acute stroke, stenting is an
additional option. A recent retrospective review (29)
showed good results in patients with acute carotid
occlusion who were stented, in most cases with a self-
expanding Wallstent (Boston Scientific, Nattick, MA),
especially when there was no tandem intracranial
occlusion present. Acute intracranial and extracranial
stenting have been reported in a recent retrospective
review of 168 consecutive patients who underwent
multimodal reperfusion therapy at the University of
Pittsburgh Medical Center (27) to be independent
predictors of recanalization.
Clot Retrieval Devices
Clot retrieval devices have pushed the treatment win-
dow for acute stroke to eight hours after onset of
symptoms.
The Mechanical Embolus Removal in Cerebral
Ischemia (MERCI) trial enrolled 151 patients who
presented within eight hours from stroke onset (30).
It was a prospective, single-arm, multicenter trial. The
patients treated had proximal intracranial occlusions
demonstrated by conventional angiography (intracra-
nial vertebral arteries, basilar artery, intracranial
carotid artery, and middle cerebral artery M1 or M2
segment). The trial showed adequate safety for the
procedure with symptomatic ICH in 7.8% of the
patients and good clinical outcomes in those with
successful recanalization.
The Merci Retrieval System (Concentric Medical,
Inc., Mountain View, California, U.S.) consists of a
8-French or a 9-French (Fr) guide catheter with a
balloon at its distal tip and a microcatheter through
which the actual Merci retriever is expressed. The
Merci retriever is a tapered wire with five helical
loops of decreasing diameter at its distal end. The
loops are made of memory-shaped nitinol. The
Merci retriever is advanced through the clot and
then pulled back to ensnare the thrombus and allow
it to be removed. During this procedure the balloon at
the tip of the guide catheter, which is located in the
common or internal carotid artery, is inflated to min-
imize distal flow. A full description of the procedure
can be found in the original publication of the phase 1
study (31).
However, the approval of this device without
data from a randomized trial has drawn criticism
(32,33). Also, the MERCI trial showed good clinical
outcome, defined as mRS of less than or equal to 2, in
28% of the patients as opposed to 40% in PROACT II
and a mortality rate of 44%, which was significantly
higher than the 27% of the PROACT II study (32).
The Magnetic Resonance and Recanalization of
Stroke Clots Using Embolectomy (MR RESCUE) trial
is an ongoing NINDS-funded study that will assess
whether MRI can be used to assess which patients
can benefit from intervention with the Merci device.
This study will provide us with high level of evidence
regarding the safety and efficacy of the Merci
retriever.
Other clot retrieval devices, such as the Micro-
vena snare (Amplatz Goose Neck, Microvena Corpo-
ration, White Bear Lake, Minnesota, U.S.), have also
been used with success (34). The Microvena snare is
employed through a 6-Fr guide catheter. The size of
the employed snare should roughly match the size
of the treated vessel. A microcatheter is advanced into
 Chapter 16: Endovascular Treatment of Acute Ischemic Stroke 309

the intracranial vessel and in proximity to the clot, and

the snare is expressed through the microcatheter. The
microcatheter and snare are advanced into the clot,
and the snare is then retracted into the microcatheter.
After the entire system is pulled out by a few centi-
meters, a control run through the guide catheter is
obtained. If there is no adequate recanalization, the
procedure can be repeated (34).

Angiojet Catheter
The Possis AngioJet thrombectomy catheter (Possis
Medical, Inc., Minneapolis, Minnesota, U.S.) uses
high-pressure, pulsed saline to fragment and draw
the thrombus into the catheter lumen. The AngioJet
has been used mainly in peripheral and cardiac endo-
vascular procedures. Its use in neuroendovascular
procedures has been limited (35). It could be consid-
ered especially in patients with a large clot burden.

EKOS MicroLysUS Infusion Catheter

The EKOS ultrasound-emitting infusion catheter
(EKOS Corporation, Bothell, Washington, U.S.) was
created because of the evidence, from experimental
(36) and clinical studies (37), that ultrasound can
enhance the effect of thrombolytic medications on
clots. The EKOS catheter was used in the Interventional
Management of Stroke (IMS) II trial, the preliminary
results of which were announced at the 2006 Interna-
tional Stroke Conference. Those results established the
safety of combined intravenous thrombolysis and intra-
arterial thrombolysis delivered through the EKOS cath-
eter. The results, though promising in terms of clinical
outcomes, will require further validation.

Flow Grading Scales

To assess the efficacy of intra-arterial treatment, scales
that grade blood flow need to be employed. The
Thrombolysis in Myocardial Infarction (TIMI) grading
scale (38) remains the most commonly used scale.
Grade 0 on the TIMI scale means absence of flow,
grade 1 indicates that contrast material passes beyond
the area of obstruction but does not opacify the entire
distal vascular bed, grade 2 denotes complete but
delayed opacification of the distal vascular bed, and
grade 3 denotes normal flow.
The Qureshi grading scale, first reported in 2002,
has been shown to have better interobserver reliability
and correlation with neurological recovery and mor-
tality (39). This scale grades flow from 0 to 5 and
accounts for both the site of occlusion and the pres-
ence of collateral flow (Fig. 9).
FUTURE GOALS
Advances in stroke care are likely to be made at
multiple fronts in the near future. There will likely
be safer and more effective thrombolytic and antipla-
telet medications. Neuroimaging techniques might
evolve to help screen patients, so that interventions
are carried out for those patients who are most likely
Figure 9 Qureshi grading scheme. The patterns of occlusion
observed in patients with acute ischemic stroke. Note that ICA
occlusion (highlighted) constitutes the highest severity grades
because of its association with poor outcome. ICA indicates
internal carotid artery; MCA, middle cerebral artery; ACA, anterior
cerebral artery; VA, vertebral artery; BA, basilar artery; LSA,
lenticulostriate arteries; and LMC, leptomenungeal.
to benefit and the least likely to suffer complications.
Catheter technology advances will continue to make
endovascular procedures safer and allow for more
sophisticated interventions.
Multimodal intra-arterial thrombolysis will
likely be the treatment of choice for many stroke
patients in the future, but safety and efficacy will
have to be studied further, preferably in the setting
of prospective randomized trials.
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 17

Endovascular Treatment of Extracranial

Carotid Atherosclerotic Disease

Eric Sauvageau
Department of Neurosurgery and Toshiba Stroke Research Center, Millard Fillmore
Gates Hospital, Kaleida Health, University at Buffalo, State University of New York,
Buffalo, New York, U.S.A., and Department of Neurological Surgery, University
of South Florida College of Medicine, Tampa, Florida, U.S.A.
Robert D. Ecker
Department of Neurosurgery and Toshiba Stroke Research Center, Millard Fillmore
Gates Hospital, Kaleida Health, University at Buffalo, State University of New York,
Buffalo, New York, U.S.A., and Department of Neurological Surgery,
U.S. Naval Hospital, Okinawa, Japan
Junichi Yamamoto, Ramachandra P. Tummala, Elad I. Levy, and L. Nelson Hopkins
Department of Neurosurgery and Toshiba Stroke Research Center, Millard Fillmore
Gates Hospital, Kaleida Health, University at Buffalo, State University
of New York, Buffalo, New York, U.S.A.

INTRODUCTION Carotid Surgery Trial (ACST) (12), and the European

Stroke is the third largest cause of death and is the
leading cause of permanent disability and disability-
adjusted loss of independent life years in Western
countries (13). Approximately 700,000 people in the
United States experience a stroke annually (3). This
number is expected to grow because of aging and
changes in the ethnic distribution of the population (4).
An estimated one-fourth of strokes are attributable to
ischemic events related to occlusive disease of the cervi-
cal internal carotid artery (ICA) (5).
The benefit of carotid endarterectomy (CEA) in
reducing the risk of stroke in patients with moderate
to severe (>50%) symptomatic (69) or asymptomatic
(>60%) (1013) carotid stenosis has been demonstrated
in randomized trials. Although CEA is one of the most
common surgical procedures performed in the United
States, many patients cannot safely undergo such an
extensive operation because of technical or anatomical
factors or underlying severe medical illnesses such as
coronary artery disease and cardiac failure (1416). In
an analysis of results of the North American Symp-
tomatic Carotid Endarterectomy Trial (NASCET),
CEA was approximately 1.5 times more likely to be
associated with medical complications in patients
with a previous history of myocardial infarction
(MI), angina, or hypertension (17). Moreover, the
benefits of carotid revascularization surgery shown
by the NASCET (6,9), the Asymptomatic Carotid
Atherosclerosis Study (ACAS) (11), the Asymptomatic
Carotid Surgery Trial (ECST) (18,19) are lost if the
30-day rate of perioperative stroke or death exceeds
6% for patients with symptomatic carotid stenosis or
3% for those with asymptomatic carotid stenosis.
With the recent advent of embolic protection
techniques, standard surgical techniques for extracra-
nial carotid artery (CA) stenosis in high-risk surgical
patients have been challenged by catheter-based
angioplasty and stenting (20). In August 2004, the
U.S. Food and Drug Administration (FDA) approved
the first CA stenting system (Acculink stent and
Accunet embolic protection device, Guidant, Santa
Clara, California, U.S.) for use in patients, with
greater than or equal to 50% symptomatic and greater
than or equal to 80% asymptomatic carotid stenosis,
who were viewed by the treating surgeon as high-risk
for CEA because of anatomical risks or medical
comorbidities (21,22). The subsequent Centers for
Medicare & Medicaid Services (CMS) coverage deci-
sion (23), which allowed reimbursement for patients
with greater than or equal to 70% symptomatic
stenosis or who were enrolled in FDA-sponsored
clinical trials, gave CA stenting an entry to the clinical
arena as a legitimate alternative to CEA. In this chap-
ter, trials comparing CA stenting with CEA before
and after the availability of embolic protection devices
are reviewed, indications for treatment of cervical CA
disease and patient selection are reviewed, endovas-
cular technique for carotid revascularization is
described, and advantages of this approach are
312 Sauvageau et al.
discussed. Procedure-related limitations and compli-
cations are also discussed.
CAROTID ANGIOPLASTY AND STENTING:
THE EVOLUTION
The results of major trials have validated CEA and have
shown annual absolute reductions in risk for stroke of
approximately 1% for asymptomatic patients (1013)
and 8% for symptomatic patients (8,9,24). However,
trials evaluating CEA have systematically excluded
patients considered to be high-surgical-risk candi-
dates (Table 1) (6,813). These important limitations
were behind the rationale for developing CA stenting
as a less-invasive endovascular approach to carotid
revascularization. Moreover, the publication of results
obtained with coronary balloon angioplasty and stent-
assisted balloon angioplasty played a supporting role in
the performance of studies in which endovascular and
surgical approaches for the treatment of CA disease
were initially compared.
Patient Selection
Evidence in the literature documents a much greater
risk for CEA in clinical practice than is reflected in
major CEA trials in which the lowest risk patients were
operated on by experienced surgeons performing a
relatively high volume of procedures (2529). Never-
theless, although surgical experience may be an impor-
tant factor contributing to this significant difference in
complication rates, careful patient selection has been
found to be the key determinant in maintaining a low
perioperative complication rate (14,15,17,30).
The following conditions or characteristics have
been shown to predispose patients to a high perioper-
ative risk of stroke and death in various CEA reports
(14,15,17,30). Because patients with one or more of
these risk factors were generally excluded from enroll-
Table 1 Exclusion Criteria for CEA Trials
l Older than 79 years of age
l Heart, kidney, liver, or lung failure
l Cancer likely to cause death within 5 yr
l Cardiac valvular lesion or rhythm disorder likely to
be associated with cardioembolic stroke
l Previous ipsilateral CEA
l Contralateral CEA within 4 mo
l Angina or MI within the previous 6 mo
l Progressive neurological signs
l Major surgical procedure within 30 days
l Severe comorbidity due to other surgical or
medical illness
l
Cerebrovascular events in the distribution of the study
CA with ongoing disabling symptoms
l Symptoms referable to the contralateral side within
the previous 45 days
l More severe stenosis of an intracranial lesion than of
the treated lesion
Abbreviations: CEA, carotid endarterectomy; MI, myocardial
infarction; CA, carotid artery.
ment in prospective CEA trials, the indications for and
the results of surgery in the following subgroups have
not been established.
Severe Coronary Artery Disease
The coexistence of severe CA disease and symptomatic
coronary artery disease represents a dilemma for the
clinician (17). Surgical repair of one condition cannot be
accomplished without significant risk of complication
from the other. In a NASCET subgroup analysis, patients
who had prior treatment of coronary artery disease had a
lower CEA complication rate than those who had
undiagnosed coronary artery disease (31). This differ-
ence may be the result of improved cardiac and general
medical care in patients undergoing treatment for coro-
nary artery disease, many of whom may not have
previously received regular long-term medical care.
Adjunct to Coronary Bypass Operation
In a series of 539 patients who underwent noninvasive
testing for the detection of CA occlusive disease before
undergoing coronary artery bypass grafting (CABG),
carotid stenosis severity of more than 75% was an
independent predictor of stroke risk during the
bypass operation (32). For patients with severe coex-
istent disease of the carotid and coronary arteries,
there is some debate whether revascularization is
appropriate for both conditions. Certainly, contro-
versy exists regarding the timing of the procedures.
Surgical options include the performance of a simul-
taneous procedure or a staged approach in which one
procedure is performed several days after the other. A
combination of CEA and CABG reportedly is associ-
ated with a risk of stroke or death ranging from 7.4%
to 9.4%, which is roughly 1.5 to 2.0 times the inde-
pendent risk of each operation (17). In a multicenter
review, the composite risk of stroke and death was
higher in patients who had CEA performed in con-
junction with CABG (18.7%) than in those who had
CEA alone (2.1%) (15). Conversely, patients who
undergo CEA before CABG also have a higher risk
of perioperative complications (33,34). A meta-analy-
sis of 56 studies regarding staged CEA and CABG
published by the American Heart Association
reported a composite incidence of stroke, MI, and
death of 16.4% for combined carotid and coronary
operations, 26.2% for CEA proceeded by CABG, and
16.4% for CABG proceeded by CEA (35). These high
complication rates would clearly offset the long-term
benefit from secondary stroke prevention. In this high-
risk subgroup, avoiding a major operation or general
anesthesia by performing CA stenting may represent a
valid alternative to CEA (36). Nevertheless, contro-
versy regarding the potential for stroke risk reduction
for CA stenting preceding CABG exists (37).
Congestive Heart Failure
Patients with congestive heart failure have a higher
rate of perioperative stroke or death with CEA. A
multicenter review of patients undergoing CEA found
a perioperative stroke or death rate of 8.6% in patients
 Chapter 17: Endovascular Treatment of Extracranial Carotid Atherosclerotic Disease
with congestive heart failure as opposed to 2.3% in
patients without the same condition (14,15).
Anatomical Features and Tandem Lesions
Anatomical variations may increase the technical dif-
ficulty of CEA and adversely influence the results. A
high carotid bifurcation near the skull base, especially
in a patient with a short or thick neck or a long CA
stenosis that extends to the skull base, can be difficult
to expose surgically. Surgical dissection of the CA in
these cases can be very difficult and often extremely
traumatic. Low lesions can also be technically difficult
and should be avoided.
The presence of tandem lesions in which the
distal lesion was more severe than the proximal lesion
was a NASCET exclusion criterion (6). Among symp-
tomatic patients with ipsilateral carotid siphon steno-
sis, the risk of postoperative stroke or death associated
with CEA in a multicenter review of 1160 procedures
was 13.9% versus 7.9% in patients without distal
stenosis (14). In a systemic review of 36 studies, an
increased risk for perioperative stroke or death was
associated with CEA in patients with stenosis of the
ipsilateral siphon (16).
Ipsilateral Intraluminal Thrombus
In a multicenter review of 1160 procedures, the risk of
postoperative stroke or death with CEA was found to
be 17.9% in symptomatic patients with intraluminal
thrombus in the ipsilateral CA versus 8.1% in those
without thrombus (14). In a subgroup analysis of
53 patients enrolled in the NASCET who had intra-
luminal clot superimposed on atherosclerotic plaque
identified by angiographic procedures, the 30-day risk
of stroke was 10.7% in those randomly assigned to
receive medical treatment and 12% in those who
underwent CEA (38). The high morbidity rate in this
subgroup is related to the presence of fresh clot and
the substantial risk of emboli dislodgment during
surgical dissection of the CA.
Contralateral Carotid Occlusion
Patients with recent symptoms referable to severe CA
stenosis and coexistent contralateral CA occlusion
have a high risk of ipsilateral ischemic stroke. The
risk of ipsilateral stroke in medically treated patients
with severe stenosis of the symptomatic CA and
occlusion of the contralateral CA was 69.4% at two
years in a NASCET subgroup analysis (39). Although
CEA led to a significant reduction in stroke risk in this
group, the perioperative risk of stroke or death in the
presence of contralateral CA occlusion was as high as
14.3%. This increased risk may be related to the use of
CA shunting during CEA for patients with contrala-
teral occlusions in up to 83% of (39).
Postendarterectomy Restenosis
Recurrent CA stenosis is a potential problem after
CEA (40). Technically, a repeat operation is more
challenging than the initial procedure because of
313
scarring around the arteries, friability of the recurrent
plaque, and the necessity for complex anastomosis
techniques. Among 82 patients undergoing operations
for recurrent carotid stenosis at one institution, the
composite rate of major morbidity and mortality was
10.8%, a rate that was five times the risk associated
with primary CEA at the same institution (40). Inves-
tigators at another institution found an increased risk
of cerebral ischemic events associated with CEA for
recurrent stenosis (41). The 30-day rates of perioper-
ative stroke and transient ischemic attack (TIA) were
4.8% and 4%, respectively, in the reoperation group as
compared with 0.8% and 1%, respectively, in the pri-
mary endarterectomy group. The investigators also
found a high rate (17%) of cranial nerve palsy with
reoperation.
Radiation-induced Carotid Stenosis
Accelerated radiation-induced carotid stenosis presents
an increased risk for perioperative complications, pri-
marily because of the technical pitfalls associated with
a surgical approach. The presence of a long lesion, lack
of well-defined dissection planes, and scarring around
the vessels make the surgery more difficult (42,43),
exposing these patients to a higher risk of wound
infections and cranial nerve palsies. Additionally, reste-
nosis occurs more frequently after CEA in patients with
radiation-induced atheromatous disease (44,45).
Specific Considerations
Recurrent nerve palsy is a risk of CEA. For a patient
who already has a contralateral palsy, bilateral palsy
would result in the need for tracheostomy. Addition-
ally, those who rely significantly on their voice (such as
actors, speakers, and singers) are better served by CA
stenting considering the lower risk of cranial nerve
injury associated with the endovascular procedure (46).
Early Trials
The Carotid and Vertebral Artery Transluminal
Angioplasty Study (CAVATAS), the first randomized
comparison of endovascular versus surgical treatment
in patients with carotid stenosis, was started in 1992
and completed in 1997 (47). This study was designed
to compare balloon angioplasty, with or without
stenting (stents developed for the CA were not intro-
duced until after the study had begun), to CEA. As in
the major CEA trials, patients considered unsuitable
for surgery because of medical or surgical risk factors
were excluded from enrollment. A total of 504 patients
from 24 centers in Europe, Australia, and Canada were
randomized, 253 to CEA and 251 to CA stenting.
Endovascular treatment was technically successful (bal-
loon inflated across the stenosis at least once or stent
successfully used) in 213 of 240 treated patients. Balloon
angioplasty was performed in 158 of 213 patients (74%).
Only 55 (26%) patients received a stenteither the
Wallstent (Schneider, Minneapolis, Minnesota, U.S.),
Palmaz stent (Johnson & Johnson, Interventional
Systems, Warren, New Jersey, U.S.), or the strecker
314 Sauvageau et al.
(Meditech/Boston Scientific, Natick Massachusetts,
U.S.) stent. No embolic protection devices were used.
The results were essentially equivalent between the
stenting and endarterectomy groups at 30 days with
respect to the postprocedure rate of disabling stroke or
death (6.4% vs. 5.9%, respectively). No significant dif-
ference was found in the ipsilateral stroke rate with
survival analysis up to three years after randomization.
The rate of severe (7099%) restenosis documented by
ultrasound imaging at one year after treatment was 14%
in the endovascular group and 4% in the surgical group.
Patients in the surgical group were found to have a
higher incidence of cranial nerve palsy and major neck
hematoma.
The Wallstent trial was a multicenter equivalency
trial of CEA and CA stenting in which 209 symptom-
atic patients with 60% to 99% stenosis were enrolled;
107 patients were assigned to CA stenting and 112 to
CEA (48,49). The 30-day periprocedural complication
rate (any stroke or death) occurred in 12.1% of the CA
stenting group and 4.5% of the CEA group. The pri-
mary endpoint of ipsilateral stroke, procedure-related
death, or vascular death at one year was reached by
12.1% of patients randomized to stenting and 3.6% of
those randomized to endarterectomy. The major stroke
rates were 3.7% for stenting and 0.9% for endarterec-
tomy. The study was terminated before completion
because of the inferiority of CA stenting.
Another randomized clinical trial featuring the
Wallstent compared CA angioplasty and stenting
(CAS) with CEA among patients with symptomatic
severe (>70%) ICA stenosis (50). The main outcome
measures included death or stroke (disabling or non-
disabling) within 30 days. Twenty-three patients were
randomized to CEA with patch grafting or CA angio-
plasty with stenting; however, only 17 patients under-
went the allocated treatment before the study was
suspended because of an unacceptably high morbidity
rate in the stenting group. Thirty days after the treat-
ment, none of the 10 patients who underwent CEA
had a periprocedural TIA or stroke, whereas five of
seven patients who underwent CA angioplasty with
stenting had a periprocedural TIA or nondisabling
stroke and three had disabling stroke. The Wallstent
trials showed that CA stenting without embolic pro-
tection was not acceptable as an alternative to CEA for
the majority of patients with symptomatic CA disease.
Embolic Protection Devices
Cerebral embolization of friable atheromatous mate-
rial from the aortic arch and CA has been found to
occur during all stages of the CA stenting procedure
and may cause periprocedural neurological deficits
(5154). Three types of embolic protection devices
have been developed: those that arrest antegrade
ICA flow, those that reverse ICA flow, and filters for
distal embolic protection (DEP). In the United States,
only four such devices have received FDA approval
for carotid use and each is a distal filter: the Accunet
(with the Acculink stent), the EmboShield (with the
Xact stent, Abbott Vascular, Redwood City, California,
U.S.), the Spider (ev3, Plymouth, Minnesota, U.S.), and
the EZ filter wire (Boston Scientific, Natick, Massachu-
setts, U.S.). Several non-approved, commercially made
filters exist. Nonapproved flow-reversal devices
include the Parodi Anti-Embolic System (Gore Neuro
Protection System, W.L. Gore & Associates, Flagstaff,
Arizona, U.S.). Nonapproved flow-arrest devices
include the PercuSurge Guardwire (Medtronic, Minne-
apolis, Minnesota, U.S.), TriActiv System (Kensey
Nash, Exton, Pennsylvania, U.S.) balloon occlusion
catheters, and the MOMA (Invatec, Brescia, Italy) prox-
imal occlusion device.
A clear indication for proximal versus distal pro-
tection has not been established. Logically, intralumi-
nal thrombus, soft plaque, and poor distal landing zone
(tortuous poststenotic vessel) would be indications for
proximal protection. The results of the European Imag-
ing in Carotid Angioplasty and Risk of Stroke
(ICAROS) prospective registry showed that gray-scale
median (GSM) scores of 25 or less (representing echo-
genic plaque) are associated with higher embolic
potential (55). Out of 155 patients, 11 patients (7.1%)
with preprocedural GSM scores of 25 or less had
strokes after stenting versus 4 of 263 (1.5%) patients
with GSM greater than 25 (p 0.005). The authors,
therefore, then validated the use of DEP in patients
with GSM greater than 25 (p 0.01). However, for
patients with GSM of 25 or less stenting with proximal
embolic protection devices or CEA may prove safer.
Trials of Angioplasty and Stent Placement
with DEP Vs. CEA in High-Risk Patients
EVA-3S
Endarterectomy versus Angioplasty in Patients with
Symptomatic Severe Carotid Stenosis (EVA-3S) is a
French multicenter, noninferiority randomized trial
that was designed to compare the efficacy of CA
angioplasty and stent placement with or without
embolic protection against CEA for secondary preven-
tion of ischemic stroke (56). Enrollment in the study
group in which CA angioplasty and stent placement
were performed without protection devices was
halted because unprotected treatment was associated
with an excess 30-day stroke or death rate. Starting in
January 2003 (57), patients presenting within four
months of ischemic cerebral or retinal stroke with
ipsilateral carotid stenosis of 60% or more (according
to NASCET criteria) (6) were randomized into either
the protected CA angioplasty and stent placement
group or the CEA group. Primary endpoints included
any death or recurrent stroke within 30 days and at
two to four years. Secondary outcomes included MI,
TIA, cranial neuropathy, functional status at the end
of the study, and the degree of restenosis in treated
vessels. The incidence of stroke or death at 30 days
was 3.9% after CEA versus 9.6% after stenting; at six
months, it was 6.1% and 11.7%, respectively (46).
Cranial nerve injury was more common after CEA
than stenting. There were more major local complica-
tions after stenting and more systemic complications
(mainly pulmonary) after endarterectomy, but the
differences were not significant.
 Chapter 17: Endovascular Treatment of Extracranial Carotid Atherosclerotic Disease
EVA-3S was designed to test noninferiority of CA
stenting, but technical shortcomings limit the interpre-
tation of this study. Patients treated without DEP had a
25% 30-day stroke or death rate versus 7.9% in those
treated with DEP. Comparing this 7.9% stroke or death
rate with the rate in the CEA group (3.9%), the relative
risk becomes 2.05 (95% confidence interval: 0.974.36),
which is not statistically significant (SAS software, SAS
Institute, Inc., Cary, North Carolina, U.S.; Chi square
test, values not adjusted for multiple testing). Surgeons
were fully trained and completed 25 endarterectomies
in the year before enrollment. However, intervention-
ists were certified after performing as few as five
carotid stent procedures (5 carotid stents among at
least 35 stent procedures of supra-aortic vessels or 12
carotid stents) or were allowed to enroll patients in the
trial while they were receiving their training in carotid
stenting. The 12.3% stroke or death rate among endo-
vascular physicians tutored in CA stenting during the
trial, the overall 9.6% associated with CA stenting with
or without DEP, and 7.9% with DEP are higher than
those of other recent trials or registries (5863). The
Carotid Revascularization Endarterectomy versus Stent
Trial (CREST) (see below) requires more extensive
credentialing and has shown a 4.6% 30-day stroke or
death rate during the lead-in phase (64). Therefore, we
must carefully consider the findings of EVA-3S and
hope that future trials require stenting with DEP by
more experienced interventionists.
CaRESS
Carotid Revascularization using Endarterectomy or
Stenting Systems (CaRESS) was a multicenter, non-
randomized, prospective study comparing CA stent-
ing with DEP and CEA (59,65). Importantly, the choice
of the procedure was left up to the treating physician.
In this way, the CaRESS study may represent a more
real world perspective on carotid intervention. slightly higher than those reported in ACAS (61)
Symptomatic patients with more than 50% stenosis
and asymptomatic patients with more than 75% steno-
sis were considered for treatment. The primary end-
point was all-cause mortality at 30 days and 1 year.
The results of this trial are summarized in Table 2.
Overall, in the real world setting of the CaRESS 11.9%, which was significantly higher than for patients
study, CA stenting exhibited a trend toward lower
morbidity and mortality than CEA but appeared
slightly less durable at 30 days and 1 year. Importantly,
morbidity and mortality approached the range of
Table 2 Summary of CaRESS Results
CEA CA stenting
(%) (%) p value
Death or stroke at 30 days 3.6 2.1 NS
Death or stroke at 1 yr 13.6 10 NS
Death, stroke, or MI at 30 days 4.4 2.1 NS
Death, stroke, or MI at 1 yr 14.3 10.9 NS
Restenosis at 1 yr 3.6 6.3 NS
Abbreviations: CaRESS, carotid revascularization using endarter-
ectomy or stenting systems; CEA, carotid endarterectomy; CA,
carotid artery; MI, myocardial infarction; NS, not statistically
significant.
315
ACAS (11) and NASCET (6,9). In reviewing the dem-
ographics of the CaRESS study, the only statistically
significant difference was the inclusion of more
patients who had undergone previous CEA and CA
stenting in the stenting cohort. Of note, no statistically
significant difference was found between CaRESS
cohorts with respect to many of the high-risk criteria
in other studies (including contralateral stenosis, coro-
nary artery disease, and congestive heart failure). The
lack of statistical significance in the primary endpoint
suggests that the treating physicians were able to triage
these high-risk groups successfully.
CREST
The CREST is a randomized trial that compares the
efficacy of CEA with that of CA angioplasty and stent
placement performed with the aid of an embolic pro-
tection device in the prevention of stroke, MI, and
death in symptomatic patients (TIA or ipsilateral non-
disabling stroke within the previous 180 days) with
more than 50% CA stenosis and asymptomatic
patients with more than 70% stenosis. The primary
endpoints are death, stroke, or MI at 30 days or
ipsilateral stroke within 60 days of the procedure.
The trial has multiple participating centers in North
America, with the goal of enrolling 2500 patients. A
credentialing phase for interventionists was included
that required previous carotid stenting experience and
monitoring of the performance of up to 20 procedures
using the Acculink stent and Acculink embolic pro-
tection system (64). During the lead-in phase, major
adverse event rates were 5.7% for symptomatic
patients and 3.5% for asymptomatic patients. The
30-day composite rate of stroke and death for symp-
tomatic patients was slightly lower than the rates
reported in NASCET and ECST (61). For asymptomatic
patients, 30-day stroke and death rates have been
but slightly lower than those reported in the ACST
(12). Similar periprocedural morbidity was observed in
women and men (66) and for those treated with or
without an embolic protection device (67). For octoge-
narians (68,69), the 30-day stroke and death rate was
aged 79 years and younger. The study is still in the
enrollment phase, but promises to provide direct evi-
dence for the role of CA angioplasty and stent place-
ment in the community at large.
SAPPHIRE
The aims of the Stenting and Angioplasty with Pro-
tection in Patients at High Risk for Endarterectomy
(SAPPHIRE) randomized trial were to compare CA
stenting with CEA and to demonstrate statistical
noninferiority of stenting to CEA (63). The study
population consisted of high-risk patients with greater
than or equal to 50% symptomatic stenosis and greater
than or equal to 80% asymptomatic stenosis. For the
endovascular group, the Smart or Precise stent (Cordis
Corp., Miami Lakes, Florida, U.S.) and the Angio-
guard or Angioguard XP (Cordis Corp.) DEP device
were used. During the study period, 747 patients were
316 Sauvageau et al.
enrolled out of which 344 underwent randomization.
Primary endpoints included a composite of death/
stroke/MI within 30 days and death or ipsilateral
stroke between 31 days and 1 year. Secondary end-
points included target vessel revascularization at one
year, cranial nerve palsy, and complications at the
surgical site or the vascular access site. SAPPHIRE
had a broad endpoint by comparison with previous
CA intervention trials, in particular with NASCET and
ACAS in which MI and death after 30 days were not
primary endpoints. Similar to coronary intervention
studies, MI was included in the primary composite
endpoint of SAPPHIRE and the secondary endpoint of
CaRESS and is a component of the primary endpoint
in CREST. Moreover, perioperative non-Q wave MI
after peripheral vascular operations has been associ-
ated with a sixfold increase in mortality and a 27-fold
increase in recurrent MI during the six months after
the operation (70).
The results of the SAPPHIRE trial are summarized
in Table 3. At one year, 12.2% of patients undergoing
CA stenting had reached the primary endpoint versus
20.1% of the CEA group (p value for superiority: 0.053; p
value for lack of inferiority: 0.004). Target vessel revas-
cularization occurred in 4.3% of the CEA group versus
0.6% of the CA stenting group (p 0.04). Considering
secondary endpoints at one year, CA stenting was
superior to CEA with respect to MI (2.5% stenting vs.
8.1% CEA; p 0.03) and major ipsilateral stroke (0%
stenting vs. 3.5% CEA; p 0.02). Superiority was an
unexpected finding, and one that was not necessary for
the trial to succeed in its goal of providing data for
regulatory approval of CA stenting in high-risk patients.
Moreover, an analysis of the trial outcome that excludes
MI confers noninferiority of stenting compared with
CEA and does not change the results of this trial.
Preliminary three-year follow-up data for
SAPPHIRE has been presented (71). At three years,
the overall major adverse event rate (30.3% CEA, 25.5%
stenting; p 0.20) and incidence of death (24.2% CEA,
20.0% stenting; p 0.280), ipsilateral stroke (7.1% CEA
vs. 6.7% stenting; p 0.945), and target lesion revascu-
larization (7.1% CEA vs. 3.0% stenting; p 0.084), all
favor CA stenting over CEA but not to statistical
Table 3 Summary of SAPPHIRE Results
1 yr
Death, stroke, or MI within 30 days and death or ipsilateral
stroke between 31 days and 1 yr
Target vessel revascularization within 1 yr
3 yr
Overall major adverse event rate
Death
Ipsilateral stroke
Target lesion revascularization
Absolute percentage of stroke (all strokes to 30 days and major ipsilateral strokes from 311080 days)
All randomized patients
Randomized asymptomatic patients
Randomized symptomatic patients
Abbreviations: SAPPHIRE, stenting and angioplasty with protection in patients at high risk for endarterectomy; CEA, carotid
endarterectomy; CA, carotid artery; MI, myocardial infarction.
significance (Table 3). The absolute percentage of stroke
(all strokes within 30 days and major ipsilateral strokes
from 31 to 1080 days) was calculated as follows: for all
randomized patients, 3.6% CEA versus 3.5% stenting;
for randomized symptomatic patients, 3.2% CEA
versus 5.0% stenting; and for randomized asympto-
matic patients, 3.8% CEA versus 2.9% stenting. With
respect to stroke morbidity, these data suggest that
asymptomatic patients are slightly better served by
CA stenting and symptomatic patients by CEA. At
three years, the end result is that among the high-risk
patients studied and with the endpoints chosen, CA
stenting was not inferior to CEA in MI, stroke, and
target lesion revascularization.
ICSS (CAVATAS-2)
The finding of higher rates of restenosis in the CA
angioplasty group of CAVATAS resulted in the initi-
ation of a second prospective, randomized trialthe
International Carotid Stenting Study (ICSS), also
known as CAVATAS-2to compare the risks and
benefits of primary CA stent placement with those
of conventional CEA in patients at high risk for stroke
(72). According to the study protocol, use of a cerebral
protection device is recommended whenever the oper-
ator thinks that the device can be safely deployed. As
of September 2006, 1024 of the planned 1500 to 2000
patients from 47 centers have been randomized to
participate in the trial.
SPACE
To compare the safety and prophylactic efficacy of
CEA with CA angioplasty and stent placement against
stroke in patients with symptomatic CA stenosis, the
German Ministry of Science sponsored the Stent-
Supported Percutaneous Angioplasty of the Carotid
Artery versus Endarterectomy (SPACE) trial, a pro-
spective, randomized, multicenter study (73). Eligibil-
ity for this study was extended to patients with severe
CA stenosis [70% by duplex ultrasonography, 50%
by NASCET criteria (6), or 70% by ECST criteria (18)]
who had experienced amaurosis fugax, TIA, or mild
stroke within 180 days of randomization. A total of
CEA (%) CA stenting (%) p value
20.1 12.2 0.053 for superiority,
0.004 for lack of inferiority
4.3 0.6 0.04
30.3 25.3 0.20
24.2 20.0 0.280
7.1 6.3 0.945
7.1 3.0 0.084
3.6 3.5
3.2 5.0
3.8 2.9
 Chapter 17: Endovascular Treatment of Extracranial Carotid Atherosclerotic Disease
1200 patients were randomized to CA stenting (n
605) or CEA (n 595). Primary outcome measures
included 30-day incidence of ipsilateral cerebrovascu-
lar events or death. A total of 1183 patients were
included in the 30-day results analysis (62). The rate
of death or ipsilateral ischemic stroke from the time of
randomization up to 30 days after the procedure was
6.84% with CA stenting and 6.34% with CEA. SPACE
failed to prove noninferiority of CA stenting compared
with CEA for the periprocedural complication rate. The
failure of this trial to show non-inferiority may have
resulted from an underpowered sample and higher
than expected event rates in both groups of patients
evaluated. Results at 6 to 24 months are pending.
Trials of Angioplasty and Stent Placement
with DEP Vs. CEA in Low-Risk Patients
The results encountered in the high-risk population
have led to the evaluation of CA stenting as a revas-
cularization alternative for low-risk patients. Three
prospective, randomized trials in low-risk patients
are under way: the Asymptomatic Carotid Stenosis,
Stenting versus Endarterectomy Trial (ACT I), the
Asymptomatic Carotid Surgery Trial-2 (ACST-2),
and the Transatlantic Asymptomatic Carotid Interven-
tional Trial (TACIT).
ACT I is currently enrolling low surgical risk
patients with asymptomatic CA stenosis (a single ICA
lesion with 80% but 99% stenosis) at multiple
centers in North America. The devices used in this
trial are the EmboShield DEP device and the Xact stent
(Abbott Vascular). The randomization scheme is 3:1
for CA stenting to CEA.
The ACST-2 is also randomizing asymptomatic
patients with severe CA stenosis to CEA versus stenting
(74). The primary analysis will include clinical MI, stroke,
and death within 30 days of either treatment, and
chances of long-term (five years) stroke-free survival.
The investigators will use Conformite Europeenne-
marked devices, usually with cerebral protection.
TACIT will study all-risk patients with asymp-
tomatic CA stenosis, assigning these patients to one of
two treatment groups (74,75). The first group will be
optimal medical therapy alone, consisting of antipla-
telet, antilipidemic, and antihypertensive therapy, as
well as strict serum glucose control and tobacco ces-
sation efforts. The second group will provide optimal
medical therapy plus CA stenting using embolic pro-
tection (with commercially available devices). The aim
of the TACIT investigators is to enroll approximately
2400 patients, equally divided between the two treat-
ment groups. The primary endpoint is a composite of
30-day mortality, all strokes within the five-year study
period, and a neurocognitive component (neurocog-
nitive decline, which is defined as vascular dementia
or vascular depression) measured using predomi-
nantly depression scales. Secondary endpoints will
include a detailed quality-of-life and cost-effective
analysis as well as plaque characterization (detailed
core lab assessments of ultrasound plaque features).
As mentioned, CREST is ongoing for both high-
risk and low-risk patients to compare the efficacy of
317
CA stenting and CEA in preventing stroke, MI, or
death in both symptomatic and asymptomatic
patients with carotid stenosis. If CA stenting is
found equal to or superior to CEA or to rigorous
medical therapy in the low-risk patients enrolled or
scheduled for enrollment in the aforementioned trials,
the results may lead to broader application of stenting
for carotid intervention.
CA STENTING PROCEDURE
Procedural Overview
The CA stenting procedure is an evolving procedure
that has been modified according to operator experi-
ence and device development. The usual sequence of a
procedure performed in conjunction with the use of a
filter device for embolic protection is outlined below.
The procedure is performed in an angiography
suite with biplane digital subtraction and fluoroscopic
imaging capabilities. The patient is sedated but arous-
able for neurological assessment. A Foley catheter and
two peripheral IV lines are inserted. Blood pressure,
oxygen saturation, and cardiac rhythm are monitored
during the procedure. The CA is generally ap-
proached percutaneously from the common femoral
artery. The interventionist should also be familiar with
radial and brachial approaches in case femoral artery
access is not possible.
An aortic arch angiogram is initially performed
to define the atherosclerotic burden as well as the
anatomical configuration of the great vessels, which
allows the operator to predict the feasibility of carotid
cannulation and select the devices needed for the
procedure. Selective carotid angiography is then per-
formed, and the severity of the stenosis is defined. The
diameters of the common carotid artery (CCA) and
ICA are measured with attention paid to determining
a landing zone for the protection device. Intracranial
angiography is also essential prior to intervention
because the presence of tandem lesions should be
considered in the management strategy.
The processes of angioplasty and stenting create
intimal injury that promotes thrombosis (76). There-
fore, patient preparation with adequate antiplatelet
and anticoagulation therapy is essential. Patients
receive a dual antiplatelet regimen consisting of aspi-
rin (325 mg daily) and a thienopyridine derivative
(i.e., clopidogrel, 75 mg daily; or ticlopidine, 250 mg
twice daily) for at least three days before stent treat-
ment. A loading dose of clopidogrel (300600 mg)
administered early on the day of the procedure is
an alternative for patients who are already taking
aspirin. An intravenous bolus dose of heparin (50
60 U/kg) is administered after catheterization of
the CCA. An activated coagulation time of 250 to
300 seconds is maintained throughout the procedure.
The heparin infusion is usually discontinued at the
conclusion of the procedure.
Bradycardia occurs occasionally during angio-
plasty. Atropine and vasopressors should be readily
available should significant bradycardia and hypoten-
sion develop. Continuous intraprocedural monitoring
318 Sauvageau et al.
of heart rate, blood pressure, and neurological status
is essential.
After completion of the diagnostic angiogram
and positioning of the catheter in the CCA, road
mapping of the cervical CA is performed. An
exchange-length 0.035-inch wire is positioned in the
external CA. The diagnostic catheter is exchanged
over the wire for a 90-cm, 6- to 10-French (Fr) sheath
that is then advanced into the CCA below the bifur-
cation. For patients who have undergone complete
diagnostic cerebral angiography before the stenting
procedure, a combination of a 6-Fr, 90-cm shuttle over
a 6.5-Fr head-hunter 125-cm slip-catheter (Cook, Inc.,
Bloomington, Indiana, U.S.) or a 5-Fr 125-cm Vitek
catheter (Cook) can be used. In these cases, the shuttle
is introduced primarily in the femoral artery over a
0.35-inch wire and is parked in the descending aorta.
The inner obturator and wire are removed. The
125-cm catheter is then advanced into the shuttle
and the target vessel is catheterized. The shuttle is
brought over the wire and the catheter in the CCA.
The size of the shuttle is usually dictated by the
embolic protection device profile and compatibility
with the stent system. An optimal angiographic view
that maximizes the opening of the bifurcation and
facilitates crossing of the stenosis should be sought.
The lesion is crossed with the protection device.
Predilation of the stenotic vessel segment is per-
formed at the operators discretion. A 3- to 4-mm
coaxial angioplasty balloon is advanced to the lesion
over the 0.014-inch wire holding the protection device.
On rare occasions, predilation needs to be performed
prior to the introduction of an embolic protection
device. In such cases, the balloon system is then
exchanged for a stent system.
The diameter of the stent should be sized to the
caliber of the largest segment of the CA to be covered
(usually 1 to 2 mm more than the normal caliber of the
CCA). Oversizing of the stent in the ICA does not
usually result in adverse events, but a tapered stent
can better conform to the vessel wall. Particular atten-
tion should be paid to the selection of a stent that is
long enough to cover the entire lesion.
After removing the stent system, poststent dila-
tion should be performed using a balloon with a
diameter matching that of the ICA distal to the stent.
A coaxial balloon is usually preferred for this purpose.
The embolic protection device is then removed, using
its retrieval catheter. When a balloon occlusion catheter
is used for cerebral protection, the embolic debris is
aspirated before deflation and retrieval of the balloon.
The most common settings for difficulty in cap-
turing deployed filter protection devices are with an
open-celled stent on a significant vessel curve (in
which a stent strut may impinge on the vessel intima)
and when the device is parked in a tortuous distal
vessel. A systematic approach will generally lead to
successful recapture of the device. Advancing the
guide catheter into the stent will bias the wire away
from the stent wall, allowing the recaptured sheath to
pass. Having the patient inhale deeply or turn his or
her head opposite to the direction of the vessel curve
can help straighten the curve or elongate the artery
enough for passage of the sheath. More aggressively,
pressing on the stent in the patients neck will also
change the bias of the wire. If the sheath is impeded
by a stent strut, redilatation with a larger balloon or
spinning the sheath with forward pressure will help
flatten the strut or allow passage for the sheath. If
other maneuvers fail, a 4- or 5-Fr-angled glide catheter
can be passed over the DEP wire to capture the filter.
A device may be used for closure of the access site
(e.g., Starclose, Abbott Vascular; Perclose, Abbott Vas-
cular; or Angio-Seal, St. Jude Medical, Minnetonka,
Minnesota, U.S.) on the basis of operator preference,
patient anatomy, and puncture site location.
Postintervention Follow-Up
Good hydration should be maintained after the pro-
cedure. Hypotension and hypertension should be
avoided. Particular attention must be paid in cases
of severe stenosis and contralateral occlusion to pre-
vent reperfusion hemorrhage. If a closure device has
not been used, the arterial sheath should be removed
when the activated coagulation time is less than
150 seconds. The patient is usually discharged the
following morning. Patients require surveillance
imaging to evaluate vessel patency. Duplex sonogra-
phy evaluation should be obtained before discharge,
at six months, one year, and then annually thereafter.
The dual antiplatelet regimen of aspirin and clopidog-
rel is maintained for four to six weeks postprocedure,
after which patients remain on aspirin therapy.
Markers of High-Risk CA Stenting
Unfavorable anatomical and lesion characteristics are
factors that may impact the risk of CA stenting.
Stenotic or occluded iliac arteries or abdominal aorta
are among the unfavorable access characteristics. A
difficult arch (type 2 or 3, calcification or bovine con-
figuration) can be challenging for a less-experienced
operator. Occlusion of the external CA or stenosis
involving the CCA may increase the risk in positioning
the guiding catheter or shuttle. Tortuosity of the ICA,
severity of the lesion, degree of calcification, and pres-
ence of intraluminal thrombus represent other adverse
factors. Low plaque echolucency (GSM) is also an
adverse prognosticator (55,77).
Durability of CA Stenting
Durability of carotid revascularization with CA stent-
ing is a concern frequently expressed by the surgical
community. In a retrospective study of patients
undergoing stenting for de novo (119 arteries) and
postendarterectomy (76 arteries) carotid stenosis, 80%
or more stenosis was detected by follow-up Doppler
imaging in 5.2% of the vessels stented (78). Restenosis
after endarterectomy was the major risk for in-stent
restenosis. Significant (symptomatic or 80%) recur-
rent stenosis was detected by follow-up Doppler
imaging in 6 (5%) of 112 patients in our CA stenting
series (79).
 Chapter 17: Endovascular Treatment of Extracranial Carotid Atherosclerotic Disease
COMPLICATION OCCURRENCE
AND AVOIDANCE
From puncture of the femoral artery to retrieval of the
protection device and performance of the final angio-
gram, potential exists for complications during CA
stenting that can be threatening to life, limb, or brain.
Delayed neurological, cardiac, and peripheral compli-
cations can also occur and may require immediate
intervention for meaningful salvage. Knowledge of
these complications is essential to ensure quick recog-
nition and effective management. Patient selection is
the most important factor in minimizing complications
associated with CA stenting. The experience of the
interventionist and staff is the second most important
factor. It is essential that all personnel are familiar with
all the equipment, devices, pharmacological agents,
critical care management, and the disease process
treated.
Many risks associated with CA stenting can
be mitigated before and during the procedure.
Guide catheters are flushed frequently with normal
saline (0.9% NaCl) with 5000 units of heparin in each
pressure bag. The air should be actively removed from
each flush bag.
Access Site Complications
The rate of local complications occurring during diag-
nostic cerebral angiography can be as high as 5% (80).
The most common access problems include retrograde
dissection, pseudoaneurysm, arteriovenous fistula,
extravasation of blood around the sheath, tortuosity,
and the inability to gain access. Femoral artery occlu-
sion and bleeding can also occur in an acute or
delayed fashion.
The external CA and its branches are used to
support a guidewire during the exchange of a diag-
nostic catheter for a guide sheath or catheter. Vessel
perforation in this setting has been described by our
group (81). To prevent this complication, large
branches of the external CA, preferably the internal
maxillary artery or occipital artery, should be used for
exchange maneuvers.
Carotid dissection is another complication that
can be encountered during the stenting procedure. For
cases of small, asymptomatic and non-flow-limiting
dissections, clinical observation is recommended.
Stenting is warranted if the dissection is symptomatic
or flow limiting.
Spasm is frequently encountered when the DEP
device or the guide catheter straightens or moves a
kink in the CA. This can be ignored, as it will resolve
with device retrieval and often resolves after stenting
and postdilatation angioplasty.
Neurological Complications
Stroke can occur at any point after femoral artery
access has been obtained. If a patient develops a
sudden neurological change, the differential diagnosis
entertained should include hemorrhage and ischemia,
most often due to embolism. On the basis of findings
319
of the neurological examination, rapid access should
be gained to the vessel suspected of harboring the
problem. If the patients airway is compromised,
intubation should be performed. If no vessel cutoff
or slow flow is appreciated, hemorrhage must be
ruled out and the patient should undergo a CT scan
of the head. On the basis of transcranial Doppler
ultrasound data in which protected stenting with the
PercuSurge device was compared to unprotected
stenting, the highest-risk maneuvers for embolism in
conjuction with risk in unprotected stenting, from
lowest to highest risk, were predilation angioplasty,
stenting, and postdilation angioplasty (51).
The intracranial complications of CA stenting
can be grouped into large vessel occlusion, shower
of emboli, and hemorrhage. If a clear large vessel
cutoff can be seen, an immediate attempt should be
undertaken to recanalize the occluded vessel. If an
angiogram documents slow flow and the CT scan is
negative for hemorrhage, IIb/IIIa antiplatelet agents
are administered. If a hemorrhage is identified, hep-
arin anticoagulation is reversed with protamine, the
blood pressure tightly controlled, and a repeat CT
scan is obtained within 6 to 12 hours. Life-threatening
hematomas in neurologically salvageable patients can
be evacuated.
Systemic Complications
Systemic complications may also occur following CA
stenting. These include seizures, MI, contrast material
nephropathy, and contrast material allergy. The inter-
ventionist, treating institution, and ancillary staff
should be versed in the management of all four of
these conditions as in most patients, seizures, MI,
contrast nephropathy, and allergic reaction can be
readily treated.
ILLUSTRATIVE CASES
Case 1 (Tortuous Anatomy)
A 68-year-old woman with a remote history of two left
hemispheric strokes was found to have severe left ICA
origin stenosis on noninvasive studies. Her past med-
ical history also included diabetes, hypertension, mor-
bid obesity, and inactive congestive heart failure. She
had a mild residual right hemiparesis and no addi-
tional ischemic symptoms since her strokes three
years earlier. Angiography confirmed 80% stenosis
of the left ICA origin. Because she had a short, immo-
bile neck and a high carotid bifurcation at the level of
the C2 vertebral body, the patient was selected for CA
stenting. The tortuosity of the ICA prohibited safe
advancement of a DEP device (Fig. 1A, B). Carotid
stenting with angioplasty was performed successfully
using proximal protection with a flow-reversal system
(Gore Neuro Protection System) (Fig. 1C). Care was
taken not to position the stent in the tortuous segment
of the ICA (Fig. 1D). Occlusion time was approxi-
mately 12 minutes, and the patient tolerated the pro-
cedure well. She was discharged the next day at her
baseline neurological condition.
320 Sauvageau et al.
Case 2 (Intraoperative Plaque Rupture)
A 62-year-old man with a history of left frontal stroke
resulting in aphasia and left hemiparesis was found to
have bilateral ICA origin stenosis. He recovered well
from his stroke and underwent successful left carotid
angioplasty with stenting. He returned for endovas-
cular treatment of the asymptomatic 90% right ICA
stenosis (Fig. 2A, B). DEP was obtained with a 5-mm
EmboShield. Angioplasty was done before and after
placement of an Xact stent (6  30 mm to 8  30 mm).
An opacity, consistent with plaque debris or throm-
bus, was seen just distal to the stent (Fig. 2C). Intra-
vascular ultrasonography confirmed that this was a
plaque fragment, and a second Xact stent (7  20 mm)
was placed (Fig. 2D, E). The lesion was now covered
completely by the stents, and the embolic protection
device contained visible debris. The patient remained
unchanged neurologically and was discharged the
next day.
Figure 1 (A) AP and (B) lateral projections of left CCA
injection demonstrating 80% stenosis of the ICA origin.
Note the sharp turn in the ICA distal to the stenosis.
Such tortuosity is a relative contraindication to DEP
devices. (C) AP view showing the establishment of flow
reversal after occlusion in the external CA and distal
CCA. An arteriovenous conduit had been created
between the left ICA and the left common femoral
vein prior to flow reversal. (D) AP view shows good
positioning of the stent. The stent does not involve the
tortuous segment of the ICA. Abbreviations: CCA, com-
mon carotid artery; ICA, internal carotid artery; DEP,
distal embolic protection.
CONCLUSIONS
In 2007, the CAS procedure is considered not infe-
rior to CEA for the treatment of high-risk patients
with symptomatic and asymptomatic CA disease.
CAS and CEA are complementary procedures. The
availability of both approaches at a single center can
certainly optimize patient care (82). Evaluation of CA
stenting in the low-risk population is ongoing. The
results of such studies may have a significant influ-
ence on CEA, considering that in the case of clinical
equivalence between CA stenting and CEA, patients
are likely to favor the less-invasive endovascular
approach. In terms of durability, stenting is slightly
inferior to endarterectomy (as shown in studies men-
tioned in this chapter), but this will likely not limit its
widespread use if equipoise between the two thera-
pies is proved. With future technological develop-
ments including improved embolic protection
systems and refined stents with smaller delivery
Figure 2 (A) AP and (B) lateral projections
of right CCA injection show 90% stenosis of
ICA distal to its origin. (C) Lateral view shows
resolution of the stenosis after stenting and
angioplasty. The embolic protection device is
positioned in the distal cervical ICA. However,
opacity (arrow) is seen distal to the stent.
Intravascular ultrasonography confirmed that
this was a fragment of plaque. (D) AP and (E)
lateral views show a good angiographic result
after placement of an overlapping stent to
cover this fragment. Abbreviations: CCA,
common carotid artery; ICA, internal carotid
artery.
 Chapter 17: Endovascular Treatment of Extracranial Carotid Atherosclerotic Disease
platforms, CA stenting may become the new gold
standard for carotid revascularization.
DISCLOSURES
L. N. Hopkins: Research GrantsBoston Scientific,
Cordis, Micrus; HonorariaBard, Boston Scientific,
Cordis, Medsn; Stock or ShareholderAPW Holding
Inc., Boston Scientific, EndoTex, Micrus; Consultant/
Advisory BoardAbbott, Bard, Boston Scientific,
Cordis, EndoTex, Access Closure, market Rx, Micrus.
E. I. Levy: Research GrantsBoston Scientific; Cordis;
Other Research Support (<10K)Wingspan devices
(Boston Scientific); HonorariaBoston Scientific,
Cordis; OtherAbbott Vascular (carotid stent train-
ing), ev3 (carotid stent training), Zimmer Spine
(patent royalties).
The remaining authors have no financial disclosures.
ACKNOWLEDGMENT
The authors of this chapter thank Paul H. Dressel for
preparation of the illustrations.
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 18
Stenting and Angioplasty for Intracranial
Atherosclerotic Occlusive Disease
Nabil M. Akkawi and Ajay K. Wakhloo
Division of Neuroimaging and Intervention, University of Massachusetts Medical School,
Worcester, Massachusetts, U.S.A.
INTRODUCTION
In 1964, the father of interventional radiology Charles
T. Dotter introduced the concept of transluminal
angioplasty at the University of Oregon in Portland,
United States, and applied it to the peripheral vascular
system. At that time, he had already discussed its
potential use for the renal and coronary circulation.
However, his idea was ignored in the United States for
nearly 15 years. The German-born cardiologist
Andreas R. Gruentzig, who was introduced to angio-
plasty by Eberhart Zeitler, performed the first success-
ful balloon angioplasty on human coronary artery in
1977 in Zurich, Switzerland. Since then percutaneous
transluminal angioplasty (PTA) has rapidly evolved
as a safe endovascular revascularization procedure for
vascular occlusive diseases of the peripheral, renal,
and coronary vascular system. In newer endovascular
technologies, PTA is being replaced by primary stent-
ing. Developments in microguidewire and balloon
catheter technology have enabled the interventional-
ists to expand their experience gradually from the
cervical parts of the carotid and vertebral arteries to
the cerebrovascular circulation for treatment of symp-
tomatic and medically refractory focal stenosis. Until
recently, the introduction of stent technology to the
anterior and posterior intracranial vascular systems has
been limited by the lack of specific stents and delivery
systems capable of safe, easy, and effective navigation
through the neurovascular system. The advent of a
new generation of more flexible stents and flexible
delivery systems has prompted consideration of stent-
assisted angioplasty as an alternative approach in intra-
cranial stenoses (15). In addition, recent advances in
imaging, including 3D angiography, high-resolution
and high-speed angiography, zoom digital fluoros-
copy, biplane road mapping, and 3D road map,
provide a precise and safe deployment of bioimplants.
Although limited experience exists, short- and midterm
angiographic and follow-up studies are encouraging.
In this chapter, the rationale and indications as well as
the technical aspects of endovascular revascularization
for intracranial atherosclerotic occlusive disease (ICD)
are presented.
DEMOGRAPHICS OF INTRACRANIAL
OCCLUSIVE DISEASE
As suggested by the increasing number of publica-
tions, important differences are observed in the
distribution of occlusive vascular disease among
African-Americans, Hispanics, and Caucasians and
among men and women (6,7). Baker and Iannone
described the location and severity of atherosclerosis
in 173 consecutive autopsies (8). The most common
sites of involvement were the internal carotid artery
(ICA) origin, the distal basilar artery, and the proximal
and midportion of the basilar artery, while the middle
cerebral artery (MCA) was the next most frequently
involved, followed by the vertebral arteries and the
posterior cerebral artery (PCA). The posterior inferior
cerebellar arteries (PICAs), the superior cerebellar
artery (SCA), and the distal anterior cerebral artery
(ACA) were frequently spared from atherosclerosis.
Angiography and autopsy studies all confirm
that African-Americans are more prone to develop
intracranial atherosclerosis, while Caucasians are
prone to develop extracranial disease (9). In the Joint
Study of Extracranial Arterial Occlusion, 91% of
patients with ICA occlusions were Caucasians, while
only 9% were African-Americans (10). In another
study, the ratio of MCA to ICA occlusive disease in
Caucasians and African-Americans was 13:84 and
10:1, respectively (11). It is suggested that Japanese
and Chinese populations, like African-Americans, also
have a predilection for occlusive lesions of the intra-
cranial vascular system, rather than the extracranial
ICA (12,13).
A female preponderance of intracranial occlu-
sive disease, with female to male ratio of 1:4 to 5:9, has
been reported in contrast to the male preponderance
of extracranial disease (1416). Flora et al. analyzed
5033 consecutive autopsies and made the following
observations (17). From the fourth to sixth decades of
life, the percentage of women without any intracranial
atherosclerotic disease was higher than that of men,
but beyond age 65 the frequency of atherosclerotic
lesions was similar in both sexes. Interestingly, dia-
betic women had higher incidence of intracranial
326 Akkawi and Wakhloo
atherosclerosis than nondiabetic men, and after the
fourth decade they had at least as much involvement
as diabetic men.
INDICATIONS FOR TREATMENT
In the United States, ICD causes approximately 10% of
ischemic strokes, i.e., nearly 70,000 to 90,000 ischemic
strokes annually (18). The estimated risk of stroke in
the setting of intracranial arterial stenosis varies from
approximately 7% to 40% per year with or without
medical treatment (1923). The natural history of
intracranial stenosis has been determined angiograph-
ically in a follow-up period of seven years: 61% of
ACA, MCA, and PCA stenotic lesions progressed
compared with 20% of intracranial ICA lesions (24).
Many patients with MCA stenosis have recurrent
cerebral ischemic events despite standard medical
therapy with antiplatelet agents or oral anticoagulants
(25,26). In the extracranial/intracranial bypass trial,
patients with symptomatic MCA stenosis randomized
to medical therapy had annual ipsilateral stroke rates
of 7.8% and total stroke rates of 9.5% (19,21). Only
about one-third of patients had a warning transient
ischemic attack (TIA) prior to stroke. The most com-
mon presentation was a stroke attack without a warn-
ing TIA (19).
The Warfarin versus Aspirin for Symptomatic
Intracranial Disease (WASID) study was a randomized
clinical trial that compared warfarin (target interna-
tional normalized ratio, 2 to 3) and aspirin (1300 mg/
day) for preventing stroke and vascular death in
patients with stenosis (5099%) of a major intracranial
artery (27). The study was prematurely terminated
because of safety concerns with warfarin. The drug
was associated with significantly higher rates of
adverse events, e.g., gastrointestinal bleeding, and
provided no significant benefit over aspirin for pre-
venting stroke and vascular death. The risk of stroke
was still significant in both the warfarin and the aspi-
rin arm during the mean follow-up period of 1.8 years.
Of the 280 patients treated with aspirin, 15% suffered
strokes in the territory of the stenotic artery. Of the 289
patients receiving warfarin, 12.1% had ischemic stroke
in the same territory.
Similarly, the Warfarin-Aspirin Recurrent Stroke
Study (WARSS) trial showed that warfarin had no
benefit over aspirin for secondary prevention in
the subgroup of patients with large artery thrombotic
stroke (stenosis or occlusion) (28). However, this study
was not specifically designed for patients with intra-
cranial atherosclerotic disease.
Medical therapy is mainly used to reduce arterio-
arterial thromboembolic stroke risk in case of athero-
sclerotic plaque ulceration. Although reduced regional
cerebral blood flow may be associated with ICD,
embolic events remain the major cause of stroke in
this patient population. Because of the poor response to
medical treatment, endoluminal revascularization of
intracranial athero-occlusive disease has been intro-
duced. This procedure would facilitate blood flow
through the affected area and prevent platelet activa-
tion related to high shear within the stenotic area. A
smooth neointimal growth after stenting/angioplasty
across the atherosclerotic lesion may also prevent a
plaque rupture and platelet adherence. However, ini-
tial attempts of revascularization were associated with
complication rates as high as 30%. Thus, most clinicians
reserve this modality for patients with at least 50%
symptomatic stenosis and refractory to optimal medi-
cal treatment (29,30). Today, with rapid development
of endovascular tools, percutaneous transluminal bal-
loon angioplasty and primary stenting are being dis-
cussed as an option for endoluminal revascularization.
PERCUTANEOUS TRANSLUMINAL
BALLOON ANGIOPLASTY
In 1964, Dotter and Judkins first described PTA for
femoral artery stenosis using a coaxial catheter system
(31). Later, in 1980, Sundt et al. first reported success-
ful intracranial angioplasty of the basilar artery in two
patients (32). Several case reports and case series
studies followed with varying results. Angioplasty
can be beneficial for patients with intracranial athero-
sclerosis who remain symptomatic despite aggressive
antiplatelet and anticoagulation therapy. Although
some investigators have reported good results after
intracranial PTA (3336), others have described high
rates of morbidity and mortality (30,37,38). The major
problems of intracranial balloon angioplasty are distal
embolization, vessel dissection and occlusion, vaso-
spasm and vessel rupture, as well as arterial throm-
bosis during or immediately after the PTA. Another
major disadvantage of the procedure is the risk of
restenosis at follow-up, which can result from over-
shooting neointimal proliferation caused by injury to
smooth muscle layer or a progression of the underly-
ing disease.
A retrospective study on 36 patients with 37
symptomatic intracranial atherosclerotic lesions who
underwent PTA showed a significant stroke risk
reduction within the mean follow-up period of
52.9 months. The periprocedural death and stroke
rate was 8.3%. The annual stroke rate in the PTA-
treated territory was 3.36%. However, when residual
stenosis was found to be greater than 50%, annual
stroke risk increased to 4.5% (39).
Restenosis has been reported to be approximately
30% at three months (40). Mori et al. investigated
lesion-specific features for predicting successful PTA
and a low restenosis rate (40). A short, less than 5 mm,
concentric or moderately eccentric lesion, which is not
totally occlusive on angiograms and less than three
months old, was defined as type A lesion. A type
B lesion was tubular, 5 to 10 mm long, extremely
eccentric or occluded, and older than three months. A
type C lesion was diffused, more than 10 mm long,
extremely angulated (>90%) with excessive tortuosity
of the proximal segment or occluded, and older than
three months. The highest success rate for PTA (92%)
and the lowest incidence of restenosis were found in
type A lesions (0% at 1 year) (Fig. 1), whereas in type B
 Chapter 18: Stenting and Angioplasty for Intracranial Atherosclerotic Occlusive Disease 327

Figure 1 A 59-year-old male with recurrent episodes of transitory ischemic attacks on antiplatelet therapy and a previous history of left
hemiparesis associated with a right hemispheric hemorrhagic infarction. (A) Right ICA angiogram shows a short and concentric
atherosclerotic type A lesion at the origin of the MCA (arrow). (B) PTA with a noncompliant 3  9 mm coronary PTA balloon at 6 atm
pressure (arrow, Maverick, BSC, Natick, Massachusetts, U.S.). (C) Post angioplasty angiography shows an excellent revascularization
with a visible shelf corresponding to the remaining compressed plaque and probably a small plaque dissection (arrow). Abbreviations:
ICA, internal carotid artery; MCA, middle cerebral artery; PTA, percutaneous transluminal angioplasty.

lesions the success rate was 82% and restenosis at one
year was 33%. The lowest success rate (33%) and the
highest restenosis rate or occlusion were found in type
C lesions (100% at 1 year) (41).
Connors et al. published their experience with
PTA for intracranial atherosclerotic stenosis. The report
focused on clinical and angiographic outcome related
to applied technique and operator experience (33).
The authors distinguished three subgroups of patients.
In the early period, in which eight patients were
treated, the angioplasty balloon size approximated
the vessel size or was smaller. Time of balloon inflation
was rapid and brief (1530 seconds). Despite good
clinical outcome in seven (87.5%) of eight patients,
dissection occurred in 50% of the patients and residual
stenosis was found in three of the eight treated
patients.
In the second subgroup of 12 patients, the PTA
balloon size approximated the vessel size, but was
permitted to be oversized by up to 0.25 mm. Angio-
plasty was extremely rapid and brief. Dissection
occurred in 9 of 12 patients, resulting in death of
one patient due to vessel occlusion. In their most
recent experience, which included 50 patients, the
PTA balloon was always undersized and inflation
was extremely slow and over several minutes. Dissec-
tion occurred in 7 of 50 patients (14%), necessitating
regional intra-arterial thrombolysis in 2 of 50 patients
(4%) with uneventful outcome in both patients. No
occlusion or ischemic stroke was observed in any of
these patients. Residual stenosis greater than 50% was
seen in 8 of 50 patients (16%). Late restenosis was
observed in 4 of 44 follow-ups (9%), and a successful
reangioplasty was performed in all four patients.
Unlike in the coronary or peripheral system,
angioplasty of intracranial arteries poses a higher
risk of vessel rupture and fatal outcome because of
the lack of surrounding supportive soft tissue and the
composition of the vessel wall. Thus, technical details,
such as selection of PTA balloon size (length and
diameter), inflation pressure, and speed and duration
of inflation, may all determine the short- and long-
term outcome and the periprocedural morbidity.
Balloon overdilatation may be dangerous in the
basilar artery and the MCA, where different authors
advocate underdilating (not more than one-half of the
normal vessel diameter) because of the presence of
stiffer adventitia, less elastic tissue, and a greater
proportion of smooth muscle, resulting in elevated
risk of perforation (42,43). However, there has been no
consensus among the interventionalists on techniques
of angioplasty in the neurovascular system.
Recently, Yoon et al. published their experience
with angioplasty of symptomatic MCA stenosis
(>70%) on 32 patients (44). The procedure was
successful in reducing the stenosis to less than 50%
in 91% of the patients. Disabling stroke or death
occurred in 6% of cases. The rate of periprocedural
TIA was 19%. Five patients had asymptomatic intimal
dissection. During a median follow-up period of
20 months, an ipsilateral TIA was seen in one patient,
while other patients remained asymptomatic.
Although only a small number of intracranial
PTAs have been reported, the high risk of periproce-
dural morbidity associated with artery dissection and
acute vessel occlusion and the risk of recoil and
delayed restenosis are unacceptable. Compared with
the evolution in the coronary system, primary stenting
of intracranial atherosclerotic disease is gradually
replacing balloon angioplasty.
PRIMARY STENTING AND STENT-ASSISTED
ANGIOPLASTY
The term stent is derived from the name Charles
Stent (18451901), an English dentist who developed a
mold that was used to form an impression of the teeth
and oral cavity. Later, the term was used in associa-
tion with a device that held a skin graft in position, a
support for tubular structures that were being anas-
tomosed. More recently, the term is used for an
endovascular scaffolding to relieve and prevent vas-
cular obstructions (45).
Analogous to the development in peripheral,
carotid, and coronary occlusive diseases, primary
stenting will replace angioplasty (46). The purported
328 Akkawi and Wakhloo
advantages of stent placement over simple angio-
plasty include avoiding plaque dislodgment, intimal
dissection, elastic vessel recoil, plaque regrowth, and
potentially late restenosis. Compared with balloon
angioplasty, stent placement also achieves a better
angiographic result (Fig. 2). However, intracranial
stent placement has potential hazards, such as arterial
rupture, in-stent thrombosis, malpositioning and mal-
apposition of the stent, or the inability to pass the stent
to the appropriate location due to the tortuosity of the
cerebrovascular system. Primary stenting of the sten-
otic arterial segment without predilatation is fre-
quently feasible (Fig. 4). Only severely stenotic and
long lesions may require predilatation for a safe stent
placement (47).
In a series of 12 patients who underwent an
elective stenting of the basilar artery after episodes
of vertebrobasilar ischemia, stent placement was suc-
cessful in all patients; no periprocedural complica-
tions were encountered (4). On clinical follow-up
between 0.5 to 16 months, all patients remained
asymptomatic, except one with nonspecific symptoms
and another with TIA. Symptomatic occlusion of
penetrating vessels and pontine perforators poten-
tially jailed by stent struts were not observed. Stenting
of the MCA was a technical challenge primarily
because of the difficulty of tracking coronary balloon-
expandable stents around the internal carotid siphon
(48). Using coronary stents, elective revascularization
of symptomatic MCA stenosis was successful in 8 of
Figure 2 A 62-year-old female with a successful thrombolysis of
a basilar trunk occlusion presents with dysarthria and vertigo,
intermittently for several days after the procedure and on thera-
peutic heparinization. (A) Right vertebral artery angiogram shows
a long and ulcerated atherosclerotic type C lesion of the verte-
brobasilar system with a poor filling of the posterior circulation,
the right AICA, and both SCAs. (B) Primary stenting and place-
ment of four overlapping short balloon-expandable 2.5  13-mm
coronary stents. While an improved flow to the posterior circula-
tion is noted, the right AICA and the left SCA is still poorly
visualized (arrow). (C) Eight-month follow-up angiogram shows
an improved flow to the jailed AICA (arrow). Some plaque growth is
seen at the level of the AICA. Straightening of the artery is noted
within the stented segments (arrowheads). Abbreviations: AICA,
anterior inferior cerebellar artery; SCAs, superior cerebellar
arteries.
14 patients, without any complications. Stent place-
ment failed in two cases because of the tortuosity of
the ICA siphon. Four patients (30%) experienced
periprocedural complications, including arterial rup-
ture in two patients and thrombotic occlusion in two
other patients (49). In a larger study, Jiang et al. used
balloon-expandable coronary stents in 40 patients
with MCA stenosis. They reported a procedural-
related complication rate of 10%, including a vessel
occlusion in one patient and subarachnoid hemor-
rhage in three. The periprocedural mortality rate
was 2.5% (50).
The Stenting of Symptomatic atherosclerotic
Lesions in the Vertebral or Intracranial Arteries
(SSYLVIA) trial was a multicenter, nonrandomized,
prospective feasibility study that evaluated a new,
flexible, stainless steel stent (Neurolink, Guidant
Corporation, Indianapolis, Indiana, U.S.) designed
for the treatment of extracranial vertebral or intra-
cranial cerebral artery stenosis (51). The study
included 61 patients with symptoms attributed to a
single lesion with greater than 50% stenosis. Of these
61 patients, 43 (70.5%) had an intracranial stenosis and
18 (29.5%) had an extracranial vertebral artery steno-
sis. The 30-day stroke and mortality rates were 6.6%
and 0%, respectively. Successful stent deployment
was achieved in 58 of 61 patients (95%). At six months,
32.4% of intracranial vessels and 42.9% of extracranial
vertebral arteries that were treated by stenting dem-
onstrated a recurrent stenosis. Seven (39%) patients
presenting with restenosis were symptomatic. Four of
55 patients (7.3%) suffered a stroke between 30 days
and 1 year. Sixty-one percent of the patients treated
remained asymptomatic during the follow-up. Predic-
tors identified for a postoperative restenosis were
vertebral ostial lesion, diabetes mellitus, residual
stenosis of more than 30% after stent placement, and
the diameter of the treated artery. On the basis of
study results, the U.S. FDA granted the stent a human-
itarian device exemption (HDE) for the treatment of
high-risk patients with significant intracranial and
extracranial atherosclerotic diseases who have failed
medical therapy.
Morphology and hemodynamics of intracranial
arteries are substantially different from peripheral and
coronary arteries. These vessels lack robust adventitia.
External elastic lamina and vasa vasorum are nearly
absent, the media are thin, and there are multiple
perforators originating from the diseased vessel seg-
ment supplying healthy brain tissue. In addition, the
cerebrospinal fluid rather than a supportive soft tissue
is the microenvironment for the pial vessels (52,53).
This environment limits the transmural pressure used
for the PTA balloon and the balloon diameter, which
may possibly be contributing to greater recoil (54,55).
On the other hand, the flow and flow velocity as well
as the pulse index in cerebral arteries are higher than
the values found in the coronary system. In the past,
the endovascular treatment of atherosclerotic disease
has focused on angioplasty and placement of balloon-
expandable stents. The advantage of a PTA balloon is
its flexibility, while the major advantage of balloon-
expandable stents is their high radial force. The
 Chapter 18: Stenting and Angioplasty for Intracranial Atherosclerotic Occlusive Disease 329

disadvantage of a PTA balloon is the risk of postpro-

cedural elastic recoil of the vessel and dissection. The
major drawbacks of a balloon-expandable stent are its
limited flexibility and the risk of injury and dissection
due to high expansile force used for deployment.
Thus, it was imperative to develop easy trackable
neurovascular stents specifically designed for intra-
cranial use with adequate radial force to avoid recoil
and provide improved restoration of vessel diameter,
while reducing the incidence of complications (Fig. 3).
Recently, a new concept was reported for cere-
bral artery revascularization by using balloon dilata-
tion, followed by the deployment of a self-expanding
nitinol microstent, the WingSpan system (Smart
Therapeutics, Boston Scientific, Freemont, California, Figure 3 Low-profile, highly flexible, self-expanding nitinol
U.S.) (56,57). The results of the WingSpan Multicenter (nickel-titanium alloy) cerebrovascular stents, which are deployed
European Study were recently presented. In through a microcatheter. Arrows indicate radiopaque markers at
45 patients, enrolled from 12 European sites, with the end of the stent. (A) Closed cell design (Enterprise, Cordis
symptomatic intracranial atherosclerosis of greater Neurovascular J&J, Miami Lakes, Florida, U.S.). (B) Open cell
than 50%, revascularization using the WingSpan design (Neuroform, BSC, Natick, Massachusetts, U.S.).
stent was performed (Fig. 4). Of these patients, 95%
had prior strokes and 29% had TIAs. Technical success
with angioplasty and stenting was achieved in 98% of
patients (57). The periprocedural 30-day death or ipsi- U.S. FDA granted an HDE approval for the WingSpan
lateral stroke rate was 4.5% (2/44), and the 6-month stent system in 2005 for treatment of symptomatic
death or ipsilateral stroke rate was 7.1% (3/42), with an intracranial stenosis of greater than 50% and refractory
all-cause stroke rate of 9.5% (4/42). Interestingly, to maximal medical therapy. Approval for this stent
implantation of the self-expanding stent showed a system was also obtained in Europe. Randomized trials
further lumen gain in some patients after initial under- for symptomatic intracranial atherosclerotic disease
dilatation, with a mean residual stenosis of 28% at the comparing the best medical treatment and stenting/
six-month follow-up. On the basis of these data, the angioplasty are being designed.

Figure 4 Symptomatic 61-year-old female with arterial hypertension and an MCA atherosclerotic occlusive disease that was treated with
a Wingspan stent system and the Gateway PTA balloon. (A) Illustration of the highly flexible and trackable Wingspan self-expanding stent
system with Gateway PTA balloon catheter that were developed for the intracranial circulation. (B) Baseline angiogram of the right ICA
shows a concentric atherosclerotic lesion of the M1 segment (arrow) with poststenotic dilatation (arrowhead ) and involvement of the
MCA bifurcation (double arrow), the origin of the ACA and the ICA. (C) Postangioplasty angiogram shows no major change in lesion
characteristics. The microwire is left in place for placement of the stent. (D) Poststenting angiogram shows smooth vessel boundaries and
lumen increase. (E) Six-month follow-up angiogram shows smooth vessel boundaries, slight narrowing at the central part of the stented
segment, and remodeling of the dilated M1 section. Abbreviations: MCA, middle cerebral artery; PTA, percutaneous transluminal
angioplasty; ICA, internal carotid artery; ACA, anterior cerebral artery. Source: Fig. 4A, courtesy of BSC, Natick, Massachusetts, U.S.
330 Akkawi and Wakhloo
RESTENOSIS AFTER STENTING
Stents may induce myointimal hyperplasia and reste-
nosis (Fig. 5). The restenosis rate after stenting of ICD
is approximately 10% to 13%. However, recently pre-
sented data from several centers showed that at 6- and
12-month follow-up angiography study, WingSpan
self-expanding stents may have an incidence of up
to 40% in-stent stenosis. To address these issues, stents
coated with antiproliferative agents have been devel-
oped to reduce the in-stent stenosis and are being
considered for the neurovascular system (58).
Sirolimus (rapamycin), an antifungal agent, and pacli-
taxel, a microtubule inhibitor, have shown to prevent
neointimal proliferation and restenosis in the coronary
vessels when compared with bare metal stents (59).
These clinical results provided the impetus to study
Figure 5 A 57-year-old man with vertebrobasilar insufficiency
associated with a high-grade left vertebral artery stenosis.
(A) Left vertebral artery angiogram shows an ulcerated athero-
sclerotic stenotic lesion distal to the origin of the PICA (arrow).
(B) Postprimary stenting angiogram shows a recanalization with
smooth vessel boundaries. A remnant narrowing of the diseased
arterial segment is noted (arrow) as well as some decreased flow
within the jailed PICA. (C) Six-month follow-up angiogram shows
nonsymptomatic but significant stenosis of the entire stented
arterial segment most probably because of intimal hyperplasia
(arrow). Note the improved filling of the PICA. (D) Successful
angioplasty of the in-stent stenosis (arrow). (E) Left MCA cross
section from another patient previously stented for a symptomatic
intracranial atherosclerotic disease (arrow), who died of a right
intracranial hemorrhage, shows in-stent neointimal hyperplasia
(arrowhead) with approximately 65% estimated stenosis. Abbre-
viations: PICA, posterior inferior cerebellar artery; MCA, middle
cerebral artery. Source: Fig. 5E, Movats pentachrome stain,
courtesy of Dr. D. Lopes.
the effect of antiproliferative agents for the intracranial
system. Levy et al. studied the effects of heparin-
coated and sirolimus-eluting stents, which were
implanted in canine basilar arteries (60,61). The
mean percentage of stenosis 12 weeks after implanta-
tion was less (12%) in the group with heparin-coated
stents compared with 22% in the group with uncoated
devices. Compared with bare-metal stents, the
sirolimus-coated devices did not impair endotheliali-
zation and, furthermore, tended to reduce the prolif-
eration of smooth muscle cells. However, currently no
single appropriate animal model exists for the study of
intracranial atherosclerotic disease and of the effects of
drug-eluting devices.
STENTING PROCEDURE
Patients are selected for intracranial angioplasty or
stenting by using the inclusion criteria listed in
Table 1. Patients are excluded from the revasculariza-
tion if they meet any of the exclusion criteria listed in
Table 2. An experienced physician neurologically eval-
uates patients prior to the procedure. After selection of
the patient for the endovascular treatment, imaging
studies should include brain MRI, MR angiograms, CT
study, and CT angiograms to assess any preexisting
ischemic condition, to rule out a hemorrhage, and to
obtain information on cerebrovascular anatomy. Cath-
eter angiography before placement of the stent or bal-
loon angioplasty confirms the degree of vascular
stenosis. The percentage of stenosis is calculated as
the ratio of the smallest diameter to the diameter of the
vessel distal to lesion. In cases of a poststenotic col-
lapse, the diameter of the vessel proximal to the
stenosis is used. The dimensions of the normal artery
adjacent to the lesion, the length of artery, and the
smallest diameter of the stenosis are measured to
choose the appropriate balloon or stent size.
Table 1 Inclusion Criteria for Intracranial Stenting
>50% stenosis of a major intracranial vessel and refractory to
medical treatment
Minimum vessel diameter of 2.0 mm
Previous stroke
TIA
Neurological symptoms referable to the target lesion
Presence of symptoms during the 6 mo prior to treatment
Acute vessel occlusion or dissection after PTA
Abbreviations: TIA, transient ischemic attack; PTA, percutaneous
transluminal angioplasty.
Table 2 Exclusion Criteria for Intracranial Stenting
Severe neurological deficit from stroke
Chronic total occlusion
History of intracranial hemorrhage, hemorrhagic
stroke, major stroke, or any stroke with mass effect within 6 wk
of procedure
Contraindication for or resistant to antiplatelet therapy
 Chapter 18: Stenting and Angioplasty for Intracranial Atherosclerotic Occlusive Disease 331

Patients receive aspirin 325 mg/day orally and
Plavix 75 mg/day orally, starting three days prior to
the procedure. Aggrenox can be used in patients who
are allergic to Plavix. After the procedure, patients are
maintained on Plavix 75 mg/day for a minimum of six
weeks and aspirin 81 mg/day lifelong.
After explaining the procedure and possible
complications, an informed consent is obtained from
all patients. Most of the procedures can be performed
with conscious sedation and analgesia that helps to
monitor the neurological status continuously. One of
the femoral arteries is accessed with a 5-French (Fr) or
a 6-Fr sheath, and rarely a 7-Fr sheath if a larger guide
catheter is necessary. A 5-Fr or a 6-Fr (rarely a 7-Fr)
guide catheter is then placed in the distal cervical ICA
or the cervical vertebral artery. The stents are placed
over a guidewire (0.014 inch) passed through the
guiding catheter across the lesion (Fig. 6). In cases
where a primary stenting cannot be performed, an
angioplasty is carried out using a low-profile flexible
PTA balloon over a 0.014-inch exchange-length guide-
wire. PTA balloon is inflated slowly over several
minutes, and most of the lesions yield at 6- to 8-atm
pressure. In a number of patients with extremely
tortuous vascular anatomy, a microcatheter is
advanced over a more flexible guidewire to cross the
lesion, and then the wire can be exchanged for a stiffer
one to navigate the stent delivery system after
removal of the microcatheter. Stent insertion is per-
formed under biplane fluoroscopy and road-mapping
technique. Proper stent placement is confirmed by
high-resolution fluoroscopy or a plain radiogram.
Special attention should be paid to avoid overdilata-
tion of the stented arterial segment. Another potential
complication during placement of a stent and angio-
plasty is a snow plow effect on atherosclerotic
plaques. Plaque may be dislodged in side branches,
leading to instant occlusion (Fig. 7). To protect major
side branches, placement of protective guidewires or
the kissing balloon technique has been suggested.

Figure 6 A 76-year-old male with diplopia, dysarthria, and nausea who was refractory to heparin, Coumadin, Plavix, and aspirin. After
stenting, the patient has been asymptomatic for four years. (A) Right vertebral artery angiograms in frontal and (B) lateral views show an
atherosclerotic stenotic lesion of the right distal vertebral artery (arrowhead ) with extension into the proximal basilar trunk (arrow).
(C) Because of proximal tortuosity of the vertebral artery, the primary placement of a coronary stent over a 0.014-inch exchange wire
(arrow) was carried out through a left vertebral artery approach. The PTA balloon is being slowly inflated to a maximal pressure of 6 atm.
(D) Fully deployed stent (arrow). The exchange wire is kept in place for distal access if needed. (E) Control angiograms in frontal and (F)
lateral views show excellent revascularization without obliteration of the right distal vertebral artery. (G) A 14-month follow-up angiograms
in frontal and (H) lateral views show mild in-stent neointimal hyperplasia. Some progression of the distal plaque is noted (arrow). (I) Right
vertebral artery angiogram shows significant progression of distal vertebral artery atherosclerotic disease (double arrow) but still patent
vertebrobasilar junction. Abbreviation: PTA, percutaneous transluminal angioplasty.
332 Akkawi and Wakhloo

Figure 7 A 67-year-old man presenting with recurrent episodes of hypesthesia, dysarthria, and diplopia while being on Coumadin. The
patient has been asymptomatic for five years following stent placement. (A) Left vertebral artery angiograms in frontal and (B) lateral
views show a high-grade atherosclerotic stenosis with involvement of the PICA origin (arrow). (C) Primary stenting using coronary
balloon-expandable system (arrow). (D) Control angiography during partially inflated stent-balloon system (double arrows) shows
snowplowing of the plaque into the PICA origin. Further dilatation was terminated. (E) Control angiograms show patent flow within the
PICA, the plaque (arrowhead ) (F), and some residual narrowing of the stented arterial segment. (G) Six-month follow-up studies in frontal
and (H) lateral views show some mild restenosis and narrowing of the PICA origin (arrows). (I) Twenty-month follow-up studies in frontal
and (J) lateral views show no further progression of the stented atherosclerotic lesion (arrow) and remodeling of the PICA origin with
excellent distal flow (arrowhead ). Abbreviation: PICA, posterior inferior cerebellar artery.

CONCLUSION
Endovascular treatment of symptomatic intracranial
atherosclerotic disease has rapidly evolved and has
adopted technology and experience from the periph-
eral and coronary systems. Angioplasty and stenting
appear to be both safe and highly effective. Patient
selection, periprocedural medications, use of appro-
priate endovascular tools, and proper training are
vital for positive clinical results. Advances in bioma-
terials engineering such as polymer technology,
microfabricated stents, and delivery systems will in
future allow a safe navigation of the stent through the
intracranial arterial circulation. The natural history of
intracranial stenosis will have to be better understood
to determine acceptable rates of risks for revasculari-
zation. Advances in technology and endovascular
tools will ensure a low periprocedural morbidity
and mortality. New generations of drug-eluting intra-
cranial stents will further improve the long-term out-
come currently hampered by a high rate of in-stent
stenosis. Nevertheless, prevention, which includes a
healthy diet, cessation of smoking, and control of
blood pressure, statins, antiplatelet, and nonsteroidal
anti-inflammatory drugs, will remain the long-term
goal of combating ICD.
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 19

Endovascular Management of Dural Arteriovenous Fistulas

J. Marc C. van Dijk

Department of Neurosurgery, University Medical Center, Groningen,
Groningen, The Netherlands
Robert A. Willinsky
Department of Medical Imaging, Toronto Western Hospital, Toronto, Ontario, Canada

INTRODUCTION development of DAVFs has been described following

Excluding traumatic lesions and carotid-cavernous
fistulas, three basic categories of dural arteriovenous
(AV) shunts can be discriminated: the pediatric dural
sinus malformation with AV shunting, the infantile
high-flow dural arteriovenous fistula (DAVF), and the
adult-type DAVF. Since the dural lesions in the pedi-
atric age group are beyond the scope of this chapter,
the focus will be on the adult-type DAVF.
The adult-type DAVF is a rare neurovascular
lesion. A recent population-based study mentions a
crude detection rate of 0.16 per 100,000 adults per
year, and from angiographic studies it has been esti-
mated that dural lesions represent just 10% to 15% of
all intracranial AV shunts (1,2). Nevertheless, as a
unique neuropathological entity, the subject DAVF
deserves full attention.
A DAVF consists of one or more true fistulas,
i.e., direct AV connections without an intermediate
capillary network or even a nidus. The fistula itself is
confined to the leaflets of the dura mater, which
unquestionably differentiates a DAVF from an arterio-
venous malformation (AVM) that has a (sub)pial
localization within the brain or spinal cord. In addi-
tion, considering the general acknowledgment that a
DAVF is acquired (36), in contrast to the congenital
nature of a vascular malformation (7), the term
dural arteriovenous fistula is clearly preferable to hypothesis arose from the positive staining of excised
dural arteriovenous malformation. dural fistulas for venous thrombosis (11) and angio-
The anatomical setting of the fistula within the
dura mater explains the fact that both cranial and
spinal DAVFs are recognized. Although their underly-
ing pathophysiology is the same, their clinical presen-
tation and behavior (and therefore their classification)
are quite distinct. Consequently, cranial and spinal
DAVFs are discussed in separate sections of this
chapter.
PATHOPHYSIOLOGY
The cause of DAVFs is still a matter of debate, although
many causes have been posited in the literature. The
surgery (even in remote parts of the body) or head
trauma and in relation to sinus thrombosis, without
revealing a definite etiological pathway.
Over the decades, two main hypotheses of
pathogenesis have been advanced. The first postulates
that DAVFs normally exist within the dura mater as
dormant channels between the meningeal arterial
circulation and the venous system. Histological and
radiological studies have demonstrated that these
communications are indeed present in the dura of
normal individuals (8). According to this theory, the
channels open because of the venous hypertension
associated with sinus thrombosis or sinus outflow
obstruction (9). Similarly, the existence of thin-walled
venous pouches close to small meningeal arteries has
been reported. Rupture of these fragile pouches might
be responsible for direct AV communications within
the dura (10). The second hypothesis claims that the
development of DAVFs is a direct consequence of
neovascularization processes within the dura mater,
attributable to the release of angiogenetic factors.
These factors, e.g., vascular endothelial growth factor
and basic fibroblast growth factor, can be either
directly produced by the organization of a venous
sinus thrombosis or indirectly induced by the
increased intraluminal venous pressure through a tis-
sue hypoxia pathway. Major support for the second
genetic factors (12), as well as by the demonstration
that the development of DAVFs in a rat model can be
reproduced using a combination of venous sinus
thrombosis and venous hypertension (3,6).
Histopathological studies prove that DAVFs are
located within the meningeal wall of a venous sinus,
although originally they had been described to reside
within the thrombosed lumen of a dural sinus.
The location within the wall clarifies the existence of
the type of DAVF that drains directly into the cortical
venous network, without venous drainage into the
involved sinus (13). On close examination, the fistula
consists of small venules with a diameter of
336 van Dijk and Willinsky
approximately 30 mm. These vessels have been named
crack-like vessels, since they resemble cracks in the
wall of the dural sinus after histological staining.
Further immunohistochemical assessment of the
crack-like vessels revealed a layer of endothelial and
smooth muscle cells and no internal elastic lamina,
thus confirming their venous origin (14).
In spinal DAVFs, a small series of high-resolution
microangiography after en bloc resection of the fistula
has been reported. The ex vivo surgical removal
included the involved dural root sleeve, proximal
nerve root, and adjacent spinal dura. The subsequent
detailed imaging showed that in all of the lesions,
the artery split into daughter vessels that coalesced
one to three times to form a network of arterial loops
in the dura that invariably emptied into a medullary
vein without an intervening capillary plexus. Several
collateral vessels arising from adjacent intercostal or
lumbar arteries were commonly present in the dura
and converged at the site of the fistulous point to join a
single medullary vein, providing an anatomical expla-
nation for the presence of a multiple segment arterial
supply (15).
CRANIAL DURAL AV FISTULAS
Early descriptions of cranial DAVFs date from the first
decades of the 20th century, typically in the form of
single case reports, such as by Tonnis in 1936 (16). The
first presentation of the concept of dural fistulas
originates from a publication by Fincher in 1951 (17).
Despite the development of cerebral angiography in
the late 1920s (18), it took nearly 40 years before the
DAVF emerged as a distinct entity because of the
advances in angiography, such as magnification, sub-
traction techniques, and selective arterial catheteriza-
tion. In those days, all DAVFs were regarded as
benign in comparison with the pial AVMs (19).
In the early 1970s, pioneers like Aminoff,
Newton, and Djindjian expanded the anatomical and
clinical understanding of the dural fistulas. In 1972,
the perception grew that the pattern of venous drain-
age was related to the clinical signs and symptoms;
nevertheless, not until 1975 were the particular risks
associated with cortical venous reflux (CVR) recog-
nized (20,21). Djindjian and Merland proposed the
first classification based on this concept, emphasizing
that DAVFs with a free outflow into a sinus are
relatively harmless and that the presence of CVR is
related to severe complications (22).
Dominated by the publication of three large
reviews in the literature, the 1980s were an important
decade for the cranial DAVFs. In 1984, on the basis of
a series of 223 cases, Malik concluded that venous
outflow was a key factor in the occurrence of hemor-
rhage or neurological symptoms and stressed the
importance of location of the fistula within or outside
a major venous sinus (23). Lasjaunias performed a
meta-analysis on 195 cases, concluding that focal neu-
rological deficits were dependent on the territory of
draining veins and that CVR was related to a high risk
of intradural bleeding (24). Studying 377 cases, Awad
did the third major review. In this report, the term
aggressive was introduced for DAVFs presenting
with a hemorrhage or a focal neurological deficit.
Awad not only emphasized the importance of CVR
but also pointed out venous ectasias and galenic
drainage as additional risk factors (25).
During the 1990s and the beginning of the 21st
century, the accumulation of information was further
consolidated in the classification schemes by Cognard
and Borden. The formation of multidisciplinary neuro-
vascular study groups has elaborated the understand-
ing of the cranial DAVF and underscored the technical
and clinical significance of the CVR. By reporting large
series, many authors have confirmed the clinical behav-
ior first delineated in the 1980s. In addition, the ongo-
ing development of endovascular techniques has
proven invaluable in the treatment of these lesions.
Cranial Classification
A number of classification schemes have been pro-
posed on the basis of different aspects of DAVFs. At
first, the anatomical location of the fistula was
considered the key discriminating feature. In 1973,
Aminoff recommended the arrangement in an ante-
roinferior group and a posterosuperior group (26).
Subsequently, other large studies pointed out an asso-
ciation between location and clinical presentation of a
DAVF by noticing that cavernous sinus and transverse
sinus lesions behave differently than tentorial or ante-
rior fossa fistulas. Over the years, however, it became
evident that not location but location-related venous
drainage pattern was crucial in determining the clin-
ical presentation. Cranial DAVFs in some locations
have a higher likelihood of developing CVR because
of the local venous anatomy, e.g., the absence of a
venous sinus in the direct vicinity. Although no loca-
tion of a cranial DAVF is immune from aggressive
behavior, it was recognized that certain regions raise
the index of suspicion for the development of CVR.
Following Djindjians original format based on
the venous drainage pattern, numerous classification
schemes for cranial DAVFs have been put forward, of
which the Borden and Cognard classifications are most
frequently applied (Table 1) (27,28). Both are used in
everyday practice and have their own advantages: the
three-step Borden classification is very simple to apply
and requires only little knowledge of cerebral angiog-
raphy; the Cognard classification is certainly theoreti-
cally superior, since it incorporates the additional effect
of the flow direction in the dural sinus, but its multiple
steps require a more advanced comprehension of
DAVFs. The importance of judging the flow direction
in the sinus is evident: retrograde flow can prohibit the
cortical veins to drain into the involved sinus and can
subsequently lead to venous congestion of the brain,
without the occurrence of CVR. Both classifications
have been validated (29).
Cranial Clinical Features
The expressions benign and aggressive have been
put forward in the literature and used in this chapter in
relation to the typical clinical signs and symptoms of
 Chapter 19: Endovascular Management of Dural Arteriovenous Fistulas
Table 1 Classification Schemes for DAVFs
Borden classification
1 Venous drainage directly into dural venous sinus or
meningeal vein
2 Venous drainage into dural venous sinus with CVR
3 Venous drainage directly into subarachnoid veins
(CVR only)
Cognard classification
I Venous drainage into dural venous sinus with
antegrade flow
IIa Venous drainage into dural venous sinus with
retrograde flow
IIb Venous drainage into dural venous sinus with
antegrade flow and CVR
IIa b Venous drainage into dural venous sinus with
retrograde flow and CVR
III Venous drainage directly into subarachnoid veins
(CVR only)
IV Type III with venous ectasias of the draining
subarachnoid veins
V Venous drainage into the perimedullary plexus
Abbreviation: CVR, cortical venous reflux.
Table 2 Benign and Aggressive Clinical Features of DAVFs
Benign features Aggressive features
Pulsatile bruit Intracranial hemorrhage
Orbital congestion Nonhemorrhagic focal neurological
deficit
Cranial nerve palsy Dementia
Chronic headache Papilledema
Asymptomatic Death
cranial DAVFs. Features such as nonhemorrhagic
neurological deficits (NHND), hemorrhage, and death
are regarded aggressive, whereas complaints of chronic
headache, pulsatile bruit, and orbital symptoms,
including cranial nerve deficits, e.g., due to cavernous
sinus fistulas, are considered benign, even though these
signs and symptoms might be deemed intolerable by
the patient (Table 2).
Benign DAVFs
There is a proven relationship between the so-called
benign symptoms and the absence of CVR in the
venous drainage pattern. Borden type 1 and Cognard
type I and IIa DAVFs are thus regarded as benign
fistulas. Large series have acknowledged that the
benign DAVFs never present with grave pathology
(25,30,31). Most frequently, benign fistulas include
those involving the cavernous sinus or the transverse-
sigmoid sinus. Although DAVFs can occur at any age,
typically the patient is over 50 years old and complains
about a disturbing pulse-synchronous tinnitus. The
bruit can be very loud and audible by the physician,
indicative of a high turbulent flow through a venous
sinus in direct contact with the petrous bone. Another
characteristic complaint is the red eye, indicative of
a DAVF involving the cavernous sinus with subse-
quent proptosis, conjunctival injection, and chemosis
of one or both eyes. The orbital symptoms may be
337
progressive, and the congestion can lead to raised
intraocular pressure that may end in decrease of visual
acuity. However, (transient) cranial nerve dysfunction
may as well worsen the visual function or diplopia,
leading to ophthalmoplegia or orbital edema with
extraocular muscle swelling. Hence, in cavernous
sinus DAVFs, close interaction with the ophthalmolo-
gist is essential to decide when clinical symptoms are
no longer to be considered benign and palliative endo-
vascular treatment is necessary.
Even more important than the clinical presenta-
tion is the subsequent natural course of benign DAVFs.
In a retrospective evaluation of 205 cases, Cognard
reported the probable benign course of 111 fistulas
without CVR (28), but significant follow-up could
only be obtained in 66% of the cases, and it is difficult
to draw conclusions on clinical stability from this
study, since clinical events that occur before and after
presentation are not well differentiated. Two years
later, the authors mentioned seven patients in their
experience who initially had a DAVF without CVR but
showed a worsening in the venous drainage pattern
during a mean seven-year follow-up. Five patients
were embolized with particles, one patient had proxi-
mal ligation of the occipital and middle meningeal
artery, and one had conservative management. In all
cases, the change in venous pattern was accompanied
by a worsening of the clinical symptoms (32).
Davies reported the first large prospectively col-
lected series of patients with a benign DAVF concern-
ing a cohort of 55 cases without CVR over a mean
follow-up period of 33 months. These cases made
clear that the vast majority of DAVFs without CVR
behave in a benign fashion, with stability over time.
One patient, nevertheless, died after palliative endo-
vascular treatment, without angiographic conversion
into a lesion with CVR. This unusual course of a
predicted benign disease was explained as the result
of venous hypertension due to functional obstruction
of the superior sagittal sinus (31).
In 2002, Satomi further confirmed the benign
disease course of DAVFs without CVR in a prospective
study of 117 cases. Observation resulted in a tolerable,
stable disease in 67 of 68 patients. One patient had a
seizure during follow-up because of a hemorrhage after
the development of CVR. Treatment was performed in
44 patients, aimed at the palliation of unbearable
symptoms or in reversing ophthalmological phenom-
ena. In 15 patients, multiple treatment sessions (up to 4)
were required to obtain a satisfactory result. Treatment
resulted in a tolerable disease in all but one patient.
Both in the observational and in the palliatively treated
group, approximately 66% of the patients were cured
after mean 28 months, demonstrating that a benign
DAVF in essence is a self-limiting disease. The remain-
ing one-third of patients had symptoms that were well
tolerated. In conclusion, the restricted management
resulted in a stable and tolerable disease course in
more than 98% of the cases (33).
One should, however, bear in mind that benign
DAVF is a dynamic disease and progression of the
venous thrombosis may very well result in rerouting
of the venous drainage. From this point of view, two
338 van Dijk and Willinsky

Figure 1 Venous congestive encephalopathy secondary to a DAVF. A 58-year-old male presented with ataxia. The axial T2-weighted
MR (A) shows a central hyperintensity within the right cerebellar hemisphere surrounded by diffuse hypointensity. Note the prominent
flow voids (arrows). The gadolinium-enhanced MR (B) shows diffuse peripheral enhancement. A selective arteriogram (C) of a dural
artery (arrows) arising from the right vertebral artery shows a DAVF inferior to the straight sinus with marked reflux into the cortical veins
of the right cerebellar hemisphere. Abbreviation: DAVF, dural arteriovenous fistula.

cautionary points have to be made: the possible sig-

nificance of retrograde flow in the sinus, and the small
but noteworthy risk of conversion into an aggressive
DAVF. First, the importance of retrograde flow in the
sinus without CVR is stressed in the Cognard classi-
fication. Type IIa was, according to the describing
author, related to papilledema and raised intracranial
pressure in 8 of 27 patients (30%). In the series by
Davies and Satomi, however, this phenomenon was
seen in a much smaller percentage. Theoretically, ret-
rograde flow can indeed prohibit the cortical veins
from draining into the involved sinus and lead to
venous congestion of the brain. Among other authors,
Hurst has related this venous congestion of the brain
to global neurological deficits, such as dementia (34).
The congestion has been shown to project as T2
hyperintensity on MRI (Figs. 1 and 2) (35). Willinsky
additionally pointed out the presence of tortuous,
engorged veins on the cerebral angiography in cases
of venous congestion and labeled this the pseudophle-
bitic pattern (36). The other point of concern in benign
DAVFs is the chance of secondary development of
CVR. In the series by Davies and Satomi, this phe-
nomena occurred in approximately 2% of the cases.
This finding mandates close clinical follow-up and
renewed radiological evaluation with any sudden or
unexpected change in symptoms. Figure 2 Resolution of T2 hyperintensity after treatment. A
58-year-old female presented with a progressive quadriplegia.
Aggressive DAVFs Axial T2-weighted MR (A) shows diffuse central hyperintensity
within the medulla (arrow). AP view of the right vertebral arterio-
Cranial DAVFs with CVR on angiography are associ- gram (B) shows a DAVF at the foramen magnum with drainage
ated with grave pathology. In the classification schemes, into a large perimedullary vein (arrow). Selective arteriogram
Borden type 2/3 and Cognard type IIb/IIa+b/III/IV/V (C) of the dural branch feeding the fistula better defines the
DAVFs are therefore labeled aggressive. Initially, the fistula. Embolization was not done because it proved impossible
term aggressive was based on the frequent clinical to obtain a safe position to inject liquid adhesives. Surgical
presentation with intracranial hemorrhage, NHND, or disconnection was done with a single clip to close the intradural
even death. Nevertheless, presentation with pulsatile draining vein. The patients clinical condition gradually improved
tinnitus or orbital congestions, mimicking a benign and at six months the T2 hyperintensity on the MR had resolved
DAVF, is also possible (25,28). The hemorrhage may (D). Abbreviation: DAVF, dural arteriovenous fistula.
be subdural, subarachnoid, or intracerebral, since the
 Chapter 19: Endovascular Management of Dural Arteriovenous Fistulas
refluxing cortical veins traverse each of these different
compartments. As stated before, location of the DAVF is
not correlated with hemorrhage; however, because of
local venous anatomy, some locations are more prone
to present with a hemorrhage, e.g., anterior cranial fossa
DAVFs. The NHND is typically focal and directly
related to regional venous congestion (24), although
more global neurological deficits are also encountered
analogous to the Cognard type IIa fistulas with retro-
grade flow in the sinus (see above). Cranial DAVFs can
also be responsible for spinal neurological disorders
in case of perimedullary CVR from a Cognard type V
lesion (37,38).
The natural course of aggressive DAVFs has
been under debate for a long time. In the literature,
contradictory reports have been published, with post-
presentation annual hemorrhage rates varying from
1.8% in a series by Brown (39) to almost 20% in a series
by Davies (40). Brown followed patients for a mean of
6.6 years but did not select for the presence of CVR, so
it is very likely that he underestimated the annual risk
because of a large proportion of benign DAVFs in the
cohort. On the other hand, Duffau in another series
found a rebleeding percentage up to 35% within two
weeks after the presenting hemorrhage in case of
Cognard type III/IV fistulas (41). Davies calculated
an annual mortality of 19.3%, with a 19.2% annual rate
of hemorrhage and a 10.9% annual rate of NHND
during the disease course of DAVFs with persistent
CVR. Van Dijk, in his study, recalculated these rates
on the basis of a larger population and four times the
follow-up time. During a combined follow-up time of
86.9 patient-years, an annual mortality rate of 10.4%
was yielded, with an annual hemorrhage rate of 8.1%
and an annual NHND rate of 6.9% (42). These data
mandate prompt and curative management of the
aggressive DAVFs.
Cranial Diagnostic Imaging
CT
In the absence of CVR with congestion of the brain,
benign DAVFs are nearly always occult on CT imaging.
339
In case of an aggressive DAVF, unenhanced CT may
show hypodensities, representing areas of edema or
venous ischemia. Abnormally enlarged pial veins can
sometimes be visualized as increased densities in com-
parison to the brain parenchyma. Contrast-enhanced CT
shows enhancement of the refluxing cortical venous
network. A promising technique is the development of
3D CT angiography, especially in emergencies. The
disadvantage of 3D CT angiography is its poor charac-
terization of hemodynamic details.
MRI/MRA
On MRI, it is difficult to detect a benign DAVF, although
irregular or stenotic venous sinus might raise suspicion.
MRA is more sensitive, but still has limitations in
depicting the fistula. Aggressive DAVFs are better
visualized by MRI, characterized by flow voids on the
cortex corresponding to dilated pial vessels. The brain
parenchyma can show T2 hyperintensity in the white
matter secondary to the venous congestion of the brain,
especially in the deep white matter (43). The differential
diagnosis for T2 hyperintensity includes sinus throm-
bosis (with venous infarction or venous congestion),
demyelinization, and neoplasm. However, T2 hyper-
intensity in the parenchyma in combination with a
surplus of pial vessels is highly suggestive of a vascular
malformation (Fig. 1). This T2 hyperintensity resolves
after treatment (Fig. 2).
A new technique that in time will potentially
replace conventional angiography is the real-time
autotriggered elliptic centric-ordered 3D gadolinium-
enhanced MRA (ATECO-MRA) (44). ATECO-MRA is
effective in demonstrating DAVFs, especially those
with CVR (Fig. 3). The technique is also ideally suited
to follow up DAVFs. However, the protocol for follow-
ing untreated DAVFs needs to be validated.
Digital Subtraction Angiography
Conventional angiography is important to confirm the
diagnosis of a DAVF and to plan the treatment. Selec-
tive contrast injections into the divisions of the external
carotid artery will show rapid AV shunting through
Figure 3 Gadolinium-enhanced MRA detects
DAVF and its cortical venous drainage. A
58-year-old male presented with conjunctival
injection and chemosis in the right eye. The
collapsed axial image from the gadolinium-
enhanced MR angiogram (A) shows an early
draining cortical vein (short arrow) and drain-
age into the right superior ophthalmic vein (long
arrow). The lateral view from the right external
carotid arteriogram (B) confirms that there is a
cavernous sinus DAVF with CVR (arrow).
Abbreviations: DAVF, dural arteriovenous fis-
tula; CVR, cortical venous reflux.
340 van Dijk and Willinsky
the fistula into the cranial venous system. Contrast
injection selectively into the internal carotid or verte-
bral arteries may reveal a delayed cerebral circulation
time, compatible with venous congestive encephalop-
athy (36). In the venous phase of the angiogram, tor-
tuous dilated collateral veins may be evident over the
surface of the brain indicating long-standing venous
hypertension. This finding has been referred to as the
pseudophlebitic pattern and correlates with a greater
risk of future hemorrhage or NHND (35). Careful
analysis of the venous phase of the cerebral circulation
is critical in planning treatment. Beyond doubt, the
main goal in the imaging of cranial DAVFs is to detect
the existence of CVR. Global nonselective angiography
should be avoided as subtle CVR might be missed.
Another important objective is to look for venous sinus
outflow obstruction, which can result in extracranial
drainage through collateral routes, including the orbital
system. Venous stenosis or obstruction is a common
finding in patients with retrograde flow into the corti-
cal and cerebellar veins. Careful analysis of the venous
phase of the angiogram may reveal distinct pathways
that separately drain the fistula and the brain. This
compartmentalization of the involved dural sinus may
allow closure of the fistula and preservation of that
compartment of the fistula that drains the brain (45).
Finally, in diagnostic imaging the existence of multiple
DAVFs within one patient should be considered, since
it is reported with a frequency of 7% to 8% (46).
Cranial Therapeutic Considerations
Awareness of the natural history of a given disease is
essential to every clinician, because an active treat-
ment is supposed to ameliorate the outcome of the
disease. If treatment of a DAVF is indicated, the
endovascular approach is the first choice. Surgery is
used either in combination with the endovascular
techniques or when the endovascular technique fails.
Surgery can allow access for an endovascular
approach or be used to directly occlude the diseased
sinus or disconnect the CVR. The endovascular treat-
ment can be accomplished from a transarterial
approach, a transvenous route, or a combination of
both. The transvenous approach is now the preferred
treatment in most DAVFs because of its effectiveness
in obliterating the fistula or eliminating the CVR.
Management of Benign DAVFs
In benign cranial DAVFs, reports show that 98% of
patients have an excellent natural history, indicating
that, in general, observation with gadolinium-
enhanced MRA reevaluation is the best available
management. A three-year follow-up catheter DSA is
advised in patients with stable clinical signs and
symptoms. If there is any sudden or unexpected
change in the clinical status, either worsening or
improvement (even disappearance), repeat catheter
angiography is needed to exclude the development
of CVR or progressive thrombosis with retrograde
flow in the venous sinus (47).
In patients who either suffer an intolerable bruit
or have severe orbital symptoms, e.g., compromise of
vision, palliative arterial endovascular embolization
could be considered to reduce symptoms. Arterial
embolization often reduces the symptoms, but one
should realize that as a rule it is not effective in obtaining
a complete angiographic obliteration of the fistula. In
some cases, arterial embolization with liquid adhesives
can permanently close the fistula (Fig. 4). With arterial
particle embolization, an early improvement of
Figure 4 Embolization of a cavernous sinus DAVF
with liquid adhesives. A 64-year-old male presented
with chemosis, conjunctival injection, and raised intra-
ocular pressure in the right eye. Lateral right external
carotid arteriogram (A) shows a DAVF draining exclu-
sively into the superior ophthalmic vein (open arrow).
The fistula is into a small compartment in the anterior
aspect of the cavernous sinus (long arrow). A selective
injection (B) into a dural branch of the middle menin-
geal artery (small arrow) delineates the fistula site (long
arrow). The cast of the liquid adhesive (arrow in C)
shows that there is good penetration through the fistula.
The control right external carotid arteriogram (D) con-
firms that the fistula is closed. Abbreviation: DAVF,
dural arteriovenous fistula.
 Chapter 19: Endovascular Management of Dural Arteriovenous Fistulas 341

symptoms is expected, but symptoms typically recur
over time. In cases where palliative arterial treatment is
deemed to be insufficient, transvenous coil embolization
of the diseased venous sinus is very effective in resolv-
ing symptoms and frequently results in total angio-
graphic obliteration of the DAVF (Fig. 5). Sacrifice of
the venous sinus should only be done when it exclu-
sively drains the fistula and does not participate in the
venous drainage of the brain. Targeted embolization of a
compartment of the sinus may be effective in obliterat-
ing the fistula with preservation of that part of the
venous sinus that is not participating in the fistula
(Fig. 6) (48). If necessary, sacrifice of the sinus is per-
formed by a transvenous approach. Only in exceptional
cases, catheterization of the venous sinus can be reached
using a transarterial approach, e.g., in traumatic DAVFs
due to the large connection between the dural artery and
the adjacent vein (Fig. 7). In most spontaneous DAVFs,
the feeding arterial network is too small and tortuous to
allow catheterization of the sinus from the arterial
approach.
Management of Aggressive DAVFs with Direct CVR
Aggressive cranial DAVFs have the potential to cause
severe complications as a result of their natural course,
thus mandating aggressive treatment. Treatment pro-
cedures aimed at the selective disconnection of CVR
have been reported for DAVFs with direct CVR with-
out dural sinus drainage (Borden type 3/Cognard type
III and IV). Pathophysiologically, a DAVF is considered
a venous disease, and a permanent cure of a cranial
DAVF with direct CVR can thus be obtained by a
selective intradural division of the venous outlet of
the fistula, analogous to the well-known treatment of
a spinal DAVF. Primarily, this procedure has been
described as a neurosurgical technique; however,
with the advances in interventional neuroradiology,
the same result has been demonstrated with endovas-
cular means as well (4953). A transvenous approach is
the most likely endovascular technique to disconnect
the CVR (Fig. 8). The transvenous approach requires a
road-map technique from an arterial injection that
demonstrates the fistula. Only in a small percentage
of patients can transarterial embolization with liquid
adhesives obliterate the fistula.
This technique is performed with a wedged
catheter and a liquid adhesive that has a long poly-
merization time. The arterial catheter must be
wedged close to the fistula site to allow the slow
push of the liquid adhesive through the fistula into
the proximal venous outlet. Too proximal emboliza-
tion allows persistent arterial shunting and recruit-
ment of collateral flow; too distal embolization may
result in venous occlusion and venous infarction.
Particle embolization from the arterial approach
may transiently reduce the flow through the fistula
and should usually be used in high-flow, complex
DAVFs in combination with a curative transvenous
approach or with surgery.

Figure 5 Transvenous facial approach to bilateral cavernous DAVFs. A 52-year-old female presented with diplopia, bilateral chemosis,
and bilateral conjunctival injection. Lateral right (A) and left (B) external carotid arteriograms show bilateral cavernous sinus DAVFs
draining into both superior ophthalmic veins. Note the subtle CVR (arrow in A) on the right. Using a femoral venous approach, a left
transfacial route (C) was used to reach the contralateral cavernous sinus. On the AP view, note the selective catheter position in the
contralateral cavernous sinus (D). The right cavernous sinus venogram (E) during the coil embolization of the right cavernous sinus
shows the reflux into cortical veins (arrow in E). Coil embolization of both cavernous sinuses was done (F). The control AP external right
and left arteriograms (G) show that the DAVFs were closed. The patients orbital symptoms improved over time; however, her
ophthalmoplegia had not resolved at six months. Abbreviations: DAVF, dural arteriovenous fistula; CVR, cortical venous reflux.
342 van Dijk and Willinsky

Figure 6 Targeted transvenous embolization of a cavernous DAVF. A 54-year-old male presented with chemosis, conjunctival injection,
and proptosis in the left orbit. His raised intraocular pressure in the right eye could not be relieved with topical medication. Lateral left
internal (A) and external (B) carotid arteriograms showed shunting into the left cavernous sinus and drainage into the superior ophthalmic
vein and inferior petrosal sinus (arrow). Transvenous catheterization (C) was done via the inferior petrosal sinus. The site of the fistula
was identified to be in the anterior lateral compartment of the cavernous sinus. Four Hydrocoils (MicroVention, Aliso Viejo, California, U.S.)
were used to close the fistula site (arrow in D). Control left internal (E) and external (F) carotid arteriograms show closure of the fistula. The
patients signs and symptoms resolved completely within a few weeks. Abbreviation: DAVF, dural arteriovenous fistula.

Management of Aggressive DAVFs with Dural disease course (59). The endovascular disconnection
Sinus Drainage and CVR may be done either using a transarterial approach
with liquid adhesives (Fig. 9) or a transvenous
In case of combined dural sinus drainage and CVR approach with coils (Figs. 10 and 11). The transvenous
(Borden type 2, Cognard type IIb or IIa+b), the oblit- route is preferred because it is more likely to be
eration of the whole fistula including excision or successful compared with the injection of liquid adhe-
packing of the involved dural sinus has been advo- sives from the arterial feeders.
cated (5457). On the other hand, the drawback of
If the endovascular treatment fails to eliminate
permanent occlusion of an involved sinus may be
the CVR, then there are a number of surgical options.
impairment of the venous drainage of the normal
A burr hole can be placed over the diseased sinus,
brain, resulting in (hemorrhagic) venous infarction
followed by a direct puncture to allow packing of the
and or leading to chronic complications of venous
sinus with a microcatheter placed through a small
hypertension, e.g., dementia. In this perspective,
sheath. The burr hole can be localized using a road-
Mironov (58) reported the treatment of two Borden
map technique from an arterial injection. Packing of
type 2 cases, in which he endovascularly disconnected
the sinus must be done under fluoroscopic guidance
the CVR without changing the venous drainage of the
and control angiography can be done from the arterial
dural sinus. In this way, the fistula itself was not
side to determine when the fistula is closed or if the
obliterated, but instead converted into a benign
CVR has been eliminated. Alternatively, direct pack-
DAVF (without CVR). This conversion is clinically
ing of the sinus can be done after surgical exposure of
important, since Davies and Satomi in their series
the entire sinus. Surgical resection of a sinus is often
demonstrated that benign DAVFs follow a disease
associated with high morbidity and mortality, even in
course without any grave neurological events and
experienced hands (60). However, the surgical tech-
that in the majority, benign DAVF is a self-limiting
nique of selective disconnection of CVR, leaving the
disease (31,33). The converted benign DAVFs have
actual fistula in the wall of the dural sinus untouched,
been demonstrated to follow the same benign clinical
 Chapter 19: Endovascular Management of Dural Arteriovenous Fistulas 343

Figure 7 Transarterial approach to venous packing of a traumatic DAVF. A 22-year-old male complained of a pulsatile tinnitus after
trauma. The left lateral external carotid arteriogram (A) shows an osseous fistula draining toward the pterygoid plexus. The selective
middle meningeal arteriogram (B) shows a high-flow fistula within the sphenoid bone draining into an extracranial venous pouch (arrow).
Selective catheterization (C) of the venous pouch allowed deposition of coils into the pouch (arrow in D). Liquid adhesives were injected
into the pouch from the fistula site after the coils had significantly reduced the flow (arrow in D). A control left external carotid arteriogram
(E) shows that the fistula is closed. Abbreviation: DAVF, dural arteriovenous fistula.

Figure 8 Transvenous disconnection of a

Borden type 3. A 62-year-old male presented
with a brain stem hemorrhage (A). The left
lateral internal carotid arteriogram (B) shows
a DAVF fed by an inferior marginal tentorial
artery (single arrow) draining into a cortical
vein (double arrows). Note the venous pouch
that likely represented a pseudoaneurysm
at the site of the previous bleed. Using a
transvenous approach catheterization of
the venous pouch was feasible (C). Coils
were deposited within the cortical vein and
the venous pouch. A control internal carotid
arteriogram (D) showed that the fistula was
closed. A six-month control catheter angio-
gram confirmed the stability of the emboliza-
tion. Abbreviation: DAVF, dural arteriovenous
fistula.
344 van Dijk and Willinsky

Figure 9 Conversion of an aggressive Borden type 2 DAVF to a benign Borden type 1 DAVF by arterial embolization with liquid adhesives.
A 72-year-old male presented with pulsatile tinnitus and a bruit 12 months after a motor vehicle accident. The lateral left external carotid
arteriogram (A) shows shunting into an irregular transverse sinus and reflux into the vein of Labbe (arrow). Selective catheterization of the
posterior branch of the left middle meningeal artery allowed deposition of the liquid adhesive (NBCA) (arrow in B) at the site of the CVR.
Control occipital (C) and external carotid (D) arteriograms at the time of the embolization shows persistence of the shunting into the
transverse sinus with elimination of the CVR. A repeat catheter angiogram two years later showed no change from the immediate post
embolization study. Abbreviations: DAVF, dural arteriovenous fistula; NBCA, N-butyl cyanoacrylate; CVR, cortical venous reflux.

Figure 10 Conversion of an aggressive Borden type 2 DAVF to a benign Borden type 1 DAVF in the cavernous sinus by transvenous
embolization with coils. A 77-year-old female presented with bilateral conjunctival injection and chemosis. The left external carotid
arteriogram (A) shows a DAVF of the cavernous sinus draining into cortical veins (arrow) and the inferior petrosal sinus. Using a
transvenous approach through the ipsilateral inferior petrosal sinus (small arrows in B), we were able to catheterize the sphenoparietal
sinus (arrow). We packed the sphenoparietal sinus and the adjacent cavernous sinus with coils (C). A control left external arteriogram
(D) shows that the CVR was eliminated and there was less flow through the fistula. On the venous phase of the lateral internal carotid
arteriograms before (E) and after (F) treatment, we see that the cortical veins over the temporal lobe (arrows) could drain the brain after
the cortical venous disconnection. The patients symptoms resolved and she has been stable for five years. Abbreviations: DAVF, dural
arteriovenous fistula; CVR, cortical venous reflux.
 Chapter 19: Endovascular Management of Dural Arteriovenous Fistulas 345

Figure 11 Conversion of an aggressive Borden type 2 DAVF to a benign Borden type 1 DAVF by transvenous embolization of a parallel
channel. A 37-year-old female developed superior sagittal sinus thrombosis (arrow in A) one year after renal transplantation. Three years
later, the patient developed a bruit and her MR showed prominent, tortuous flow voids (arrows) over the surface of the brain (B). Multiple
intracranial DAVFs were found on a cerebral angiogram. The lateral left external arteriogram (C) shows a DAVF of the transverse sinus
with CVR (arrows) and occlusion of the ipsilateral sigmoid sinus. A transvenous approach via the contralateral transverse sinus allowed
selective catheterization of a parallel channel that connected to the cortical veins that participated in the reflux. Venography in this parallel
channel (D) shows the veins that were draining the fistula. This parallel channel was embolized (arrow in E) with a combination of
platinum coils and Hydrocoil (MicroVention). A control left external arteriogram (F) shows that the CVR was eliminated, although the
fistula persists. On the venous phase of the lateral internal carotid arteriograms before (G) and after (H) treatment, we see that these
cortical veins can participate in the venous drainage of the brain after disconnection. Abbreviations: DAVF, dural arteriovenous fistula;
CVR, cortical venous reflux.

is relatively simple. Coagulation and division of the
refluxing cortical veins as they enter the subarachnoid
space is sufficient to convert the aggressive type
DAVF into a benign one. In case of complex, high-
flow DAVFs, preoperative embolization with liquid
adhesives or particles is helpful to reduce blood loss
during surgery and may improve the results of a
surgical disconnection or packing of the sinus. The
permanent application of aneurysm clips has been
increasingly avoided during the past decade because
of local distortions of the magnetic field in MRI (59).
Transvenous Approaches to the Cavernous Sinus:
Special Considerations
There are a number of transvenous endovascular
approaches to the cavernous sinus. From the femoral
venous route, these include opacified ipsilateral or
contralateral inferior petrosal sinus, unopacified ipsi-
lateral or contralateral inferior petrosal sinus, superior
petrosal sinus, pterygoid plexus, and facial vein.
Using the contralateral inferior petrosal sinus, one
needs to cross the midline through the basal venous
plexus or the intracavernous venous sinus. Surgical
exposure of the superior ophthalmic vein can allow
transvenous navigation into the cavernous sinus. In
Meyers report of 117 DAVFs of the cavernous sinus,
the transvenous access was achieved through the
inferior petrosal sinus or superior ophthalmic vein in
76% of cases (61). Klisch reported that 60% of their
cavernous DAVFs were treated transvenously
through the inferior petrosal sinus, with complete
obliteration of the fistula in 78% of cases. Intracranial
surgical exposure of the superficial middle cerebral
vein allows access to the cavernous sinus through the
sphenoparietal sinus. On the basis of the venous drain-
age, Klisch divided the cavernous DAVFs into four
compartments: anterior, posterior, lateral, and inferior
(62). Recognition of the different types of cavernous
DAVFs based on these compartments may help to plan
the approach, and the treatment can be targeted to the
involved compartment (Fig. 6) (48).
Transvenous Approaches to the Transverse Sinus:
Special Considerations
If the affected sinus is isolated from the circulation,
then sinus occlusion is effective to close the fistula and
eliminate the CVR. The risk of venous infarction is low
since the cortical veins do not drain into the affected
sinus. In some patients, the isolated sinus can be
reached transvenously through an occluded segment.
346 van Dijk and Willinsky
If the transvenous route is unsuccessful, a burr hole or
direct surgical exposure can allow packing of the
isolated sinus. If the affected sinus drains both the
fistula and the cortical veins, occlusion of the sinus
carries a significant risk of venous infarction. It is now
clear that a number of transverse/sigmoid sinus
DAVFs have a parallel venous channel as the recipient
compartment for the fistula that is distinct from the
compartments draining the cortical veins. Super-
imposition of the arterial and venous phases of the
angiogram is important to illustrate the distinct com-
partments. Recognition of the parallel channel allows
selective transvenous embolization of that part of the
sinus that participates in the CVR (Fig. 11). Caragine
recognized such a parallel venous channel in
10 patients, in all of whom selective transvenous embo-
lization with preservation of the transverse/sigmoid
sinus was possible (63). Piske also highlighted the
concept of the parallel venous channel and reported
on the selective embolization of the affected compart-
ment in the superior sagittal sinus with preservation of
the sinus itself (45).
The Role of Radiosurgery
Although reported occasionally, there is a limited role
for the radiosurgical treatment of cranial DAVFs, with
or without CVR (6466). The benign cranial DAVFs
either need no treatment or benefit from selective
embolization of the involved venous sinus. The
aggressive cranial DAVFs have a poor natural history,
so the delayed effects offered by radiosurgery are not
acceptable (42).
SPINAL DURAL AV FISTULAS
The first description of spinal AVMs dates back to
1888 by Gaupp as a cluster of hemorrhoids on the pia
mater of the spinal cord (67). Medical descriptions in
those days were based on postmortem dissection or
surgical exposure and then related to the observed
clinical symptoms. In 1900, Brasch related a severe
case of myelopathy to a serpentine-like transforma-
tion of the spinal cord vasculature (68). Krause per-
formed the first documented surgical exploration of a
spinal vascular disorder (with a poor result) in 1911,
which was followed by Elsbergs first curative
surgical exposure in 1916 (69,70). Following the
introduction of angiography techniques, radiological
descriptions of spinal pathology became available. In
spite of these primitive circumstances, Wyburn-Mason
published a relatively large series (110 patients) and
classified angiomas into venous and arteriovenous (71).
Even after the introduction of the venous congestion of
the spinal cord in the early 1970s, spinal DAVFs were
categorized into the group of the spinal AVMs (72).
This categorization led to the unfortunate assumption
that the congested perimedullary venous plexus was a
part of the nidus. It needs no explanation that the
stripping of the venous plexus as a part of the surgical
therapy therefore often gave rise to increased postop-
erative neurological deficits (73).
It was not until the late 1970s that understanding
the anatomy and pathophysiology of spinal DAVFs
led to major breakthroughs in treatment. Spinal
DAVFs were recognized as extramedullary fistula-
type lesions draining into the perimedullary venous
plexus, features that distinguished them from the
genuine spinal AVMs (74,75). Then, after the concep-
tual recognition of a single shunting vein to the
perimedullary venous plexus by Oldfield and
Symon, the characteristic clinical syndrome, and the
surgical results of simply occluding the shunting vein,
DAVFs emerged as a unique entity (76,77).
Spinal Classification
Spinal vascular AV shunts are a heterogeneous group
of congenital malformations and acquired fistulas.
Therefore, several classification schemes have been
proposed, each of which tries to regroup these sepa-
rate lesions on the basis of different insights in pathol-
ogy. The most commonly used is the following
scheme with four subdivisions: type I, dural AVF;
type II, intramedullary glomus; type III, juvenile;
and type IV, perimedullary (78). However, it does
not take an expert to realize that these categories are
too static and that classification is often difficult. In
2002, Rodesch introduced a much more advanced
classification of the intradural AV shunts based on
the Bicetre experience, in which he differentiated the
lesions on the basis of quantity (single/multiple),
general aspect (nidus or fistula), associated metameric
disorders, and myelomere location. Notably, however,
in this arrangement the spinal DAVFs are excluded
(79). Spetzler introduced a classification with a wider
scope that subdivides the spinal vascular lesions in
neoplastic vascular lesions, spinal aneurysms, spinal
AVMs, and spinal AVFs. Within the spinal AVFs,
three subgroups are identified: extradural AVFs, intra-
dural ventral AVFs, and intradural dorsal AVFs (the
latter group is essentially DAVFs).
Spinal DAVFs embody the vast majority of all
spinal vascular lesions in the adult population and are
virtually absent in the pediatric age group. The
acquired AV fistula is typically located at the thoracic
or lumbar level (80). Remarkably, at the cervical level,
DAVFs seem not to exist. This phenomenon has been
explained by the existence of numerous venous out-
lets at the cervical level, in contrast to the thoraco-
lumbar level, and by the influence of gravity
facilitating the venous reflux to the vena cava system.
Although there are reports concerning cervical loca-
tions that presented with subarachnoid hemorrhage
or without myelopathy, these cases were either cranial
DAVFs or extradural AVFs draining into the perime-
dullary venous plexus (81).
Spinal Clinical Features
The clinical features of a spinal DAVF are directly
related to the venous congestion of the spinal cord
caused by a direct fistula from the radiculomeningeal
artery to the perimedullary venous plexus. This leads
 Chapter 19: Endovascular Management of Dural Arteriovenous Fistulas
to a clinical picture of chronic progressive myelopathy
of the lower thoracic cord and conus, irrespective of
the location of the shunt (82). Venous congestion
leading to hypoxia and ischemia is accepted as the
theory of choice. The histopathological findings of an
occasional biopsy of the spinal cord support this
theory (83). Compression of the spinal cord by the
voluptuous venous plexus has been suggested, but is
highly unusual.
Spinal DAVFs typically present in the fourth to
sixth decade, commonly in males. In a study combin-
ing the clinical findings in 172 patients from five series
in the literature, leg weakness was the initial com-
plaint in 40%; however, at the time of diagnosis, it was
present in 88% of the cases. The same phenomenon is
described in bladder and bowel dysfunction (5% vs.
85%). This discrepancy is explained by the extensive
delay between the initial presentation and the actual
diagnosis. Symon reported that only one-third of
patients were diagnosed within one year of the onset
of symptoms and only two-thirds of patients had their
diagnosis within three years (84). Hemorrhage practi-
cally never occurs, although it is a major presenting
sign of the cranial DAVFs with reflux in the leptome-
ningeal veins. This phenomenon is likely explained by
the slow-flow characteristics of the spinal DAVFs (85).
Intracranial DAVFs with perimedullary venous reflux
may present with a cervical myelopathy or rarely even
with a cervical intradural hemorrhage (86).
In 2002, the Toronto database contained 49 pa-
tients with a spinal DAVF. The mean age was
63.2 years, with an 80% male predominance. The
fistulas were located between the nerve roots of C7
and S1, with 94% situated below the T5 root level and
in majority on the left side (70%). It hypothesized that
the position of the heart is related to these findings.
Multiplicity was encountered in one patient (2%). At
the time of diagnosis, all but one patient (who com-
plained of radicular pain) had signs and symptoms of
myelopathy. The majority of the patients (96%) suf-
fered from spastic paraparesis or leg weakness and
90% had sensory disturbances. Bladder and bowel
malfunctions as well as pain (either back or remote
pain) were other significant complaints. The time
interval between the initial symptoms and diagnosis
was median 10.5 months (87).
In the natural disease course of spinal DAVFs,
the thoracic myelopathy is gradually but inexorably
progressive leading eventually to a state of paraplegia
and incontinence. Eventually this process ends in the
Foix-Alajouanine syndrome, originally described in
1929 as a subacute necrotizing myelopathy (88). To
classify the severity of the thoracic myelopathy, the
classification scale for motor and bladder function as
used by Aminoff is frequently applied (Table 3) (89).
Spinal Diagnostic Imaging
The current mainstay of diagnosing a spinal DAVF is
MRI. Typically on T2 images, there is a hyperintense
signal within a slightly swollen lower thoracic spinal
cord and medullary conus, outlined by a peripheral
347
Table 3 Aminoff Score of Disability
Classification of gait disturbance
Grade 1 Leg weakness or abnormal gait; no restricted
activity
Grade 2 Grade 1 with restricted activity
Grade 3 Requires one stick or similar support for walking
Grade 4 Requires two sticks or crutches for walking
Grade 5 Unable to stand, confined to bed or wheelchair
Classification of micturition
Grade 1 Hesitance, urgency, or frequency
Grade 2 Occasional urinary incontinence or retention
Grade 3 Total urinary incontinence or retention
hypointensity (90). Spin-echo techniques are best to
reveal the vascular nature of the congestive myelop-
athy. Contrast enhancement with gadolinium can be
useful in differentiating the spinal cord effects of
DAVF from an intramedullary tumor, although in
severe congestive myelopathy due to DAVF, patchy
enhancement may be noted. Enhancement of the con-
voluted perimedullary venous plexus supports the
diagnosis of a spinal DAVF, but the abnormal flow
voids are nonspecific for the actual location of the
fistula. To find the level of the fistula, enhanced
ATECO-MRA has been demonstrated to be very effec-
tive (Fig. 12). This technique, published by Farb,
proves very useful in determining the levels of inter-
est, after which the commonly lengthy angiography
session can be focused (91). Targeted superselective
angiography can thus be limited to bilateral injections
of the radicular arteries at the level of the fistula and
the immediate adjacent levels above and below. Usu-
ally, the fistula is located at the level of a root sleeve,
however sometimes it is remote. Especially in the
latter case, a multisegmental arterial supply of the
DAVF can be expected. The fistulous point is recog-
nized on the angiogram by a caliber change between
the artery and the dilated vein. The intradural vein is
unpredictable in its location and direction. As a rule, it
follows the course of the nerve root, which implies an
upward track at the lumbar level, but at the thoracic
level the track may as well be horizontal. For treat-
ment purposes, visualization of the anterior spinal
artery (Adamkiewicz) is essential and warrants addi-
tional injections. The Adamkiewicz artery often arises
between T8 and T11; in 50% of the cases, from the
intercostal artery at T9 or T10 on the left (92). Injection
of the Adamkiewicz artery, then, reveals a prolonged
circulation time within the spinal cord, which is indic-
ative of venous congestion (93).
In case ATECO-MRA does not reveal a fistula
site, but the MRI and the clinical picture are highly
suggestive of a spinal DAVF, a more extensive, tradi-
tional angiography is necessary, including selective
injections of all intercostal and lumbar arteries as well
as both internal iliac arteries. If no spinal DAVF is
found subsequently, the cervical cord and intracranial
circulation, including the selective injections of both
vertebral arteries and the costocervical and thyrocer-
vical arteries, should be studied with angiography. A
study of the intracranial circulation should include the
vertebral, internal, and external carotid arteries (86).
348 van Dijk and Willinsky
Spinal Therapeutic Considerations
All cases of the ominous natural disease course of
spinal DAVFs should be treated by occlusion or divi-
sion of the fistulous vein. Intradural surgical ligation
has proven very effective with durable results (76,94).
Surgical interruption of the draining radicular vein is
preferentially done using bipolar coagulation. Exci-
sion of the whole fistula site is not necessary and may
cause CSF leakage or nerve sacrifice. In case of both
intradural and extradural venous drainage, surgical
interruption of the intradural vein will treat the con-
gestive myelopathy; the extradural drainage can be
left alone (95).
Endovascular techniques using diluted liquid
adhesive (e.g., N-butyl cyanoacrylate, or NBCA)
have also proven effective with durable results
(96,97). Particle embolization is not recommended
because the incidence of symptomatic recurrence is
high (98). It is essential that the embolic material
reaches the proximal part of the draining vein; other-
wise, collateral dural branches may keep the fistula
open and recurrences may occur despite what was
thought to be an adequate treatment (99). The col- days of the treatment and may warrant anticoagula-
lateral flow may not be evident at the time of embo-
lization, and therefore patients need close follow-up.
Patients may improve initially after the embolization,
but will experience delayed deterioration following
partial treatment.
Although it is generally accepted that surgery
and endovascular therapy are equally effective, a
recent meta-analysis suggests that a surgical approach
is preferable (100). On the other hand, advantages of
endovascular embolization include the facts that it is
less invasive and that it has immediate angiographic
control of the treatment. Moreover, by using ATECO-
MRI the diagnostic angiography can even be com-
bined with the treatment. Therefore, initial attempt at
endovascular embolization with liquid adhesive
Figure 12 Gadolinium-enhanced MR expedites treat-
ment of spinal DAVF. A 63-year-old male presents with
a thoracic myelopathy. The T2-weighted MR of the
spine (A) shows a central T2 hyperintensity within the
cord and prominent posterior perimedullary veins
(arrows). The gadolinium-enhanced MR angiogram
(B) identifies the fistula site (arrow) of the spinal DAVF
thereby facilitating the catheter angiogram (C) that is
done to embolize the fistula. Abbreviation: DAVF, dural
arteriovenous fistula.
material can be justified, but should not be under-
taken if catheterization of the branch to the feeding
pedicle proves to be difficult on the diagnostic angio-
gram or in cases where there is a common segmental
origin of the anterior spinal artery and the radiculo-
meningeal branch supplying the fistula (101). In case
of an incomplete closure of the DAVF or abstention
from endovascular embolization, surgical therapy
should be instituted shortly after. It is worthwhile to
go for a curative treatment. Using the Aminoff score,
Steinmetz in his meta-analysis reports that following
both microsurgery and embolization for gait distur-
bances, there is a 55% chance of improving and an
11% chance of being worse. Therefore, patients have
an 89% chance of improving or stabilizing. The results
for improvement in bladder function were less favor-
able. Only 33% of patients demonstrated an improve-
ment in micturition, whereas 11% worsened (100).
If aggravation of the symptoms occurs after
treatment and there is angiographic proof of a cure
and no multiplicity, then the clinical deterioration
may be due to venous thrombosis of the perimedul-
lary veins. Such deterioration usually occurs within
tion therapy. For this reason, some authors propose
heparin for three days following embolization for all
patients with a significantly compromised venous
drainage (99).
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spinal dural arteriovenous fistulae: results and follow-up.
Neurosurgery 1997; 40(4):675682.
100. Steinmetz MP, Chow MM, Krishnaney AA, et al. Outcome
after the treatment of spinal dural arteriovenous fistulae: a
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selective angiography of a spinal dural arteriovenous
fistula having a common segmental origin with the artery
of Adamkiewicz. Neuroradiology 1992; 34(4):352354.
 20

Inferior Petrosal Sinus Sampling in the

Diagnosis of Pituitary Adenomas

Nicholas J. Patronas
Department of Radiology, National Institutes of Health Clinical Center,
Bethesda, Maryland, U.S.A.
Donald L. Miller
Department of Radiology, National Naval Medical Center and Department of Radiology,
Uniformed Services University of Health Sciences,
Bethesda, Maryland, U.S.A.

INTRODUCTION carcinomas, primary pigmented nodular adrenal

Inferior petrosal sinus sampling (IPSS) is used in the
differential diagnosis of Cushings disease and when
there is a strong clinical suspicion of a hyperfunction-
ing pituitary adenoma and noninvasive methods have
failed to establish the diagnosis. These adenomas
may secrete prolactin, adrenocorticotropin (ACTH),
growth hormone (GH), or thyrotropin (TSH). The
initial application of IPSS was the evaluation of
patients with Cushings syndrome. This syndrome
remains the main indication for its use.
Cushings syndrome is a clinically recognizable
entity. It is characterized by a variety of symptoms, the
most important of which include hypertension, diabe-
tes mellitus, weight gain with central obesity, moon
faces, purple abdominal striae, hirsutism, hyperpig-
mentation, and osteoporosis. The common denomina-
tor of Cushings syndrome is hypercortisolemia. The
causes of the syndrome may be classified as ACTH-
dependent or ACTH-independent. Simply put, patients
with ACTH-dependent Cushings syndrome have ele-
vated levels of ACTH and cortisol, while patients with
ACTH-independent Cushings syndrome have ele-
vated levels of cortisol alone. Elevated is relative;
patients with hypercortisolism have low or undetect-
able levels of ACTH due to suppression of both cortico-
trophin-releasing hormone (CRH) and ACTH
production by the normal feedback loops in the hypo-
thalamic-pituitary-adrenal axis. Normal levels of
ACTH are abnormal in patients with Cushings syn-
drome and indicate an ACTH-dependent cause.
Overproduction of cortisol alone is typically
due to an adrenal lesion. Approximately 5% of
patients with Cushings syndrome have an adrenal
lesion that demonstrates autonomous functionit
does not require stimulation by ACTH to produce
cortisol. These non-ACTH-dependent lesions include
hyperfunctioning adrenal adenomas, adrenocortical
disease (PPNAD), and macronodular hyperplasia of
the adrenals. ACTH-independent Cushings syn-
drome can also occur as a result of exogenous steroid
administration. There is no role for IPSS in patients
with ACTH-independent Cushings syndrome.
The remaining patients with Cushings syndrome
have an ACTH-dependent cause. Approximately 80%
of these patients have an ACTH-secreting pituitary
adenoma. This etiology (and only this specific etiology)
is referred to as Cushings disease. An additional 15%
of patients with Cushings syndrome have an ACTH-
secreting tumor at a site other than the pituitary gland.
Most of these patients have an obvious primary malig-
nancy with ectopic hormone production, typically in
the lung. Some have a small, clinically occult tumor
and present with what is termed the occult ectopic
ACTH syndrome. Most commonly, these small tumors
are found in the bronchial tree, but localization of these
lesions can be extremely difficult. Both depression and
alcoholism can cause elevated CRH levels and present
as pseudo-Cushings syndrome. Very rarely, CRH-
secreting tumors are responsible for ACTH-dependent
Cushings syndrome.
The endocrinologist is responsible for determin-
ing whether the patient has the ACTH-dependent or
the ACTH-independent form of Cushings syndrome.
Patients with ACTH-independent disease require
adrenal imaging, but not pituitary imaging. Patients
with ACTH-dependent disease require further
endocrinologic evaluation to determine whether the
ACTH is from a pituitary source (Cushings disease)
or an ectopic source of ACTH. A number of biochem-
ical tests have been developed to aid in this effort.
These include suppression tests with dexamethasone
and stimulation tests with CRH. The details of bio-
chemical testing are outside the scope of this chapter.
Briefly, these tests rely on differences between
354 Patronas and Miller
pituitary adenomas and ectopic tumors. In general,
pituitary tumors retain some capacity to demonstrate
suppression of ACTH in response to high levels of
exogenous steroids and some ability to demonstrate
stimulation of ACTH in response to exogenous CRH,
while ectopic tumors do not respond. Unfortunately,
none of these biochemical tests is 100% sensitive and
100% specific.
Magnetic resonance imaging (MRI) of the pitu-
itary gland has become a routine test for evaluating
patients with ACTH-dependent Cushings syndrome.
MRI has proven useful not only for establishing the
presence of an adenoma but also for demonstrating its
location within the gland. This information is of
paramount importance for surgical planning, since
preservation of pituitary function after successful
resection of the adenoma is a cardinal objective of
the operation. The sensitivity of MRI in detecting
pituitary adenomas primarily depends on tumor
size. The sensitivity to ACTH-secreting adenomas
has been reported to be as low as 45% in postcontrast
scans. In other type of adenomas the sensitivity is
considerably higher, since they become clinically
apparent when larger in size.
One of the problems with pituitary MRI is the
absence of uniformity in the imaging protocols used at
various centers. One cause of false-negative results is
the use of suboptimal imaging techniques. In the past
we routinely used the following imaging parameters:
field strength 1.5 tesla, repetition time/echo time
400/9 msec, 192  256 matrix, two excitations, 12-cm
field of view in the coronal and 16 cm in the sagittal
plane, and 3-mm-thick sections without gap. More
recently we have used a gradient-echo T1-weighted
technique before and after contrast material adminis-
tration [0.01-mmol/kg gadopentetate dimeglumine
(Magnevist, Berlex Laboratories, Inc., Montville, New
Jersey, U.S.)], with repetition time/echo time 9.6/
2.3 msec, a 208 flip angle, 160  256 matrix, 6 excita-
tions, and 1.5-mm slice thickness. With this technique
we can exploit the superior contrast resolution of the
gradient-echo technique and acquire thinner tomo-
graphic sections.
Difficulties in demonstrating ACTH-secreting
pituitary adenomas have several other causes that
are less amenable to correction. First, these tumors
are usually very small when patients first present. The
spatial resolution limitations of current MRI scanners
may cause them to be obscured by averaging artifacts.
Second, pituitary adenomas often enhance in a fashion
similar to normal pituitary parenchyma. Finally,
detection of functioning pituitary adenomas is also
confounded by the fact that identical-appearing, small
focal spaceoccupying lesions can be encountered
within the pituitary parenchyma of normal subjects.
Autopsy studies and MR scans of normal volunteers
have demonstrated that there is a 6% to 10% incidence
of nonfunctioning adenomas (incidentalomas) in the
pituitary gland (1,2).
Neither biochemical tests nor imaging studies
can provide an accurate diagnosis in all patients with
Cushings syndrome, and an additional diagnostic
method is sometimes required. In these patients,
petrosal sinus sampling can be used to confirm or
exclude the presence of a functioning pituitary
adenoma. It is most useful when the results of bio-
chemical tests and MRI are discrepant. In addition,
when biochemical tests provide a firm indication of
Cushings disease but no lesion is identified on pitu-
itary MRI, IPSS may provide lateralization of the pitu-
itary adenoma to one side of the pituitary gland. This
lateralization permits the surgeon to perform a hemi-
hypophysectomy and preserve pituitary function.
INDICATIONS FOR PETROSAL
SINUS SAMPLING
Petrosal sinus sampling is performed in patients with
a confirmed endocrine diagnosis of ACTH-dependent
Cushings syndrome and one of the following:
l Absence of a discrete pituitary lesion on MRI
l Equivocal biochemical tests in the presence of a
discrete pituitary lesion on MRI
l Persistent Cushings syndrome after transsphenoi-
dal surgery
l Clinical need to resolve other discrepancies
between clinical, biochemical, and imaging tests
l A hyperfunctioning pituitary adenoma (acromegaly,
thyrotropin-secreting hormone overproduction):
l Consideration of surgical resection and the results
of pituitary MRI being negative
When petrosal sinus sampling is performed in
patients with Cushings syndrome for these indica-
tions, the procedure has a sensitivity of 92% and a
specificity of 90%, and lateralization provided by IPSS
is correct in 70% of patients (3).
Prior to sampling, 15 lavender-top tubes
[Vacutainer, no.6457, with ethylenediaminetetraacetic
acid (EDTA K3); Becton Dickinson, Rutherford, New
Jersey, U.S.] are labeled and placed in an ice-water
bath. Bilateral femoral vein puncture is performed
under local anesthesia with ultrasound guidance
using a micropuncture system. A sheath is placed in
each femoral vein through which a 4-French (Fr)
catheter is introduced. The sampling catheters are
preshaped over steam to form a 758 bend for the left
side and a 958 for the right. Alternatively, preshaped
vertebral catheters with no side holes may be used. At
least one of the femoral vein sheaths should be 1 Fr
larger than the catheter used. This sheath is used to
draw the peripheral vein samples that are obtained as
part of the sampling procedure.
A coaxial technique using a microcatheter to
catheterize the inferior petrosal sinus (IPS) has become
increasingly popular (3,4). This technique includes a
5-Fr or 6-Fr introducer catheter advanced into the
internal jugular vein and a Target-10 or a Tracker-18
or Tracker-25 microcatheter (Target Therapeutics,
Freemont, California, U.S.) and a Seeker 10 or a Seeker
16 wire (Target Therapeutics) for the selective cathe-
terization of the IPS. Prior to introduction of any
catheter into the petrosal sinus, a bolus of 3000 to
4000 IU of heparin is administered intravenously. In
addition 5000 IU of heparin is added to the flush
solution used to irrigate the petrosal sinus catheters
 Chapter 20: Inferior Petrosal Sinus Sampling in the Diagnosis of Pituitary Adenomas
and the femoral vein sheaths. The use of sedation is
not recommended, but during the procedure intrave-
nous midazolam and fentanyl may be used as needed.
The right femoral vein introducer catheter is
advanced into the right internal jugular vein, usually
without difficulty, along a straight line through the
inferior vena cava, the right atrium, and the superior
vena cava. Advancement of the left femoral introducer
catheter into the left internal jugular vein is usually
more problematic, since the catheter must first turn by
908 from the superior vena cava into the left innomi-
nate vein and then turn by another 908 into the left
internal jugular vein. In addition, a valve is located at
the base of the left internal jugular vein, at its junction
with the innominate vein. The valve can usually be
successfully negotiated by positioning the tip of the
catheter at the base of the internal jugular vein and
advancing a flexible guidewire into this vessel during
expiration or a reverse Valsalva maneuver.
From the internal jugular vein, selective catheter-
ization of the IPS is accomplished by rotating the
introducer catheter medially and anteriorly as it is
moved from the dome of the jugular bulb downward.
This procedure is performed while injecting contrast
to opacify the venous channels draining into this
vessel. It is not uncommon to identify more than one
such vessel. The tip of the introducer catheter is then
anchored at the orifice of the most prominent venous
channel (Fig. 1). Further advancement of the catheter
into this vessel should be attempted only over a flex-
ible guidewire coated with hydrophilic material
(Glidewire, catalogue no. 46-151, Medi-tech/Boston
Scientific, Natick, Massachusetts, U.S.). The guidewire
should never be advanced into the cavernous sinus,
and the catheter should never be advanced more than
1 to 1.5 cm into the IPS. Successful catheterization of
the IPS is documented fluoroscopically in the anterior-
posterior projection during gentle hand injection of
contrast (Fig. 2). Digital subtraction angiography
should also be obtained at this time, and opacification
Figure 1 IPS venogram in a patient with Cushings disease.
(A) Injection in the right and (B) in the left IPS. Note asymmetry of
the IPS with the left being smaller than the right. Abbreviation:
IPS, inferior petrosal sinus.
355
Figure 2 Right IPS injection. There is good opacification of
cavernous sinuses and retrograde flow into the left IPS. Arrow
heads point to the tip of the catheters on both sides. Abbreviation:
IPS, inferior petrosal sinus.
of the ipsilateral cavernous sinus as well as the oppo-
site cavernous and IPSs documented; unless there is
documentation of proper positioning of the catheter
into the IPS, the results of venous sampling become
questionable (Fig. 3).
If one IPS is difficult to identify, it is usually
advisable to abandon the attempt and switch to the
other side, which may be easier to catheterize. The
road map obtained from the contralateral catheter-
ization can then be used to assist catheterization of the
more difficult side (Figs. 4 and 5).
Successful catheterization of the IPS requires
familiarity with the anatomic variations that can be
encountered at the junction of the IPS and the internal
jugular vein, just inferior to the jugular bulb. There is
substantial variation in the diameter, number of chan-
nels, and degree of symmetry of the IPS, and in the
extent of drainage into the basilar plexus and vertebral
venous plexus (Fig. 6) (5). Shiu et al. classified the
spectrum of drainage patterns at the junction between
the IPS and the internal jugular vein into four different
variations, ranging from exclusive drainage into the
internal jugular vein to exclusive drainage into the
vertebral venous plexus (6). Miller et al. subsequently
modified this classification (7). In type I anatomy, the
IPS drains directly into the internal jugular vein as a
single large channel. There may be a small communi-
cation with the vertebral venous plexus via the ante-
rior condylar vein or other anastomotic channel. In
type II anatomy, the IPS is a single channel. Drainage
into the vertebral venous plexus is via a relatively
large channel, greater than 1.7 mm in diameter. In
type III anatomy, the IPS drains into the internal
jugular vein via multiple channels. In type IV anat-
omy, there is no anastomosis between the IPS and the
internal jugular vein. Instead, one or more veins
(typically a plexus) originating from the cavernous
sinus drains into the vertebral venous plexus. A vari-
ant of type II or III anatomy, incomplete type IV also
356 Patronas and Miller

Figure 3 Microcatheter technique of IPSS.

(A) Subtracted AP view of injection into right
IPS (inferior petrosal sinus) (white arrowhead,
introducer catheter tip at junction of right jug-
ular vein and IPSS). (B) Injection of left IPS
with cross filling into right IPS (arrowheads,
introducer catheter tips in jugular veins).
Injection through right (C) and left (D) micro-
catheters in IPS (arrows, microcatheter tips
in IPS). (E) Unsubtracted view showing
arrangement of introducer catheters and
microcatheters in position for sampling.
Abbreviations: IPSS, inferior petrosal sinus
sampling; IPS, inferior petrosal sinus.

occurs. In this variant, a very small connection is

present between the IPS and the internal jugular
vein, but the vast majority of petrosal venous drainage
is into the vertebral venous plexus.
IPS anatomy is symmetrical in about two-thirds
of the individuals; the other one-third have one
anatomic type present on the right and a different
anatomic type on the left. In a venographic study of
268 IPSs, type I anatomy (the easiest to catheterize)
was encountered in 20% of sinuses, type II in 46%,
type III in 37%, and type IV in 0.4% of sinuses (7).
Incomplete type IV anatomy was encountered in 3%
of sinuses (classified above as a variant of type II or
type III). Catheterization of IPSs with type II and III Figure 4 IPS venogram in a patient with Cushings disease.
anatomy may occasionally be difficult, since the IPS is (A) Injection in the right and (B) injection in the left IPS. Note
prominent vertebral plexus. The right IPS is hypoplastic. The road
relatively small. The incomplete type IV variant is
map from the left IPS injection was used to achieve selective
particularly difficult to catheterize. True type IV anat- catheterization of the hypoplastic right IPS. Abbreviation: IPS, infe-
omy is fortunately rare, because this variant makes rior petrosal sinus.
catheterization via the internal jugular vein impossible.
 Chapter 20: Inferior Petrosal Sinus Sampling in the Diagnosis of Pituitary Adenomas
In experienced hands, bilateral petrosal sinus catheter-
ization is possible in 93% to 99% of patients with patent
internal jugular veins (3,7,8).
Successful petrosal sinus sampling demands
meticulous attention to detail. Petrosal venous sam-
pling requires that simultaneous samples be obtained
from two catheters and a venous sheath, and that
these samples be placed immediately into correctly
numbered and labeled tubes. Multiple timed samples
are obtained from each catheter: a baseline set and sets
at 3, 5, and 10 minutes after the intravenous adminis-
tration of 1 mg/kg (maximum dose 100 mg) CRH. Prior
to sampling, 2 to 3 mL of blood is withdrawn from
357
Figure 5 Contralateral injection to aid IPSS.
(A) Unsubtracted and subtracted (B) AP views of
introducer catheter tips (arrows) in the jugular bulbs at
the junction with the IPSs. Jugular venogram in AP
(B) and lateral (C) views fills left IPS into the posterior
left cavernous sinus (arrowhead, C). Left sigmoid sinus
also fills (black arrow, C). (D) Right jugular venogram:
no filling of right IPS (arrow, introducer catheter tip).
(E) Unsubtracted and (F) subtracted AP views following
microcatheter placement into the left IPS. Contrast
injection through microcatheter (large arrow, microcath-
eter tip) fills left IPS (arrowhead, impression of left
cavernous carotid artery) with cross filling into right
IPS, demonstrating junction with right jugular vein
(small arrows), thereby aiding microcatheterization of
right IPS (G). (H) Unsubtracted AP view shows micro-
catheters in place for IPS sampling. Abbreviations:
IPSS, inferior petrosal sinus sampling; IPS, inferior
petrosal sinus.
each catheter into a waste syringe and discarded. Each
10-mL blood sample is drawn into a plastic 10-mL
syringe over 20 to 40 seconds. Each sample is then
transferred into the appropriately numbered and
labeled tube using a 16-gauge needle. The tube is
gently tilted to mix the sample with the EDTA in the
tube and is returned to the ice-water bath. In between
sampling, the position of both catheters is checked
fluoroscopically to confirm that neither catheter has
slipped out of the petrosal sinus. At the end of the
procedure, a digital subtraction venogram of each
petrosal sinus is obtained separately by gentle hand
injection of 5-mL nonionic contrast material. These
358 Patronas and Miller
data serve as a permanent record of catheter position
during sampling, if questions arise when the data are
interpreted.
Interpretation of Sampling Data
The physiologic basis for interpretation of sampling
data is straightforward: the IPSs drain pituitary
venous blood. If the patient has a functioning pituitary
adenoma, ACTH will be present at higher concentra-
tion in petrosal sinus samples than in peripheral vein
samples. If ACTH is coming from an ectopic source,
ACTH concentrations in petrosal sinus samples will be
similar to those in peripheral venous blood. In cases of
Cushings disease, petrosal sampling can provide
unequivocal evidence of ACTH-secreting adenoma by
demonstrating elevated values of ACTH in the blood
samples from the petrosal sinuses compared with those
of the peripheral venous blood. Since ACTH concen-
trations in left and right petrosal sinus blood samples
are usually not identical, it is essential to sample both
sinuses. The side with the higher ACTH concentration
in each sample set is used as the IPS value for the data
analysis.
In baseline samples (obtained prior to CRH
administration), an IPS to peripheral (IPS/P) ACTH
ratio greater than 2 is indicative of Cushings disease.
An IPS/P ACTH ratio greater than 3 in any sample set
obtained after CRH administration is also diagnostic.
Figure 6 Low junction of IPS with jugular
vein. (A) AP and (B) lateral views of right
jugular venogram show IPS junction with jug-
ular vein (arrow) several centimeters below
skull base (arrowhead, jugular bulb). (C) Lat-
eral and (D) AP views after microcatheter
placement into right IPS, injection fills IPS
bilaterally (*, introducer catheter tip in left
jugular vein; arrow, introducer catheter tip in
right jugular vein; arrowheads, course of
microcatheter in right IPS). Abbreviation:
IPS, inferior petrosal sinus.
When Oldfield et al. first reported the results of the
method, the sensitivity and specificity for detection of
a pituitary source of ACTH secretion were found to be
95% and 100%, respectively, in the baseline samples (9).
After intravenous administration of CRH, both sensi-
tivity and specificity were 100%. Subsequent investiga-
tors have found that both false-negative and, rarely,
false-positive results can be encountered (3,1012). The
sensitivity and specificity after CRH administration
range from 90% to 97% and from 67% to 100%, respec-
tively (3,11,12).
A negative result from petrosal sinus sampling is
not conclusive proof that the patient has an ectopic
ACTH source. The cause of these false-negative
results is not always clear. Displacement of the cath-
eter during sampling or incorrect catheter placement
may be responsible in some cases. IPS anatomy
particularly the presence of a hypoplastic IPSand
changes in venous drainage after surgical intervention
have also been implicated (13).
IPSS also has a role in lateralizing the pituitary
adenoma to one side of the pituitary. This lateraliza-
tion is particularly important in patients with micro-
adenomas. Successful lateralization permits the
surgeon to perform a hemihypophysectomy and pre-
serve pituitary function. A ratio of 1.4 or more
between the ACTH concentrations of the two petrosal
sinus samples from any sample set indicates that the
adenoma is located on the side of greater ACTH
 Chapter 20: Inferior Petrosal Sinus Sampling in the Diagnosis of Pituitary Adenomas
Figure 7 IPS venogram in a patient with GH-secreting pituitary
adenoma. The measured values of GH in pg/mL are recorded. A
GH-secreting adenoma was found at surgery in the right half of
the pituitary. Abbreviations: IPS, inferior petrosal sinus; GH,
growth hormone.
concentration (Fig. 7). The reported sensitivity of IPSS
for lateralization of pituitary adenomas in adults
ranges from 57% to 90% (3,4,12,1416). Occasionally,
samples obtained before and after CRH administra-
tion provide discordant lateralization. In this situa-
tion, neither lateralization can be relied upon (17).
There are several reasons for this relatively low
yield. Often, the adenoma is located in the center of
the pituitary and drains into both the cavernous
sinuses. The same drainage pattern also occurs in
larger adenomas. Anomalies in petrosal venous anat-
omy such as hypoplasia of one sinus can result in false
lateralization to the opposite side, as can asymmetry
in petrosal sinus anatomy or previous transsphenoidal
surgery (4,17). In a recent study the sensitivity of
lateralization in a series of 141 pediatric patients was
found to be only 54%, which is more than in conven-
tional MRI and no better than a chance value(18). In a
different, smaller series of 11 patients, however, later-
alization was correct in 91% of patients (19). The
reasons for this discrepancy are unclear.
Complications of IPSS
Various investigators have encountered neurologic
and other complications during IPSS (2024). The
incidence of such complications is low and ranges
from 0.2% to 1.1%. Miller et al. reported a case of
hematoma in the pons associated with hemorrhage in
the fourth ventricle, which resulted in right hemi-
plegia with partial recovery and left facial paralysis.
They also reported an ischemic infarction in the
medulla in a patient who underwent IPSS by other
operators at a different institution. Subarachnoid hem-
orrhage, Raymonds syndrome (sixth nerve palsy and
hemiparesis), and brain stem infarction have been
reported by other investigators (21,23,24).
359
A variety of other less severe or transient neuro-
logic events have also been reported, including
slurred speech, paresthesias, visual disturbances, tran-
sient sixth nerve palsy, vertigo, nausea, vomiting, and
transient muscle weakness. These complications may
not have a common cause. While the etiology is not
known, it appears that most serious complications
occur as a result of rupture or thrombosis of a venule
in the brain stem or a bridging vein within the sub-
arachnoid space. These complications may be due to
the highly variable venous anatomy in this region.
When test injections of contrast material are made to
identify the orifice of the IPS, special attention should
be paid to the size of the veins and to ensure that the
catheter tip is not in a small vein. Catheterization of an
extremely small vein or forceful hand injection of con-
trast material in a catheter wedged in such a vein can
easily lead to either elevated venous pressure or rup-
ture of that vein. However, the presence of adequate-
sized venous channels and proper position of the
catheter tip do not guarantee that a serious complica-
tion will not occur, since these complications have
occurred despite seemingly unremarkable petrosal
sinus anatomy (20). Additionally, catheterization of
extremely small petrosal sinuses has been performed
without incident (7).
A neurologic event may be heralded by minor and
seemingly insignificant symptoms. Arterial hyperten-
sion, slurred speech, difficulty swallowing, a sensation
of an enlarged tongue, a woozy feeling, and hemi-
facial paresthesias have all been encountered as initial
manifestations of a brain stem insult. These may be
subtle, and the patient may not mention them unless
asked. If present, they should not be interpreted as
evidence of anxiety, oversedation, or a reaction to con-
trast material. Brain stem injury may be preventable if
the catheter is withdrawn at the earliest sign of even a
minor, insignificant problem. Subtle symptoms and
signs that may not appear to be neurologic may herald
a clinical catastrophe if not heeded.
Patients with Cushings syndrome are also prone
to venous thrombosis, and both deep venous throm-
bosis and pulmonary embolus have been reported as
complications of petrosal sinus sampling (25).
ALTERNATIVES TO IPSS
Catheterization of, and sampling from, the cavernous
sinus has been suggested as an alternative to petrosal
sinus sampling, on the grounds that it is both safer
and more accurate (14,26,27). Other studies indicate
that sampling from the cavernous sinus is no more
accurate than petrosal sinus sampling for distinguish-
ing between Cushings disease and an ectopic ACTH
source and is less accurate for lateralization of an
adenoma within the pituitary gland (4,28). In a series
of 14 cavernous sinus sampling procedures by
Lefournier et al., transient sixth nerve palsies occurred
in two patients (4).
Doppman et al. advocated the sampling of the
internal jugular veins because of the technical difficul-
ties that can be encountered in selective catheterization
360 Patronas and Miller
of the IPS, the long learning curve for petrosal sinus
sampling, and the need to abandon the procedure in
patients who develop suspicious symptoms, systemic
hypertension, or neurologic events during the proce-
dure (29). In this simpler procedure, catheters are
placed in both internal jugular veins at the level of
the mandible. In the initial description of the proce-
dures, the catheters were inserted through bilateral
femoral vein punctures, but in a subsequent series
catheters were placed via the internal jugular vein (30).
In our own practice, we routinely use ultrasound guid-
ance and a micropuncture set to access the internal
jugular vein as inferiorly as possible in the neck, and
advance the inner 3-Fr dilator of the micropuncture set
retrogradely, so that its tip lies at the level of the man-
dible. The outer dilator is not used. No skin nick is
necessary, and the procedure is performed with local
anesthesia alone. Samples are obtained before and after
CRH administration in the same fashion as for petrosal
sinus sampling.
In a series of 79 patients, the NIH group found a
sensitivity of 83% for jugular venous sampling, using
arbitrary thresholds (jugular vein/peripheral vein
ACTH ratio >1.7 before CRH administration or >2.0
after CRH administration) to set specificity at 100%. In
the same patients, IPSS had a sensitivity of 94% when
specificity was set at 100% (30). Erickson et al. dem-
onstrated similar results in a series of 35 patients.
They suggest that the sensitivity of internal jugular
vein sampling can be improved by placing the cath-
eter near the medial rather than the lateral wall of the
internal jugular vein during sampling and by using a
jugular vein/peripheral vein ACTH ratio greater than
2.5 for the diagnosis of Cushings disease (31).
Although internal jugular vein sampling is less
sensitive than petrosal sinus sampling, it is simpler
and avoids the risk of neurologic complications inher-
ent in petrosal sinus sampling. It is reasonable to
perform jugular venous sampling first and to reserve
petrosal sinus sampling for the patients in whom
jugular venous sampling does not confirm Cushings
disease. These patients may be referred to centers
where extensive experience in performing petrosal
sinus sampling is available.
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 21
Endovascular Treatment of Spinal Vascular Malformations
Mayumi Oka and Kieran Murphy
Department of Radiology, Division of Interventional Neuroradiology, Johns Hopkins
University, Baltimore, Maryland, U.S.A.
INTRODUCTION
In 1960s and 1970s, interventional neuroradiological
techniques for the treatment of spinal vascular lesions
were developed when understanding of these lesions
deepened because of the advances in selective spinal
angiography techniques and increased knowledge.
Two groups of authors contributed the initial and
greater part of the development of selective spinal
angiography. Djindjian et al. reported their first
50 cases of transarterial embolization in 1973 (1). Di
Chiro and Doppman described their own techniques
and experiences in spinal angiography. Aminoff and
Logue contributed to an early understanding of the
pathophysiology of spinal vascular malformations (2)
and established the clinical grading system (3). Later,
Kendall and Logue recognized the dural arteriove-
nous fistula (dAVF) as a different entity from arterio-
venous shunts involving the spinal cord (4). These are
uncommon and complex pathologies, and the termi-
nology has changed over the years. We will define the
terminology of lesions and describe clinical mani-
festation, imaging findings, and management of each
lesion; all are best treated by multidisciplinary
approach.
CLASSIFICATION
Nomenclature for spinal vascular malformations has
caused confusion and controversy among clinicians,
and multiple classification systems have been pro-
posed until today (57). In 1978, Hurth et al. reported
the first large series (8), which presented a summary
of 150 cases divided into two groups: extramedullary
malformations fed by the posterior spinal artery and
intramedullary malformations fed by the anterior spi-
nal artery. Their classification was aimed at a surgical
approach focusing on the position of lesions relative to
the spinal cord, rather than the type of shunts. As
noted before, dAVFs were recognized as a distinctly
different pathology from other spinal vascular mal-
formations only in 1977 (4). Their classification likely
included most of the dAVFs in the group of extra-
medullary malformations. In 1985, Riche et al. pre-
sented their classification, close to the modern
understanding of these lesions (9), and distinguished
five different types of vascular malformations: (1)
intramedullary or mixed arteriovenous malformation
(IM-AVM), (2) retromedullary AVM, (3) extramedul-
lary arteriovenous fistula (AVF) supplied by the spi-
nal arteries, (4) extramedullary dAVF with medullary
venous drainage, and (5) complex malformations (dis-
seminated and metameric AVM). Since then, many
authors have suggested modified or new classifica-
tions, and there has been drastic advancement in
diagnostic modalities and our knowledge of spinal
vascular malformations. However, the classification
proposed by Riche et al. still retains the basic concept
of spinal vascular malformations with the exception of
retromedullary AVMs, which are simply included
with IM-AVM in the present classification.
Most authors categorize pathologies on the basis
of angioarchitecture and location of lesions. Table 1
summarizes classification of spinal vascular malforma-
tions. Most spinal vascular malformations can be div-
ided into two different types of shunts: AVFs or AVMs.
Locations of the lesions are categorized as: (1) (intra-
dural) intramedullary, (2) (intradural) perimedullary,
(3) dural, and (4) extradural (epidural and paraspinal).
A combination of morphological/hemodynamic and
topographic information, usually provided by angiog-
raphy, is used to classify these lesions. Differentiation
of AVF and AVM can be difficult at times, and inter-
pretation of angiographic images is not free from
subjective judgment. Spinal vascular malformations
are also a mixture of congenital and acquired lesions,
etiology still needs to be elucidated and the information
will be incorporated in a future classification. For now,
a simplified classification with less controversy may
ease communication between clinicians from different
specialties.
Certain genetic or hereditary syndromes/disor-
ders are known to be associated with spinal vascular
malformations. Rodesch et al. proposed the classifica-
tion of intradural spinal vascular malformations based
on genetics or biological features (7). They primarily
distinguish AVFs and AVMs, and secondarily divide
them into three categories. The first group consists of
single shunts associated with genetic or hereditary dis-
orders, mainly hereditary hemorrhagic telangiectasia
(HHT) or Rendu-Osler-Weber disease. These are usually
single-hole macro-AVFs and affect the pediatric
364 Oka and Murphy
Table 1 Classification of Spinal Vascular Malformations
Location Type
Dural AVF
Perimedullary AVF
Intramedullary AVM
Extradural AVF, AVM
Abbreviations: AVF, arteriovenous fistula; AVM, arteriovenous malformation; ASA, Anterior Spinal Artery; PSA, Posterior Spinal Artery.
population (10). The second group comprises genetic,
nonhereditary, multiple AV shunts with potential meta-
meric links. These include Cobbs syndrome, Klippel-
Trenaunay syndrome, and Parkes Weber syndrome (or
Klippel-Trenaunay-Weber syndrome). The third group
is made of single lesions consisting of a majority of
spinal vascular malformations, while the first two
groups comprise 16% of spinal cord AVMs in a series
of 19 patients at one authors institution (11). These are
categorized as complex lesions in the classification by
other authors (12,13) and as such require careful inves-
tigation of the entire pathology and determination of the
lesion responsible for clinical symptoms. The aim of
treatment should be symptomatic relief rather than
complete cure in most cases.
CLINICAL
Spinal vascular malformations are uncommon lesions.
Mourier et al. studied 210 patients treated for an AVM
of the spinal cord. The patients were classified into
dAVF (38%), IM-AVMs (45%), and perimedullary
AVFs (PM-AVFs) (17%) (14). In a series of 186 spinal
vascular malformations by Biondi et al., dAVF,
IM-AVM, and PM-AVF comprised 38%, 24%, and
39%, respectively (15). These authors suggest that
distribution of their cases was largely influenced by
a referral base and the nature of their institution being
a tertiary care center. Most reports suggest a much
higher rate of dAVFs, ranging from 60% to 80% of
spinal vascular malformations (4).
There are two main forms of presentations of
spinal vascular malformations: one is progressive
myelopathy of gradual onset and the other is sudden
onset of neurological deficit or worsening of existing
symptoms, usually secondary to hemorrhage (16). The
less common form is an acute deterioration without
hemorrhage, which is thought to be due to thrombosis
of the draining vein of the lesion itself (8).
Intradural spinal arteriovenous shunts (AVMs
and AVFs) have a high rate of hemorrhage reported
in the literature, ranging from 30% to 50% (8,1618).
Hemorrhages occur as a spinal subarachnoid hemor-
rhage (SAH) or hematomyelia. Direct destruction of
neural tissue by hematoma (hematomyelia) accounts
for more severe clinical signs than those secondary to
SAH. Symptoms of SAH depend on the level of rup-
ture; however, acute onset of pain, stabbing back
pain, is universal with or without myelopathy or
radiculopathy. When the lesion is closer to the cranio-
cervical junction, signs and symptoms resemble those
of intracranial SAH and cause a special diagnostic
Feeder Drainage
Radiculomeningeal Radicular vein
ASA and/or PSA Perimedullary vein
ASA and/or PSA Medullary or perimedullary vein
Commonly segmental Epidural and/or paraspinal
dilemma. Angiography negative for intracranial
aneurysms when examining a patient with SAH
needs further investigation for cervical spinal vascular
malformation. It should be noted that, in a series
related to spinal vascular malformations, of 150
patients 55% occurred in children less than 15 years
of age (8). This result is concordant with the findings
observed by Rodesch et al., in which 70% of the
pediatric population in their series of intradural spinal
vascular malformations (excluding dAVFs) mani-
fested hemorrhagic episodes (19). In contrast to intra-
dural AV shunts, dAVFs are not typically associated
with spinal SAH or hematomyelia (2022). The excep-
tion to this rule being cervical dAVF (23,24). These are
more typically present with complications related to
venous hypertension and impaired cord venous
drainage.
Besides spinal SAH and hematomyelia, symp-
toms of spinal vascular malformations are those of
nonspecific myelopathy or radiculopathy. Combina-
tion of paraparesis, sensory abnormalities, sphincter
disturbances, and pain, which is often radicular in
distribution, develops with highly variable speeds of
progression. Stepwise progression, with incomplete
recovery of symptoms between events, is common
(8) and not directly correlated with the level of shunts.
Progressive, slow deterioration of neurological status
is a classic feature of spinal vascular malformations,
often attributed to chronic venous hypertension, and
eventually results in ischemic hypoxia of the spinal
cord. Intermittent, transient worsening of symptoms
have been documented with exercise, cough, or cer-
tain postures (16,22,25). Pregnancy is attributed to
causing aggravation of the disease in a minority of
cases (8,15).
In 1974, Aminoff and Logue reported a series of
60 patients with spinal vascular malformations in
which dural and intradural AV shunts were all
mixed, as it was before dAVF was differentiated
from others (3,16). Ten percent of patients presented
with SAH. Severe locomotor disability occurred in
19% of patients within six months of onset and in
50% within three years. Only 9% of their patients
were able to walk independently after three years.
Some authors established a clinical grading system of
the three major symptoms associated with spinal vas-
cular malformations: problems with gait, micturition,
and defecation (3). Gait disturbances were graded as:
(1) onset of leg weakness, abnormal stance or gait,
without restriction of locomotor activity; (2) dimin-
ished exercise tolerance; (3) requirement for one stick
or some support for walking; (4) requirement for
crutches or two sticks for walking; and (5) unable to
 Chapter 21: Endovascular Treatment of Spinal Vascular Malformations 365

stand, confined to bed or wheelchair. Disturbances of evaluation of myelopathy, radiculopathy, or spinal

micturition have been classified as mildhesitancy,
urgency or frequency; moderateoccasional urinary
incontinence or retention; and severetotal urinary
incontinence or persistent retention. Disordered con-
trol of defecation has been similarly classified as
mildconstipation; moderateoccasional fecal
incontinence or severe intractable constipation;
severefecal incontinence.
Delay in diagnosis is a particular problem of
spinal vascular malformations, especially for those
who present with nonspecific, slowly progressive
radiculopathy or myelopathy, or diabetes. The dura-
tion from onset of symptoms to initial treatment
averaged 2.7 years with dAVFs and 4.2 years with
intradural AVMs in the series by Rosenblum et al.
(18). The time from first symptoms to diagnosis was
less than 1 year in 26%, 1 to 10 years in 60%, and more
than 10 years in 14%. Others reported similar results.
IMAGING
Early reports indicated that myelography demonstrates
high rate of positive findings in patients with spinal
vascular malformations. Hurth reported typical vascu-
lar filling defects (Fig. 1A) in 61%; nonspecific, abnormal
findings (complete or partial obstruction of contrast
column, or an enlarged cord) in 30%; and normal
myelogram in only 9% of their series (8). In a series of
dAVFs, dilated vessels were present in all 25 patients on
supine myelogram (26). However, magnetic resonance
imaging (MRI) has become the modality of choice in
SAH, since it can demonstrate other more common
pathologies such as disc herniation, spinal stenosis,
vertebral lesion, intra- or extramedullary neoplasm,
and discitis/osteomyelitis. It can still be difficult to
differentiate infectious or inflammatory myelitis or
intramedullary mass (neoplasm or hematoma) from
myelopathy caused by vascular malformations when
not associated with significant flow voids.
Even though MRI and magnetic resonance
angiography (MRA) often suggest and make a diag-
nosis of spinal vascular malformations, spinal angiog-
raphy is essential when lesions are being considered
for treatment. Selective spinal angiography should
focus on several points with future therapy in mind
when performed: (1) First to differentiate dAVFs from
intradural AV shunts, (2) to determine the exact level
of shunt (by vertebral levels for surgical option), (3)
identify all feeders and relationship with the radicu-
lomedullary artery (or radiculopial artery) that is not
directly feeding the fistulacontinuity of spinal artery
axis, and (4) presence of aneurysm and venous varix,
and their relationship with symptoms (compression,
rupture, etc.). Each level needs to be selected, and
angiographers must be attentive to vascular blush in
the hemivertebra, which implies that the dorsal spinal
branch has been injected (Fig. 2A, B). The ventral and
dorsal spinal branches can have separate origins from
the aorta, especially when there is a common trunk for
multiple levels (27). When the angiogram is negative
after intercostal and lumbar artery injections, verte-
bral, deep cervical, ascending cervical, and internal
iliac arteriogram should be performed.

Figure 1 PM-AVF, type I. A 28-year-old male presented with left lower extremity weakness. MRI of the thoracolumbar spine showed
central hyperintensity of the cord on T2-weighted images and central enhancement on postgadolinium images (not shown). Myelogram
(A) shows serpentine filling defect consistent with prominent draining vein at the lower thoracic levels. Left T11 intercostal artery injection
(B) reveals the mildly prominent radiculomedullary artery and the anterior spinal artery. The arterial basket, connection between the
anterior spinal artery and the posterior spinal artery, is outlined (long arrow). A fistula (arrow head ) is noted immediately distal to the
basket, a draining vein is seen faintly on this image. Lateral projection (C) of same injection shows the anterior spinal artery (small arrows)
and the fistula (large arrow). Later image (D) shows the artery (arrow) and draining veins (double arrow) posterior to the spinal cord.
Abbreviations: PM-AVF, perimedullary arteriovenous fistula; MRI, magnetic resonance imaging.
366 Oka and Murphy

Figure 2 Left T9 intercostal artery injection demon-

strated a normal dorsospinal artery with blush in the left
hemivertebra.

SPINAL dAVFs retrograde venous flow into the valveless coronal

Terms for dAVF include epidural angiomatous mal-
formations (4), dorsal extramedullary AVM, type I,
and intradural dorsal AVF (5). These are the most
common types of spinal vascular malformation (28).
Pathophysiology
The dAVFs are shunts between the dural branch (rad-
iculomeningeal artery) of the dorsospinal artery and
radicular vein (Fig. 3), which normally drains the peri-
medullary vein. The fistula is located within the dural
sleeve of the exiting spinal nerve root. The fistula drains
into the perimedullary venous system via radicular
veins in a retrograde fashion. The pathophysiology of
neurological symptoms is attributed to chronic venous
hypertension caused by retrograde flow in the perime-
dullary vein, which normally drains the cord via the
coronal venous plexus (2,4). Slow but high-pressure
venous plexus limits venous drainage of the spinal
cord by the normal radial veins and results in a
decreased arteriovenous gradient, eventually leading
to congestive cord ischemia, which may or may not be
reversible. The result of these pathological changes is
irreversible necrotizing myelopathyfirst described by
Foix and Alajouanine (29) also called angiodysgenetic
myelomalacia or subacute necrotic myelitis, where the
neural tissue may liquefy and produce a cavity (32).
Spinal dAVF is an acquired disease, although the
etiology is still unknown (30). Infection, trauma, syrin-
gomyelia, and surgery have been mentioned as an
association or cause in the form of case reports (28,31).
Venous thrombosis is the leading pathogenesis of
cranial dAVFs (32) and is also considered to be a
potential cause of spinal dAVFs. However, there was
no association between multiple prothrombotic factors
and spinal dAVFs, comparing 40 patients with dAVF
and 119 control patients (33).

Figure 3 Spinal dAVF. A 39-year-old male with paraplegia. Sagittal proton density MRI (A) shows flow voids along the posterior aspect
of the thoracic cord. Early arterial phase of right T5 intercostal arteriogram (B) shows a shunt (small arrow) between the radiculome-
ningeal branch of the dorsospinal artery and the radicular vein (large arrow). Later image shows a shunt (arrow) and venous drainage into
the perimedullary vein in both cranial and caudal directions (long arrows) (C, D). Abbreviations: dAVF, dural arteriovenous fistula; MRI,
magnetic resonance imaging.
 Chapter 21: Endovascular Treatment of Spinal Vascular Malformations
Clinical Manifestations
Spinal dAVFs commonly affect middle-aged to elderly
males with 45:1 male to female ratio. Most patients
are in their fourth to seventh decades. Patients usually
present with gradually progressive myelopathy,
which affects lower extremity and sphincter functions.
Common initial symptoms are pain (1639%), lower
extremity weakness (2955%), and sensory distur-
bance (2447%). Sphincter dysfunction was seen in
about 10% of patients. Symptoms can progress slowly
and continuously, or in stepwise fashion. Most patients
have a combination of motor, sensory, and sphincter
symptoms by the time diagnosis is made, paraparesis
in 78% to 100%, sensory disturbance in 69% to 90%,
urinary incontinence in 80% to 89%, disturbed defeca-
tion in more than 80%, and disturbed sexual function in
about a third of patients, though this symptom is often
concealed by patients (2022,34,35). Pain is a common
but nonspecific symptom that manifests as a backache
or radicular pain. This pain is often attributed to
degenerative lumbar diseases or polyradiculopathy
before dAVFs are suspected. Sensory disturbances
start with tingling paresthesia or hyperesthesia in the
feet and progress to proximal level. Flaccid and spastic
paraparesis are equally common (20). Hemorrhage
is uncommon and SAH is seen almost exclusively
with cervical dAVFs; only one lumbar dAVF with
SAH (36) and one hematomyelia in thoracic dAVF to
date (37).
Delay in making a diagnosis of dAVF is common,
ranging from months to often several years with a
median length of 10.5 to 27 months, because of the
nonspecific and insidious nature of symptoms
(20,21,26). Van Dijk in his report suggested that recent
advances in diagnostic imaging, mainly MRI and MRA,
and wide availability of the scanner may have short-
ened the delay in diagnosis of dAVFs. In their series,
30 out of 49 patients (61%) presented with dAVFs.
Imaging
MRI should be the first imaging modality performed
when any spinal vascular malformation is suspected.
Although myelogram can demonstrate enlarged veins
in most dAVFs (26), the myelogram must be obtained
in a supine position since most of the veins are located
dorsal to the spinal cord. This maneuver may not be
done unless the diagnosis is already suspected. MRI
findings commonly seen in patients with dAVFs,
listed in order of frequency, are (1) central hyper-
intensity of the cord on T2-weighted images (85
100%), (2) mild gadolinium enhancement, and (3)
vascular flow voids posterior to the spinal cord and
mild expansion of the cord (Fig. 4) (26,38,39). Central
hyperintensity on T2-weighted images reach the tip of
conus in a majority of cases (26). Peripheral hypoin-
tensity surrounding central hyperintensity has been
described by Hurst et al., which is more conspicuous
on true T2-weighted or gradient-echo images but
subtle on Fast Spin Echo (FSE) T2-weighted images.
The authors hypothesize that the finding is due to
slow flow of blood containing deoxyhemoglobin
367
within distended veins (40). One must be familiar
with the normal MR appearance of the spine, it can
be difficult to differentiate an abnormally dilated
coronal venous plexus from prominent but normal
veins on todays high-field MRI. Cerebral spinal fluid
pulsation artifact should not be mistaken as abnormal
flow voids. With recent advances in MRA techniques,
first-pass contrast-enhanced MRA is reported to iden-
tify the level of fistula within  one level with a
relatively high rate of accuracy ranging from 75% to
100% (38,41,42). Also, ever advancing multidetector
row CT angiography has demonstrated precise local-
ization of dAVFs in all eight patients (43).
Conventional catheter spinal angiography, how-
ever, is indispensable for choosing treatment options
and is still the gold standard to evaluate the vascular
pathology of the spine. The above mentioned non-
invasive imaging techniques may play a role in reduc-
ing the length of catheter angiography, thus decreasing
contrast load and radiation dose, especially in those
with renal insufficiency and severe atherosclerotic dis-
ease (38). Because of particular demographics of
patients affected by this disease, there are few false-
negative angiograms mainly because of occlusion of
the origin of feeding intercostals or lumbar arteries,
severe atherosclerosis, or aortic aneurysm (44).
Arterial feeders are commonly located in the
midthoracic to upper lumbar level with more than
80% seen between T5 and L2, and two-thirds on the
left (2022). In one series, sacral dAVF was common
(18%) (45). In case of negative spinal angiography,
after selective intercostal and lumbar artery injections,
a selective lateral sacral artery injection should be
performed. Multiple feeders to the fistula are seen in
as low as 10% to as high as 60% (20,22,45). Multiple
dAVFs are an uncommon entity with a few case
reports of double dAVFs in the literature, and their
incidence is less than 2% of all spinal dAVFs (4648).
Cervical dAVFs
Cervical dAVFs are an uncommon subgroup of
dAVFsapproximately 2.5% of all spinal dAVFs
(36) (Fig. 5). Although they have the same morphol-
ogy and pathophysiology as thoracolumbar dAVFs,
one needs to be aware of particular characteristics of
cervical dAVFs. In patients with myelopathy, motor
and sensory symptoms are not always localized in the
lower extremity. Hemiparesis or quadriparesis are as
common as paraparesis (23). Myelopathy at a cervical
level can also include brain stem signs such as cranial
neuropathy or dyspnea (49). The most important dif-
ference is that they have a much higher rate of SAH
when compared with their thoracolumbar counter-
part. Recent literature reviews reported a 30% to
45% incidence of SAH in cervical dAVFs (24,36). The
presence of a varix and superiorly directed venous
drainage were significantly associated with SAH. In a
review of 41 patients with cervical dAVFs, superiorly
directed drainage was seen in 60% (12 out of 20) of the
SAH group, which is much higher than 10% in the
non-SAH group, and reaching the cranium in 50% of
cases (10 of 20). Venous varix was noted in 35% and
368 Oka and Murphy

Figure 4 Spinal dAVF. A 34-year-old male with scoliosis presented with acute deterioration of bilateral lower extremity weakness and
urinary incontinence, which has been present over a year. His main complaint prior to this event was back pain. T2-weighted images of
the thoracolumbar spine (A, B) demonstrates flow voids dorsal to the cord and abnormal high signal in the spinal cord from T4 to the
conus. Contrast enhancement is noted in the lower thoracic cord (C). The T10 intercostal angiogram (D) shows a fistula between the
radiculomeningeal artery and the radicular vein (arrow). Later image (E) shows dilated perimedullary veins in both cranial and caudal
directions, down to the conus (arrow). Glue embolization with NBCA was performed (F). Glue penetrates the fistula (short arrow) and
occludes the proximal segment of the draining vein (large arrow). Control angiogram performed after embolization reveals residual fistula
fed by right T9 (G) and T11 (H) intercostal artery branches, contribution to the fistula from these feeders were not seen prior to
embolization of T10. Two feeders were embolized with glue subsequently and final angiogram showed no residual fistula. Abbreviations:
dAVF, dural arteriovenous fistula; NBCA, N-butyl 2-cyanoacrylate.

Figure 5 Cervical dAVF. An 84-year-old male presented with lower extremity weakness and an unsteady gait. Sagittal T2-weighted
image (A) demonstrated T2 hyperintensity in the central cord at mid- to lower thoracic region. Selective injections of all intercostal and
lumbar arteries were negative. Right vertebral artery injection (B, C) demonstrates small AVF fed by the lateral spinal artery or C1
radicular artery. Venous drainage is caudal and could be followed to midthoracic level (D), which corresponds to MRI findings.
Abbreviations: dAVF, dural arteriovenous fistula; AVF, arteriovenous fistula; MRI, magnetic resonance imaging.
 Chapter 21: Endovascular Treatment of Spinal Vascular Malformations
5% of the SAH and non-SAH group, respectively (24).
Authors also noted high prevalence of feeders from
the right vertebral artery (68%). Venous drainage is
via the coronal venous plexus, epidural or intracra-
nial. Purely epidural venous drainage is associated
with myelopathy due to mass effect, rather than
venous congestion as seen in most dAVFs (50).
Treatment
Spinal dAVF is an infrequent but potentially treatable
cause of myelopathy. As all the other spinal vascular
malformations, dAVF is best managed by a multi-
disciplinary team of neurologists, neurosurgeons, and
interventional neuroradiologists. Interruption of the
feeding artery only is not sufficient to eliminate the
fistula and often results in recurrenceas in cranial
dAVFs, the fistula recruits nearby arteries or else
existing microfeeders grow. Resection of draining
veins, which was once thought to be the pathology
of dAVFs by means of stripping dilated coronal
venous plexus, can cause a devastating outcome. It
is now known that treatment should focus on the
fistula and disconnecting the vein from the AVF.
Meta-analysis of surgical studies demonstrated
97.9% technically successful results, 55% overall
improvement, and 33% rate of improvement in mic-
turition function (51). The same authors analyzed
results of embolization and found a 46% technical
success rate; however, there was not enough data on
the outcome of the embolization series. Generally,
approximately one-half to two-thirds of patients
report improvement in motor function, one-tenth of
patients experience worsening, and the remainder
become stable. Function of the sphincter does not
recover as much as motor strength; improvement is
seen in one-third, stability of symptoms in one-third,
and continuous deterioration in one-third (52).
Jellema et al. noted that leg pain and muscle
spasms were difficult symptoms to alleviate. In their
series of 44 patients, the majority of patients who had
either pain or spasms experienced worsening of the
symptoms despite improvement in motor function (52).
369
Others noted correlation between the level of fistula
and the outcome. Better results were seen when the
lesion was in the lower thoracic region compared with
those in the midthoracic or lumbar levels (35). Shorter
duration of symptoms, less than a year, prior to treat-
ment appears to correlate with better outcome, espe-
cially with sphincter dysfunction (53).
The optimal treatment for spinal dAVFs is contro-
versial, especially with ever advancing endovascular
techniques. Many authors have addressed the impor-
tance of a multidisciplinary approach (20,21,52,53).
They have advocated an initial attempt of endovascu-
lar therapy when possible, reserving surgery for ana-
tomically unfavorable lesionsusually implied as the
segmental artery that harbors both the feeder of dAVF
and the artery of Adamkiewicz (Fig. 6A, B). Surgery
can be performed immediately after embolization, as
it does not interfere with any surgical technique, if
embolization fails or a complex network of dural
collaterals appears as a result of embolization. Those
authors reported no differences in outcomes among
those who were treated by surgery, embolization, or
combination of both.
Endovascular Technique
Those who perform endovascular treatments for spi-
nal dAVF should know that surgery for these lesions
is relatively straightforward with high success rates
and low complication rates (51) (Fig. 7A, B). If the
fistula does not have optimal anatomy for emboliza-
tion, or when technical difficulty is encountered dur-
ing the procedure, the patient should be referred for
surgery. Case selection is the key for successful endo-
vascular treatment for dAVFs. Embolization is contra-
indicated if the artery of Adamkiewicz, a major
contributor to the anterior spinal artery, arises from
the same dorsospinal artery as a feeding artery of
dAVF. This contraindication occurs in approximately
10% of patients (45,54). We consider visualization of
the radiculopial artery (a contribution to the posterior
spinal artery) also as contraindication to embolization.
Niimi et al. reported 87% technical success in 33 of
Figure 6 Spinal dAVF. A 59-year-old male
presented with progressive lower extremity
weakness. Selective left T6 intercostal artery
injection shows a plexiform network of ves-
sels at fistula (small arrow) and prominent
perimedullary vein (double small arrows). A
radiculomedullary artery arises from the same
level (long arrow). Abbreviation: dAVF, dural
arteriovenous fistula. Source: Courtesy of
Philippe Gailloud, Division of Interventional
Neuroradiology, Johns Hopkins University
(unpublished material).
370 Oka and Murphy

38 cases since the introduction of the variable stiffness
microcatheter, and noted that three out of five patients
who had inadequate embolization had a spinal cord
artery arising from the same pedicle as the feeder,
which prevented more aggressive embolization (45).
Figure 7 Spinal dAVF. A 58-year-old male presented with pro-
gressive lower extremity weakness, which worsened to complete
paraplegia in last 10 days with no sensation below T6. Sagittal
T2-weighted MRI (A) demonstrates prominent flow voids poste-
rior to the thoracic cord with abnormal high signal in the cord,
which extends down to the conus (not shown). (B) Spinal angio-
gram demonstrates arteriovenous shunt (arrow) at T6 level, fed
by T6 intercostal artery, which shares a common trunk with T5
and T7. The patient underwent surgery three days after the
angiogram. His strength improved to three-fifth in both lower
extremities, and improvement in pinprick and bilateral vibration
were observed. However, he still needs self-catheterization at
four months follow-up. Abbreviations: dAVF, dural arteriovenous
fistula; MRI, magnetic resonance imaging.
Navigation of the microcatheter through often
near-normal sized, but invariably tortuous feeder,
can be difficult and stability of the guiding catheter
can play a significant role in wire-catheter navigation.
There are many guiding catheters of different shapes
and variable stiffness suited for intercostals and
lumbar arteries. We perform all endovascular spinal
intervention under general anesthesia. The ability to
suspend respiration at the crucial moment gives a
more accurate delivery of embolic material.
The goal of embolization is to have the embolic
material reaching the proximal portion of the draining
vein through the fistula (Fig. 8). Proximal occlusion
of the feeding artery may temporarily improve symp-
toms by reducing arterial flow through the fistula, but
will not be a cure. Angiographers need to recognize
the proximal occlusion; failure to do so is the most
common cause of recurrence after embolization, since
postembolization angiogram shows obliteration of
dAVF in either case. In case of definite proximal
occlusion, surgery should be considered soon after
embolization. If there is any doubt of glue staying
proximal to the vein, short-term follow-up angiogra-
phy should be performed.
N-Butyl 2-cyanoacrylate (NBCA) is the choice of
embolization material today. Use of coils or particles
(mostly polyvinyl alcohol) is not acceptable because
of the well-documented high recurrence rate (55,56).
A mixture of NBCA and ethiodol (often 1:2) is
injected slowly through the microcatheter that is
optimally positioned in the feeding artery as close
to the fistula as possible. Speed of injection and ratio
of NBCA to ethiodol varies case by case and requires
operator experience. When there is some distance
between the microcatheter tip and the shunt, the D5
push technique can be useful. D5 solution infused
through the guiding catheter facilitates the advance-
ment of glue.

Figure 8 Spinal dAVF. A 73-year-old female presented with acute onset of paraplegia and numbness for 12 hours. (A) Right T6
intercostal artery injection shows a radiculomeningeal artery travels down to T7 level and forms a shunt (small arrow) with drainage into
the radicular vein (long arrow). (B) Later image shows prominent perimedullary vein in caudal direction. (C) The microcatheter injection of
the dorsospinal artery depict more clear images of the feeder (small arrow), the shunt (short arrow), and perimedullary vein (long arrow).
(D) Glue cast (33% NBCA) follows the course of dAVF, it outlines the feeder, shunt, and proximal portion of vein. (E) Postembolization T6
intercostal angiogram shows no residual. At three months follow-up, she was able to walk with a walker. Abbreviations: dAVF, dural
arteriovenous fistula; NBCA, N-butyl 2-cyanoacrylate.
 Chapter 21: Endovascular Treatment of Spinal Vascular Malformations
Following embolization, it is important to docu-
ment: (1) obliteration of dAVFs by injection of seg-
mental artery at several levels above and below the
treated level (Fig. 4G, H) and (2) patency of the artery
of Adamkiewicz and venous drainage of normal spi-
nal cord. The overpenetration of glue reaching beyond
the proximal draining vein can be more problematic
than the proximal occlusion of feeding artery, since it
can worsen the venous hypertension, the results of
which may be cord infarct or hemorrhage. In fact,
venous thrombosis should be considered first if the
patients symptoms deteriorate after embolization. In
those cases, intravenous heparin should be immedi-
ately started with a bolus and maintained for 24 to
48 hours with possible conversion to anticoagulation.
Recurrence of dAVFs can occur by collateralization or
recanalization of embolized vessels. The latter is an
infrequent phenomenon when NBCA is used as an
embolic agent.
With the use of modern devices and NBCA,
initial technical success, i.e. adequate embolization,
can be obtained in close to 90% in selected cases.
However, even in experienced hands, 15% to 20% of
dAVFs can recur following an initially successful
embolization.
PERIMEDULLARY ARTERIOVENOUS FISTULAS
First described by Djindjian et al. as intradural extra-
medullary spinal AVMs in 1977, PM-AVFs are also
called type IV spinal cord AVM (57), intradural ven-
tral AVF (5), intradural direct AVF (18), and spinal
cord AVF (7). Fundamentally, PM-AVFs are abnormal
direct connections between the spinal arteries and
medullary veins without nidus; the fistula is on, not
within, the spinal cord, as the name describes (57).
Classification
Riche et al. distinguished three types of PM-AVFs (9).
Type I fistulas are slow-flow, simple, single-hole fis-
tulas fed by a single feeder, usually the anterior spinal
artery, that is slightly enlarged and often flows a long
distance before ending in a small shunt (Fig. 1). It is
drained by a single mildly enlarged vein, often along
the posterior aspect of the cord. Type II fistulas are
more voluminous and are often fed by more than
one spinal artery (Fig. 9). One main feeder, usually
the anterior spinal artery, can be identified along with
multiple smaller posterior spinal arteries. Type III
fistulas are often referred as giant perimedullary fis-
tulas (Fig. 10). They are rapid and very high-flow
giant fistulas with multiple enlarged feeders. Venous
drainage is markedly dilated, ecstatic, and often
appears dysplastic, and a large venous aneurysm or
pouch is a characteristic finding at the level of shunt.
This subdivision of PM-AVF (type I, II, and III) is
applied in other classifications; the most commonly
used subclassification is type IV spinal cord AVM
(IVa, IVb, and IVc, respectively).
Type III fistulas are mostly seen in children (58)
and have a high association with HHT or Rendu-Osler-
371
Weber syndrome (19). An association with Cobb syn-
drome has also been reported (58,59). These syndromes
of vascular malformations are known to begin in early
fetal life (35 weeks). Rodesch et al. divided PM-AVF
into two subtypes: micro-AVF (mAVF) and macro-AVF
(MAVF), the latter corresponds to type III PM-AVF (7).
In their series, five of six MAVF in children were
associated with HHT, while there was no HHT associ-
ation with mAVF. Authors suggested that presence of
type III AVF in children should prompt a search for
HHT, and patients as well as family members should
undergo screening for pulmonary AVF, which is the
main cause of disability secondary to CNS disorder
ischemia due to right to left shunt, stroke, and abscess.
PM-AVF and Hemorrhagic Telangiectasia
HHT is an autosomal dominant mucocutaneous and
visceral vascular dysplasia with prevalence of 1 to 10
for every 100,000 cases. Diagnosis is made when at
least three clinical criteria are met: epitaxis, telangiec-
tasia, visceral vascular malformations, and an affected
first-degree relative. Two mutations of endoglin
(ENG) on chromosome 9 and of activin-like receptor
kinase (ALK1) on chromosome 12 have been identified
and represent two subtypes of HHT, i.e. HHT 1 and
HHT 2, respectively (60). A higher incidence of pul-
monary AVM (40%) with HHT 1, versus 3% for HHT
2, distinguishes the two types. Telangiectasias of
mucous membranes and skin causes epistaxis and
gastrointestinal symptoms, which are the most com-
mon presentations of the disease. Pulmonary AVM is
perhaps the most important abnormality to detect
because of the relatively high incidence (1020%) of
serious consequences involving the brain (stroke,
abscess). Ten to twenty percent have cerebral AVMs,
which are commonly described as mAVM (nidus less
than 10 mm) or small AVM (13 cm). Spinal cord
vascular malformations are seen in 8% of HHT with
neurological manifestations (61). Treatment of PM-
AVF in patients with HHT will be the same for
those without HHT; however, the presence of other
visceral organ AVMs and right to left shunt may differ
treatment priority and perioperative management,
including general anesthesia and anticoagulation.
Clinical
A large series of spinal AVMs reported various inci-
dences of PM AVM ranging from 13.5% (11 out of 81)
to as high as 34% (27 out of 80) (6,14,18) of all spinal
AVMs. This variability in many series can be explained
largely by different referral patterns. In one series,
dAVFs comprised only 10% of all spinal AVMs because
dAVFs were treated by physicians in smaller centers. In
a series of 157 intradural spinal AVMs without includ-
ing dAVFs, 32 patients were found to have PM-AVFs
(20%) (19).
Patients are younger than those affected by
dAVFs, most present in their second to fourth deca-
des. About two-thirds are younger than 25 years and
one-third less than 15 years (19). Many patients have
months to years of radiculomedullary symptoms,
372 Oka and Murphy

Figure 9 PM-AVF, type II. A 31-year-old male presented with progressive urinary and bowel incontinence, erectile dysfunction, and
spastic paraplegia over several months. Sagittal T2-weighted images (A, B) show expansion and extensive signal abnormality involving
the high- to midthoracic cord and prominent flow voids. Right T5 intercostal artery injection (C) shows a moderate-flow fistula fed by the
posterior spinal artery with reflux into the intrinsic veins. There is no apparent nidus. Later image (D) shows prominent draining veins,
venous drainage through the radicular vein is also noted (arrow). Selective injection of the right T7 intercostal artery (E) demonstrates
the fistula fed by a small feeder. Glue embolization of the right T5 intercostal artery (F) followed by embolization of the T7 was performed.
The patient has shown slow improvement in strength and experiences no more incontinence; however, no change is noted with erectile
dysfunction. Abbreviation: PM-AVF, perimedullary arteriovenous fistula. Source: Courtesy of Philippe Gailloud, Division of Interventional
Neuroradiology, Johns Hopkins University (unpublished material).

which are progressive with or without episodes of
acute deterioration. If untreated, complete spinal tran-
section develops in seven to nine years (62). As in
spinal dAVFs, venous ischemia due to venous con-
gestion is likely the main cause of progressive symp-
toms in type I and some type II patients, and venous
thrombosis may play a role in nonhemorrhagic epi-
sodic deterioration. Symptoms seen in some type II
and III patients are multifactorial, i.e. not only venous
hypertension but steal phenomenon and direct com-
pression are also responsible for development of
disease. A large varix at the level of shunt in type III
patients causes direct compression of the spinal cord
or nerve roots, which may explain asymmetric
distribution of signs and symptoms in some patients
(59). Approximately one-third of patients present with
spinal SAH (18,59,62). Hemorrhage likely occurs on
the venous side of malformationsvenous drainage is
commonly seen in the posterior aspect of the cord and
posterior spinal veins are located exclusively in the
subarachnoid space. On the other hand, hematomyelia
is likely a result of rupture of the anterior spinal vein,
which is subpial in location (17). A much higher
incidence of hemorrhage (SAH or hematomyelia) has
been observed in pediatric populations. In one series,
70% of patients under 15 years of age presented with
some type of hemorrhage (19), they also tend to pres-
ent with acute symptoms rather than progressive
 Chapter 21: Endovascular Treatment of Spinal Vascular Malformations 373

Figure 10 PM-AVF, type III. A 23-year-old female with known PM-AVF developed acute deterioration of spastic paraplegia with new
bladder and bowel incontinence. At age 18, the diagnosis was made by angiogram (A, B) after an episode of spinal SAH. The treatment
was offered but declined. T12 intercostals artery injection (A) shows a large anterior spinal artery supplying a high-flow fistula (arrow) and
a large venous aneurysm (double arrow). Later image (B) shows opacification of contiguous venous pouches. At the time of treatment,
the venous pouch appears more dysplastic (C). Also noted was an interval development of posterior spinal artery contribution to the
fistula (arrow). (D) A detachable coil was placed first at the site of fistula (arrow), and postcoil angiogram shows a reduction of flow
through the fistula. Glue embolization (E) was performed (90% NBCA) through the coil (large arrow), glue (small arrow) stays at the fistula
without escaping into the venous side. Postembolization angiogram of T12 (F) shows almost complete obliteration, the posterior spinal
artery is visualized. T9 intercostal artery injection (G) demonstrates contiguity of the anterior spinal artery. Abbreviations: PM-AVF,
perimedullary arteriovenous fistula; SAH, subarachnoid hemorrhage; NBCA, N-butyl 2-cyanoacrylate. Source: Courtesy of Philippe
Gailloud, Division of Interventional Neuroradiology, Johns Hopkins University (unpublished material).

symptoms of chronic nature. Delay in diagnosis is
unfortunately very common, more than 20 years of
delay has been reported (14,62).
Imaging
Type II and III lesions are easily detected as prominent
serpentine filling defects on myelography or perime-
dullary flow voids, often accompanied by signal
abnormality within the cord on MRI (Fig. 9A, B). In
type III lesions, integrity and architecture of the spinal
cord can be very difficult to assess because of the large
size of venous outflow and resulting distortion of the
cord (Fig. 11). Though early reports questioned the
ability of MRI to diagnose type I lesions (14,59), recent
case series suggested that MRI with MRA is a reliable
modality, particularly because myelotomography is
not available anymore (63). Contrast administration
increases the visualization of perimedullary vessels
and demonstrates intramedullary enhancement at the
level of signal abnormality.
For all three types of PM-AVFs, only selective
spinal angiography can provide the information nec-
essary to achieve the subclassification of a lesion and
to choose its treatment. The number and size of
feeders and the size and location of the fistula dictate
treatment. Oblique or lateral views are often neces-
sary. The feeders arise from various levels; however,
the fistula itself is commonly located at the level of
conus medullaris ranging from 64% to 75% in
reported series, followed by filum terminale (64).
Type III lesions can be seen in the cervical region.
Some lesions, mostly type II lesions, may be
mistaken as IM-AVM on angiography because of a
pseudonidus appearance caused by reflux of
venous flow into the intrinsic network of congested
veins immediately distal to the shunt (19).
374 Oka and Murphy
Treatment
Subclassification of PM-AVF does not hold significant
implications for clinical symptoms or treatment out-
comes, rather indicates therapeutic approaches. The
size of fistula and the size and number of feeders
included in classification are critical information, as
well as the location of the fistula relative to the spinal
cord. Emergent intervention is not necessary in most
of hemorrhagic cases as a high rate of spontaneous
recovery is reported (72% by Rodesch et al.) (17).
Most authors agree that surgery should be con-
sidered first in type I lesions because of the small size
of the feeder and long distance to the shunt. Trans-
arterial embolization has been attempted in a small
number of patients, with reported success, when a
lesion was located anterior to the conus medullaris or
spinal cord (63,65). It is reasonable to try an endovas-
cular approach first, in selected patients, as long as
operators recognize proximal occlusion, which results
in the same angiographic appearance as true obliter-
ation of the shunt. Those with proximal occlusion
need to undergo surgical resection without a long
interval to avoid growth of more complex, recanalized
fistula fed by collaterals.
For type II lesions, some think that embolization is
rarely effective because of multiple feeders and fistulas.
Some feeders are transmedullary branches, and catheter-
ization of those branches may not be technically possible
and may not be safe. Surgery is indicated in most
posterolateral AVFs, and embolization can be performed
in conjunction with surgery in anterior lesions. Resection
or clipping of PM-AVF that is interposed, often hidden
deep behind markedly enlarged veins, is technically
difficult (14). Although surgery may be the treatment
of choice in type II PM-AVFs, reports on the surgical
outcome of these lesions remain scarce.
Type III lesions have multiple large feeders and
giant venous ectasia, which represent high operative
risk. Thus, embolization is the first line of treatment.
Successful obliteration of giant PM-AVF has been
reported with a detachable balloon (14,58); however,
the balloon is not currently available in the U.S.
market. Acrylic glue (NBCA) should be used
Figure 11 PM-AVF, type III (same patient as
in Fig. 10). Sagittal T2-weighted images of
the lumbar spine (A, B) at the time of presen-
tation demonstrate prominent tortuous flow
voids around the distal spinal cord. There is
a large flow void suggesting a venous aneur-
ysm. The cord is distorted by dilated vessels,
and it is difficult to evaluate the cord paren-
chyma (C). Abbreviation: PM-AVF, perime-
dullary arteriovenous fistula.
whenever transarterial access to the shunt is achiev-
able. In a series of 22 patients with type III PM-AVF,
15 patients, whose angiogram showed complete dis-
appearance of the lesion at the time of embolization,
had recovered completely (14).
Endovascular Techniques
Embolization is performed under general anesthesia.
Ability to control respiration and any patients motion is
critical when visualization of fine vasculature is critical.
The patient is given 5000 units of heparin at the begin-
ning and the dose is adjusted to maintain Activated
Clotting Time (ACT) above 250 seconds. Usually, an
hourly bolus of 1000 second is effective. A nonglide
guiding catheter is placed at the origin of the feeding
artery. A 6-Fr system is used whenever possible to
acquire a better road map during navigation of the
microcatheter as well as to add stability to the system.
A braided microcatheter enables us to use either coils or
liquid adhesive. Some newer small-diameter microcath-
eters (e.g., Echelon 10, Micro Therapeutics Inc., Irvine,
California, U.S.) have a large inner diameter equipped
for detachable coil placement, but still come with an
advantage of small outer diameter that makes naviga-
tion easier and allows contrast injection through a 5-Fr
guiding catheter. It is imperative to reach the site of the
fistula, as proximal closure of the feeder results in
development of a more complex, inaccessible lesion.
Embolization should be performed with liquid adhe-
sive (NBCA mixed with iodized oil). For a type II lesion
with medium-flow, primary glue embolization is per-
formed with various concentrations of NBCA (Fig. 9F).
For very high-flow type III lesions, a glue injection
following placement of coils at the site of fistula pre-
vents glue migration through a high-flow shunt into
the venous side. Placement of coils also assures accu-
rate deposition of fast glue (Fig. 10D, E). Coil placement
at the fistula may not be possible when the feeder
continuously enlarges as it gets closer to the fistula, in
those cases, few coil loops can be positioned in the
proximal venous pouch. Communication with the
anesthesiologist is important during the procedure,
especially, immediately before injection of liquid
 Chapter 21: Endovascular Treatment of Spinal Vascular Malformations
adhesive. The anesthesiologist must know the nature of
glue embolization and that any patient motion can
cause disaster or failure of embolization. Since liquid
adhesive is a permanent agent, and failure of emboli-
zation usually means losing an access to the lesion in
the best scenario.
Some advocate a provocative test before emboli-
zation, including a balloon occlusion test of spinal
arteries and injection of barbiturate or lidocaine. We
do not use neurophysiological monitoring or provoca-
tive tests, rather detailed analysis of a pre-embolization
microcatheter angiogram provides crucial and ade-
quate information to decide where to deposit and
when to stop injecting glue.
Transient worsening of symptoms after interven-
tion is common but most return to baseline (59).
Worsening of symptoms can occur during the imme-
diate postembolization period or in the subacute
phase (46 weeks) after embolization. The former is
likely a result of progressive retrograde thrombosis of
the draining vein of fistula and veins of adjacent cord
parenchyma due to sudden hemodynamic changes. The
latter is secondary to mass effect and inflammatory
changes of thrombosis of a large venous pouch, which
peaks weeks after thrombosis happens. For the imme-
diate postoperative period, especially in high-flow fis-
tula, patients will be kept on intravenous heparization
for 24 to 48 hours to keep the normal draining vein
patent. A thrombosis can also occur on the arterial side
(57). When a large varix is obliterated, intravenous
375
steroid is used during the hospitalization, which likely
reduces the inflammatory effects of acute thrombus. A
tapering dose of oral steroid may be added in selective
cases. For patients who develop symptoms in the sub-
acute phase, again a steroid is often used to reduce
edema and inflammatory changes associated with
thrombus formation.
INTRAMEDULLARY ARTERIOVENOUS
MALFORMATION
IM-AVM is also called type II malformation, glomus
AVM, and angioma arteriovenosum. It consists of
feeding arteries, nidus, and draining veins, as in cere-
bral AVM. The nidus of AVM can be compact, called
glomus type (Fig. 12), or more diffuse in appearance
involving a longer segment, called juvenile type
(Fig. 13). Differentiation of the two types, although it
is widely used, is very loosely defined in the litera-
tures. Though it was a classification based on angio-
graphic findings, it has been used for surgical lesions
that lack a clear plane between the nidus and normal
cord. In our opinion, the juvenile type should be used
specifically to describe IM-AVM with involvement of
neighboring nonneural structures, such as dura, bone,
muscle, subcutaneous tissue, or skin, to avoid confu-
sion, although initial descriptions of the juvenile type
suggests this finding as common and not essential
(18). In a new modified classification by Spetzler, the
Figure 12 IM-AVM. A 38-year-old female
presented with progressive right lower extrem-
ity weakness associated with right-sided hip
and back pain over a year. Right T9 intercostal
artery injection (A) shows the anterior spinal
artery (small arrows) supplying the intramedul-
lary nidus (long arrow) at the T10T11 level.
Later image (B) shows early venous drainage
through the perimedullary veins (double
arrows) in both cranial and caudal directions.
Lateral projection of same artery shows the
anterior spinal artery and fistula in early phase
(C) and drainage veins ventral to the cord in
cranial direction (large arrows) and dorsal to the
cord in caudal direction(small arrows) in late
phase (D). Right T11 intercostal artery injection
(E) reveals small contribution from the posterior
spinal artery. There appears to be a small
component of AVF from the right L2 lumbar
artery (F). Abbreviations: IM-AVM, intramedul-
lary arteriovenous malformations; AVF, arterio-
venous fistula.
376 Oka and Murphy

Figure 13 A 14-year-old male with port wine stain in midline back over upper thoracic level, severe headache, nuchal rigidity, and new
onset left upper extremity weakness with paraparesis. (A, B) Sagittal and axial T2-weighted images demonstrate flow voids throughout
cord and in adjacent soft tissue and bony structures (including T1 vertebral body on sagittal images). (C, D) Left vertebral artery injection
demonstrated intramedullary spinal cord AVM with ASA supply originating from intradural vertebral artery. (E) Injection of left
T4 intercostal artery shows soft tissue component as well as supply to intramedullary component of AVM, feeding artery aneurysm on
pedicle. (F) Selective injection of intramedullary pedicle followed by glue embolization. (G) Plain film demonstrating radiopaque glue in
pedicle and nidus. (H) Postembolizationno filling of inferior intramedullary supply or aneurysm. (I) Injection of adjacent intercostals fills
soft tissue AVM component. Abbreviation: AVM, arteriovenous malformation.
 Chapter 21: Endovascular Treatment of Spinal Vascular Malformations
juvenile type is called extradural-intradural AVM (5).
Other names applied to this type are metameric
angiomatosis (66) and type III malformation (67). In
this section, this subgroup of IM-AVM is described
under metameric angiomatosis.
Clinical Manifestations
Although IM-AVM is uncommon, it is two to three
times more common than PM-AVFs (14,15). Patients
usually present in the second and third decade of life.
There is slight male predominance in many series. In
a series of 90 patients with intradural AVM/AVFs,
57% were male (8). In the series by Rodesch et al., 57%
of 155 patients with intradural AVM/AVFs were
male but no significant gender difference was seen
in the adult population (17). Approximately, one-half
to two-thirds of patients experience hemorrhage
(SAH and/or hematomyelia) by the time diagnosis
is made (15,17,68). Hemorrhage leads to acute onset
of neurological deficits in two-thirds, the rest only
have back pain (characteristic severe spinal pain with
or without root pain) without deficits (69). Recurrent
SAH is seen in 18% to 30% (15,17). Rodesch et al.
found a significantly higher risk of hemorrhage in
cervical lesions (65%) compared with thoracolumbar
lesions (40%) (17), concordant with other observa-
tions (8), although their series does not differentiate
IM-AVM from PM-AVF. Other symptoms include
back pain, motor deficits, sensory disturbance, blad-
der and bowel incontinence, and impotence. These
symptoms usually develop in a slow progressive
fashion. In the Hurth et al. series, approximately
40% of patients with untreated or partially treated
intradural AVM/AVFs had acceptable neurological
conditions after 15 years, the number is somewhat
better in cervical lesions (8).
Imaging
Diagnosis of IM-AVM is easily made by MRI. It
demonstrates intramedullary nidus and dilated drain-
ing veins along the spinal cord. It provides important
information of associated abnormalities such as SAH,
myelomalacia, gliosis, cord edema, venous ectasia,
and aneurysm.
IM-AVM distributes uniformly along the longi-
tudinal axis of the spinal cord without thoracolumbar
predominance, unlike dAVFs. IM-AVM has a nidus
fed by anterior spinal (radiculomedullary) or posterior
spinal (radiculopial) arteries. It may be supplied
directly by spinal arteries or their branches, such as
sulcocommissural arteries and pial branches. Multiple
arterial feeders are often present (Fig. 14A, B), which
can be extensive, especially in the cervical IM-AVM
due to the presence of an embryological connection of
vertebral, ascending cervical, deep cervical arteries,
and external carotid artery branches. Venous drainage
can be ventral or dorsal to the cord and cranial or
caudal in the longitudinal course. IM-AVM nidus can
be confined to the cord parenchyma, or on the pial
surface, or both. Intraoperatively, most AVMs have a
377
Figure 14 IM-AVM. A 19-year-old female presented with mild
left lower extremity weakness and numbness in abdomen and left
thigh. Right T9 angiogram (A) shows the right posterior spinal
artery feeding a nidus at T8 level. Left T8 injection (B) shows the
anterior spinal artery supply to the nidus. Embolization was
performed via right T9 feeder using glue. Abbreviation: IM-AVM,
intramedullary arteriovenous malformation.
varying degree of extramedullary/subpial component
that is accessible to surgeons (68).
Biondi et al. reported a 20% (14 out of 70) inci-
dence of aneurysm in IM-AVMs (Fig. 13D) (15). Ear-
lier reports presented a much lower frequency of
spinal aneurysm; however, this is due to mixing of
all vascular malformations, including dAVFs and PM-
AVFs, into one group. Many reports also misinter-
preted the venous pouch in PM-AVFs as an aneurysm.
There were no aneurysms associated with dAVFs
(44 patients) or PM-AVFs (72 patients) in his series.
SAH was present in 100% of patients with IM-AVMs
and associated spinal aneurysm; of those 43% of cases
had recurrent SAH. In patients with IM-AVMs and no
spinal aneurysms on the angiogram, SAH was present
in 70% (39 out of 56) with recurrent SAH in 13 patients
(15). Following embolization of IM-AVM without
obliteration of aneurysm, size of 8 out of 11 aneurysms
followed the size of an AVM, suggesting that flow
change is an important factor in the formation and
growth of aneurysms (70). It is important to carefully
study the angioarchitecture of IM-AVM, especially in
the early arterial phase, to differentiate an aneurysm
from a venous pouch. These aneurysms are thought to
be flow-related aneurysms as a result of hemody-
namic changes, though underlying dysplasia or
abnormalities of local vessels are likely to contribute
to aneurysm formation since an aneurysm is rarely
seen in high-flow PM-AVF. Pseudoaneurysms related
to rupture or dysplastic change in or near a nidus can
be seen; however, it can be difficult to differentiate the
true aneurysm from the pseudoaneurysm, and the
Biondi et al. article did not differentiate two abnor-
malities. In the series of intradural AVM/AVFs by
Rodesch et al., true arterial aneurysms were seen in 49
out of 155 patients (31.6%) and pseudoaneurysms in
378 Oka and Murphy
26 patients (17%). Interestingly, there was no increased
risk of hemorrhage in patients with true aneurysms.
Pseudoaneurysms were associated with hemorrhage in
all cases (17).
Metameric Angiomatosis
Metameric angiomatosis are complex vascular abnor-
malities involving the spinal cord in various fashions,
extending into or separately affecting the vertebrae,
muscle, subcutaneous tissue, and skin along the der-
matome. Juvenile AVM, also referred to as type III
vascular malformation, and complex spinal cord AVM
are diffuse lesions that do not respect tissue bounda-
ries and are typically seen in young patients. Well-
known associated syndromes are Cobb syndrome,
Klippel-Trenaunay syndrome, and Parkes Weber syn-
drome. Cobb syndrome is characterized by intradural
AVM/AVFs and is associated with vertebral, cutane-
ous, or paraspinal lesions in the same or adjacent
segment (Fig. 13B, C). A cutaneous angioma can be
small and subtle, but it is the hallmark of this syn-
drome (71). Klippel-Trenaunay syndrome manifests
with cutaneous angioma and limb venolymphatic
lesions without AV shunts (7275), whereas Parkes
Weber syndrome has limb lesions with high-flow
shunts (76,77). The limb lesions also follow the der-
matome distribution. Matsumaru et al. found 16% of
metameric vascular malformations in their series of
119 spinal cord AVMs (11). They include nine Cobb,
two Klippel-Trenaunay, and one Parkes Weber syn-
drome. There were seven cases of nonsyndromic asso-
ciation with bifocal intradural metameric lesions.
Incidence of metameric angiomatosis in patients
with intradural AVM/AVFs is 19% in the series of
Rosenblum et al., 38% in a series of thoracic IM-AVM
by Biondi et al., and 26% in the Hurth et al. series
(excluding HHT).
Obviously, these are extremely rare lesions;
therefore, optimal specific treatment has not been
established. Prognosis is generally poor and a com-
plete cure of lesions should not be a goal of treatment
since it is likely associated with high morbidity, given
the complexity of the abnormalities. It should be
targeted to the lesion or site responsible for clinical
symptoms, and it may be the best to leave them alone
if patients are stable and not symptomatic.
Treatment
Because of the known progressive course and poor
prognosis, treatment is recommended to prevent the
onset or progression of symptoms. Clinically, patients
with a history of hemorrhage or progressive neuro-
logical deficits should be treated more aggressively to
prevent recurrent hemorrhage or progression of dis-
ease process. Treatment by any methods should aim at
obliteration of AVM; however, some lesions are not
curable by means of surgery or embolization. In these
scenarios, the goal of treatment can be tailored to
improve clinical symptoms or to target specific
angioarchitecture such as aneurysm.
Embolization has become the first line of treat-
ment in many centers, either as a primary treatment or
as a preoperative adjunct (66,78). A liquid adhesive,
NBCA, should be used as an embolic material, when-
ever feasible, especially when embolization is per-
formed as a sole treatment. In the largest series of
glue embolization of intradural AVM/AVFs by
Rodesch et al., which consisted of 114 patients exclud-
ing patients who only consulted, 69 patients (60%)
underwent embolization, 21 (18%) received surgery,
and 24 (21%) were considered untreatable. Among
69 patients, 68 lesions were treated with acrylic glue,
and a good clinical outcome was achieved (15%
asymptomatic, 43% improved, 25% unchanged) at
mean follow-up of 5.6 years. More than 50% reduction
in size of AVM/AVF was seen in 86% of cases.
Complications were transient deficits in 10 patients
and permanent deficits in 9 (13%)three of which
(4%) suffered a mild disabling deficit, whereas other
six deficits did not limit normal activity. All compli-
cations occurred during the embolization through the
anterior spinal artery. No recanalization was noted
(79). Even in one of the most experienced centers for
treatment of spinal vascular malformations, a rela-
tively large number of patients (21%) do not receive
any treatment. All treating physicians need to know
the limits of endovascular treatment. Arterial aneur-
ysms on feeders of IM-AVM should be treated, espe-
cially in patients with a history of hemorrhage. Even
partial treatment may be acceptable to eradicate the
aneurysm and reduce risk of future hemorrhage (80).
Preoperative embolization can be useful to facilitate
surgical resection of certain lesions (81,82).
Particle embolization was used prior to the days
of liquid adhesive. Biondi et al. followed 35 patients
with thoracic IM-AVM who underwent particle
embolization (69). Multiple embolizations were usu-
ally required because of recanalization, which range
from 1 to 17 sessions. Clinical outcome was generally
good despite a high recanalization rate of 80% at the
last angiographic follow-up. Clinical status was
unchanged in 54% of patients, improved in 26%, and
worsened in 20% as compared with status after the first
embolization.
Surgical resection of IM-AVM is a challenging
procedure for surgeons, and several different
approaches have been advocated (68,82,83). In the
series by Rosenblum et al, 43 out of 54 patients with
intradural AVM/AVF (43, IM-AVM; 11, PM-AVM)
underwent surgical resectionneurological status
improved in 33% of patients, worsened in 14%, and
was stable in 51%. An acceptable outcome is seen in
84%, though persistent AVM was detected in 13 out of
32 (41%) on available postoperative angiograms (18).
In another surgical series by Connolly consisting of
15 IM-AVMs, subjective improvement was noted in
80% of patients, objective neurological improvement
in 40%, stability in 53%, but worsening of symptoms
in only 1 patient. Recurrence was noted in 3 out of
13 patients who had follow-up angiography (68).
Radiosurgery may be an alternative treatment
for symptomatic lesions that are not amenable to
surgery or embolization (84,85).
 Chapter 21: Endovascular Treatment of Spinal Vascular Malformations 379

Figure 15 IM-AVM. An 83-year-old female with severe neck pain and quadriplegia. (A, B) Right vertebral artery injection shows PSA
feeding pedicle to Spinal Cord AVM originating from right C4 level. ASA originating from right intradural vertebral artery gave small
component of AVM supply. Note soft tissue AVM at right cervico-occipital level (drainage laterally into neck veins). (CF) Plain and
subtracted images of AP and lateral views of selective injection of feeding pedicle pre-embolization. (G) Lateral plain film after
embolization demonstrating glue in nidus of AVM. (H, I) Postembolization RVA injection, minimal component from ASA remaining.
Abbreviation: IM-AVM, intramedullary arteriovenous malformation; RVA, right vertebral artery.

Endovascular Techniques (Fig. 15), which usually means catheterization of the

We perform all IM-AVM embolization under general
anesthesia. The patient is fully heparinized, and ACT
is monitored during the procedure. A nonglide guid-
ing catheter will be placed at the origin of the feeding
artery. When an AVM is high flow, a flow-guided
microcatheter can be used; however, in many instan-
ces, a braided microcatheter with support from a
guidewire is needed to navigate through tortuous
spinal arteries. Whenever a posterior spinal axis,
including a radiculopial artery, is one of the promi-
nent feeders, it should be chosen first as a target since
embolization is safer with less risk of morbidity. The
posterior spinal artery supplies the posterolateral
aspect of the cord in radial fashion and multiple
circumferential and longitudinal anastomoses exist
between them. As described before, in patients with
a history of hemorrhage, a feeder with aneurysm
should be targeted first. When the anterior spinal
artery (radiculomedullary artery) needs to be embol-
ized, superselective catheterization in or near the
nidus beyond the longitudinal axis of the artery is
essential to keep any normal branch out of danger
sulcocommissural artery. Once the catheter tip is in
position, a superselective angiogram should be done
to confirm the absence of normal branches. Emboliza-
tion is performed with NBCA mixed with iodized oil,
and dilution of NBCA depends on the angioarchitec-
ture and flow of the lesion and location of the catheter
tip. We commonly use 30% to 50% of NBCA, unless
high-flow shunt is noted within the nidus, for which
higher concentration of NBCA is used.
After embolization, patients are monitored in the
neurocritical care unit for one day, then in the floor for
another day or two before discharge. IV hepariniza-
tion is continued for 24 hours in most of the patients to
prevent progressive thrombosis of normal veins.
EXTRADURAL ARTERIOVENOUS
MALFORMATION/FISTULAS
Extradural AVMs/AVFs are rare lesions that can
cause neurological symptoms. In this group, para-
spinal or paravertebral AVM/AVF and epidural
380 Oka and Murphy
AVF are included, most common form of which is
vertebral-vertebral AVF.
Clinical
Several case report and case series are available (8690),
and they provide clinical, angiographic, and treatment
information of 22 cases. One case was reported twice
and was excluded. Extradural AVMs/AVFs are com-
mon in pediatric patients; among 22 cases, 13 patients
were less than 17 years of age, including 6 infants.
However, there is no significant gender prediction
(10 male, 12 female). It appears to occur equally
throughout the spinal axis with seven cervical, ten
thoracic, one thoracolumbar, and four lumbar lesions.
Several forms of clinical presentations were reported
but progressive neurological deficits are the most com-
mon presentation. This deficit is caused by two mech-
anisms: the first is venous hypertension or congestion
secondary to venous reflux into the perimedullary vein
via epidural venous plexus, which is comparable to the
pathophysiology of dAVFs. The second is direct com-
pression of the spinal cord or spinal nerves by dilated
arterialized veins. Other symptoms include mass effect
on other organs, one infant presented with difficulty
swallowing secondary to compression of esophagus
(89), and another patient with Klippel-Trenaunay syn-
drome was found to have asymptomatic erosion of
cervical vertebrae caused by high-pressure venous
masses (90). High-flow shunts caused congestive
heart failure because of volume and pressure overload
in one neonate (89). Only one SAH has been reported,
angiogram of the patient showed high-flow shunt with
pseudoaneurysm on venous side (88). There are three
patients with metameric angiomatosis and two patients
with metameric angiomatosis and spinal vascular mal-
formation. One patient with neurofibromatosis pre-
sented with pain and CT finding of epidural mass
through neural foramen, which led to surgery with
assumption of the lesion being neurofibroma (87). This
lesion was later treated by endovascular method. The
association of neurofibromatosis and AVF has been
reported (91).
On the other hand, vertebral-vertebral AVF is
often asymptomatic and rarely cause neurological def-
icits. Most patients are found to have a bruit or expe-
rience tinnitus. The largest series of vertebral-vertebral
AVFs by Beaujeux et al. reported that out of 46 patients
of this condition, only 3 had neurological deficits,
whereas 21 had tinnitus (92). In their series, majority
were spontaneous (59%), whereas in other series 100%
cases were spontaneous (93). Trauma was thought to
be the cause in 41% of patients. In half of the cases
vertebral-vertebral AVFs are located in C1 to C2 levels,
and C5 is the other common location.
Imaging
MRI often provides useful information regarding geog-
raphy of lesion, presence of dilated perimedullary
veins, cord compression, and coexisting abnormality
(Fig. 16). In the series by Goyal et al., 3 of 10 patients
had increased signal within the cord on T2-weighted
images and prominent perimedullary vessels (87). Two
of them had paravertebral AVF with reflux into peri-
medullary veins on angiogram. The author empha-
sized importance of this finding, since simple
clipping of the radicular vein can alter venous flow
and eliminate symptoms.
Extradural AVM/AVF can be located in the epi-
dural space, bone, or adjacent soft tissue, therefore any
neighboring artery can become feeder (Fig. 17AD).
The spinal artery (including radiculomedullary and
radiculopial arteries) does not contribute to shunts.
Venous drainage involves epidural venous plexus at
some point, which is drained by paraspinal veins such
as azygos or hemiazygos veins or reflux into the
perimedullary veins (Fig. 16EH).
Treatment
Extradural AVF/AVM with neurological symptoms
should be treated if feasible. Because of variable
angioarchitecture and involved vessels, treatment
needs to be individualized depending on clinical
symptoms and pathophysiology. If venous congestive
myelopathy is caused by perimedullary venous reflux,
treating arterial side by endovascular approach will
not resolve spinal venous hypertension unless com-
plete obliteration of shunts is achieved. However,
alteration of venous drainage by clipping of radicular
vein will likely eliminate symptoms. The lesion can be
left alone unless systemic symptoms develop. When
symptoms are caused by large high-pressure veins in
the epidural space, lesions usually have very high
flow and feeders are multiple and dilated. Transarte-
rial embolization using liquid adhesives is useful with
high rate of success (88). One can use similar method
as treating type III PM-AVF. Placement of coil at the
shunt or proximal venous pouch can facilitate precise
deposition of liquid adhesive without its migration
to systemic veins (Fig. 16IH). When arterial route is
exhausted or there is single venous drainage with
multiple arterial feeders, transvenous route can be
used (87,90), coils in the epidural space do not appear
to cause symptomatic compression of spinal cord.
Vertebral-vertebral AVF is often neurologically
asymptomatic and indication of treatment should be
thought out as in benign intracranial dAVF. When a
high-flow single-hole fistula is found, often caused by
trauma, placement of detachable coils or balloon at the
shunt or proximal venous pouch is effective in closing
the shunt (Fig. 18). This procedure can be performed
via transarterial or transvenous route (94,95). If it
results in incomplete obliteration of the fistula, sacri-
fice of the vertebral artery must be considered. The
vertebral artery harboring the fistula needs to be
occluded distal and proximal to the fistula.
ISOLATED SPINAL ARTERY ANEURYSMS
Isolated spinal artery aneurysms without associated
AVM are exceedingly rare and few have been
reported (9699). Rengachary et al. reviewed literatures
 Chapter 21: Endovascular Treatment of Spinal Vascular Malformations 381

Figure 16 Paraspinal AVF. A 28-year-old male presented with progressive lower extremity weakness with vascular malformation
identified in the lumbar region on MRI (AD). Further workup prior to embolization showed asymptomatic pulmonary hypertension. Pelvic
angiogram (E, F) demonstrates high-flow fistula fed by anterior division of the internal iliac artery bilaterally with robust venous drainage
into the internal iliac veins. Left L1 angiogram (G) demonstrates a large lumbar artery feeding the AVM nidus lateral to the spinal canal.
Venous drainage is via the large epidural vein with radicular veins (H, arrows) seen at multiple levels. Nearly all intercostals and lumbar
arteries from T10 to L4 contribute to AVM or AVF. Following first embolization of a few prominent feeders, he was asymptomatic for a
year. Second embolization was done when he presented with sensory symptoms in the lower extremities. Left L2 lumbar angiogram
(I) shows a fast-flow AVM lateral to the spinal canal. Glue embolization was performed in oblique projection that best demonstrates the
proximal segment to prevent reflux (J). Unsubtracted image (K) shows the coil mass, glue cast from current and prior embolizations.
Abbreviations: AVF, arteriovenous fistula; MRI, magnetic resonance imaging; AVM, arteriovenous malformation. Source: Courtesy of
Philippe Gailloud, Division of Interventional Neuroradiology, Johns Hopkins University (unpublished material).

and found 57 spinal artery aneurysms (97) of which
association with spinal AVM was noted in 33 cases and
coarctation of aorta in 4 additional patients. Etiology of
spinal artery aneurysms in other 20 patients is thought
to be idiopathic in eight, congenital/vascular anomaly
in four, arteritis in two, association with syphilis,
fibromuscular dysplasia, and pseudoxanthoma elasti-
cum is seen in one patient each. No information regard-
ing etiology was available in three patients. Among
eight patients with idiopathic aneurysms, five presented
with SAH and two with large aneurysms (>20 mm in
diameter) with compressive symptoms. One pea size
aneurysm in cervical region presented with leg paralysis
without SAH. Recently, Massand et al. presented four
patients, all with SAH, and three of four were thought to
have dissecting aneurysms (98). Berlis et al. had three
patients with spinal artery aneurysms and associated
SAH. One was mycotic (Candida) and was treated with
antifungal medication, which resulted in occlusion of
aneurysm as well as parent spinal artery. Other two
were thought to have dissecting aneurysms (99). Both
authors postulated that dissection is likely the etiology
382 Oka and Murphy

Figure 17 Paraspinal AVF. An 11-year-old boy status

post chest wall lymphatic malformation resection at age
six and known vascular lesion in the spine suddenly
developed near complete paralysis and urinary and
bowel incontinence. Left suprascapular artery angio-
gram (A) shows the feeder of paraspinal AVF (approx-
imate midline location is indicated by an arrow pointing
an endotracheal tube). Late arterial phase (B) demon-
strates a large venous aneurysm (large arrow) at the
level of T5 and T6, which drains into the epidural vein
on the left (small arrow). Glue embolization was per-
formed with a microcatheter tip (C, arrow) just proximal
to two main feeding branches of the AVF using D5
solution push technique. Postembolization angiogram
via the left subclavian artery (D) shows no contribution
from the suprascapular artery. Faint opacification of the
feeder fed by small collaterals via the superior intercos-
tals artery. Glue cast is outlined by small arrows. He
underwent second embolization via the T6 intercostal
artery (not shown) and recovered completely. Abbrevia-
tion: AVF, arteriovenous fistula. Source: Courtesy of
Philippe Gailloud, Division of Interventional Neuroradiol-
ogy, Johns Hopkins University (unpublished material).

Figure 18 Vertebral-vertebral fistula. A 23-year-old male presented with proptosis of the right eye two months after a motor vehicle
accident. AP (A) and lateral (B) angiogram of the left vertebral artery show high-flow direct fistula between distal cervical segment of
vertebral artery and vertebral vein. Using transarterial approach, the fistula was embolized with detachable coils (C). Postembolization AP
(D) and lateral (E) angiogram show minimal flow through the coil mass, which continuously decreased over several minutes documented
on repeated angiograms. Also noted is a high-flow carotid cavernous fistula (type I) (not shown).
 Chapter 21: Endovascular Treatment of Spinal Vascular Malformations
in many of the idiopathic spinal artery aneurysms.
Location of aneurysms varies in the artery but usually
seen along the course of artery, thus fusiform shape is
more common. This difference from intracranial saccu-
lar aneurysms, which are typically seen at branching
point, makes treatment of spinal artery aneurysms more
challenging. Trapping or wrapping of diseased segment
have been performed with success since clipping and
coiling are associated with higher risk of parent artery
damage or occlusion (99,100). If dissection is indeed the
most common etiology, wait-and-see strategy with hope
for spontaneous healing might play a role when surgical
exploration is not an option or is associated with greater
risk than benefit.
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Percutaneous Vertebroplasty
Mary E. Jensen
Departments of Radiology and Neurosurgery,
University of Virginia Health Systems, Charlottesville, Virginia, U.S.A.
INTRODUCTION
Vertebral body augmentation encompasses a group
of minimally invasive therapies that fortify vertebral
body insufficiency fractures due to osteoporosis,
osteolytic conditions, or minor trauma. Percutaneous
vertebroplasty is the best-known augmentation pro-
cedure, with a proven track record of safety and
efficacy. A similar procedure called kyphoplasty,
also known as balloon-assisted vertebroplasty, has
recently gained popularity. Evolving techniques such
as lordoplasty and new devices such as deployable
grafting systems (OptiMesh, Spineology, St. Paul,
Minnesota, U.S.) and permanent structural implants
(StaXx Fracture Repair System, Spine Wave, Inc.,
Shelton, Connecticut, U.S.) are being promoted. The
fundamental goal of all these procedures is to provide
improved compressive strength to the vertebral body
and prevent its further collapse through the introduc-
tion of a stabilizing material. The major clinical benefit
of vertebral augmentation is pain relief, the mecha-
nism of which is unclear. Other clinical benefits such
as restoration of the vertebral body height and reduc-
tion of kyphotic angulation have been suggested,
although not proven.
Although early vertebroplasty reports focused
mainly on its use in the treatment of painful vertebral
hemangiomas and bony metastases, the majority of
the current literature addresses augmentation proce-
dures in osteoporotic crush fractures, since these
fractures respond particularly well. This chapter will
focus primarily on the clinical and technical aspects of
vertebroplasty in the treatment of osteoporotic and
malignant vertebral fractures.
THE BIOMECHANICS OF VERTEBRAL
BODY AUGMENTATION
The loss of substantive bone tissue from primary or
secondary osteoporosis, tumor erosion, or osteonec-
rosis may lead to vertebral collapse when the axial
load is more than the involved vertebral body can
withstand. Polymethylmethacrylate (PMMA), an
acrylic polymer noted for its excellent compressive
strength (but poor shear strength), has long been used
22
by spine surgeons for vertebral packing following
tumor debulking (13). During the PMMA prepara-
tion phase, liquid and powdered acrylic components
are mixed together to create a dough, which is then
used to fill the surgically created void. The material
cures in a matter of minutes to form dense cement.
The curing process is an exothermic reaction, thus
generating significant heat.
Extensive research on PMMA as a suitable mate-
rial for vertebroplasty has been published. Biome-
chanical testing of PMMA injected into osteoporotic
vertebral bodies demonstrates an increase in the force
by almost 200% to compress treated vertebrae when
compared with an untreated control group (4). Even
when altered by the addition of opacification agents or
antibiotic powders (5), or by changing the monomer to
polymer ratio (6), the compressive strength easily
surpasses that of an unadulterated osteoporotic ver-
tebral body. When vertebrae are compressed past the
point of initial failure, injected specimens are more
likely to resist continued deformation than native
vertebrae (7), thereby maintaining spinal axis align-
ment. When PMMA is applied directly to tumor tis-
sue, the acrylic causes necrosis at the PMMA/tumor
interface, probably from direct cytotoxic effects and
tissue coagulation caused by the exothermic polymer-
ization process (8).
Despite the extensive biomechanical research
that has been published, the mechanism of pain relief
associated with vertebroplasty remains unclear. Many
theories have been proposed. The mechanical, vascu-
lar, chemical, and/or thermal effects of PMMA may
cause destruction of nerve endings in adjacent sensi-
tive tissues or incite tumor necrosis. Stabilization of
microfractures and decreased mechanical stresses
applied to the affected vertebrae may also play a
role (9). However, if this vertebral strengthening effect
is the cause of the therapeutic response, one would
expect to find the degree of pain relief to be propor-
tional to the total amount of injected acrylic and the
extent of vertebral filling. To date, there has been no
correlation between pain relief and the volume of
PMMA used (9), and the physiological explanation
of the analgesic effect associated with vertebroplasty
remains obscure.
388 Jensen
HISTORY OF PERCUTANEOUS
VERTEBROPLASTY IN OSTEOPOROTIC
VERTEBRAL COMPRESSION FRACTURES
In 1987, Galibert et al. (10) described the percutaneous
application of acrylic polymer (PMMA) to vertebral
body defects associated with painful hemangiomas,
with resultant good control of pain. Other small series
followed with emphasis on the treatment of heman-
giomas or metastases (1113). In 1991, the first report
of vertebroplasty in the osteoporotic spine was pub-
lished. Debussche-Depriester (14) reported five
patients suffering from painful osteoporotic vertebral
compression fractures (VCFs), all of whom showed
complete, immediate relief of pain after vertebroplasty
with no or minimal residual discomfort.
Vertebroplasty was virtually unknown in North
America until the early 1990s; Dion and Jensen suc-
cessfully treated the first patient in the United States at
the University of Virginia in 1993. The first article
focusing on the technical aspects of vertebroplasty
was published in 1997 by the authors (15). In this
small clinical trial, 29 patients with 47 osteoporotic
VCFs, who had failed conservative medical therapy,
underwent vertebroplasty. Ninety percent of this
cohort experienced significant pain relief as evidenced
by patients verbal expression of perceived pain and
analgesic use. In 1998, Deramond et al. (16) reported
the results of vertebroplasty on 80 patients with
osteoporotic fractures, with rapid and complete relief
of pain in greater than 90% of cases. Follow-up of
1 month to 10 years showed prolonged analgesic
effect, and only a single complication was reported.
The first open prospective study was not published
until 1999 (17); no control group was used and the
follow-up period ended at six months. Since then,
several retrospective (18,19) and prospective non-
randomized studies (2022) have shown statistically
significant improvement in pain and function, partic-
ularly ambulation. These results have been confirmed
in a prospective study using a control group (23) and a
prospective randomized control study (24).
Vertebroplasty was enthusiastically accepted by
interventional radiologists and embraced by the
elderly population. On the basis of the positive out-
comes seen with vertebroplasty, kyphoplasty was
introduced in 2001 (25) as an alternative approach,
and rocketed to popularity, primarily in the surgical
community.
VERTEBROPLASTY IN OSTEOPOROTIC
COMPRESSION FRACTURES
In 1995, an estimated 700,000 vertebral fractures
occurred in elderly individuals as a sequela of osteo-
porosis (26). The lifetime risk of a clinically detected
VCF is 15.6% for white females and 5% for white
males (27). Clearly, osteoporosis of the spine and its
clinical consequences are important health care and
public health issues that deserve attention.
Osteoporotic VCFs most likely occur in postme-
nopausal Caucasian and Asian females. Although the
majority of fractures result from age-related bone loss,
underlying factors that may contribute to osteoporosis
include steroid therapy, early oophorectomy, hypogo-
nadism in males, hyperthyroidism, chronic obstruc-
tive pulmonary disease, immobility, anticonvulsant
use, smoking, and alcohol consumption. Twenty per-
cent of females and 40% of males presenting with
vertebral or hip fractures have one of these associated
conditions (28). Both low bone mass and a history of
previous fracture independently predict the risk of
subsequent fracture, with a sevenfold increased risk in
females with low bone mass and a 25-fold risk in
females with low bone mass and a single fracture (29).
A vertebral fracture may be defined as reduction
in vertebral height by 15% or greater, or classified by
degree and type of deformity (wedge, biconcavity, or
compression) (30). The most common locations for the
development of a compression fracture are the T8,
T12, L1, and L4 levels (31,32). The physiologic thoracic
kyphosis places the greatest axial load at T8, and the
thoracolumbar spinal junction is frequently affected
because of the change in mobility between the rela-
tively restricted thoracic spine and the more freely
moving lumbar vertebrae (31).
Although many fractures are asymptomatic,
clinically detected VCFs are associated with some
degree of pain in 84% of patients (33). Most fractures
occur spontaneously (59%) (31) or are associated with
trivial strain or exertion (32). Pain is often described as
intense and deep, localized to the level of the involved
vertebra, and exacerbated by palpation over the
affected site (32,33). Pain is often position dependent
with reduction or relief when supine, while weight
bearing or bending causes the most discomfort. In
some cases, pain may be referred to adjacent levels of
the vertebrae as far removed as four levels, or radiate
to the flank or along the ribs (32). Frank radicular pain
involving the legs is uncommon (32) and may be
caused by foraminal stenosis due to a retropulsed
bone fragment or severe vertebral collapse.
Pain associated with VCFs is usually self-limiting,
lasting from two weeks to three months. For this rea-
son, treatment of acute fractures has been largely con-
servative, with current medical therapy emphasizing
pain control using narcotic and/or anti-inflammatory
medications and strict bed rest (34). However,
extended bed rest and narcotic use in the elderly is
not without risk, and the decision to treat sooner rather
than later should be on the basis of the patients overall
medical condition, degree of infirmity, and rapidity of
improvement. Surgery is rarely indicated, and internal
fixation is reserved for patients with gross deformity,
instability, or neurological deficits (35).
Local application of heating pads and ice packs,
massage therapy, or trigger point injections may be
useful. Other treatments, such as back bracing, phys-
ical therapy, and exercise, are introduced once the
patient is capable of bearing weight. Patients should
be evaluated by their primary care physician, gerion-
tologist, or endocrinologist for initiation of preventive
medical therapy [bisphosphonates, calcitonin, or hor-
monal replacement therapy (HRT)] to prevent new
fractures.

Quality of life and functional status are severely
affected by vertebral osteoporosis. Elderly females
with symptomatic fractures demonstrate significant
performance impairments in physical, functional,
and psychosocial testing when compared with a con-
trol group with no fractures (36). A late consequence
of the disease is the development of progressive
kyphosis, which may lead to chronic pain and dis-
ability, decreased exercise tolerance, fear of falling,
early satiety, weight loss, and depression (33).
CONSEQUENCES OF CONSERVATIVE
THERAPY
Before vertebroplasty, VCFs were essentially the only
fracture not treated orthopedically. As noted above,
initial treatment usually is conservative, consisting lation two or more times with partial or no assistance)
of immobilization and narcotic analgesia. Although
conservative therapy implied safe, it is neither showed decline in activities of daily living, new
benign nor risk-free, and its complications are well
documented (3739).
Narcotic analgesia, commonly used in conjunc-
tion with bed rest in the treatment of acute and
chronic nonmalignant musculoskeletal pain (37,40),
may lead to adverse drug reactions (ADRs) in over
70% of individuals, with the elderly more likely to
suffer severe ADR such as confusion.
Immobilization encompasses enforced bed decreases in analgesic requirement when adminis-
rest, use of braces or corsets, and pain causing pro-
tective limitations of motion. During bed rest, virtu-
ally every organ system is adversely affected, and
these effects tend to be more pronounced in older
patients who have less reserve than younger ones.
Bone density declines approximately 2% per week
(37), with the most dramatic changes seen in the first
12 weeks of immobilization. Muscle strength declines
10% to 15% per week and the rate of recovery from
disuse is slower than the rate of loss (38). Decreased
endurance is seen with a sense of fatigue and reduced
patient motivation, setting up a vicious circle of
greater inactivity. Muscle and ligament complexes
are affected, resulting in muscular shortening and
contracture formation (38). There is abundant evi-
dence that early active mobilization after initial stabi-
lizationa benefit of both vertebroplasty and
kyphoplastyis the key to contracture prevention.
Early mobilization also leads to the prevention of
pressure sores, the prevalence of which tends to
increase significantly with age. Cardiovascular effects
include increased heart rate, shorter diastolic times,
and reduced coronary blood flow. Overall cardiac
output, stroke volume, and left ventricular function
decline as well as cerebral perfusion (38). Depending
on the length of bed rest, it may take 20 to 72 days to
restore pre-bed rest cardiac function.
The lungs suffer from decreased ciliary clear-
ance, less effective coughing, atelectasis, and a predi-
lection for pneumonia. Respiratory capacity decreases
by 25% to 50% from deconditioning of the respiratory
muscles and restrictive impairment (39). In one study
of patients immobilized by pelvic fracture, the inci-
dence of deep vein thrombosis (DVT) was 61%, with
Chapter 22: Percutaneous Vertebroplasty 389
proximal DVT occurring in 29%. Pulmonary embolism
is seen in 2% to 12% of patients and is fatal in 0.5% to
10% (41). Patients are at increased risk of genitourinary
calculus formation, incontinence, urinary tract infec-
tions, and urosepsis. Gastrointestinal effects include
reduced appetite, constipation, and fecal impaction,
all exacerbated by the administration of narcotics.
Even the central nervous system is not immune;
patients at bed rest exhibit higher levels of anxiety,
depression, insomnia, and pain intolerance (39).
In a recent prospective study of 498 hospitalized
patients (70 years or older), low mobility (defined as
bed rest or ability to transfer to chair) and intermedi-
ate mobility (defined as ambulation one to two times
with total assistance) were independent predictors of
several poor hospital outcomes at discharge (42).
When compared with high mobility (defined as ambu-
patients, the low and intermediate mobility patients
institutionalization, and death. The contribution of
low mobility to these outcomes remained statistically
significant in multivariate analyses even after control-
ling for age, sex, severity of illness, and comorbidities.
In a recent study of vertebroplasty in an affected in-
patient population (43), treatment facilitated a rapid
discharge as well as long-term improvement in refrac-
tory pain. In addition, vertebroplasty leads to greater
tered earlier in hospitalization.
In short, conservative treatment leads to adverse
outcomes associated with low mobility and bed
rest, which may be viewed as iatrogenic events lead-
ing to complications such as functional decline.
Restoring mobility quickly and minimizing narcotic
use should be major goals of compression fracture
therapy, and vertebral augmentation has proven
effective for both.
PATIENT SELECTION CRITERIA
The primary goal of vertebroplasty is to alleviate pain
and improve mobility; vertebral body stabilization for
prevention of further collapse is a secondary goal.
Treatment is directed toward affected patients who
have failed a reasonable course of medical therapy.
Selection criteria are outlined in detail in the American
College of Radiology (ACR) Standards Guidelines
for the Performance of Percutaneous Vertebroplasty
(44). All practitioners should be familiar with this
documents content. In short, appropriate candidates
include patients with painful VCF refractory to med-
ical therapy, with failure defined as no or minimal
pain relief following the administration of prescrip-
tion analgesics for an unspecified time period; patients
who are unable to ambulate because of the pain;
painful VCF associated with osteonecrosis (Kummells
disease) (45); and unstable VCF that demonstrates
movement at the wedge deformity. Patients with mul-
tiple compression deformities, who are at risk for
pulmonary compromise, gastrointestinal dysfunction,
or altered center of gravity if further collapse occurs,
390 Jensen
are also specified in the ACR document, although no
data to support this position is available.
Absolute contraindications are few. Patients
with asymptomatic stable fractures or who are clearly
improving with conservative treatment are not candi-
dates. There is no evidence to support prophylactic
vertebroplasty in osteopenic patients with no acute
fracture. Systemic infection, osteomyelitis, uncorrect-
able coagulopathies, and allergic sensitivity to any of
the required components are other contraindicated
conditions. Although traumatic compression fracture
of nonosteoporotic vertebra is considered an absolute
contraindication in the ACR guidelines, a recent study
has shown a positive clinical outcome from vertebro-
plasty in patients suffering from thoracolumbar burst
fractures (46).
Relative contraindications are not defined and are
often operator specific. Patients with significant spinal
canal compromise from retropulsed fragments, verte-
bra plana, or chronic fractures may be candidates, but
relief is variable. Radicular pain or radiculopathy
involving the lower extremities is an infrequent finding
with VCFs, and an appropriate search for other com-
pressive pathology unrelated to the collapse should be
performed prior to vertebroplasty.
PATIENT SCREENING AND EVALUATION
A clinical coordinator, such as a nurse, nurse practi-
tioner, or experienced assistant, is invaluable for the
smooth operation of a busy vertebroplasty service.
The coordinator can collect pertinent information
such as a pain history, other relevant medical con-
ditions or previous surgeries, current analgesic use,
and radiological studies, prior to scheduling an
appointment. In many cases, non-candidates are dis-
covered early on and can be redirected. Requiring a
referral from an individuals primary care physician
also helps to eliminate inappropriate patients who are
self-referred. Potential candidates for treatment
should fulfill relevant clinical and radiological criteria,
and the information should be appropriately docu-
mented in the patients chart. Inevitably, the practi-
tioner will be faced with the previously treated patient
who experiences a new VCF and demands an imme-
diate vertebroplasty. Following the same screening
methods used for evaluation of the initial fracture
will ensure that the practitioner considers all potential
pathologic processes prior to performing a second
procedure.
History of Present Illness
A detailed history concentrating on the patients back
pain, mobility, relevant medication use (including
analgesics, steroids, bisphosphonates, calcitonin,
HRT), and general medical condition is obtained.
Presenting symptoms, indications for the procedure,
pertinent medical and surgical history, a list of all
current medications, history of allergies, and detailed
documentation of failed medical therapy are recorded.
Use of visual analog scales for determining pain level,
dermatome drawings for pain localization, or ques-
tionnaires are useful for collecting data.
Patients with atypical back pain should be eval-
uated for a concomitant disease process. Any condi-
tion that results in bacteremia, e.g., urinary tract
infection, may seed the spinal column resulting in
discitis or epidural abscess.
Neurological and Physical Examination
A focused physical and neurological examination to
identify painful vertebral levels and evaluate for pos-
sible radicular symptoms or neurological deficits is
mandatory. Sites of point tenderness to percussion or
palpation and positional trigger points are identi-
fied. In patients with multiple acute or subacute com-
pression fractures, the site of point tenderness often
correlates with the pain generator that should be
targeted at the initial treatment. A lack of preoperative
spinous process tenderness does not preclude clinical
success of vertebroplasty (47). Patients with diffuse or
nonfocal pain, low back pain that radiates to the hip
or iliac crest, or lumbar radiculopathy may have other
pathology such as facet or disc disease, which should
first be excluded. Evaluation of the patients ability to
lie prone without pulmonary compromise is recom-
mended, particularly in individuals with known
chronic obstructive pulmonary disease. A detailed
physical examination is indicated when significant
concurrent illnesses are suspected.
Radiological Evaluation
Osteoporotic postmenopausal females with a docu-
mented new or subacute fracture on conventional
radiographs and who meet the clinical criteria may
proceed to vertebroplasty without other imaging.
Occasionally, plain films will show intravertebral
gas-filled clefts indicating the presence of avascular
necrosis (45,48). Kyphotic movement at the fracture
site on flexion/extension films also may be associated
with a cleft (49). Bony sclerosis and osteophyte for-
mation are indicative of healed chronic fractures.
Adjunctive imaging is indicated in patients with
single or multiple fractures of uncertain age, when serial
conventional radiographs are unavailable or when a
marrow-replacement disease process, such as multiple
myeloma, is suspected. For all practical purposes, most
patients have had MRI as part of their diagnostic eval-
uation prior to referral. MRI and/or bone scan imaging
are very useful for identifying active fractures (50,51)
and predicting outcome (48,5255). Uncomplicated
VCFs typically exhibit decreased signal on T1-weighted
sequences (Fig. 1A) and increased or inhomogeneous
signal on T2-weighted sequences (Fig. 1B) (56). Edema
may involve the entire vertebral body or may be limited
to the area adjacent to an endplate. Fluid-filled clefts are
readily identified but their presence is underestimated
when compared to vertebroplasty findings, with only
50% of clefts seen on MRI (48). Subacute or chronic
painful fractures may demonstrate normal (fatty) mar-
row signal intensity on T1- and T2-weighted images.
 Chapter 22: Percutaneous Vertebroplasty 391

Figure 1 T1-weighted sagittal image (A) shows low

signal intensity involving the L3 vertebral body in addi-
tion to the inferior endplate of L5 and the superior
endplate of L2. The corresponding areas on the
T2-weighted image (B) show mild hyperintensity,
which is inhomogeneous. STIR sequence (C) clearly
identifies edema at all three levels. Abbreviation: STIR,
short-tau inversion recovery.

A limited MR study consisting of T1 (Fig. 1A) from retropulsed bone is not considered an absolute
and short-tau inversion recovery (STIR) (Fig. 1C) contraindication provided there is no cord or nerve
sagittal images may be the only study needed to root compression resulting in neurological symptoms
spot vertebral body edema. Although MRI is sensitive or dysfunction.
for the detection of acute compression fractures, the In ambiguous cases, fluoroscopic examination of
duration of vertebral body edema with respect to the painful sites may reveal an alternative explanation
the presence of pain is unknown. Three recent studies for back pain. Most common are patients with low
(5355) have correlated clinical outcomes with prepro- back pain radiating to the hip who demonstrate facet
cedural MR findings. Patients whose fractures showed hypertrophy and point tenderness over the joint.
extensive bone marrow edema were more likely to Diagnostic facet injection can be performed first as
exhibit a positive clinical response to vertebroplasty part of the screening process.
than those patients whose fractures did not display
edema. However, the lack of edema did not preclude
a positive response, and these individuals should not
be automatically ineligible for vertebroplasty.
Bone scans (Fig. 2) and MRIs are usually positive
in the first three to four months, but bone scintigraphy
has been shown to be more accurate than MRI in the
detection of older fractures (51). In patients suspected
of having active VCFs with no obvious acute fracture
on MRI, bone scintigraphy is often the next study
performed. In evaluating the use of scintigraphy in
preprocedural evaluation of patients being considered
for vertebroplasty, Maynard et al. (52) found that a
high percentage of patients (94%) achieved nearly
complete pain relief after treatment of those levels
that showed increased uptake of tracer, even in
patients with multiple fractures of uncertain age.
One pitfall of bone scanning is that activity in chronic
facet disease may be confused with activity in a par-
tially collapsed vertebral body on a routine scan
(Fig. 3). SPECT scanning can localize the tracer uptake
within the vertebral body as opposed to the adjacent
facet joints.
In patients with complex or severe fractures,
computed tomography (CT) prior to vertebroplasty
may be used to evaluate the integrity of the posterior
wall of the vertebral body, to locate fracture lines Figure 2 Anterior and posterior whole body bone scan show
involving the vertebral body and pedicles, to detect intense focal uptake of tracer at the L4 level consistent with a
intravertebral gas-filled clefts, and to assess posterior compression fracture.
displacement of fragments (Fig. 4). Canal compromise
392 Jensen
Figure 3 Anterior (A) and posterior (B) bone scan images show
increased tracer activity throughout the whole vertebral body at
L3, but focal uptake most notable overlying the posterior and
lateral aspects of the vertebral hemispheres at L4. This patient
was found to have a new compression fracture at L3 and signif-
icant degenerative joint disease at L4 and L5.
Preprocedure Preparation and Counseling
Vertebroplasty is usually performed on an outpatient
basis. Important preprocedure instructions should be
given at the time of the evaluation or the night prior to
the procedure. Patients are asked to receive nothing
by mouth after midnight and to avoid taking their
morning analgesics. Transdermal narcotic patches
need not be removed. A responsible adult must be
available to transport the patient home after comple-
tion of the observation period. Informed consent is
obtained in all cases. Risks cited should include infec-
tion, bleeding, fracture, extravasation of acrylic into
the surrounding epidural or paravertebral veins
resulting in worsening pain or paralysis, pulmonary
compromise, and death. The potential need for imme-
diate surgical intervention should be discussed, and
surgical backup at the time of the procedure must be
available.
Elderly patients often have chronic conditions
that require special consideration. When indicated,
preprocedure laboratory testing is done and often
includes tests for hemoglobin, hematocrit, electrolytes
and renal function, coagulation parameters, and com-
plete blood count with differential and sedimentation
rate.
On an outpatient basis, individuals taking Cou-
madin can be given enoxaparin (Lovenox) subcuta-
neously once or twice a day. Lovenox can be reversed
with protamine sulfate at the time of the procedure
and immediately reinstituted on its completion, fol-
lowed by resumption of Coumadin therapy. This
process eliminates the need for a lengthy hospitaliza-
tion but requires coordination with the patients pri-
mary care physician.
Vertebroplasty should be avoided in patients
with known infections, fevers, or elevated white
blood count (unless due to steroid use). Patients
with chronic obstructive pulmonary disease or asthma
may have difficulty in breathing when lying prone,
and anesthesia-managed conscious sedation may be
required. General anesthesia is usually not indicated,
except in the uncooperative or unstable patient.
TECHNICAL ASPECTS OF VERTEBROPLASTY
Different techniques have evolved on the basis of the
predominant European (16,57,58) and North American
(15,5961) experiences. Descriptions of the procedure
abound primarily in the radiology literature; variations
in technique are mostly minor and related to the
availability of the products and equipment utilized,
and the operators training and personal style. How-
ever, there is no substitute for hands-on experience,
and interested operators are strongly encouraged to
attend one of the many educational courses currently
available.
Figure 4 Coronal (A) and sagittal (B) reconstructions
of a lumbar CT showing an intraosseous air-filled cleft
with mild sclerosis along the inferior border. Note the
vertical fracture through the posterior third of the verte-
bral body with gas in the disc spaces and retropulsion
of the posterior fracture fragment into the spinal canal.
Abbreviation: CT, computed tomography.

Equipment Requirements and Operator Skills
Needle placement within the vertebral body has been
described using standard fluoroscopy (15,16,57), CT
guidance (58,62), or CT fluoroscopy (63). Regardless of
the modality used to position the needle, acrylic injec-
tion into the trabecular space is, in essence, a venous
embolization and should always be performed under
continuous fluoroscopic observation. Operators
should strive to use the highest quality fluoroscopy
available, with multiple levels of magnification and
small focal spot sizes. Use of a biplane digital angiog-
raphy unit is ideal; biplane monitoring of fluoroscopic
images decreases procedural time and enables orthog-
onal visualization of the acrylic injection. However, a
high-quality single-plane unit that can rapidly move
from the lateral to the anteroposterior (AP) positions
will suffice. Low-quality analog fluoroscopy portable
units are to be avoided as the image quality is usually
too poor for adequate visualization of bony landmarks
and acrylic flow.
In addition to a high-quality imaging chain, the
operator should possess appropriate cognitive and
technical skills to ensure quality and safety of the
study. These skills include but are not limited to
knowledge of the radiographic anatomy of the spine
and associated structures on both CT and fluoroscopy;
formal training in radiation physics, equipment, and
techniques to minimize exposure to self and patient;
skill in CT or fluoroscopic-guided biopsy procedures
of the spine, including radiographic triangulation; and
knowledge of proper embolization technique.
Patient Preparation and Monitoring
From start to finish, a dedicated nurse or other trained
professional, whose primary responsibility is to estab-
lish and maintain venous access, administer conscious
sedation, monitor the patients physiologic status, and
maintain the medical record, must be present. Partic-
ularly, patients with decreased respiratory excursion
when in the prone position are problematic because of
unsatisfactory oxygenation. Patients with respiratory
compromise may require supplemental oxygen or
anesthesia support. Performing the procedure in the
decubitus position or in a myelogram suite with the
table tilted and the patient semierect are other options.
Equipment and medications for emergency resuscita-
tion should always be immediately available.
Many patients are anxious about rolling into the
prone position, and intravenous administration of 25 to
50 mg of fentanyl (Sublimaze, Abbott Laboratories,
North Chicago, Illinois, U.S.) five minutes prior to
positioning is useful. The patient is placed prone on
the angiography table, and physiological monitors,
including EKG leads, pulse oximeter, and blood pres-
sure cuff, are attached, in addition to oxygen via nasal
cannula. Additional conscious sedation may be given
in the form of fentanyl and midazolam (Versed, Roche
Pharma, Manati, Puerto Rico, U.S.) in small increments.
To minimize infection risk, the procedure is
performed under strict sterile conditions. All person-
nel in the room don surgical caps and masks, and the
Chapter 22: Percutaneous Vertebroplasty 393
operators and their assistants wear sterile gowns and
gloves. The level to be treated is identified under
fluoroscopy and marked, and the overlying skin sur-
face is sterilely prepped and draped. If the drape
fenestration does not expose all levels to be treated,
sterile Tegaderm is applied over the area that will be
covered by the drape to keep it sterile. The image
intensifiers are covered with sterile bags, as they will
be in close position to the sterile filed devices as well
as vertebroplasty devices. Prophylactic antibiotic ther-
apy, either given intravenously and/or mixed with
the acrylic polymer, has been advocated (15,16,5961).
Pedicle Targeting
The pedicle to be punctured is isolated under AP
fluoroscopy. In the simple bulls-eye approach to
the pedicle, the fluoroscopic tube is either in a straight
AP position or obliqued slightly. In this approach, the
largest surface area of the pedicle is presented for
targeting and its entire cortical circumference is easily
seen. This approach is most likely to be used in the
upper and midthoracic vertebral bodies (Fig. 5) as the
pedicles jut posteriorly from the vertebral body at a 908
angle in the axial plane. The needle is advanced until
its tip is positioned in the midportion of the ipsilateral
vertebral hemisphere. If holovertebral filling is desired,
a contralateral puncture may be necessary.
Puncture of the pedicle using the more oblique
(*208 of ipsilateral angulation) scotty-dog view will
result in a steeper lateral-to-medial needle track with
the final needle position near the midline of the verte-
bral body (Fig. 6). From this location, it is more likely
that a single transpediculate injection will fill the
central portion of the vertebra between the pedicles,
minimizing the need for a contralateral puncture. This
approach is more technically challenging since the
pediculate cortex is not as well seen as it is in the
bulls-eye view, and the surface area is smaller, par-
ticularly in the thoracic spine. If the needle is positioned
too laterally, it may traverse the transverse process or
the thoracic cavity with subsequent fracture or pneu-
mothorax. However, the unipediculate approach results
in a shorter procedure time, diminished risk as only
one needle is placed, and better visualization during
injection since only a single injected bolus of acrylic is
observed (64).
With either approach, the puncture site should
avoid the medial and inferior borders of the pedicles.
Tracks in these locations can result in a breach of the
cortical wall and entry into the spinal canal or neural
foramen.
Once the angle of approach is determined, the
skin, subcutaneous soft tissues, and pediculate peri-
osteum are anesthetized with 7 to 10 cc of bupivacaine
hydrochloride (0.25%) (Abbott Laboratories), using a
2-inch, 25-G spinal needle. Prior to removing this
needle, AP and lateral fluoroscopy should show the
tip of the needle approximating the same location on
the pedicle in the superior-inferior plane. If there is a
discrepancy between the two and the patient is in the
true lateral position, then the AP tube needs to be
adjusted in either the cranial or caudal direction until
394 Jensen

Figure 5 The pedicle to be traversed is first

anesthetized using a 25-G spinal needle
(A, B). In this illustration, the anesthesia nee-
dle tip is slightly inferior, and the actual punc-
ture site will be made higher on the pedicle to
parallel the superior endplate fracture (C, D).
Note the difficulty in visualizing the inferior
aspect of the pedicles on the lateral view (D)
due to overlapping bony edges from the ribs,
and burnout from the lung fields. After verte-
broplasty (E, F), the PMMA is noted to fill a
cavity superior to the inferior endplate. Abbre-
viation: PMMA, polymethylmethacrylate.

Figure 6 In the scotty-dog approach, the

AP tube is obliqued approximately 208 (A).
The needle is advanced through the pedicle
(B) and is positioned in the midline (C), in the
anterior one-third of the vertebral body (D). In
this patient, a large cavity was filled within the
central portion of the L4 vertebral body (E, F).
A small amount of PMMA has decompressed
into the needle track (arrow) but remains
within the vertebra. Abbreviations: AP, ante-
rioposterior; PMMA, polymethylmethacrylate.

the needle tip approximates the same location on the
pedicle as on the lateral view. A small skin incision is
made with a number 11 scalpel blade to allow easy
passage of the vertebroplasty needle.
Positioning of the Needle
A variety of disposable vertebroplasty needles or
trocars are available for use, and there are no perfor-
mance comparison studies among the different prod-
ucts that might guide selection. These devices are
generally listed as bone biopsy needles and range dle in the midportion of the vertebral body and per-
in size from 11 to 13 G; injection of acrylic is difficult
through smaller gauge needles, although 15-G needles
have been used particularly in the cervical region.
Important features for consideration include the avail-
ability of different stylet tip shapes and cannula sizes
and lengths, radiolucency of the handle, locking of fill the entire vertebra at a single sitting and will place
the stylet within the cannula, and compatibility of the
cannula Luer lock hub with various injection devices
and methacrylates. Specialty needles are also available
with beveled cannulas to direct acrylic flow or with
curved tips to reach specific locations in the vertebral
body. (Fig. 16A, B).
The needle is advanced until the stylet tip abuts
the cortical surface in the superior to midpoint portion
of the pedicle. Depending on the shape of the pedicle,
the needle should enter at the widest point, away from
the medial and inferior borders. With hourglass-
shaped pedicles, the operator may need to choose
the extreme superior or inferior aspect for entrance.
The angle of approach on the lateral view is deter-
mined by the degree of endplate compression or
anterior wedging. Often the course of the needle will
parallel that of the superior endplate (Fig. 5D), in
which case the stylet tip position will begin more
superiorly on the pedicle. On the AP view, the needle
should traverse the pedicle and vertebral body from
lateral to medial (Fig. 5C); otherwise it may abut or
exit the lateral wall of the vertebral body.
The stylet tip of the needle should be positioned
precisely before a cortical break is made. Positioning is
best made with a diamond-point stylet, as beveled
stylets have a tendency to slip off the pedicle. Once the
track is started, repositioning becomes difficult as the
stylet has a tendency to slide into the initial divot. In
this situation, changing the angle of approach by
rotating the AP tube slightly may present a better
entrance point, or the contralateral pedicle can be used
instead. A slight back-and-forth twisting motion is
used to advance the tip through the cortex, with
frequent fluoroscopic checks in both the AP and lat-
eral planes as the needle traverses the pedicle. Alter-
natively, a small sterile orthopedic hammer can be
used to tap gently on the needle handle, advancing the
tip in small increments. Once within the trabecular
bone, less pressure is required to advance the needle
and care must be taken not to pierce the endplates or
vertebral wall. Use of the single-bevel stylet often will
deflect the needle tip in the direction opposite to the
bevel, allowing minor adjustments in either plane. The
needle is advanced using continuous or intermittent
Chapter 22: Percutaneous Vertebroplasty 395
lateral fluoroscopy until the stylet tip is placed in the
anterior one-third to one-quarter of the vertebral
body. The closer the tip is to the midline on the AP
view, the further anterior it may be positioned on the
lateral view. Because the stylet tip projects beyond the
end of the cannula, the final cannula tip position will
be slightly more posterior.
Placement of a Contralateral Needle
Many experienced practitioners position a single nee-
form only a single injection of acrylic, filling the
midportion of the body (Fig. 6C). If the initial needle
placement is within the lateral aspect of the hemi-
vertebra, the acrylic will more than likely remain in
the ipsilateral hemivertebra. Some operators prefer to
a second needle if the initial fill pattern is deemed
unsatisfactory or incomplete. Whether this procedure
is necessary for a good clinical result is a matter of
debate. An in vitro study by Tohmeh et al. (65),
evaluating PMMA augmentation of osteoporotic ver-
tebrae from a single or bipedicular approach, showed
no significant difference in height changes between
either augmented group; specifically, preferential
deformation of the single-side augmented group
was not noted. In a retrospective clinical study by
Kim et al. (64), use of a unipediculate approach
resulted in filling of both vertebral halves from a
single puncture site with no statistically significant
difference in clinical outcome from that of biped-
iculate vertebroplasty.
The bipediculate approach presents unique chal-
lenges. One problem is the obscuration of the basi-
vertebral plexus during injection by overlapping
needles. Changing the lateral obliquity makes the
visualization around the single needle easy, but the
presence of a second trocar makes observation of this
critical area difficult. Waiting to place the second
needle after completion of the first injection is one
solution, and if acrylic fills the contralateral hemi-
sphere, the second injection is not needed. If both
needles are placed at the same time, the contralateral
stylet remains in place during the initial ipsilateral
acrylic injection; otherwise, the material will track
through the trabecular space and egress out the con-
tralateral needle. The first needle can be removed
prior to injection of the second hemivertebra. Another
technical difficulty is observing acrylic flow during
contralateral injection because of the presence of
PMMA in the ipsilateral hemisphere. Potential solu-
tions include adding extra barium sulfate to the
acrylic mixture used during the contralateral injection
so that it is seen through the ipsilateral acrylic cast;
using final images of the ipsilateral injection dis-
played on an adjacent monitor as a guide by looking
for acrylic extending outside of the existing cast; or
injecting under a combination of lateral and AP
oblique views. Use of road-mapping technique is
not advised as respiratory and bowel gas movement
makes precise visualization impossible.
396 Jensen
Vertebrography
The initial technical description of vertebroplasty (15)
advocated the use of vertebrography prior to acrylic
injection as a safety feature. Injection of small amounts
of contrast into the vertebral body confirms the cannula
location within the trabecular space, evaluates potential
routes of acrylic extravasation, and clearly defines the
location of the basivertebral plexus, which channels
much of the vertebral venous outflow into the anterior
internal epidural venous plexus. On the lateral view,
the egress point of this plexus is seen as a bony
depression located anterior to the posterior vertebral
body margin between the pedicles, which may not be
easily visualized in osteoporotic bone. The location of
this vascular junction is critically important, as extrav-
asation of acrylic into the epidural veins is the major
cause of neurological complications in vertebroplasty.
Controversy exists over the need for vertebrog-
raphy, particularly in the hands of experienced practi-
tioners (66,67). Gaughen et al. (68) retrospectively
evaluated the safety and efficacy of vertebroplasty
performed in two patient populations, one in which
venography was performed and the other without
venography. No significant differences in frequency
or amount of venous extravasation, or in clinical out-
come between the two groups were found. However,
this study was done at a major medical center by
senior interventionalists with extensive experience,
and its conclusions may not be valid for all operators.
In short, some operators may find the vertebro-
gram helpful, as it easily identifies the location of the
needle tip, visualizes the exact point where the basiver-
tebral plexus exits the vertebral body, outlines the
epidural and paraspinal venous system, and may pre-
dict PMMA flow characteristics and possible sites of
egress (66). However, contrast that extravasates through
fracture lines into the paravertebral spaces may obscure
visualization and make injection of PMMA difficult to
see (Fig. 8B). The decision to perform vertebrography
either consistently, on a case-by-case basis, or not at all is
left to the individual operator.
Acrylic Preparation
Although a variety of bone filler substances have been
used in the treatment of vertebral body disease, cur-
rently the only biomaterial approved for use in verte-
broplasty in the United States is PMMA. There are
several commercially available PMMA products that
are used for vertebroplasty, all with different handling
characteristics. PMMA consists of two componentsa
fine-grained powdered polymer and a volatile liquid
monomer. When the two substances are combined, an
exothermic chemical reaction begins that leads to pro-
gressive polymerization of the mixture to its solid state.
Users should be familiar with PMMA prior to starting a
vertebroplasty service. Bench testing is the recom-
mended way to evaluate the material to ensure that
the resultant mixture can be injected effectively
through a needle and visualized fluoroscopically.
This testing is best done at a formal course in which
acrylic preparation and injection is performed on
models or cadavers and a variety of materials and
mixtures can be tried.
The major parameters of PMMA that impact its
use in vertebroplasty are polymerization time and
opacification. The polymerization time, or curing
rate, varies among the different products, and the
slurry may be suitable for injection from as little as
5 minutes to close to 20 minutes. The polymerization
time of any PMMA can be prolonged by refrigerating
the kit prior to its use, cooling the procedure room, or
by chilling the prepared acrylic in an ice bath. For
acrylics with longer curing times, the powdered poly-
mer component needs to dissolve completely in the
liquid monomer before injection. If adequate solva-
tion time (12 minutes after mixing) is not allowed,
the pressure from injection may cause the monomer to
leach out of the mixture, leaving a powder plug in the
cannula.
The second parameter of great significance is
opacification. As most clinically relevant complica-
tions are due to the migration of acrylic into the
extraosseous spaces, fluoroscopic visualization of the
material during injection is of paramount importance.
Visualization is influenced by the amount of barium
sulfate within the product, size of the patient, location
of the treated vertebral body, and quality of the
imaging chain. The percent of barium sulfate by
weight or volume varies between products, and oper-
ators must be knowledgeable about their chosen
materials opacification characteristics. Sterile barium
sulfate for use in vertebroplasty is commercially avail-
able and users should be prepared to supplement
their mix with extra barium sulfate if necessary. Anti-
biotic powders for infection prophylaxis, such as
tobramycin or vancomycin, also may be added to
the powdered polymer. Added substances should be
thoroughly mixed with the powdered polymer first to
guarantee homogeneity of the slurry.
Certain caveats applyany alteration of the
manufacturers product or mixing instructions, either
by adding substances or changing the powder to
liquid ratio, may change the consistency and/or poly-
merization time of the material. Readers are advised
that, strictly speaking, any altered material is no
longer FDA-approved.
Acrylic Injection
Injection of the acrylic slurry is performed using either
1-mL Luer lock syringes or commercially available
cement delivery systems. The 1-mL syringes are inex-
pensive, require minimal storage space, and allow
exquisite tactile feedback during injection, which
improves acrylic flow control; however, their use
places the operators hands close to or within the
radiation field. Commercially available injection devi-
ces are self-contained systems, with a reservoir into
which the PMMA is loaded and a twist-type or trigger-
activated plunger that advances the material into the
tubing. Some newer systems also incorporate a mixing
chamber attached to the reservoir, making the device
entirely self-contained. The system is attached to
the cannula hub via high-pressure tubing. Each turn
 Chapter 22: Percutaneous Vertebroplasty 397

of the plunger or pull on the trigger delivers a consis-

tent amount of acrylic into the cannula. Injection
devices increase the distance between the operator
and the X-ray tube, thus minimizing the dose to the
hands, especially in the AP plane (69). With a delivery
system, only a single connection of the tubing to the
cannula hub is necessary, resulting in less exposure of
the acrylic to the atmosphere and of the hubs Luer lock
threads to the acrylic. Unfortunately, the tactile feed-
back with delivery systems is diminished and the
operator has to rely more on visual cues, such as
crowding of the barium particles in the cannula, to
detect compromised acrylic flow. In addition, pressure
buildup in the system resulting in sudden expulsion of
acrylic from the cannula tip is more likely with injec-
tion devices than 1-mL syringes. Regardless of the
system used, operators should practice first on models
or cadavers to become familiar with the tactile feedback
and visual cues used during acrylic injection.
The application of PMMA to the trabecular space Figure 7 Multiple adjacent compression fractures were treated
is an embolization procedure, and all injections are at one sitting. All three needles were placed followed by sequen-
tial PMMA injection. Note the cloud-like, wispy pattern of trabec-
visualized under continuous fluoroscopic monitoring. ular filling. The embolization is terminated when the PMMA
Some authors have advocated injection of small ali- reaches the posterior quarter of the vertebral body. Abbreviation:
quots (0.10.2 cc) using intermittent fluoroscopy PMMA, polymethylmethacrylate.
(70,71). However, as with any vascular embolization,
direction of flow can shift suddenly as the emboliza-
tion progresses. Small amounts of material can move
quickly into unintended vascular spaces without rec-
ognition (69). Embolization of acrylic to the pulmo-
nary system is particularly problematic because the
material does not remain in the field of view, and
deposition into the lungs may not be suspected until
the patient becomes symptomatic. Furthermore,
small aliquots are difficult to measure with injection
devices and the amount perceived to be delivered
may be different from what is actually delivered
because of compliance in the system. Lateral imaging
is used primarily to ensure that epidural extravasation
of cement does not occur; intermittent AP fluoroscopy
monitors any lateral paravertebral extravasation. As
the acrylic exits the cannula, it permeates the trabec-
ular space, giving the appearance of a concentrically
expanding cloud (Fig. 7). Alternatively, it may seep
along intraosseous cracks, leak through endplate frac-
tures, or fill an internal cavity (Fig. 6). In some
instances, vertebral body expansion with reduction
Figure 8 This 70-year-old male presented with an acute wedge
of kyphotic and wedge angulation will occur (Fig. 8) compression fracture of the L3 vertebral body (A). Following
(7274). The cannula is withdrawn slightly whenever filling of an intraosseous cavity with PMMA, the fracture is
injection becomes difficult, creating a space for acrylic reduced and the height is restored (B). The density surrounding
flow. When using an injector, forward pressure is the anterior inferior border of the vertebral body (arrows) is from
removed prior to needle withdrawal to avoid sudden contrast extravasation into the surrounding tissues during verte-
PMMA deposition into a new space. Typically, the brography. Abbreviation: PMMA, polymethylmethacrylate.
injection is terminated when the acrylic reaches the
posterior one-quarter of the vertebral body to avoid
embolization of the basivertebral plexus (Fig. 7). Good
pain relief occurs with filling of two-third of the verte- liquid monomer out of the slurry. The resultant plug
bral body (64), and overzealous attempts at complete will obstruct the cannula lumen, necessitating its
vertebral filling risks complication for little clinical gain. removal. Compaction is best identified by the lack of
Failure of the acrylic to egress from the cannula movement of PMMA into the vertebra, with crowding
tip may be due to obstruction from bony trabeculae, or of the constrained barium particles within the cannula.
from a blockage within the 1-mL syringe, injector tub- If repositioning of the cannula tip slightly posteriorly
ing, or cannula. Acrylic compaction occurs when con- does not result in acrylic flow, then the syringe or
tinued injection against a relative obstruction forces the delivery system is disconnected and evaluated for
398 Jensen
plug formation. If no obstruction is present, the cannula
is cleared with the stylet under fluoroscopic observa-
tion and injection resumes.
Small acrylic leaks through endplate fractures
are acceptable, but large amounts of PMMA within
the disc space may act as a wedge causing fracture of
the adjacent vertebra (75). If the acrylic preferentially
flows to a paravertebral or epidural vein, the needle is
repositioned more posteriorly and the material is
allowed to thicken. Injection is terminated if continued
venous filling occurs.
Occasionally, partially solidified PMMA will dis-
connect from the needle tip during withdrawal and
deposit in the subcutaneous soft tissues. This retained
fragment may become a source of pain or infection.
Decompression of PMMA along the needle track has
been seen with needle removal after filling large intra-
osseous cavities. Several techniques can be employed
to prevent subcutaneous deposition. Prior to needle
removal, a 360( twisting motion is performed to sep-
arate any stream of acrylic that may be attached to the
material within the cannula dead space. The needle is
withdrawn slightly and the needle track is observed
for retrograde acrylic movement. It may be left in
place until the acrylic hardens as long as connection
between the intraosseous bolus and the needle has
been broken. If necessary, redirection and advance-
ment of the needle across the acrylic core will separate
the two (76).
If inadequate filling of the vertebral body
requires a contralateral puncture, then the procedure
is repeated on the opposite side. Otherwise, the skin
incision is cleaned and dressed with small adhesive
bandages, and the patient is transferred to the recov-
ery room for further observation and care.
POSTPROCEDURAL CARE
In the outpatient setting, most postvertebroplasty
patients are observed for two hours prior to discharge.
Individuals remain supine for one hour and are grad-
ually allowed to sit up and/or stand over the next
hour under direct nursing or physician supervision.
Ambulatory patients are discharged to the care of a
responsible adult after recovery. In many instances,
patients experience some immediate pain relief either
from the residual effects of the local anesthetic or from
the procedure, or a combination of both. Patients are
advised that focal pain at the puncture sites is com-
mon and may last up to 48 hours. Pain medication
may be taken as needed; however, they are encour-
aged to limit narcotic use so that efficacy can be
determined. Nonsteroidal anti-inflammatory agents
such as ibuprofen may be substituted.
Prior to discharge, patients are evaluated for
chest or back pain, new neurological dysfunction,
dyspnea, or other potential complications of the pro-
cedure. Most significant complications are due to
extraosseous acrylic deposition and patients quickly
become symptomatic. Early recognition is vital so that
appropriate treatment can be instituted, and suspected
complications should be treated as emergencies. For
this reason, immediate access to CT scanning and
surgical backup is an absolute requirement for any
vertebroplasty service.
Small waterproof bandages placed over the
puncture sites may be removed the next day, and
skin incisions are kept clean and dry. Follow-up either
by direct contact or telephone interview is done within
48 hours and at 7 days following the procedure.
Patients are to notify the physician of redness or
discharge at the operative site, recurrent or new back
pain, chest pain, or shortness of breath, or unex-
plained fever or neurological symptoms. Any new
symptom requires clinical evaluation and possibly
imaging. New back pain may indicate recurrent or
new fracture, unrecognized facet pain, or epidural
abscess. Chest pain may be the result of rib fractures
or unsuspected pulmonary embolization of acrylic.
All neurological symptoms require immediate CT
scanning to search for misplaced PMMA, and sus-
pected osteomyelitis or abscess is best investigated
with MRI.
For people who have been immobilized for a
long period of time, a gradual increase of activity is
recommended. Some individuals who feel better
immediately try to return to full activity only to
develop new vertebral fractures or fall and break a
hip or a wrist. A short course of physical therapy with
continued use of a brace may be helpful. Patients who
are not receiving preventative medical therapy are
referred to endocrinology or geriatrics for further eval-
uation and implementation of appropriate treatment.
CLINICAL OUTCOMES
Over 450 articles concerning vertebroplasty have been
published in the last 20 years. Among these papers,
about 100 studies address the clinical outcomes of
patients treated with percutaneous vertebroplasty.
Without exception, these reports describe vertebro-
plasty as a successful therapy for the relief of the
pain associated with VCFs caused by either osteopo-
rosis or tumor involvement. The earliest literature
consisted of small, retrospective, uncontrolled case
series introducing the technique, and claiming excel-
lent results for the patients involved (1014). Since that
time, larger case series have been published (9,1522,
47,52,57,58,7779). Vertebroplasty has consistently
shown immediate and considerable improvement in
pain and patient mobility following treatment (1524).
In a recent prospective, nonrandomized study of
79 consecutive patients with osteoporotic compression
fractures, of whom 55 (70%) were treated with verte-
broplasty and 24 (30%) with conservative therapy, the
vertebroplasty group showed statistically significant
reduction in pain and improvement in physical func-
tioning at 24 hours over the conservative treatment
group (23). In addition, 24% of the treated patients
were able to cease all analgesia after 24 hours com-
pared to none in the conservative treatment group.
These markedly different clinical outcomes at
24 hours to 1 week represent the enormous benefit of
vertebroplasty over conservative therapy in terms of

early mobilization, even though at 6 weeks, 6 months,
and 12 months the clinical outcomes were the same in
the two groups.
In a prospective trial of vertebroplasty versus
best medical therapy (24), 40 patients with acute
osteoporotic compression fractures were randomized
to vertebroplasty or conservative therapy, with
crossover for the medically treated group allowed
at six weeks. The vertebroplasty group showed sta-
tistically significant improvement in pain and mobil-
ity, and reduction in medication use immediately
after vertebroplasty. None of the patients random-
ized to medical therapy showed significant improve-
ment, and 16 of the 19 patients were offered
vetebroplasty. This postmedical therapy vetebro-
plasty group also showed statistically significant
improvement in all three parameters immediately
following the procedure. At 12 weeks, both groups
showed statistically significant durability of the ther-
apeutic response.
It is well documented that the natural history of
healing compression fractures is comprised of gradual
improvement in pain over 2 to 12 weeks with variable
return of function. What is not described as natural
history is sudden improvement in pain and return in
functionthe hallmark picture of a positive therapeu-
tic response with vertebroplasty. Most of the patients
enrolled in the initial vertebroplasty studies did not
undergo treatment until all noninvasive therapeutic
options had been exhausted. These patients acted as
their own internal controls, as vertebroplasty was
performed at a point in their clinical course in which
if improvement associated with healing were to occur,
it should have happened. It is therefore unlikely that
the rapid marked improvement in clinical findings
following vertebroplasty was associated with the nat-
ural course of the disease.
It may also be argued that patients treated med-
ically are just as likely to have a long-term positive
outcome similar to that of the treated population, a
finding noted in the Diamond study. However, equal-
ity in long-term outcomes does not negate the early
positive effects of a successful vertebroplasty. The
potential complications associated with conservative
therapy are more likely to happen early in the course of
a patients immobilization, leading to physiological
losses from which the patient may not recover.
Another consideration is that the positive out-
comes seen in vertebroplasty are due to the placebo
effect. Vertebroplasty reports have consistently shown
positive responses in the range of 80% to 90% for
osteoporotic fractures, regardless of cohort demo-
graphics, etiology of osteoporosis, geographic loca-
tion, or type of institution where the procedure was
performed. The question will be laid to rest with the
completion of a sham trial. A feasibility study
reported in an abstract by Kallmes et al. (80) showed
that patients could be successfully randomized to
vertebroplasty or a sham procedure, but no meaning-
ful clinical information was obtained. This small study
was used to obtain NIH funding for a multicenter
vertebroplasty versus sham procedure trial that is bulk. Direct percutaneous puncture with instillation
currently enrolling patients.
Chapter 22: Percutaneous Vertebroplasty 399
In summary, despite the general endorsement in
the literature of the procedure to date, published
reports suffer from at least one of three primary
methodological limitations: (1) retrospective assess-
ment of patient status (pain and functional ability);
(2) assessment of patient status using either nonvali-
dated instruments, e.g., self-developed, or validated
instruments nonspecific to VCFs; and (3) lack of con-
trol subjects. Though it is true that surgical therapies
are rarely subjected to the same prospective random-
ized evaluation as medical therapies, it must be
admitted that at this time, there is actually little
Level 1 scientific evidence that vertebroplasty is an
effective therapy.
TREATMENT OF VCFs ASSOCIATED
WITH NEOPLASTIC DISEASE
Malignancies involving the spinal axis are not uncom-
mon in the cancer population. Each year, approxi-
mately 5% of cancer patients will develop spinal
metastases, although not all will become clinically
relevant (81). Malignant cells may access the spinal
column by direct extension from a paravertebral tumor
or via hematogenous, lymphatic, or perineural spread
(82). Pain arises from tumor impingement on nerve
roots or the spinal cord, or from periosteal irritation
caused by cortical erosion and vertebral collapse. Treat-
ment options include medical therapy, systemic
chemotherapy, radiation therapy, chemoembolization,
transarterial embolization, surgery, or a combination
of modalities. Radiation therapy is highly effective in
many patients, but relief may be delayed by two weeks,
and minimal if any bone strengthening is not recog-
nized for up to two to four months (83). Extensive
multifocal disease is most likely to be treated by radi-
ation therapy, or conventional medical therapy consist-
ing of immobilization and corticosteroid medication or
narcotic analgesia. Conservative treatment is associated
with multisystem complications as discussed earlier
in this chapter.
Unlike osteoporotic VCFs, surgery may be indi-
cated in selected individuals. Patients with compres-
sive neurological symptoms from single or adjacent
level disease with a life expectancy of six months or
greater are often considered for surgical intervention.
Most techniques consist of anterior decompression
and stabilization by replacement of the affected ver-
tebral bodies with PMMA, with the addition of
pedicle screws, cages, or distraction rods as needed
(13). However, there is a significantly increased peri-
operative morbidity and mortality in surgical patients
who have received previous chemotherapy, radiation
therapy, or steroids (2,3).
A variety of minimally invasive techniques have
been effective as primary or adjunctive treatment of
vascular metastases. Percutaneous transarterial embo-
lization may be used for preoperative devasculariza-
tion (84,85), delivery of chemotherapeutic agents (86),
and pain palliation (87,88) through shrinkage of tumor
of a cytotoxic material such as absolute ethanol (89)
400 Jensen

has also been described. However, with the exception
of surgery, none of these therapies restore strength
and stability to the spinal column, and patients remain
at risk for vertebral collapse. Vertebroplasty of meta-
static lesions presumably palliates pain and provides
structural stability to the spine through the solidifi-
cation of the osteolytic lesion. In addition, there may
be some cytotoxic effect of PMMA that results in
tumor necrosis and shrinkage. In some patients,
vertebroplasty may facilitate surgery by providing
stabilization of the anterior column in an otherwise
nonsurgical candidate.
relative contraindication. Severely compressed verte-
brae are technically difficult to treat, and compression
of the cord or nerve roots by displaced fracture frag-
ments and/or significant epidural tumor bulk may be
made worse with the injection of PMMA. Disease
involving the posterior elements cannot be treated
with PMMA; instead, vascular tumors may be injected
in a manner similar to that described for hemangio-
mas (93), with N-butyl cyanoacrylate prior to surgical
removal.
Imaging Evaluation

Patient Selection Spinal MRI is the most common study obtained in

Because of the variety of therapeutic choices available
to this patient population, the decision to treat is made
by a multidisciplinary team and takes into consider-
ation the local and general extent of the disease, the
patients medical condition, response to previous ther-
apy, general state of health, and life expectancy.
In general, patients suffering from significant
focal, mechanical pain unresponsive to analgesia are
potential candidates for vertebroplasty (16,57,90,91).
Blastic metastases with an osteolytic component may
be considered for vertebroplasty. Patients with mini-
mal or no pain but impending or frank vertebral
collapse due to extensive vertebral involvement may
be treated for spinal stabilization.
Absolute contraindications for vertebroplasty in
malignancies are the same as for osteoporotic VCFs.
Relative contraindications unique to neoplastic dis-
ease also exist. In many of the early studies, patients
with cortical osteolysis were excluded from treatment
for fear of causing canal compromise (92); however,
further studies show that these lesions can be success-
fully treated provided there is no significant epidural
involvement (9,16). Extensive destruction and signifi-
cant collapse leading to height loss of 70% or more is a
patients with malignant disease. MRI is extremely
useful for identifying the extent of the disease, includ-
ing the location and number of involved vertebrae,
the presence of canal compromise, and the compres-
sion of neural structures (Fig. 9A). However, MRI
does not adequately visualize the bony cortex, and
CT is better at defining the degree of osseous destruc-
tion and cortical involvement (Fig. 9B) as well as
identifying displaced fragments that may encroach
upon the canal. The addition of intrathecal contrast
in conjunction with preoperative CT scanning may
provide valuable information about the presence of
epidural disease. In patients with severe vertebral
destruction or lesions in difficult locations such as
the cervical spine, CT can be utilized for treatment
planning, needle placement, and in some cases,
acrylic injection.
Preprocedure plain films also play an important
role in lesion evaluation as it allows the operator to
assess the visibility of the bony cortex, particularly the
appearance of the pedicles. Since most vertebral
bodies are entered via the transpedicular route under
fluoroscopic guidance, poor definition of the pedicles
may alter the approach or necessitate the need for
needle placement under CT.

Figure 9 This 65-year-old male with renal cell carcinoma was evaluated for acute back pain and was found to have an L1 metastatic
deposit on MRI (A). Note the marked tumor involvement of the vertebral body, and the left pedicle and lamina with epidural extension into
the left lateral recess. (B) CT confirms the osseous destruction and better demonstrates the cortical erosion at the lateral recess. CT after
vertebroplasty (C) shows PMMA within the tumor located in the vertebral body with extension into the lateral recess. The needle track
through the right pedicle was sealed with PMMA. Lateral plane film (D) shows the PMMA bulging into the spinal canal (arrows). The
PMMA within the needle track can also be seen (open arrow). The patient developed a radiculopathy that responded completely to a short
course of oral steroids. Abbreviations: MRI, magnetic resonance imaging; CT, computed tomography; PMMA, polymethylmethacrylate.

Patients with multiple myeloma or lymphoma
may have plain film findings identical to osteoporotic
patients (Fig. 14A). Individuals who present with an
osteoporotic fracture but who do not fit the clinical readily accept smaller (15 G or less) biopsy systems
picture of primary or secondary osteoporosis (e.g.,
most males, African-American females) should be
evaluated with MRI and biopsy, if necessary.
Special Considerations in the Performance
of Vertebroplasty for Malignant Disease
The basic principles that guide the injection of acrylic
into osteoporotic VCFs also apply to neoplastic
lesions. However, there are certain technical issues
that are unique to the treatment of patients with tumor
involvement. Cancer-ridden individuals are often
more uncomfortable in the prone position than osteo-
porotic patients and may require large amounts of
narcotic analgesia or general anesthesia. In addition,
these people are more prone to infection as a side effect
of chemotherapy or radiation treatments, and prophy-
lactic intravenous injection of a broad spectrum antibi-
otic prior to vertebroplasty coupled with the antibiotic
powder mixed with the PMMA is recommended.
As noted above, the traditional approach for
thoracic and lumbar vertebrae is via the transpedicu-
lar route. However, with tumor involvement the bony
landmarks often are not seen, making the trans-
pedicular approach problematic. One technique is to
estimate the location of the affected pedicle using the
medial and lateral borders of the adjacent pedicles as
markers. As long as the needle tip remains lateral to
the medial border of the adjacent pedicles, the needle
will not pass through the spinal canal. If the trans-
pedicular approach is not viable, the posterolateral
approach for lumbar or lower thoracic vertebrae or the
intercostopedicular approach for upper thoracic ver-
tebrae may be used.
Unlike osteoporosis, the cervical spine is often
involved with malignant processes. The anterolateral
approach for cervical lesions may be done under
fluoroscopic guidance alone (94) or with the use of
CT. Fluoroscopic visualization of the lower cervical
vertebrae may be difficult because of the overlying
shoulder density. Placement of the needle using CT
guidance allows the operator to observe and avoid
major vascular structures. Injection of PMMA under
CT is problematic, as the 3D movement of the acrylic
cannot be adequately monitored without excessive
table movement. There have been recent reports of
injection of minute aliquots of PMMA using CT-
fluoroscopy but extensive use of this technique has
not been described. PMMA injection should be done
under continuous fluoroscopic monitoring whenever
possible, and should not be performed unless the
posterior wall of the vertebral body can be seen.
Vertebrography is not routinely performed in
neoplastic vertebrae. Unlike osteoporosis, the signifi-
cant cortical destruction and bony erosion present
with tumors lead to substantial leakage of contrast
into the canal and paravertebral spaces. Contrast can-
not be readily removed from these spaces and its
Chapter 22: Percutaneous Vertebroplasty 401
presence may obscure visualization, impeding or pre-
venting cement injection.
The larger vertebroplasty trocars (1011 G)
for sampling of tumor, or a specialized vertebroplasty
trocar with a biopsy cannula can be used (Fig. 10).
Some authors advocate using small 15-G trocars for
acrylic injection of cervical lesions, or in vertebrae with
extensive destruction or extreme vascularity. Use of
small needles may decrease the risk of hematoma
formation or leakage of acrylic out of the needle track.
Because of the variable density of tumor tissue
relative to osteoporotic bone, the acrylic pattern may
appear spotty and discontinuous. One exception is
multiple myeloma, where the affected vertebrae may
fill in a similar manner as osteoporotic fractures.
Hypervascular tumors may demonstrate free arterial
flow through the cannula once the stylet is removed,
and the operator should be prepared to deposit acrylic
material within the track during needle withdrawal to
prevent excess bleeding (Fig. 9C). There has been one
reported case of tumor displacement into the canal as
a result of vertebroplasty (95). The introduction of
intrathecal contrast immediately prior to treatment
may allow the operator to identify tumor displace-
ment during acrylic injection.
Routine postprocedure CT scanning is recom-
mended in malignant lesions. Studies provide infor-
mation about the distribution of the acrylic (Fig. 9C)
and may show changes in position of the tumor mass,
cement leakage, intratumoral epidural cement, iatro-
genic fracture or hematoma, or other unsuspected
Figure 10 This patient underwent a biopsy prior to vertebro-
plasty. Note the hollow cannula (arrow) extending outside of the
trocar. The biopsy cannula is inserted in place of the stylet
when the trocar is located at the posterior wall of the vertebral
body. The trocar is then advanced to the anterior third of the
vertebral body, the biopsy cannula is removed and the tissue core
is retrieved.
402 Jensen
complications. It also provides a permanent record for
comparison to future studies.
Vertebroplasty and Adjunctive Therapies
Radiation therapy is typically used concomitantly with
vertebroplasty (9,90,96,97). The timing of the radiation
therapy does not affect the vertebroplasty response (96)
and the radiation does not affect the integrity of the
acrylic. Most investigators advocate initial treatment
with vertebroplasty because of its immediate analgesic
effect and improved spinal stability (9,57,90,96), fol-
lowed by radiation therapy.
Transarterial or direct puncture embolization of
a particulate or liquid agent may be useful in reducing
frank epidural disease or posterior element involve-
ment. Recent reports of radiofrequency ablation of
tumor followed by vertebroplasty have shown posi-
tive results in a small number of patients (98,99).
Clinical Outcomes
As noted above, percutaneous vertebroplasty was
initially described in 1987 as a treatment for painful
vertebral hemangiomas (10). In 1989, Kaemmerlen et al.
reported the first series limited to twenty patients with
malignant disease (11). Eighty-five percent had sub-
stantial pain relief in less than 48 hours, and one
complication was reported. No recurrent local pain or
secondary vertebral body collapse was observed in an
average follow-up period of 2.8 months.
In 1996, Weill et al. (77) reported their experience
with vertebroplasty in 37 patients. Seventy-three per-
cent of patients had complete or marked relief in pain,
which remained stable at six months, and in 65% of
patients at one year. Recurrence of pain in five
patients was attributed to the development of adjacent
metastatic vertebral lesions. Five (13.5%) local compli-
cations were notedthree patients developed sciatica
and two patients with treated cervical vertebrae expe-
rienced dysphagia. Three patients were successfully
treated with steroid therapy, while one patient
required surgical removal of epidural cement.
The same year, Cotten et al. (9) published a
prospective study focusing on patient outcomes in
37 patients with 40 involved vertebrae. The efficacy
of the treatment was evaluated by a different physi-
cian from the one who performed the procedure, and
the efficacy criterion was the change in the pain score
on the McGill-Melzack verbal scale (05 scale).
Patients were evaluated at 48 hours, 3 months, and
6 months following vertebroplasty, with a mean fol-
low-up period of 4.2 months. All patients received
radiation therapy 12 to 22 days following the proce-
dure. Thirty-six patients (97.3%) reported some pain
relief within the first 48 hours; 13.5% were pain-free,
55% showed substantial improvement, and 30% were
moderately improved. The extent of vertebral body
filling was compared to the degree of pain relief and
no correlation was found. Of 40 vertebral bodies,
29 (72.5%) demonstrated leakage of PMMA outside
of the vertebral body, but the majority of leaks were
clinically silent. Three patients (8.1%) developed rad-
icular pain from leaks into the neural foramen, and
two of these patients required decompressive surgery
for relief. The beneficial effects of vertebroplasty
appeared to be durable. All patients who were avail-
able for reevaluation had sustained or increased pain
relief at one month, with 88.9% at three months and
75% at six months. In addition, no new or progressive
vertebral collapse was seen in the injected vertebrae.
Deramond et al. (16) reported their experience in
101 patients treated for spinal malignancies. Eighty
percent of patients had moderate to complete pain
relief following vertebroplasty, with a 10% reported
complication rate. Fifty percent of treated vertebrae
had osteolysis of the posterior wall, yet radicular pain
accounted for only 4% of the complications. The
remaining complications were associated with the
patients primary disease.
The North American literature on vertebroplasty
outcomes in metastatic lesions is not as extensive as
the European literature. In the first report by Barr et al.
(91), 8 of 48 patients suffered from metastatic disease,
of which 50% described substantial pain relief follow-
ing vertebroplasty. Seven of eight patients (87.5%)
demonstrated no further collapse of the treated verte-
brae at follow-up. In 2003, Fourney et al. (100)
described a larger series of 56 patients. Eighty-four
percent of patients noted marked or complete pain
relief following vertebroplasty or kyphoplasty, and no
patient had worsening symptoms or suffered a com-
plication. Asymptomatic acrylic leakage occurred in
9% of vertebroplasty patients and none in the kypho-
plasty patients. Median follow-up was 4.5 months,
and reductions in visual analog pain scores remained
significant up to one year.
All of these series point out the difficulty in
determining the efficacy and durability of vertebro-
plasty in a patient population suffering from malig-
nancies. Many patients are too ill to attend follow-up
sessions or have died. Also, the addition of radiation
therapy or other concomitant therapies cloud the pic-
ture as to the long-term benefits derived from verte-
broplasty. The initial pain relief easily could be
ascribed to the effects of vertebroplasty, but its role in
the durability of the pain relief versus that of the
additional therapy remains uncertain.
COMPLICATIONS
The number of percutaneous augmentation proce-
dures being performed around the world is steadily
increasing. Neophyte operators are most likely to
experience complications during their learning
phase. Complications are best avoided by awareness
of the factors that contribute to their occurrence.
Often, it is the overzealous quest for complete verte-
bral body filling that results in complications, and
practitioners new to the procedure must realize that
more definitely is not better where augmentation
is concerned.
The primary cause of a symptomatic vertebro-
plasty complication is the passage of acrylic into

adjacent spaces via fracture lines or cortical destruc-
tion (Fig. 9D), along the needle track, or into the
epidural and paravertebral venous complexes
(9,16,57,90,96). Acrylic material located within the
epidural venous plexus or foraminal veins may cause
spinal cord or nerve root compression, with resultant
radiculopathy or myelopathy (Fig. 11). Migration of
small amounts of PMMA through the epidural or
paravertebral venous system to the pulmonary vascu-
lature (Fig. 12) is usually without clinical significance,
but symptomatic pulmonary embolus and death have
been reported (101). Perivertebral acrylic is usually
asymptomatic, although dysphagia from esophageal
compression after a cervical vertebroplasty for malig-
nancy has occurred (96). Acrylic within the disc space
may decrease its cushioning ability, leading to focal
fractures at adjacent endplates (102).
More often than not, PMMA leakage is asymp-
tomatic, even in malignant lesions. Cotten et al. (9)
demonstrated acrylic leaks by CT, both venous and
cortical, in 29 of 40 patients with osteolytic metastases
or myeloma. Most of these leaks were asymptomatic,
but two of eight foraminal leaks produced nerve root
compression that required decompressive surgery. In
a later series, Cotten et al. (57) reported that 1 patient,
of 258 treated, experienced spinal cord compression
that required surgery. Of 13 patients with radicular
pain, only 3 required surgical decompressions, while
10 responded to local anesthetic infiltration or medical
therapy. Deramond et al. (16) noted a single transient
neurological complication in 80 patients with osteo-
porotic fractures. Review of all major vertebroplasty
Figure 11 This patient complained of leg pain following verte-
broplasty done at an outside institution. CT showed PMMA within
the L2L3 neural foramina bilaterally, causing nerve root com-
pression. The patient responded to steroid therapy. Note the
PMMA located within the paravertebral veins draining into the
IVC (open arrow). Abbreviations: CT, computed tomography;
PMMA, polymethylmethacrylate; IVC, inferior vena cava.
Chapter 22: Percutaneous Vertebroplasty 403
Figure 12 The history is unknown of this woman who presented
for a chest film. A midthoracic level vertebroplasty is seen
through the cardiac silhouette in addition to extensive pulmonary
PMMA in the apices and the right hilum. Lateral film (not shown)
demonstrated six other vertebroplasty sites. Abbreviation:
PMMA, polymethylmethacrylate. Source: Courtesy of Jonas
Goldstein, M.D., Asheville, North Carolina, U.S.A.
series shows that the complication rate ranges from
1% to 10%; Murphy and Deramond (90) divide it
further into 1.3% for osteoporosis, 2.5% for hemangio-
mas, and 10% for neoplastic disease. Fortunately, most
patients with radicular symptoms respond to anti-
inflammatory or narcotic analgesics or local anesthetic
infiltration. But if significant neurological compromise
were to occur, surgical colleagues must be available
for immediate consultation or intervention. Vertebro-
plasty should only be performed at sites where surgi-
cal backup is available.
Complications also may occur from inappropriate
needle positioning. Improper placement of the cannula
tip within or near the basivertebral plexus places the
patient at risk for deposition of PMMA into the epi-
dural venous plexus. Advancement of the needle
through the anterior vertebral body wall could damage
the aorta or inferior vena cava. Use of the paravertebral
approach may injure the intercostal or lumbar artery.
Also, leakage of PMMA into the paravertebral space
through the needle track is more common with verte-
brae that are accessed through the vertebral body
rather than the pedicle. Transgression of the dura
may lead to a symptomatic cerebrospinal fluid (CSF)
leak or decompression of PMMA into the thecal sac
after cannula removal (Fig. 13). Pneumothorax is a
potential complication of thoracic vertebroplasty.
Other complications that have occurred, as
reported in the literature or through personal knowl-
edge, include fracture of the transverse process or
pedicle, paravertebral hematoma, epidural abscess,
pneumothorax, rib fractures, CSF leak, seizure or
respiratory arrest from oversedation, and acute disc
extrusion. Severely osteoporotic patients may sustain
rib fractures (15) or sternal fractures from lying prone
on the procedure table. Padding the table, performing
the puncture with the patient in the decubitus posi-
tion, or advancing the needle through the bone with
404 Jensen
Figure 13 This 80-year-old female with a T11 compression
fracture underwent vertebroplasty at an outside institution. Fol-
lowing the procedure, she complained of incontinence and leg
weakness. Spiral CT with axial reconstruction shows decompres-
sion of PMMA along the needle track through the subarachnoid
space. MRI (not shown) demonstrated application of the PMMA
along the lateral aspect of the conus. Abbreviations: CT, com-
puted tomography; PMMA, polymethylmethacrylate; MRI, mag-
netic resonance imaging.
the use of a hammer may help to decrease the chance
of a rib fracture.
Hemodynamic compromise has been associated
with packing of the acetabulum with PMMA during
hip replacement surgery. Transient systemic hypoten-
sion during acrylic injection in vertebroplasty has been
reported (103), but a large retrospective study of the
cardiovascular effects of PMMA in vertebroplasty
found no generalized association between acrylic injec-
tion and systemic cardiovascular derangement (104).
One theoretical complication is thermal injury to
adjacent neurological structures during acrylic poly-
merization. There have been no clinical reports of this
phenomenon and its possibility appears unlikely on
the basis of in vitro tests, which showed no significant
temperature rise in the spinal canal with vertebro-
plasty (105), and in vivo animal experiments, which
showed no spinal cord damage from PMMA located
adjacent to the dural sac in dogs (106).
Exposure to methylmethacrylate and the radia-
tion used for its application are potential occupational
hazards to physicians, staff, and patients. Cloft et al.
studied the exposure of medical personnel to methy-
methacrylate vapor during vertebroplasty (107). A
vertebroplasty exposes the physician to less than 5
ppm (parts per million) of methacrylate vapor, well
below the allowable limit of 100 ppm per eight hours
set by Occupational Safety and Health Administration
(OSHA). Exposure to the patient and other personnel
is presumed to be even lower as they are usually
further away from the acrylic mixing area. However,
even though vapor exposure is negligible, some
people may experience an idiosyncratic reaction or
asthma exacerbation in response to the pungent smell
of the material. Radiation doses to the operator have
already been described in the technical aspects portion
of this chapter. When stringent radiation safety prac-
tices are followed, operators can perform up to 500
vertebroplasties in a year before reaching the extrem-
ity dose limit (69). Patient peak skin doses in verte-
broplasty have also been studied (108). In 61 treated
patients, the mean peak skin dose was 684 mGy, and
in only 1 patient did peak skin dose exceed 2 Gy. At
no time did the peak dose ever exceed 3 Gy even
though more than one level was treated in many of
these individuals.
New fractures following vertebroplasty often
occur and may represent the natural history of osteo-
porosis rather than a complication of the procedure.
However, the issue of increased risk for fracture at an
adjacent level has been raised in the literature. Grados
et al. (19) found a slight but statistically significantly
increased risk of vertebral fracture in the vicinity of an
augmented vertebra when compared to a vertebral
fracture in the vicinity of an untreated fracture. Lin et
al. (102) evaluated a small group of patients who
developed adjacent endplate fractures following ver-
tebroplasty and found a higher proportion than those
who did not have an acrylic leak into the adjacent disc
space. These results must be considered with caution
as association does not necessarily mean causation,
and avoiding treatment of fractures that involve the
endplate may change the clinical response (109). It has
been suggested that the location and degree of height
restoration of the treated level (110), or filling of an
intraosseous cavity (111) may play a role in the devel-
opment of adjacent fractures.
In summary, complications are most commonly
associated with (1) poor visualization owing to inad-
equate fluoroscopic equipment, poor patient coopera-
tion (the moving target), or unsatisfactory acrylic
opacification; (2) operator error, such as inappropriate
patient selection; lack of knowledge of the radio-
graphic spinal anatomy, particularly bony and
venous; poor fluoroscopic-triangulation skills; unfa-
miliarity with equipment, devices, and PMMA; and
poor embolization technique; (3) lack of patient mon-
itoring; and (4) improper aseptic technique. By recog-
nizing and avoiding these potential pitfalls, and
thoroughly educating oneself prior to performing
vertebroplasty, operators will markedly decrease
their chances of causing a significant complication.
KYPHOPLASTY
In 2001, a new technique for percutaneous augmenta-
tion of osteoporotic VCFs called kyphoplasty was
described in the literature (25). In kyphoplasty, the
vertebral body is accessed in a similar manner as
vertebroplasty, but a balloon catheter (KyphX Inflatable
Bone Tamp, Kyphon, Inc., Sunnyvale, California, U.S.)
is used to create a space within the hemivertebra prior
to acrylic injection (Fig. 14). Kyphoplasty is quite sim-
ilar to vertebroplasty, differing only in the use of the
 Chapter 22: Percutaneous Vertebroplasty 405

Figure 14 Kyphoplasty performed on a patient with a T12 compression fracture from biopsy-proven multiple myeloma. With the exception
of the superior endplate compression, the vertebral body looks normal. After positioning of the balloons (A, B) they are symmetrically inflated
(C, D), resulting in lifting of the superior endplate (arrows). After the created cavities are filled with PMMA and the cannulas are removed
(E, F), the superior endplate returns to its original position. Abbreviation: PMMA, polymethylmethacrylate.

balloon, and has been referred to as balloon-assisted
kyphoplasty. Theoretical advantages of kyphoplasty
over vertebroplasty include the potential for vertebral
body height restoration, reduction of kyphotic angula-
tion of the spine, and lower rate of acrylic leakage into
adjacent soft tissues. The realization of these benefits,
however, has not been established in clinical studies.
Although several papers have been published
(112121), the clinical outcome data are not as exten-
sive as for vertebroplasty. The majority of the kypho-
plasty literature addresses outcomes in the treatment
of acute or subacute fractures, usually defined as
vertebral levels that are edematous on MRI or show
tracer uptake on nuclear medicine studies. However,
similar positive outcomes in pain relief and improved
mobility regardless of fracture age have been
described. In one study (119), patients with fractures
over four months old had nearly as favorable clinical
outcomes (87% response) as patients with fractures
less than ten weeks old (90% response). However,
most series describe a positive clinical response rate
that is very similar to what is seen in vertebroplasty-
treated populations. All these reports have been ham-
pered by the same methodologic flaws that were
described for the vertebroplasty literature.
Complications associated with kyphoplasty are
similar to those seen in vertebroplasty. Six major
complications in 531 patients (1.1%) treated with
kyphoplasty were reported in a multicenter collection
of patients, four of which were neurological compli-
cation. Nussbaum et al. (122) evaluated vertebroplasty
and kyphoplasty complications reported to the FDA
and found a number of kyphoplasty complications not
reported elsewhere. Eighteen cases involving spinal
canal intrusion were reported, of which thirteen cases
required surgical decompression and five cases resulted
406 Jensen
Figure 15 This elderly lady underwent an L4 kyphoplasty (A)
and showed clinical improvement. Six weeks later, she devel-
oped new back pain. Lateral plain film (B) shows new compres-
sion fractures from T12 through L3.
in permanent neurological deficit. Kyphoplasty has also
been reported to be associated with adjacent fracture
formation, occurring primarily within a two-month
window following the treatment (Fig. 15) (123).
CONTROVERSIES IN VERTEBRAL BODY
AUGMENTATION PROCEDURES
The major controversy between kyphoplasty and ver-
tebroplasty groups relates to height restoration,
kyphosis correction, and safety. Currently, there are
multiple studies that show improved height and
reduced kyphosis can occur with both techniques.
There is no data to support that these changes provide
any additional clinical benefit. Kyphoplasty propo-
nents state that the risk of PMMA extravasation is
diminished due to the creation of a cavity, thus mak-
ing kyphoplasty safer than vertebroplasty. However,
studies have shown that the rate of leakage is similar,
and in both instances the rate of clinical relevant
complication due to leakage remains small.
Because of additional equipment, anesthesia,
and hospital costs, kyphoplasty has been estimated
to cost 10 to 20 times more than vertebroplasty (124). It
is possible that certain subgroups of patients may drive
more benefit from one particular procedure. Features
that might affect choice of procedure include degree
of compression deformity, age of the fracture, and
the presence of neoplastic involvement, but the benefits
of kyphoplasty relative to vertebroplasty in such sub-
groups currently remain totally undefined. With the
considerable added financial expense of kyphoplasty, a
significant clinical benefit over vertebroplasty would
have to be proven to justify this cost.
Sacroplasty
Sacral insufficiency fractures are another cause of lower
back, hip, and leg pain in the elderly. These fractures
are usually difficult to diagnose as the symptoms are
nonspecific or radicular in nature, and the imaging
findings are less obvious than those found with VCFs.
Plain radiographs are often nondiagnostic or difficult to
interpret because of the curvature of the sacrum and
overlying bowel gas. MRI may show marrow edema,
and cortical disruption and bony sclerosis may be
detected on CT. The H- or butterfly-pattern of uptake
in the sacrum on bone scintigraphy is typical of frac-
tures of the body of the sacrum that involve the sacral
alae (125). Like vertebroplasty, medical treatment is
usually limited to immobilization and analgesics.
In 2002, Garant (126) first described sacroplasty.
A natural extension of vertebroplasty, sacroplasty,
involves the injection of acrylic into the sacral alar
fracture site under fluoroscopic control (127). The
operator is faced with unique technical challenges.
The sacrum is a thin, curved bone and localization of
the needle tip with respect to the fracture line, the sacral
foramina, and the inner cortex on the pelvic side is often
problematic. Poor visualization of the sacral foramina
during acrylic injection is a significant hazard.
When performed under fluoroscopy, the needle
is placed either through the dorsal cortex along the
short axis of the sacrum (126) or in the plane of the
long axis of the upper sacrum between the foramina
and the sacroiliac joint (128). Contrast injection to
confirm trocar placement and positioning of 20-G
Chiba needles at the sacral foramina for localization
may be useful safeguards (126). Placement of the
trocar under CT guidance with acrylic injection
under direct fluoroscopic visualization (127,129) or
performance of the entire procedure under CT fluo-
roscopy (130) has also been described.
Acrylic injected along the short axis has a ten-
dency to pool as a round collection at the needle tip
with only a short length of PMMA deposited along the
fracture (128). Placement of needles at each sacral
segment may be required to adequately fill the frac-
ture (126,127). As the injection is viewed in a frontal
oblique view, extravasation into the pelvis may not be
detected. The long-axis approach places a vertical
column of acrylic along the fracture line. With this
approach, only one needle per sacral ala is needed.
Since the ventral border of the sacrum is visualized
during the lateral injection, extraosseous extravasation
is more readily identified (128). With either approach,
acrylic is deposited along the track from anterior to
posterior in the short-axis approach and from superior
to inferior in the long-axis approach.
In the case studies and small series reported to
date (126,127,129,131), almost all patients reported
marked or complete relief of pain following sacro-
plasty. This technique has also been used in sacral
fractures associated with hemangiomas (132) and
metastatic lesions (131,133) (Fig. 16). Although techni-
cally more challenging than vertebroplasty, sacro-
plasty is another tool in the radiologists kit of
advanced augmentation procedures.

SUMMARY
Percutaneous vertebroplasty has advanced from an
obscure technique reserved for a few special cases to a
highly utilized procedure that consistently benefits a
significant number of patients worldwide. The prac-
tice of vertebroplasty continues to grow in size and
scope, fostering new developments, research, and
products. Hopefully in the near future, conclusive
data through randomized controlled trials will con-
firm what seems apparentthat vertebroplasty is safe
and efficacious in the vast majority of treated individ-
uals. It is vital to the growth of minimally invasive
spine procedures that all interventional radiologists
take an active interest in bringing this exciting tech-
nology to their patients and their practices.
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110. Kim SH, Kang HS, Choi JA, et al. Risk factors of new
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Abciximab, 168
Absolute ethyl alcohol, 178
Acetabulum, 404
Acrylic compaction, 396, 397
ACTH. See adrenocorticotropin (ACTH)
hormone
Activated clotting time (ACT), 164
Activated coagulation time (ACT), 247
Acute ischemic infarct, 101, 103
Acute ischemic stroke (AIS), 168
Adamkiewicz artery, 41, 49
Adjunctive imaging, 390
Adrenal lesion, overproduction of cortisol,
353. See also Cushings syndrome
Adrenals, macronodular hyperplasia
of, 353
Adrenocorticotropin (ACTH) hormone
dependent disease, 353
independent Cushings syndrome, 353
and adrenal imaging, 353
secreting pituitary adenomas, 353
difficulties in demonstration of, 354
Adult polycystic kidney disease, 126
Adverse drug reactions (ADRs), 389
African-Americans and intracranial
atherosclerosis, 325
Aggressive Borden type 2 DAVF
conversions, 344345
Allens test, 162
Allergic reaction, 161
Alteplase thrombolysis for acute noninter-
ventional therapy in ischemic stroke
(ATLANTIS) trial, 305
Amaurosis, 215
American Society of Interventional and
Therapeutic Neuroradiology
(ASITN), 246
Amplatz Goose Neck Snare, 179
Amyloid angiopathy, 92, 99, 105
Anastomoses, 29, 32. See also intracranial
collateral routes and anastomoses;
intraparenchymal venous
anastomoses
in aneurysm, 8182
arterial blood supply and, 3940,
4445
cerebellar, 59, 7581
interventional neuroradiology and,
5787
intracranial atherosclerosis disorders and,
7072
intraspinal extradural, arterial blood
supply in, 3940
ischemic stroke and, 6571, 82
lateral geniculate, 82
leptomeningeal, 5761, 66, 81
pericallosal, 82
pericallosal-pericallosal, 29
persistent caroticobasilar, 2931
transmedullary midline, 4748
venous midline, 49
Aneurysm, 27, 9296, 109
associated with brain AVM. See brain
arteriovenous malformations (AVMs)
clinical applications of MRA in
intracranial, 124127
Index
clips, 90
coiled intracranial, surveillance,
143144
coil protocol, 246248
CT techniques clinical applications
in, 9296
decision matrix for treatment
of, 239241
disorders, 8182
endovascular therapy of ruptured
unsecured, 270271
endovascular treatment of associated, 223
fusiform thrombosed, 82
intracranial. See intracranial aneurysms
intracranial collateral routes and
anastomoses in, 8182
isolated spinal artery, 380383
nonaneurysmal subarachnoid
hemorrhage, 96
pericallosal, 109
radiographic follow-up of treated, 248
reconstructive repair of, 246
recurrence, following coiling, 249
ruptured cavernous, 231
saccular aneurysmal rupture, 9296
subarachnoid hemorrhage, 9296
AngiJet Rheolytic Thrombectomy
System, 179
Angiogenesis, 6061
Angiographic diagnosis
extradural ICA dissection, 216218
extradural VA dissection, 216218
Angiography
3D, 325
catheter, 141
conventional, 94, 124, 131132
CT. See CT angiography (CTA)
digital subtraction angiography (DSA).
See digital subtraction angiography
(DSA)
high-resolution, 325
iliac artery, 181
spinal, catheter for, 164
Angioplasty, 169
balloon, 266270
carotid, 146147
coronary, 146
percutaneous, in posterior
arteries, 147
of symptomatic MCA stenosis, 327
transluminal, concept of, 325
Angioplasty and stenting
case illustrations, 319320
complications and preventive
measures, 319
early trials, 313314
evolution, 312317
postintervention follow-up, 318
risk factors, 318
stenting procedure, 317318
trials of angioplasty and stent placement
with dep vs. cea in high-risk patients,
314317
trials of angioplasty and stent placement
with dep vs. cea in low-risk patients,
317
Angio-Seal, 181
Angular artery (AngA), 27
Anterior cerebral artery (ACA), 2529, 31,
5759, 66, 69, 7273, 82, 94, 109,
138139, 141143, 202
dissection, 213, 215
Anterior choroidal artery (AchA), 25
Anterior communicating artery (ACoA),
5758, 62, 7475, 81, 90, 9293, 138,
143144
Anterior ethmoidal artery (AeA), 25
Anterior inferior cerebellar artery (AICA),
4, 30, 3233, 59
Anterior internal frontal artery (AntIFA), 25
Anterior radiculomedullary artery, 41
Anterior spinal artery (ASA), 4, 3234,
4145, 51
Anterior temporal artery (AntTemp), 27
Anticoagulation, 164
therapy, 180
Aortic arch
atheroma, 146
and branches, 12
Arterial access, 162
Arterial and venous occlusion tests,
183187, 190
brain stemevoked potentials
monitoring, 186
cerebral blood flow measurements, 185
complications, 186
CT perfusion, 185
electroencephalography, 185186
induced hypotension, 185
measurement of stump pressures, 185
MR perfusion, 185
neurophysiological monitoring, 186
perfusion imaging, 185
single-photon emission tomography, 185
somatosensory-evoked potentials
monitoring, 185186
techniques, 183187, 190
transcranial Doppler examinations,
185186
xenon CT, 185186
Arterial blood supply
in cauda equina, 43
in cervical region, 4243
extra- and intraspinal extradural
anastomoses, 3940
intrinsic spinal cord arteries and, 44
radicular supply, 4042
by region of spinal cord, 4245
sources, 3940
to spine and spinal cord, 3945
superficial and intrinsic arterio-arterial
anastomoses, 4445
superficial spinal cord arteries and,
4042
in thoracic region, 43
in thoracolumbar region, 43
Arterial collateral anatomy, 57
Arterial dissection, 103104
in duplex US sonography, 150
Arterial feeders, classification of,
279280
Arterial spin-labeled perfusion MRI, 89
412 Index
Arterioarterial thromboembolic stroke,
medical therapy for, 326
Arteriogenesis, 6061
Arteriovenous fistula (AVF), 92, 9697, 106,
108
vertebral-vertebral, 380
Arteriovenous malformation (AVM), 20, 23,
51, 92, 140, 144, 146, 178, 189190.
See also specific AVMs
anatomical evaluation, 5254
associated with intracranial arterial
aneurysms. See intracranial arterial
aneurysms
CT techniques clinical applications in,
9699
embolization. See embolization, of AVMs
endovascular management of, 205210
facial, 162, 206
mandibular, 207
nasomaxillary, 206
nontraumatic hemorrhage, 9699
vascular malformations, 205208
venous occlusive disorders, 9799
Ascending aortic arch (AOA), 1
Ascending cervical artery, 1, 4, 3940
Ascending pharyngeal artery (APA), 710,
3132
ASITN. See American Society of
Interventional and Therapeutic
Neuroradiology (ASITN)
Aspirin, 172
therapy, 180
Associated aneurysms, endovascular
treatment, 223
Asymptomatic carotid artery surgery
(ACAS) trial, 148
Asymptomatic carotid atherosclerosis study
(ACAS), 311
Atherosclerosis, 83, 101103
Atherosclerosis, location and severity of
in internal carotid artery (ICA) origin, 325
in middle cerebral artery (MCA), 325
in posterior cerebral artery (PCA), 325
proximal and midportion of basilar
artery, 325
spared areas
anterior cerebral artery (ACA), 325
posterior inferior cerebellar arteries
(PICAs), 325
superior cerebellar artery (SCA), 325
Atherosclerotic CVD, 146
endovascular treatment of, 328
Atherosclerotic plaques, 331
Atretic carotid arteries, 102
Atrial fibrillation, 146
Autotriggered elliptic centric-ordered 3D
gadolinium enhanced MRA
(ATECO-MRA), 339, 347. See also
magnetic resonance angiography
(MRA)
AVF. See arteriovenous fistula
Aviator balloon catheter, 168
AVM. See arteriovenous malformation
Balloon(s), 168
endovascular, 168
high-pressure, 168169
hyperform, 171
low-pressure, 169171
occlusion, 183, 185186
occlusive devices, 171
sentry, 269
Balloon angioplasty, 266270
first success, 325
and stent placement, comparison, 328
for vasospasm, 170
Balloon-assisted kyphoplasty.
See kyphoplasty
Balloon-assisted remodeling, 170
Balloon-assisted vertebroplasty, 387
Balloon-expandable coronary stents, 328
drawbacks, 329
Balloon overdilatation, in basilar artery and
MCA, 327
Balloon test occlusion (BTO), 170171
technique, 241242, 251252
of the ICA, 244
Balt Magic, 165
Barium sulfate, 396
Basilar artery (BA), 30, 3334, 138139,
141, 143
Basilar plexus, 59
Bench testing, 396
Bernasconi tentorial artery, 18, 2324
Bioeffects and safety, of US imaging,
135136
Bioimplants, 325
Bipediculate approach, 395
Biplane road mapping, 325
Blastic metastases, 400
Bleeding diathesis, 161
Blood-brain barrier (BBB), 153154, 186
Blood urea nitrogen, 161
Blood velocity measurements, use of US
imaging, 136
Blood vessel anatomy, clinical application
of, 5254
Blunt carotid injury (BCI), 108
Blunt carotid vertebral injury (BCVI),
108109
Blunt injury, CT techniques clinical
applications in, 107109
Blunt neck trauma, 107
Bolus contrast CT perfusion, 8992
Bone scintigraphy, 390, 406
Bony sclerosis, 390
Boston Scientific, 329
Bovine arch, 2
Brachiocephalic artery (BCA), 12
Brain
applied neurovascular anatomy
of, 2337
coronal view of, 27
MRI through rostral midbrain, 24
Brain arteriovenous malformations (AVMs).
See also arteriovenous malformation
(AVM)
aneurysms associated with
classification, 281282
clinical implications, 284286
epidemiology, 282283
pathogenesis of, 283284
treatment approaches, 286287
angioarchitecture of, 279287
angiography of, 277279
classification and pathogenesis, 275276
embolization of
background, 288289
complications, 297299
cure rates, 297
indications for, 289290
palliative, 297
postprocedural care, 296
preradiosurgical result, 296297
presurgical result, 296
tools and technique, 290296
epidemiology, 276
grading systems for, 287288
natural history of, 276277
nidus, 280281
Brain stemevoked potentials
monitoring, 186
Bruit, 103
Bupivacaine hydrochloride, 393
Calcarine artery (CalcA), 34
Calcification, in duplex US sonography, 151
Callosomarginal artery (Call-MargA),
2526
Capillary hemangiomas, 195196
Capillary malformations, 205, 208
Cardiopulmonary arrest, 99
Cardiovascular effects, 389
Carney triad, 199
Carotid and vertebral arteries
dissections of, 213227
2D TOF for imaging, 117
US imaging of, 147151
Carotid angioplasty, 146147
Carotid angioplasty and stenting (CAS),
146147, 150, 163164. See also
stenting
Carotid artery stenosis
contrast-enhanced MRA for, 119
MRA clinical applications in, 127129
Carotid-basilar anastomosis, 188
Carotid body tumors, 200201
Carotid cavernous fistula (CCF)
anatomy and pathophysiology, 232233
classification, 233
clinical features, 231232
etiology, 231
follow-up, 237
imaging studies, 234235
indications for treatment, 233234
symptoms and signs associated with,
233234
treatment options and considerations,
235237
endovascular therapy, 235237
medical therapy, 235
surgical therapy, 235
transarterial approach, 235237
transorbital approach, 237
transvenous approach, 237
Carotid duplex, clinical utility of, 149150
Carotid endarterectomy (CEA), 146148,
150. See also angioplasty and stenting
Carotid ligation surgery, 241
Carotid occlusion
in duplex US sonography, 150151
testing, 183
Carotid occlusion surgery study (COSS), 75
Carotid revascularization of stenosis, 7475
Cassinari tentorial artery, 18, 2324
Catheter angiography, 141
Catheter-based thrombolysis, 105
Catheterization
intra-arterial (IA), 163
transfemoral, 163
Catheters. See specific catheter
Caucasians, proneness to extracranial
disease, 325
Cauda equina, arterial blood supply in, 43
Cavernous hemangiomas, 195
Cavernous segment, 18
Cavernous sinus sampling, 359
Central artery (CenA), 27
Central retinal artery (CrA), 25
occlusion, 215
Cephalosporin, 181
Cerebellar anastomoses, 59, 7881
Cerebral angiography, 146
Cerebral arteriovenous malformation
(CAVMs), 64. See also arteriovenous
malformation (AVM)
intracranial collateral routes and
anastomoses in, 7881

Cerebral artery revascularization, by using
balloon dilatation, 329
Cerebral blood flow (CBF), 89, 9192,
100101, 105, 132, 140, 143, 185186
imaging, 171
Cerebral blood volume (CBV), 91, 101,
132, 185
Cerebral hypoperfusion, 179
Cerebral ischemia, 83, 146
Cerebral perfusion imaging, 104
Cerebral perfusion pressure (CPP), 105106
Cerebral vascular disease, 146
Cerebral vascular malformations. See brain
arteriovenous malformations (AVMs)
Cerebral vasospasm, 264
diagnosis and monitoring, 141143
Cerebral veins, 3537
deep venous system, 37
superficial venous system, 3537
Cerebral venous thrombosis (CVT), 60, 63
intracranial collateral routes and
anastomoses in, 7578
Cerebrospinal fluid (CSF) leak, 403
Cerebrovascular CTA, 101104
arterial dissection, 103104
atherosclerosis, 101103
stenotic-occlusive disease, 101103
Cerebrovascular disease (CVD), 135
atherosclerotic, 146
endovascular treatment of, 328
Cervical angiogram, 169
Cervical region
arterial blood supply in, 4243
venous drainage in, 48
Cervical segment, 18
Cervical veins, 19
Chiba needles, 406
Circle of Willis, 45, 5758, 61, 63, 7475, 79,
81, 88, 92, 119, 139, 143, 183, 231
Cisternography, 8788
Clinical applications of CT techniques,
92109
in ischemia, 99106
in nontraumatic hemorrhage, 9299
in trauma, 105109
in traumatic intracranial aneurysms, 109
Clopidogrel, 172, 180
CLOTBUST study, 153154
Clot formation, 306
Coagulopathy, 92, 96, 99, 105, 209
Cobra 1 and 2, 164
Coiled intracranial aneurysms surveillance,
143144
Coil occlusion technique, 244
Collagen deficiency diseases, 231
Collagen-vascular disease, 126
Common carotid arteries (CCAs), 32, 151,
198, 200204, 207, 216217, 220
cervical carotid variations, 6
external carotid artery, 518
ascending pharyngeal artery, 710
external carotid anastomotic network,
1417
facial artery, 1011
internal maxillary artery, 12, 1415
lingual artery, 1011
occipital artery, 1012
posterior auricular artery, 11
restoration of flow, 17
superficial temporal artery, 1214
superior thyroid artery, 78
terminal branching, 7
internal carotid artery, 1518
Common femoral artery (CFA), 162
Computed tomographic angiography
(CTA), 6264, 8890, 92109, 138,
140141, 216
Computed tomographic venography
(CTV), 77
Computed tomography (CT), 391, 400.
See also CT techniques
conventional, 8788
fluoroscopy, 393
guidance, 401, 406
myelography, 8788
Computed tomography perfusion (CTP),
8992, 100101, 185
Computer-assisted tomography. See CT
techniques
Contrast-enhanced CT (CECT), 88
Contrast-enhanced MRA, 119121
Conventional angiography, 94, 124,
131132
Coronary angioplasty, 146
Coronary artery bypass grafting
(CABG), 312
Coronary catheterization, 146
Corpus callosum, 34
Cortical venous reflux (CVR) and DAVFs,
336339, 342
Corticosteroid therapy, 196
Corticotrophin- releasing hormone
(CRH), 353
Coumadin therapy, 392
Cranial DAVFs. See dural arteriovenous
fistula (DAVF)
Cranial nerve defects, 103
Craniocerebral angiographic anatomy, 23
Creatinine, 161
CT techniques. See also computed
tomography
angiography, 8890, 92109, 138,
140141, 216
bolus contrast CT perfusion, 8992
cisternography, 8788
clinical applications, 92109
in ischemia, 99106
in nontraumatic hemorrhage, 9299
stroke-like conditions, 104106
subacute and chronic setting, 101
in trauma, 105109
conventional CT, 8788
development of, 87
myelography CT, 8788
perfusion CT, 8992
stable xenon, 92
CT venogram (CTV), 88, 9899
Curative embolization, 290
Curing, 387
Cushings syndrome, 354
ACTH-dependent or ACTH-independent,
353
symptoms of, 353
Cystic medial necrosis, 214
Decision matrix for treatment,
of aneurysms, 239241
Deconstructive approach, to intracranial
arterial aneurysms
safety and efficacy, 241
therapeutic vessel occlusion techniques,
241246
Deconvolution techniques, 91
Deep cervical artery, 3940
Deep middle cerebral vein, 59
Deep venous system, in cerebral
veins, 37
Dexamethasone, 177, 235
Diagnostic catheters, 164
Diagnostic US imaging
carotid angioplasty, 146147
cerebral vasospasm diagnosis and
monitoring, 141143
Index 413
coiled intracranial aneurysms
surveillance, 143144
in interventional neuroradiology,
136147
intracerebral venous system, 145
intracranial
aneurysms endovascular treatment
monitoring, 147
arterial occlusion detection, 137140
atherosclerotic stenosis, 140141
microemboli detection, 145147
in neurointerventional procedures
monitoring, 146147
percutaneous angioplasty in posterior
arteries, 147
reference values, 137
stenting, 146147
TCD imaging, 136137
vascular malformations diagnosis, 144
Diamox, 235
Diffusion-tensor imaging-based MR
tractography, 183
Diffusion-weighted imaging (DWI),
99100, 132133
Digital subtraction angiography (DSA),
8889, 9294, 9699, 101102, 106, 108,
125127, 130132, 141144, 148149,
189, 355. See also angiography
of SDAVF, 5354
Dimethyl sulfoxide (DMSO), 178
Diphenhydramine, 161
Direct CCF. See carotid cavernous fistula
(CCF)
Direct current cardioversion, 146
Direct puncture, 162
embolization, 402
Dissections, 231. See also dissection of
carotid and vertebral arteries
distal cervical carotid, 103
intracranial, 96
MRA clinical applications in, 129
Dissection of carotid and vertebral arteries,
213227
angiographic diagnosis, 216218
extradural ICA dissection, 216218
extradural VA dissection, 216218
clinical manifestations
extradural ICA dissection, 215
extradural VA dissection, 215
intradural ICA dissection, 215216
intradural VA dissection, 216
endovascular treatment
associated aneurysms, 223
extradural dissection, 220223
intradural dissection, 224226
epidemiology, 213
medical treatment
extradural dissection, 219
intradural dissection, 220
pathogenesis, 213215
pathophysiological process of, 221
prognosis and outcome, 226227
surgical treatment
extradural dissection, 219220
intradural dissection, 223
treatment, 219226
endovascular treatment, 220226
medical treatment, 219, 223
surgical treatment, 219220, 224
Distal internal carotid artery (dICA), 3132
Distal middle cerebral artery, 2930
Distal posterior cerebral artery, in
vertebrobasilar system, 35
Distal vasospasm, 264
Doppler display modes, in US imaging, 136
Dorsal meningeal artery, 18, 23
Dotter, Charles T., 325
414 Index
Duplex US sonography, 147151
arterial dissection, 150
calcification, 151
carotid occlusion, 150151
clinical utility of carotid duplex, 149150
degree of stenosis, 148149
extracranial VA, 151
high bifurcation, 151
monitoring after revascularization
procedures, 149150
pitfalls, 150151
reference values, 149
tortuosity, 151
vascular pathology sonographic
assessment, 147148
Dural arteriovenous fistula (DAVF), 7778,
131132. See also dural arteriovenous
shunts disorders; Spinal vascular
malformations
adult type, 335
aggressive forms, 338339
anatomical setting of the fistula, 335
benign and aggressive clinical features
of, 337
classification schemes
Borden classification, 337
Cognard classification, 337
cranial
classification, 336
clinical features, 336339
diagnostic imaging, 339340
therapeutic considerations, 340346
pathophysiology, 335336
spinal
classification, 346
clinical features, 346347
diagnostic imaging, 347
therapeutic considerations, 348
transarterial approach, to venous packing
of a traumatic, 343
transvenous facial approach, to bilateral
cavernous, 341
Dural arteriovenous shunts disorders,
intracranial collateral routes and
anastomoses in, 7778
Dural sinus drainage, in DAVF
management, 342346
Dyspnea, 398
Echo time, in TOF techniques, 119
Eclampsia, 92, 99, 105, 143
Ectopic tumors and pituitary adenomas, 354
Edema, 105, 390
Ehlers-Danlos syndrome, 103, 214, 231
EKOS ultrasound-emitting infusion
catheter, 309
Electroencephalography (EEG),
185186, 188
Embolectomy, 180
mechanical, 178179
Embolic agents, 292
Embolic material microcoils, 175177
Embolic protection devices, 171172
Embolization
of a cavernous sinus DAVF with liquid
adhesives, 340
endovascular, 196
IM-AVM, 378379
percutaneous transarterial, 399
PM-AVF, 374375
preoperative meningioma, 177
preradiosurgical, 289290
presurgical, 289
for spinal dAVF, 369371
targeted transvenous, of a cavernous
DAVF, 342
transarterial, 402
tumors, 177
Embolization, of AVMs, 167, 183. See also
AVMs
background, 288289
complications, 297299
cure rates, 297
indications for, 289290
palliative, 297
postprocedural care, 296
preradiosurgical result, 296297
presurgical result, 296
tools and technique, 290296
Embosphere microspheres, 177
Embospheres, 177
EMI Mark I scanner, 87
Endovascular embolization, 196
Endovascular infusions
vasodilator infusions, 167168
Wada testing, 167
Endovascular management, of tumors and
vascular malformations of head and
neck, 195211
Endovascular occlusion, of the ICA, 241
Endovascular strategies
acute ischemic stroke. See intra-arterial
thrombolysis
for atherosclerotic disease, 328
for AVMs. See embolization, of AVMs
for DAVFs, 348
intracranial atherosclerotic occlusive
disease (ICD), 332
for post-subarachnoid hemorrhage
vasospam
balloon angioplasty, 266270
intra-arterial antispasmodics, 264266
of a ruptured unsecured aneurysm,
270271
treatment outcomes, 271
in the treatment of aneurysms
conditions favouring, 250251
deconstructive approach, 241246
reconstructive approach, 246,
248249
Endovascular treatment, 70
associated aneurysms, 223
extradural dissection, 220223
intradural dissection, 224226
Endovascular US thrombolysis, 153
Enoxaparin (Lovenox), 392
Entry slice phenomenon, 113
Envoy catheter, 165
Envoy guide catheter, 166
Epilepsy, 183, 186
Epistaxis, 177, 208210
Ethanol, 178
Ethiodol, 178, 293
Ethmoidal artery, 24
European carotid surgery trial (ECST),
148, 311
European cooperative acute stroke study
(ECASS), 305
External carotid artery (ECA), 3, 518, 3132,
198, 200, 202204, 206, 209210
anatomic considerations, 3132
ascending pharyngeal artery, 710, 3132
external carotid anastomotic network,
1417
facial artery, 1011
internal maxillary artery, 12, 1415
lingual artery, 1011
occipital artery, 1012
posterior auricular artery, 11
restoration of flow, 17
superficial temporal artery, 1214
superior thyroid artery, 78
terminal branching, 7
External jugular vein (EJV), 19
Extracranial arterial stenosis disorders,
intracranial collateral routes and
anastomoses in, 7476
Extracranial tumors, 82
Extracranial vertebral arteries, 151
Extradural arteriovenous malformation/
fistulas
clinical presentation, 380
imaging, 380
treatment, 380
Extradural dissection, 213
angiographic findings in, 216217
associated aneurysms, 223
endovascular treatment, 220223
medical treatment, 219
surgical treatment, 219220
Extradural ICA dissection, 213, 215
Extradural VA dissection, 213, 215
Extradural venous spaces, venous drainage
in, 52
Extraspinal extradural anastomoses, arterial
blood supply in, 3940
Facial artery, 31
Facial AVM, 162, 206
Facial veins, 19
False lumen (FL), 2
Falx cerebri, 26
Fat embolization syndrome, 146
Feeding arteries, 280
Fentanyl, 393
Fibromuscular dysplasia (FMD), 103, 105,
126, 214, 216, 219, 223, 231
Fisher four point grading scale, 263
FLAIR MRI vascular hyperintensity (FVH),
64, 6768
Flow compensation, in TOF techniques, 118
Flow-guided microcatheters, 165166, 178
Fluid-attenuated inversion recovery
(FLAIR), 64, 6769, 73, 75, 204
Fluoroscopic visualization, 401
Frontopolar artery (FpA), 25
Functional magnetic resonance imaging
(fMRI), 183, 188, 190. See also
magnetic resonance imaging (MRI)
Fusiform thrombosed aneurysm, 82
Gadolinium-enhanced MR, in treatment
of spinal DAVF, 348
Gadolinium-enhanced MRA, 119121, 127
Gastrointestinal effects, 389
GDC system. See Guglielmi detachable
coil (GDC) system
General anesthesia, 178
Gerstmanns syndrome, 27
Glomus jugulare tumors, 199201
Glomus tumors. See paragangliomas
Glomus tympanicum tumors, 199
Glycoprotein (GP)
IA, 168
IIb/IIIa inhibitors, 306
Gradient echo imaging sequences, 100
Gradient-recalled echo (GRE) sequences,
6465
Granulomatous angiitis, 105
Gray-scale imaging, in US imaging, 136
Groin closure, 181
Groin fibrosis, 163
Guglielmi detachable coils (GDC), 175,
245246, 249
Guide catheters, 164165
Guidewire-directed microcatheters, 166
Guidewires, 166167
Gyral AVMs, 278279. See also arteriovenous
malformation (AVM)

Headache, 103
Head veins, 1820
HEAL trial, 250
Hemangiomas, 195196
Hemangioma thrombocytopenia
syndrome, 196
Hematuria, 207
Hemorrhagic and stroke-like conditions,
T techniques clinical applications,
104106
Hemorrhagic complications, 180
Heparin, 162, 164
Heparin-coated stents, 173
Hereditary hemorrhagic telangiectasia
(HHT), 363
diagnostic criteria for, 209210
Herniation, 105
Herpes virus, 105
Heubner artery, 25
High-resolution angiography, 325
Homocysteinuria, 103
Horners syndrome, 103
ipsilateral, 215
Humanitarian device exemption (HDE),
stent as, 328
Hydrogel coils, 175
Hyperacute and acute setting
CT techniques clinical applications,
99101
in ischemia, 99101
Hypercortisolemia. See Cushings syndrome
Hyperform balloon, 171
Hyperperfusion syndrome, 105
Hypertension, 92
Hypertensive encephalopathy, 105
Hypertensive hemorrhage, 99, 105
Hypertensive therapy, 179180
Hypervascular tumors, 401
Hypervolemic therapy, 180
Hypoglossal artery, 31
Hypoxic-ischemic injury, 99
Ibuprofen, 398
Iliac artery angiography, 181
Induced hypotension test, 185
Inferior hypophyseal artery, 18, 23
Inferior petrosal sinus (IPS), 59, 232, 237
Inferior petrosal sinus sampling (IPSS), 353
alternatives to, 359360
coaxial technique using microcatheter to
catheterize, 354
complications of IPSS, 359
contralateral injection for, 357
for differential diagnosis of Cushings
disease, 353354
indications for, 354
interpretation of sampling data, 358359
lavender-top tubes in, 354
microcatheter technique of, 356
negative result from, 358
role in lateralizing pituitary adenoma,
358359
successful catheterization of IPS, 355
use of sedation in, 354
Inferolateral trunk, 23
Innominate artery, 1
Insufflator device, 169
Insula, arterial anatomy of, 28
Intelligel, 175
Intercostopedicular approach, 401
Interferon therapy, 196
Interhemispheric fissure, 96
Intermediate lenticulostriate artery (IL), 28
Internal carotid artery (ICA), 5, 60, 62, 70,
72, 7475, 9295, 97, 102103, 105,
108109, 138140, 144145, 148,
150151, 198, 200203, 209210,
214221, 223, 226, 231238
anatomic considerations, 2730
anterior cerebral artery, 2729
distal middle cerebral artery, 2930
angiogram of, 30
anterior cerebral artery, 2529, 31
anterior choroidal artery, 25
bifurcation, 28
diagnostic parameters for, 149
lateral angiographic projection of right, 24
middle cerebral artery, 2630
ophthalmic artery, 2325
posterior communicating artery, 2425, 28
stenosis, 146, 149
Internal iliac arteries, 3940
Internal jugular vein sampling, 360. See also
inferior petrosal sinus sampling
(IPSS)
Internal mammary (INM) artery, 1
Internal maxillary artery (IMA), 67, 3132
Internal parietal artery (IpA), 34
International Study of Unruptured Intra-
cranial Aneurysms (ISUIA), 239240
International subarachnoid aneurysm trial
(ISAT), 246
Interventional neuroradiology
CT imaging and physiologic techniques
in, 87109
intracranial collateral routes and anasto-
moses in, 5787
MR angiography applications in,
113133
ultrasonographic imaging and
physiological techniques in,
135154
Interwoven microfilaments, 175
Intra-arterial antispasmodics, 264266
Intra-arterial thrombolysis, 168, 221
combined intravenous and intra-arterial
approach, 306
combined with glycoprotein IIb/IIIa
inhibitors, 306
multimodal, 306309
as sole treatment, 305306
and thrombolysis in myocardial infarction
(TIMI) grading scale, 309
Intracerebral venous system, 145
Intracranial aneurysms
endovascular treatment monitoring, 147
MRA clinical applications in, 124127
Intracranial angioplasty. See stent
techniques
Intracranial arterial aneurysms
AVMs associated with
classification, 281282
clinical implications, 284286
epidemiology, 282283
pathogenesis of, 283284
treatment approaches, 286287
clinical presentation, 239
definitions and epidemiology, 239
incidence rate, 239
treatment, 241, 249251
aneurysm coil protocol, 246248
balloon test occlusion (BTO), 251252
decision matrix, 239241
deconstructive approach, 241246
follow-up, 248
improved techniques, 252253
reconstructive approach, 246,
248249
stent techniques, 253256
surgery following partial embolization,
252253
thromboembolic complications, 254
using neuroform devices, 254
Index 415
Intracranial arterial occlusion detection,
137140
Intracranial arteries, morphology and
hemodynamics of, 328
Intracranial arteriovenous malformations
(AVMs), 129. See also arteriovenous
malformation (AVM)
Intracranial atherosclerosis disorders,
intracranial collateral routes and
anastomoses in, 7072
Intracranial atherosclerotic occlusive disease
(ICD)
aspects of endovascular revascularization
for, 325
demographic characteristics, 325
endoluminal revascularization of, 326
endovascular treatment of (by angioplasty
and stenting), 332
natural history of, 326
stenting and angioplasty for, 325
treatment indications, 326
warfarin-aspirin recurrent stroke study
(WARSS) trial, 326
warfarin versus aspirin study, 326
Intracranial atherosclerotic stenosis,
140141
Intracranial collateral routes and
anastomoses
anatomy of, 5759
cerebral hemodynamics and, 62
clinical correlates, 62
disorders, 6583
aneurysms, 8182
cerebral arteriovenous malformations,
7881
cerebral venous thrombosis, 7577
dural arteriovenous shunts, 7778
extracranial arterial stenosis, 7476
intracranial atherosclerosis, 7072
ischemic stroke, 6571
moyamoya syndrome, 7274
occlusion, 7476
tumors, 8283
epidemiology of, 60
imaging, 62, 65
in interventional neuroradiology, 5787
pathophysiology of, 6062
angiogenesis, 6061
arteriogenesis, 6061
Intracranial dissection, 96
Intracranial embolization coils, 90
Intracranial neoplasms, 92, 99, 105
Intracranial pressure monitoring, 162
Intracranial stenotic-occlusive disease, 102
Intracranial tumors, 82
Intracranial vascular malformations, MRA
clinical applications in, 129131
Intradural dissection, 213
angiographic findings in, 217, 218
clinical manifestations, 216
endovascular treatment, 224226
medical treatment, 223
surgical treatment, 224
Intradural ICA dissection, 213, 215216
Intradural VA dissection, 213
angiographic features in, 219
angiographic findings in, 217, 218
clinical manifestations, 216
Intramedullary arteriovenous malformation
(IM-AVMs). See also arteriovenous
malformation (AVM)
clinical manifestations, 377
imaging, 377378
metameric angiomatosis, 378
treatment, 378379
Intraparenchymal venous anastomoses,
venous drainage in, 4748
416 Index
Intraspinal extradural anastomoses, arterial
blood supply in, 3940
Intravascular deoxygenation, 61
Intraventricular hemorrhage, 96
Intrinsic arterio-arterial anastomoses,
arterial blood supply in, 4445
Intrinsic spinal cord arteries, 44, 4647
Intrinsic veins, venous drainage in, 4647
Introducer sheaths, standard, 163164
IPSS. See inferior petrosal sinus sampling
(IPSS)
IPS venogram, patient with Cushings
disease, 355
ISAT. See international subarachnoid
aneurysm trial (ISAT)
Ischemia, 132
cerebrovascular CTA, 101104
CT techniques clinical applications in,
99106
hemorrhagic and stroke-like conditions,
104106
hyperacute and acute setting, 99101
subacute and chronic setting, 101
Ischemic complications, 179180
Ischemic event, risk of, 104
Ischemic optic neuropathy, 215
Ischemic stroke
intracranial collateral routes and
anastomoses in, 6571, 82
MRA clinical applications in, 132133
Isobutyl-2-cyanoacrylate (IBCA), 289
Isolated spinal artery aneurysms, 380383
ISUIA. See International Study of
Unruptured Intracranial Aneurysms
(ISUIA)
Joint Study of Extracranial Arterial
Occlusion, 325
Jugular venous sampling, 360
Jugulotympanic paragangliomas, 199200
Juvenile angiofibroma (JAF), 196199, 209
Kaposiform hemangioendothelioma, 196
Kasabach-Merritt syndrome, 196
Kissing balloon technique, 331 Maximum intensity projection (MIP), 90, 93,
Klippel-Trenaunay syndrome, 275
Kommerells diverticulum, 1
Kummells disease, 390
Kyphoplasty, 387, 402, 404
advantages over vertebroplasty, 405
controversies with vertebroplasty, 406
Kyphosis, 389
Lacrimal artery (LA), 2425
LAO arch configuration, 2
Laser thrombectomy, 179
Lateral geniculate anastomoses, 82
Lateral lenticulostriate artery (LL), 28
Lateral posterior choroidal artery
(LpcA), 34
Left common carotid artery (LCCA), 1
Left internal carotid artery (LICA), 222, 224
Left subclavian artery (LSUB), 1
Lenticulostriate arteries (LentStrA), 2527
Lenticulostriate collaterals, 70, 72, 81
Leptomeningeal anastomoses, 5761, 66, 81
Leptomeningeal collaterals, 6264, 70, 82
Lidocaine, 162
cardiac, 162, 167
Lingual artery, 1011, 31
Liquid coils, 176
Luer lock syringes, 396397
Lumbar arteries, 4
Lumbar region, venous drainage in, 50
Luminal stenosis, assessment with
MRA, 127
Lymphatic malformations, 205, 208
Lymphoma, 401
Magnetic resonance and recanalization
of stroke clots using embolectomy
(MR RESCUE) trial, 308
Magnetic resonance angiography (MRA),
39, 57, 6264, 6769, 71, 88, 97, 99,
101102, 216, 248, 365
application in interventional
neuroradiology, 113133
autotriggered elliptic centric-ordered
3D gadolinium enhanced
(ATECO-MRA), 339, 347
clinical applications, 124133
carotid stenosis, 127129
dissections, 129
intracranial aneurysms, 124127
intracranial vascular malformations,
129131
ischemic stroke, 132133
spinal vascular malformations,
131132
contrast-enhanced MRA, 119121
gadolinium-enhanced, 119121, 127
multiplanar reconstructions (MPRs)
in, 126
phase contrast MRA, 121124
TOF techniques, 113119
Magnetic resonance digital subtraction
angiography (MR DSA), 97, 130
Magnetic resonance imaging (MRI), 39,
97, 99101, 216, 354, 365. See also
functional magnetic resonance
imaging (fMRI)
arterial spin-labeled perfusion, 89
pituitary. See pituitary MRI
through rostral midbrain, 24
Magnetic resonance venography (MRV), 64,
7677, 80
Magnetization transfer imaging (MTI), 118
Magnetoencephalography (MEG), 183
Marfans syndrome, 103, 214
Massive oral bleeding, 2
MATRIX-ACTIVE trial, 250
Narcotic analgesia, 389
97, 99, 105
MCA. See middle cerebral artery
McConnels capsular artery, 18, 23
Mechanical embolus removal in cerebral
ischemia (MERCI) trial, 308
Medial posterior choroidal artery
(MpcA), 34
Medical treatment
extradural dissection, 219
intradural dissection, 220
MEG test, 188189
Meningiomas, 82, 202204
Meningohypophyseal trunk, 23
Merci Retrieval System, 308
Merci Retriever, 163, 178179
Metameric angiomatosis, 378
Methylmethacrylate, 404
Microbubble-augmented US
thrombolysis, 154
Microcatheters, 179
flow-guided, 165166
guidewire-directed, 166
shapes, 166
Microembolic signals (MES),
145146
Microemboli detection, by diagnostic US
imaging, 145147
Microguidewires, 167, 179
MicroLysUS infusion catheter, 179
Microvena snare, 308309
Midazolam, 393
Middle cerebral artery (MCA), 2530, 5859,
6264, 6670, 7273, 79, 82, 92, 109,
138143, 151, 153154, 222
aneurysms, 9394
balloon overdilation, 327
dissection, 213, 215
stenosis, 70
Middle internal frontal artery (MidIFA), 25
Middle lenticulostriate artery (ML), 28
Middle meningeal artery (MMA), 31, 200,
202204
Middle temporal artery (MidTemp), 27
Milrinone, 266
Mirage wire, 167
Mixed (sulcogyral) type AVMs, 279.
See also arteriovenous malformation
(AVM)
MOTSA technique. See multiple
overlapping thin slab acquisition
(MOTSA) technique
Moyamoya syndrome, 96, 105
intracranial collateral routes and
anastomoses in, 7274, 83
transient ischemic attacks (TIAs) of, 62
MRA. See magnetic resonance angiography
MR DSA methods. See magnetic resonance
digital subtraction angiography
(MR DSA)
MRI, 406
spinal, 400
MR perfusion, 185
Multidetector CT (MDCT), 8788, 101,
107, 109
Multiholed pigtail catheters, 164
Multimodal thrombolysis, 306309
Multiplanar reconstructions (MPRs), in
MRA, 126
Multiple overlapping thin slab acquisition
(MOTSA) technique, 117
Murrays law, 61
Myelography CT, 8788
Myeloma, 401
Myocardial infarction, 146
N-acetylcysteine, 161
Nasal telangiectasias, 210
NASCET trial, 127
Nasomaxillary AVMs, 206
National institute of neurological diseases
and stroke (NINDS) study, 305
National Institutes of Health Stroke Scale
(NIHSS), 306
N-butyl cyanoacrylate (NBCA), 235236,
292, 400
in the nidus, 293
polymerization of, 292293
technique, 294295
N-butyl 2-cyanoacrylate (NBCA), 370371
N-butyl cyanoacrylic acid (NBCA), 177178
Neck
pain, 103
veins, 1820
Neo-endothelialization, 172
Neointimal hyperplasia, 173
Neurofibromatosis type 1, 199
Neuroform, 254
Neuroform Microdelivery System, 173
Neuroform stent, 173175
Neuronet Endovascular Snare, 179
Neurophysiological monitoring (NPM)
test, 186
Nicardipine, 168, 266
Nitinol (nickel-titanium alloy), 172, 179
cerebrovascular stents, 329
wire, 178
Nitroglycerin, 162
 Index 417

Nonaneurysmal subarachnoid Perfusion-weighted imaging (PWI), Presurgical embolization, 289

hemorrhage, 96
Nonbifurcated common carotid artery, 5
Nondeconvolution methods, 91
Nonenhanced CT (NECT), 88, 9095,
97101, 104, 106
Nonsteroidal anti-inflammatory agents, 398
Nontraumatic hemorrhage
AVM, 9699
causes of, 99
CT techniques, clinical applications
in, 9299
venous occlusive disorders, 9799
North-American symptomatic carotid
endarterectomy trial (NASCET),
148, 311
Occipital artery (Occ), 31
Occipital auricular arteries, 7
Occlusion, 92, 105, 138, 150
disorders, 7476
Occlusion test, measures, 242
Occlusive vascular disease
distribution, 325
Occupational Safety and Health
Administration (OSHA), 404
Ocular ischemic syndromes, 215
Onyx, 178, 253, 292, 294
technique, 295296
Opacification, 396
Ophthalmic artery, 2325
Orbitofrontal artery (Ofr), 27
Osler-Weber-Rendu disease, 363
Osteogenesis imperfecta, 214, 231
Osteolysis, 400, 402
Osteonecrosis, 390
Osteophyte formation, 390
Osteoporotic fractures, 403
Pain, 399
Palliative embolization, 290
Papaverine, 168, 264266
Paragangliomas, 199202
Paravertebral approach, 403
Parenchyma, 96
Parent artery occlusion (PAO), 2829
Parietooccipital artery (PoA), 34
Parks-Weber syndrome, 275
Patient screening and evaluation
history of present illness, 390
neurological and physical
examination, 390
preprocedure preparation and
counseling, 392
radiological evaluation, 390392
Patient selection criteria, 389390
Penetrating injury, CT techniques clinical
applications in, 107108
Percutaneous angioplasty in posterior
arteries, 147
Percutaneous transarterial embolization, 399
Percutaneous transluminal angioplasty
(PTA), 147, 325327
balloon
advantage of, 328
disadvantage of, 329
for femoral artery stenosis, 326
for intracranial atherosclerotic
stenosis, 327
problems of intracranial balloon
angioplasty, 326
success rate for PTA (92%), 326
Perfused blood volume (PBV), 92
Perfusion CT, 82
Perfusion harmonic imaging (PHI), 140
Perfusion imaging, 104, 185
100101, 132
Pericallosal anastomoses, 82
Pericallosal aneurysms, 109
Pericallosal artery (PeriA), 25
Pericallosal-pericallosal anastomosis, 29
Perimedullary arteriovenous fistulas
(PM-AVFs)
classification, 371
clinical presentation, 371373
imaging, 373
treatment, 374375
Perinatal asphyxic injury, 99
Perivertebral acrylic, 403
Persistent caroticobasilar anastomoses,
2931
Petrous segment, 18
Pharmacological testing, 189190
noninvasive alternatives, 190
technique, 190
Phase contrast MRA, 121124
Pituitary adenomas and inferior petrosal
sinus sampling (IPSS), 353
Pituitary MRI. See also magnetic resonance
imaging (MRI)
absence of uniformity in the imaging
protocols, 354
for evaluating ACTH-dependent
Cushings syndrome, 354
Pneumothorax, 403
Polycystic kidney disease, 239
Polyglycolic acid lactide copolymer
(PGLA)-coated coils, 250
Polymethylmethacrylate (PMMA), 387, 396,
397, 398, 399, 400, 401, 403
acetabulum with, 404
extravasation, 406
Polyurethane filter, 171
Polyvinyl alcohol particles, 177, 292
Positron emission tomography (PET), 68, 73,
7576, 189
Possis AngioJet thrombectomy catheter, 309
Posterior auricular arteries, 7
Posterior cerebral artery (PCA), 138139,
141, 143, 188
in vertebrobasilar system, 27, 3235
Posterior communicating artery (PCoA),
2425, 28, 5758, 7375, 81, 92, 138
Posterior ethmoidal artery (PeA), 25
Posterior inferior cerebellar artery (PICA), 4,
3133, 43, 59, 69, 9294, 127, 226
Posterior intercostal artery, 4, 3940
Posterior internal frontal artery (PostIF), 25
Posterior reversible encephalopathy
syndromes (PRES), 105
Posterior temporal artery, 27, 33
Posterior venous plexus, 50
Post-revascularization injury, 180
Post-subarachnoid hemorrhage vasospasm.
See also vasopasm
diagnosis and medical management, 264
endovascular therapy
balloon angioplasty, 266270
intra-arterial antispasmodics,
264266
of a ruptured unsecured aneurysm,
270271
treatment outcomes, 271
Fisher four point grading scale, 263
historical aspects, 264
pathophysiology, 263264
Postvertebroplasty care, 398
Precentral artery (PcA), 25
Prednisone, 161
Preoperative meningioma embolization, 177
Preprocedure plain films, 400
Preradiosurgical embolization, 289290
Primary pigmented nodular adrenal disease
(PPNAD), 353
PROACT trial, 306, 308
Prophylaxis, 396
Prosthetic cardiac valves, 146
Protamine sulfate, 164
Proximal posterior cerebral artery (PCA),
5759, 66, 6869, 73, 82
Pseudoaneurysm, 109. See also aneurysm
Pseudo-Cushings syndrome, 353. See also
Cushings syndrome
Pseudoxanthoma elasticum, 214
Pterygoid canal artery, 18
Pterygoid plexus, 59
Pterygopalatine venous plexus (PVP),
1920
Pulmonary arteriovenous, 210
Pulmonary embolism, 389
Pulsatile tinnitus, 103
Pulse oximetry, 162
Radial artery, 162
Radiation therapy, 196, 399, 402
Radicular pain, 390
Radicular supply arteries, and arterial blood
supply, 4042
Radiculomedullary artery, 3940
Radiculomedullary veins, venous drainage
in, 5051
Radiculopathy, 390
Radiographic follow-up, of treated
aneurysms, 248
Radionucleotide, 171
Radiopacity, 178
Radiosurgical treatment, of cranial
DAVFs, 346
Rated burst pressure (RBP), 168
Raymonds syndrome, 359
Recombinant tissue plasminogen activator
(r-tPA), 305
Reconstructive repair, of aneurysms, 246
with aneurysm coils, 248249
Rendu-Osler-Weber syndrome, 209, 275
Reperfusion injury, 99
Reperfusion syndrome, 105
Restenosis, 173
after stenting, 330
Restorative neurology, 61
Retroperitoneal hematoma, 162
Revascularization procedures monitoring,
149150
Right aortic arch, 2
Right common carotid artery (RCCA), 1
Right subclavian artery (RSUB), 1
Right vertebral artery, 2
Ringers solution, 176
Robust leptomeningeal collaterals, 67
Ruptured cavernous aneurysms, 231
RX Acculink Carotid Stent System, 168
Saccular aneurysmal rupture, 9296
Sacral arteries, 3940
Sacral foramina, 406
Sacroplasty, 406
Sacrum, 406
SAH. See subarachnoid hemorrhage (SAH)
Sclerotherapy, 162
Seldinger technique, 163
Selective angiographic evaluation, of brain
AVMs, 278
Selective arterial spin-labeled (SASL)
perfusion, 65
Self-expanding stent implantation, 329
SENSE technique, 119, 130
Sentry balloon, 269
418 Index
Shaded surface display (SSD) methods, 89
Short-tau inversion recovery (STIR), 390
Shuttle Select Tuohy-Borst Introducer, 164
Sickle cell disease, 96, 105
Simmons II catheter, 164
Single-photon emission computerized
tomography (SPECT), 68, 185, 263
Sinus access, 168
Sinus anatomy, 36
Sirolimus (rapamycin), 330
Skull
applied neurovascular anatomy of, 2337
base veins, 1820
SMASH technique, 119
Snow plow effect, of atherosclerotic
plaques, 331
Sodium bicarbonate, 161
Somatosensory-evoked potentials (SSEP)
monitoring, 185186
Specialty needles, 395
SPECT scanning, 390
Spetzler-Martin grading system, for AVMs,
288. See also arteriovenous
malformation (AVM)
Spinal angiography, catheter for, 164
Spinal DAVFs. See dural arteriovenous
fistula (DAVF)
Spinal dural arteriovenous fistulas
(SDAVFs), 5254
Spinal radicular arteries, 40
Spinal vascular malformations
classification, 363364
clinical presentation, 364365
dAVFs
cervical, 367369
clinical manifestations, 367
imaging, 367
pathophysiology, 366
treatments, 369371
extradural arteriovenous malformation/
fistulas
clinical presentation, 380
imaging, 380
treatment, 380
imaging, 365
intramedullary arteriovenous
malformation (IM-AVFs)
clinical manifestations, 377
imaging, 377378
metameric angiomatosis, 378
treatment, 378379
isolated spinal artery aneurysms, 380383
perimedullary arteriovenous fistulas
(PM-AVFs)
classification, 371
clinical presentation, 371373
imaging, 373
treatment, 374375
Spinal vascular malformations, MRA
clinical applications in, 131132
Spine and spinal cord
arterial blood supply, 3945
in cauda equina, 43
in cervical region, 4243
extra- and intraspinal extradural
anastomoses, 3940
intrinsic spinal cord arteries and, 44
radicular supply, 4042
by region, 4245
sources, 3940
superficial and intrinsic arterio-arterial
anastomoses, 4445
superficial spinal cord arteries
and, 4042
in thoracic region, 43
in thoracolumbar region, 43
AVMs anatomical evaluation, 5254
vascular anatomy of, 3954
venous drainage, 4552
in cervical region, 48
in extradural venous spaces, 52
intraparenchymal venous anastomoses,
4748
intrinsic veins, 46
in lumbar region, 50
in radiculomedullary veins, 5051
superficial veins, 4647
in thoracic region, 4850
in transdural course, 5051
Spinnaker Elite, 165
Splenial artery, 34
Stable xenon CT perfusion, 89, 92, 101, 105,
185186
Stenosis, degree of, 148149
Stenotic-occlusive disease, 101103
Stent(s), 172175
balloon-expandable coronary, 328
coated, 173
drugeluting, 173
evaluation, 89
grafts, 175
as humanitarian device exemption
(HDE), 328
intracranial, 172
Neuroform, 173175
notion of, 327
placement, and success rates, 328
self-expanding, 172
sirolimus-eluting, 330
smaller, 172173
Wingspan, 175
Stenting, 146147. See also carotid
angioplasty and stenting (CAS)
and angioplasty for intracranial
atherosclerotic occlusive disease
(ICD), 325
endovascular treatment of, 332
restenosis after, 330
Stenting and angioplasty
case illustrations, 319320
complications and preventive
measures, 319
early trials, 313314
evolution, 312317
postintervention follow-up, 318
risk factors, 318
stenting procedure, 317318
trials of angioplasty and stent placement
with dep vs. cea in high-risk patients,
314317
trials of angioplasty and stent placement
with dep vs. cea in low-risk patients,
317
Stenting of symptomatic atherosclerotic
lesions in the vertebral or intracranial
arteries (SSYLVIA), 328
Stent techniques, 306308
advanced, 254
assisted angioplasty, 325
advantages over simple angioplasty,
328
as replacement to angioplasty, 327
balloon-expandable coronary stents, 328
drawbacks, 329
complications, 254256
effects of heparin-coated, 330
exclusion criteria for, 330
humanitarian device exemption
(HDE), 328
inclusion criteria for, 330
for intracranial atherosclerotic occlusive
disease (ICD), 325
nitinol (nickel-titanium alloy)
cerebrovascular stents, 329
procedure and possible complications,
330331
rationale for, 253254
restenosis, after stenting, 330
sirolimus-eluting stents, 330
stent, notion of, 327
stent placement, and success rates, 328
technology, 325
Sternal fractures, 403
Steroid therapy, 402
Stroke-like conditions, CT techniques
clinical applications, 104106
Stroke outcomes and neuroimaging
of intracranial atherosclerosis
(SONIA) study, 140
Stump pressures, measurement of, 185
Sturge-Weber disease, 275
Subacute and chronic setting
CT techniques clinical applications, 101
in ischemia, 101
Subarachnoid hemorrhage (SAH), 9296, 98,
104, 124125, 141143, 214216, 218,
224226, 239240
Subclavian steal syndrome, 151
Subdural hematoma (SDH), 94
Sulcal AVMs, 278. See also arteriovenous
malformation (AVM)
Superficial arterial anastomoses, arterial
blood supply in, 4445
Superficial spinal cord artery, 3940
arterial blood supply in, 4042
Superficial spinal cord veins, 48, 52
Superficial temporal artery (STA), 31
Superficial veins, venous drainage in, 4647
Superficial venous system, in cerebral veins,
3537
Superior cerebellar artery (SCA), 3234,
59, 69
Superior ophthalmic vein (SOV), 19
Superior petrosal sinus, 59
Superior thyroid artery (SUT), 78
Superior thyroid (ST), 31
Superselective angiographic evaluation, of
brain AVMs, 278
Super Stiff wire, 167
Supraclinoid segment, 18
Surgical treatment
extradural dissection, 219220
intradural dissection, 223
Swan-Ganz catheter, 247
Sylvian fissures, 96
Symptomatic vertebroplasty, complications
in, 402404
Syphilis, 105
Takayasu arteritis, 105
Tantalum powder, 178
Targeted transvenous embolization,
of a cavernous DAVF, 342
TCD ultrasonography, 67
Tegaderm, 393
Temporal artery (Tp), 27
Temporooccipital artery (OccTemp), 27
TempoVert, 164
Terumo Glidecath Angled Taper, 164
Terumo glidewire, 163
Therapeutic vessel occlusion techniques,
241246
Thoracic region
arterial blood supply in, 43
venous drainage in, 4850
Thoracolumbar region, arterial blood
supply in, 43
3D angiography, 325
3D gadolinium-enhanced sequence, 117
Three-dimensional coil shapes, 252

3D road map, 325
3D SPGR technique, 119
3D TOF techniques, 117118, 125127,
130131
Thrombolysis, 138, 179
catheter-based, 105
endovascular ultrasound, 153
intra-arterial. See intra-arterial
thrombolysis
mechanism of US-accelerated, 152
microbubble-augmented US, 154
multimodal, 306309
transcutaneous US-enhanced, 153154
transvenous, 168
Thrombolysis in myocardial infarction
(TIMI) grading scale, 309
Thrombolytic infusions, 168
Thrombosis
dural venous sinus, 168, 179
prevention, 162, 164, 173, 175, 178,
180, 181
transverse sinus, 99
Tilted optimized nonsaturating excitation
(TONE), 118
Time-of-flight magnetic resonance
angiograph (TOF MRA), 7374
Time-of-flight (TOF) techniques, 113122,
125127, 130131
2D TOF, 115117, 119, 121, 127
3D TOF, 117118, 125127, 130131
echo time, 119
flow compensation, 118
limitations, 118
Titanium-nitrous-oxide (TiNOX), 173
Tobramycin, 396
Tortuosity, 34, 151
Tortuous vasculature, 118
Tractography, 190
Transarterial approach, to venous packing
of a traumatic DAVF, 343
Transarterial embolization, 402
Transbrachial approach, 162
Transcranial color-coded duplex
sonography (TCCS), 136146
Transcranial Doppler (TCD), 64, 71, 264
imaging, 96, 135147, 152154, 185186
Transcranial low-frequency US mediated
thrombolysis in brain ischemia
(TRUMBI) trial, 153
Transcutaneous US-enhanced thrombolysis,
153154
Transdural course, venous drainage
in, 5051
Transfemoral approach, 162163
complications in, 162
Transient ischemic attacks (TIAs), 62, 212
Transluminal angioplasty, concept of, 325
Transmedullary midline anastomoses,
4748
Transradial approach, 162
Transvenous disconnection, of a Borden
type 3, 343
Transvenous facial approach, to bilateral
cavernous DAVFs, 341
Transverse sinus thrombosis, 99
Trauma
blunt injury, 108109
CT techniques clinical applications in,
105109
penetrating injury, 107108
Traumatic intracranial aneurysms, CT
techniques clinical applications
in, 109
Triple-H therapy, 270
Trocars, 395, 406
15-G, 401
vertebroplasty, 401
Tufted angioma, 196
Tumors
embolization, 177
endovascular management of, 195211
intracranial collateral routes and
anastomoses in, 8283
Two 2D TOF techniques, 115117, 119,
121, 127
Ulcerations, 102
Ultrasonographic imaging. See US imaging
University of Oregon in Portland, 325
Unruptured intracranial aneurysm.
See intracranial arterial aneurysms
US imaging
accelerated thrombolysis mechanism, 152
bioeffects and safety, 135136
contrast agents effects, 136
nonthermal effects, 135136
thermal effects, 135
blood velocity measurements, 136
of carotid and vertebral arteries, 147151
diagnostic imaging in interventional
neuroradiology, 136147
carotid angioplasty, 146147
cerebral vasospasm diagnosis and
monitoring, 141143
coiled intracranial aneurysms
surveillance, 143144
intracerebral venous system, 145
intracranial aneurysms endovascular
treatment monitoring, 147
intracranial arterial occlusion detection,
137140
intracranial atherosclerotic stenosis,
140141
microemboli detection, 145147
neurointerventional procedures
monitoring, 146147
percutaneous angioplasty in posterior
arteries, 147
reference values, 137
stenting, 146147
TCD imaging, 136137
vascular malformations diagnosis, 144
diagnostic techniques, 136
Doppler display modes, 136
duplex sonography, 147151
arterial dissection, 150
calcification, 151
carotid occlusion, 150151
clinical utility of carotid duplex,
149150
degree of stenosis, 148149
extracranial VA, 151
high bifurcation, 151
monitoring after revascularization
procedures, 149150
pitfalls, 150151
reference values, 149
tortuosity, 151
vascular pathology sonographic
assessment, 147148
endovascular US thrombolysis, 153
gray-scale imaging, 136
in interventional neuroradiology,
135154
microbubble-augmented US
thrombolysis, 154
technical aspects, 135147
therapeutic use in acute stroke, 151154
transcutaneous US-enhanced
thrombolysis, 153154
Valsalva maneuver, 354
Vancomycin, 396
Index 419
Varicose convolutions, 50
Vascular access, 162
Vascular access sites
common femoral artery, 162
direct puncture, 162
radial artery, 162
Vascular access technique
micro access approach, 163
standard approach, 162163
Vascular malformations, 205211
AVM, 205208
diagnosis, 144
endovascular management of, 195211
epistaxis, 208210
Vascular pathology sonographic
assessment, 147148
Vascular smooth muscle cells, 263
Vascular tumors, 195204
capillary hemangioma, 195196
juvenile angiofibroma (JAF), 196199
meningiomas, 202204
paragangliomas, 199202
Vasculitis, 92, 99, 105
Vasculopathies, 96, 105
Vasoconstriction, 263264
Vasodilation, 263264
Vasospasm (VSP), 97, 104
balloon angioplasty for, 170
cerebral, diagnosis and monitoring,
141143
distal, 264
post-subarachnoid hemorrhage.
See post-subarachnoid hemorrhage
vasospasm
Vein of Labbe, 59, 7677
Vein of Trolard, 59
Venogenesis, 60
Venography, 396
Venous collateral anatomy, 59
Venous drainage, 59
in cervical region, 48
in extradural venous spaces, 52
intraparenchymal venous anastomoses,
4748
intrinsic veins, 46
in lumbar region, 50
in radiculomedullary veins, 5051
in spine and spinal cord, 4552
superficial veins, 4647
in thoracic region, 4850
in transdural course, 5051
Venous hypertension, 92, 105
Venous midline anastomoses, 49
Venous occlusion testing. See arterial
and venous occlusion tests
Venous occlusive disorders, 9799
Verapamil, 162, 167168, 266
infusion, 180
Vertebral arteries (VA), 32, 3940, 43,
138139, 141, 143, 150151, 200
cervical branches, 35
dissections, 213, 216218, 223225
distal variations, 5
extracranial, 151
scope on head turning, 4
tortuosity, 34
Vertebral compression fractures (VCF), 388
associated with neoplastic diseases,
treatment of, 399
clinical outcomes, 402
imaging evaluation, 400401
patient selection, 400
vertebroplasty and adjunctive
therapies, 402
vertebroplasty for malignant disease,
401402
Vertebral fracture, 388, 404
420 Index
Vertebral-vertebral AVF, 380
Vertebrobasilar system, 3235
anatomic considerations, 35
distal posterior cerebral artery, 35
posterior cerebral artery, 3235
Vertebrography, 401
Vertebroplasty, 388, 392
balloon-assisted, 387
clinical outcomes, 398399
controversies with kyphoplasty, 406
symptomatic, complications in, 402404
technical aspects, 392
acrylic injection, 396398
acrylic preparation, 396
equipment requirements and
operator skills, 393
patient preparation and
monitoring, 393
pedicle targeting, 393395
placement of a contralateral
needle, 395
positioning of needle, 395
vertebrography, 396
trocars, 401
Viatrac 14 Plus balloon catherer, 168
Vidian artery, 18
Vinblastine therapy, 196
Vincristine therapy, 196
Vista Brite Tip, 164
Von Hippel-Lindau disease, 199
Wada test, 186190
alternative agents, 188
epilepsy, 186
MEG, 188189
noninvasive testing, 188
predictive value, 188
technique, 187188
Warfarin-aspirin recurrent stroke study
(WARSS) trial, 326
Warfarin aspirin symptomatic intracranial
disease (WASID) trial, 71
Warfarin versus aspirin for symptomatic
intracranial disease (WASID)
study, 326
Warfarin versus aspirin study, 326
Wheal, 162
Willisian collaterals, 5761, 6364, 67, 6970,
7475
WingSpan Multicenter European Study, 329
WingSpan self-expanding stents, 330
WingSpan system (Smart Therapeutics), 329
for treatment of symptomatic intracranial
stenosis, 329
and treatment with Gateway PTA
balloon, 329
Wyburn-Mason syndrome, 275
XeCT perfusion. See stable xenon CT
perfusion
Y-stents, 254, 256
Zoom digital fluoroscopy, 325
Zygomatic-orbital artery, 24