European Stroke Organization Guidelines for the Management of Intracranial Aneurysms and ...

20 Pages·2013·1.37 MB·English

Guidelines
Cerebrovasc Dis 2013;35:93–112 Received: October 9, 2012
DOI: 10.1159/000346087 Accepted: November 22, 2012
Published online: February 7, 2013
European Stroke Organization Guidelines for
the Management of Intracranial Aneurysms
and Subarachnoid Haemorrhage
Thorsten Steiner a Seppo Juvela d Andreas Unterberg b Carla Jung b

Michael Forsting c Gabriel Rinkel e

Departments of a Neurology and b Neurosurgery, Heidelberg University, Heidelberg , and c Department of

Radiology, University of Essen, Essen , Germany; d Department of Clinical Neurosciences, University of Helsinki,

Helsinki , Finland; e Department Neurology, Utrecht University, Utrecht , The Netherlands

Key Words European Federation of Neurological Societies. Members of
Subarachnoid haemorrhage · Intracranial aneurysm · the Guidelines Committee of the European Stroke Organiza-
Perimesencephalic subarachnoid haemorrhage · tion reviewed the guidelines. R esults: These guidelines pro-
Management · Guidelines vide evidence-based information on epidemiology, risk fac-
tors and prognosis of SAH and recommendations on diag-
nostic and therapeutic methods of both ruptured and
Abstract unruptured intracranial aneurysms. Several risk factors of an-
Background: Intracranial aneurysm with and without sub- eurysm growth and rupture have been identified. We provide
arachnoid haemorrhage (SAH) is a relevant health problem: recommendations on diagnostic work up, monitoring and
The overall incidence is about 9 per 100,000 with a wide general management (blood pressure, blood glucose, tem-
range, in some countries up to 20 per 100,000. Mortality rate perature, thromboprophylaxis, antiepileptic treatment, use
with conservative treatment within the first months is 50– of steroids). Specific therapeutic interventions consider tim-
60%. About one third of patients left with an untreated aneu- ing of procedures, clipping and coiling. Complications such
rysm will die from recurrent bleeding within 6 months after as hydrocephalus, vasospasm and delayed ischaemic deficit
recovering from the first bleeding. The prognosis is further were covered. We also thought to add recommendations on
influenced by vasospasm, hydrocephalus, delayed ischaemic SAH without aneurysm and on unruptured aneurysms. C on-
deficit and other complications. The aim of these guidelines clusion: Ruptured intracranial aneurysm with a high rate of
is to provide comprehensive recommendations on the man- subsequent complications is a serious disease needing
agement of SAH with and without aneurysm as well as on prompt treatment in centres having high quality of experi-
unruptured intracranial aneurysm. Methods: We performed ence of treatment for these patients. These guidelines pro-
an extensive literature search from 1960 to 2011 using Med- vide practical, evidence-based advice for the management of
line and Embase. Members of the writing group met in per- patients with intracranial aneurysm with or without rupture.
son and by teleconferences to discuss recommendations. Applying these measures can improve the prognosis of SAH.
Search results were graded according to the criteria of the Copyright © 2013 S. Karger AG, Basel
© 2013 S. Karger AG, Basel Prof. Dr. Thorsten Steiner
1015–9770/13/0352–0093$38.00/0 Klinikum Frankfurt Höchst
Fax [phone] Gotenstrasse 6–8
E-Mail [email protected] Accessible online at: DE–65929 Frankfurt (Germany)
www.karger.com www.karger.com/ced E-Mail Thorsten_steiner @ med.uni-heidelberg.de
General Considerations fore, since the neurological condition can change dur-
ing the clinical course after SAH, it is important to have
Introduction a reliable (i.e. high inter- and intra-observer agreement)
and valid (i.e. good relation with outcome) grading sys-
Subarachnoid haemorrhage (SAH) is a relevant tem for unequivocal and understandable documenta-
health problem with an approximate incidence of 9 per tion. Several grading systems, in most cases consisting
100,000 and a mortality rate of about 60% within 6 of approximately 5 categories of severity, have been de-
months. The prognosis is influenced by multiple non- veloped for the initial assessment of SAH patients. A
modifiable factors and by factors that can be influenced still widely used scale is that of Hunt and Hess [ 3] : be-
by therapeutic interventions and management proce- sides the level of consciousness (graded into drowsiness,
dures. International guidelines are only available in the stupor and deep coma), headache (minimal, moderate
United States [ 1]. However, those guidelines mainly deal and severe), neck stiffness (slight nuchal rigidity vs. nu-
with SAH from ruptured aneurysm and there might be chal rigidity) and focal neurological deficits (mild,
some differences in the conception of technical and moderate and severe hemiparesis) constitute this scale.
management aspects and in terms of epidemiology. Due to the unclear definition of the neurological status
Therefore, it is necessary to publish guidelines on the described above, this scale is neither reliable nor valid
management of SAH and unruptured aneurysms from [4]. As grading scales based on the Glasgow Coma Scale
a European standpoint. (GCS) have the advantage of a reasonable inter-observ-
The writing group consists of experts in neurology, er agreement, a committee of the World Federation of
neurosurgery, neuroradiology and neurointensive care Neurological Surgeons (WFNS) proposed a grading
medicine. We performed a literature search including all scale of again five levels, essentially based on the GCS,
available literature using Medline and Embase. Literature with focal deficits making up one extra level for patients
was evaluated and assessed using the predefined criteria with a GCS of 14 or 13 [ 5] . The cut-off points in the
of the European Federation of Neurological Societies [2]. WFNS scale are based on consensus, not on formal
Level of evidence is reported in classes from I to IV. Rec- analysis. Another scale based on the GCS, and assessed
ommendations are rated by levels A–C and GCP (good only retrospectively, performed better than the Hunt
clinical practice). and Hess scale and the WFNS scale [ 6] . For one grading
scale based solely on the GCS, the Prognosis on Admis-
sion of Aneurysmal Subarachnoid Haemorrhage
Definitions – Terminology (PAASH) grading scale, the cut-off points between the
categories were selected by calculating at which point 2
Statement on Definition consecutive categories corresponded to a statistically
• We differentiate ‘ruptured intracranial aneurysm’ (RIA) from
significant different outcome at 6 months [7] . This
‘unruptured intracranial aneurysm’ (UIA); the latter can ei-
PAASH scale has a good internal and external validity
ther be ‘asymptomatic’ or ‘symptomatic’
in regard to clinical outcome [ 8] . In a study comparing
• A symptomatic UIA usually causes brain nerve palsy or rarely
can cause arterial embolism prognostic accuracy, both scales, WFNS and PAASH,
• Asymptomatic UIAs are usually found incidentally (‘inci- had a good prognostic value for patient outcome. How-
dental aneurysm’) because of symptoms unrelated to aneu-
ever, the PAASH scale showed a more gradual increase
rysm (long-term headache, dizziness, etc.) or can be discov-
in the proportionate distribution of patients with poor
ered after SAH as an ‘additional aneurysm’, which is not the
outcome per each increasing PAASH grade than the
bleeding source
WFNS scale and seems, therefore, slightly preferable to
the WFNS scale ( table 1 ) [ 8] .
Clinical Appearance and Grading
Recommendation
• It is recommended that the initial assessment of SAH pa-
In aneurysmal SAH three variables are most closely
tients, and therefore the grading of the clinical condition, is
related to outcome: the neurological condition of the
done by means of a scale based on the GCS
patient on admission, age, and the amount of extrava-
• The PAASH scale performs slightly better than the WFNS
sated blood seen on CT scans. The neurological condi- scale, which has been used more often
tion, particularly the level of consciousness, is the most (class III, level C)
important determinant for outcome after SAH. There-
94 Cerebrovasc Dis 2013;35:93–112 Steiner/Juvela/Unterberg/Jung/Forsting/
DOI: 10.1159/000346087 Rinkel
Table 1. T wo SAH grading scales with criteria per grade and in angiographic and prospective autopsy series is approx-
relation with outcome imately 3–4% [ 11] . Those with a family history of aneu-
rysms have a higher prevalence of 9.5%. More than 90%
Scale Grade Criteria Proportion of OR
of aneurysms are less than 10 mm in diameter and 90%
patients with for poor
poor outcome outcome exist in anterior cerebral circulation.
WFNS I GCS 15 14.8% reference
Statement on Incidence
II GCS 13–14 2.3
• The overall incidence of SAH is 9.1 per 100,000 person-years
no focal deficits 29.4%
in most regions, and is higher in Finland and Japan; in the
III GCS 13–14 6.1
European community that means around 36,000 SAH cases
focal deficits 52.6%
per year
IV GCS 7–12 58.3% 7.7
V GCS 3–6 92.7% 69
Outcome/Prognosis
PAASH I GCS 15 14.8% reference
Data on the natural history of aneurysmal SAH is very
II GCS 11–14 41.3% 3.9
III GCS 8–10 74.4% 16 poor. The most reliable knowledge of the natural history
IV GCS 4–7 84.7% 30 of ruptured saccular intracranial aneurysms has been ob-
V GCS 3 93.9% 84 tained from a study reported by Pakarinen [13] with an
unselected population and few surgical withdrawals [13,
Poor outcome defined as Glasgow outcome scale 1–3 or mod-
14]. Cumulative case fatality rates over time after SAH are
ified Rankin score 4–6. WFNS = World Federation of Neurologi-
as follows: day 1: 25–30%; week 1: 40–45%; first month:
cal Surgeons Grading Scale for Subarachnoid Haemorrhage [5].
PAASH = Prognosis on Admission of Aneurysmal Subarachnoid 50–60%; sixth month: 55–60%; year 1: 65% and year 5
Haemorrhage grading scale [7]. GCS = Glasgow Coma Score [157]. after SAH: 65–70%. Approximately 12% of patients die
Data in this table are adapted from van Heuven et al. [8]. before reaching medical attention [ 15].
If those patients who die before medical attention are
included, 43% of all SAH patients die without recovering
from the initial bleeding [ 13]. Of those, 74% die within
Aneurysmal SAH – Ruptured Aneurysm (RIA) the first 24 h, 7% within 2–3 days, 12% within 4–7 days,
5% within week 2, 1% within week 3, and 1% later than 3
Epidemiology weeks after the initial SAH [ 13].
I f a ruptured aneurysm is left untreated, about one third
Incidence of the patients who recover from the initial haemorrhage
The incidence of SAH varies widely throughout the die because of recurrent bleeding within 6 months after
world. An estimate of 9.1 (95% confidence interval, CI, SAH [ 13, 16]. The cumulative risk of rebleeding by 6 months
8.8–9.5) per 100,000 per year is generally accepted as the after SAH is 50%. Thereafter, the annual risk of rebleeding
overall incidence of SAH worldwide, with the exclusion decreases to 3% during the next 10 years. Two thirds of
of the regionally high incidences in Finland and Japan [ 9] . these late, recurrent bleedings cause death [17–19].
In Finland and Japan incidences of SAH of 15–17 per D espite improvements in surgical and medical treat-
100,000 per year during the CT era and of 22.7 per 100,000 ment, rupture of an aneurysm is still associated with high
per year (95% CI, 21.9–23.5) were reported, respectively rates of case fatality (roughly one third) and of severe dis-
[9–12] . SAH incidence increases linearly with patient age. ability (one sixth) [ 14, 20]. Between 1973 and 2002 case
The median age of onset at the first SAH is 50–60 years. fatality rate decreased by approximately 17% [ 21], and the
Furthermore, the incidence of SAH is approximately 1.6 possibility to recover an independent state has increased
times higher in women than in men, but the predomi- by 1.5% per year [14]. However, data on recovery are based
nance of women is not apparent until the fifth decade only on a few studies with a small number of patients.
[ 9–11] . In general, there is a tendency of reduction in in- Case fatality and functional outcome after SAH are
cidence during later decades [ 9, 10, 12]. determined by the severity of the initial bleeding [ 14, 22,
Intracranial aneurysms in the general population as 23]. Another very important parameter is age, with a tri-
well as in selected populations have been studied in vari- pled case fatality in octogenarians compared with young
ous retrospective and prospective autopsy and angiogra- adults [ 22–26]. Other determinants are aneurysm site
phy studies [ 11]. Among adults, the prevalence appears to [ 24] and size [ 23, 24], history of hypertension [ 22–24],
be 2–5%. Reported frequencies of unruptured aneurysms high systolic blood pressure [ 23] and heavy alcohol con-
Guidelines for Management of Cerebrovasc Dis 2013;35:93–112 95
Intracranial Aneurysms and SAH DOI: 10.1159/000346087
sumption [ 22]. All these factors have been reported inde- predictors for subsequent aneurysm rupture. The ad-
pendently of the severity of SAH to predict outcome. In justed RR of cigarette smoking for aneurysm rupture,
addition, in a large meta-analysis cigarette smoking has tested as a time-dependent covariate, was 3.0 (95% CI,
been reported to increase the risk for delayed cerebral 1.2–7.7) if the patient continued smoking during follow-
ischaemia (DCI) [ 27]. The role of biomarkers for evalua- up [ 42] .
tion has not been studied in large cohorts. Small studies In a prospective follow-up study, cigarette smoking
suggest that catecholamine levels in cerebrospinal fluid and female gender were only significant independent
(CSF) are elevated in patients who experience early mor- factors affecting both aneurysm formation and growth
tality or disability [ 28] . Serum S100 has been associated [ 43] . Women in particular were at higher risk for aneu-
with poor outcome after SAH [ 29]. rysm formation than men, and cigarette smoking has-
After aneurysm rupture, the possibility of poor out- tened aneurysm growth rate. These findings are impor-
come rises because of different factors: (1) disease-associ- tant since aneurysms grow before the rupture. The fast-
ated events (e.g. rebleeding, DCI, hydrocephalus), (2) er the growth, the more likelihood there is of rupture
treatment-associated factors [surgical (clipping) or endo- [ 43] .
vascular (coiling) complications] and (3) complications
associated with prolonged bed rest [14, 22–24, 30]. Aneu- Alcohol Use
rysm rupture itself can cause stress hyperglycaemia, car- The role of alcohol as a risk factor for SAH has not
diopulmonary complications and increased blood coag- been as well established as smoking. Several cohort (RR
ulability, which, independent of severity of bleeding or of >150 g/week, 2.1) and case-control (OR >150 g/week,
metabolic syndrome, may elevate the risk of poor out- 1.5) studies have shown that excessive alcohol consump-
come [ 25, 30–32]. Outcome after SAH is thus probably tion increases the risk for SAH in both men and women,
determined by multiple independent factors. independently of cigarette smoking, age, and history of
There are not many data on health-related quality of hypertension [ 34–38]. In the study from Ruigrok et al.
life (HRQoL) after SAH. HRQoL may be remarkably re- [ 39], drinking more than 300 g/week of alcohol attrib-
duced in patients with SAH compared to the normal pop- uted to 20% of instances of SAH in the population, and
ulation. Female gender, severe SAH, functional disability, drinking 100–299 g/week accounted for 11% of cases of
depression, lower level of education and the lack of a sta- SAH [ 36, 39].
ble partnership were found to be independent predictors
of HRQoL [33]. Hypertension
History of hypertension as a risk factor for SAH (RR,
Risk Factors 2.5; OR, 2.6) seems to be less crucial than for other
Risk Factors can be divided into risk factors for SAH, stroke subtypes [ 34–38]. The prevalence of hyperten-
aneurysm formation and aneurysm growth. sion among SAH patients (20–45%) is somewhat higher
Independent modifiable risk factors for SAH seem to than in the general population; after adjustment for age,
be only cigarette smoking, excessive alcohol consump- gender, cigarette smoking and alcohol consumption,
tion and hypertension (class III evidence) [ 34–36]. history of hypertension has not been shown to signifi-
cantly increase the risk for SAH, as demonstrated in 2
Cigarette Smoking case-control studies [36, 38]. However, combining all
Cigarette smoking is an independent and the most im- cohort and case-control studies, hypertension still was
portant risk factor for SAH, which has already been an important risk factor [ 34].
proved in several cohort (relative risk, RR of current In a long-term cohort study, patients with hyperten-
smoking, 2.2) and case-control studies (odds ratio, OR, sion did not have de novo aneurysms or aneurysm growth
3.1) all over the world [ 34–38]. In North America and Eu- more often than non-hypertensive patients, nor did blood
rope, the prevalence of smoking in SAH patients ranges pressure values during follow-up correlate with aneu-
from 45 to 75% whereas in the general adult population rysm formation or growth [ 43] . However, patients who
it is 20–35%. Of SAH cases, 40% can be attributed to cig- had used antihypertensive medication may have de-
arette smoking [ 35–39]. creased risk for aneurysm formation [43] . On the other
After diagnosis of an unruptured aneurysm, the size hand, in another long-term follow-up study hypertension
of aneurysm [ 40–42], and possibly location [41], age in- at the time of the initial SAH was a risk factor for de novo
versely [ 42] and cigarette smoking [ 42] are independent aneurysm formation [ 44].
96 Cerebrovasc Dis 2013;35:93–112 Steiner/Juvela/Unterberg/Jung/Forsting/
DOI: 10.1159/000346087 Rinkel
Statement independent of cigarette smoking and hypertension risk
• Hypertension can be considered to be an important risk factor factors for SAH [ 58].
for SAH and possibly for aneurysm formation and fatal aneu-
The annual rate of new (de novo) aneurysm formation
rysm rupture
was 0.6–0.9% in patients with a treated ruptured aneu-
• Cigarette smoking is the most important modifiable risk fac-
tor for aneurysm formation, growth and rupture, and should rysm [ 43, 59, 60]. These angiographic follow-up studies
be discouraged were done for all survivors and not only for those with a
• Alcohol abuse and particularly sudden intake of high quanti- later new SAH, as this kind of patient selection errone-
ties is a risk factor for aneurysm rupture and should be de-
ously would have increased this formation rate. Women
sisted
and cigarette smokers had independently increased risk
(class III, level C)
(OR, 4–5) for de novo aneurysm formation [ 43] . De novo
Family History aneurysms developed during a mean follow-up time of
Recently, family history of intracranial aneurysms has 19 years, a follow-up period not differing significantly
been suggested to be evidence for genetic causality of ce- from that of those without de novo aneurysms. In cases
rebral aneurysms [ 35, 45–47]. However, cigarette smok- where a de novo aneurysm caused SAH, the follow-up
ing and other health-related habits should be analysed as time was somewhat shorter (14.7 ± 8.1 years; range, 3.4–
a confounding factor for this association since correlation 28.4 years) [43] .
of these habits between family members is higher than in MR angiography (MRA) follow-up of 610 patients
the general population [45, 48]. Smoking and alcohol in- with a mean follow-up of 9 years after SAH revealed a
take habits may even to some degree be influenced by cumulative 16% chance of finding a new aneurysm [44] .
genetic factors [ 48] . Part of the familial preponderance In this study, risk factors for aneurysm formation and
may also be attributed to familial occurrence of hyper- growth were the presence of multiple aneurysms at time
tension [ 49, 50]. of SAH (hazard ratio, HR, 3.2; 95% CI, 1.2–8.6), current
Less than 10% of SAH can be attributed to first-degree smoking (HR, 3.8; 95% CI, 1.5–9.4) and hypertension
relatives only [ 35, 39, 45], and 5–8% to first or second- (HR, 2.3; 95% CI, 1.1–4.9).
degree relatives [ 35, 45] . Also, many studies show that Of 752 SAH patients with 6,016 follow-up years (mean
around 10% of patients with SAH have a family history. follow-up 8.0 years), 18 had a recurrence of SAH. In the
The chance of finding an aneurysm at screening is around first 10 years after the initial SAH, the cumulative inci-
10% if 2 or more first-degree relatives are affected [51–57]. dence of recurrent SAH was 3.2% (95% CI, 1.5–4.9%) and
A family history of polycystic kidney disease seems to the incidence rate was 286 of 100,000 patient-years (95%
increase the risk of SAH [11] . CI, 160–472 per 100,000). Risk factors were smoking
(HR, 6.5; 95% CI, 1.7–24.0), age (HR, 0.5 per 10 years; 95%
Recommendation CI, 0.3–0.8) and multiple aneurysms at the time of the
• Screening should in general not be advised in the case of only
initial SAH (HR, 5.5; 95% CI, 2.2–14.1). Thus, after SAH,
1 affected first-degree relative
the incidence of a recurrence within the first 10 years is
• If 2 or more first-degree relatives are affected, the lifetime risk
22 (12–38) times higher than expected in populations
of SAH in the other relatives is considerable, and screening
should be considered with comparable age and sex. Whether this increased
(class III, level C) risk justifies screening for recurrent aneurysms in pa-
tients with a history of SAH requires further study [ 44,
Other Risk Factors 60].
Besides the above-mentioned risk factors many other
factors have been implicated in the pathogenesis of sac- Statement on Risk Factor
• Risk factors for SAH can be divided into risk factors for aneu-
cular aneurysms and SAH. Of these, non-white ethnic-
rysm formation, aneurysm growth and rupture
ity has been associated with increased risk for SAH,
• The most important modifiable risk factors for SAH: cigarette
while hormone replacement therapy among women, hy-
smoking, hypertension and excessive alcohol intake, and non-
percholesterolemia, and diabetes mellitus may reduce modifiable risk factors: sex, age, size of aneurysm and family
this risk [ 34]. According to a recent systematic review, history
• Risk factors for de novo formation of aneurysms: female sex,
the use of oral contraceptives does not seem to affect
current cigarette smoking, hypertension, age (at diagnosis)
SAH risk, and the significance of low body mass index
and family history
or rigorous exercise seems inconsistent [34]. Of these,
• Risk factors for aneurysm growth: current cigarette smoking
low serum total cholesterol and triglyceride levels may be
Guidelines for Management of Cerebrovasc Dis 2013;35:93–112 97
Intracranial Aneurysms and SAH DOI: 10.1159/000346087
Diagnosis Recommendation for Diagnosis
• CT/CTA and MRI with multiple sequences are equally suit-
able for the diagnosis of SAH within 24 h (class II, level B)
Subarachnoid blood is almost always detectable on CT
• CT/CTA and multisequential MRI/MRA may confirm the
scans on the first day of SAH with its typical distribution
underlying cause
in the subarachnoid space/basal cisterns. Therefore, if • Lumbar puncture must be performed in a case of clinically
SAH is clinically suspected a cranial CT should be per- suspected SAH if CT or MRI does not confirm the diagnosis
formed to confirm the diagnosis. Modern CT technology (class II, level B); however, within the first 6–12 h the differ-
entiation between genuine subarachnoidal blood and trau-
provides a sensitive method to detect subarachnoid blood
matic admixture of blood may be difficult
in the early phase after SAH. However, sensitivity of CT
• DSA of all cerebral arteries should be performed if a bleeding
decreases with resorption and redistribution of sub- source was not found on CTA and the patient has a typical
arachnoid blood over the time course after the initial basal SAH pattern on CT (class II, level B)
SAH: 5 days after the initial bleeding SAH is detectable • If no aneurysm was found, CTA or DSA should be repeated
as described below: SAH without aneurysm (class III, level C)
in about 85% of cases and after 2 weeks in under 30% of
SAH cases. MRI with Flair technology seems comparable
with CT in the acute phase of SAH [61]. In the weeks fol- Treatment
lowing SAH, MRI is clearly superior to CT [ 62] and re-
veals a reliable tool in the follow-up of endovascular- General Medical Management
treated aneurysms. After surgical treatment (clipping) of Monitoring and Physical Management
aneurysms MRI is of reduced value due to metal arte- Recommendations for monitoring and general man-
facts. In the case of anamnestically or clinically suspected agement are summarized in table 2. Patients should be
SAH, despite negative/inconspicuous CT and/or MRI under continuous observation in an intensive care unit,
scans, a lumbar puncture has to be performed. Water- or in an intermediate care facility of a stroke or neurovas-
clear, normal CSF excludes SAH within the last 2–3 cular unit [ 67]. Staff in this unit should have ample expe-
weeks. In the case of bloody CSF a traumatic tap must be rience in assessing swallowing function to prevent pneu-
kept in mind. More assuring than bloody CSF but not monia, a frequent complication after SAH and indepen-
specific is the detection of xanthochromia caused by deg- dent risk factor for poor outcome [ 68] . ECG, level of
radation of blood. As blood degradation takes some consciousness (GCS), focal deficits, temperature and pu-
hours, lumbar puncture is recommended 6–12 h after the pils should be monitored frequently for at least the first 7
initial SAH. days after SAH, or longer as required depending on the
Cerebral panangiography continues to be the gold patient’s clinical condition. A urinary catheter is advised
standard for detection, demonstration and localization of in all patients as well as a calculated fluid balance every 6
ruptured aneurysms. Complication rate of this invasive h during the initial week. In the intensive care unit, blood
diagnostic procedure is below 0.5% in experienced cen- pressure is monitored continuously via an arterial line.
tres [63] . Further less invasive methods are MRA and CT Patients in a good clinical condition in whom the aneu-
angiography (CTA) [ 62, 63]. MRA is a secure procedure, rysm has been secured may be transferred to a regular
which was reported to be less sensitive than digital sub- care bed in the stroke unit.
traction angiography (DSA, conventional angiography) Headache can sometimes be managed with just mild
and less feasible in agitated patients or those who require analgesics such as paracetamol (acetaminophen); salicy-
monitoring during the acute phase after SAH. CTA is less lates are best avoided because their antihaemostatic effect
time consuming than MRA. Sensitivity and specificity of is unwanted in patients who may have to undergo exter-
CTA detecting cerebral aneurysms are described to be nal ventricular drainage and interferes with possibly
0.77–0.97 and 0.87–1.00, respectively. However, sensitiv- pending neurosurgical interventions. In practice, the
ity decreases with aneurysm size: for small aneurysms pain is usually so severe that codeine and even a synthet-
(<3 mm) CTA sensitivity ranges around 0.4–0.9. A simi- ic opiate might be needed.
lar loss of sensitivity is reported and observed in MRA
[ 64, 65]. In the context of further prospective improve- Statement on Physical Management
• To avoid situations that increase intracranial pressure, the pa-
ment of CTA and MRA technology a decrease in DSA is
tient should be kept in bed and the application of antiemetic
anticipated. Recently, Agid et al. [66] showed that CTA in
drugs, laxatives and analgetics should be considered before
patients with a specific CT pattern of subarachnoid blood
occlusion of the aneurysm (GCP)
distribution is as good as DSA.
98 Cerebrovasc Dis 2013;35:93–112 Steiner/Juvela/Unterberg/Jung/Forsting/
DOI: 10.1159/000346087 Rinkel
Glucose Table 2. Recommendations for monitoring and general manage-
Hyperglycaemia develops in one third of SAH pa- ment of patients with aneurysmal SAH
tients. Hyperglycaemia is associated with poor clinical
Monitoring
condition on admission, and is independently associated
– Intensive continuous observation at least until occlusion of
with poor outcome [ 25, 30, 31, 69] . Whether correction of
the aneurysm
hyperglycaemia results in improved outcome remains – Continuous ECG monitoring
unclear. In a small trial comparing intensive versus con- – Start with GCS, focal deficits, blood pressure and tempera-
ture at least every hour
ventional insulin therapy, intensive therapy reduced in-
fection rate during the initial 14 days after admission. Blood pressure
However, the trial was too small to detect differences in – Stop antihypertensive medication that the patient was using
– Do not treat hypertension unless it is extreme; limits for ex-
clinical outcome [ 70] (class III, level C).
treme blood pressures should be set on an individual basis,
taking into account age of the patient, pre-SAH blood pres-
Recommendation for Blood Glucose Management
sures and cardiac history; systolic blood pressure should be
• Hyperglycemia over 10 mmol/l should be treated (GCP)
kept below 180 mm Hg, only until coiling or clipping of rup-
tured aneurysm, to reduce risk for rebleeding
Temperature Fluids and electrolytes
Despite treatment with paracetamol to relieve pain, – Intravenous line mandatory
fever develops in more than half of all SAH patients [ 71] , – Insert an indwelling urinary catheter
– Start with 3 litre/day (isotonic saline, 0.9%), and adjust infu-
predominantly in those with poor clinical condition on
sion for oral intake
admission and in those with intraventricular extension
– Aim for normovolaemia also in case of hyponatraemia and
of the haemorrhage [71]. Furthermore, fever is an inde- compensate for fever
pendent risk factor for poor outcome [69]. In around 20% – Monitor electrolytes, glucose and white blood cell count at
of patients no infection is found, and fever is attributed least every other day
to inflammatory responses to extravasated blood in the Pain
subarachnoid space. There are neither controlled studies – Start with paracetamol (acetaminophen) 500 mg every 3–4 h;
on the effect of cooling in SAH patients nor studies that avoid aspirin before aneurysm occlusion
– For severe pain, use codeine, tramadol (suppository or i.v.) or,
have shown that treatment of fever does improve out-
as a last resort, piritramide (i.m. or i.v.)
come. A randomized trial of mild hypothermia (33 ° C)

Prevention of deep venous thrombosis and pulmonary embolism
during aneurysm surgery after SAH showed no benefit
– Compression stockings and intermittent compression by
[72].
pneumatic devices in high-risk patients
Recommendation for Temperature Management
• Increased temperature should be treated medically and phys-
ically (GCP)
pressure if the systolic pressure exceeds 180 mm Hg, for
example by means of esmolol or labetolol [74] ; it seems
Arterial Blood Pressure reasonable to aim for a modest (e.g. 25%) decrease in
The treatment of high blood pressure after SAH re- mean arterial pressure.
mains controversial because of lack of evidence from
randomized trials. Data from observational studies sug- Recommendation for Blood Pressure Management
• Until coiling or clipping, systolic blood pressure should be
gest that aggressive treatment of blood pressure may de-
kept below 180 mm Hg; this may be already achieved by
crease the risk of rebleeding but at the cost of an in-
applying analgetics and nimodipine (GCP)
creased risk of secondary ischaemia [73]. It seems rea-
• If systolic pressure remains high despite these treatments fur-
sonable, but without good evidence, to stop any ther lowering of blood pressure should be considered (class
antihypertensive medication that the patients were us- IV, level C)
• If blood pressure is lowered the mean arterial pressure should
ing and not to treat hypertension unless the blood pres-
be kept at least above 90 mm Hg (GCP)
sure is extreme. It is not possible to give limits for ‘ex-
treme’ blood pressures, because ‘extreme’ differs in dif-
ferent patients according to their age, previous blood Thromboprophylaxis
pressure, cardiac history and other factors. If the aneu- In a placebo-controlled trial of enoxaparin (a low-mo-
rysm is not yet secured it seems prudent to treat blood lecular-weight heparin) administered subcutaneously 40
Guidelines for Management of Cerebrovasc Dis 2013;35:93–112 99
Intracranial Aneurysms and SAH DOI: 10.1159/000346087
mg once a day after surgical aneurysm occlusion, intra- matose SAH patients, only 1 patient temporarily improved
cranial bleeding complications occurred somewhat more after antiepileptic treatment, and all 8 patients eventually
often in the enoxaparin group while there was no overall died [ 84] . Since prolonged EEG recording is expensive, la-
influence on outcome or appearance of post-SAH cere- bour intensive, subject to misinterpretation [86], and lacks
bral infarction [ 75, 76]. Enoxaparin also increased the in- proof of effectiveness, there are no grounds to use it as part
cidence of postoperative intracranial haemorrhage when of the routine monitoring strategy in patients with SAH.
initiated pre-operatively for deep venous thrombosis pro- Predictive factors for epileptic seizures have not been
phylaxis in patients with brain tumours [ 77]. identified. Intracranial surgery increases the risk [ 87], but
Because of this increased risk of intracranial bleeding a randomized trial of antiepileptic drugs after supratento-
from thromboprophylaxis by means of low-molecular- rial craniotomy for benign lesions (not only aneurysms) in
weight heparins, the use of stockings or pneumatic de- 276 patients failed to show benefit in terms of seizure rate
vices seems more appropriate in SAH patients. A study or case fatality, although the CIs were wide [ 88]. Also, an
with non-randomized controls suggested that deep vein observational study performed on 3,552 patients partici-
thrombosis can be successfully prevented by the use of pating in 4 prospective, randomized, double-blind, place-
pneumatic devices [ 78]. A Cochrane review on the use of bo-controlled trials suggested that outcome was worse in
graduated compression stockings or intermittent pneu- the 65% of patients receiving prophylactic antiepileptic
matic compression in patients with stroke did not find drugs than in the other 35% of patients who did not receive
support for the use of either method [79]. In a randomized prophylactic antiepileptic medication [ 89]. Given the lack
trial in patients with intracerebral haemorrhage (ICH), of evidence in favour of prophylactic treatment with anti-
the combination of stockings and intermittent pneumatic epileptic drugs and the possible disadvantage of serious
compression resulted in a smaller risk of deep venous adverse drug reactions, the current advice should be not to
thrombosis than prevention by stockings alone [ 80]. This start antiepileptic drugs as prophylactic treatment.
combination may be the preferred strategy because there
is no reason to suppose that this effect would be any dif- Recommendation for Seizure Management
• Antiepileptic treatment should be administered in patients
ferent in patients with SAH, but it needs further study.
with clinically apparent seizures (GCP)
• There is no evidence that supports the prophylactic use of an-
Recommendation for Thromboprophylaxis
tiepileptic drugs (class IV, level C)
• Patients with SAH may be given thromboprophylaxis with
pneumatic devices and/or compression stockings before oc-
Steroids
clusion of the aneurysm (class II, level B)
A Cochrane review last updated in 2005 found 1 pla-
• In case deep vein thrombosis prevention is indicated, low-
molecular-weight heparin should be applied not earlier than cebo-controlled trial on hydrocortisone in patients with
12 h after surgical occlusion of the aneurysm and immedi- SAH [ 90]. There was no difference in clinical outcome
ately after coiling (class II, level B)
between patients with secondary ischaemia treated with
hydrocortisone and those treated with placebo, but the
Antiepileptic Treatment risk of hyperglycaemia almost doubled [ 90]. A random-
Seizures at onset occur in around 7% of patients, but ized trial published after the Cochrane review showed
their impact on prognosis is uncertain [ 81]. Another 10% that in patients treated with hydrocortisone, serum so-
develop seizures in the first few weeks [82], and convulsive dium level and plasma osmolarity were controlled better
status epilepticus occurs in 0.2% [ 83]. In patients who are than in controls, but clinical outcome was not better [ 91] .
comatose, non-convulsive status epilepticus has been de- Based on these studies, routine hydrocortisone for pa-
tected in 8% of patients [ 84] , but the proportion in this tients with SAH is not warranted.
study might be an overestimation due to selection of EEG
by indication. Whether continuous EEG monitoring Statement on the Use of Steroids
• There is no proof that steroids are effective in patients with
should be performed in all SAH patients or in the subset
SAH (class IV, level C)
that is comatose is an unresolved issue. In 1 retrospective
study continuous EEG monitoring had additional prog-
nostic information for poor outcome [ 85], but there are no Specific Prevention of Rebleeding
data that outcome is improved by continuous EEG moni- General Considerations – Timing
toring. Of all 8 instances of non-convulsive status epilep- Up to 15% of patients rebleed during the first few hours
ticus detected by continuous EEG monitoring in 101 co- after the initial haemorrhage [ 92] , that is, during trans-
100 Cerebrovasc Dis 2013;35:93–112 Steiner/Juvela/Unterberg/Jung/Forsting/
DOI: 10.1159/000346087 Rinkel
portation or before the treatment team is able to occlude ping and wrapping as sole therapeutic approaches are an-
the aneurysm. Patients surviving the first day after the tiquated, both methods are exceptionally used in combi-
initial SAH have a cumulative risk of 35–40% to suffer nation with other surgical techniques such as aneurysm
rebleeding of the aneurysm with a mortality rate of about clipping and/or bypass surgery. Since the development of
40%. After 4 weeks the risk of rebleeding decreases to aneurysm clips, risk of rebleeding significantly decreased.
about 3%/year [93]. With the establishment of microsurgery, surgical ap-
The primary goal of the treatment of aneurysmal SAH proaches became smaller and less traumatizing. Further-
is the occlusion of the ruptured aneurysm, i.e. to close the more, intra-operative indocyanine green angiography
bleeding source preventing a rebleeding. For this, two and Doppler sonography lead to extra intra-operative
major treatment options are available: neurosurgical clip- quality control [ 96]. After the invention of detectable
ping and endovascular coiling. A meta-analysis of 11 out platinum coils by G. Guglielmi in 1990, an alternative to
of 268 studies with a total of 1,814 patients revealed in a surgical clipping developed.
comparative evaluation of early versus late surgical clip-
ping of ruptured aneurysms that early treatment (within Clip versus Coil
72 h after SAH) of patients with a good clinical/neuro- To compare both therapeutic approaches, clipping and
logical condition on admission (WFNS 1–3) leads to a coiling, factors including morbidity, mortality, complete
significantly better outcome. A similar trend, without and durable occlusion of the aneurysm, rebleeding (intra-
statistical significance, could be detected in patients with and postprocedural aneurysm rupture) and others have
worse WFNS grades of 4–5 [ 94]. Even earlier treatment to be evaluated: The International Subarachnoid Aneu-
(within 12 h) of SAH patients with WFNS grades IV and rysm Trial (ISAT) was a randomized controlled trial that
V did not increase the number of dependent survivors compared clipping and coiling (without balloon or stent
[ 95] . Although there are no good evidence-based data, a techniques) [ 87, 97]. The ISAT study followed the ‘uncer-
general long-lasting consensus exists that ruptured aneu- tainty principle’. The main inclusion criterion of ISAT
rysms of patients with good and moderate clinical SAH was that an RIA seemed equally accessible and treatable
grades (WFNS 1–4; Hunt and Hess grade I–IV) should be by either surgical clipping or endovascular coiling (‘clin-
treated in the early phase after the initial bleeding (<72 h ical equipoise’). This inclusion criterion was met by 22.4%
after SAH). In patients presenting with multiple intracra- of patients (2,143 of 9,559 patients) with RIAs treated dur-
nial aneurysms, i.e. with one ruptured aneurysm causing ing the study period at the study centres. The remaining
SAH and several unruptured incidental aneurysms, the 77.6% of patients suffered from aneurysms which were
ruptured aneurysm is primarily treated. Subsequent preferably treated by either coiling or clipping. Those pa-
treatment of the unruptured incidental aneurysms de- tients were not randomized and were excluded from the
pends on clinical course after SAH, outcome, age, size, study. Besides a highly selected patient cohort, ISAT was
location and configuration of the aneurysm. also criticized for its high (90%) proportion of patients
with good clinical grades after SAH (Hunt and Hess
Recommendation for Timing of Intervention grades 1–2) and underrepresentation of middle cerebral
• Aneurysm should be treated as early as logistically and tech-
artery aneurysms, which are often anatomically more
nically possible to reduce the risk of rebleeding; if possible it
difficult to be coiled than aneurysms in other locations.
should be aimed to intervene at least within 72 h after onset
However, for this subpopulation of ruptured aneurysms,
of first symptoms
• This decision should not depend on grading which were equally coilable or clippable, ISAT showed
(class III, level C) that endovascular coiling had an advantage over surgical
clipping, with better clinical outcome: absolute risk re-
Neurosurgical Clipping and Endovascular Coiling of duction of death and severe disability after 1 year was
Ruptured Aneurysm 6.9% in favour of coiling versus clipping, based on the
In the early beginnings of cerebral aneurysm treat- observation that 23.7% of endovascular-treated patients
ment, surgery was the only approach for RIAs. Starting (compared to 30.6% of patients after clipping) stayed se-
with proximal ligation of vessels (trapping) like the ca- verely disabled or died after 1 year [ 97] . The 9-year follow-
rotid artery and followed by wrapping of the aneurysm up of ISAT also revealed a reduction in the relative 5-year
with muscle tissue to strengthen the aneurysm wall to mortality risk in favour of coiling. No difference could be
prevent rebleeding, surgical aneurysm treatment is now- observed in the amount of independent SAH survivors
adays based on clip occlusion (clipping). Although trap- between the clip (82%) and coil group (83%). Both early
Guidelines for Management of Cerebrovasc Dis 2013;35:93–112 101
Intracranial Aneurysms and SAH DOI: 10.1159/000346087
as well as follow-up ISAT analysis showed that patients Summarizing the current studies, ruptured aneu-
treated with coiling had a higher rebleeding risk, which rysms are complex lesions. The primary goal of treatment
was comparable to the risk of suffering SAH from a new should be a complete occlusion of the aneurysm sack to
aneurysm [ 97, 98]. The postoperative risk of rebleeding reduce postprocedural rerupture and bleeding. In the
appears to be associated with the degree of insufficient case of aneurysms which can be treated equally with clip-
aneurysm occlusion. Another follow-up study of the pa- ping or coiling, without stent or balloon (clinical equi-
tients treated in the ISAT was performed to compare the poise), endovascular therapy is preferred. However, indi-
frequency and consequences of aneurysm recurrence. cations and treatments should be discussed in an inter-
Retreatment was performed in 17.4% of patients after pri- disciplinary dialogue. In the case of an accompanying
mary endovascular coiling and in 3.8% of patients after space occupying intracerebral hematoma, surgical treat-
neurosurgical clipping. Late retreatment was 6.9 times ment and clipping is favoured.
more likely after coiling. Younger age, larger lumen size, As a rough guidance, aneurysms with a wide neck,
and incomplete occlusion were risk factors for late re- branching vessels out of the aneurysm sack, middle ce-
treatment after coiling [ 99] . A post hoc modelling study rebral artery aneurysms or patients with intracerebral
with mortality as outcome parameter only after coiling hematoma should preferably be treated by clipping,
and clipping for patients from the ISAT emphasized that while aneurysms of the basilar artery or elderly pa-
no advantage of coil embolization over clip ligation can tients (patients >70 years, small aneurysm neck, poste-
be assumed for patients younger than 40 years. For these rior circulation) should be coiled (level B) [ 104] . Any
patients clipping might even be the better treatment op- decision concerning treatment should be interdisci-
tion in terms of life expectancy [100]. plinary and based on the experience and treatment re-
Because of the highly selected aneurysm subpopula- sults of the neurosurgeon and endovascular radiolo-
tion in ISAT, ISAT results cannot be generalized. Recent gist, and should be adapted to the individual aspects
studies, which consider increasing endovascular treat- including parameters such as age, general state of
ment during the last years, could not detect any differ- health, location, configuration and size of the aneu-
ence in mortality and morbidity between coiling and rysm, as well as the request of the patient. RIAs should
clipping [101, 102]. be treated in centres that offer high-quality treatment
The Cerebral Aneurysm Rerupture after Treatment with both modalities.
(CARAT) trial was a non-randomized trial that included
1,010 patients with SAH from 1996 to 1998 and followed Recommendation for Interventional Prevention of Rebleeding
• The best mode of intervention should be discussed in an in-
them up in 2005. Coiling was applied in 299 and clipping
terdisciplinary dialogue between Neurosurgery and Neuro-
in 711 patients. After a mean observation period of 4
radiology
years it turned out that the degree of aneurysm occlusion
• Based on this discussion patients should be informed and in-
after treatment was strongly associated with risk of re- cluded in the process of decision making whenever possible
rupture. The overall risk of rerupture tended to be great- • In cases where the aneurysm appears to be equally effectively
treated either by coiling or clipping, coiling is the preferred
er after coil embolization compared with surgical clip-
treatment (class I, level A)
ping, but the difference did not persist after adjustment
• In general, the decision on whether to clip or coil depends on
[103]. Intraprocedural aneurysm rupture and bleeding is
several factors related to 3 major components:
common in patients undergoing treatment of RIAs. In (1) Patient: age, comorbidity, presence of ICH, SAH grade,
the CARAT study patient collective the intraprocedural aneurysm size, location and configuration, as well as on
status of collaterals (class III, level B)
rupture rate was 5% with endovascular and 19% with sur-
(2) Procedure: competence, technical skills and availability
gical treatment. The risk of intraprocedural rupture-as-
(class III, level B)
sociated death/disability was doubled in the endovascu-
(3) Logistics: the grade of interdisciplinarity (class III, level B)
lar group (63% coiling vs. 31% clipping) [ 104]. In patients with aneurysmal SAH:
Further results from 2 randomized trials which re- • Factors in favour of operative intervention (clipping) are:
younger age, presence of space occupying ICH (class II, level
cently stopped recruitment are awaited: the HELPS study
B), and aneurysm-specific factors such as:
(HydroCoil Endovascular Aneurysm Occlusion and
– location: middle cerebral artery and pericallosal aneu-
Packing study) [105], comparing hydrogel-coated coils rysm (class III, level B)
with standard platinum coils and the Cerecyte Coil study – wide aneurysm neck (class III, level B)
[ 106], which compares polymer-coated coils with stan- – arterial branches exiting directly out of the aneurysmal
sack (class III, level B)
dard platinum coils.
102 Cerebrovasc Dis 2013;35:93–112 Steiner/Juvela/Unterberg/Jung/Forsting/
DOI: 10.1159/000346087 Rinkel