Brain, Vol. 124, No. 2, 249-278,
February 2001
© 2001 Oxford University Press
Invited review |
Subarachnoid haemorrhage: diagnosis, causes and management
Department of Neurology, University Medical Centre, Utrecht, The Netherlands
Correspondence to:
J. van Gijn, MD, Department of Neurology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands E-mail: J.vanGijn{at}neuro.azu.nl
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Abstract |
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 Top Abstract IntroductionEpidemiological aspectsDiagnosis of SAHThe search for the...Causes other than saccular...Patients without identifiable...Early assessment of prognosis...Causes of poor clinical...Prevention of rebleedingPrevention of secondary cerebral...References |
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The incidence of subarachnoid haemorrhage (SAH) is stable, at around six cases per 100 000 patient years. Any apparent decrease is attributable to a higher rate of CT scanning, by which other haemorrhagic conditions are excluded. Most patients are <60 years of age. Risk factors are the same as for stroke in general; genetic factors operate in only a minority. Case fatality is ~50% overall (including pre-hospital deaths) and one-third of survivors remain dependent. Sudden, explosive headache is a cardinal but non-specific feature in the diagnosis of SAH: in general practice, the cause is innocuous in nine out of 10 patients in whom this is the only symptom. CT scanning is mandatory in all, to be followed by (delayed) lumbar puncture if CT is negative. The cause of SAH is a ruptured aneurysm in 85% of cases, non-aneurysmal perimesencephalic haemorrhage (with excellent prog nosis) in 10%, and a variety of rare conditions in 5%. Catheter angiography for detecting aneurysms is gradually being replaced by CT angiography. A poor clinical condition on admission may be caused by a remediable complication of the initial bleed or a recurrent haemorrhage in the form of intracranial haematoma, acute hydrocephalus or global brain ischaemia. Occlusion of the aneurysm effectively prevents rebleeding, but there is a dearth of controlled trials assessing the relative benefits of early operation (within 3 days) versus late operation (day 10–12), or that of endovascular treatment versus any operation. Antifibrinolytic drugs reduce the risk of rebleeding, but do not improve overall outcome. Measures of proven value in decreasing the risk of delayed cerebral ischaemia are a liberal supply of fluids, avoidance of antihypertensive drugs and administration of nimodipine. Once ischaemia has occurred, treatment regimens such as a combination of induced hypertension and hypervolaemia, or transluminal angioplasty, are plausible, but of unproven benefit.
aneurysm; epidemiology; outcome; subarachnoid haemorrhage; treatment
ADPKD = autosomal polycystic kidney disease; AVM = arteriovenous malformation; CI = confidence interval; CTA = CT angiography; GCS = Glasgow Coma Scale; MRA = MR angiography; SAH = subarachnoid haemorrhage; WFNS = World Federation of Neurological Surgeons
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Introduction |
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TopAbstractIntroductionEpidemiological aspectsDiagnosis of SAHThe search for the...Causes other than saccular...Patients without identifiable...Early assessment of prognosis...Causes of poor clinical...Prevention of rebleedingPrevention of secondary cerebral...References |
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Subarachnoid haemorrhage (SAH), mostly from aneurysms, accounts for only 3% of all strokes (Sudlow and Warlow, 1997
), but for 5% of stroke deaths and for more than one-quarter of potential life years lost through stroke (Johnston et al., 1998a). The 20th century has seen great advances in diagnosis, starting with the ability to recognize the condition at all during life (Cushing, 1923; Symonds, 1923). Advances in treatment and prevention of complications have also occurred, but these have led to only modest improvement in overall outcome (Hop et al., 1997); hence there are still formidable challenges ahead for neurologists, neurosurgeons and radiologists. |
Epidemiological aspects |
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TopAbstractIntroductionEpidemiological aspectsDiagnosis of SAHThe search for the...Causes other than saccular...Patients without identifiable...Early assessment of prognosis...Causes of poor clinical...Prevention of rebleedingPrevention of secondary cerebral...References |
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The incidence of SAH has remained stable over the last 30 years. In a meta-analysis of relevant studies, the pooled incidence rate was 10.5 per 100 000 person years (Linn et al., 1996
). There seemed to be a decline over time, but this was caused by diagnostic bias. That more recent studies reported lower incidence rates than older studies could be entirely explained by the increasing proportion of patients investigated with CT scanning. In a virtual study in which CT is applied to all patients, the incidence is calculated to be 5.6 per 100 000 patient years (Linn et al., 1996) (Table 1); this is only slightly lower than the incidence of 6.9 published later for a study spanning a 30-year period of the population in Olmsted, Minn., USA (Menghini et al., 1998). The average age of patients with SAH is substantially lower than for other types of stroke, peaking in the sixth decade (Longstreth et al., 1993; Lanzino et al., 1996).
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Gender, race and region have a marked influence on the incidence of SAH. Women have a 1.6 times [95% confidence interval (CI) 1.5–2.3] higher risk than men (Linn et al., 1996
), and black people a 2.1 times (95% CI 1.3–3.6) higher risk than whites (Broderick et al., 1992). In Finland and Japan, the incidence rates are much higher than in other parts of the world (Table 1
).
Risk factors
An important, but non-modifiable risk factor is familial predisposition to SAH. Between five and 20% of patients with SAH have a positive family history (Schievink, 1997). First-degree relatives of patients with SAH have a 3- to 7-fold increased risk of being struck by the same disease (Bromberg et al., 1995; Schievink et al., 1995; Wang et al., 1995; De Braekeleer et al., 1996; Gaist et al., 2000). In second-degree relatives, the incidence of SAH is similar to that found in the general population (Bromberg et al., 1995).
The occurrence of SAH is also associated with specific heritable disorders of connective tissue, but these patients account for only a minority of all patients with SAH. Even though autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable disorder associated with SAH, it is found in only 2% of all patients with SAH (Schievink et al., 1992). Other genetically determined disorders that have been associated with SAH are Ehlers–Danlos disease IV and neurofibromatosis type 1, but these associations are weaker than between ADPKD and aneurysms and these syndromes are seldom found in patients with SAH (Schievink et al., 1994; Pepin et al., 2000). Marfan's syndrome has often been associated with SAH, but in a clinical cohort of 129 patients with Marfan's syndrome, none had a history of SAH (Van den Berg et al., 1996).
Modifiable risk factors for SAH have been addressed in a systematic review of eight longitudinal and 10 case-control studies that fulfilled predefined methodological criteria; only smoking, hypertension and heavy drinking emerged as significant risk factors, with odds ratios in the order of two or three (Teunissen et al., 1996). In this study, the use of oral contraceptives did not present a significantly increased risk, but was found to do so in a meta-analysis published 2 years later (relative risk 1.42; 95% CI 1.12–1.80) (Johnston et al., 1998b). The risks were not clear for hormone replacement therapy or an increased level of plasma cholesterol (Teunissen et al., 1996).
Outcome
Case fatality ranged between 32 and 67% in a review of population-based studies from 1960 onward. The weighted average was 51%. Of patients who survive the haemorrhage, approximately one-third remain dependent (Hop et al., 1997). Recovery to an independent state does not necessarily mean that outcome is good. In a study on quality of life in patients after SAH, only nine of 48 (19%; 95% CI 9–33%) patients who were independent 4 months after the haemorrhage had no significant reduction in quality of life (Hop et al., 1998a). Re-evaluation of this cohort at 18 months after the haemorrhage showed that outcome had improved considerably in terms of handicap and quality of life, but that still only 15 of the 48 patients (31%; 95% CI 19–46%) had no reduction in the quality of life (J. W. Hop, G. J. E. Rinkel, A. Algra and J. van Gijn, unpublished data). The improvement in the first year and a half shows that long-term follow-up is essential in studies on effectiveness of new treatment strategies on functional outcome after SAH. All in all, only a small minority of all patients with SAH have a truly good outcome. The relatively young age at which SAH occurs and the poor outcome together explain why the loss of years of potential life before age 65 from SAH is comparable to that of ischaemic stroke (Johnston et al., 1998a).
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Diagnosis of SAH |
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TopAbstractIntroductionEpidemiological aspectsDiagnosis of SAHThe search for the...Causes other than saccular...Patients without identifiable...Early assessment of prognosis...Causes of poor clinical...Prevention of rebleedingPrevention of secondary cerebral...References |
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Clinical features
The clinical hallmark of SAH is a history of unusually severe headache that started suddenly. A period of unresponsiveness of >1 h occurs in almost half the patients and focal signs develop at the same time as the headache or soon afterwards in one third of patients (Linn et al., 1998
; Hop et al., 1999). In patients with such neurological deficits, it is straightforward that they should be referred for further investigation. In patients in whom headache is the only symptom, it is often more difficult to recognize the seriousness of the underlying condition. Classically, the headache from aneurysmal rupture develops in seconds. Therefore it is important to make specific enquiries about how quickly the headache developed; patients often complain only about the severity of the headache and do not know that the speed of onset is a pivotal piece of information. However, even an accurate history does not reliably distinguish between aneurysmal rupture and innocuous forms of headache, such as benign vascular headache or a muscle contraction headache. First, only half the patients with aneurysm rupture describe the onset as instantaneous, the other half describe it as coming on in seconds to even a few minutes (Linn et al., 1998). Secondly, in the group of patients whose headache came on within a split second, innocuous forms of headache outnumber SAH by 10 to one (Linn et al., 1994). Other features are equally unhelpful in making the distinction: the severity of headache is rated similar, vomiting occurs in 70% of patients with aneurysmal rupture, but also in 43% of patients with innocuous thunderclap headache. Also, preceding bouts of similar headaches are recalled in 20% of patients with aneurysmal rupture and 15% of patients with innocuous thunderclap headache (Linn et al., 1998). Neck stiffness is a common sign in SAH of any cause, but takes hours to develop and therefore cannot be used to exclude the diagnosis if a patient is seen soon after the sudden-onset headache. It does not occur if patients are in deep coma. Subhyaloid haemorrhages require experience with fundoscopy and occur in ~17% of patients, at least of those who reach hospital alive (Pfausler et al., 1996; Frizzell et al., 1997).
If explosive headache is the only symptom, the chance of SAH being the cause is only 10% (Linn et al., 1994). Nevertheless, the lack of clinical features that distinguish reliably and at an early stage between SAH and innocuous types of sudden headache necessitate a brief consultation in hospital for all patients with an episode of severe headache that comes on within minutes. Such an approach serves the patient's best interests and is also cost effective. The discomfort and cost of referring the 90% of patients with innocuous headache is outweighed by avoidance of the disaster in the other 10% so that a ruptured aneurysm is avoided (Tolias and Choksey, 1996).
It is even more difficult to suspect aneurysmal rupture if the patient does not report a history of sudden headache, or if other symptoms seem to prevail over the headache, such as in patients presenting with a seizure or a confusional state, or if there is an associated head trauma. Epileptic seizures at the onset of aneurysmal SAH occur in ~6–16% of patients (Sarner and Rose, 1967; Hart et al., 1981; Pinto et al., 1996). Of course the majority of patients with de novo epilepsy above age 25 years will have underlying conditions other than SAH, but the diagnosis should be suspected if the post-ictal headache is unusually severe. One to 2% of patients with SAH present with an acute confusional state and in most such patients a history of sudden headache is lacking (Reijneveld et al., 2000). The differential diagnosis of acute confusional state is extensive and SAH accounts for, at most, a few percent of all patients seen in an emergency ward because of an acute confusional state (Benbadis et al., 1994). In such patients, the diagnosis emerges only if the careful history of an eyewitness reveals the sudden onset of the symptoms; also detection of focal deficits or absence of a psychiatric history should raise the index of suspicion and lead to a brain imaging study.
Trauma and spontaneous SAH are sometimes difficult to disentangle. Patients may be found alone after having been beaten in a brawl or hit by a drunken driver who made away, without external wounds to indicate an accident, with a decreased level of consciousness or with retrograde amnesia, making it impossible to obtain a history and with neck stiffness, causing the patient to be worked up for SAH. Conversely, patients may cause an accident whilst riding a bicycle or driving a car at time of the aneurysmal rupture. The diagnostic conundrum is particularly difficult when patients sustain a skull fracture having fallen after aneurysm rupture (Sakas et al., 1995) or when head trauma causes an aneurysm to burst (Sahjpaul et al., 1998). Meticulous reconstruction of traffic or sports accidents may therefore be rewarding, especially in patients with disproportionate headache or neck stiffness.
Clinical clues to the cause of SAH
Past history may contain useful information. In patients with previous head injury, and particularly with a skull fracture, a dural arteriovenous malformation (AVM) should be suspected, since healing of the fracture may be accompanied by the development of such a malformation (Chaudhary et al., 1982). Although SAH from a septic aneurysm is a rare presentation of infective endocarditis in patients not known to have a disorder of the heart valves (Vincent et al., 1980; Salgado et al., 1987), this diagnosis should be considered in patients with a history of malaise in the days or weeks preceding the haemorrhage, even more so if the haemorrhage is located at the convexity of the brain. Usually it will not be hard for the physician to get acquainted with the existence of sickle cell disease, a history of cardiac myxoma, or coagulation disorders. Pain at onset in the lower part of the neck (upper neck pain is common also with ruptured intracranial aneurysms), or a sudden and stabbing pain between the shoulder blades (coup de poignard or dagger thrust), with or without radiation to the arms, suggests a spinal AVM or fistula as the source of SAH (Kinouchi et al., 1998). A history of even quite minor neck trauma or of sudden, unusual head movements before the onset of headache may provide a clue to the diagnosis of vertebral artery dissection as a cause of SAH. Cocaine ingestion as a risk factor may not immediately be known in the case of an unconscious patient. Even if the family turns up in large numbers, one may find that not every relative is aware of illicit drugs being used or willing to volunteer this information even if they are. In cocaine-associated SAH there is often an underlying aneurysm (Levine et al., 1991; Nolte et al., 1996).
The physical examination can also provide an indication about the cause of SAH. Monocular blindness may result from anterior communicating artery aneurysms if it is exceptionally large (Chan et al., 1997). Complete or partial third nerve palsy is a well-recognized sign after rupture of an aneurysm of the internal carotid artery at the origin of the posterior communicating artery (Hyland and Barnett, 1954). The third nerve can also be involved with aneurysms of the basilar bifurcation or the superior cerebellar artery, but these are relatively infrequent sites (Vincent and Zimmerman, 1980). Sixth nerve palsies, often bilateral in the acute stage, usually result from a non-specific and sustained rise of cerebrospinal fluid pressure, either at the time of rupture or later. A combination of visual and oculomotor deficits should raise the suspicion of a pituitary apoplexy (McFadzean et al., 1991). Usually, the underlying adenoma has insidiously manifested itself before the dramatic occurrence of the haemorrhage by a dull retro-orbital pain, fatigue, a gradual decrease of visual acuity or a constriction of the temporal fields. Lower cranial nerve palsies point to dissection of the vertebral artery, through direct compression of the ninth or tenth nerve (Senter and Sarwar, 1982). Lower cranial nerve palsies (ninth to twelfth nerve) may also accompany dissection of the carotid artery in the neck, but this is an extremely uncommon cause of SAH (Sturzenegger and Huber, 1993). Deficits indicating lesions of the cerebellum or brainstem, such as dysmetria, scanning speech, rotatory nystagmus or Horner's syndrome, also strongly suggest vertebral artery dissection (Caplan et al., 1988). The presence or absence of hemiparesis does not contribute much to the diagnosis of uncommon causes, because the rare occurrence of hemiparesis with a ruptured aneurysm (mostly of the middle cerebral artery) will still outnumber all other potential causes of SAH, in which hemiparesis may be relatively common, for example with septic aneurysms.
Brain scanning (CT and MRI)
If SAH is suspected, CT scanning is the first line in investigation because of the characteristically hyperdense appearance of extravasated blood in the basal cisterns. The pattern of haemorrhage often suggests the location of any underlying aneurysm (van Gijn and van Dongen, 1980a), although with variable degrees of certainty (Van der Jagt et al., 1999). A false-positive diagnosis of SAH on CT is possible in the presence of generalized brain oedema, with or without brain death, which causes venous congestion in the subarachnoid space and in this way may mimic SAH (van Gijn and van Dongen, 1982; Avrahami et al., 1998). The CT scan should be carefully scrutinized because small amounts of subarachnoid blood may easily be overlooked (Fig. 1). If after a thorough review no blood is found, aneurysmal SAH cannot be excluded. Even if CT is performed within 12 h after the haemorrhage and with a modern CT machine, studies are negative in ~2% of patients with SAH (van der Wee et al., 1995).
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Brain CT may also help in distinguishing primary SAH from traumatic brain injury, but the aneurysmal pattern of haemorrhage is not always immediately appreciated in patients admitted with a trauma (Vos et al., 2000
). If trauma is the cause of SAH, the blood is usually confined to the superficial sulci at the convexity of the brain, adjacent to a fracture or to an intracerebral contusion; these findings dispel any lingering concern about the possibility of a ruptured aneurysm. Nevertheless, patients with basal-frontal contusions may show a pattern of haemorrhage resembling that of a ruptured anterior communicating artery aneurysm (Sakas et al., 1995), and in patients with blood confined to the sylvian fissure or ambient cistern it may also be difficult to distinguish trauma from aneurysmal rupture by the pattern of haemorrhage alone (Rinkel et al., 1993). In patients with direct trauma to the neck or with head injury associated with vigorous neck movement, the trauma can immediately be followed by massive haemorrhage into the basal cisterns resulting from a tear or even a complete rupture of one of the arteries of the posterior circulation, which is often rapidly fatal (Harland et al., 1983; Dowling and Curry, 1988).
MRI with FLAIR (fluid attenuated inversion recovery) techniques demonstrates SAH in the acute phase as reliably as CT (Noguchi et al., 1995), but MRI is impracticable because the facilities are less readily available than CT scanners, and restless patients cannot be studied unless anaesthesia is given. After a few days (up to 40), however, MRI is increasingly superior to CT in detecting extravasated blood (Ogawa et al., 1995; Noguchi et al., 1997). This makes MRI a unique method for identifying the site of the haemorrhage in patients with a negative CT scan but a positive lumbar puncture (see below), such as those who are not referred until 1 or 2 weeks after symptom onset (Renowden et al., 1994).
Lumbar puncture
Lumbar puncture is still an indispensable step in the exclusion of SAH in patients with a convincing history and negative brain imaging. Lumbar puncture should not be carried out rashly or without some background knowledge. The first rule is that at least 6 and preferably 12 h should have elapsed between the onset of headache and the spinal tap. The delay is essential, because if there are red cells in the CSF, sufficient lysis will have taken place during that time for bilirubin and oxyhaemoglobin to have formed (Vermeulen and van Gijn, 1990). The pigments give the CSF a yellow tinge after centrifugation (xanthochromia), a critical feature in the distinction from a traumatic tap, and are invariably detectable until at least 2 weeks later (de Paepe et al., 1988). The `three tube test' (a decrease in red cells in consecutive tubes) is notoriously unreliable, and a false-positive diagnosis of SAH can be almost as invalidating as a missed one. Spinning down the blood-stained CSF should be done immediately, otherwise oxyhaemoglobin will form in vitro. If the supernatant appears crystal-clear, the specimen should be stored in darkness until the absence of blood pigments is confirmed by spectrophotometry (Vermeulen and van Gijn, 1990). Although the sensitivity and specificity of spectrophotometry have not yet been confirmed in a series of patients with suspected SAH and a negative CT scan (Beetham et al., 1998), it is the best technique currently available.
Keeping patients in an emergency department or admitting them to hospital until 6–12 h after symptom onset may be a practical problem, yet we see no alternative until a scientifically sound method has been devised to distinguish reliably between blood caused by a traumatic tap from blood that was already present. Even the smoothest puncture can end in a vein. Immediately proceeding with CT or MR angiography in all patients with blood-stained CSF is not a good idea, because a small (<5 mm) aneurysm may well be coincidental and should be left untreated, while a negative study may still leave concerns, not only with the patients themselves but also with insurance company advisors.
The main cause: saccular aneurysms
Approximately 85% of all spontaneous haemorrhages into the subarachnoid space arise from rupture of saccular aneurysms at the base of the brain (van Gijn and van Dongen, 1980b; Kassell et al., 1990a; Velthuis et al., 1998). Such aneurysms are not congenital, but develop during the course of life. Cerebral aneurysms almost never occur in neonates and they are also rare in children (Heiskanen, 1986). In those exceptional cases, there is usually a specific underlying cause for the aneurysm, such as trauma, infection or connective-tissue disorder (Ferry et al., 1974; Stehbens, 1982). The frequency at which saccular aneurysms are found in the general population depends on the definition of size and the diligence with which the search for unruptured aneurysms has been performed. In a systematic overview of studies reporting the prevalence of intracranial aneurysms in patients studied for reasons other than SAH, 23 studies were identified, totalling 56 304 patients; 6685 (12%) of these were from 15 angiography studies (Rinkel et al., 1998). The prevalence was lowest in retrospective autopsy studies and highest in prospective angiography studies (Table 2). The prevalence of aneurysms was relatively high in patients with autosomal polycystic kidney disease, a familial predisposition or atherosclerosis.
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It is largely unknown why only some adults develop aneurysms at arterial bifurcations and most do not. The once popular notion of a congenital defect in the muscle layer of the wall (tunica media) being a weak spot through which the inner layers of the arterial wall would bulge has been largely dispelled by a number of contradictory observations. First, gaps in the muscle layer of intracranial arteries are equally common in patients with and without aneurysms (Stehbens, 1989
) and are usually strengthened by densely packed collagen fibrils (Fujimoto, 1996; Finlay et al., 1998). Secondly, if an aneurysm has formed, any defect in the muscle layer is located not at the neck of the aneurysm, but somewhere in the wall of the aneurysmal sac (Stehbens, 1989).
A role of acquired changes in the arterial wall is likely because hypertension, smoking and alcohol abuse are risk factors for SAH in general (Teunissen et al., 1996). It may well be the influence of these factors that leads to local thickening of the intimal layer (`intimal pads') in the arterial wall, distal and proximal to a branching site, changes that some investigators regard as the earliest stage in the formation of aneurysms (Walker and Allegre, 1954; Hassler, 1962). The formation of these pads, in which the intimal layer is inelastic, may cause increased strain in the more elastic portions of the vessel wall (Crompton, 1966). Also, structural abnormalities in structural proteins of the extracellular matrix have been identified in the arterial wall at a distance from the aneurysm itself (Chyatte et al., 1990).
Some neoplastic conditions may lead to the formation of aneurysms, i.e. cerebellar haemangioblastoma (Guzman and Grady, 1999) or metastasis from bronchial carcinoma (Gliemroth et al., 1999). Iatrogenic causes include radiation therapy (Jensen and Wagner, 1997), acrylate applied externally for microvascular decompression (Tokuda et al., 1998) and operation for a superficial temporal artery-middle cerebral artery bypass, with the aneurysm at the site of the anastomosis (Sasaki et al., 1996).
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The search for the ruptured aneurysm: is catheter angiography still necessary? |
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TopAbstractIntroductionEpidemiological aspectsDiagnosis of SAHThe search for the...Causes other than saccular...Patients without identifiable...Early assessment of prognosis...Causes of poor clinical...Prevention of rebleedingPrevention of secondary cerebral...References |
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The gold standard for detecting aneurysms is conventional angiography, but this procedure can be time consuming and it is not an innocuous procedure. A systematic review of three prospective studies in which patients with SAH were distinguished from other indications for catheter angiography found a complication rate (transient or permanent) of 1.8% (Cloft et al., 1999
). At any rate, the aneurysm may re-rupture during the procedure, as occurs in 1–2% of cases overall (Hayakawa et al., 1978; Koenig et al., 1979; Saitoh et al., 1995). The rupture rate in the 6 h period following angiography has been estimated at 5% (Saitoh et al., 1995), which is higher than the expected rate.
Other imaging modalities are MR angiography (MRA) and CT angiography (CTA). MRA is safe, but less suitable in the acute stage, because in the acute stage patients are often restless or need extensive monitoring (Anzalone et al., 1995). A recent review of studies comparing MRA and intra-arterial angiography in patients with recent SAH, under blinded-reader conditions, showed a sensitivity in the range of 69–100% for detecting at least one aneurysm per patient. For the detection of all aneurysms the sensitivity is 70–97%, with specificity in the range 75–100% (Wardlaw and White, 2000). In a screening study for unruptured aneurysms in first-degree relatives of patients with SAH, the agreement between neuroradiologists about the presence of aneurysms was poor, not surprisingly, given the low prevalence (4%) of aneurysms (Raaymakers et al., 1999). Despite its limitations, but thanks to its non-invasive nature, MRA is a feasible tool for detecting aneurysms in relatives of patients with SAH (Ronkainen et al., 1995; Kojima et al., 1998; Raaymakers et al., 1999).
CT angiography is based on the technique of spiral CT. It can easily be obtained immediately after the non-contrast CT upon which the diagnosis is first made. It is minimally invasive because it does not require intra-arterial catheterization. Compared with MRA, it involves radiation and it requires injection of iodine-based contrast, but is much simpler to perform, especially in ill patients. After the data acquisition, which can be done within 1 min, post-processing techniques are needed to produce an angiogram-like display. The most practical procedure for daily routine is cine review of the axial source images combined with maximum intensity projection (MIP) of a limited volume of interest (Fig. 2) (Velthuis et al., 1997). In addition, MIP images derived from CTA can be rotated and studied on a computer screen at every conceivable angle, which is a great advantage over the limited views with conventional angiography.
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The sensitivity of CTA (compared with catheter angiography) is 85–98%, in the same range as that of MRA (Alberico et al., 1995
; Hope et al., 1996; Wardlaw and White, 2000). On the other hand, with CTA aneurysms can be detected that were missed by conventional angiography (Hashimoto et al., 2000). In a study in which CTA and conventional angiography were compared in 80 patients with SAH, neurosurgeons assessed CT angiography as equal or superior to conventional angiography in 83% (95% CI 73–90%) of 87 aneurysms (Velthuis et al., 1998). It is not surprising, therefore, that an increasing proportion of patients with a ruptured aneurysm is successfully operated with CTA as the only imaging method (Anderson et al., 1999; Velthuis et al., 1999a). There is no doubt that catheter angiography is on its way out for the pre-treatment assessment of cerebral aneurysms, as the techniques of CTA and MRA are still improving and as neurosurgeons and interventional radiologists are growing familiar with them.
The technique of transcranial Doppler can be combined with echo imaging (duplex technique) and with colour coding (transcranial colour-coded duplex sonography). A recent modification of colour Doppler called Colour Doppler Energy or Power Doppler offers greater sensitivity to flowing blood than standard colour flow imaging (Wardlaw and Cannon, 1996). The sensitivity of power Doppler increases further by using an ultrasonic contrast agent, but even then the sensitivity is only 55% with a corresponding 83% specificity (Turner and Kirkpatrick, 2000). Another drawback of this technique is that ~15% of patients have no adequate bone window, which prevents adequate insonation (Seidel et al., 1995). Also, the technique is highly dependent on the skills of the operator.
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Causes other than saccular aneurysms |
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TopAbstractIntroductionEpidemiological aspectsDiagnosis of SAHThe search for the...Causes other than saccular...Patients without identifiable...Early assessment of prognosis...Causes of poor clinical...Prevention of rebleedingPrevention of secondary cerebral...References |
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Of the 15% of SAHs not attributable to saccular aneurysms, two-thirds (10% of the total) are caused by non-aneurysmal SAH and the remaining 5% by a variety of rare conditions (Table 3
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Non-aneurysmal perimesencephalic haemorrhage
Perimesencephalic haemorrhage constitutes ~10% of all episodes of SAH and two-thirds of those with a normal angiogram (van Gijn et al., 1985a
; Farrés et al., 1992; Ferbert et al., 1992; Kitahara et al., 1993; Pinto et al., 1993; Vermeer et al., 1997). In this radiologically distinct and strikingly harmless variety of SAH, the extravasated blood is confined to the cisterns around the midbrain, and the centre of the bleeding is immediately anterior to the midbrain (Fig. 3) (van Gijn et al., 1985a; Rinkel et al., 1991a; Schwartz and Solomon, 1996). In some cases, the only evidence of blood is found anterior to the pons (Zentner et al., 1996). For this reason some have proposed the term pre-truncal haemorrhage (Schievink and Wijdicks, 1997), but in other patients the blood is found mainly in the ambient cistern (Fig. 4) or only in the quadrigeminal cistern (van Gijn et al., 1985a; Rinkel and van Gijn, 1995; Schwartz and Mayer, 2000). There is no extension of the haemorrhage to the lateral sylvian fissures or to the anterior part of the interhemispheric fissure. Some sedimentation of blood in the posterior horns of the lateral ventricles may occur, but frank intraventricular haemorrhage or extension of the haemorrhage into the brain parenchyma indicates arterial haemorrhage and rules out this particular condition (Rinkel et al., 1991a). This disease entity is defined only by the characteristic distribution of the extravasated blood on brain CT, in combination with the absence of an aneurysm.
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Perimesencephalic haemorrhage can occur in any patient over the age of 20 years, but most patients are in their sixth decade, as with aneurysmal haemorrhage. A history of hypertension was obtained more often than expected in a single study (Canhao et al., 1999
), but not in another (Rinkel et al., 1991b). In one-third of the patients, strenuous activities immediately precede the onset of symptoms, a proportion similar to that found in aneurysmal haemorrhage (van Gijn et al., 1985a; Linn et al., 1998).
Clinically, there is little to distinguish idiopathic perimesencephalic haemorrhage from aneurysmal haemorrhage. The headache onset is more often gradual (minutes rather than seconds) than with aneurysmal haemorrhage (van Gijn et al., 1985a; Linn et al., 1998), but the predictive value of this feature is poor. Loss of consciousness and focal symptoms are exceptional and then only transient; a seizure at onset virtually rules out the diagnosis (Linn et al., 1998). On admission, all patients are, in fact, in perfect clinical condition, apart from their headache (van Gijn et al., 1985a; Rinkel et al., 1991b). Transient amnesia is found in about one-third and is associated with enlargement of the temporal horns on the initial CT scan (Hop et al., 1998b). Typically, the early course is uneventful: rebleeds and delayed cerebral ischaemia simply do not occur. Approximately 20% of patients have enlarged lateral ventricles on their admission brain CT scan, associated with extravasation of blood in all perimesencephalic cisterns, which probably causes blockage of the CSF circulation at the tentorial hiatus (Rinkel et al., 1992). Only few have symptoms from this ventricular dilatation and even then an excellent outcome can be anticipated (Rinkel et al., 1990a, b). The period of convalescence is short and almost invariably patients are able to resume their previous work and other activities (Rinkel et al., 1990a; Brilstra et al., 1997). Rebleeds after the hospital period have not been documented thus far (Rinkel et al., 1991c; Canhao et al., 1995) and the quality of life in the long term is excellent (Brilstra et al., 1997).
A perimesencephalic pattern of haemorrhage may occasionally (in 2.5–5% of cases) be caused by rupture of a posterior fossa aneurysm (Rinkel et al., 1991a; Pinto et al., 1993; Van Calenbergh et al., 1993). The chance of finding an aneurysm in 5% of patients has to be weighed against the risks of complications from angiography imposed upon the remaining 95% of patients. In recent years, CTA has been studied as a method to confirm or exclude the presence of an aneurysm in patients with a perimesencephalic pattern of haemorrhage on CT. In a prospectively collected series of 40 patients with either a perimesencephalic haemorrhage or a posterior circulation aneurysm in whom CTA and conventional angiography were performed, radiologists detected an aneurysm in 16 patients and no aneurysm in the remaining 24 patients. These findings were confirmed after reading the angiograms. (Velthuis et al., 1999b). A formal decision analysis based on these observations indicated that a strategy where CTA is performed and not followed by conventional angiography, if negative, results in a better utility than a strategy where CTA is followed by conventional angiography or if all patients are initially investigated by conventional angiography (Y. M. Ruigrok, G. J. E. Rinkel, E. Buskens, B. K. Velthuis and J. van Gijn, unpublished data).
Arterial dissection
Dissection, in general, tends to be recognized more often in the carotid than in the vertebral artery, but SAH from a dissected artery occurs mostly in the vertebral artery (Fig. 5) (Kaplan et al., 1993; Rinkel et al., 1993). It is unknown what precise proportion of all SAH cases arise from a dissected vertebral artery. All miscellaneous causes together account for only ~5%, against 85% for aneurysmal haemorrhages and 10% for idiopathic perimesencephalic haemorrhages. In a post-mortem study of fatal SAH, dissection was found in five of 110 patients (Sasaki et al., 1991a).
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Neurological deficits that may accompany SAH from vertebral artery dissection are palsies of the ninth and tenth cranial nerves, by subadventitial dissection (Senter and Sarwar, 1982
), or Wallenberg's syndrome (Caplan et al., 1988). Rebleeds occur in between 30 and 70% of cases (Caplan et al., 1988; Aoki and Sakai, 1990; Yamaura et al., 1990; Mizutani et al., 1995). The interval can be as short as a few hours or as long as a few weeks. The second episode is fatal in approximately half of the patients.
Dissection of the intracranial portion of the internal carotid artery or one of its branches as a cause of SAH is much less common than with the vertebral artery. Reported cases have affected the terminal portion of the internal carotid artery (Adams et al., 1982; Massoud et al., 1992), the middle cerebral artery (Kunze and Schiefer, 1971; Sasaki et al., 1991b; Piepgras et al., 1994) and the anterior cerebral artery (Guridi et al., 1993).
Cerebral AVMs
Subarachnoid bleeding at the convexity of the brain may occur from superficial AVMs, but only in <5% of all ruptured AVMs is the extravasation only in the subarachnoid space, without intracerebral haematoma (Fig. 6) (Aoki, 1991). Saccular aneurysms form on feeding arteries of 10–20% of AVMs, presumably because of the greatly increased flow and the attendant strain on the arterial wall. If bleeding occurs in these cases, it is more often from the aneurysm than from the malformation. In those cases the site of the aneurysms is different from the classical sites of saccular aneurysms on the circle of Willis and again the haemorrhage is more often into the brain itself than into the subarachnoid space (Brown et al., 1990; Marks et al., 1992).
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Dural arteriovenous fistulae
Dural arteriovenous fistulae of the tentorium can give rise to a basal haemorrhage that is indistinguishable on CT from aneurysmal haemorrhage (Fig. 7
) (Lasjaunias et al., 1986; Brown et al., 1994). The anomaly is rare and can be found from adolescence to old age. The risk of haemorrhage from dural AVMs depends on the pattern of venous drainage. Patients with direct cortical venous drainage have a relatively high risk, which is further increased if a venous ectasia is present. Patients with drainage into a main sinus have a low risk of haemorrhage and if no reflux occurs into the smaller sinuses or cortical veins, it is negligible (Cognard et al., 1995). After a first rupture, rebleeding may occur; in a series of five patients presenting with SAH, three had one or more rebleeds (Halbach et al., 1987).
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Cervical AVMs
Spinal AVMs present with SAH in ~10% of cases; in >50% of these patients, the first haemorrhage occurs before the age of 20 years (Caroscio et al., 1980
; Kandel, 1980). Clues pointing to a cervical origin of the haemorrhage are onset with a sudden and excruciating pain in the lower part of the neck, or pain radiating from the neck to the shoulders or arms (Acciarri et al., 1992). In the absence of such symptoms, the true origin of the haemorrhage emerges only when spinal cord dysfunction develops, after a delay that may be as short as a few hours or as long as a few years (Kandel, 1980; Swann et al., 1984). Rebleeds may occur, even repeatedly (Aminoff and Logue, 1974). CT scanning of the brain in patients with a ruptured cervical AVM may show blood throughout the basal cisterns and ventricles (Acciarri et al., 1992). If a cervical origin of the haemorrhage is suspected, MRI or MRA angiography are the first line of investigation, because spinal angiography is impractical without localizing signs or symptoms.
Saccular aneurysms of spinal arteries
Saccular aneurysms of spinal arteries are extremely rare, with recorded incidents in ~12 patients (Handa et al., 1992; Mohsenipour et al., 1994). As with AVMs of the spinal cord, the clinical features of spinal SAH may be accompanied by those of a transverse lesion of the cord, either partial or complete.
Cardiac myxoma
Cardiac myxoma are uncommon to start with, and if present they may in exceptional cases metastasize to an intracranial artery, infiltrate the wall and thus cause an aneurysm to develop, even >1 year after operation on the primary tumour (Furuya et al., 1995).
Septic aneurysms
Infected tissue debris entering the blood stream may lodge in the wall of cerebral arteries and lead to aneurysmal dilatation. The traditional term `mycotic aneurysms' refers only to fungi and should perhaps be discarded; after all, bacterial endocarditis is more common as an underlying condition than aspergillosis. Most strokes in the context of infective endocarditis are not SAH but (haemorrhagic) infarcts or intracerebral haemorrhages from pyogenic arteritis (Hart et al., 1990; Masuda et al., 1992; Krapf et al., 1999). Aneurysms associated with infective endocarditis are most often located on distal branches of the middle cerebral artery, but ~10% of the aneurysms develop at more proximal sites (Brust et al., 1990). Therefore, rupture of a septic aneurysm causes an intracerebral haematoma in most patients, but some have a basal pattern of haemorrhage on CT that is very similar to that of a ruptured saccular aneurysm (Fig. 8). CT-documented rebleeds have been reported (Steinberg et al., 1992). Usually patients present with clinical features of infected heart valves before SAH occurs, but sometimes rupture of a septic aneurysm is the initial manifestation of infective endocarditis (Hart et al., 1990; Salgado, 1991). Septic aneurysms can be obliterated by surgical or endovascular treatment (Steinberg et al., 1992; Frizzell et al., 1993), or they may resolve after adequate antibiotic therapy (Brust et al., 1990; Corr et al., 1995).
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Septic aneurysms in patients with aspergillosis are usually located on the proximal part of the basilar or carotid artery (Lau et al., 1991
). Rupture of such an aneurysm causes a massive SAH in the basal cisterns, indistinguishable from that of a saccular aneurysm (Kowall and Sobel, 1988). Aspergillosis is difficult to diagnose, but should particularly be suspected in patients undergoing long-term treatment with antibiotics or immunosuppressive agents. Most patients with haematogenous dissemination have pulmonary lesions, but X-ray films of the chest may be normal early in the course (Young et al., 1970; Kowall and Sobel, 1988).
Severely HIV-infected children may develop cerebral aneurysms secondary to generalized arteriopathy (Husson et al., 1992; Shah et al., 1996; Dubrovsky et al., 1998). In HIV-infected adults, aneurysmal SAH can also be coincidental (Maniker et al., 1996).
Pituitary apoplexy
The precipitating event of arterial haemorrhage occurring in a pituitary tumour is thought to be tissue necrosis, involving one of the hypophyseal arteries. Several contributing factors may precipitate haemorrhagic infarction of a pituitary tumour, such as pregnancy, raised intracranial pressure, anticoagulant treatment, cerebral angiography or the administration of gonadotrophin-releasing hormone (Reid et al., 1985; Masson et al., 1993). The initial features are a sudden and severe headache (Dodick and Wijdicks, 1998), with or without nausea, vomiting, neck stiffness or a depressed level of consciousness (Reid et al., 1985). The hallmark of pituitary apoplexy is that most patients have a sudden decrease in visual acuity: in one series of 15 patients, only two had normal visual acuity. In most patients with pituitary apoplexy eye movements are disturbed as well, because the haemorrhage compresses the oculomotor, trochlear and abducens nerves in the adjacent cavernous sinus (McFadzean et al., 1991). Brain CT or MRI scanning indicate the pituitary fossa as the source of the haemorrhage and in most instances the adenoma itself is visible (Post et al., 1980; McFadzean et al., 1991).
Cocaine abuse
In patients with SAH related to the use of HCl (`crack') cocaine, ~70% have an underlying aneurysm, against 30–40% of those who used the alkaloid form (Levine et al., 1991). The pattern of haemorrhage on brain CT may be comparable to that of a ruptured saccular aneurysm (Wojak and Flamm, 1987) and the diagnosis rests on a confirmatory history or on the results of toxicological tests. Rebleeds do occur, even in patients with a normal angiogram, and the outcome is often poor (Mangiardi et al., 1988). The source of the haemorrhage in patients without an aneurysm is unknown. Although biopsy-proven vasculitis has been found (Krendel et al., 1990), changes suggestive of vasculitis often fail to show up on angiograms, admittedly a very insensitive test (Mangiardi et al., 1988; Levine et al., 1990).
Anticoagulants
Anticoagulant drugs are seldom the sole cause for SAH. In a series of 116 patients with intracranial, extracerebral haemorrhage while on anticoagulant treatment, seven had only SAH and in only three of these patients was there no cause for the haemorrhage other than anticoagulation (Mattle et al., 1989). Severe coagulopathy other than by anticoagulant drugs, e.g. congenital deficiency of factor VII, is also a rare cause of haemorrhage confined to the subarachnoid space (Papa et al., 1994). If aneurysmal haemorrhage occurs in a patient on anticoagulants, the outcome is relatively poor (Rinkel et al., 1997).
Sickle cell disease
Thirty per cent of patients with sickle cell disease and SAH are children (Carey et al., 1990). CT scans in these children show blood in the superficial cortical sulci; angiograms show no aneurysm, but often show multiple distal branch occlusions and a leptomeningeal collateral circulation. The SAH is attributed to rupture of these collaterals (Carey et al., 1990). The outcome is poor: only three of 11 recently reviewed children recovered in a good functional state (Carey et al., 1990). Most adult patients in whom sickle cell disease underlies SAH have a ruptured aneurysm at the base of the brain.
Superficial siderosis of the CNS
This condition is characterized by iron overload of the pial membranes, through chronic oozing of blood from any source in the subarachnoid space. It has been included in this review only for semantic reasons; the clinical picture is completely different from that with sudden haemorrhages and does not include sudden headache (Tomlinson and Walton, 1964; Bonito et al., 1994; Fearnley et al., 1995). The clinical syndrome is almost invariably characterized by sensorineural deafness (95%), furthermore by cerebellar ataxia (88%) and pyramidal signs (76%). Possible other features include dementia, bladder disturbance and anosmia. Men are more often affected than women (3 : 1). A source of bleeding has been identified in a little more than half of the cases reported up to 1995 (Fearnley et al., 1995). Causes of chronic bleeding include a CSF cavity lesion or cervical root lesion, a vascular tumour (such as an ependymoma) or any other vascular abnormality. Probably the remaining cases are also caused by chronic haemorrhage. The high iron content of the pial membranes cause a characteristic signal on MRI scanning (Bonito et al., 1994; River et al., 1994; Uchino et al., 1997).
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Patients without identifiable cause |
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