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In Clinical Practice

Gabriel J.E. Rinkel


Paut Greebe

Subarachnoid
Hemorrhage
in Clinical
Practice

In Clinical Practice

For further volumes:


http://www.springer.com/series/13483

Taking a practical approach to clinical medicine, this series of


smaller reference books is designed for the trainee physician, primary care physician, nurse practitioner and other general medical
professionals to understand each topic covered. The coverage is
comprehensive but concise and is designed to act as a primary
reference tool for subjects across the field of medicine.

Gabriel J.E. Rinkel Paut Greebe

Subarachnoid
Hemorrhage in Clinical
Practice

Gabriel J.E. Rinkel


Department of Neurology
and Neurosurgery
Brain Center Rudolf Magnus
University Medical Center
Utrecht
The Netherlands

Paut Greebe
Department of Neurology
and Neurosurgery
Brain Center Rudolf Magnus
University Medical Center
Utrecht
The Netherlands

ISSN 2199-6652
ISSN 2199-6660 (electronic)
In Clinical Practice
ISBN 978-3-319-17839-4
ISBN 978-3-319-17840-0 (eBook)
DOI 10.1007/978-3-319-17840-0
Library of Congress Control Number: 2015940550
Springer Cham Heidelberg New York Dordrecht London
Springer International Publishing Switzerland 2015
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Acknowledgments

This book owes its existence to the uncountable numbers of


patients with an unruptured aneurysm or subarachnoid hemorrhage who helped in improving our knowledge. Therefore,
in the first place, we would like to express our gratitude to
them and to their partners and families. By making us part of
their experience of the disease, by their questions, by expressing their complaints, and by cooperating in our research, we
have acquired the knowledge that forms the basis of this
book. We hope that by writing this book, we can distribute
the results of their collaboration with us and thereby optimize the care and information to future patients and to
research.
Further, we would like to thank all the people who have
taken care of patients with subarachnoid hemorrhage and
intracranial aneurysms and with whom we have worked
together in our institution over the last two decades from the
department of Neurology and Neurosurgery, the department
of Radiology, the department of Rehabilitation and Sports,
and the Trial Office Cerebrovascular diseases and the neuropsychologists who work in our department. We would like to
list some of these co-workers in alphabetical order: Ale
Algra, Jaap Kappelle, Patricia Passier, Ynte Ruigrok, Dorien
Slabbers, Birgitta Velthuis, Mervyn Vergouwen, Anne VisserMeily and Janny Wagensveld.
Not only patients but also residents and PhD students ask
and have asked questions that made us think and rethink and,
v

vi

Acknowledgments

by doing so, increased our knowledge. The research for their


thesis has contributed to many topics in this book. A special
thanks therefore to all of them.
Also the collaboration with and hospitality of colleagues
in other hospitals in the Netherlands and abroad have had an
enormous impact on our knowledge. We keep good memories
of visits to centers in Australia, Belgium, Canada, Chile,
England, Finland, France, Germany, Hong Kong, Italy, Japan,
New Zealand, Norway, Portugal, Scotland, Sweden,
Switzerland, and USA. A special thanks in this respect to our
colleagues in neuroradiology at the Toronto Western Hospital
in Canada, where we have spent many micro-sabbaticals.
Wiebe Bosma, a general practitioner in Meppel,
Netherlands, made comments on previous versions of the
chapters and gave us indispensable insight in the medical
world outside the hospital. We thank him for sharing his
knowledge of daily practice and detailed comments.
Last but not least, we would like to thank Springer and
specially Joanna Bolesworth for her confidence in us and her
patience. This book which is all about subarachnoid hemorrhage and aneurysms allows us to make our knowledge
accessible for stakeholders and interested parties.

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Why This Handbook . . . . . . . . . . . . . . . . . . . . . . . . . .

What Is an Aneurysm and What


Is a Subarachnoid Hemorrhage. . . . . . . . . . . . . . . .
Aneurysms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prevalence of Aneurysms . . . . . . . . . . . . . . . . . . .
Risk of Rupture of Aneurysms . . . . . . . . . . . . . . .
Trigger Factors for Rupture. . . . . . . . . . . . . . . . . .
Subarachnoid Hemorrhage . . . . . . . . . . . . . . . . . . . .
Incidence, Case Fatality, Dependency Rates
and Long-Term Outcome . . . . . . . . . . . . . . . . . . .
Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . .
Perimesencephalic Hemorrhage:
A Benign Subset . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

17
18

Aneurysms and Subarachnoid Hemorrhage


in General Practice . . . . . . . . . . . . . . . . . . . . . . . . . .
Management of Unruptured Aneurysms . . . . . . . . .
General Approach . . . . . . . . . . . . . . . . . . . . . . . . .
Interventions to Occlude the Aneurysm . . . . . . .
General and Medical Management . . . . . . . . . . .
Follow-Up Imaging. . . . . . . . . . . . . . . . . . . . . . . . .

25
26
26
29
30
32

1
1

3
5
5
6
9
10
10
12
15

vii

viii

Contents

Indications for and Methods of Screening . . . . . . . .


Risk Groups and Indications for Screening . . . .
Method of Screening . . . . . . . . . . . . . . . . . . . . . . .
Recognition of Subarachnoid Hemorrhage
and Initial Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

34
34
36
38
40

In Hospital Course . . . . . . . . . . . . . . . . . . . . . . . . . .
Diagnostic Procedures and Initial Management . . .
Complications During the Hospital Course. . . . . . .
Rebleeding. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Delayed Cerebral Ischemia . . . . . . . . . . . . . . . . . .
Acute Hydrocephalus. . . . . . . . . . . . . . . . . . . . . . .
Treatment of the Aneurysm: Clipping or Coiling . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

47
48
51
51
51
52
53
53

Initial Post-hospital Course and After-Care . . . . .


Discharge Destinations. . . . . . . . . . . . . . . . . . . . . . . .
Home . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Rehabilitation Facility . . . . . . . . . . . . . . . . . . . . . .
Nursing Home . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aftercare. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Schedule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Outpatient Clinic . . . . . . . . . . . . . . . . . . . . . . . . . .
Follow-up Imaging of Aneurysms. . . . . . . . . . . . .
Symptoms and Deficits . . . . . . . . . . . . . . . . . . . . . . . .
Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mood Disorders: Anxiety, Depression
and Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Senses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Symptoms Specific to Treatment . . . . . . . . . . . . .
Seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Reintegration into Work. . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

57
58
58
58
59
60
61
64
66
67
69
69
70
71
74
74
75
77

Contents

ix

Long-Term Prognosis . . . . . . . . . . . . . . . . . . . . . . . .
Continuing Recovery . . . . . . . . . . . . . . . . . . . . . . . . .
Recovery in General . . . . . . . . . . . . . . . . . . . . . . .
New Cardiovascular and Other Events
and Life Expectancy . . . . . . . . . . . . . . . . . . . . . . . . . .
Risk of New Aneurysm and New
Subarachnoid Hemorrhage . . . . . . . . . . . . . . . . . .
Risk of Other Cardiovascular Events . . . . . . . . .
Risk of Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Secondary Prevention . . . . . . . . . . . . . . . . . . . . . . . . .
Screening for New Aneurysms . . . . . . . . . . . . . . .
Lifestyle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Medical Management. . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

81
82
82

Clinical Research and Patient Participation . . . . .


Future Prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

93
95
96

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

83
83
85
86
86
88
88
89
89
90

99

Chapter 1
Introduction

Why This Handbook


A subarachnoid hemorrhage from a ruptured aneurysm is a
subset of stroke. Although it constitutes only 5 % of all
strokes, the loss of productive life years from aneurysmal
subarachnoid hemorrhage in the general population is as
large as that from brain infarcts, the most common type of
stroke. Moreover, its economic burden is considerable. The
huge impact of subarachnoid hemorrhage is explained by the
young age at which it occurs and the poor outcome. Around
one of every three patients dies within the initial 4 weeks
after the hemorrhage, and one of five survivors remains
dependent on help for activities of daily living. Moreover,
many patients without obvious focal deficits have cognitive
complaints or deficits, minor neurological deficits, a sleep
disorder or increased fatigue, and symptoms of anxiety and/
or depression. All these decrease day-to-day functioning,
hamper reintegration in social and professional roles and
reduce quality of life.
Although subarachnoid hemorrhage is a rare disease with
an incidence of about 10 per 100,000 persons per year, intracranial aneurysms from which they derive are, with a prevalence of around 3 %, not so rare. Given the increased
sensitivity and availability of brain imaging equipment and

G.J.E. Rinkel, P. Greebe, Subarachnoid Hemorrhage


in Clinical Practice, In Clinical Practice,
DOI 10.1007/978-3-319-17840-0_1,
Springer International Publishing Switzerland 2015

Chapter 1.

Introduction

the increasing use of total body screening in commercial magnetic resonance screening facilities, the number of unruptured aneurysms detected incidentally has increased
considerably over the last two decades. Incidental detection
of an aneurysm is a threat for a persons health and raises
many questions in these persons and their families.
The acute care of patients with aneurysmal subarachnoid
hemorrhage is provided in tertiary care centers, but a large
part of the burden of aneurysmal subarachnoid hemorrhage
is in the aftermath and occurs far beyond the reach of these
tertiary care centers. The care in this phase rests on general
practitioners, rehabilitation physicians, nursing home physicians, physicians working for health insurance companies,
occupational health physicians, other health care professionals in these fields such as physiotherapists, neuropsychologists and occupational therapists and, not to forget, caregivers.
These health care professionals often have limited experience with this disease because it is a relatively rare one. In
contrast, they will be increasingly confronted with persons in
whom an aneurysm is detected incidentally. This handbook
aims to be a reference of information and a practical guide on
intracranial aneurysms and on subarachnoid hemorrhage,
with focus on the long-term complications and their management for health care professionals outside tertiary care hospitals. Furthermore, it aims to provide answers on questions
from patients and relatives on secondary prevention, familial
burden of subarachnoid hemorrhage and screening.

Chapter 2
What Is an Aneurysm
and What Is a Subarachnoid
Hemorrhage
Aneurysms are bulges of the intracranial arteries caused by
local weakness of the arterial wall. They are often referred to
as saccular or berry aneurysms because of their shape and to
discriminate these aneurysms from the much rarer dissecting
aneurysms, which are caused by a tear in the aneurysm wall.
Aneurysms are usually located at the basal intracranial arteries in the subarachnoid space (Figs. 2.1 and 2.2). Most aneurysms go unnoticed, unless they are very large, rupture, or are
incidentally found during brain imaging. Rupture of an aneurysm gives rise to a subarachnoid hemorrhage, which may
extend into the brain parenchyma or ventricular system.
A subarachnoid hemorrhage from an intracranial aneurysm
is a subset of stroke that carries a high risk of death or permanent disability and usually occurs at relatively young age.
There are many more causes of subarachnoid hemorrhage
than rupture of an aneurysm, with trauma being the most
common, and the most appropriate term would be aneurysmal subarachnoid hemorrhage, but for the sake of simplicity
and because it is often used as such, we will refer to a
hemorrhage from a (presumed) rupture of an intracranial
aneurysm as subarachnoid hemorrhage. Similarly, we will use
the term aneurysm for intracranial saccular aneurysms. This
chapter describes the prevalence and risk of rupture of intracranial aneurysm, the incidence and risk factors for

G.J.E. Rinkel, P. Greebe, Subarachnoid Hemorrhage


in Clinical Practice, In Clinical Practice,
DOI 10.1007/978-3-319-17840-0_2,
Springer International Publishing Switzerland 2015

Chapter 2. What Is An Aneurysm/SAH

Anterior communicating artery


Middle cerebral artery
Carotid artery
Basilar artery

Figure 2.1 MR-angiography showing basal arteries of the brain


seen from above with preference sites of aneurysm

Aneurysm at bifurcation of
middle cerebral artery

Figure 2.2 MR-angiogram with intracranial aneurysm at the middle


cerebral artery

Aneurysms

subarachnoid hemorrhage, the clinical syndrome of subarachnoid hemorrhage and case fatality and dependency
rates after subarachnoid hemorrhage.

Aneurysms
Prevalence of Aneurysms
Around 3 % of the population has an unruptured intracranial
aneurysm, which means that in the European Union, there
are around 15 million people with an aneurysm [1]. Aneurysms
develop during life and are extremely rare under the age of
20. Women have a higher risk, in particular after the fifth
decade. The prevalence of aneurysms is also higher in persons
with a family history of subarachnoid hemorrhage or patients
with autosomal dominant polycystic kidney disease
(Table 2.1). In these higher-risk groups, the chance of finding
an aneurysm at a first screening is around 10 % [35], but
these subgroups are small. Around 3 % of the population has
one or more first-degree relatives with a subarachnoid hemorrhage, and 1 in 1,000 has autosomal polycystic kidney disease. The prevalence of unruptured intracranial aneurysms is
not higher in Finland and Japan than in other parts of the
world [1], which contrasts with the finding that the incidence
of subarachnoid hemorrhage is higher in these countries
compared to most other countries [6].
Smoking and hypertension are important environmental
factors that increase the risks for having an aneurysm [1]. The
risk in persons with both risk factors is higher than the sum
of risks separately, which suggests that smoking and hypertension have an additive effect [2].
Some environmental factors are associated with a lower
risk of rupture. In a recent case control study, the risk was
lower in persons who regularly exercise and contra-intuitively
also in those with hypercholesterolemia [2]. The relation with
hypercholesterolemia is uncertain, however, because Japanese
investigators reported that hypercholesterolemia increases

Chapter 2. What Is An Aneurysm/SAH

Table 2.1 Prevalence and risk factors of aneurysms


Overall prevalence
3.2 %
Risk factor
RR
95 % CI
Non-modifiable risk factors
Female sex

1.6

1.02.5

Age <30 years

0.01

0.000.12

Atherosclerosis

1.7

0.93.0

Family history

3.4

1.95.9

ADPKD

6.9

3.514

Current smoking

3.0

2.04.5

Hypertension

2.9

1.94.6

Physical exercise

0.6

0.30.9

Environmental risk factors

Data based on Refs. [1, 2]


RR risk ratio for non-modifiable risk factors prevalence ratios and
for environmental risk factors odds ratios, ADPKD adult dominant
polycystic disease

the risk of aneurysms [7] and a Chinese study found no effect


[8]. Persons with regular physical exercise seem to have a
lower risk of aneurysms (Table 2.1) [2].

Risk of Rupture of Aneurysms


Although around 15 million people in the EU have an aneurysm, per year the number of patients with subarachnoid
hemorrhage in the EU is around 50,000 [6], which shows that
the chance of rupture of intracranial aneurysms in general is
small. One of the explanations is that two-thirds of the unruptured aneurysms are smaller than 5 mm, which means that
they have a very small risk of rupture [1].
In a meta-analysis based on individual patient data from
six cohort studies, risk factors for rupture were age,
hypertension, previous history of subarachnoid hemorrhage,

Aneurysms

aneurysm size, aneurysm location (Table 2.2) and geographic


region. Compared with other Western populations, Finnish
and Japanese people had an increased risk of aneurysm rupture. In a non-Finnish, non-Japanese population, the estimated 5-year absolute risk of aneurysm rupture ranges from
0.3 to over 15 %. Based on the data from this meta-analysis,

Table 2.2 Predictors composing the PHASES aneurysm rupture


risk score [9]
Non-Japanese/Finnish
0
Population
Japanese

Finnish

No

Yes

<70

70

<7.0

7.09.9

10.019.9

20

13

Earlier SAH from another


aneurysm

No

Yes

Site of aneurysm

ICA

MCA

ACA

Pcom/posterior

Hypertension

Age (years)

Size of aneurysm (mm)

SAH subarachnoid hemorrhage, ICA internal carotid artery, ACA


anterior cerebral arteries (including the anterior cerebral artery,
anterior communicating artery, and pericallosal artery), MCA middle cerebral artery, Pcom posterior communicating artery, posterior
posterior circulation (including the vertebral artery, basilar artery,
cerebellar arteries, and posterior cerebral artery)

Chapter 2. What Is An Aneurysm/SAH

the PHASES aneurysm rupture risk score was developed to


assess absolute 5 year risk of rupture based on six predictors
(Tables 2.2 and 2.3).
The data here are presented as 5 year risk of rupture. It is
important to realize that data for longer periods of follow-up
are scarce and cannot be simply derived from extrapolating
the observed data because unruptured aneurysms exhibit
short periods of fast growth and long periods of stability [10,
11]. Thus, it is over-simplistic to calculate a presumed 15 year
risk of rupture by tripling the 5 year risk of rupture. Indeed,
in the meta-analysis, the risk of rupture seems to decrease
over time, even within a 5 year period [9]. A similar observation was done in a large prospective follow-up study in
Finland [12].
The meta-analysis did not provide data on family history
as a risk factor for rupture, probably because most patients
with a positive family history and an unruptured aneurysm
found by chance or screening will ask for preventive treatment
instead of follow-up. Two pieces of evidence suggest that a
positive family history is associated with an increased risk of
rupture. First, for persons with a positive family history, the
relative risk of a ruptured aneurysm is much higher (odds
ratio 51) than the relative risk for an unruptured aneurysm
(odds ratio 4) [3, 12]. Second, in a comparison between
patients with unruptured familial aneurysms and patients
Table 2.3 Cumulative
5 year risk of rupture of
aneurysms based on the
PHASES score

Phases risk
score
05

% aneurysm
rupture in 5 years
0.6 (0.21.7)

67

1.0 (0.51.7)

89

1.7 (1.12.5)

1011

2.4 (1.83.2)

1213

3.2 (2.44.3)

1415

6.4 (4.78.6)

16+

14.6 (12.317.0)

Aneurysms

with sporadic aneurysms matched for site and size, the


patients with familial aneurysms had a 17 times higher risk of
rupture [13].
Shape of the aneurysm is in case control studies an important risk factor (Fig. 2.3) [14]. Because data on shape were not
available for most of the patients included in the metaanalysis, this factor could not be included in the risk score.
Finally, smoking could not be included in the risk score
because not all cohorts had prospectively collected data on
smoking. In one of the cohorts, a Finnish cohort with a
median follow-up of more than 20 years, current smokers had
a three times higher risk of rupture than patients who have
never smoked or have stopped smoking [15, 16].

Trigger Factors for Rupture


Trigger factors are activities that provoke the actual rupture
of aneurysms. For aneurysmal rupture, coffee and cola consumption, anger, startling, straining for defecation, sexual
intercourse, nose blowing and vigorous physical exercise have
been identified as triggers, with relative risks ranging
roughly from 2 (for coffee intake) to 20 (for startling) [1719].

Figure 2.3 Different shapes of aneurysms with different risks of


rupture. left: aneurysm with three characteristics that increase the
risk of rupture: it is large, has an irregular shape, and has an oblong
shape. middle: large aneurysm with more round and less irregular
shape than aneurysm on the left, and accordingly a smaller risk of
rupture. right: small aneurysm with small risk of rupture

10

Chapter 2. What Is An Aneurysm/SAH

These triggers have in common that they induce a sudden and


short increase in blood pressure, which seems a possible common cause for aneurysmal rupture. Although these findings
are interesting from a pathophysiological standpoint of view,
one cannot conclude that avoiding these activities has any
clinically significant effect on the risk of rupture. Aneurysms
that are left untreated usually have a 5 year risk of rupture of
less than 2 %. This confers to a risk of 0.0000004/h. Even a
15 times higher risk from heavy exercise then gives a risk of
0.000006 in the hour after the exercise. Similarly, it has been
calculated that patients with such a small risk of aneurysmal
rupture need to avoid 1.3 million episodes of sexual intercourse (i.e. 20,000 years of sexual activity) to avoid one episode of subarachnoid hemorrhage [20].

Subarachnoid Hemorrhage
Incidence, Case Fatality, Dependency Rates
and Long-Term Outcome
In high-income countries, subarachnoid hemorrhage constitutes around 5 % of all strokes [21]. Compared to other stroke
types, subarachnoid hemorrhage occurs at an earlier age, with
a mean age of onset of around 55 years [6, 22], but subarachnoid hemorrhage is extremely rare under the age of 20 years
[6]. A retrospective cohort study in northern California estimated an incidence of 0.2/100,000 children under the age of 20
per year [23]. The incidence is higher in women, but the gender difference starts only in the sixth decade and increases
thereafter (Fig. 2.4) [6]. The reason for the higher incidence in
women is unknown [24]. There are striking regional differences in the incidence of subarachnoid hemorrhage. In most
Western countries, the incidence is around 9 per 100,000 persons per year; in Finland and Japan it is around 20 and in
Central and South America around 4 per 100,000 persons per
year [6]. In a systematic review and meta-analysis on 48 studies, subarachnoid hemorrhage had a seasonal pattern, with
higher rates in winter, in particular in January [25].

Subarachnoid Hemorrhage

incidence per 100,000 patient years

30
25

11

men
women

20
15
10
5
0

<25

25-34

35-44

45-54

55-64

65-74

75-84

age

Figure 2.4 Incidence of subarachnoid hemorrhage according to age


and sex

Of all patients with subarachnoid hemorrhage, around


12 % die immediately or within the initial hours after the
hemorrhage, often before they can be brought into hospital
[26]. In population-based studies, case fatality rates have
decreased by 17 % over the last three decades, but still
around a third of patients die within the first month after the
hemorrhage [22]. Population-based studies also found that
within the first year after the hemorrhage, around half the
patients regain independence for activities of daily living [22].
Being independent for activities of daily living does not mean
that patients have recovered completely. Many patients who
return home have remaining deficits, often cognitive ones. Of
those former patients who have returned home, only a third
resume previous employment completely [27], and no more
than 5 % feel to have recovered completely [28].
Because of the early age that subarachnoid hemorrhage
occurs and the poor outcome, the socio-economic burden of
subarachnoid hemorrhage is high. The loss of productive life
years as result of subarachnoid hemorrhage is as large as that
of ischemic stroke [29], the most common type of stroke. The

12

Chapter 2. What Is An Aneurysm/SAH

total economic burden (including informal care and using the


human capital method to estimate production losses) of subarachnoid hemorrhage in the United Kingdom has been
estimated in 2010 to be 510 million annually [30].

Risk Factors
The risk factors for subarachnoid hemorrhage are not the
same as risk factors for aneurysms because the risk of subarachnoid hemorrhage consists of the risk of formation of an
aneurysm and the risk of rupture of an aneurysm. The most
important modifiable risk factors for subarachnoid hemorrhage are smoking and hypertension [31, 32], and together
these risk factors explain half the occurrences of subarachnoid hemorrhage [33]. Moreover, smoking and hypertension
have probably an additive effect, meaning that the joint effect
of current smoking and hypertension on the risk of subarachnoid hemorrhage is stronger than the sum of the independent
effects of each factor [34]. Both a nationwide case control
study and a cohort study in South Korea found that persons
who had stopped smoking 5 or more years ago had half the
risk of current smokers [35, 36]. Moreover, also reducing the
number of cigarettes smoked per day seems to reduce the
risk of subarachnoid hemorrhage [36].
Excessive alcohol consumption is also often mentioned as
risk factor for subarachnoid hemorrhage [31], but the effect
is probably explained by the concurrent smoking since in
several studies with multivariable analysis, excessive alcohol
intake was not an independent risk factor [33, 37, 38].
Although in 2005 a systematic review of studies on risk
factors for subarachnoid hemorrhage showed conflicting
results for physical exercise [39], a well-designed populationbased follow-up study in Finland performed after the publication of that review showed that physical exercise reduces
the risk of subarachnoid hemorrhage [40]. These findings
were confirmed in a study using controls from the general
population in the Netherlands [38]. Obesity and diabetes are

Subarachnoid Hemorrhage

13

no risk factors for subarachnoid hemorrhage [39, 41, 42].


Patients with hypercholesterolemia probably have a reduced
risk of subarachnoid hemorrhage since both in a systematic
review of the literature and in a population-based case control study, such an inverse relation was found [38, 39],
although a Japanese study found an increased risk for elderly
women [43] and a Finnish study found an increased risk for
men [37]. There is no good evidence that female hormone
replacement therapy reduces the risk of subarachnoid hemorrhage [24].
Besides age and female sex, the most important nonmodifiable risk factors for subarachnoid hemorrhage are
autosomal dominant polycystic disease and a positive family
history for subarachnoid hemorrhage. In fact, these risk factors increase the risk to a much greater extent than the environmental risk factors, but because the environmental factors
are much more common, their contribution to the occurrence of subarachnoid hemorrhage in the population is much
greater [44]. Ehlers-Danlos syndrome type IV, the vascular
type, is often mentioned as having an important association
with subarachnoid hemorrhage or intracranial aneurysms. It
is associated with dissection and aneurysms of large and
medium arteries including intracranial arteries. In a survey
of 131 patients who died from Ehlers-Danlos syndrome, the
cause of death in 9 (7 %) was subarachnoid hemorrhage [45].
However, in many patients with Ehlers Danlos syndrome,
the subarachnoid hemorrhage occurs without preceding
aneurysm or dissection and is probably explained by spontaneous rupture of an intracranial artery [46]. Marfan disease
has also been associated with intracranial aneurysms, but
several large surveys did not find an increased risk of aneurysms or subarachnoid hemorrhage in patients with Marfan
disease [4749].
Patients with autosomal dominant polycystic disease, a
genetic disorder affecting 1 in 1,000 people worldwide, have an
increased risk of subarachnoid hemorrhage. Two surveys published in the last decade of the previous century found subarachnoid hemorrhage as cause of death in 617 % of the

14

Chapter 2. What Is An Aneurysm/SAH

patients [50, 51]. Although both surveys may have been


affected by selection bias, these proportions nevertheless show
that subarachnoid hemorrhage is much more often a cause of
death in patients with polycystic disease than in persons from
the general population. Although familial clusterings of aneurysms or subarachnoid hemorrhage have been described in
families with polycystic kidney disease [5, 52], a recent large
study in Germany found that more than 90 % of the instances
of subarachnoid hemorrhage had occurred in polycystic kidney disease families wherein no other relatives had had a subarachnoid hemorrhage or aneurysm detected [53].
A positive family history is a potent risk factor for the
lifetime risk of subarachnoid hemorrhage (Table 2.4). Within
families with familial occurrence of subarachnoid hemorrhage, smoking and hypertension are as important as risk
factors as in persons with no family history of subarachnoid
hemorrhage [56] and maybe even to a higher extent [57].
In Table 2.4, the risk of having an aneurysm seems lower
than the lifetime risk of subarachnoid hemorrhage for persons with two or more affected first-degree relatives. The
explanation is that the proportion presented is the chance of
finding an aneurysm at initial screening in such persons. The

Table 2.4 Risk of aneurysms and subarachnoid hemorrhage according the number of relatives with subarachnoid hemorrhage
Number affected 1
Risk of
Life time risk of SAH
relatives
aneurysm (%)
(%)
0
3
0.7
1

11

25a

Data based on Refs. [3, 12, 54, 55]


1: first degree
SAH subarachnoid hemorrhage
a
The 25 % life time risk is based on an odds ratio with a wide interval, but the lower limit of the 95 % confidence interval still confers
to a life time risk of 6 %; the upper limit of the 95 % confidence
interval to a life time risk of 70 %

Subarachnoid Hemorrhage

15

proportion with initial negative screen have however a considerable risk of developing new aneurysms that can be
found at repeated screening [3].
Incidences and remaining lifetime risks for subarachnoid
hemorrhage can be calculated based on age and sex and four
risk factors for subarachnoid hemorrhage. With these determinants remaining lifetime risks of subarachnoid hemorrhage vary between 0.02 for women 3545 years of age
without a positive family history who do not smoke and have
no hypertension and more than 7 % for women 5565 years
of age with a positive family history who smoke, have hypertension and no hypercholesterolemia (Fig. 2.5) [38].

Clinical Syndrome
The hallmark of a subarachnoid hemorrhage is the acute
onset of the most severe headache ever. Patients typically
describe the onset as in a split second or a few seconds,
although one in five report an onset within a few minutes but
never more than 5 [58]. More than half the patients lose consciousness at onset [59]. Some patients report headache
before they lose consciousness, but others lose consciousness
almost instantaneously, or the initial headache is unwitnessed.
If patients regain consciousness, they all report headache.
About 1015 % of patients never regain consciousness and
die before reaching the hospital or soon thereafter [26]. Some
patients remain in an acute confusional state after improvement of consciousness.
Vomiting soon after the onset is reported by two of every
three patients [58]. Seizures are rare at onset and reported
by no more than 1 in 14 patients [58]. One in three patients
report focal signs, which usually are short lasting [58]. These
focal signs can be the result of cerebral ischemia due to acute
vasoconstriction, a typical example being a patient reporting
weakness of a leg for a couple of minutes in case of an aneurysm of the anterior communicating artery. Focal deficits can
also result from extension of the hemorrhage into the brain
parenchyma, but in such instances, the focal deficits persist

16

Chapter 2. What Is An Aneurysm/SAH


No smoking
No hypertension
Hypertension

Men, 35-45y
Family No
history Yes

0.03
0.12
0.10
0.45
Yes
No
Hypercholesterolemia

Women, 35-45y
Family No
0.02
history Yes 0.07
Yes

0.09
0.33
No

Hypercholesterolemia
Men, 45-55y
Family No
history Yes

0.03
0.12
Yes

0.15
0.56
No

Hypercholesterolemia
Women, 45-55y
0.03
Family No
history Yes 0.13
Yes

0.15
0.57
No

Hypercholesterolemia
Men, 55-65y
Family No
history Yes

0.03
0.12
0.10
0.45
Yes
No
Hypercholesterolemia

Women, 55-65y
0.04
0.16
Family No
History Yes 0.13
0.60
Yes
No
Hypercholesterolemia

Current smoking
No hypertension
Hypertension

0.06
0.28
0.15
0.66
0.33
1.51
0.23
1.04
0.54
2.43
1.24
5.50
Yes
No
Yes
No
Yes
No
Hypercholesterolemia Hypercholesterolemia Hypercholesterolemia

0.04
0.16
Yes

0.20
0.75
No

Hypercholesterolemia

0.08
0.28
Yes

0.34
1.28
No

Hypercholesterolemia

0.08
0.29
Yes

0.35
1.30
No

0.10
0.39
Yes

0.47
1.75
No

Hypercholesterolemia

0.18
0.66
Yes

0.80
2.97
No

Hypercholesterolemia

0.18
0.68
Yes

0.83
3.05
No

0.24
0.89
Yes

1.08
3.98
No

Hypercholesterolemia

0.41
1.51
Yes

1.84
6.69
No

Hypercholesterolemia

0.42
1.56
Yes

1.89
6.87
No

Hypercholesterolemia

Hypercholesterolemia

Hypercholesterolemia

0.06
0.27
0.23
1.02
Yes
No
Hypercholesterolemia

0.14
0.65
0.53
2.39
Yes
No
Hypercholesterolemia

0.33
1.48
1.22
5.41
Yes
No
Hypercholesterolemia

0.08
0.37
0.30
1.37
Yes
No
Hypercholesterolemia

0.19
0.87
0.44
1.98
0.71
3.19
1.63
7.18
Yes
No
Yes
No
Hypercholesterolemia Hypercholesterolemia

Figure 2.5 Remaining life time risk (%) of subarachnoid hemorrhage according to age, sex, and presence or absence of current
smoking, hypertension, hypercholesterolemia and family history of
stroke other than subarachnoid hemorrhage

on admission. Persisting deficits are however not as common


as the short-lasting ones.
Neck stiffness takes a couple of hours to develop, and
absence of neck stiffness in the initial hours after the onset
of hemorrhage does therefore not rule out a subarachnoid
hemorrhage. In a hospital-based study where neck stiffness
was tested by neurology residents with different levels of
experience, the negative predictive value of neck stiffness

Subarachnoid Hemorrhage

17

was only 69 % within the initial 6 h after onset of the headache (D. Backes et al. 2015, unpublished data). The negative predictive value was however 90 % if neck stiffness
was tested between 6 and 72 h after onset of the headache.
Positive predictive values were 89 % for patients examined
within 6 h after onset and 77 % for patients examined
672 h after headache onset.

Perimesencephalic Hemorrhage: A Benign Subset


Perimesencephalic hemorrhage is a non-aneurysmal subset
of subarachnoid hemorrhage that occurs in around 10 % of
all patients with subarachnoid hemorrhage. Without brain
imaging, patients with perimesencephalic hemorrhage cannot
be discriminated from patients with a ruptured aneurysm,
although on group level the onset is more often in minutes
than in seconds than in subarachnoid hemorrhage from a
ruptured aneurysm. On imaging, perimesencephalic hemorrhage is characterized by a typical pattern of hemorrhage on
CT (Fig. 4.2) and absence of an aneurysm. The source of
perimesencephalic hemorrhage probably is a venous one
such as tear of an anomalous draining vein as these patients
often have a primitive venous drainage on the side of the
hemorrhage [60]. In a study using controls from the general
population, smoking was a risk factor for perimesencephalic
hemorrhage, but hypertension and excessive alcohol intake
were not. Apart from the rare patients that develop hydrocephalus in the initial 12 days after the hemorrhage [61],
patients with perimesencephalic hemorrhage usually have no
in-hospital complications, an invariable good outcome and a
normal life expectancy [62].
It is important to realize that the benign outcome and normal life expectancy hold true only for patients without an
aneurysm and a perimesencephalic pattern of hemorrhage on
CT. Patients with another pattern of hemorrhage on CT but
no aneurysm on initial angiography are a mixed bag and still
are at risk of complications [6365].

18

Chapter 2. What Is An Aneurysm/SAH

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1991;338(8773):9648.

Chapter 3
Aneurysms and Subarachnoid
Hemorrhage in General
Practice
With the increasing availability of imaging techniques and
facilities, the numbers of patients in whom an unruptured
aneurysm is detected has increased over the last decades [1].
Unruptured intracranial aneurysms may rupture, giving rise
to subarachnoid hemorrhage. Sometimes, preventive occlusion is indicated, but most aneurysms have a less than 1 %
risk of rupture in the initial 5 years after detection, and in
these instances, the risks of neurosurgical clipping or endovascular occlusion are much larger than the small risk of
rupture. Having to live with an untreated aneurysm however
imposes a threat on quality of life, and it is pivotal to reduce
anxiety and to refrain from restrictions.
Most instances of subarachnoid hemorrhage derive from
aneurysms that had gone unnoticed until rupture, and warning signs before rupture are lacking. For persons at high risk
of having an aneurysm and of developing subarachnoid
hemorrhage, screening for aneurysms can be considered.
With an incidence of around 9/100,000 patients per year
[2], subarachnoid hemorrhage is a rare event in general practice. In case of loss of consciousness or focal deficits, it will
usually be straightforward that the patient needs to be
referred to a hospital. Immediate supportive care and transport to an emergency department is indicated for all because
complete recovery can occur also in deeply comatose patients.
In half the patients, headache is the only symptom. Recognition

G.J.E. Rinkel, P. Greebe, Subarachnoid Hemorrhage


in Clinical Practice, In Clinical Practice,
DOI 10.1007/978-3-319-17840-0_3,
Springer International Publishing Switzerland 2015

25

26

Chapter 3.

Aneurysms and SAH in General Practice

of these patients is a real challenge but pivotal because early


referral and treatment are needed to prevent devastating
rebleeding.

Management of Unruptured Aneurysms


Most incidental intracranial aneurysms do not need treatment, but
all patients with incidental aneurysms do

General Approach
Unruptured intracranial aneurysms may give rise to subarachnoid hemorrhage in the near or distant future, and sometimes,
these lesions warrant preventive intervention. However, in
many instances, the pros and cons of preventive occlusion are
uncertain, and in many other situations, intervention is likely
to do more harm than good. In the history taking, it is pivotal
to pay attention to smoking, blood pressure, family history
and comorbidities that reduce life expectancy because these
are important determinants of risk of rupture and effectiveness of preventive treatment. In encountering persons with a
recently detected unruptured aneurysm, risks of rupture and
treatment should be discussed, and the balance of risks and
benefits of all treatment options should carefully be explained
(Fig. 3.1). In these considerations, it should be kept in mind
that the main goal of managing patients with unruptured
aneurysms is not to prevent subarachnoid hemorrhage but to
find the management option that brings the highest number of
quality-adjusted life years. The management option with the
worst outcome in the long term is often not the worst management option (Fig. 3.2). A slight or moderate reduction in quality of life from a treatment complication can be a worse
option than a severe reduction in quality of life from a subarachnoid hemorrhage that occurs 15 years after the decision
not to intervene because the initial years have more weight
and because a large number of years with a slight reduction in

Management of Unruptured Aneurysms

risk of rupture
anxiety
restrictions due to
aneurysm

27

risk of
complications
comorbitidy
patients time lost
for treatment
costs

Figure 3.1 Balance of risks of treatment of unruptured aneurysms.


A high risk of rupture, persisting anxiety and restrictions encountered by presence of an unruptured aneurysm (e.g. loss of professional driving license or denial of life insurance) favor treatment.
The risk of complications, comorbidity, the time patients have to
invest for treatment (hospitalization, recovery from treatment) and
costs of treatment are factors against treatment

quality of life give more overall reduction than a smaller


number of years with severe reduction in quality of life.
Preventive treatment is often considered as investment for
the future. However, there is a glaring lack of long-term follow-up data on risk of rupture of unruptured aneurysms. It is
too simplistic to multiply the risk of rupture during the initial
5 years after detection with the remaining life expectancy of
the particular patient. First, the growth and rupture rates are
not constant over time [3]. Second, the risk of rupture of
aneurysms seems to decline over time. In a meta-analysis
including individual patient data of 8,382 participants in six
prospective cohort studies, risk of rupture was higher in the
initial year after detection of the aneurysm than 5 years later
(Fig. 3.3) [4], and in a unique study from Finland with almost
lifelong follow-up of 142 patients diagnosed between 1956
and 1978 with an unruptured aneurysm, all 34 hemorrhages
occurred within the initial 25 years of follow-up and none

28

Chapter 3.

Aneurysms and SAH in General Practice

Health state

100%

50%

dead
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Follow up in years

Figure 3.2 Hypothetical graph showing the effects of treatment


(with complication solid line) versus no treatment (with aneurysm
rupture 13 years after detection dashed line). From 13 years
onward the health state is much better in the treatment strategy
than in the non-treatment strategy due to the rupture. However, the
number of life years in good health lost from treatment is considerable in the initial 13 years after detection, and it is therefore too
simplistic to state that at year 13 the lines cross and thus in long term
treatment is the best option. A better way of assessing the effects is
considering the areas above the lines showing the total loss of years
in good health for both treatment strategies

thereafter [5]. Thus, as in many other cases, we dont know


what the future will bring. In our institution, we therefore try
to stick to the data there are and use as rule of thumb that we
advise treatment if the risk of complications is lower than the
risk of rupture in the initial 5 years after detection of the
aneurysm.
The knowledge of having an unruptured aneurysm evokes
uncertainty. It is therefore of utmost importance to refrain
from descriptions as a time bomb in your head or to impose
restrictions such as refraining from lifting or other physical
exercise before referral of the unfortunate patient. Such
restrictions are unnecessary, do more harm than good, and
may even increase the risk of rupture instead of decreasing it
[6]. For many of these patients, no intervention is the best

Management of Unruptured Aneurysms

29

1,00

Cum Survival

0,98

0,96

0,94

0,92

0,90
,00

1,00

2,00

3,00

4,00

5,00

FU_5years

Figure 3.3 Risk of rupture of untreated aneurysms over time,


showing a decrease in risk of rupture over time

option, but having to live with an untreated aneurysm


imposes a threat on quality of life [7]. In most instances, the
best that can be done is reassurance by sharing with the
patient the very low risk of rupture and trying to avoid that
the patient imposes restrictions to his or her life.

Interventions to Occlude the Aneurysm


Reports from single centers describe complication rates
under 2 % for surgical treatment of aneurysms smaller than
10 mm [810], but methodology of outcome assessment in

30

Chapter 3.

Aneurysms and SAH in General Practice

single center studies is usually moderate or poor. Thus, the


2 % complication rate for surgical treatment may very well
be an underestimation. Moreover, these studies usually come
from specialized centers, and results from such centers may
not be applicable to other, less specialized centers. There are
no randomized studies comparing surgical and endovascular
treatment of unruptured aneurysms. Several nationwide
observational studies have shown that in general the risk of
complications is less after endovascular than after microsurgical treatment [1113] and that this difference increases with
increasing age [14]. Overall risk of death after surgical treatment was around 1.2 % and after coiling 0.6 %, and the risk
of discharge to a nursing home was 14 % after clipping and
5 % after coiling [11]. The risks of complications seem therefore lower after coiling than after clipping, but it should be
kept in mind that these comparisons are not randomized and
many uncontrolled factors can have influenced these comparisons. Another caution before concluding that coiling
should be preferred is the uncertainty regarding efficacy of
coiling. After coiling, around 20 % of aneurysms reopen [15],
leaving the patient at risk for rupture and necessitating
retreatment. In a statewide observational study in California
of patients treated for unruptured aneurysms, retreatment
occurred 2.5 times more often after endovascular than after
surgical treatment [16]. Moreover, after a mean period of 7
years of follow-up in this study, the initial survival advantage
of endovascular over surgical treatment had been lost [16].
All in all, preventive treatment of unruptured aneurysms is
not without risks. For aneurysms smaller than 10 mm (which
is the vast majority of incidentally discovered aneurysms), a
risk of complications of at least 23 % should be taken into
account if patients are treated in highly specialized centers.

General and Medical Management


In all patients (going to have aneurysm treatment or not), it
is pivotal to persuade them to quit smoking because smoking
is a risk factor for growth and rupture of aneurysms and also

Management of Unruptured Aneurysms

31

for development of new aneurysms [5, 1719]. Apart from the


advice to quit or not to restart smoking, to not (or no longer)
use cocaine [20, 21] and to have blood pressure properly
checked and treated, we do not impose any restriction on
persons with an unruptured aneurysm that is left untreated.
Many persons with an aneurysm ask whether they are
allowed to fly, but there is no reason that they should not fly
as a passenger. However, in many countries, a professional
flying license is lost in case an unruptured aneurysm is found.
There is also no reason to refrain from normal physical exercise or sexual activity (an advice we now and then hear being
given and for which we have some doubts regarding compliance). As described in section Trigger factors for rupture in
Chap. 2, despite the fact that shortly after sexual intercourse
the risk of subarachnoid hemorrhage is 10 times higher than
in periods without preceding sexual intercourse, the absolute
risk is still very low shortly after sexual intercourse, and
20,000 years of sexual activity need to be avoided to prevent
one episode of subarachnoid hemorrhage. We usually explain
this paradox between relative and absolute risks to patients
with the example of the Dutch National Lottery. The chance
of winning is very small if you have one lottery ticket. If you
buy ten tickets, you have a ten times greater chance, but still
the chance of winning is very small.
There is no evidence from randomized clinical trials for
any medical treatment to reduce the risk of rupture of intracranial aneurysms. Despite this lack of evidence, it seems
logical to treat hypertension in persons with unruptured
aneurysms, not with the purpose to reduce the risk of rupture
but to reduce the risk of cardiovascular disease in general.
There is increasing interest in and evidence for a key role
of inflammation in the process leading to aneurysms, but
there is no evidence that aspirin or other anti-inflammatory
drugs reduce the risk of rupture of aneurysms. Likewise,
there are also no data showing that aspirin or other antiplatelet agents are contra-indicated in patients with an unruptured
aneurysm. There is no evidence from cohort studies that such
drugs increase the risk of rupture, and although many fear a
worse outcome in patients with subarachnoid hemorrhage

32

Chapter 3.

Aneurysms and SAH in General Practice

who are on antiplatelet agents, there are no data supporting


that fear. In contrast, the little data we have even suggest a
slightly better outcome in patients who were on aspirin at
time of aneurysm rupture [22]. Similarly, although the outcome after subarachnoid hemorrhage is worse in patients on
anticoagulants [23], there is no good evidence that anticoagulants increase the risk of rupture, and even if they do, the risk
remains so small that the benefits of anticoagulants by far
outweigh the risks of poor outcome from subarachnoid
hemorrhage.

Follow-Up Imaging
The rationale behind follow-up imaging of aneurysms that
are left untreated is that small aneurysms tend to increase in
size and larger aneurysms have a higher risk of rupture.
Although there is no (and probably never will be) evidence
from randomized clinical trials that follow-up imaging of
untreated, unruptured aneurysms and treatment of those
that have enlarged is beneficial, several data however do
support such a strategy. First, unruptured aneurysms in
patients with subarachnoid hemorrhage from another aneurysm have a higher risk of rupture than aneurysms in
patients without (a history of) subarachnoid hemorrhage [4].
Second, size is the most important predictor of aneurysm
rupture [4], and we do know that some aneurysms enlarge
over time. An enlarged aneurysm has therefore a higher risk
of rupture than at the size before enlargement, and a larger
increase in size confers a larger risk of rupture [24]. The pace
of enlargement is however unknown. Aneurysm growth is
not constant over time but irregular and discontinuous [3].
This means that aneurysms have episodes of stability without growth and with low risk of rupture interspersed with
episodes of instability characterized by growth or rupture
(Fig. 3.4). The duration of episodes of instability is unknown
thus, if at follow-up imaging an aneurysm is larger than
before, this does not mean that the aneurysm is unstable:
it may very well be that the aneurysm has gone through an

Management of Unruptured Aneurysms

33

Figure 3.4 Progression of aneurysms over time a drawing we


often make when encountering patients with unruptured aneurysms.
Upper row: outdated notion that aneurysms grow at a constant rate
until rupture. Second row: Instead aneurysms develop in a short
period of time, than remain stable for a longer period of time and
then grow again during a second short episode of instability. Third
row: Likewise an aneurysm may develop in a short period of time,
than remain stable for a longer period of time and then rupture during a second short episode of instability. Lower row: Aneurysms may
also develop and rupture in a single short period of instability

episode of instability, has fortunately not ruptured but


enlarged but is now stable again, however at a size with
greater risk of rupture. The irregularity of aneurysm growth
makes recommendations on intervals of follow-up a bit cumbersome, but data of several follow-up studies provide some
help (Table 3.1). At 1 year follow-up of 93 patients with 125
small aneurysms that were left untreated, enlargement
occurred in 3 % with a largest growth of 1.5 mm in none of
the enlarged aneurysms was intervention considered necessary [25]. In another cohort with 2 year follow-up of 403
small (less than 7 mm at baseline) aneurysms, 37 (9 %) had
enlarged [19], and in a series of 53 aneurysms that were followed up for a mean of 9 years, 13 (25 %) had enlarged [26].
In a Finnish study on 87 patients with a mean follow-up of
18 years, 37 (45 %) had enlarged aneurysms [17]. Risk factors for growth are smoking, hypertension, female sex and
size, site and shape of the aneurysm (Table 3.1).

34

Chapter 3.

Aneurysms and SAH in General Practice

Table 3.1 Aneurysm growth over time and risk factors for growth
[17, 19, 25, 26]
Follow up (years)
Enlarged aneurysms (%)
95 % CI (%)
1

2.4

0.86.8

9.2

6.712

25

1538

19

45

3555

Risk factor

Risk ratio

Smoking

2.23.9

Female sex

3.3

Hypertension

2.3

95 % CI

1.110

1.14.9
0.81.5

Initial aneurysm size

1.1

Multilobed
aneurysm

2.9

1.08.5

Oblong aneurysm

2.4

1.05.8

Posterior circulation

2.0

0.67.0

CI confidence interval
a
Range over several studies
b
Per mm increase in size

Indications for and Methods of Screening


Risk Groups and Indications for Screening
The most obvious group where screening for aneurysms
should be considered is patients with a positive family history
of subarachnoid hemorrhage (defined as two or more firstdegree relatives with subarachnoid hemorrhage). Admittedly,
there are no data from randomized clinical trials on screening
and preventive treatment in such persons, but such a trial will
probably never be performed. Persons who have two or more
first-degree relatives with a subarachnoid hemorrhage usually
do not want to be randomized between screening yes or no.

Indications for and Methods of Screening

35

However, the data we have strongly support a screening


strategy in case of familial subarachnoid hemorrhage. In persons with two or more affected relatives, the lifetime risk of
subarachnoid hemorrhage is considerable, with point estimates as high as 25 % [27]. At initial screening, the chance of
finding an aneurysm is around 10 % [28]. If this first screening is negative, the chance of finding a new aneurysm at
repeated screening 5 years later is around 5 %, and this
chance remains the same after two or three negative screenings with 5 year intervals [28]. Modeling studies found that
the optimal screening strategy for persons with two or more
affected first-degree relatives is to screen from age 20 until 70
every 57 years given a cost-effectiveness threshold of
20,000 Eu/quality-adjusted life year [29].
In persons with only one affected relative with subarachnoid hemorrhage, risk of having an aneurysm and lifetime
risk of subarachnoid hemorrhage are not as high as in persons
with two or more affected first-degree relatives. Although for
long it has been considered ineffective to screen such persons,
a modeling study using recent data showed that screening
once between age 30 and 55 results in substantial health benefits at low costs or even reduced costs (E. Hopmans et al.,
2015, unpublished data).
Whether monozygotic twins should be screened if one
of the twins had a subarachnoid hemorrhage is uncertain
because identical twins with subarachnoid hemorrhage are
rare. Several data, however, favor screening or at least a
discussion about screening if one of the twins had a subarachnoid hemorrhage. First, in the Nordic twin study, the
chance that both twins had a subarachnoid hemorrhage was
10 times higher for monozygotic than for dizygotic twins [30].
Second, in the more than 30 monozygotic twins with both
twins affected with subarachnoid hemorrhage [3033], many
pairs had the aneurysm at the same site, and in many pairs
subarachnoid hemorrhage occurred at around the same age,
although in some twins subarachnoid hemorrhage happens
decades apart [34]. Moreover, monozygotic twins discordant
for presence of aneurysms do occur [35, 36] and are likely to
be under-reported.

36

Chapter 3.

Aneurysms and SAH in General Practice

For patients with polycystic kidney disease, there are less


data on effectiveness of screening, and opinions whether or
not to screen differ considerably. We feel however that the
risk of subarachnoid hemorrhage and the possibility of
screening should at least be discussed with patients with subarachnoid hemorrhage. Reasons for this advice are twofold.
First, in patients with polycystic kidney disease, subarachnoid
hemorrhage is an important cause of death (section Risk
factors in Chap. 2). Second, characteristics of intracranial
aneurysms and of patients with subarachnoid hemorrhage in
the context of polycystic kidney disease resemble more
closely those of familial than sporadic aneurysms and hemorrhages [37].
Patients with Ehlers-Danlos syndrome type IV are typically advised against screening not only because in these
patients the subarachnoid hemorrhage is often a result from
spontaneous rupture of an intracranial artery without preceding aneurysm [38] but also the vessel wall of these patients
can be very fragile, which increases the risk of preventive
aneurysm treatment considerably [39, 40]. In patients with
Marfan disease, there is no indication for screening because
an increased risk of subarachnoid hemorrhage has not been
confirmed in these patients [4143].
Screening for new aneurysms in patients who have survived an episode of subarachnoid hemorrhage is discussed in
section Screening for new aneurysms in Chap. 6.

Method of Screening
Before intracranial vessels are imaged, the risks and benefits
of screening should be discussed with the potential screenee.
This discussion should not only include the risks of having an
aneurysm, lifetime risks of subarachnoid hemorrhage and
risks of complications of treatment but also other pros
and cons of screening. Although the invitation for screening
and informing potential screenees on the risk in itself does
not lead to increased feelings of anxiety or depression [44],
the actual screening and outcome of screening can have

Indications for and Methods of Screening

37

considerable psychosocial consequences both positive and


negative and both for screen positives and screen negatives.
In the long term, half of the screen positives reduce their
work and two-thirds experience changes in independence,
self-esteem, future outlook or personal relationships [45]. In
contrast, screen-negative persons rarely reduce working, but
one-fifth experience changes in their self-esteem, future outlook or relationships. Despite these psychosocial effects, only
a few persons regret in retrospect to have participated in
screening [45].
During the pre-imaging encounter, it is important to
explicitly mention the potential results of screening and the
consequences of screening. If no aneurysm is found, the
advice for persons with a familial subarachnoid hemorrhage
defined as two or more affected relatives is to return for
screening at 5 year intervals [29], a strategy that the large
majority of these persons adhere to [46]. If no aneurysm is
found but only a small bulging, we advise to return already
1 year later to repeat the imaging. If an aneurysm is found,
this not only has implications for preventive treatment but
also implications for flying and driving licenses and life insurances depending on the local legislation. Besides, persons
should be informed about the risk of other incidental findings
such as arachnoid cysts, meningiomas or white matter lesions.
Finally, potential screenees should be aware that even screening, repeated screening and preventive treatment cannot
prevent all episodes of subarachnoid hemorrhage. We have
one person on record who had no aneurysm on screening but
had a subarachnoid hemorrhage 3 years later from a large
aneurysm that was even in retrospect not visible on the
screening images, and similar instances have been described
in literature [47].
Screening is usually done by means of MR angiography.
The sensitivity of MR angiography is very good (over 95 %)
[48, 49], and the small aneurysms that are missed are typically
not treated if detected. MR angiography is safe, has only few
contra-indications and has the advantage over CT angiography that contrast injection is not needed and there is no
radiation exposure. In patients who have previously received

38

Chapter 3.

Aneurysms and SAH in General Practice

neurosurgical clipping treatment, the clips cause extensive


artifact on magnetic resonance angiography [50], and in these
patients, CT angiography is the preferred assessment technique [51]. MR angiography is the best imaging modality in
patients who have been treated with coiling because coils
produce little artifact on this technique [15].

Recognition of Subarachnoid Hemorrhage


and Initial Prognosis
A timely referral and diagnosis of subarachnoid hemorrhage
is important because these patients are at risk of rebleeding.
Rebleeding has the highest peak in the initial 24 h after the
initial bleeding [52] and carries a poor prognosis [5355].
Thus, it is important to recognize the symptoms that suggest
a subarachnoid hemorrhage. Almost all patients with subarachnoid hemorrhage have a severe headache, the rare
exception being patients who lose consciousness before
being able to complain of headache and who die without
recovery of consciousness. The hallmark of the headache in
patients with subarachnoid hemorrhage is however not the
severity but the speed at which it develops. Typically, the
headache starts suddenly within one or a few seconds as a
blow on the head. A minority of patients report an onset in
a few minutes but no longer than 5 [56]. It is pivotal to take
a careful history in patients who complain about severe
headache because patients do not realize that the sudden
onset is a cardinal feature. They experience the worst headache ever and thus complain of a worst headache ever and
not of a sudden onset of the headache. Except for not asking
for the speed of onset, other pitfalls in diagnosing are
patients who often consult a general practitioner for headache such as patients with migraine and patients who do not
seek medical attention immediately but defer it for 1 or
more days [57]. In a patient who walks into the office complaining of a headache for the last couple of days, it is difficult to realize that it may be a patient who has to be sent to
a hospital on an emergency basis.

Recognition of Subarachnoid Hemorrhage

39

How long headache lasts in subarachnoid hemorrhage is


not exactly known. In most patients, it lasts for at least a
couple of days, but it may disappear already after 6 h [56].
With acute onset of headache being present in almost all
patients with subarachnoid hemorrhage, a pivotal question
for general practitioners is its predictive value. In other
words, how many patients have to be referred to a hospital to
detect one with a subarachnoid hemorrhage? This question
has been addressed in a study in practices of 250 general
practitioners in the Netherlands. During 5 years, these general practitioners recorded baseline characteristics and final
outcome of all patients who consulted them with acute headache. In total, 148 patients with acute headache were included
in the study, of which 103 had acute headache as the only
symptom. In 12 of these 103 patients, a subarachnoid hemorrhage from a ruptured aneurysm was diagnosed. Thus, the
number of patients to refer to detect one patient with subarachnoid hemorrhage is around nine. Moreover, in another
18 patients, other serious neurological conditions were found.
We feel it is therefore worthwhile to refer all patients with
acute headache to a hospital immediately for further examinations [58]. Absence of nuchal rigidity is no reason to not
refer because nuchal rigidity is absent in one-third of the
patients in the initial 6 h after the hemorrhage (D. Backes
et al., 2015, unpublished data).
Loss of consciousness occurs in around half the patients at
time of aneurysmal rupture or shortly thereafter [59]. In these
patients, it is usually straightforward that they should be transferred to a hospital. Rarely, patients with subarachnoid hemorrhage are in an acute confusional state without actively
complaining of headache [60]. In these patients, the diagnosis
of subarachnoid hemorrhage is often delayed because subarachnoid hemorrhage is a rare cause of acute confusional
state and other causes are considered first [61, 62].
In a systematic review of population-based incidence studies where all episodes of sudden death were carefully investigated, around 1015 % of patients with subarachnoid
hemorrhage had died before reaching the hospital [63]. These
instances of early death are probably explained by cardiac

40

Chapter 3.

Aneurysms and SAH in General Practice

arrest as result of the intracranial hemorrhage [64, 65]. This


does, however, not mean that patients in a poor condition
shortly after the hemorrhage invariably have a poor prognosis. Around 5 % of patients who are deeply comatose (no eye
opening, no motor response on pain and no vocal response
on pain) upon admission in the hospital have a good outcome
[66]. Besides the clinical condition shortly after the hemorrhage, also age is an important prognosticator. One-month
case fatality increases from 10 % in patients younger than 30
years of age to 60 % in those older than 80 years of age [67].
However, 15 % of patients older than 75 are independent for
activities of daily living at time of discharge [68], and in many
elderly patients, aneurysm occlusion is cost effective [69].
Thus, also elderly patients should be referred to hospital if a
subarachnoid hemorrhage is suspected.

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25. Wermer MJ, van der Schaaf IC, Velthuis BK, Majoie CB,
Albrecht KW, Rinkel GJE. Yield of short-term follow-up CT/
MR angiography for small aneurysms detected at screening.
Stroke. 2006;37(2):4148.
26. Wermer MJ, van der Schaaf IC, Velthuis BK, Algra A, Buskens
E, Rinkel GJE. Follow-up screening after subarachnoid haemorrhage: frequency and determinants of new aneurysms and
enlargement of existing aneurysms. Brain. 2005;128:24219.
27. Bor AS, Rinkel GJE, Adami J, Koffijberg H, Ekbom A, Buskens
E, et al. Risk of subarachnoid haemorrhage according to number of affected relatives: a population based case-control study.
Brain. 2008;131(10):26625.
28. Bor AS, Rinkel GJE, van Norden J, Wermer MJ. Long-term,
serial screening for intracranial aneurysms in individuals with
a family history of aneurysmal subarachnoid haemorrhage:
a cohort study. Lancet Neurol. 2014;13(4):38592.
29. Bor ASE, Koffijberg H, Wermer MJ, Rinkel GJE. Optimal
screening strategy for familial intracranial aneurysms: a costeffectiveness analysis. Neurology. 2010;74(21):16719.

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30. Korja M, Silventoinen K, McCarron P, Zdravkovic S, Skytthe


A, Haapanen A, et al. Genetic epidemiology of spontaneous subarachnoid hemorrhage: Nordic Twin Study. Stroke.
2010;41(11):245862.
31. Leung HK, Lam Y, Cheng KM, Chan CM, Cheung YL. Intracranial
aneurysms in twins: case report and review of the literature.
Hong Kong Med J. 2011;17(2):1514.
32. Mackey J, Brown RD, Sauerbeck L, Hornung R, Moomaw CJ,
Koller DL, et al. Affected twins in the familial intracranial aneurysm study. Cerebrovasc Dis. 2015;39(2):826.
33. Ohno S, Ikeda Y, Onitsuka T, Nakajima S, Uchino H, Haraoka
J, et al. Cerebral aneurysms in identical twins. No Shinkei Geka.
2004;32:8759.
34. Hager P, Steiger HJ. Identical cerebral aneurysms in siblings:
report of two families. J Clin Neurosci. 2004;11:804.
35. Astradsson A, Astrup J. An intracranial aneurysm in one
identical twin, but no aneurysm in the other. Br J Neurosurg.
2001;15:16871.
36. Puchner MJ, Lohmann F, Valdueza JM, Siepmann G, Freckmann
N. Monozygotic twins not identical with respect to the existence of intracranial aneurysms: a case report. Surg Neurol.
1994;41:2849.
37. Gieteling EW, Rinkel GJE. Characteristics of intracranial aneurysms and subarachnoid haemorrhage in patients with polycystic
kidney disease. J Neurol. 2003;250(4):41823.
38. Beridze N, Frishman WH. Vascular Ehlers-Danlos syndrome:
pathophysiology, diagnosis, and prevention and treatment of its
complications. Cardiol Rev. 2012;20(1):47.
39. Wesley JR, Mahour H, Woolley MM. Multiple surgical problems in two patients with Ehlers-Danlos syndrome. Surgery.
1980;87:31924.
40. North KN,Whiteman DAH,Pepin MG,Byers PH.Cerebrovascular
complications in Ehlers-Danlos syndrome type IV. Ann Neurol.
1995;38(6):9604.
41. Chan YC, Ting CW, Ho P, Poon JT, Cheung GC, Cheng SW.
Ten-year epidemiological review of in-hospital patients with
Marfan syndrome. Ann Vasc Surg. 2008;22(5):60812.
42. Conway JE, Hutchins GM, Tamargo RJ. Marfan syndrome is not
associated with intracranial aneurysms. Stroke. 1999;30:16326.
43. van den Berg JSP, Limburg M, Hennekam RCM. Is Marfan
syndrome associated with symptomatic intracranial aneurysms?
Stroke. 1996;27:102.

44

Chapter 3.

Aneurysms and SAH in General Practice

44. Bossuyt PM, Raaymakers TWM, Bonsel GJ, Rinkel GJE.


Screening families for intracranial aneurysms: anxiety, perceived
risk, and informed choice. Prev Med. 2005;41:7959.
45. Wermer MJ, van der Schaaf IC, Van Nunen P, Bossuyt PM,
Anderson CS, Rinkel GJE. Psychosocial impact of screening for
intracranial aneurysms in relatives with familial subarachnoid
hemorrhage. Stroke. 2005;36(4):83640.
46. Wermer MJ, Rinkel GJE, van Gijn J. Repeated screening for
intracranial aneurysms in familial subarachnoid hemorrhage.
Stroke. 2003;34:278891.
47. Schievink WI, Limburg M, Dreissen JJ, Peeters FL, ter Berg
HW. Screening for unruptured familial intracranial aneurysms:
subarachnoid hemorrhage 2 years after angiography negative
for aneurysms. Neurosurgery. 1991;29:4347.
48. Li MH, Cheng YS, Li YD, Fang C, Chen SW, Wang W, et al.
Large-cohort comparison between three-dimensional timeof-flight magnetic resonance and rotational digital subtraction angiographies in intracranial aneurysm detection. Stroke.
2009;40(9):31279.
49. Sailer AM, Wagemans BA, Nelemans PJ, de Graaff R, van Zwam
WH. Diagnosing intracranial aneurysms with MR angiography: systematic review and meta-analysis. Stroke. 2014;45(1):
11926.
50. Gonner F, Lovblad KO, Heid O, Remonda L, Guzman R, Barth A,
et al. Magnetic resonance angiography with ultrashort echo
times reduces the artefact of aneurysm clips. Neuroradiology.
2002;44:7558.
51. van der Schaaf IC, Velthuis BK, Wermer MJ, Majoie C,
Witkamp T, de Kort G, et al. New detected aneurysms on
follow-up screening in patients with previously clipped intracranial aneurysms. Comparison with DSA or CTA at the time of
SAH. Stroke. 2005;36(8):17538.
52. Germans MR, Coert BA, Vandertop WP, Verbaan D. Time
intervals from subarachnoid hemorrhage to rebleed. J Neurol.
2014;261(7):142531.
53. Naidech AM, Janjua N, Kreiter KT, Ostapkovich ND, Fitzsimmons
BF, Parra A, et al. Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage. Arch Neurol. 2005;62(3):
4106.
54. Ohkuma H, Tsurutani H, Suzuki S. Incidence and significance of
early aneurysmal rebleeding before neurosurgical or neurological management. Stroke. 2001;32(5):117680.

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55. Roos YBWEM, De Haan RJ, Beenen LF, Groen RJM,


Albrecht KW, Vermeulen M. Complications and outcome in
patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in the Netherlands. J Neurol
Neurosurg Psychiatry. 2000;68(3):33741.
56. Linn FHH, Rinkel GJE, Algra A, van Gijn J. Headache characteristics in subarachnoid haemorrhage and benign thunderclap
headache. J Neurol Neurosurg Psychiatry. 1998;65(5):7913.
57. Visser F, Rinkel GJE. Isolated headache in general practice:
determinants for delay in referral in patients with subarachnoid
haemorrhage. Eur J Gen Pract. 2012;18(3):14953.
58. Linn FHH, Wijdicks EFM, van der Graaf Y, Weerdesteyn-van
Vliet FAC, Bartelds AIM, van Gijn J. Prospective study of sentinel headache in aneurysmal subarachnoid haemorrhage. Lancet.
1994;344:5903.
59. Hop JW, Rinkel GJE, Algra A, van Gijn J. Initial loss of consciousness and risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Stroke. 1999;30(11):226871.
60. Reijneveld JC, Wermer MJ, Boonman Z, van Gijn J, Rinkel
GJE. Acute confusional state as presenting feature in aneurysmal subarachnoid hemorrhage: frequency and characteristics.
J Neurol. 2000;247(2):1126.
61. Calandre L, Esteban J, Bermejo F. Acute confusional syndrome
of unknown cause. Prospective study in the emergency room.
Neurologia. 1990;5(6):1969.
62. Benbadis SR, Sila CA, Cristea RL. Mental status changes and
stroke. J Gen Intern med. 1994;9:4857.
63. Huang J, Van Gelder JM. The probability of sudden death from
rupture of intracranial aneurysms: a meta-analysis. Neurosurg.
2002;51(5):11017.
64. Inamasu J, Miyatake S, Tomioka H, Suzuki M, Nakatsukasa M,
Maeda N, et al. Subarachnoid haemorrhage as a cause of outof-hospital cardiac arrest: a prospective computed tomography
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65. Mitsuma W, Ito M, Kodama M, Takano H, Tomita M, Saito N,
et al. Clinical and cardiac features of patients with subarachnoid
haemorrhage presenting with out-of-hospital cardiac arrest.
Resuscitation. 2011;82(10):12947.
66. van Heuven AW, Dorhout Mees SM, Algra A, Rinkel
GJE. Validation of a prognostic subarachnoid hemorrhage grading scale derived directly from the Glasgow Coma Scale. Stroke.
2008;39(4):13478.

46

Chapter 3.

Aneurysms and SAH in General Practice

67. Koffijberg H, Buskens E, Granath F, Adami J, Ekbom A, Rinkel


GJE, et al. Subarachnoid haemorrhage in Sweden 19872002:
regional incidence and case fatality rates. J Neurol Neurosurg
Psychiatry. 2008;79(3):2949.
68. Nieuwkamp DJ, Rinkel GJE, Silva R, Greebe P, Schokking
DA, Ferro JM. Subarachnoid haemorrhage in patients older
than 75 years: clinical course, treatment and outcome. J Neurol
Neurosurg Psychiatry. 2006;77(8):9337.
69. Koffijberg H, Rinkel GJE, Buskens E. Aneurysm occlusion
in elderly patients with aneurysmal subarachnoid hemorrhage: a cost-utility analysis. J Neurol Neurosurg Psychiatry.
2011;82:71827.

Chapter 4
In Hospital Course

The diagnosis of subarachnoid hemorrhage is typically


made with CT; if CT is negative, usually a lumber puncture
needs to be performed unless the CT is made within 6 h
after onset of the hemorrhage and read by a staff radiologist. Once the diagnosis of subarachnoid hemorrhage has
been made, the ruptured aneurysm is usually searched for
by means of CT angiography. The most feared complication
is rebleeding from the aneurysm, which has its highest peak
in the initial hours after the hemorrhage. Currently, no
therapy is available that can reduce this risk in the initial
hours. If the patient has survived the initial hours and is
admitted in a referral center, the aneurysm will usually be
occluded early after admission by either coiling or clipping
to prevent rebleeding during the clinical course; if both
treatment options are technically feasible, coiling is the preferred option. Other neurological complications that can
occur in the initial 12 weeks after the hemorrhage are
delayed cerebral ischemia, for which treatment with oral
nimodipine is the only effective preventive treatment, and
hydrocephalus.

G.J.E. Rinkel, P. Greebe, Subarachnoid Hemorrhage


in Clinical Practice, In Clinical Practice,
DOI 10.1007/978-3-319-17840-0_4,
Springer International Publishing Switzerland 2015

47

48

Chapter 4. In Hospital Course

Diagnostic Procedures and Initial


Management
The first-line procedure in hospital to diagnose or rule out a
subarachnoid hemorrhage is a CT scan. The sensitivity of CT
scanning is high in the initial days after the hemorrhage but
gradually diminishes over time. If CT is negative, a lumber
puncture is needed to definitively rule out a subarachnoid
hemorrhage. Until recently, this was also true for patients
who had the CT within the initial first hours after onset of
the headache. Three studies (one in Canada and two in the
Netherlands) have shown that the negative predictive value
of CT scanning is extremely high in patients who have been
investigated within the initial 6 h after the onset of headache
if the CT is read by a staff radiologist [1, 2]. Accordingly, the
yield of lumber puncture is extremely low; in 1 of the studies
from the Netherlands conducted in 11 non-academic centers,
the number of patients needed to puncture to detect one
subarachnoid hemorrhage from a ruptured aneurysm is
15,200 [3]. As a consequence, in many centers within a health
care system comparable to the Dutch or Canadian system,
lumbar puncture will be withheld in patients with a negative
CT scan performed within 6 h after the onset of headache.
In patients arriving later than 6 h after the onset of headache, lumbar puncture is still obligatory because sensitivity
drops fast after the initial hours [1]. Sensitivity of lumbar
puncture remains high in the initial 2 weeks after the subarachnoid hemorrhage but gradually drops to 50% at 4
weeks [4]. Thus, in patients who come in late, a subarachnoid
hemorrhage can be ruled out with certainty if lumbar puncture is performed within 14 days; thereafter, a negative lumbar puncture is no longer helpful. Lumbar puncture should
still be done in the third and fourth week after onset of
headache because a positive lumbar puncture proves that
the patient had a subarachnoid hemorrhage. We prefer not
to replace lumbar puncture by CT or MR angiography
because of the 3 % of the population that has an intracranial
aneurysm. If an aneurysm is found in a patient with acute

Diagnostic Procedures and Initial Management

49

headache and a negative CT but no examination of the cerebrospinal fluid, it will not be possible to tell whether or not
the aneurysm had ruptured.
If a subarachnoid hemorrhage is diagnosed, the next
step is to find its cause (Fig. 4.1). This is usually done by CT
angiography. CT angiography can usually be made immediately after the CT has demonstrated subarachnoid blood
and has a high sensitivity and specificity [5]. Moreover, CT
angiography can visualize the configuration of the aneurysm and surrounding vessels properly [6], which is helpful
in the decision whether the aneurysm can be clipped or
coiled. If CT angiography is negative, a catheter angiography is usually performed, which has additional value if CT
angiography is negative [7]. The only exception is patients
with a perimesencephalic pattern of hemorrhage on CT

Diffuse blood in basal cisterns

Extension of bleeding through


parenchyma into temporal horn

Extension of bleeding into lateral


Aneurysm
ventricles

Extension of bleeding into lateral part of Sylvian fissure

Figure 4.1 CT scan showing a typical subarachnoid hemorrhage


from a ruptured aneurysm. Left and middle: CT scans with diffuse
blood in the basal cisterns, with extension into the lateral Sylvian
fissure, and extension through the brain parenchyma into the ventricles. Right: CT-angiogram showing the aneurysm

50

Chapter 4. In Hospital Course

Center of bleeding in front of brainstem


Some extension of blood into anterior interhemispheric fissure

No blood in third ventricle


No blood in lateral ventricles
No blood in lateral part Sylvian fissure

Some extension of blood into basal part of Sylvian fissure


No blood in fourth ventricle

Figure 4.2 CT scans showing a typical perimesencephalic pattern of


hemorrhage with the center of the bleeding in front of the brainstem, and no extension into the lateral Sylvian fissure, the frontal
part of the anterior interhemispheric fissure, the ventricles or the
brain parenchyma

(Fig. 4.2). If in such instances CT angiography is negative,


no further investigations are needed, and the perimesencephalic hemorrhage diagnosis can be made [8].
Patients with subarachnoid hemorrhage are at risk of many
medical and neurological complications and should be treated
in a specialized center where a multidisciplinary team is available 24 h a day 7 days a week. These patients are typically
admitted in an intensive or high-care unit. If patients are in a
poor clinical condition, the team should evaluate the cause of
it and if possible treat it to provide a condition as optimal as
possible during aneurysm occlusion, which is usually done
early after admission. Initial management in all patients consists of analgesics, proper fluid management because patients
with subarachnoid hemorrhage are at risk of hypovolemia and
administration of oral nimodipine, a calcium antagonist that
reduces the risk of secondary ischemia [9].

Complications During the Hospital Course

51

Complications During the Hospital Course


Rebleeding
Around 15 % of patients rebleed in the first few hours after
the initial hemorrhage [10], that is, before or during transportation and before the treatment team is able to occlude the
aneurysm. Thus, treatment strategies that can be initiated
early after the hemorrhage to protect patients until the aneurysm is occluded are needed, but currently, no such treatment
is available. Although antifibrinolytic drugs do reduce the
risk of rebleeding, there is no evidence that these drugs
improve overall outcome [11]. If patients have survived the
initial 24 h after the hemorrhage, the risk of rebleeding in the
following weeks if the aneurysm is not occluded is around
30 % [12].

Delayed Cerebral Ischemia


Delayed cerebral ischemia after SAH is a complication that
occurs in around 20 % of patients [13] and usually starts 210
days after the hemorrhage, hence the term delayed. Clinically,
it is characterized by a gradual onset of focal signs, a
decreased level of consciousness or both. Initially, the symptoms can be waxing and waning. The gradual onset and the
often accompanying decrease in consciousness distinguish
this syndrome from the more common ischemic, thromboembolic stroke that typically has a sudden onset of symptoms
with a normal level of consciousness. Despite many years of
research, the cause has not been elucidated yet. Traditionally,
it has been linked to vasospasm because vasospasms are
present in the same time frame as delayed cerebral ischemia
is and because vasospasms are usually not focal but multifocal or generalized, which is in keeping with the multifocal or
diffuse nature of the clinical manifestations of delayed cerebral ischemia. Finally, it is appealing for intervention.
However, several factors argue against vasospasm as the

52

Chapter 4. In Hospital Course

main or only cause of delayed cerebral ischemia. First,


around a third of the patients with vasospasm do not develop
delayed cerebral ischemia, and one-third of the patients with
delayed cerebral ischemia do not have vasospasm [14].
Second, none of the treatments tested over the last decades
to prevent or treat vasospasm, decreased occurrence of
delayed cerebral ischemia or improved clinical outcome
despite improvement in vascular diameter with several of
these treatments [15, 16]. Thus, other factors such as microthrombosis must play a role as well in the development of
delayed cerebral ischemia, but more research is needed to
fully understand it [17].
The focus on strategies to reduce vasospasm has hampered the progress in prevention and treatment of delayed
cerebral ischemia. The only drug that is proven effective in
preventing delayed cerebral ischemia and improving outcome in patients with subarachnoid hemorrhage is oral
nimodipine, a calcium antagonist [9]. For the treatment of
delayed cerebral ischemia, many rely on inducing hypervolemia and hypertension, sometimes combined with hemodilution, the so-called triple H therapy. However, there is no
evidence better than small uncontrolled observational studies. Even on the level of improving cerebral perfusion, the
evidence is almost absence, the exception being maybe for
induced hypertension [18]. Induced hypertension is not
benign and carries risks of cerebral edema, hemorrhagic
transformation in areas of infarction, reversible leucencephalopathy, myocardial infarction and congestive heart failure
[19, 20]. For these reasons, we do not routinely induce hypertension in patients deteriorating from secondary ischemia.

Acute Hydrocephalus
Enlarged ventricles are present in around 20 % of the admission CT scans in patients with subarachnoid hemorrhage. The
typical presentation of acute hydrocephalus is that of an alert
patient who becomes increasingly drowsy or even comatose
a few hours after the subarachnoid hemorrhage. Treatment

References

53

options are lumbar puncture or drainage or, in case of


obstruction of flow of cerebrospinal fluid within the ventricular system, external ventricular drainage.

Treatment of the Aneurysm: Clipping


or Coiling
The mainstay of preventing rebleeding has for long been
neurosurgical clipping. There are no randomized clinical trials that have compared surgical clipping of aneurysms versus
no surgical clipping, but modeling studies suggest that around
ten patients have to undergo surgical clipping of the aneurysm to gain one patient with a good outcome [21]. Shortly
after the introduction of endovascular coiling, trials have
started comparing the two therapies. If the aneurysm is amenable for both coiling and clipping, coiling is the preferred
option. A systematic review of the trials performed showed
that one additional patient has a good outcome if seven are
coiled instead of clipped [22]. The largest trial has found that
also at 10 year follow-up, the probability of disability-free
survival was significantly greater in the coiling group than in
the neurosurgical group [23].

References
1. Perry JJ, Stiell IG, Sivilotti ML, Bullard MJ, Emond M, Symington
C, et al. Sensitivity of computed tomography performed within
six hours of onset of headache for diagnosis of subarachnoid
haemorrhage: prospective cohort study. BMJ. 2011;343:d4277.
2. Backes D, Rinkel GJE, Kemperman H, Linn FH, Vergouwen
MD. Time-dependent test characteristics of head computed
tomography in patients suspected of nontraumatic subarachnoid
hemorrhage. Stroke. 2012;43(8):21159.
3. Blok KM, Rinkel GJ, Majoie CB, Hendrikse J, Braaksma M,
Tijssen CC, et al. CT within 6 hours of headache onset to rule out
subarachnoid hemorrhage in nonacademic hospitals. Neurology.
2015 (Published online).

54

Chapter 4. In Hospital Course

4. Vermeulen M, Hasan D, Blijenberg BG, Hijdra A, van Gijn


J. Xanthochromia after subarachnoid haemorrhage needs no revisitation. J Neurol Neurosurg Psychiatry. 1989;52:8268.
5. Westerlaan HE, van Dijk MJ, van Dijk MJ, Jansen-van der Weide
MC, de Groot JC, Mooij JJ, et al. Intracranial Aneurysms in
Patients with Subarachnoid Hemorrhage: CT Angiography as a
primary examination tool for diagnosis systematic review and
meta-analysis. Radiology. 2011;258(1):13445.
6. Yoon DY, Choi CS, Kim KH, Cho BM. Multidetector-row
CT angiography of cerebral vasospasm after aneurysmal subarachnoid hemorrhage: comparison of volume-rendered images
and digital subtraction angiography. AJNR Am J Neuroradiol.
2006;27(2):3707.
7. Agid R, Andersson T, Almqvist H, Willinsky RA, Lee SK, ter
Brugge KG, et al. Negative CT angiography findings in patients
with spontaneous subarachnoid hemorrhage: when is digital
subtraction angiography still needed? AJNR Am J Neuroradiol.
2010;31(4):696705.
8. Ruigrok YM, Rinkel GJE, Buskens E, Velthuis BK, van Gijn
J. Perimesencephalic hemorrhage and CT angiography: a decision analysis. Stroke. 2000;31(12):297683.
9. Dorhout Mees SM, Rinkel GJE, Feigin V, Algra A, van den
Bergh WM, Vermeulen M, et al. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst
Rev. 2007;(3):CD000277.
10. Germans MR, Coert BA, Vandertop WP, Verbaan D. Time
intervals from subarachnoid hemorrhage to rebleed. J Neurol.
2014;261(7):142531.
11. Baharoglu MI, Germans MR, Rinkel GJE, Algra A, Vermeulen
M, van Gijn J, et al. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev.
2013;(8):CD001245.
12. Brilstra EH, Rinkel GJE, Algra A, van Gijn J. Rebleeding,
secondary ischemia, and timing of operation in patients with
subarachnoid hemorrhage. Neurology. 2000;55(11):165660.
13. Hop JW, Rinkel GJE, Algra A, van Gijn J. Initial loss of consciousness and risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Stroke. 1999;30(11):226871.
14. Rabinstein AA, Friedman JA, Weigand SD, McClelland
RL, Fulgham JR, Manno EM, et al. Predictors of cerebral
infarction in aneurysmal subarachnoid hemorrhage. Stroke.
2004;35(8):18626.

References

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15. Vergouwen MD, Algra A, Rinkel GJE. Endothelin receptor


antagonists for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update. Stroke. 2012;43(10):
30036.
16. Zwienenberg-Lee M, Hartman J, Rudisill N, Madden LK,
Smith K, Eskridge J, et al. Effect of prophylactic transluminal
balloon angioplasty on cerebral vasospasm and outcome in
patients with Fisher grade III subarachnoid hemorrhage. Results
of a phase II multicenter, randomized, clinical trial. Stroke.
2008;39(6):175965.
17. Vergouwen MD, Vermeulen M, Coert BA, Stroes ES, Roos
YB. Microthrombosis after aneurysmal subarachnoid hemorrhage: an additional explanation for delayed cerebral ischemia.
J Cereb Blood Flow Metab. 2008;28(11):176170.
18. Dankbaar JW, Slooter AJ, Rinkel GJE, van der Schaaf I. Effect
of different components of triple-H therapy on cerebral perfusion in patients with aneurysmal subarachnoid haemorrhage: a
systematic review. Crit Care. 2010;14(1):R23.
19. Amin-Hanjani S, Schwartz RB, Sathi S, Stieg PE. Hypertensive
encephalopathy as a complication of hyperdynamic therapy for
vasospasm: report of two cases. Neurosurgery. 1999;44(5):11136.
20. Wartenberg KE, Parra A. CT and CT-perfusion findings of
reversible leukoencephalopathy during triple-H therapy for
symptomatic subarachnoid hemorrhage-related vasospasm.
J Neuroimaging. 2006;16(2):1705.
21. Brilstra EH, Algra A, Rinkel GJE, Tulleken CAF, van Gijn
J. Effectiveness of neurosurgical clip application in patients
with aneurysmal subarachnoid hemorrhage. J Neurosurg.
2002;97(5):103641.
22. Brilstra EH, Rinkel GJE, van der Graaf Y, van Rooij WJJ, Algra
A. Treatment of intracranial aneurysms by embolization with
coils: a systematic review. Stroke. 1999;30(2):4706.
23. Molyneux AJ, Birks J, Clarke A, Sneade M, Kerr RS. The
durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the
UK cohort of the International Subarachnoid Aneurysm Trial
(ISAT). Lancet. 2014;28.

Chapter 5
Initial Post-hospital Course
and After-Care

A third of patients with a subarachnoid hemorrhage from a


ruptured aneurysm die within the first few weeks after the
event. Typically, patients remain hospitalized during the initial 1 or 2 weeks, even those who are in good clinical condition and have undergone aneurysm occlusion during the first
days after the hemorrhage. The reason for this prolonged stay
is the risk of complications that need urgent treatment such
as delayed cerebral ischemia and hydrocephalus. Most
patients are discharged home after hospitalization, but many
of them have cognitive, emotional and social problems, which
often interfere with reassuming premorbid social and occupational roles and reduce quality of life. The most common
complaints in patients discharged home are fatigue, anxiety
and depression. A third of the patients who survive the initial
weeks after the hemorrhage are still dependent on help at
discharge and transferred to a rehabilitation facility or nursing home. It is important that patients and their family
receive proper information and aftercare after discharge by a
multidisciplinary team where a specialized nurse or physician
assistant can play a central role.
Because of the good prognosis after a perimesencephalic
hemorrhage, these patients can be discharged home.
Nevertheless, some complain of non-specific symptoms such
as headaches, dizziness, fatigue and forgetfulness.

G.J.E. Rinkel, P. Greebe, Subarachnoid Hemorrhage


in Clinical Practice, In Clinical Practice,
DOI 10.1007/978-3-319-17840-0_5,
Springer International Publishing Switzerland 2015

57

58

Chapter 5. Initial Post-hospital Course and After-Care

Discharge Destinations
Home
Most patients who survive a subarachnoid hemorrhage can be
discharged home (Table 5.1). However, in the initial weeks
after discharge, they often feel weak or tired; many also experience feelings of depressed mood, irritability, emotionality or
passivity, and some fear recurrence of the illness and are, for
example, unhappy going out alone. These symptoms may
relate to the ongoing recovery from the hemorrhage, surgery
or anesthesia, the lack of being observed and taken care of in
the hospital or reduced self-esteem because of being struck by
a stroke. These symptoms and feelings generally improve with
time, and confidence will slowly be regained as recovery continues. Fatigue is present in almost all patients and can last for
a very long time. A daily schedule with alternating rest, daily
activities and exercises will be helpful to recover. In patients
who have no physical limitations, it is important to refrain
from unnecessary restrictions such as avoiding strenuous
activities, sauna or flying. In general, for patients with good
recovery, the only restrictions are those imposed by law on
driving in some countries and some extra care for head injury
in the early weeks after craniotomy.

Rehabilitation Facility
Many patients who are dependent for help on activities of
daily life are transferred to a rehabilitation facility wherefrom they often can be discharged home. Typically, patients in

Table 5.1 Discharge


destinations in a consecutive
series of 200 patients from
the University Medical
Center Utrecht

Destination
Home

%
68

Rehabilitation facility

19

Nursing home

13

Discharge Destinations

59

whom the subarachnoid hemorrhage is complicated by an


extension of the hemorrhage into the brain parenchyma
(intracerebral hemorrhage) or by delayed cerebral ischemia
leading to brain infarction fall into this category. Deficits
from intracerebral extension or delayed cerebral ischemia
will be similar to those in patients with cerebral hemorrhage
or infarction from other causes. Also, patients with severe
cognitive deficits are often discharged to a rehabilitation
clinic for intensive cognitive rehabilitation. During the rehabilitation program, it is important to address not only the
physical and cognitive limitations but also the emotional and
social problems and coping style because these factors play a
role in quality of life and participation [1, 2].

Nursing Home
In population-based studies, the proportion of patients who
are dependent on help in activities of daily living in the first
year after the subarachnoid hemorrhage varies between 10
and 20 % [3, 4]. From the series of the University Medical
Center Utrecht, around 1015 % of all patients with aneurysmal subarachnoid hemorrhage are discharged to a nursing
home, and this proportion of patients has remained stable
throughout the last 20 years (Table 5.1) [5]. In contrast to
most patients admitted to nursing homes, the prognosis of
patients with a subarachnoid hemorrhage discharged to a
nursing home is not gloomy. Almost half the patients admitted to a nursing home after a subarachnoid hemorrhage survive longer than 5 years, which is probably explained by the
fact that patients with a subarachnoid hemorrhage are
younger than the usual patients in nursing homes. Moreover,
subarachnoid hemorrhage patients tend to improve in
functional outcome and quality of life over time (Table 5.2).
In a retrospective cohort study of 92 patients with subarachnoid hemorrhage discharged from the University Medical
Center Utrecht to a nursing home, 45 had died after a median
of 1.1 years (range, 0.08.5 years), 35 were discharged to
home or a sheltered housing or rehabilitation facility after a

60

Chapter 5. Initial Post-hospital Course and After-Care

Table 5.2 Long term follow up of a consecutive series of 92 patients


with aneurysmal subarachnoid hemorrhage discharged to a nursing
home
Time
Destination
0 m 3 m 6 m 1 y 2 y 5 y 10 y
Still in nursing home
92 67 59 47 29 17 12
Discharged and alive

10

17

24

28

12

Death in nursing home

15

16

21

33

42

45

Death after discharge

10

Follow-up ended

15

21

m month, y year

median of 0.6 years (range, 0.19.6 years), and 12 remained in


a nursing home after a median of 4.8 years (range,
2.212.0 years) [5]; 44 (43 %) had survived longer than
5 years, and 29 (31 %) had regained functional independence
within the initial 2 years after admission to the nursing home.
We found a tendency for a better prognosis for patients discharged to a nursing home over time. This might be explained
by the implementation of reactivation facilities in nursing
homes in the more recent years in the Netherlands [6]. These
reactivation facilities within nursing homes result in better
survival and higher discharge rates [7].
Thus, also for patients admitted to a nursing home after a
subarachnoid hemorrhage, rehabilitation is pivotal, albeit at a
slower pace than in a rehabilitation clinic. This is the very
reason that we aim to see at our outpatient clinic also those
patients that were discharged to a nursing home.

Aftercare
Because subarachnoid hemorrhage is a rare disease, the
knowledge on the disease-specific complaints and deficits is
limited in regional hospitals and other care facilities. Given
the numerous physical and cognitive problems that patients

Aftercare

61

may encounter after subarachnoid hemorrhage, we recommend an organized multidisciplinary outpatient clinic where
all patients and their partners are seen by a multidisciplinary
team experienced in identifying and treating or counseling
the emotional, physical and cognitive problems related to
subarachnoid hemorrhage. Such a clinic should at least
involve a specialized nurse, a neuropsychologist and a rehabilitation physician; a stroke neurologist should be at hand
for specific neurological problems, and participation of the
neurosurgeon or endovascular specialist who treated the
aneurysm in hospital is also important for continuity of care
and for further treatment decisions. In such multidisciplinary
clinics, a rehabilitation plan tailored to individual patients
need can be developed, and patients can be advised about the
importance of smoking cessation and better control of blood
pressure because of the future risk of cardiovascular events
(see Chap. 6).

Schedule
In our center, we have a standard aftercare program that
applies not only to patients who are discharged home but also
for those who are discharged to a rehabilitation facility or
nursing home. This program also applies to patients with a
perimesencephalic hemorrhage or other types of subarachnoid hemorrhage without a proven aneurysm because these
patients often have similar questions as those who have been
treated for a ruptured aneurysm and feelings of anxiety and
cognitive complaints occur also in these patients, albeit to a
lesser extent.
Based on our experiences and those from others, we suggest the following schedule for aftercare (Fig. 5.1).
Outcome assessment at 3 months is preferably done by
means of a handicap scale such as the modified Rankin scale
(Table 5.3). Initially installed for research purpose, all our
patients receive once per year a standardized follow-up questionnaire asking for health status, new cardiovascular events

62

Chapter 5. Initial Post-hospital Course and After-Care


Clinical course

Post hospital course

Long term follow up

specialized nurse visits


patient and spouse
14 days after discharge
telephone call for initial
questions

18 months after SAH


encounter during follow up
MRA after coiling

6-8 weeks after


discharge visit to
SAH outpatient clinic

Once per year follow up


with short questionnaire

3 months after SAH telephone call


for assessment of clinical condition
6 months after SAH encounter during
follow up MRA after coiling

Figure 5.1 Follow up scheme for patients with subarachnoid hemorrhage. SAH subarachnoid hemorrhage, MRA magnetic resonance
angiography
Table 5.3 Modified Rankin scale (mRS)
Grade
Disability
Description
5
Severe
Someone needs
to be available
at all times;
care may be
provided by
either a trained
or an untrained
caregiver

Question to ask
Does the person
require constant care?

Moderate
severe

Need for
assistance with
some basic
ADL, but
not requiring
constant care

Is assistance essential
for eating, using the
toilet, daily hygiene,
or walking?

Moderate

Need for
assistance
with some
instrumental
ADL but not
basic ADL

Is assistance essential
for preparing a simple
meal, doing household
chores, looking after
money, shopping, or
traveling locally?

Aftercare

63

Table 5.3 (continued)


Grade

Disability

Description

Slight

No
significant

Limitations in
participation
in usual social
roles, but
independent for
ADL

None

No limitations
and no
symptoms

Question to ask
Has there been a
change in the persons
ability to work or look
after others if these
were roles before
stroke? Has there
been a change in the
persons ability to
participate in previous
social and leisure
activities? Has the
person had problems
with relationships or
become isolated?

ADL activities daily living

Does the person have


difficulty reading
or writing, difficulty
speaking or finding
the right word,
problems with balance
or coordination, visual
problems, numbness
(face, arms, legs,
hands, feet), loss of
movement (face,
arms, legs, hands,
feet), difficulty with
swallowing, or other
symptom resulting
from the hemorrhage?

64

Chapter 5. Initial Post-hospital Course and After-Care

and readmissions. However, together with this questionnaire,


patients are invited to ask any questions they have, and in our
experience many patients use this possibility and are satisfied
with its existence. For many of the questions they have, they
do not seek a new appointment or telephone consultation,
but this low-threshold opportunity gives them the opportunity to ask these questions. Usually, these questions can be
answered in a telephone consultation with the specialized
nurse; rarely, a new visit to the outpatient clinic is needed.
Given the many questions asked by these patients, we recommend that former patients can at least reach a specialized
nurse in an accessible way for questions they consider to be
potentially related to the subarachnoid hemorrhage.

Outpatient Clinic
In our hospital, the outpatient team consists of a specialized
nurse, a neuropsychologist, a rehabilitation physician and a
neurosurgeon for those patients in whom the aneurysm has
been occluded by clipping. An interventional neuroradiologist and neurologist can be consulted if necessary (Fig. 5.2).

Multidisciplinary SAH-outpatient clinic:

1. questionnaires
2. specialized nurse
3. neuropsychologist
4. rehabilitation physician
5. neurosurgeon

Figure 5.2 Composition of the multidisciplinary outpatient clinic

Aftercare

65

We send questionnaires to patients 2 weeks before the


visit at the outpatient department. The questionnaires
include standardized self-reported measures of coping,
depression and anxiety to assess complaints and deficits
(Table 5.4). The patients are asked to bring these questionnaires with them or fill these out in the web patient portal
of the hospital.

Table 5.4 Questionnaires and tests used at the outpatient clinic of


the University Medical Center Utrecht
Domain
Test
Postal questionnaires sent 2 weeks before interview
Coping

The Utrecht Coping list

Depression

Beck Depression Inventory-II

Anxiety

State-Trait- Anxiety Inventory (STAI-DY-1)

Questionnaires at interview
Cognitive and
emotional
complaints

Checklist for Cognitive and Emotional


consequences following stroke (CLCE-24)

Neuropsychological tests
Attention

Forward Digit Span of the WAIS III and the


Stroop Color Word test

Memory

Backward Digit Span of the Wechsler


Adult Intelligence Scale III (WAIS III) and
Category Fluency (semantic memory) using
animal naming

Verbal learning

Rey Auditory Verbal Learning Task

Non-Verbal recall

Delayed Rey-Osterrieth Complex Figure test


(CFT)

Executive
functioning

Brixton spatial Anticipation Test for strategic


thinking and phonological fluency (N and
A) for concept generation

Visuospatial
functioning

Copy score of the Rey-CFT

66

Chapter 5. Initial Post-hospital Course and After-Care

During the appointment, the specialized nurse interviews


the patient about complaints causing restrictions in day-to-day
life and assesses the presence of cognitive and emotional complaints. The specialized nurse will also provide information
about risk factors such as hypertension, smoking and familial
aneurysmal subarachnoid hemorrhage. If the patient has continued smoking after discharge, we advise to stop and provide
help and plan follow-up telephone calls for repeated reinforcement. Patients are also informed about long-term prognosis
(see Chap. 6) and about restrictions on driving license. It is
important to be aware of the risk of anxiety and depression
and, if these are suspected, to apply screen tests. If confirmed,
appropriate treatment is indicated, which we often do together
with the general practitioner.
The neuropsychologist examines the patient with a brief
neuropsychological screening on cognition and coping
(Table 5.4). The rehabilitation physician assesses physical
restrictions and uses all the other collected information from
the questionnaires, the specialized nurse and neuropsychologist to develop a rehabilitation program tailored to the individual patients needs. In our set-up, the rehabilitation
physician is also the contact person for other physicians in
rehabilitation centers and nursing homes. The neurosurgeon
will see the patient for specific neurosurgical issues and
questions.

Follow-up Imaging of Aneurysms


After endovascular treatment of a ruptured aneurysm, there
is a risk of 20 % for reopening in the initial months after
treatment, and in half of these instances, it is necessary to
treat the aneurysm again [8, 9]. In most centers, two or three
control MRAs are made in the initial 1 or 2 years after the
hemorrhage. The risk of reopening in the long term is small
[10], as is the risk of late rebleeding [11]. Hence, late followup imaging is often not performed.

Symptoms and Deficits

67

Symptoms and Deficits (Fig. 5.3)


We describe here the symptoms and deficits that are present
in the initial weeks to months after the hemorrhage. Although
many patients continue to recover over a long period of time
(see section Recovery in general in Chap. 6), in others
these symptoms and deficits described here will persist. The
time it takes to recover varies considerably and will be influenced by many factors. Recovery will take a minimum of
68 weeks, but on average individuals will need at least
36 months before they feel capable of returning to their
previous level of activity. We usually advise to plan one or

Anxiety
Concentration
Depression
Emotional
Fatigue
Headaches
Hearing loss
Irritable
Memory
Pain
Passivity
Sleep disorder
Smell
Speech
Taste
Vision problems

Figure 5.3 Alphabetical list of most common complaints after subarachnoid hemorrhage

68

Chapter 5. Initial Post-hospital Course and After-Care

more rest periods each day. To build up the condition, physical exercise or fitness may help.
Most patients have one or more emotional and cognitive
complaints at the initial assessment in the outpatient clinic. In
a consecutive series of 111 persons who visited our subarachnoid hemorrhage outpatient clinic, 105 (94.6 %) reported at
least one cognitive or emotional complaint that hampered
everyday functioning according to the Checklist for Cognitive
and Emotional Consequences following stroke (CLCE-24)
[12]. The most reported cognitive complaints were mental
slowness, short-term memory problems and attention problems, whereas the most reported emotional complaints were
fatigue, feelings of anxiety and being emotionally less stable
(Table 5.5). On neuropsychological exam, 52 patients (47 %)
showed mild and 28 (25 %) severe cognitive impairments on
one or more neuropsychological tests. Moreover, 44 patients
(40 %) had depressive symptoms, typically in the minor to
moderate depression range (score 1018), and feelings of
anxiety were present in 58 patients (52 %).

Table 5.5 Emotional


and cognitive
complaints, as assessed
with the CLCE-24, in a
consecutive series of
111 patients attending
the SAH outpatient
clinic from the
University Medical
Center Utrecht [12]

Emotional complaints

Fatigue

90.1

Anxiety

42.3

Emotional, crying faster

36.9

Irritable

32.4

Depression

30.6

Cognitive complaints
Become slower

60.4

Remembering new
information

48.6

Attending to things

44.1

Multitasking

36.9

Symptoms and Deficits

69

The fatigue, cognitive and emotional complaints and posttraumatic stress disorder often interfere with the relation
with the spouse and other family members, work and social
interactions (see Case 5.1). Based on these and similar data
from other studies, we advise systematic screening for cognitive and emotional complaints 12 months after the hemorrhage. If this screen test is positive for such complaints of
disturbances, a formal neuropsychological exam should be
performed to guide the rehabilitation program.

Fatigue
After the hemorrhage, more than 90 % of the patients complain of fatigue. It is unknown whether this is caused by the
hemorrhage, the occurrence of a life-threatening event or
both. Physical and cognitive impairments, emotional complaints, passive coping style, sleep disturbances and posttraumatic stress symptoms are common contributors to
fatigue [13] and reduce health-related quality of life. Sleep
problems are probably also an important contributor. In a
consecutive series of patients assessed 13 years after the subarachnoid hemorrhage, one-third reported severe problems
with sleep [14]. Frequently reported problems were initiating
or maintaining sleep and excessive sleepiness during the day.
A post-traumatic stress disorder can also contribute to fatigue.
Pituitary disturbances have also been implicated, and some
studies found high proportions of patients with such dysfunction, but others, using rigorous criteria for dysfunction, found
only small proportions of patients with pituitary dysfunction
[15]. Apart from focus on such specific causes, we usually also
advise improving condition by fitness or sports and making a
schedule to limit tasks per time period.

Pain
In our experience, around four out of five patients report
pain. Usually, it concerns headache or neck pain, but some

70

Chapter 5. Initial Post-hospital Course and After-Care

patients also complain of limb pain. The pain can have a


severe impact on quality of life. Headaches often are a
tension-type headache. In extreme rare cases (in our experience less than 1 %), patients complain of severe pain (stabbing or burning) in one or both sides of the body without an
obvious cause such as a thalamic infarct, but we feel it is
important that readers know that it can occur and that these
patients are not malingering. Although some patients experience pain or numbness around the scar in the initial weeks
after surgical treatment, a true neuralgia is very rare in our
experience. The altered sensation is probably due to lesions
of small intracutaneous sensory nerve fibers during the
surgery.

Mood Disorders: Anxiety, Depression and Stress


Almost half the patients with a subarachnoid hemorrhage
have increased feelings of anxiety and a third increased feelings of depression (Table 5.5) [12]. The reasons patients
report for increased anxiety and depression vary. Some fear
recurrence of the hemorrhage or to remain disabled forever;
others are afraid to be alone. Some patients feel insecure
while walking and fear falling or bumping the head. Physical
and cognitive impairments may affect mood disorders. Posttraumatic stress disorder is common in the early years after
the subarachnoid hemorrhage. From a prospectively collected cohort of 143 patients with a subarachnoid hemorrhage, one out of four patients had post-traumatic stress
disorder even 3 years after the event. Passive coping style was
the most important predictor [16].
Many people are nervous about having sex, especially if
the hemorrhage occurred whilst having sex. However, there
is no rationale to refrain from sexual activity or other physical
disability. Libido can be reduced but also increased after the
hemorrhage, and both changes can have a negative impact on
the relation with partners. If so, psychological help may be
offered. Some patients experience less control of behavior

Symptoms and Deficits

71

such as swearing, gambling, shoplifting and food or sexual


addiction.
For women who have had a subarachnoid hemorrhage, it
is still safe to become pregnant and have a normal childbirth.
Furthermore, there is no increased risk for new hemorrhages
from activities such as flying, going to the sauna, scuba diving
or playing sports intensively.

Senses
Invisible, but not less important than pain or fatigue, are sensory deficits: smell, taste, vision and hearing, and all have a
considerable impact on quality of life.

Smell and Taste


For patients, it is usually difficult to recognize smell versus
taste dysfunction, and frequently they confuse the concepts
of flavor and taste. Loss of smell (anosmia) is often
neglected by physicians [17], although many patients have
reduced or no smell after the hemorrhage and the influence
of anosmia on life is considerable. Anosmia leads to a
reduced quality of life, reduced appetite with weight loss as
result and reduced libido [18, 19]. Commonly reported problems are interpersonal relations because of impaired disability to smell body odor and impaired sexual life. Also reported
are safety issues as spoiled food or toxic materials and cooking [20]. Loss of taste has an impact on nutritional input with
the result of losing weight.
Overall, around one out of three to four patients experience
a loss of smell (anosmia) after subarachnoid hemorrhage,
which is associated with loss of appetite and therefore reduced
weight, quality of life and psychosocial well-being [21]. Anosmia
occurs more often after surgical, among others due to dissection of the olfactory tract, than after endovascular treatment,
and recovery over time is rare after surgical but frequent after
endovascular treatment [22]. The risk of anosmia is highest in

72

Chapter 5. Initial Post-hospital Course and After-Care

patients with ruptured aneurysms of the anterior communicating artery, but it occurs also after subarachnoid hemorrhage
from aneurysms at other sites [21, 23]. In those with endovascular occlusion of the aneurysm, the cause of the anosmia is
probably the hemorrhage itself and not the treatment because
anosmia rarely occurs after endovascular treatment of unruptured aneurysms [24]. In patients with a perimesencephalic
non-aneurysmal hemorrhage, the prevalence of anosmia is
only 1 in 16. Therefore, the anosmia should be attributed, at
least in part, to the hemorrhage itself and is related not only to
the suddenly increased intracranial pressure from a ruptured
aneurysm but also to the presence of blood in the basal cisterns
(in the vicinity of the olfactory nerves) [25]. There are no specific treatments for anosmia after subarachnoid hemorrhage,
but a combination of problem- and emotion-focused coping
strategies may be helpful [18]. In our experience, patients have
only rarely a genuine loss of taste (i.e. sweet, salt, sour, bitter).
Some patients describe that food tastes over-salted or not
salted at all even if they use abundant quantities of salt.

Visual Problems
Visual deficits can occur in three different forms: scotomas
due to Tersons syndrome, double vision and hemianopia.
The most common visual problem after subarachnoid
hemorrhage is related to intra-ocular hemorrhages, the socalled Tersons syndrome, named after the French ophthalmologist Albert Terson. Patients notice small or large black
spots that move concurrent with eye movement and often
hamper proper vision. In case of a vitreous hemorrhage, the
vision can be severely disturbed or even absent. In a systematic review of the literature, Tersons syndrome occurs in
1020 % of patients [26, 27]. It occurs more often in patients
who had been admitted in a poor clinical condition after the
subarachnoid hemorrhage and, in relation with that, in
patients with a poor outcome at discharge. In particular in
patients who are discharged to a rehabilitation facility or
nursing home, it is important to specifically look for intra-

Symptoms and Deficits

73

ocular hemorrhages because patients with poor cognitive


functioning often do not complain about poor vision, whereas
the poor vision can hamper the rehabilitation. In patients
with vitreous hemorrhages that do not resolve spontaneously
in the initial weeks after the hemorrhage, ophthalmosurgical
therapy is indicated to improve visual acuity [28]. In case of
subhyaloid or retinal hemorrhages, the natural history is
often good [29]. Intra-ocular hemorrhages do not occur in
patients with perimesencephalic hemorrhage.
Double vision is mainly caused by dysfunction of one of
the three cranial nerves involved in eye movements. During
the clinical course, dysfunction of the abducens nerve is very
common, but this is usually temporary, lasting for only a few
days, and is an uncommon cause at the outpatient clinic.
Double vision from an oculomotor palsy is often more long
lasting. This nerve runs close to the posterior communicating
artery and thus is often affected in patients with aneurysms
from the posterior communicating artery. In our experience,
double vision from an oculomotor palsy occurs in no more
than a few percent of patients; in a retrospective series of
more than 900 patients, it had been noted in 0.5 % [30]. In a
systematic review of the literature, complete, spontaneous
recovery had occurred in half the patients after surgical
occlusion of the aneurysm and a third of the patients after
endovascular occlusion [30]. During the recovery phase,
masking glasses of one of the eyes is easy and helpful. If
double vision persists for more than 1 or 2 years, corrective
surgery can alleviate the symptoms.
Patients can also have classical hemianopia or smaller cortical field deficits if they have had focal cerebral lesions from
the hemorrhage or its complications, in particular delayed
cerebral ischemia.

Hearing Problems
We are not aware of systematic studies on the prevalence of
hearing problems after subarachnoid hemorrhage, but in our
experience around 20 % of patients experience hearing prob-

74

Chapter 5. Initial Post-hospital Course and After-Care

lems at 6 weeks follow-up after the hemorrhage. In half of the


patients, the complaint is bilateral. In the few patients
reported, the hearing loss disappeared or improved within
the initial months after the hemorrhage [31], which is in line
with our own experience. Given the rarity of hearing loss
after subarachnoid hemorrhage, other causes should be specifically searched for if patients have persisting hearing loss
after subarachnoid hemorrhage. Another group of patients
do not report loss of hearing but just the opposite: hypersensitive for excessive and loud noises, which are most irritating.
Also, persistent tinnitus is frequently reported.

Symptoms Specific to Treatment


After endovascular treatment, patients may experience some
discomfort in the groin area where the catheter was inserted
in the artery. In particular if the endovascular procedure took
very long, such as in patients with giant aneurysms, patients
can have focal loss of hair. This is a temporary symptom and
resolves after a few months.
Symptoms that occur sometimes specifically after surgical
treatment are facial swelling, numbness around the scar and
discomfort in jaw, such as stiffness and a limitation of opening. This latter is caused by cutting of the muscle temporalis
and will heal by exercise.

Seizures
Epilepsy develops in the first year after discharge in 57 % of
patients with surgical treatment and in around 3 % of those
with endovascular treatment of the aneurysm [32, 33]. At
5 year follow-up, these risks have increased to 10 % after
surgical and 6 % after endovascular treatment of the aneurysm [33]. Epilepsy develops more often in patients who have
a poor clinical outcome, related to focal neurological deficits,
and is related to quality of life [32]. There is no evidence for

Reintegration into Work

75

prophylactic treatment with anti-epileptic drugs [34], but if


epilepsy develops after discharge, it should be treated as
usual.

Reintegration into Work


Return to work after subarachnoid hemorrhage depends
mainly on age, initial neurological condition, physical disability and the preservation of cognitive and sensorimotor function [35]. Three years after the hemorrhage, almost two-thirds
of the patients with employment before the subarachnoid
hemorrhage had returned to work, but only half of them had
completely resumed their former job. The others worked less
hours a week than before or had shifted to a less demanding
position. Also, time pressure, multi-tasking work and environmental factors such as noisy offices can be burdensome after
subarachnoid hemorrhage. Return to work is an important
determinant for life satisfaction after subarachnoid hemorrhage, and because it is so important for patients, reintegration
into work merits specific attention during rehabilitation.

Case 5.1: Letter from a 58-Year Old Woman, 6 Months


After the Subarachnoid Hemorrhage
I cycled to my work and it seemed like I got a blow on
my head. My neck ached and I could move it barely and
I had an extreme severe headache.
At work a colleague called 112 and I was rushed to
the hospital. The neurologist told me that I was seriously ill and I suffered a subarachnoid hemorrhage. Did
not know what that meant. It did not matter to me if
only anything was done to relieve the pain.
The aneurysm was coiled.

76

Chapter 5. Initial Post-hospital Course and After-Care

I felt very tired after the coiling procedure, but


expected that everything would be okay.
At home, I tried as much as possible to take things
slowly and to gradually increase tasks. But with increasing tasks, problems increased:
Multitasking is a challenge. This was my job, I was the
spider in the web, taking care of everything. Now I get
really upset when I have to do two things at once, or if
I have to do something unexpectedly, without being
able to plan it at beforehand.
Cooking food I always did easily, without the need to
think or plan. Nowadays, it is a huge effort to get everything on the table in the same time. I forget, for example, to cook potatoes, while vegetables are already done,
or, even worse, I go into the garden for some herbs and
forget about the meat, which then get burnt.
Reading a book used to be a hobby, but is now too
difficult to do. Only if there is no music playing, no TV
on, and nobody says a word, I can read a page. However,
the next day I dont remember what I have read. So
reading is no fun anymore, which frustrates me.
I changed to Knitting instead, but reading a knitting
pattern and then knitting it is a bridge too far. Even
after five attempts and starting over again I cannot
manage knitting a simple cardigan. Only knitting a tie
works, that I know by heart.
Driving a car and even sitting next to the driver
today is stressful. If I do, I can just drive half an hour
and then Im exhausted. Thats why I only drive very
short distances. I leave more space between my car and
the car in front of me so I can handle the situation.
When my husband is driving and he let other cars too
little space (in my opinion) I get panicked totally.
Sound makes me tired. Entering a store with music is
like taking a hurdle, it is impossible to concentrate on
my daily household shopping. Without a list I forget
what I need. Going to a concert is no longer an option,

References

77

because the sounds and lights make me intensely tired


and halfway I have to go home.
Energy is limited. In busy environments, such as
birthdays, parties, barbecues, visits of friends, screaming
children, Im a total lost. The day after a party always is
the next day is an off-day.
I was the manager of the company and my life but
now, after the subarachnoid hemorrhage nothing is
what it was before. Thats frustrating and hard to accept.
Everybody says: Youre looking good. Yes, you
cant see anything from the outside, nothing seems
wrong, but my life and feelings are totally different.
Im trying to find out what I can do with my the limited amount of energy that is left.
I certainly do not want to be depressed!

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2. Passier PE, Visser-Meily JM, Rinkel GJE, Lindeman E, Post
MW. Determinants of health-related quality of life after aneurysmal subarachnoid hemorrhage: a systematic review. Qual Life
Res. 2013;22(5):102743.
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6. Nijmeijer NM, aan de Stegge BM, Zuidema SU, Sips HJ,


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7. Murray PK, Singer M, Dawson NV, Thomas CL, Cebul
RD. Outcomes of rehabilitation services for nursing home residents. Arch Phys Med Rehabil. 2003;84(8):112936.
8. Schaafsma JD, Velthuis BK, Majoie CB, van den Berg R, Brouwer
PA, Barkhof F, et al. Intracranial aneurysms treated with coil
placement: test characteristics of follow-up MR angiographymulticenter study. Radiology. 2010;256(1):20918.
9. Schaafsma JD, Velthuis BK, van den Berg R, Brouwer PA,
Majoie CB, Barkhof F, et al. Coil-treated aneurysms: decision making regarding additional treatment based on findings of MR angiography and intraarterial DSA. Radiology.
2012;265(3):85863.
10. Ferns SP, Sprengers ME, van Rooij WJ, van Zwam WH, de
Kort GA, Velthuis BK, et al. Late reopening of adequately
coiled intracranial aneurysms: frequency and risk factors in 400
patients with 440 aneurysms. Stroke. 2011;42(5):13317.
11. Rinkel GJE, Algra A. Long-term outcomes of patients
with aneurysmal subarachnoid hemorrhage. Lancet Neurol.
2011;10(4):34956.
12. Passier PE, Visser-Meily JM, van Zandvoort MJ, Post MW,
Rinkel GJE, van Heugten C. Prevalence and determinants of
cognitive complaints after aneurysmal subarachnoid hemorrhage. Cerebrovasc Dis. 2010;29(6):55763.
13. Passier PE, Post MW, van Zandvoort MJ, Rinkel GJE, Lindeman
E, Visser-Meily JM. Predicting fatigue 1 year after aneurysmal
subarachnoid hemorrhage. J Neurol. 2011;258(6):10917.
14. Schuiling WJ, Rinkel GJE, Walchenbach R, de Weerd
AW. Disorders of sleep and wake in patients after subarachnoid
hemorrhage. Stroke. 2005;36(3):57882.
15. Gardner CJ, Javadpour M, Stoneley C, Purthuran M, Biswas
S, Daousi C, et al. Low prevalence of hypopituitarism after
subarachnoid hemorrhage using confirmatory testing and with
BMI-specific growth hormone cut-off levels. Eur J Endocrinol.
2013;168(4):47381.
16. Visser-Meily JM, Rinkel GJE, Vergouwen MD, Passier PE,
van Zandvoort MJ, Post MW. Post-traumatic stress disorder in
patients 3 years after aneurysmal subarachnoid hemorrhage.
Cerebrovasc Dis. 2013;36(2):12630.

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17. Bromley SM. Smell and taste disorders: a primary care approach.
Am Fam Physician. 2000;61(2):427. 36, 438.
18. Blomqvist EH, Bramerson A, Stjarne P, Nordin S. Consequences
of olfactory loss and adopted coping strategies. Rhinology.
2004;42(4):18994.
19. Hummel T, Nordin S. Olfactory disorders and their consequences for quality of life. Acta Otolaryngol. 2005;125(2):11621.
20. Miwa T, Furukawa M, Tsukatani T, Costanzo RM, DiNardo
LJ, Reiter ER. Impact of olfactory impairment on quality
of life and disability. Arch Otolaryngol Head Neck Surg.
2001;127(5):497503.
21. Wermer MJ, Donswijk M, Greebe P, Verweij BH, Rinkel
GJE. Anosmia after aneurysmal subarachnoid hemorrhage.
Neurosurgery. 2007;61(5):91822.
22. Bor AS, Niemansburg SL, Wermer MJ, Rinkel GJE. Anosmia
after coiling of ruptured aneurysms. Prevalence, prognosis, and
risk factors. Stroke. 2009;40(6):22268.
23. Martin GE, Junque C, Juncadella M, Gabarros A, de Miquel
MA, Rubio F. Olfactory dysfunction after subarachnoid hemorrhage caused by ruptured aneurysms of the anterior communicating artery. J Neurosurg. 2009;111(5):95862.
24. Moman MR, Verweij BH, Buwalda J, Rinkel GJE. Anosmia
after endovascular and open surgical treatment of intracranial
aneurysms. J Neurosurg. 2009;110(3):4826.
25. Greebe P, Rinkel GJE, Algra A. Anosmia after perimesencephalic nonaneurysmal hemorrhage. Stroke. 2009;40(8):28856.
26. McCarron MO, Alberts MJ, McCarron P. A systematic review of
Tersons syndrome: frequency and prognosis after subarachnoid
hemorrhage. J Neurol Neurosurg Psychiatry. 2004;75:4913.
27. Czorlich P, Skevas C, Knospe V, Vettorazzi E, Richard G,
Wagenfeld L, et al. Terson syndrome in subarachnoid hemorrhage, intracerebral hemorrhage, and traumatic brain injury.
Neurosurg Rev. 2015;38(1):12936.
28. Skevas C, Czorlich P, Knospe V, Stemplewitz B, Richard G,
Westphal M, et al. Tersons syndrome-rate and surgical approach
in patients with subarachnoid hemorrhage: a prospective interdisciplinary study. Ophthalmology. 2014;121(8):162833.
29. Stiebel-Kalish H, Turtel LS, Kupersmith MJ. The natural history
of nontraumatic subarachnoid hemorrhage-related intraocular
hemorrhages. Retina. 2004;24:3640.
30. Guresir E, Schuss P, Setzer M, Platz J, Seifert V, Vatter
H. Posterior communicating artery aneurysm related oculomotor nerve palsy: the influence of surgical and endovascular

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31.
32.

33.

34.

35.

Chapter 5. Initial Post-hospital Course and After-Care


treatment on recovery. Single center series and systematic
review. Neurosurgery. 2011;68(6):15334.
Kang S. Hearing loss after surgery of ruptured cerebral aneurysm. Br J Neurosurg. 2001;15(3):25863.
Claassen J, Peery S, Kreiter KT, Hirsch LJ, Du EY, Connolly ES,
et al. Predictors and clinical impact of epilepsy after subarachnoid hemorrhage. Neurology. 2003;60(2):20814.
Hart Y, Sneade M, Birks J, Rischmiller J, Kerr R, Molyneux
A. Epilepsy after subarachnoid hemorrhage: the frequency of
seizures after clip occlusion or coil embolization of a ruptured
cerebral aneurysm. J Neurosurg. 2011;115(6):115968.
Marigold R, Gunther A, Tiwari D, Kwan J. Antiepileptic drugs
for the primary and secondary prevention of seizures after
subarachnoid hemorrhage. Cochrane Database Syst Rev.
2013;6:CD008710.
Passier PE, Visser-Meily JM, Rinkel GJE, Lindeman E,
Post MW. Life satisfaction and return to work after aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis.
2011;20(4):3249.

Chapter 6
Long-Term Prognosis

The number of patients in the population who survived an


episode of subarachnoid hemorrhage is increasing because
the incidence of subarachnoid hemorrhage has remained
stable and the case fatality has decreased significantly over
the last decades. The number of expected life years for former patients is considerable because the mean age at which
subarachnoid hemorrhage occurs is only 55 years of age.
Since aneurysms develop during life and hypertension and
smoking are important risk factors for subarachnoid hemorrhage, former patients are at risk of new aneurysms, new
episodes of subarachnoid hemorrhage and increased risk of
other cardiovascular diseases. The risk of a new episode of
subarachnoid hemorrhage in survivors is 15 times higher
than in the general population. The absolute risk is however
only 3 % in the initial 10 years, and screening for new aneurysms is in general not efficient but should be discussed with
patients with familial subarachnoid hemorrhage and in
patients who had a first hemorrhage at young age (i.e. under
3540 years of age). Persons who have survived an episode
of subarachnoid hemorrhage have in the initial two decades
after the hemorrhage a 1.52 times greater risk of death than
the general population; in absolute terms, the risk of death is
around 40 % after these initial two decades. The majority of
causes of death are cardiovascular. Recovery of physical and
cognitive deficits continues over the initial years after the

G.J.E. Rinkel, P. Greebe, Subarachnoid Hemorrhage


in Clinical Practice, In Clinical Practice,
DOI 10.1007/978-3-319-17840-0_6,
Springer International Publishing Switzerland 2015

81

82

Chapter 6. Long-Term Prognosis

hemorrhage, and beyond these initial years of recovery, quality of life continues to improve despite no further improvement in handicap. To reduce the risk of cardiovascular
events, all patients should refrain from smoking and should
have blood pressure properly checked and treated in case of
hypertension.

Continuing Recovery
Recovery in General
Patients who had a subarachnoid hemorrhage are relatively
young (age 4060), and the impact of residual complaints and
deficits on everyday life for family, work and social functioning is high. Because patients with subarachnoid hemorrhage
are young, their capacity to recover is better than for most
people with stroke who are in general older. Persisting disability and quality of life have not only considerable impact
for patients but also for their families and for health economics. In a long-term follow-up study of a cohort of patients, we
found that between 4 months and 5 years after the hemorrhage, half the surviving patients showed an improvement in
terms of handicap [1]. Between 5 and 12.5 years follow-up,
there was no further improvement but even a slight decrease
in functional outcome. At 12.5 years follow-up, patients
reported the functional status to be normal for my age
despite a decline in physical functioning because they attributed this reduced physical functioning to other diseases they
had, such as osteoporosis, emphysema, cancer, diabetes, heart
failure and impairment of vision and hearing. Despite the
lack of further functional improvement, quality of life had
improved over this period (Table 6.1). This suggests that
patients continue to adapt regarding their disability, probably
by improved coping with restrictions in functioning, as is seen
also in other chronic diseases. The overall good quality of life
indicates an improved appreciation of life also long after
recovery of a life-threatening illness. Similar observations

New Cardiovascular and Other Events

83

Table 6.1 Visual Analogue Scale scores for appreciation of life


according to time after subarachnoid hemorrhage in a consecutive
series of 64 patients

VAS score
10
9
8
7
6
5
4
3
2
1
0
before SAH

4 month

18 month

5 years

12.5 years

have been done in long-term survivors of ischemic stroke


who have an overall quality of life not much different from
the normal population [2].

New Cardiovascular and Other Events


and Life Expectancy
Risk of New Aneurysm and New Subarachnoid
Hemorrhage
Intracranial aneurysms have long been considered to be
congenital lesions. Accordingly, until the end of the last
century, the prevailing perception on the fate of patients
who survived an episode of subarachnoid hemorrhage was
that if the ruptured aneurysm was occluded and no other
aneurysms were found, these former patients were not at
risk for new episodes. This notion no longer holds true.
Aneurysms are not present at birth but develop during life.
Thus, patients who have survived an episode of subarachnoid hemorrhage may develop new aneurysms and also
new episodes of subarachnoid hemorrhage from these

84

Chapter 6. Long-Term Prognosis

newly developed aneurysms. Other sources for new episodes of subarachnoid hemorrhage are the initially ruptured and treated aneurysm if the aneurysm was not
entirely occluded or if it reopened or regrew at this site or
from additional aneurysms that were left untreated. The
overall incidence of subarachnoid hemorrhage in patients
who have had an episode of subarachnoid hemorrhage and
in whom the aneurysm is occluded is around 190 per
100,000 patient-years, which is 15-fold the risk observed in
age- and sex-matched persons in the general population [3].
In a follow-up study in the Netherlands, the risk of a new
episode of subarachnoid hemorrhage in the first decade
after the initial episode was 3 % [4]. The risk does not differ
importantly between neurosurgical or endovascular occlusion of the aneurysm [3, 5], although the risk of late recurrent subarachnoid hemorrhage from the initial ruptured
and treated aneurysm is higher after endovascular than
neurosurgical treatment [5]. If during follow-up imaging of
the intracranial vessels a new aneurysm is detected at a site
remote from the initially treated one(s), this aneurysm may
be truly new or missed at the initial investigation. In a study
on follow-up screening with CT angiography of 610 patients
219 years after clipping of the ruptured aneurysm, 151
aneurysms were found in 112 patients (18 %) of which 22
aneurysms in 17 patients had already been detected at the
time of the initial subarachnoid hemorrhage [6, 7]. Of the
129 newly detected aneurysms, 105 (81 %) were located at
a site remote from the clip site, and one-third of these aneurysms were truly de novo. Of those that were already present at time of the initial hemorrhage, one in four had grown
in size during follow-up. Thus, after a mean follow-up of
9 years after a subarachnoid hemorrhage, aneurysms are
found in one in five patients, of which one-third is truly
de novo.
The several risk factors that have been identified for
development of new aneurysms and new episodes of subarachnoid hemorrhage are listed in Table 6.2 [4, 7].

New Cardiovascular and Other Events

85

Table 6.2 Risk factors for development of new aneurysms and new
episodes of subarachnoid hemorrhage in patients who have survived
an episode of subarachnoid hemorrhage and in whom the ruptured
aneurysm has been treated
Risk ratio (95 % CI)
Risk factors for new aneurysm
Familial SAH

2.7 (1.07.4)

Current smoking

3.2 (1.09.7)

Multiple aneurysms

3.3 (1.28.9)

Risk factors for new SAH


Age (each 10 years younger)

1.7 (1.12.5)

Familial SAH

3.8 (1.113.2)

Current smoking

4.8 (1.317.4)

Multiple aneurysms

5.7 (2.314.5)

CI confidence interval, SAH subarachnoid hemorrhage

Risk of Other Cardiovascular Events


Since smoking and hypertension are important risk factors
not only for subarachnoid hemorrhage but also for other
cardiovascular diseases, persons who have survived an episode of subarachnoid hemorrhage may be at risk not only for
new episodes of subarachnoid hemorrhage but also for other
cardiovascular diseases. Several studies indeed found an
increased risk of ischemic or hemorrhagic stroke other than
subarachnoid hemorrhage, myocardial infarction or sudden
death in the life after a subarachnoid hemorrhage. In a follow-up study in the Netherlands, the risk of vascular events
other than a new episode of subarachnoid hemorrhage in the
initial 10 years after a subarachnoid hemorrhage was 11.2 %
(95 % CI 7.014.4 %) [8]. Compared to age- and sex-adjusted
persons from the general Dutch population, the incidence of

86

Chapter 6. Long-Term Prognosis

fatal and non-fatal cardiovascular events other than subarachnoid hemorrhage is doubled for former subarachnoid
hemorrhage patients (standardized incidence ratio 2.0;
95 %CI 1.92.1) [9]. If new episodes of subarachnoid hemorrhage are included as outcome events, the standardized incidence ratio is 2.7 (95 %CI 2.62.8) [9]. A population-based
study in Sweden found that standardized incidence ratio for
fatal or non-fatal vascular diseases ranged from 2.4 to 3.4 for
women and from 1.7 to 2.1 for men between ages 50 and 65
and were increased for almost all age groups until the age
group older than 85 years of age [10].

Risk of Cancer
Patients who have survived an episode of subarachnoid hemorrhage may be at increased risk of cancer, in particular lung
cancer, because subarachnoid hemorrhage and lung cancer
share smoking as risk factor. The few data that are available
indeed show an increased risk of lung cancer in the life after
subarachnoid hemorrhage. A follow-up study on 2,285
patients with subarachnoid hemorrhage admitted between
1980 and 2007 in eastern Finland found an increased risk of
incidence of lung cancer both in men (standardized incidence
ratio 2.0; 95 % CI 1.33.0) and in women (standardized incidence ratio 2.5; 95 % CI 1.15.0) [11]. This increased incidence of lung cancer does not translate into an increased risk
of death from cancer overall. In a long-term follow-up study
from 1,765 patients admitted between 1985 and 2010 in our
hospital, we found a standardized mortality rate from cancer
of 1.0 (95 % CI 0.71.4) [12].

Mortality
Overall absolute risks of death have been assessed in several
studies. In a series of 1,765 patients from our own institution
who had survived the initial 3 months after the subarachnoid
hemorrhage, the risk of death ranged from 9 % at 5 years to

New Cardiovascular and Other Events


Table 6.3 Absolute risks
of death in patients who
have survived an episode
of subarachnoid hemorrhage and in whom the
ruptured aneurysm has
been treated [12]

87

Follow up
(years)
5

Risk of
death (%)
8.7

95 %
CI (%)
7.310.1

10

17.9

16.119.9

15

29.5

27.331.8

20

43.6

41.246.1

CI confidence interval

44 % at 20 years after subarachnoid hemorrhage (Table 6.3)


[12]. A study based on Dutch hospital discharge and mortality registers and another study based on Swedish registries
found similar results [9, 10]. Given the higher risk of cardiovascular diseases and cancer in patients who have recovered
from aneurysmal subarachnoid hemorrhage, these risks of
death may be higher than those in the general population.
Indeed, a Finnish study on 1,746 patients with subarachnoid
hemorrhage who had survived the initial year after the hemorrhage found a 12 % excess at 15 years compared with sex
and age-matched people from the general population in the
same catchment area [13]. A study based on Swedish hospital
discharge and death registries found similar data, with a
10.5 % excess all cause death per 1,000 person-years [10].
This increased mortality persists for decades after the hemorrhage and is not only explained by increased smoking and
hypertension in the years before the subarachnoid hemorrhage. In a study on 102 children with aneurysmal subarachnoid hemorrhage, mortality of these former pediatric patients
was compared with mortality of the general Finnish population matched by age, sex and calendar time. There was an
overall excess mortality of 10 % at 20 years and 19 % at
40 years after the diagnosis in those patients who had survived the first year after the subarachnoid hemorrhage [14].
In terms of standardized mortality rates, population-based
studies in Finland, Sweden and the Netherlands found that
survivors of subarachnoid hemorrhage have a 1.52.5 times
greater risk of death compared with matched controls from

88

Chapter 6. Long-Term Prognosis

the general population, with the risk varying with age of the
patient and duration of follow-up [10, 12, 15]. The increased
risk of death for patients who have survived an episode of
subarachnoid hemorrhage seems not to differ between those
with a familial and those with sporadic subarachnoid hemorrhage [13].
Long-term outcome after perimesencephalic hemorrhage
is better than after aneurysmal subarachnoid hemorrhage. In
a series of 160 patients from our institution with more than
1,200 follow-up years, none had a new episode of perimesencephalic (or aneurysmal) hemorrhage, and age- and sexmatched life expectancy was not reduced compared to that in
the general population (standardized mortality ratio 0.61
(95 % confidence interval 0.341.1)) [16]. The normal life
expectancy and absence of new episodes of hemorrhage in
the life after perimesencephalic hemorrhage indicate that no
restrictions should be imposed on these patients by physicians or health or life insurance companies.

Secondary Prevention
Screening for New Aneurysms
The risks for new or enlarging aneurysms and new episodes
of subarachnoid hemorrhage pose the question whether
patients who have successfully been treated for subarachnoid
hemorrhage should be screened from time to time for new
aneurysms. In fact, some actually do advocate such screening
[17]. A study addressing this question, however, concluded
that follow-up screening is in general not indicated [18]. This
decision analysis showed that screening saved costs and
increased quality-adjusted life years only in patients with a
relatively high risk of both aneurysm formation and rupture.
For clinical practice, this suggests that serial screening every
35 years should be considered for former patients who had
a first episode at young age (roughly defined as age younger
than 3540), in particular if they had multiple aneurysms at

Secondary Prevention

89

that time [19]. Serial screening should definitely be considered for patients who turn out to have a positive family history and for their first-degree relatives and also for patients
with polycystic kidney disease (see section Indications for
and methods of screening in Chap. 3) [2022].
For follow-up imaging of additional unruptured aneurysms that are left untreated, we refer to section Follow up
imaging in Chap. 3.

Lifestyle
Despite explaining that smoking is a risk factor for the formation and rupture of intracranial aneurysms, more than a third
of prior smokers continue to smoke after subarachnoid hemorrhage [23]. Young age at smoking onset and a history of
depression or alcohol use are risk factors for continued cigarette use [23]. Thus, targeted smoking cessation programs are
needed to reduce the high rate of smoking resumption after
subarachnoid hemorrhage. Similarly, the use of cocaine
should be discouraged. Also, hypertension is a risk factor for
formation and rupture, and therefore patients have to have
their blood pressure regularly checked and treated in case of
hypertension.

Medical Management
Although the risk of cardiovascular diseases is increased in
the life after subarachnoid hemorrhage, there are no data
showing a beneficial effect of antiplatelet drugs in the life
after subarachnoid hemorrhage. Because of this lack of evidence, we do not routinely prescribe these drugs. Similarly,
there are no data showing that aspirin is contra-indicated in
patients who have survived an episode of subarachnoid hemorrhage. Thus, if there is an indication to prescribe aspirin, the
previous history of subarachnoid hemorrhage should not be
a contra-indication with an unruptured aneurysm. The same

90

Chapter 6. Long-Term Prognosis

holds true for oral anticoagulants. There is no good evidence


that anticoagulants increase the risk of rupture of newly
developed aneurysms, and even if they would do so, the risk
remains so low that the benefits of anticoagulants by far outweigh the risks.
Although women have a higher risk than men for subarachnoid hemorrhage, the reasons for this sex difference are
not clear. Several studies have investigated the use of oral
contraceptives and hormone replacement therapy on incidence of subarachnoid hemorrhage, but results are confusing
and effect sizes small [24]. We therefore do not advise against
use of such medication.

References
1. Greebe P, Rinkel GJE, Hop JW, Visser-Meily JM, Algra
A. Functional outcome and quality of life 5 and 12.5 years after
aneurysmal
subarachnoid
hemorrhage.
J
Neurol.
2010;257(12):205964.
2. Kempen GI, Ormel J, Brilman EI, Relyveld J. Adaptive responses
among Dutch elderly: the impact of eight chronic medical conditions on health-related quality of life. Am J Public Health.
1997;87(1):3844.
3. Rinkel GJE, Algra A. Long-term outcomes of patients with
aneurysmal subarachnoid hemorrhage. Lancet Neurol.
2011;10(4):34956.
4. Wermer MJ, Greebe P, Algra A, Rinkel GJE. Incidence of recurrent subarachnoid hemorrhage after clipping for ruptured intracranial aneurysms. Stroke. 2005;36(11):23949.
5. Molyneux AJ, Birks J, Clarke A, Sneade M, Kerr RS. The durability of endovascular coiling versus neurosurgical clipping of
ruptured cerebral aneurysms: 18 year follow-up of the UK
cohort of the International Subarachnoid Aneurysm Trial
(ISAT). Lancet. 2015;385(9969):6917.
6. van der Schaaf IC, Velthuis BK, Wermer MJ, Majoie C, Witkamp
T, de Kort G, et al. New detected aneurysms on follow-up screening in patients with previously clipped intracranial aneurysms.
Comparison with DSA or CTA at the time of SAH. Stroke.
2005;36(8):17538.

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7. Wermer MJ, van der Schaaf IC, Velthuis BK, Algra A, Buskens
E, Rinkel GJE. Follow-up screening after subarachnoid hemorrhage: frequency and determinants of new aneurysms and
enlargement of existing aneurysms. Brain. 2005;128:24219.
8. Wermer MJ, Greebe P, Algra A, Rinkel GJE. Long-term mortality and vascular event risk after aneurysmal subarachnoid hemorrhage. J Neurol Neurosurg Psychiatry. 2009;80(12):1399401.
9. Nieuwkamp DJ, Vaartjes I, Algra A, Rinkel GJE, Bots ML. Risk
of cardiovascular events and death in the life after aneurysmal
subarachnoid hemorrhage: a nationwide study. Int J Stroke.
2014;9(8):10906.
10. Nieuwkamp DJ, Algra A, Blomqvist P, Adami J, Buskens E,
Koffijberg H, et al. Excess mortality and cardiovascular events in
patients surviving subarachnoid hemorrhage: a nationwide study
in Sweden. Stroke. 2011;42(4):9027.
11. Huttunen T, Riihinen A, Pukkala E, von und zu Fraunberg M,
Koivisto T, Ronkainen A, et al. Increased relative risk of lung
cancer in 2,904 patients with saccular intracranial aneurysm disease in Eastern Finland. Neuroepidemiology. 2012;38(2):939.
12. Nieuwkamp DJ, de Wilde A, Wermer MJ, Algra A, Rinkel
GJE. Long-term outcome after aneurysmal subarachnoid
hemorrhage-risks of vascular events, death from cancer and allcause death. J Neurol. 2014;261(2):30915.
13. Huttunen T, von und zu Fraunberg M, Koivisto T, Ronkainen A,
Rinne J, Sankila R, et al. Long-term excess mortality of 244
familial and 1502 sporadic one-year survivors of aneurysmal
subarachnoid hemorrhage compared with a matched Eastern
Finnish catchment population. Neurosurgery. 2011;68(1):207.
14. Koroknay-Pal P, Laakso A, Lehto H, Seppa K, Kivisaari R,
Hernesniemi J, et al. Long-term excess mortality in pediatric
patients with cerebral aneurysms. Stroke. 2012;43(8):20916.
15. Korja M, Silventoinen K, Laatikainen T, Jousilahti P, Salomaa V,
Kaprio J. Cause-specific mortality of 1-year survivors of subarachnoid hemorrhage. Neurology. 2013;80(5):4816.
16. Greebe P, Rinkel GJE. Life expectancy after perimesencephalic
subarachnoid hemorrhage. Stroke. 2007;38(4):12224.
17. Thomas AJ, Ogilvy CS. ISAT: equipoise in treatment of ruptured
cerebral aneurysms? Lancet. 2015;385(9969):6668.
18. Wermer MJ, Koffijberg H, van der Schaaf I. Effectiveness and
costs of screening for aneurysms every 5 years after subarachnoid hemorrhage. Neurology. 2008;70(22):205362.

92

Chapter 6. Long-Term Prognosis

19. Wermer MJ, Rinkel GJE, Greebe P, Albrecht KW, Dirven CM,
Tulleken CA. Late recurrence of subarachnoid hemorrhage after
treatment for ruptured aneurysms: patient characteristics and
outcomes. Neurosurgery. 2005;56(2):197204.
20. Bor AS, Rinkel GJE, Adami J, Koffijberg H, Ekbom A, Buskens
E, et al. Risk of subarachnoid hemorrhage according to number
of affected relatives: a population based case-control study.
Brain. 2008;131(10):26625.
21. Bor AS, Rinkel GJE, van Norden J, Wermer MJ. Long-term,
serial screening for intracranial aneurysms in individuals with a
family history of aneurysmal subarachnoid hemorrhage: a
cohort study. Lancet Neurol. 2014;13(4):38592.
22. Bor ASE, Koffijberg H, Wermer MJ, Rinkel GJE. Optimal
screening strategy for familial intracranial aneurysms: a costeffectiveness analysis. Neurology. 2010;74(21):16719.
23. Ballard J, Kreiter KT, Claassen J, Kowalski RG, Connolly ES,
Mayer SA. Risk factors for continued cigarette use after subarachnoid hemorrhage. Stroke. 2003;34(8):185963.
24. Algra AM, Klijn CJ, Helmerhorst FM, Algra A, Rinkel
GJE. Female risk factors for subarachnoid hemorrhage: a systematic review. Neurology. 2012;79(12):12306.

Chapter 7
Clinical Research
and Patient Participation

This handbook is based on clinical research in patients with


an aneurysm or subarachnoid hemorrhage. Clinical research
is unthinkable without patients willingness to participate,
and their collaboration is of great importance not only to
improve knowledge on causes, diagnosis, prognosis and therapy of subarachnoid hemorrhage and intracranial aneurysms
but also to obtain new ideas.
The prognosis of patients with subarachnoid hemorrhage
has improved considerably over the last 30 years, with a
reduction of case fatality of 17 % [1]. This improved prognosis is not explained by one single factor but based on many
factors in a wide range of aspects of diagnosis, treatment and
care for these patients. To provide a few examples, the diagnosis of aneurysms in the setting of patients with subarachnoid hemorrhage has improved by advent of CT angiography.
This technique enables to demonstrate the ruptured aneurysm a couple of minutes after the diagnosis of subarachnoid
hemorrhage and has thereby facilitated early aneurysm treatment. Moreover, in many instances, conventional catheter
angiography with its inherent complications is no longer
needed, which in turn has created more time in the angiosuite
for endovascular treatment of aneurysms. Coiling of aneurysms is the most often used endovascular technique and has
been studied in randomized clinical trials early after its introduction. In the subset of patients that can be treated both

G.J.E. Rinkel, P. Greebe, Subarachnoid Hemorrhage


in Clinical Practice, In Clinical Practice,
DOI 10.1007/978-3-319-17840-0_7,
Springer International Publishing Switzerland 2015

93

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Chapter 7.

Clinical Research and Patient Participation

endovascularly and surgically, coiling leads to better outcome


[2] also in the long term [3]. Therefore, the advent of endovascular techniques is another contributor to the improved prognosis for patients with subarachnoid hemorrhage. In parallel
with the development of endovascular treatment options,
also microsurgical techniques have improved. Non-occlusive
intracranial bypass techniques have facilitated surgical treatment for very large aneurysms [4], and intra-operative visualization of flow in the aneurysm and adjacent vessels have
provided intra-operative control of aneurysm occlusion and
patency of surrounding vessels [5]. Stroke care units and
intensive care units have been proven to be beneficial for all
intracerebral hemorrhages including subarachnoid hemorrhage [6].
After discharge, there is more attention for the patient and
long-term deficits at home as well as in rehabilitation facilities and nursing home reactivation.
After discharge, follow-up imaging is needed after coiling
of aneurysm because around 20 % have not completely
occluded or reopened aneurysms at 36 months and half of
these patients need retreatment. This follow-up used to be
done with conventional catheter angiography. Thanks to
300 patients who were willing to undergo catheter angiography and MR angiography simultaneously, we know now that
we can use MR angiography to control coiled aneurysms for
reopening [7, 8]. MR angiography has the advantage over
catheter angiography that it can easily be done in an outpatient setting and carries no risks.
Through willingness of patients for long-term follow-up
after subarachnoid hemorrhage, we have learned that new
episodes of subarachnoid hemorrhage do occur [9]. In an ensuing study where 600 patients with a clipped aneurysm after
subarachnoid hemorrhage were willing to undergo CT angiography, we learned about the chances to detect new aneurysms
in the first decade after the hemorrhage. We therefore know
that in general, follow-up imaging is not indicated [10, 11] but
that patients with subarachnoid hemorrhage at young age and
those with a familial subarachnoid hemorrhage form an exception to this rule [11, 12].

Future Prospects

95

Also regarding unruptured aneurysms, knowledge has


advanced. We have identified risk factors for development of
risk of rupture of intracranial aneurysms. As a result, we can
identify subgroups of patients who may benefit from screening with MRA such as persons with two or more first-degree
relatives with subarachnoid hemorrhage. Moreover, we have
absolute risk estimates of rupture according to easily retrievable patient and aneurysm characteristics [13].
Finally, not only patients and their proxies but also other
relatives have been indispensable for improving our knowledge. In an initial study on familial occurrence, we collected
data of 1,290 first- and 3,588 second-degree relatives of
patients with subarachnoid hemorrhage. Based on participation of many of these relatives, we found that first-degree relatives have an increased risk of subarachnoid hemorrhage [14].
Based on these data, we embarked on a study to assess
whether screening these first-degree relatives with MR angiography for aneurysms and treating the aneurysms found would
be effective in terms of increasing quality of life. Of 796 eligible
first-degree relatives of patients with subarachnoid hemorrhage, 626 agreed to undergo MR angiography. The results of
the study showed that at time of the study (early 1990s), implementation of a screening program for first-degree relatives of
patients with subarachnoid hemorrhage was not warranted
[15]. New data from our group based on willingness of these
screenees to respond to follow-up questionnaires 20 years later
[16] suggest that this negative advice needs revision
(E. Hopmans et al., 2015, unpublished data).

Future Prospects
Despite the progress that has been made over the last three
decades, more clinical research is needed. Rebleeding is still an
important cause of poor outcome, and it will never be possible
to avoid all episodes of rebleeding by very early aneurysm
occlusion because many episodes of rebleeding occur within
the first 24 h and almost half of these within the initial 3 h after
the initial hemorrhage. Thus, we need other than surgical or

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Chapter 7.

Clinical Research and Patient Participation

endovascular methods to reduce the risk of rebleeding within


the initial hours and thereby improve outcome. Currently, a
trial on antifibrinolytic drugs is ongoing [17]. A question more
important from a population perspective is a refined prediction of rupture of aneurysm and treatment strategies to reduce
the risk of aneurysms that are currently too small to make
endovascular or surgical treatment beneficial. Also in this area,
medical treatment would be helpful. Since inflammation of the
aneurysm wall is likely to be involved in growth and rupture of
aneurysms, anti-inflammatory drugs may be beneficial for
patients with unruptured aneurysms, and such treatments
should be investigated in clinical trials. For future genetic studies, we ask all patients with subarachnoid hemorrhage or
unruptured aneurysms for blood samples to collect DNA, and
more than 90 % are willing to do so.
Most, if not all, of the progress in research on subarachnoid
hemorrhage and intracranial aneurysms is based on investigator-driven clinical research for which participation of patients,
proxies and relatives has been essential. This research would
also not have been possible without funding from non-industry agencies. For future increase in knowledge, continued
participation of patients and their families and support from
non-market-driven funding agencies is crucial.

References
1. Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK,
Rinkel GJE. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region:
a meta-analysis. Lancet Neurol. 2009;8(7):63542.
2. van der Schaaf IC, Algra A, Wermer MJ, Molyneux AJ, Clarke
M, van Gijn J, et al. Endovascular coiling versus neurosurgical
clipping for patients with aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2005;(4):CD003085.
3. Molyneux AJ, Birks J, Clarke A, Sneade M, Kerr RS. The durability of endovascular coiling versus neurosurgical clipping of
ruptured cerebral aneurysms: 18 year follow-up of the UK cohort
of the International Subarachnoid Aneurysm Trial (ISAT). Lancet.
2015;385(9969):6917.

References

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4. van Doormaal TP, van der Zwan A, Verweij BH, Regli L,


Tulleken CA. Giant aneurysm clipping under protection of
an excimer laser-assisted non-occlusive anastomosis bypass.
Neurosurgery. 2010;66(3):43947.
5. Dashti R, Laakso A, Niemela M, Porras M, Hernesniemi J.
Microscope-integrated near-infrared indocyanine green videoangiography during surgery of intracranial aneurysms: the
Helsinki experience. Surg Neurol. 2009;71(5):54350.
6. Sarker SJ, Heuschmann PU, Burger I, Wolfe CD, Rudd AG,
Smeeton NC, et al. Predictors of survival after haemorrhagic stroke in a multi-ethnic population: the South London
Stroke Register (SLSR). J Neurol Neurosurg Psychiatry.
2008;79(3):2605.
7. Schaafsma JD, Koffijberg H, Buskens E, Velthuis BK, van der
Graaf Y, Rinkel GJE. Cost-effectiveness of magnetic resonance
angiography versus intra-arterial digital subtraction angiography to follow-up patients with coiled intracranial aneurysms.
Stroke. 2010;41(8):173642.
8. Schaafsma JD, Velthuis BK, van den Berg R, Brouwer PA,
Majoie CB, Barkhof F, et al. Coil-treated aneurysms: decision making regarding additional treatment based on findings of MR angiography and intraarterial DSA. Radiology.
2012;265(3):85863.
9. Wermer MJ, Greebe P, Algra A, Rinkel GJE. Incidence of recurrent subarachnoid hemorrhage after clipping for ruptured intracranial aneurysms. Stroke. 2005;36(11):23949.
10. Wermer MJ, van der Schaaf IC, Velthuis BK, Algra A, Buskens
E, Rinkel GJE. Follow-up screening after subarachnoid haemorrhage: frequency and determinants of new aneurysms and
enlargement of existing aneurysms. Brain. 2005;128:24219.
11. Wermer MJ, Koffijberg H, van der Schaaf IC. Effectiveness and
costs of screening for aneurysms every 5 years after subarachnoid hemorrhage. Neurology. 2008;70(22):205362.
12. Bor AS, Rinkel GJE, van Norden J, Wermer MJ. Long-term,
serial screening for intracranial aneurysms in individuals with
a family history of aneurysmal subarachnoid haemorrhage:
a cohort study. Lancet Neurol. 2014;13(4):38592.
13. Greving JP, Wermer MJ, Brown Jr RD, Morita A, Juvela
S, Yonekura M, et al. Development of the PHASES score
for prediction of risk of rupture of intracranial aneurysms:
a pooled analysis of six prospective cohort studies. Lancet
Neurol. 2014;13(1):5966.

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14. Bromberg JEC, Rinkel GJE, Algra A, Greebe P, van Duyn CM,
Hasan D, et al. Subarachnoid haemorrhage in first and second
degree relatives of patients with subarachnoid haemorrhage.
BMJ. 1995;311:2889.
15. MARS Study Group. Risks and benefits of screening for intracranial aneurysms in first-degree relatives of patients with sporadic
subarachnoid hemorrhage. N Engl J Med. 1999;341:134450.
16. Rasing I, Ruigrok YM, Greebe P, Velthuis BK, Witkamp TD,
Wermer MJ, et al. Long-term risk of aneurysmal subarachnoid
hemorrhage after a negative aneurysm screen. Neurology.
2015;84(9):9127.
17. Germans MR, Post R, Coert BA, Rinkel GJE, Vandertop WP,
Verbaan D. Ultra-early tranexamic acid after subarachnoid hemorrhage (ULTRA): study protocol for a randomized controlled
trial. Trials. 2013;14(1):143.

Index

A
Activities of daily living, 1, 11,
40, 59
Aftercare, 57, 6066
Alcohol, 12, 17, 89
Anaesthesia, 58
Analgetics, 50
Aneurysm, berry, 3
Aneurysm, familial, 8, 9, 66
Aneurysm, formation, 12
Aneurysm, multilobed, 34
Aneurysm, saccular, 3
Aneurysm, shape, 3, 9, 33
Aneurysm, site, 4, 7, 9, 33
Aneurysm, size, 7, 9, 3234
Aneurysm, sporadic, 9
Anger, 9
Angiography, 4, 17, 37, 38, 4750,
84, 9395
Anosmia, 71, 72
Anticoagulants, 32, 90
Antifibrinolytic drugs, 51, 96
Antiplatelet agents, 31, 32
Anxiety, 1, 25, 27, 36, 57, 61, 65,
66, 68, 7071
Appetite, 71
Atherosclerosis, 6
Attention problems, 68
Autosomal dominant polycystic
kidney disease, 5

B
Basal cisterns, 49, 72
Blood pressure, 10, 26, 31,
61, 82, 89

C
Calcium-antagonist, 50, 52
Cancer, 82, 86, 87
Cardiac arrest, 40
Case fatality, 5, 1012, 40, 81, 93
Cerebrospinal fluid, 49, 53
Clipping, 25, 30, 38, 53, 64, 84
Cocaine, 31, 89
Coffee, 9
Cognitive deficit, 59, 81
Cognitive rehabilitation, 59
Coiling, 30, 38, 47, 53, 76,
93, 94
Coping style, 59, 69, 70
CT, 17, 4750, 52
CT-Angiography, 37, 38, 47, 49,
50, 84, 93, 94

D
Deafness, 7374
Delayed cerebral ischemia, 47,
5152, 57, 59, 73
De novo, 84

G.J.E. Rinkel, P. Greebe, Subarachnoid Hemorrhage


in Clinical Practice, In Clinical Practice,
DOI 10.1007/978-3-319-17840-0,
Springer International Publishing Switzerland 2015

99

100

Index

Depression, 1, 36, 57, 65, 66, 68,


7074, 89
Determinants, 15, 20, 26, 75
Diabetes, 12, 82
Disability, 3, 53, 62, 63, 70,
71, 75, 82
Dissection, 13, 71
Dizziness, 57
Double vision, 72, 73
Driving license, 66

Hemianopia, 72, 73
Hormone replacement
therapy, 13, 90
Hydrocephalus, 17, 47, 5253, 57
Hypercholesterolemia, 5, 13, 15
Hypertension, 57, 12, 1417, 31,
33, 34, 52, 62, 81, 82,
85, 87, 89
Hypervolaemia, 52
Hypovolaemia, 50

E
Ehlers Danlos syndrome, 13, 36
Emotional problems, 57
Endovascular occlusion, 25, 72,
73, 84
Epilepsy, 74, 75
External ventricular
drainage, 53

I
Incidence, 1, 3, 5, 1012, 15, 25,
39, 81, 84, 86, 90
Infarction, cerebral, 52
Infarction, myocardial, 85
Intracerebral hemorrhage,
59, 94
Irritability, 58

F
Family history, 5, 6, 8, 1316, 26,
34, 89
Fatigue, 1, 57, 58, 6871
First degree relative, 5, 14, 34, 35,
89, 95
Fluid management, 50
Flying, 31, 37, 58, 71
Follow up imaging, 3234, 66, 84,
89, 94
Forgetfulness, 57

L
Libido, 70, 71
Life expectancy, 17, 26, 27,
8388
Life insurance, 27, 37, 88
Life time risk, 14, 16
Lumbar puncture, 48, 53

G
Genetics, 13, 96
Growth, 8, 27, 30, 3234, 96

H
Headache, 15, 17, 25, 38, 39, 48,
49, 57, 69, 70, 75
Hearing, 71, 7374, 82

M
Marfan disease, 13, 36
Migraine, 38
Modified Rankin Scale, 61, 62
Mortality, 8688
MR-angiography, 4, 37, 48, 94, 95

N
Neck stiffness, 16, 17
Neuropsychological test, 65, 68
Nimodipine, 47, 50, 52
Nose blowing, 9

Index
Nuchal rigidity, 39
Nursing home, 2, 30, 5761, 66,
73, 94

O
Obesity, 12
Oculomotor palsy, 73
Outpatient clinic, 60, 61, 6466,
68, 73

P
Perimesencephalic hemorrhage,
17, 50, 57, 61, 73, 88
PHASES, 7, 8
Physical exercise, 6, 9, 12, 28, 31, 68
Physician assistant, 57
Pituitary disturbances, 69
Post-traumatic stress disorder,
69, 70
Predictor, 7, 8, 32, 70
Pregnancy, 71
Prevalence, 1, 3, 56, 72, 73

Q
Quality of life, 1, 2527, 29, 57, 59,
6971, 75, 82, 83, 95

R
Rebleeding, 26, 38, 47, 51, 53, 66,
95, 96
Rehabilitation facility, 5759,
61, 72
Retinal hemorrhage, 73
Risk factor, 3, 5, 6, 8, 9, 1215,
17, 30, 33, 34, 36, 66, 81, 8486,
89, 95
Rupture, 3, 510, 12, 13, 2533,
36, 39, 8890, 95, 96

101

S
Screening, 2, 5, 8, 14, 15, 25,
3438, 66, 69, 81, 89, 95
Seizures, 15, 7475
Sexual intercourse, 9, 10, 31
Sleep, 1, 69
Smell, 7172
Smoking, 5, 6, 9, 12, 14, 16, 17, 26,
30, 31, 33, 34, 61, 66, 81, 82,
8587, 89
Social problems, 57, 59
Specialized nurse, 57, 61, 62,
64, 66
Startling, 9
Straining, 9
Subhyaloid hemorrhage, 73
Sudden death, 39, 85
Surgical treatment, 29, 30, 70, 74,
84, 94, 96

T
Taste, 71, 72
Tersons syndrome, 72
Tinnitus, 74
Trauma, 3
Trigger factors, 910, 31
Twins, 35

V
Vasospasm, 51, 52
Ventricular system, 3, 53
Vision, 7173, 82, 95
Visual Analogue Scale (VAS)
score, 83
Vomiting, 15