Subarachnoid haemorrhage (spontaneous aneurysmal)

Abstract

Introduction

Subarachnoid haemorrhage (SAH) may arise spontaneously or as a result of trauma. Spontaneous SAH accounts for about 5% of all strokes. Ruptured aneurysms are the cause of 85% of spontaneous SAH. The most characteristic clinical feature is sudden-onset severe headache. Other features include vomiting, photophobia, and focal neurological deficit or seizures, or both. As the headache may have insidious onset in some cases, or may even be absent, a high degree of suspicion is required to diagnose SAH with less typical presentations.

Methods and outcomes

We conducted a systematic review, aiming to answer the following clinical question: What are the effects of surgical treatments for people with confirmed aSAH? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2014 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review).

Results

At this update, searching of electronic databases retrieved 82 studies. After deduplication and removal of conference abstracts, 47 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 33 studies and the further review of 14 full publications. Of the 14 full articles evaluated, one systematic review, one RCT, and four further reports were added at this update. We performed a GRADE evaluation for six PICO combinations.

Conclusions

In this systematic overview, we categorised the efficacy for one comparison based on information about the effectiveness and safety of endovascular coiling versus surgical clipping.

Key Points

Subarachnoid haemorrhage (SAH) may arise spontaneously or as a result of trauma. Spontaneous SAH accounts for about 5% of all strokes. Ruptured aneurysms are the cause of 85% of spontaneous SAH. This overview deals with only spontaneous aneurysmal SAH (aSAH).

• Without treatment, mortality rates of about 50% at 1 month after spontaneous aSAH have been reported.

Treatment is aimed at prevention of re-bleeding from the same aneurysm. This can be performed by endovascular coiling or by surgical clipping.

• In people suitable for either procedure, endovascular coiling has lower rates of poor functional outcome compared with surgical clipping, but it is also associated with increased rate of recurrent haemorrhage from the treated aneurysm and a higher rate of re-treatment for the same aneurysm. Most evidence is in small (<11 mm) aneurysms of the anterior circulation. Therefore, the conclusions cannot be applied to all aneurysms (particularly large and giant aneurysms and aneurysms with broad necks).

• Factors that should be considered when deciding on the method of treatment include the morphology and anatomical location of the aneurysm, the age and clinical condition of the person, and the presence or absence of a space-occupying intracranial haematoma.

Clinical context

General background

Aneurysmal subarachnoid haemorrhage (aSAH) is a neurosurgical emergency that comes with high morbidity and mortality. Accurate and timely diagnosis is imperative, along with the management of intra-cranial complications such as vasospasm/delayed ischaemic neurological deficit, hydrocephalus, seizure disorder, as well as extra-cranial complications such as cardiac abnormalities or neurogenic pulmonary oedema. The prevalence of unruptured aneurysms is 2% to 4%. Only a proportion of these rupture. Annual worldwide incidence of aSAH has been reported to be approximately 9 per 100,000 person/years; 10% of aSAH patients die before hospital, 25% die in the first 24 hours, and 40% to 50% die within the first 30 days. Of those who survive, up to 20% can be dependent on others for activities of daily living due to neurological deficits or cognitive impairment. Other sequela of aSAH that have major implications for patients is neuropsychological outcomes such as depression. There are two treatment approaches: open transcranial surgery, which primarily involves clipping of the aneurysm via performing a craniotomy and navigating through the cisterns and natural subarachnoid corridors of the brain to reach the aneurysm, at which point a metallic clip is applied to the exterior of the aneurysm to occlude it.; and endovascular treatment, which primarily involves coiling of the aneurysm via an arterial puncture (usually femoral).

Focus of the review

Until recently, surgical clipping of aneurysms has been the gold standard treatment. With advancement in neuro-interventional techniques and technology, this minimally invasive procedure offers an alternative treatment option for most aneurysms. Therefore, we focused this update on a comparison of these surgical treatments.

Comments on evidence

Neuro-interventional techniques and technology is advancing at a rapid pace and any evidence quoted here must be put in context of the date of publication against the timeline of evolution of this field.

Search and appraisal summary

The update literature search for this overview was carried out from the date of the last search, March 2009, to October 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the review, please see the Methods section. Searching of electronic databases retrieved 82 studies. After deduplication and removal of conference abstracts, 47 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 33 studies and the further review of 14 full publications. Of the 14 full articles evaluated, one systematic review, one RCT, and four further reports were added at this update.

About this condition

Definition

Subarachnoid haemorrhage (SAH) is a type of haemorrhagic stroke in which there is bleeding into the subarachnoid space. It can be subdivided into traumatic SAH and spontaneous (non-traumatic) SAH. Spontaneous SAH is further subdivided into aneurysmal and non-aneurysmal types. This overview deals only with spontaneous aneurysmal SAH (aSAH). Diagnosis The most characteristic clinical feature is sudden-onset severe headache. Other features include vomiting, photophobia, neck stiffness, impaired level of consciousness, acute confusional state, agitation/restlessness, and focal neurological deficit or seizures, or both. As the headache may have insidious onset in some cases, or may even be absent, a high degree of suspicion is required to diagnose SAH with these less-typical presentations. Examination findings may include a reduced level of consciousness, confusion/agitation, nuchal rigidity, retinal haemorrhage, or focal neurological signs (e.g., cranial nerve palsies and hemiplegia). When SAH is suspected, an unenhanced CT scan of the head should be obtained as soon as possible. However, CT scan does not always identify the haemorrhage, and the false-negative rate increases with time after the bleed. In a prospective observational study of 3451 people with confirmed SAH, 3% (51/1553) had a normal CT scan within 24 hours of ictus.[1] By day 5, 27% (9/33) had a normal CT scan.[1] Even if the CT scan is done within 12 hours of ictus, 2% (95% CI 0.2 to 6) of people have a normal scan.[2] Therefore, a lumbar puncture should be performed in anyone with suspected SAH and a normal CT scan. CSF findings in SAH may include elevated opening pressure, uniformly blood-stained CSF across all tubes, excess red blood cell count, and elevated protein or lymphocytic cellular reaction, or both. However, to differentiate genuine SAH from a traumatic tap (blood introduced into the needle at the time of lumbar puncture), CSF must be analysed for presence of xanthochromia (yellow discoloration of supernatant after centrifugation of CSF, caused by the presence of bilirubin). It has been recommended that the lumbar puncture should be delayed until 12 hours after the onset of symptoms (unless meningitis is suspected) to allow sufficient time for haemoglobin to degrade into oxyhaemoglobin and bilirubin. Earlier sampling may produce false-negative results.[3] The colour of the supernatant should be compared with water against a white background, in bright light. Yellow discoloration of the supernatant (xanthochromia) indicates SAH. To reduce the subjectivity of this test, it has been recommended that CSF should, in all cases, be examined for bilirubin and oxyhaemoglobin using spectrophotometry, rather than by visual inspection alone.[3] In a study of 111 people with CT-confirmed SAH, the sensitivity of CSF spectrophotometry was reported to be 100% up to 2 weeks after the ictus.[4] However, the false-negative rate of spectrophotometry in the diagnosis of SAH in CT-negative people is not known.[5] If a person presents more than 2 weeks after the onset of symptoms, no test can rule out SAH with 100% certainty, although MRI (particularly fluid-attenuated inversion recovery [FLAIR] and gradient echo sequences) may be useful in detecting subarachnoid blood in some people. The sensitivity of CSF spectrophotometry drops significantly after 2 weeks, decreasing to 90% by 3 weeks post-bleed.[4] These people should be referred urgently to a neuroscience unit for consideration of further investigations. The correct diagnosis of SAH is pivotal to successful outcome. Pitfalls in diagnosis include: (1) the headache of SAH does not have any specific distinguishing features and may resemble migraine; (2) the pain of SAH may be relieved by migraine acute-attack treatments such as triptans — response to a triptan may provide false and unjustified reassurance; (3) there is an over-reliance on the classical presentation of the reported feeling of a 'sudden blow to the head'; (4) because SAH may often cause fever, some people may be misdiagnosed as having meningitis; (5) approximately 20% of people with SAH develop cardiac arrhythmia, and some people will have an ECG suggestive of ischaemia (thrombolysis can have disastrous consequences in this situation); (6) people may occasionally present with an isolated acute confusional state; (7) people may present in a coma; and, (8) in some people, the predominant feature may be vomiting, leading to gastrointestinal investigations. Once SAH has been confirmed by CT scan or CSF examination, the source of haemorrhage must be identified. The gold-standard technique is catheter cerebral angiography. However, CT angiography (CTA) and magnetic resonance angiography (MRA) provide non-invasive means of diagnosing a cerebral aneurysm. A systematic review found that, for aneurysms larger than 3 mm, the sensitivity of CTA was 96% (95% CI 94% to 98%) and of MRA was 94% (95% CI 90% to 97%). For aneurysms 3 mm or smaller, the sensitivity of CTA was 61% (95% CI 51% to 70%) and of MRA was 38% (95% CI 25% to 53%).[6] In people with confirmed SAH in whom CTA or MRA is negative, catheter angiography must be performed. There are two treatment approaches for aSAH: open transcranial surgery, which primarily involves clipping of the aneurysm via performing a craniotomy and navigating through the cisterns and natural subarachnoid corridors of the brain to reach the aneurysm, at which point a metallic clip is applied to the exterior of the aneurysm to occlude it; and endovascular treatment, which primarily involves coiling of the aneurysm via an arterial puncture (usually femoral). A catheter is advanced under fluoroscopic guidance to either the carotid or vertebral artery to locate the aneurysm. Once identified, a coil is deployed and deposited within the aneurysm via a smaller microcatheter to achieve occlusion.

Incidence/ Prevalence

Spontaneous SAH accounts for about 5% of all strokes. In most populations, the incidence of SAH is 7.8/100,000 population a year (95% CI 7.2/100,000 to 8.4/100,000).[7] However, there is significant regional variation — from a low reported incidence in South American to high incidence in Japan and Finland (Finland: 21.4/100,000 a year, 95% CI 19.5/100,000 to 23.4/100,000).[7] The overall incidence in women is 1.6 times that in men (95% CI 1.1 to 2.3).[7]

Aetiology/ Risk factors

Ruptured aneurysms are the cause of 85% of spontaneous SAHs. Other causes of spontaneous SAH include benign perimesencephalic SAH, other idiopathies, some drugs (e.g., amphetamines), coagulation disorders, vascular malformations, dural venous sinus thrombosis, tumours, and vasculitides. The exact aetiology of intracranial aneurysms remains unclear. Risk factors include smoking (RR 2.2, 95% CI 1.3 to 3.6), hypertension (RR 2.1, 95% CI 2.0 to 3.1), and excessive alcohol intake (RR 2.1, 95% CI 1.5 to 2.8).[8] Genetic factors may also be involved. Aneurysms are associated with defined heritable disorders, including connective tissue disorders and autosomal dominant polycystic kidney disease. They may also occur in a familial setting.

Prognosis

Aneurysmal SAH (aSAH) has a poor prognosis, particularly if the aneurysm is not occluded. Observational studies from the 1960s reported mortality rates of 10% to 32% on day 1, 27% to 43% during the first week, and 49% to 56% at 1 month after SAH.[9] [10] Most deaths occur as a result of re-bleeding from the same aneurysm. If untreated, re-bleeding occurs in 15% of people on day 1, and in 40% of people by 1 month after SAH.[9] [11] The rate of re-bleeding decreases with time to 3% a year after the initial 6 months.[9] A systematic review of population-based studies found that the overall case fatality rate after aSAH ranged from 32% to 67%.[12] It also found that the case fatality rates had decreased by +0.5% a year (95% CI –0.1% to +1.2%) between 1960 and 1992, suggesting that improved management of people with SAH may be the reason for the better outcomes.[12] A more recent population-based study found a case fatality rate of 39% (95% CI 34% to 44%).[13] These reported case fatality rates include people who die before reaching hospital, which was found in a meta-analysis of population-based studies to be 12.4% (95% CI 11% to 14%).[13] Between 10% and 20% of all people with SAH (17%–46% of survivors) become dependent.[12] As well as physical disability, SAH results in cognitive impairment in a large number of people. In a population-based study, 105/230 (46%) of survivors interviewed at 1 year reported incomplete recovery, with ongoing problems with memory (50%), mood (39%), and speech (14%).[14]

Aims of intervention

To reduce mortality and disability (neurological and other); to reduce secondary complications of SAH, to prevent re-bleeding (recurrent haemorrhage from the same aneurysm); and to decrease rates of delayed cerebral ischaemia, with minimal adverse effects of treatment.

Outcomes

Mortality or disability disability measured by scales such as Modified Rankin Scale, Glasgow Outcome Scale and dependency on others to carry out daily tasks (measured as a component of scale used to rate disability); risk of seizures/epilepsy; rate of re-bleeding (including recurrent haemorrhage from the same aneurysm, rate of re-treatment of same aneurysm, and rates of occlusion); cerebral infarction; vasospasm; neuropsychological outcomes; quality of life; and adverse effects (including procedural complications) .

Methods

Search strategy BMJ Clinical Evidence search and appraisal October 2014. The databases used to identify studies for this systematic review include: Medline 1966 to October 2014, Embase 1980 to October 2014, The Cochrane Database of Systematic Reviews 2014, issue 10 (1966 to date of issue), Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this systematic overview were systematic reviews and RCTs published in English, at least single-blinded, and containing 20 or more individuals (10 in each arm), of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as ‘open’, ‘open label’, or not blinded unless blinding was impossible. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributors. In consultation with the expert contributors, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our predefined criteria for inclusion in the benefits and harms section, may have been reported in the 'Further information on studies' or 'Comment' section. Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributors may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Structural changes this update At this update, we have removed the following previously reported questions: What are the effects of medical treatments to prevent delayed cerebral ischaemia in people with confirmed aneurysmal subarachnoid haemorrhage? from this overview. Data and quality To aid readability of the numerical data in our overviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue that may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Subarachnoid haemorrhage (spontaneous aneurysmal).

Important outcomes	Cerebral infarction, Mortality or disability, Neuropsychological outcomes, Quality of life, Rate of re-bleeding, Risk of seizure/epilepsy, Vasospasm
Studies (Participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of surgical treatments for people with confirmed aneurysmal subarachnoid haemorrhage?
6 (4185)	Mortality or disability	Endovascular coiling versus surgical clipping	4	–1	0	–1	0	Low	Quality point deducted for significant difference between groups in length of time between SAH and treatment; directness point deducted for narrowness of included population affecting generalisability
1 (1288)	Risk of seizure/epilepsy	Endovascular coiling versus surgical clipping	4	–1	–1	–1	0	Very low	Quality point deducted for significant difference between groups in length of time between SAH and treatment; consistency point deducted for variable effect over time; directness point deducted for narrowness of included population affecting generalisability
6 (at least 2861)	Rate of re-bleeding	Endovascular coiling versus surgical clipping	4	–1	0	–1	0	Low	Quality point deducted for significant difference between groups in length of time between SAH and treatment; directness point deducted for narrowness of included population affecting generalisability
2 (226)	Cerebral infarction	Endovascular coiling versus surgical clipping	4	0	–1	–1	0	Low	Consistency point deducted for variable results; directness point deducted for queries in generalisability
1 (186)	Vasospasm	Endovascular coiling versus surgical clipping	4	–2	0	–1	0	Very low	Quality points deducted for sparse data and significant difference between groups in length of time between SAH and treatment; directness point deducted for narrowness of included population affecting generalisability
1 (474)	Neuropsychological outcomes	Endovascular coiling versus surgical clipping	4	–1	0	–1	0	Low	Quality points deducted for subset analysis; directness point deducted for narrowness of included population affecting generalisability

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Glasgow Outcome Scale (GOS)

A five-point scale widely used to assess outcome after head injury. Score of 5 = good recovery (able to return to work or school); 4 = moderate disability (disabled but able to live independently); 3 = severe disability (dependent on daily support); 2 = persistent vegetative state; 1 = dead.

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Modified Rankin Score (mRS)

A six-point scale used to assess functional outcome after stroke. Only symptoms that become apparent after stroke are considered. Grade 0 = I have no symptoms at all. Grade 1 = I have some symptoms but I am able to carry out all usual duties and activities. Grade 2 = I am unable to carry out all previous activities but I am able to look after my own affairs without help from another person. Grade 3 = I require some help, but I am able to walk without help from another person. Grade 4 = I am unable to walk without help from another person or I am unable to attend to my own bodily needs without help from another person, or both. Grade 5 = I am bedridden, incontinent, and require constant nursing care and attention.

Very low-quality evidence

Any estimate of effect is very uncertain.

World Federation of Neurosurgical Societies (WFNS) grade

A clinical grading system for subarachnoid haemorrhage based on the Glasgow Coma Scale (GCS) score and presence or absence of focal neurological deficit. The WFNS grade is an important prognostic factor. Grade 1 = GCS 15 with no focal neurological deficit; 2 = GCS 13–14 and no focal neurological deficit; 3 = GCS 13–14 with focal neurological deficit; 4 = GCS 7–12 with or without focal neurological deficit; 5 = GCS 3–6 with or without focal neurological deficit.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.