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AACN Clinical Issues

Volume 16, Number 4, pp. 421440

C 2005, AACN

Acute Stroke
Pathophysiology, Diagnosis, and Treatment
Joan Parker Frizzell, PhD, RN

It is most often due to either cellular

ischemia/infarction or intracranial hemorrhage. Since it occurs in adults in the middle and later years of life, it is responsible
for considerable morbidity and mortality of
older individuals. Risk factors for the occurrence of a stroke include: hypertension, cardiac arrhythmias, alcohol abuse, and cocaine
abuse. Although stroke can and does occur in
infants and children, the focus of this article
is the adult population.
Cerebral ischemia is reduction in blood
flow that can last from several seconds to
minutes. Symptoms occur in about 10 seconds due to hypoxia and energy depletion.1,2
The return of function can occur if blood flow
is restored within a few minutes. When the
symptoms are only transient (ie, less than 24
hours), this would be considered a transient
ischemic attack (TIA). Infarction or death of
brain tissue occurs if the lack of blood flow
lasts for more than a few minutes. In cerebral
infarction, the symptom duration persists due
to cell death and often results in permanent
disability. The symptoms of cerebral hemorrhage are due to either pressure on surrounding tissues or the toxic effects of blood on the
tissue. The extent of the cellular damage and
neurologic deficit is determined by actual destruction of neural tissue.3

Stroke, a neurologic event due to altered

cerebral circulation, is the third leading
cause of death in the United States. Risk
factors for stroke include hypertension,
family history, and diabetes mellitus. The
subtypes of stroke are ischemia,
infarction, and hemorrhage. Ischemia and
infarction are the result of atherosclerotic
development of thrombi and emboli.
Decreased and/or absent cerebral
circulation causes neuronal cellular injury
and death. Intracerebral hemorrhage
occurs from rupture of cerebral vessels
often as the result of hypertension. Patient
assessment and diagnosis include the
use of computed tomography scans,
magnetic resonance imaging, and the
National Institute of Health Stroke Scale,
and treatment depends on the etiology of
the stroke. Thrombolytic therapy is the
mainstay of treatment for thrombotic and
embolic events. Current recommendations
for future stroke care include the
development of designated stroke
centers. Directions for research in stroke
treatment includes examining
neuroprotective therapies. (KEYWORDS:
cerebral hemorrhage, cerebral infarction,
cerebral ischemia, stroke diagnosis,
stroke pathophysiology, stroke treatment)


From the School of Nursing, La Salle University,

Philadelphia, Pennsylvania.
Reprinted requests to Joan Parker Frizzell, Assistant Professor, School of Nursing, La Salle University, 1900 Olney Ave, Philadelphia, PA 19141 (Frizzell@

Stroke is an abrupt disturbance in cerebral circulation causing neurological deficits.



AACN Clinical Issues


skull is the foramen magnum, an opening

through which the spinal cord forms a continuous connection with the brain. The brain
has 3 coverings. They are the pia mater (the
innermost layer), the arachnoid (the middle),
and the dura mater (the outermost, tough
layer). Pia is directly continuous with the
brain and spinal cord. It is a vascular layer
through with blood vessels pass to the internal central nervous system (CNS) to nourish
the neural tissue. The area between the pia
and the avascular arachnoid is the subarachnoid space, and it contains the cerebral arteries. The dura is composed of two layers; the
inner most is referred to as the meninges. The
brain contains gray matter and white matter.
Gray matter is external and the myelinated
white matter is internal.


Stoke is the third leading cause of death in the

United States accounting for 1 out of every
15 deaths. The direct and indirect costs associated with stroke are about $56.8 billion.4
Approximately 700,000 people are diagnosed
with a stroke each year, and approximately
200,000 of them are experiencing their second stroke. Men have strokes at a younger
age than women, therefore the age adjusted
incidence of stroke is 1.25 times greater for
men than for women.4 The risk of stroke for
blacks is almost double that of whites, and
Hispanics have a greater incidence hemorrhagic stroke at a younger age.5 Most strokes
(88%) are ischemic events, while other etiologies include intracerebral hemorrhage (9%)
and subacrachnoid hemorrhage (3%).4,6

The cerebrum is the largest part of

the brain and is divided into 2 hemispheres
and consists of 4 lobes: frontal, parietal, temporal, and occipital. On its surface, or cortex, are located the centers from which motor impulses are carried to the muscles and to
which sensory impulses come from the various sensory nerves. It contains an area in its
inner core referred to as the thalamus. The
thalamus is composed of 2 ovoid structures
and is an important relay station in the brain.
All the main sensory pathways form synapses
with the thalamic nuclei on their way to the
cerebral cortex. These pathways also serve as
vehicles for transmitting pain, emotions, etc.
The location of specific functions within
the brain is related to the concept of complementary specialization. The cerebral hemisphere associated with language comprehension skills and sequential analytic processes
is referred to as the categorical hemisphere.
This was previously referred to as the dominant hemisphere; however, the other cerebral
hemisphere is not considered to be nondominant, it just has a different type of specialization. The other hemisphere focuses primarily on recognition of faces, music, and visual
spatial relationships; therefore, it is referred
to as the representational hemisphere.1
For approximately 96% of right-handed individuals, the left hemisphere is the categorical hemisphere. Thus, the left hemisphere
contains areas for language comprehension (Wernickes area) and speech and
word formation (Brocas area). Injury to


 Risk Factors
The major or more common risk factors
for cerebral ischemia and infarction include
family history, hypertension, smoking tobacco, diabetes mellitus, higher body mass
index, and other risk factors for the development of atherosclerosis such as hypercholesterolemia. Smoking increases the risk of a
stroke due to either arterial wall damage and
atherosclerosis or formation and rupture of
aneurysms. Cardiac risk factors of stroke include atrial fibrillation and a recent myocardial infarction. Evidence of a prior TIA also
increases the risk of a stroke. Additionally,
the risk of having a stroke increases with
age.79 The use of hormonal contraceptives
can also increase the risk of cerebral ischemia
or infarction.10 The risk of hemorrhagic stroke
is increased in persons of Asiatic or African
decent. Other risk factors include hypertension, trauma, advanced age, heavy alcohol
consumption, and cocaine and amphetamine
 Overview of Anatomy and
Physiology of the Brain
The Brain

The brain is divided into the cerebrum, cerebellum, and the brain stem. At the base of the

Vol. 16, No. 4, Oct-Dec 2005

this hemisphere is associated with language

The cerebellum
regulates coordinated activities such as gait
and performance of motor tasks.8 The brain
stem includes the midbrain, pons, and
medulla oblongata. The midbrain connects
the pons and the cerebellum with the cerebral hemispheres. The cerebellum is located
below and behind the cerebrum. The pons is
located in front of the cerebellum between
the midbrain and the medulla. It serves a
bridge between the 2 halves of the cerebellum as well as between the medulla and
the cerebrum. It contains important centers
for controlling the heart, respiration, and
blood pressure and gives rise to 4 cranial


Cells appear quite similar,

but functions will vary depending on their
location within the cortex. There are 4 lobes:
frontal, parietal, occipital, and temporal. The
frontal lobes are thought to contain areas associated with emotional attitudes and the development of thought processes. Nerve fibers
from all portions of the cortex converge in
each hemisphere and make their exit in the
form of tight bundles (internal capsule).
These cross the corresponding bundle from
the opposite side; therefore, a right stroke
means left-sided weakness.


Cerebrospinal Fluid

Each cerebral hemisphere has a central cavity, a ventricle that is filled with clear cerebrospinal fluid. It traverses from the ventricle through narrow tubular openings to the
subarachnoid space to bathe the entire surface of the brain and spinal cord. The average amount of cerebrospinal fluid (CSF) is
150 mL.
Neural Tissue

The neuron is the structural, genetic, and functional unit of the nervous system and is composed of cell bodies, dendrites, and axons. The cell bodies are located in layers on the surface of the brain,
or cortex, and comprise what is referred to
as gray matter. The neurons contain intracel-




lular structures found in many cells, such as

the nucleolus, microtubules, golgi apparatus,
and rough endoplasmic reticulum. Intracellular structures specific for neurons include
neurofilaments, synaptic vesicles, and Nissl
substance.11 Neurons use glucose as their energy source and are dependent on oxidative
metabolism. They produce and release neurotransmitters.
Neurotransmitters are chemicals synthesized in the neurons that are stored in synaptic vesicles in the axon terminals. They are released from the axon terminal by exocytosis
and are also reabsorbed and recycled. These
chemicals cause changes in the cell permeability of neuron, making it more or less able
to conduct an impulse.
Neuroglia are the supporting cells
for the neurons of the CNS, whereas Schwann
cells have this function in the peripheral nervous system (PNS). The neuroglia comprise
about 40% of the brain and spinal cord. They
outnumber the neurons approximately 4 to 1.
Four distinct neuroglia cell types have been
identified: microglia, ependyma, astroglia,
and oligodendroglia. Microglia have phagocytic properties to ingest and digest tissue debris. They are found throughout out the CNS
and are also believed to have a role in fighting infection. Ependyma line the ventricular
system and are involved in the production
of CSF. Oligodendroglia are the glial cells responsible for myelin production within the
CNS. Astroglia (astrocytes) are located between blood vessels and neurons, possibly controlling movement of macromolecules
between the blood, CSF, and brain as the
blood-brain barrier. When there is death of
neurons due to injury, astrocytes proliferate
and fill in the space formerly occupied by the
nerve cell body and its processes. This activity is known as replacement gliosis.


Myelin is a white lipid-protein complex that provides insulation along a nerve

process. It prevents the flow of sodium and
potassium ions across the neuronal membrane almost completely where it is present.
Within the CNS, nerve fibers with myelin
sheaths are found within the white matter.
Fibers that have no myelin are found within
the gray matter.



AACN Clinical Issues


Cerebral Circulation

The CNS, like all body tissue, is dependent

upon an adequate blood supply for its nutrients and for removal of metabolic waste
products. The arterial blood supply to the
brain is complex. However, an understanding of blood flow enables some correlation
of area of injury with symptoms.
On the right, the brachiocephalic trunk (innominate) artery divides into the right common carotid and
the right subclavian. On the left, the left
common carotid and left subclavian arteries each arise directly from the aortic arch.
There are both internal and external carotid
arteries that branch off from the common
carotids at about the level of the thyroid
gland (carotid sinus). The carotid sinuses respond to changes in arterial blood pressure
to reflexively maintain blood supply to the
brain and the rest of the body. The external
carotids branch off into vessels that supply
the face. The internal carotids enter the skull
and divide into the anterior and middle cerebral arteries. The middle cerebral arteries are


considered to be continuations of the internal

carotid arteries (see Figure 1).12
Right and
left vertebral arteries originate from the subclavian arteries of their respective sides. The
vertebrals enter the skull via the foramen
magnum. At the level of the brainstem, they
fuse to form the basilar artery. This continues
to the level of the midbrain where it branches
to form the posterior cerebral arteries.


Cerebral arteries are classified as either penetrating or conducting.

The conducting arteries form an extensive
network over the surface of the brain. The
penetrating arteries are nutrient vessels that
are derived from the conduction arteries.
They enter the brain at right angles and provide the blood supply for the deep cerebral


The internal carotids and the vertebral-basilar arteries are 2

separate systems delivering blood to the
brain. They do however, unite to form the
crcle of Willis through a specialized system


Figure 1. Carotid circulation. Reprinted with permission from Book D. Disorders of brain function. In: Porth CM,
ed. Pathophysiology Concepts of Altered Health States. Philadelphia: Lippincott Williams & Wilkins; 2005, 1243.

Vol. 16, No. 4, Oct-Dec 2005



Figure 2. Circle of Willis. Reprinted with permission from Book D. Disorders of brain function. In: Porth CM, ed.
Pathophysiology Concepts of Altered Health States. Philadelphia: Lippincott Williams & Wilkins; 2005, 1244.

of communicating arteries. There is usually

only slight blood flow through these arteries;
however, they serve as a fail-safe mechanism
in case of dramatic changes in arterial blood
pressure. Collateral circulation may gradually
develop when there is an alteration in normal
blood flow. Most cerebral collateral circulation is between major arteries via the circle
of Willis (see Figure 2).12

ergy source.1 Neurons do not store glycogen,

so energy depletion is rapid.3
Although glutamate is an excitatory neurotransmitter within the brain, metabolically,
it has a neuroprotective action. It aids in
the removal of the ammonium ion through
conversion to glutamine. Since ammonia is
very toxic to brain cells, this glutamateglutamine conversion serves as a detoxifying

Brain Metabolism

Autoregulation of Blood Flow

Brain metabolism is steady and continuous

with no rest periods, requiring a continuous
supply of glucose and oxygen. It is highly
depended upon oxygen and accounts for
20% of the bodys oxygen usage.1,2,11 Consciousness may be lost in as little as 10 seconds once blood flow has ceased. Dependent
upon oxygen, the brain does not switch to
anaerobic metabolism, and a lapse of even
a few minutes may cause irreversible damage. Sustained hypoglycemia may also damage brain tissue, since glucose is its major en-

The normal brain has the ability to regulate its

own blood supply to maintain arterial pressure between 65 and 140 mm Hg.1,2 Factors
that affect this can be viewed as extrinsic
(outside the brain) and intrinsic (inside the
The extrinsic factors affecting cerebral
blood flow (CBF) are related primarily to
the cardiovascular system and include blood
pressure (BP), cardiovascular function, and
blood viscosity. If systemic mean BP drops
below 60 mm Hg, the brains autoregulatory


AACN Clinical Issues


mechanism becomes less effective. The brain

will initially attempt to compensate by extracting more oxygen from the available
blood supply. If BP continues to drop, signs
of cerebral ischemia will occur. Alterations
in cardiovascular function that affect cardiac
output also can reduce CBF. If the cardiac
output is decreased by more than one third,
there is often a fall in CBF. Cerebral blood
flow increases with anemia, but the increased
viscosity of polycythemia may reduce it by
The intrinsic factors are influenced by
cerebral perfusion pressure. This is the pressure difference between the cerebral arteries and veins. The goal is that cerebral perfusion pressure will remain constant despite
changes in systemic BP. Cerebral vascular resistance increases or decreases in response
to systemic BP to maintain a constant flow of
blood to the brain. Cerebral blood vessels are
important because of their response in maintaining constancy of flow. Cerebral blood
vessels are under the control of the sympathetic nervous system or sympatho-adrenal
response. Sympathetic reflexes are believed
to cause vasospasm in some types of brain
Intracranial pressure (ICP) is also an important regulatory mechanism. An increase
in ICP will increase cerebrovascular resistance, reducing cerebral blood flow. Cerebral
blood flow will not decrease until there is a
considerable increase in ICP.1 ICP is affected
by these 3 metabolic factors: CO2 concentration, H+ concentration, and O2 concentration.
High CO2 tension is a strong vasodilator and
can produce a marked increase in cerebral
blood flow.1 A decreased pH (increased H+
levels) will increase blood flow. Low O2 tension is a powerful vasodilator, and high O2
Levels are a moderate vasoconstrictor.2
Cerebral Perfusion Pressure

Cerebral perfusion pressure (CPP) is the difference between mean arterial blood pressure (MAP) and the ICP. The normal range is
60 to 80 mm Hg.
The cranial cavity contains the brain,
blood, and CSF. Of this, the brain takes up

80% with the blood volume and CSF each

comprising 10%. Together, they maintain normal ICP of 50 to 200 mm H2 O (4 to 15 mm
Hg). Changes in one will cause a compensatory change in the other to maintain normal
ICP. This is referred to as the Monro-Kellie hypothesis. The ICP will remain within normal
range as long as any increase that occurs does
not exceed the compensatory displacement
of blood or CSF. If an overcompensatory displacement occurs, the ICP will rise, resulting in cerebral hypoxia, or brain herniation,
or sideways or downward movement of the
brain. If the CPP falls below 50 mm Hg, cellular death occurs.2,11
When the pressure in the ICP exceeds
MAP, tissue perfusion falls and demand exceeds supply, and cellular hypoxia occurs.
The neurons of the cortex are the most sensitive to changes in oxygenation. That is why
one of the earliest and most reliable signs is
changing level of consciousness.2
Increases in ICP cause the CNS ischemic
response. This is evidenced by a marked increase in MAP, reflexive slowing of heart rate,
and widened pulse pressure. This triad of
signs, Cushing reflex, is an important but a
late indicator of increased ICP.2
 Stroke Subtypes
Ischemia and Infarction

Cerebral ischemia and infarction occur from

decreased or disrupted blood flow. Ischemia
occurs when there is a decrease in blood flow
to less than 20 mL/100 g of brain tissue per
minute. Reduction of blood flow to less than
16 mL/100 g of brain tissue per minute leads
to tissue death within one hour. In the absence of blood flow, death of brain tissue
occurs within 4 to 10 minutes.3
The most common etiology that results
in cerebral ischemia or infarction is local
damage to a vessel wall from atherosclerosis. This may occur in the aortic arch,
carotid arteries, or cerebral vessels. The development of atherosclerosis begins with endothelial injury and inflammation, leading
to plaque formation. The plaque becomes
thick and fibrous with loss of muscle cells.
The sclerotic material partially fills and/or occludes the lumen of the vessel. Platelets adhere to this, releasing factors that initiate the

Vol. 16, No. 4, Oct-Dec 2005

coagulation-clotting cascade, forming a clot

or thrombus. The clot may either break off
as an embolus traveling to a distal vessel or
remain in place, occluding the vessel.8 Lacunar infarcts occur with complete occlusion of
end-arteries that supply a small area of brain
tissue.3 Symptoms from ischemic events occur fairly rapidly since the brain is very dependent upon adequate oxygen and circulation. Lack of adequate oxygenation to the
cerebral cortex can produce unconsciousness
in a little as 10 seconds.1
Thrombotic events most often affect the
internal carotids, middle cerebral, or basilar
arteries.8,11 Strokes that are the result of emboli are frequently considered to be cardiac
in origin. Referred to as cardioembolic stroke,
these account for about 20% of all strokes.3
Although the embolus is from a thrombus
in the either the atria or the ventricle, the
actual thrombus is often not observed. The
diagnosis of a cardiac origin is based on
known cardiac etiology of emboli, such as
atrial fibrillation or recent myocardial infarction. Cardioembolic strokes most often occlude the middle cerebral artery or the posterior cerebral artery.3 However, emboli may
also develop from the aortic arch or carotid
In contrast to an atherosclerotic event,
symptoms due to an embolus are often
sudden with immediate, noticeable maximal
neurological deficits. In embolic events, the
effected tissue often contains petechial hemorrhages, or red infarction (see Figure 3).
The appearance of brain tissue in thrombotic
events is different. With thrombotic ischemia,
the tissue is often paler, or non hemorrhagic
Since atherosclerotic occlusion of the vessel can occur gradually, symptoms are progressive. The symptoms or deficits increase

Figure 3. Gross anatomy of hemorrhagic infarction.

A, Sections of the brain showing a large, discolored,
focally hemorrhagic region in the left middle cerebral artery distribution (hemorrhagic, or red, infarction). B, A hemorrhagic infarction is present in the inferior temporal lobe of the left side of this brain. C,
A bland infarct with punctate hemorrhages, consistent
with ischemia-reperfusion injury, is present in the temporal lobe. Reprinted with permission from Robbins &
c 2005 Elsevier.
Cotran Pathologic Basis of Disease, 




AACN Clinical Issues


over several hours to several days. There

is a large area of tissue ischemia that increases over time. Survival of this ischemic
tissue is dependent upon 2 major factors:
(1) the availability of collateral circulation
and (2) the duration of the ischemia.11 If
the blood flow is not restored, the ischemic
tissue becomes necrotic and cell death occurs. As cerebral blood flow falls to zero,
death of brain tissue can occur within 4 to 10
minutes.3 Anoxic encephalopathy may occur
with cerebral thrombosis. The brain distal to
the clot becomes swollen. There may discoloration, with the appearance being muddylooking due to changes in the line between
gray and white matter. As nerve cells disintegrate, they are replaced by the neuroglia
At the onset of the cerebral ischemic
event, there is a gradation in brain perfusion.
Whereas the central area may become infarcted, the surrounding tissue exhibits zones
of ischemia and injury, the ischemic penumbra. The area of ischemia and injury is atrisk tissue. The normal cerebral autoregulation of circulation is not operating and is unable to restore blood flow to the area. Unless
treatment is begun immediately, that tissue
will become necrotic as well.3
Ischemia affects both gray and white matter portions of the brain equally, thus the size
of ischemic area is equally distributed. However, the volume of at-risk tissue is greater in
gray matter than in white matter. Despite this,
it appears that more white matter is potentially viable and responsive to therapy than
gray matter.13
Cerebral infarction is also associated with
cerebral edema. About 5 to 10 stroke patients
develop severe cerebral edema, increasing
the risk of brain herniation.3
Acute neuronal injury is
the result of CNS hypoxia and ischemia. Injured cells respond with a series of reversible
and irreversible changes. These responses include recruitment of white blood cell release,
inflammatory mediators, and elevation in C
reactive protein levels.11,14
During ischemic injury, there is failure
of the ion pumps. Potassium flows out of
the cell into the extracellular space. The altered potassium gradient causes depolarization of neuronal membranes and increased


intracellular calcium levels.3 With depolarization, there is the release of neurotransmitters into the synaptic space. Glutamate,
an excitatory neurotransmitter, accumulates
at excitatory synapses and in the extracellular
space. Glutamate further damages the neurons through overstimulation and opening of
membrane channels. The increased influx of
calcium ions and overstimulation ultimately
lead to cell death.1,8,11
Cellular death occurs either through irreversible neuronal cellular damage or through
the apoptotic pathway of programmed cell
death. Altered mitochondrial function with
increased release of free radicals damages
cell membranes and alters cellular functions. Once the necrotic changes begin,
there is currently no treatment to stop the
Irreversible changes accompanying cell
death include shrinkage of the cell body,
disappearance of the nucleolus, and loss of
Nissl substance. Since the cytoplasm stains
red with hematoxylin and eosin (H & E) staining preparations, they are referred to as red
neurons (see Figure 4).11
Regardless of the etiology, the clinical presentation of symptoms
in a cerebral ischemic/infarction event depend upon: (1) the location of the vessels
and (2) the presence of collateral circulation (see Table 1). However, embolic strokes
have a greater risk of subsequent bleeding into the infarcted area than thrombotic


These are small cavity infarcts (usually <15 mm wide) are usually associated with hypertension. They can
be either silent with no associated clinical symptoms or present with very obvious
symptoms.11 The most common symptoms
seen with lacunar infarcts are either pure motor deficits or pure sensory deficits.8

Lacunar infarcts:

Complete occlusion
of the middle cerebral artery results in loss
of movement and sensation on the contralateral or opposite side of the infarction. However, there may be a gaze preference to the
ipsilateral or same side as the injury. If this
is the categorical hemisphere, there is also a
global aphasia.3 If it is the representational

The middle cerebral artery:

Vol. 16, No. 4, Oct-Dec 2005



Figure 4. Cellular changes with cerebral infarction. A, At low magnification, it is possible to see the demarcated
areas of an acute infarction. In the underlying white matter, the areas of infarction are well shown by the myelin stain.
B, Acute ischemic injury causes diffuse eosinophilia of neurons, which are beginning to shrink. C, Infiltration of a
cerebral infarct by neutrophils begins at the edges of the lesion where vascular supply has remained intact. D, After
about 10 days, an area of infarction is characterized by the presence of macrophages and surrounding reactive
gliosis. E, Remote small intracortical infarcts are seen as areas of tissue loss with a small amount of residual gliosis.
c 2005 Elsevier.
Reprinted with permission from Robbins & Cotran Pathologic Basis of Disease, 

hemisphere, there is a neglect syndrome, or

forgetting that there are 2 sides of the body.
Partial occlusion of the middle cerebral artery
could include weakness of a hand or arm, facial weakness, and partial aphasia.8

There are 2 syndromes observed with occlusion of the posterior cerebral artery: P1 and P2. The P1
syndrome includes the midbrain, subthalamic, and thalamic regions of the brain. The

The posterior cerebral artery:


AACN Clinical Issues



Clinical Presentation in Ischemic Stroke

Anterior cerebral
Middle cerebral

Posterior cerebral

Weakness and loss of sensation of the contralateral leg and foot
Contralateral sensory loss and weakness; Loss of the nasal half of vision on the opposite
side and loss of the temporal half of vision on the same side
Categorial hemisphere: aphasia
Representational hemisphere: neglect syndrome
Lid lag, with papillary contraction; Ataxia, vertigo, hiccupping, and difficulty swallowing
Dizziness, double vision, ataxia, hemi- or quadriparesis
Memory loss, visual hallucinations, dyslexia, sensory loss, ataxia, altered level of

Adapted with permission from Messing RO. Nervous system disorders. In: McPhee SJ, Lingappa VR, Ganong WF, eds.
Pathophysiology of Disease: An Introduction to Clinical Medicine, 4th ed. New York: Lange Medical Books/McGraw-Hill
Medical Publishing Division; 2003:183.

symptoms include a third-nerve palsy with

weakness and ataxia. Extensive infarction
in this area can result in coma, unreactive
pupils, and decerebrate rigidity. The P2 syndrome results in injury to the medial temporal
and occipital lobes. This results in memory
loss, disturbances, or loss of vision on the
contralateral or opposite side of the infarct.
In some individuals, visual disturbances can
produce hallucinations.3
The clinical presentation
seen with occlusion of the basilar artery includes the locked-in state of preserved consciousness with total quadriplegia. A TIA in
this area may produce dizziness or a feeling
of light-headedness.3

The basilar artery:

Occlusion of this
vessel causes cerebellar ataxia, partial deafness, nausea, vomiting, and loss of pain
and temperature sensation on the opposite

Superior cerebellar artery:

The symptoms seen with occlusion of this vessel include ipsilateral deafness, facial weakness,
and vertigo.3

Anterior inferior cerebellar artery:

Cerebral Hemorrhage

Cerebral hemorrhage is the third most common cause of stroke and is associated with
about a 50% mortality rate.3 In addition to intraparenchymal hemorrhage, symptoms can
occur from subdural or epidural hematomas.
These are usually the result of some sort of

trauma and may occur several hours after the

initial injury. Subarachnoid hemorrhage can
occur either as a result of trauma or from the
rupture of an aneurysm. Intraparenchymal
hemorrhages usually occur from the rupture
of small penetrating arteries. They are most
often the result of hypertension. They usually
occur in the basal ganglia, thalamus, pons,
and cerebellum. However, they can also occur from vascular malformations. Substance
abuse of cocaine and amphetamines results
in a rapid increase in blood pressure, leading
to vessel rupture.8
Ruptured cerebral arteries are the usual
source of the bleed.11 Extravasation of blood
occurs in the brain and/or the subarachnoid space. The adjacent tissue may be
displaced and compressed. Movement of
the blood into the ventricles is associated
with increased morbidity and mortality.3 Exposure to blood irritates and causes vasospasms of adjacent vessels. A clot will form
that will eventually resolve and decrease in
size. However, the brain tissue next to the
clot can become swollen and necrotic (see
Figure 5).8
Neurological deficits depend upon the site
and severity of the hemorrhage. The onset
is usually abrupt and rapid developing over
30 to 90 minutes. This is often seen in hypertensive intraparenchymal hemorrhage. In
contrast to this rapid onset, bleeding association with anticoagulant therapy will develop
slowly over 24 to 48 hours. The clinical presentation can include complaints of: severe
headache, vomiting, nuchal rigidity, stupor,
coma, and convulsions. However, almost one

Vol. 16, No. 4, Oct-Dec 2005



Figure 5. Hypertensive intraparenchymal hemorrhage. A, Massive hypertensive hemorrhage rupturing into a

lateral ventricle. B, Hypertensive hemorrhage in the pons, with extension to fill the fourth ventricle. Reprinted with
c 2005 Elsevier.
permission from Robbins & Cotran Pathologic Basis of Disease, 



half of the patients with hypertensive cerebral

hemorrhage die.3
In acute hemorrhage, the
volume of blood pushes against and compresses the adjacent tissue, ultimately leading to ischemic injury of that tissue. Eventually, the tissue will be come swollen and
necrotic. Macrophages begin to phagocytize
the hemorrhagic area within 48 hours of onset. Both the blood and necrotic tissue are
phagocytized by the macrophages. As part of
the inflammatory response, the area is liquefied and a cavity is formed. Astrocytes begin
to fill in the cavity and new capillaries are


AACN Clinical Issues

Stroke, as part of the National Institutes of
Health, has developed specific criteria to aid
in categorizing deficits due to a stroke.
Differential diagnosis should identify the
presence of a TIA or stroke while ruling out
other pathologic processes with symptoms
that could mimic a TIA or stroke. The most
common factors would be hypoglycemia,
hyperglycemia, vasculitis, migraine, seizure
disorders, metabolic encephalopathy, recent
head trauma, and tumors. Thus, diagnostic
blood work would include: complete blood
count with platelet count, electrolyte levels,
blood glucose level, blood urea nitrogen, creatinine, and coagulation studies.3,9,15
Computed Tomographic Scan

 Assessment and Diagnosis

Any patient with a sudden alteration in neurologic function should be evaluated for a
TIA or stroke. With ischemia or infarction,
it is imperative that thrombolytic therapy be
given within 180 minutes of onset of symptoms. Therefore, patients should use the 911
Emergency Medical Service system for transport to the nearest hospital that can determine the need for and administer tissue plasminogen activator (t-PA).9
There is no reliable clinical presentation
to differentiate between ischemia, infarction, and hemorrhage. However, a more depressed level of consciousness with an elevated blood pressure is more suggestive
of hemorrhage. Improvement of neurologic
deficits would most often indicate ischemia.3
Diagnostic criteria are used to provide optimal patient care and treatment during a
stroke. Patients can then be classified according to symptoms and disease progression as well as the underlying etiology of
the event. The initial examination should include a full neurological and cardiovascular
assessment. This would include auscultation
of carotid arteries for bruits, comparison of
blood pressure in both arms, and ophthalmoscopic examination of retina for effects of hypertension. Diagnostic testing would include
an electrocardiogram (EKG), chest X-ray, urinalysis, blood work, and brain imaging including computed tomographic (CT) scan or
magnetic resonance imaging (MRI). The National Institute of Neurological Disorders and

Computed tomography scans can identify or

exclude a hemorrhage as the cause of the
stroke. They can also identify neoplasms,
abcesses, or other conditions that can produce similar symptoms. However, ischemia
and infarctions may not be evident on a CT
scan during the first 24 hours of the stroke.
Some infarcts are not evident on CT scan
even 48 hours after onset of symptoms. The
use of contrast enables visualization of larger
cerebral vessels (see Figure 6).3,16 The use of
a CT scan is often preferred during the acute
Magnetic Resonance Imaging

New advances in imaging studies have enabled the magnetic resonance imaging (MRI)
to become an ultrafast imaging method that
is able examine some of the physiologic aspects of brain disorders. Diffusion-weighted
imaging (DWI) methods, used as part of the
MRI study, provide additional information as
to the extent of the ischemia and irreversible
injury.17,18 Therefore, an MRI is able to identify the presence of an infarction within the
brain as well as hemorrhagic transformation
or an ischemic infarct.19 In the future, it will
also be possible to use the MRI to distinguish between reversible or irreversible tissue injury.17,18
An MRI can also be used to determine
the presence of a clot or dissection of a
vessel wall. This can be particularly useful in diagnosing severe carotid occlusive
disease.18 Additional modification of MRI

Vol. 16, No. 4, Oct-Dec 2005



Figure 6. Neuroimaging of middle cerebral artery infarction. A, Computed tomography (CT) scan of the brain of
a patient with a left middle cerebral artery (MCA) stroke of 3 hours duration. As an earliest indicator of infarction,
the insular ribbon sign is caused by edema (darker signal) within the left insular cortex and basal ganglia (arrow).
B, Embolic occlusion of the MCA imaged with CT angiography during the acute stroke (arrow). C, Cerebral blood
flow measured with CT perfusion; blood flow is reduced over a wider region of brain than appeared edematous
in A. D, CT angiogram of a carotid artery showing high-grade stenosis (arrow) from atheroma in another patient.
Reprinted with permission from Smith WS, Johnston S, Easton JD. Cerebrovascular diseases. In: Kasper DL, Fauci
AS, Longo DL, Braunwald E, Hauser SL, Jameson JL, eds. Harrisons Principles of Internal Medicine, 16th ed. New
York: McGraw-Hill Medical Publishing Division; 2005, 2386.


AACN Clinical Issues


stimulation relaxation rates can provide different types of information about stroke damage. These modifications are referred to as
T1W and T2W. T1W images are more sensitive for identifying subacute hemorrhage and
fat structures. T2W images are used to identify edema, demyelination, infarctions, and
chronic hemorrhage.16 Thus, an MRI is a better option for studying cerebral ischemia and
National Institutes of Health Stroke Scale

The National Institutes of Health Stoke Scale

(NIHSS) was developed as a graded neurologic examination to rate deficits that occur as
a result of a stroke (see Table 2).20 The examination evaluates motor function, visual fields,
ataxia, speech, language, cognition, and motor and sensory impairments. Points are given
for levels of functioning in each of these areas. The points are then combined for a total score. The higher the score on the scale,
the greater neurologic deficits present following a stroke. Training methods have been
developed in order to ensure valid and reproducible results when this scale is used to
quantify neurologic deficits. Therefore, this
score is a fairly reliable measure that can be
used to both evaluate treatment and research
new treatment modalities. It is possible to
correlate the score with the patients clinical
presentation. Scores <5 indicate mild neurologic impairment, between 5 and 15 indicate
mild to moderately severe impairment, between 15 to 25 indicate severe impairment,
and scores >25 indicate very severe neurologic impairment.20,21
The NIHSS score in combination with the
volume of the ischemia as measured with
DWI-MRI, and the time since onset of symptoms until obtaining the MRI enables the
identification of patients who have the best
potential for a good recovery from a stroke
(see Table 3). Essentially, the smaller the
size of the infarct, the better the potential
of recovery; additionally, those patients with
lower NIHSS scores did better as well. Combining the information from the NIHSS and
the DWI-MRI resulted in a 7-point score.
Analysis of this scoring system demonstrated
the following: scores of 5 to 7 had the best
outcome, with 87% demonstrating recovery.

Of those patients who scores ranged from

3 to 4, 57% recovered from the stroke. As
expected, only 7% of patient with scores
ranging from 0 to 2 recovered from the
Treatment goals include stabilization of the
patient and prevention of further brain injury by improving cerebral perfusion to ischemic tissue. The treatment should include
supportive medical therapy. Of utmost importance is to maintain a patent airway in the
event that the patient suffers a loss of consciousness. Both blood pressure and cardiac
rhythm need to be stabilized as well.3 The
next step in treatment protocol is based on
the determination as to whether the stroke
is due to a hemorrhage versus a thrombus
or embolus. Therefore, a CT scan should be
obtained as soon as possible.
Supportive medical therapy should include 1 adrenergic antagonists to reduce
the workload of the heart and maintain blood
pressure. Since fever and hyperglycemia
have been shown to be detrimental to recovery, regulation of glucose level and body
temperature is important as well. Blood glucose levels should be below 200 mg/dL.3

Upon determination that the patient is suffering from an ischemic event, treatment will
involve the used of thrombolytic therapy,
anticoagulants, antiplatelet agents, and neuroprotection. It is important to maintain adequate cerebral perfusion pressure. Even minor drops in blood pressure could effect the
recovery of the area of ischemic penumbra. It
is therefore recommended that the patients
blood pressure should not be lowered unless
it is greater than 185/110 mm Hg and thrombolytic therapy is being used.3 However, patients with the following conditions should
have their blood pressure reduced: acute myocardial infarction, hypertensive crises or encephalopathy, renal failure, aortic dissection,
or retinal hemorrhage. When antihypertensive therapy is begun, blood pressure reduction should be done gradually to prevent further ischemia.3,11,2325

Vol. 16, No. 4, Oct-Dec 2005




National Institute of Health Stroke Scale

1.a. Level of consciousness:

1.b. Ask patient the month and their age:

1.c. Ask patient to open and close eyes and

to grip and release hand
2. Best gaze (only horizontal eye movement):

3. Visual field testing:

4. Facial paresis (ask patient to show teeth or

raise eyebrows and close eyes tightly):

0: Alert
1: Not alert, but arousable with minimal stimulation
2: Not alert, requires repeated stimulation to attend
3: Coma
0: Answers both correctly
1: Answers one correctly
2: Both incorrect
0: Obeys both correctly
1: Obeys one correctly
2: Both incorrect
0: Normal
1: Partial gaze palsy
2: Forced deviation
0: No visual field loss
1: Partial hemianopia
2: Complete hemianopia
3: Bilateral hemianopia (blind including cortical blindness)
0: Normal symmetrical movement
1: Minor paralysis (flattened nasolabial fold, asymmetry on
2: Partial paralysis (total or near total paralysis of lower face)
3: Complete paralysis of one or both sides (absence of facial
movement in the upper and lower face)

5. Motor functionarm (right and left):

Right arm
Left arm

0: Normal (extends arms 90 (or 45) degrees for 10 seconds

without drift)
1: Drift
2: Some effort against gravity
3: No effort against gravity
4: No movement
9: Untestable (joint fused or limb amputated)

6. Motor functionleg (right and left):

Right leg
Left leg

0: Normal (hold leg 30 degrees position for 5 seconds)

1: Drift
2: Some effort against gravity
3: No effort against gravity
4: No movement
9: Untestable (joint fused or limb amputated)
0: No ataxia
1: Present in one limb
2: Present in two limbs
0: Normal
1: Mild to moderate decrease in sensation
2: Severe to total sensory loss
0: No aphasia
1: Mild to moderate aphasia
2: Severe aphasia
3: Mute
0: Normal articulation
1: Mild to moderate slurring of words
2: Near unintelligible or unable to speak
9: Intubated or other physical barrier
0: Normal
1: Inattention or extinction to bilateral simultaneous stimulation
in one of the sensory modalities
2: Severe hemi-inattention or hemi-inattention to more than
one modality

7. Limb ataxia:

8. Sensory (use pinprick to test arms, legs,

trunk and facecompare side to side):
9. Best language (describe picture, name
items, read sentences)

10. Dysarthria (read several words):

11. Extinction and inattention:

Reprinted from the National Institute of Health. Available at:


AACN Clinical Issues



Three-item Scale for the

Prediction of Stroke

DWI-MRI volume (mL)
Time from onset (hours)

Assigned Points

Adapted with permission from Baird AE, Dambrosia J, Janket

SJ, Eichbaum Q. A three-item scale for the early prediction
of stroke recovery. Lancet. 2001;357(9274):20952100.
DWI-MRI, diffusion weighted imaging-magnetic resonance
imaging; NIHSS, National Institutes of Health Stroke Scale.

Improvement of blood flow to the ischemic area of the brain involves the use of
thrombolytic therapy, which should be initiated as soon as possible. However, there
are several caveats associated with the use of
this therapy, the most serious being the risk
of hemorrhage. Therefore, recombinant t-PA
is the preferred treatment for acute ischemic
It is extremely important to identify the
patients who will benefit most from the administration of t-PA. Certain types of stroke,
such as lacunar infarcts, have not shown
any major improvement in outcome with the
use of t-PA. Therefore, diagnostic imaging
needs to be reviewed to identify the presence
of ischemic tissue that could be reperfused
through thrombolysis.18
The risk of hemorrhage following the
use of thrombolytic agents increases with
larger strokes, higher doses of medication,
and longer time intervals from the onset of
symptoms.3 Since timing is an important issue, it is recommended that the thrombolytic
agent be administered within 180 minutes of
the onset of symptoms. Prompt administration of thrombolytic agents decreases the risk
of disability following stroke by as much as
30%. The patients with the most improvement were younger, had smaller ischemic areas and lower NIHSS scores. Overall, judi-

cious use of t-PA demonstrated improvement

of 4 or more points on the NIHSS score.2426
Recommended criteria for treatment with
t-PA includes: (1) an ischemic stroke with
a clearly defined time of onset of no more
than 180 minutes, (2) evidence of neurologic
deficit measurable on the NIHSS, and (3) a
CT scan of the brain with no evidence of intracranial hemorrhage. Additionally, patients
should not be given thrombolytic therapy if
they have had: (1) a stroke or serious head
trauma within the past 3 months, (2) have
had major surgery within the past two weeks,
(3) have a prior history of intracranial hemorrhage or bleeding from any other body
site such as a gastrointestinal hemorrhage,
and (4) have a systolic blood pressure above
185 mm Hg or diastolic blood pressure above
110 mm Hg.27
When appropriate guidelines are followed
for the administration of t-PA, the rate of
hemorrhage as a result of thrombolytic use
was approximately 5.2% in one study28 and
6.5%24 in another. However, for patients who
did not receive t-PA, the risk of hemorrhage
after cerebral infarction was 0.6%. The National Institute of Neurologic Disorders and
Stroke has identified these factors related to
an increase risk of hemorrhage following the
administration of t-PA: over the age of 70,
NIHSS score of more than 20 points, blood
glucose levels greater than 300 mg/dL, and
evidence of cerebral edema on CT scan. The
risk of hemorrhage was greater in those patients who had more than one risk factor.24
There have been studies that have examined intracranial administration of thrombolytics. Although these studies demonstrated reversal of ischemia with less systemic
bleeding, this method is not yet approved by
the Food and Drug Administration for use in
the United States.3
Other agents that are used in the treatment
of stroke include antiplatelet therapy and the
use of anticoagulants. Aspirin used within
48 hours of onset of symptoms have been
shown to reduce risk and mortality. The use
of the anticoagulant heparin is also beneficial
in preventing further clot formation. Current
research is being done to develop neuroprotective agents that would block amino acid
pathways and decrease neurotransmitter activity of injured tissue.3

Vol. 16, No. 4, Oct-Dec 2005

Cerebral Hemorrhagic

Most cerebral hemorrhages develop rapidly

over 30 to 90 minutes, often with rapid
loss of consciousness. Therefore, it is imperative to maintain a patent airway. Initial treatment includes intubation, hyperventilation, elevation of the head of the bed,
and administration of intravenous mannitol
to prevent and reduce elevated intracranial
Other than reversal of pre-existing anticoagulation, nothing can be done to stop the
hemorrhage once it begins. If ICP is elevated,
osmotic agents and hyperventilation are used
to reduce it. Cerebral spinal fluid can also be
removed from the ventricles in an attempt to
lower ICP.3
Patients who survive a cerebral hemorrhage have the potential for good recovery.
However, the prognosis is dependent upon
the size of the hemorrhage. A hemorrhage
volume <30 mL may have a good prognosis, whereas a volume >60 mL has a much
poorer prognosis.3
Recovery Phase

Blood pressure levels usually stabilize during the first 2 weeks following a stroke. For
many patients, their blood pressure is lower
and then gradually increases. Any patient
with persistent elevation in blood pressure
should be evaluated for end-organ damage.25
Patients whose blood pressure is controlled
with angiotensin-converting enzyme (ACE)
inhibitors have done better than those treated
with other antihypertensive medications.14
Prevention of a stroke involves lifestyle
changes as well as medication and surgery.
It is important to review the risk factors with
patients to be able to identify areas that need
to be addressed. Additionally, it is hoped that
by discussing these issues with patients, they
will be more likely to comply with the therapeutic regimen. Both diet and exercise can
be used to help control both blood pressure and cholesterol levels. Smoking cessation and reduction of alcohol intake also
must be part of lifestyle modifications. There



is a much greater risk of having a stroke

in smokers, with the risk increasing with
the number of cigarettes smoked per day.7
Patients can also find further information
from the following organizations Web sites:
(1) National Instituted of Neurological Disorders and Stroke at: http://www.ninds.nih.
gov/, (2) National Institute of Health
Stroke Scale at:
doctors/index.htm, (3) American Stroke Association: A Division of American Heart Association at:,
and (4) National Stroke Association at:
Medications may be needed to control
blood pressure. Adequate control of blood
pressure has been shown to reduce the risk
of stroke in older adults. The use of ACE
inhibitors appears to be helpful in preventing strokes, possibly through the reduction
of C reactive protein levels. Treatment goals
should include maintaining blood pressure
<130/80 mm Hg.3,14,25 Additional research is
also examining the use of angiotensin receptor blocking agents, such as losartan, for
stroke prevention.29
Elevated cholesterol levels are a risk factor for the development of atherosclerosis
and can be viewed as a risk factor for ischemic stroke. Elevated high-density lipoprotein (HDL) levels and lower total cholesterol
(TC) HDL ratios have been associated with
a decreased incidence of stroke. However,
for many people, diet and exercise do not
sufficiently lower the TC-HDL ratio. Therefore, the use of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-C0-2A) reductase inhibitors, such as pravastatin, is recommended
to reduce the risk of ischemic stroke.30
Medical therapy also includes the use of
antiplatelet agents. The most frequently used
agents are aspirin, clopidogrel, and the combination of aspirin plus dipyridamole. The
use of antiplatelet agents is currently preferred rather than using anticoagulants such
as warfarin. For patient with atrial fibrillation,
warfarin is preferred. However, the International Normalized Ratio measurement for
anticoagulant action should be maintained
at 2.0 or greater for the best effect. Surgical intervention with endarterectomy can
improve circulation in patients with carotid


AACN Clinical Issues


 Future Directions for Stroke Care

and Research
Just as designated trauma centers have improved treatment and outcome for patients
involved in major trauma, the hope for the
future is the development of specific stroke
centers. Since not all hospitals are equipped
with advanced radiological imaging methods such as DWI-MRI, transport of patients
to hospitals that do have them can aid in
rapid diagnosis and early intervention and
treatment. Thus, the National Institute of
Neurological Disorders and Stroke is developing guidelines for the establishment of
designated stroke centers.32
In addition to the development of stroke
centers, The National Institute of Neurological Disorders and Stroke is identifying new
avenues of research for stroke prevention
and treatment. Specific areas of interest include defining the biology of stroke through
the examination of genetic factors, inflammatory mediators, and the process of stroke
Genetic research can be a valuable part
of the biology of stroke research. There are
genetic responses involved in cellular adaptation to injury in ischemic events. Further
research into their role can provide additional insight into mechanisms of neuronal
survival during hypoxia and ischemia. This
could be used to minimize the negative effects of ischemia.6,33
Since the inflammatory response plays an
integral role in the stroke injury, further research should examine the relationship between BP levels, inflammatory mediators,
and C reactive protein levels. Initial studies of
patients taking ACE inhibitors have demonstrated that levels of C reactive protein levels
are reduced.14 Thus, further study could determine if there are neuroprotective effects
from the action of ACE inhibitors.14
Agents such as abciximab (ReoPro), an antiplatelet agent that exerts its effects through
the glycoprotein IIb/IIIa receptor, are being
studied. It is hoped that administering them
during the first 6 hours following the onset of
symptoms will also be beneficial. Current research is examining their role either alone or
in conjunction with thrombolytic therapy.34
The role of neuroprotective agents in the
treatment of stroke is also an important area

for research. Anti-excitatory agents can be

developed with the goal of blocking of glutamate activity,1 although it was postulated
that the administration of magnesium, since
it normally blocks the glutamate receptor,
would provide neuroprotective effects. Early
studies have only demonstrated a reduction
in patient blood pressure.35 However, more
research still needs to be done on neuroprotective agents. Most of the studies36,37 examining the role of neuroprotective agents have
not used them in combination with thrombolytic therapy to examine their effectiveness
with concurrent effective reperfusion.
Additional suggested research would examine the role of other imaging techniques
such as perfusion-weighted MRI (PWI) in
providing information about the status of microvascular perfusion and in the clinical setting is an index of cerebral blood flow. This
would enable the identification of patients
who will derive greatest benefit with the least
risk from t-PA.33,37
Currently research is being done examining the use of endovascular photoacoustic recanalization. This new technology uses laser
technology for mechanical clot fragmentation. The goal of this therapy is to rapidly
open cerebral vessels and reduce the use of
New treatment options also need to be
explored. This includes direct intra-arterial
injection of thrombolytic agents, use of defibrinogenating agents such as ancrod, and
carotid artery stenting. Additionally, work is
being done to determine of ultrasound technology can be used to enhance clot lyses in
combination with thrombolytic agents.3,33,37,39
Cerebrovascular disease and its sequelae are
a significant cause of morbidity and mortality among older adults. Although lifestyle
modifications can reduce the risk of developing a stroke, for many individuals, medications are part of their risk reduction regimen.
Once a stroke has occurred, there needs to
be rapid identification of the type and extent
of the event so that immediate and appropriate treatment can be initiated. Future designation of specific stroke centers would be a significant step in improving patient outcome.

Vol. 16, No. 4, Oct-Dec 2005

However, much research still needs to be

done to promote the best level of neurological recovery following a stroke.

1. Ganong WF. Review of Medical Physiology, 22nd ed. New York: Lange Medical
Books/McGraw-Hill Medical Publishing Division; 2005.
2. Guyton AC, Hall JE. The Textbook of Medical
Physiology, 10th ed. Philadelphia, Penn: W.B.
Saunders; 2000, chap 45, 61.
3. Smith WS, Johnston S, Easton JD. Cerebrovascular diseases. In: Kasper DL, Fauci AS, Longo
DL, Braunwald E, Hauser SL, Jameson JL, eds.
Harrisons Principles of Internal Medicine,16th
ed. New York: McGraw-Hill Medical Publishing Division; 2005,23722393.
4. American Heart Association (AHA). Heart Disease and Stroke Statistics2005 Update. Dallas, Tex.: AHA; 2004.
5. American Stroke Association. Stroke among
Hispanics. 2003. Available at: http://strokeassociation . org / presenter . jhtml ? identifier =
3030389. Accessed July 19, 2005.
6. National Institute of Neurological Disorders
and Stroke. Report of the Stroke Progress Review Group. 2004. Available at: http://www. people/groups/stroke prg/
04 2002 stroke prg report.htm. Accessed January 10, 2005.
7. Kurth T, Kase CS, Berger K, Gaziane JM, Cook
NR. Smoking and risk of hemorrhagic stroke
in women. Stroke. 2003;34:2792.
8. Messing RO. Nervous system disorders. In:
McPhee SJ, Lingappa VR, Ganong WF, eds.
Pathophysiology of Disease: An Introduction to
Clinical Medicine, 4th ed. New York: Lange
Medical Books/McGraw-Hill Medical Publishing Division; 2003,143188.
9. Solenski NJ. Transient ischemic attacks: part
Idiagnosis and evaluation. Am Fam Physician. 2004;69(7):16651674,16791680.
10. Bradberry JC, Fagan SC. Stroke. In: Dipiro JT,
Talbert RL, Yee GC, Matzke GR, Wells BG,
Posey LM, eds. Pharmacotherapuy: A Pathophysiology Approach. New York: McGraw Hill
Medical Publishing Division; 2002,375394.
11. Frosch MP, Anthony DC, De Girolami U. The
central nervous system. In: Kumar V, Abbas
AD, Fausto N, eds. Robbins & Cotran Pathologic Basis of Disease, 7th ed. Philadelphia:
Elsevier Saunders; 2005,13471419.
12. Book D. Disorders of brain function. In: Porth
CM, ed. Pathophysiology Concepts of Altered
Health States. Philadelphia, Penn: Lippincott
Williams & Wilkins; 2005, 12431244.



13. Falcao ALE, Ruetens DC, Maarkus R, Koga

M, Read SJ, Tochon-Danguy H, Sachinidis J,
Howells DW, Donnan GA. The resistance of
ishemia of white and gray matter after stroke.
Ann Neurol. 2004;56:695701.
14. Di Napoli M, Papa F. Antiotensin-converting
enzyme inhibitor use is associated with reduced plasma concentration of C reactive protein in patients with first ever ischemic stroke.
Stroke. 2003;34:2922.
15. Aminoff MJ. Nervous system. In: Tierney LM,
McPhee SJ, Papadakis MA. Current Medical Diagnosis and Treatment, 43rd ed. New
York: McGraw-Hill Medical Publishing Division; 2005,9411000.
16. Dillon WP. Neuroimaging in neurologic disorders. In: Kasper DL, Fauci AS, Longo DL,
Braunwald E, Hauser SL, Jameson JL, eds. Harrisons Principles of Internal Medicine,16th ed.
New York: McGraw-Hill Medical Publishing
Division; 2005,23502357.
17. Kidwell CS, Warach ST. Acute ischemic
cerebrovascular syndrome. Stroke. 2003;34:
18. Neumann-Haefelin T, Moseley MD, Albres
GW. New magnetic resonance imaging methods for cerebrovascular disease: emerging
clinical applications. Ann Neurol. 2000;47:
19. Kidwell CS, Chalela JA, Saver JL, Starkman S,
Hill MD, Demchuk AM, Butman JA, Patrones
N, et al. Comparison of MRI and CT for detection of acute intracerebral hemorrhage. JAMA.
20. National Institute of Health. National Institute
of Health stroke scale. 1997. Available at:
Accessed January 10, 2005.
21. Goldstein LG, Samsa GP. Reliability of the National Institutes of Health Stroke Scale. Stroke.
22. National Institute of Neurological Disorders
and Stroke. New tool allows early predication
of patients stroke outcome. 2005. Available at: and events/
press releases/pressrelease stroke outcome
063001.htm. Accessed January 10, 2005.
23. Baird AE, Dambrosia J, Janket S-J, Eichbaum
Q, Chaves C, Silver B, Barber PA, Parsons
M, Darby D, Davis S, Caplan DR, Edelman
RR, Warach S. A three-item scale for the early
prediction of stroke recovery. Lancet. 2001;
24. OFallon WM, Asplund K, Goldfrank LR,
Hertzberg VS, Ingall TJ, Louis TA. Report of
the t-PA Review Committee. Bethesda, Md: National Institute of Neurological Disorders and
Stroke; 2005,175.
25. Solenski NJ. Transient ischemic attacks: part







AACN Clinical Issues


IItreatment. Am Fam Physician. 2004;69(7):

Chalela JA, Kang D-W, Luby M, Ezzeddine M,
Latour LL, Todd JW, Dunn B, Warach S. Early
MRI findings in patients receiving tissue plasminogen activator predict outcome: insights
into the pathophysiology of acute stroke in the
thrombolysis era. Ann Neurol. 2004;55:105
The National Institute of Neurological Disorders and Stroke, t-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic
stroke. N Eng J Med. 1995;333:15811587.
Graham GD. Tissue plasminogen activator
for acute ischemic stroke in clinical practice: a meta-analysis of safety data. Stroke.
Adams HP. New strategies for prevention of
ischemic stroke: the LIFE study. Curr Neurol
Neurosci Rep. 2003;3(1):4651.
Bowman TS, Sesso HD, Ma J, Kurth T, Kase CS,
Stampfer MJ, Gaziean JM. Cholesterol and the
risk of ischemic stroke. Stroke. 2003;34:2930.
Hylek EM, Go AS, Chang Y, Jensvold NG,
Henault LE, Selby JV, Singer DE. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J
Med. 2003;349:10191026.
Jagoda A, Pacioli AM, Asimos AW, Barsan WG,
Baumlin K, Dalsey W, Delaney KA, et al.





Improving the Chain of Recovery for Acute

Stroke in Your Community: Task Force Report.
Bethesda, Md: National Institute of Neurological Disorders and Stroke; 2002,112.
Fisher M, Ratan R. New perspectives on developing acute stroke therapy. Ann Neurol.
Winkley JM, Adams HP. Potential role of abciximab in ischemic cerebrovascular disease.
Am J Cardiol. 2000;85(8a):47c51c.
Muir KW, R Lees KR, Ford I, Davis S. Magnesium for acute stroke (intravenous magnesium
efficacy in stroke trial): randomised controlled
trial. Lancet. 2004;363(9407):439445.
Goldstein LB. Neuroprotective therapy for
acute ischaemic stroke: down, but not out.
Lancet. 2004;363(9407):414415.
Fisher M. recommendations for advancing development of acute stroke therapies: stroke
therapy academic industry roundtable 3.
Stroke. 2003;34:15391546.
Berlis A, Helmi L, Barnwell S, Norbash A,
Wechsler L, Jungreis CA, Woolfenden A, et al.
Mechanical thrombolysis in acute ischemic
stroke with endovascular photoacoustic recanalization. Stroke. 2004;35:11121116.
Eggers J, Koch B, Meyer K, Konig I, Seidel
G. Effect of ultrasound on thrombolysis of
middle cerebral artery occlusion. Ann Neurol.