Etiology, clinical manifestations, and diagnosis of aneurysmal ...

09/04/2010 Etiology, clinical manifestations, and dia… 

Official reprint from UpToDate ® www.uptodate.com 

©2010 UpToDate ® 

Etiology, clinical manifestations, and diagnosis of aneurysmal 

subarachnoid hemorrhage 

Authors 

Robert J Singer, MD 

Christopher S Ogilvy, MD 

Guy Rordorf, MD 

Section Editor 

Jose Biller, MD, FACP, FAAN, 

FAHA 

Deputy Editor 

Janet L Wilterdink, MD 

Last literature review version 18.1: January 2010 | This topic last updated: January 28, 

2010 

INTRODUCTION — Twenty percent of strokes are hemorrhagic, with subarachnoid hemorrhage 

(SAH) and intracerebral hemorrhage each accounting for 10 percent. The epidemiology, etiology, 

clinical manifestations, and diagnosis of aneurysmal SAH are reviewed here. The treatment of this 

disorder and the epidemiology and pathogenesis of intracranial aneurysms and management of 

unruptured aneurysms are discussed separately. Mycotic aneurysms and nonaneurysmal 

subarachnoid hemorrhage are also discussed separately. (See "Treatment of aneurysmal 

subarachnoid hemorrhage" and "Unruptured intracranial aneurysms" and "Mycotic aneurysm" and 

"Nonaneurysmal subarachnoid hemorrhage" and "Perimesencephalic nonaneurysmal subarachnoid 

hemorrhage".) 

EPIDEMIOLOGY — Most SAHs are caused by ruptured saccular aneurysms. Other causes include 

trauma, arteriovenous malformations/fistulae, vasculitides, intracranial arterial dissections, amyloid 

angiopathy, bleeding diatheses, and illicit drug use (especially cocaine and amphetamines). 

The prevalence of intracranial saccular aneurysms by radiographic and autopsy series is 5 percent, 

or 10 to 15 million people in the United States. Approximately 20 to 30 percent of patients have 

multiple aneurysms [1]. Aneurysmal SAH occurs at an estimated rate of 3 to 25 per 100,000 

population [2,3]. The mean age at onset is 55 years [4]. In North America, this translates into 

approximately 30,000 affected persons per year. Thus, most aneurysms do not rupture. The risk of 

rupture of intracranial aneurysms is related in part to aneurysm size and is discussed separately. 

(See "Unruptured intracranial aneurysms", section on 'Natural history of unruptured aneurysms'.) 

Most aneurysmal SAH occur between 40 and 60 years of age; however young children and the 

elderly can be affected [5,6]. African Americans appear to be at higher risk than caucasian 

Americans [7]. There is a slightly higher incidence of aneurysmal SAH in women, which may relate 

to hormonal status (see 'Estrogen deficiency' below [5,8]. 

RISK FACTORS — Most SAHs are due to the rupture of intracranial aneurysms. Because of this, risk 

factors for aneurysm formation overlap with risk factors for SAH. Risk factors that are primarily 

associated with formation of intracranial aneurysms are discussed separately. (See "Unruptured 

intracranial aneurysms".) 

Cigarette smoking — Cigarette smoking appears to be the most important preventable risk factor 

for SAH [9-13]. The importance of cigarette smoking is illustrated by the following reports: 

A case-control study of 432 adults with SAH found that current cigarette smokers had a 

significantly increased risk of SAH compared with nonsmokers not exposed to secondhand smoke 

(odds ratio 5.0) [10]. Current and lifetime exposures showed a clear dose-dependent effect, and 

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the risks appeared to be more prominent in women and in aneurysmal SAH. The risk attributable to 

cigarette smoking declined rapidly and largely disappeared within a few years of quitting. There was 

no significant effect of secondhand smoke. 

In a systematic review of 14 longitudinal and 23 case-control studies that included 3936 

patients with SAH, current smoking was a significant risk factor for SAH in both the longitudinal 

(relative risk [RR] 2.2, 95% CI 1.3-3.6) and case-control studies (odds ratio [OR] 3.1, 95% CI 2.7- 

3.5) [11]. 

An analysis of data from the Asia Pacific Cohort Studies Collaboration (APCSC) involving 26 

cohorts with 306,620 participants and 236 SAH events found that the risk for SAH was significantly 

associated with current smoking (hazard ratio [HR] 2.4, 95% CI 1.8-3.4) [12]. 

Hypertension — Hypertension is a major risk factor for SAH [9,11-15]. The best data come from 

the systematic review cited above that included 3936 patients with SAH [11]. Hypertension was 

significantly associated with SAH risk in both the longitudinal (RR 2.5, 95% CI 2.0-3.1) and casecontrol 

studies (OR 2.6, 95% CI 2.0-3.1). 

Alcohol — Moderate to heavy alcohol consumption appears to increase the risk of SAH (graph 

1) [11,16]. In the systematic review cited above, excessive alcohol intake was a significant risk 

factor for SAH in both the longitudinal (RR 2.1, 95% CI 1.5-2.8) and case-control studies (OR 1.5, 

95% CI 1.3-1.8) [11]. 

Genetic risk — A number of inherited conditions are associated with increased risk of cerebral 

aneurysm and SAH. These include autosomal dominant polycystic kidney disease, glucocorticoidremediable 

aldosteronism, and Ehler Danlos syndrome. The risk of aneurysmal SAH associated with 

these conditions is discussed separately. (See "Screening for intracranial aneurysm", section on 

'Hereditary syndromes associated with aneurysm formation'.) 

A family history of SAH also increases the risk of SAH in individuals without one of these conditions. 

As an example, one case-control study found that patients with a family history of SAH had an 

odds ratio of 4.0 (95% CI 2.0-8.0) for SAH compared with controls [17]. 

Similarly, another study found that first-degree relatives of patients with SAH have a three to fivefold 

increased risk of SAH compared with the general population [18]. It may be reasonable to 

screen some family members for the presence of cerebral aneurysm. This issue is discussed in detail 

separately. (See "Screening for intracranial aneurysm", section on 'Relatives of patients with 

cerebral aneurysm'.) 

The genetic susceptibility to SAH appears to be heterogeneous. Some familial SAH pedigrees are 

most consistent with autosomal dominant inheritance, while others are more consistent with 

autosomal recessive or multifactorial transmission [19,20]. One study found evidence of anticipation 

in two successive generations of familial SAH, with affected parents significantly older than 

affected children (55.2 versus 35.4 years, respectively) [21]. 

Some evidence points to the elastin gene on chromosome 7q as a candidate gene related to the 

development of familial [22,23] and sporadic [24] SAH. Other evidence supports linkage of familial 

SAH t o c hromosomes 1p [25], 2p [26], 11q, 14q [27], 19q [28-30], and Xp22 [28,30]. 

A polymorphism affecting the platelet adhesive glycoprotein GPIIIa HPA-1 (HPA comes from human 

platelet alloantigen; GPIIIa HPA-1 is also called PIA) is associated with increased risk of thrombosis 

and a decreased risk of SAH (odds ratio 0.48; 95% CI 0.24-0.96) [31]. 

Sympathomimetic drugs — In case-control studies, phenylpropanolamine in appetite 

suppressants, and possibly cold remedies, appeared to be an independent risk factor for 



hemorrhagic stroke (including intracerebral hemorrhage and subarachnoid hemorrhage) in women 

[32,33]. 

Cocaine abuse has been associated with both aneurysmal and nonaneurysmal SAH [34-36]. (See 

"Nonaneurysmal subarachnoid hemorrhage", section on 'Other causes'.) 

Estrogen deficiency — There is a female preponderance for aneurysms ranging from 54 to 61 

percent [8]. In one case-control study, premenopausal women without a history of smoking or 

hypertension were at reduced risk of SAH compared with age-matched postmenopausal women 

(odds ratio 0.24) [37]. Furthermore, the use of estrogen replacement therapy was associated with 

a reduced risk of SAH in postmenopausal women (odds ratio 0.47). Risk reduction with the use of 

estrogen replacement therapy has been seen in other studies as well [11,38]. 

Antithrombotic therapy — Sufficient data are not available to determine whether anticoagulant 

(eg, warfarin) or antiplatelet therapy increase the risk of aneurysm rupture. However, 

anticoagulation therapy does appear to increase the severity of a SAH. (See "Anticoagulant and 

antiplatelet therapy in patients with an unruptured intracranial aneurysm".) 

Statins — The relationship between cholesterol status, statin use, and the risk of ischemic versus 

hemorrhagic cerebrovascular events is complex. Statin use is associated with an overall lower risk 

of total and ischemic cerebrovascular events, but there is some concern that low cholesterol levels 

and statin use may increase the risk of intracerebral hemorrhage. (See "Secondary prevention of 

stroke: Risk factor reduction".) 

One case control study found that current statin use was not significantly associated with a lower 

SAH risk, and that recent statin drug withdrawal increased the risk of SAH [39]. However, the 

effect of statin withdrawal was highest in patients who had also stopped taking antihypertensive 

drugs. 

CLINICAL MANIFESTATIONS — Rupture of an aneurysm releases blood directly into the 

cerebrospinal fluid (CSF) under arterial pressure. The blood spreads quickly within the CSF, rapidly 

increasing intracranial pressure. The bleeding usually lasts only a few seconds, but rebleeding is 

common and occurs more often within the first day. 

Consistent with the rapid spread of blood, the symptoms of SAH typically begin abruptly, occurring 

at night in 30 percent of cases. The premier symptom is a sudden, severe headache (97 percent of 

cases) classically described as the "worst headache of my life." The headache is lateralized in 30 

percent of patients, predominantly to the side of the aneurysm. The onset of the headache may or 

may not be associated with a brief loss of consciousness, seizure, nausea or vomiting, and 

meningismus (graph 2) [40]. In one series, these occurred in 53, 77, and 35 percent respectively 

[41]. Meningismus and often lower back pain may not develop until several hours after the bleed 

since it is caused by the breakdown of blood products within the CSF, which lead to an aseptic 

meningitis [42]. 

Approximately 30 to 50 percent of patients have a minor hemorrhage or "warning leak," manifested 

only by a sudden and severe headache (the sentinel headache) that precedes a major SAH by 6 to 

20 days [40]. A systematic literature review through September 2002 found that the incidence of 

sentinel headaches in aneurysmal SAH ranged from 10 to 43 percent [43]. 

The complaint of the sudden onset of severe headache is sufficiently characteristic that a minor 

SAH should always be considered. In a prospective study of 148 patients presenting with sudden 

and severe headache, for example, SAH was present in 25 percent overall and in 12 percent of 

those in whom headache was the only symptom [44]. Similar findings were noted in another report 

in which 20 of 107 patients with the "worst headache of my life" had an SAH [45]. 



Physical exertion may be an acute trigger for SAH. A case-crossover study in 338 patients with SAH 

found that patients were more likely to have engaged in moderate or greater exertion in the two 

hours prior to SAH than in the same two-hour period on the previous day (odds ratio 2.7, 95% CI 

1.6-4.6) [46]. Physical exertion or stress preceding SAH is not invariable [36]. 

COMPLICATIONS — Subarachnoid hemorrhage (SAH) is associated with a high mortality rate [47]. 

A systematic review found that the average case fatality rate for SAH was 51 percent [48]. 

Approximately 10 percent of patients with aneurysmal SAH die prior to reaching the hospital, 25 

percent die within 24 hours of SAH onset, and about 45 percent die within 30 days [49]. 

Mortality rates due to SAH appear to be decreasing over time in Western populations [50-52]. 

Improvements in rates of smoking, treatment of hypertension, and management of SAH are plausible 

but unproven reasons for the reduction in mortality. Improved diagnostic accuracy over time, 

including exclusion of SAH mimics, may also be playing a role. 

A number of additional complications commonly occur in patients who have suffered a SAH: 

Rebleeding 

Vasospasm and delayed cerebral ischemia 

Hydrocephalus 

Increased intracranial pressure 

Seizures 

Hyponatremia 

Cardiac abnormalities 

Hypothalamic dysfunction and pituitary insufficiency [53] 

Rebleeding — Most studies have found that the risk of rebleeding is highest in the first 24 hours 

after SAH [54-56], particularly within six hours of the initial hemorrhage [55]. The risk of rebleeding 

in the first 24 hours ranges from 2.6 to 4 percent [54,56]. Most rebleeding (73 percent) occurs 

within the first 72 hours of ictus [56]. Factors that may be independent predictors of rebleeding 

include: 

the Hunt-Hess grade on admission [55,56] 

maximal aneurysm diameter [56] 

a higher initial blood pressure [36] 

a sentinel headache preceding SAH [57] 

a longer interval from ictus admission [36] 

early ventriculostomy (prior to aneurysm treatment) [36] 

The overall incidence of rebleeding after initial SAH in the modern era is uncertain. A prospective 

study from a tertiary care center involving 574 hospitalized patients admitted within 14 days of SAH 

found a rebleeding rate of 6.9 percent by three months [56]. This rate may have been biased by 

over representation of high-risk aneurysms (eg, large, anatomically complex, or located in the 

posterior circulation). 

Rebleeding is usually diagnosed on the basis of an acute deterioration of neurologic status 

accompanied by appearance of new hemorrhage on head CT scan. Lumbar puncture is harder to 

evaluate because xanthochromia can persist for two weeks or more. (See 'Lumbar puncture' below.) 

Only aneurysm treatment is effective for the prevention of rebleeding. (See "Treatment of 

aneurysmal subarachnoid hemorrhage", section on 'Treatment of aneurysms'.) 

The prognosis of rebleeding after SAH is discussed separately. (See "Treatment of aneurysmal 

subarachnoid hemorrhage", section on 'Management of complications'.) 

Vasospasm — Vasospasm causes symptomatic ischemia and infarction in approximately 20 to 30 



percent of patients with aneurysmal SAH; it is the leading cause of death and disability after 

aneurysm rupture [58,59]. Vasospasm typically begins no earlier than day three after hemorrhage, 

reaching a peak at days seven to eight. The onset of clinical vasospasm is characterized by a 

decline in neurologic status, including the onset of focal neurologic abnormalities. The severity of 

symptoms depends upon the artery affected and the degree of collateral circulation. 

Transcranial Doppler (TCD) sonography is useful for detecting and monitoring vasospasm in 

spontaneous SAH, and it is probably useful for detecting vasospasm after traumatic SAH [60,61]. 

Velocity changes detected by TCD typically precede the clinical sequelae of vasospasm. Daily 

recordings offer a window of opportunity to treat patients prior to clinical decline. (See "Treatment 

of aneurysmal subarachnoid hemorrhage".) 

Preliminary but accumulating data suggest that brain perfusion asymmetry demonstrated on CT 

perfusion (CTP) scanning in the acute stage of SAH may be a useful and highly sensitive method for 

predicting delayed cerebral ischemia, which is most cases is presumably due to vasospasm [62-64]. 

However, the clinical utility of this method remains to be established. 

Pathogenesis — The pathogenesis of delayed cerebral vasospasm involves an interaction between 

the metabolites of blood and the vasculature. Spasmogenic substances generated during the lysis 

of subarachnoid blood clots can cause endothelial damage and smooth muscle contraction [65]. The 

vascular endothelium produces nitric oxide, which tonically dilates the cerebral vasculature; 

endothelial damage may interfere with nitric oxide production, leading to vasoconstriction and an 

impaired response to vasodilators [66]. In addition, increased release of the potent vasoconstrictor 

endothelin may play a major role in the induction of cerebral vasospasm after SAH [65]. 

Risk factors — The location of blood on computed tomography (CT) scan and its extent can help 

predict the likelihood of complicating cerebral vasospasm [67,68]. In one series, severe vasospasm 

was correctly predicted and localized in 20 of 22 patients using the CT criteria of clots larger than 3 

x 5 mm or layers of blood more t han 1 mm t hic k [68]. Radiologic grading scales including those of 

Fisher (table 1) and Claassen (table 2) are often used to predict the likelihood of vasospasm and 

cerebral ischemia. (See "Subarachnoid hemorrhage grading scales".) 

Other factors that may increase the risk of vasospasm include age less than 50 years and 

hyperglycemia [69,70]. Most [71-73] but not all [69] studies have found that poor clinical grade 

(eg, Hunt-Hess grade 4 or 5, or Glasgow Coma Scale score

09/04/2010 [ ] g 

Etiology, clinical manifestations, and dia… 

EVSP was significantly more likely in patients with a poor neurologic grade on admission, 

intracerebral hematoma, larger aneurysm, thick SAH on CT scan, intraventricular hemorrhage, a 

history of previous SAH, and a history of hypertension. 

EVSP was not associated with delayed cerebral vasospasm, suggesting that the etiology of the 

two types of vasospasm is different. 

EVSP was associated with cerebral infarction, neurologic worsening, and unfavorable outcome at 

three months, after adjustment for differences in admission characteristics. 

Cerebral infarction — Cerebral infarction is a frequent complication of SAH. Hypodense brain 

lesions on head CT have been noted in 40 to 60 percent of survivors at 3 to 12 months after SAH 

[4,78,79]. In a case series of 143 patients with acute aneurysmal SAH admitted from 1998 to 2000 

at a single center, cerebral infarction defined on CT scan was found in 56 patients (39 percent) 

[80]. The time from SAH onset to the last CT scan during the acute hospital stay ranged from 5 to 

32 days (mean 12 days). 

The two most common patterns of infarction in these 56 patients were: 

Single cortical infarcts, typically located near the site of the ruptured aneurysm, in 23 (40 

percent) 

Multiple widespread infarcts, often involving bilateral and subcortical regions and frequently 

located distal to the ruptured aneurysm, in 28 (50 percent) 

The most common cause of infarction after SAH is assumed to be vasospasm (see 

'Vasospasm' above [81]. Hypovolemia may add to the risk of cerebral ischemia in the setting of 

vasospasm [82]. Other mechanisms of ischemia include occlusion (temporary or permanent) of or 

damage to cerebral arteries during aneurysm surgery, thromboembolism related to turbulent or 

stagnant aneurysmal blood flow or clip application, and embolism unrelated to SAH. 

Hypodense lesions on CT consistent with infarction appear to be more likely with larger volume SAH 

and poor initial clinical condition [4,78,79,83]. These observations are supported by the results of a 

study that analyzed CT scans of 156 patients three months after SAH; additional independent risk 

factors for hypodense lesions included nocturnal occurrence of SAH (between 12:01 and 8:00 AM), 

fixed symptoms of delayed ischemia, duration of temporary artery occlusion during surgery, and 

body mass index [84]. The mechanism of increased ischemia risk with nocturnal SAH is unknown. 

Hydrocephalus — Hydrocephalus (acute and chronic) is a common complication of SAH. In one 

large series, hydrocephalus was documented by CT scan in 15 percent of patients, 40 percent of 

whom were symptomatic [85]. Factors associated with an increased risk for hydrocephalus included 

intraventricular hemorrhage, posterior circulation aneurysms, treatment with antifibrinolytic agents, 

and a low Glasgow score on presentation. The incidence was also increased in patients with 

hyponatremia or a history of hypertension. Older age is an additional risk factor. 

Hydrocephalus after SAH is thought to be caused by obstruction of cerebrospinal fluid (CSF) flow by 

blood products or adhesions, or by a reduction of CSF absorption at the arachnoid granulations 

[86]. The former occurs as an acute complication; the latter tends to occur two weeks or later, 

and is more likely to be associated with shunt dependence. 

Spontaneous improvement occurs in one-half of patients with acute hydrocephalus and impaired 

consciousness, usually within 24 hours [87]. In the remainder, acute hydrocephalus is associated 

with increased morbidity and mortality secondary to rebleeding and cerebral infarction [88]. 



Increased ICP — Patients with SAH may develop increased intracranial pressure (ICP) due to a 

number of factors, including increased cerebrospinal fluid outflow resistance, acute hydrocephalus, 

hemorrhage volume, reactive hyperemia after hemorrhage, vasoparalysis, and distal cerebral 

arteriolar vasodilation [89-92]. In a series of 234 patients with SAH who had ICP monitoring, 

increased ICP occurred during the hospital stay in 54 percent, including 49 percent of those 

considered to have a good clinical grade (Hunt and Hess grades I to III) [93]. 

Seizures — Seizures at the onset of SAH appear to be an independent risk factor for late seizures 

and a predictor of poor outcome [94]. One study of 247 patients with SAH found that 7 percent 

developed new-onset epilepsy (defined as two or more unprovoked seizures after hospital 

discharge), and these patients had poor functional recovery and quality of life [95]. Associated 

cerebral infarction and subdural hematoma predicted epilepsy, suggesting that epilepsy in this 

setting is due to focal rather than diffuse brain injury. 

The incidence of late epilepsy (more than two weeks after surgery) after surgical management of 

SAH is unclear. Multiple studies have cited an incidence of up to 25 percent [96-98]. However, the 

true incidence now may be lower, given advances in surgical management that have occurred since 

these studies took place. Patients with a poor grade SAH appear to have a higher incidence of late 

epilepsy [99]. (See "Treatment of aneurysmal subarachnoid hemorrhage", section on 'Antiepileptic 

drug therapy'.) 

Hyponatremia — Hyponatremia following subarachnoid hemorrhage is relatively common, and is 

probably mediated by hypothalamic injury. The water retention that leads to hyponatremia is due to 

increased secretion of antidiuretic hormone, which may result from either the syndrome of 

inappropriate ADH secretion or, much less often, volume depletion induced by cerebral salt wasting. 

These issues are discussed separately. (See "Cerebral salt-wasting".) 

Cardiac abnormalities — Cardiac abnormalities and electrocardiographic (ECG) changes are 

commonly seen after SAH and appear to be more common and more severe in those with more 

severe SAH [100,101]. The most frequent ECG abnormalities are ST segment depression, QT 

interval prolongation, deep symmetric T wave inversions, and prominent U waves. Life-threatening 

rhythm disturbances such as torsades de pointes have also been described, as well as atrial 

fibrillation and flutter. ST-T wave abnormalities along with bradycardia and relative tachycardia 

were found in one large series to be independently associated with mortality [102]. (See "Cardiac 

complications of stroke".) 

The ECG changes are predominantly reflective of ischemic changes in the subendocardium of the 

left ventricle. The development of actual myocardial injury (in as many as 20 percent of patients) 

can be established by elevations of CK-MB or serum troponin I (>0.1 µg/L), which is a specific and 

more sensitive marker of myocardial necrosis [101,103]. Patients with elevated troponin I 

concentrations are more likely to have ECG abnormalities and clinical evidence of left ventricular 

dysfunction. Subendocardial ischemia is an independent predictor of poor outcome in patients with 

SAH and must be managed aggressively (although without the use of aspirin) [100]. (See 

"Troponins and creatine kinase as biomarkers of cardiac injury" and "Overview of the ac ute 

management of unstable angina and acute non-ST elevation myocardial infarction".) 

A wide spectrum of regional left ventricular wall motion abnormalities, demonstrable by 

echocardiography, can occur with SAH; these are typically but not always reversible [101,104,105]. 

Some patients develop a pattern of transient apical left ventricular dysfunction that mimics 

myocardial infarction (but in the absence of significant coronary artery disease), a condition known 

as takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome [105,106]. 

(See "Stress-induced (takotsubo) cardiomyopathy".) 

Acute troponin elevation after SAH appears to be associated with increased risk of cardiopulmonary 



and cerebrovascular complications [100,107]. In a series of 253 patients with SAH who had serial 

troponin measurements for clinical or ECG signs of potential cardiac injury, elevated peak troponin 

levels were associated with an increased risk of left ventricular dysfunction, pulmonary edema, 

hypotension requiring pressors, and delayed cerebral ischemia from vasospasm [107]. These findings 

were confirmed in a meta-analysis of 25 studies of SAH including 2960 patients; in this analysis, 

elevated troponin levels were also associated with increased mortality and worse functional 

outcome [100]. (See "Elevated cardiac troponin concentration in the absence of an acute coronary 

syndrome", section on 'Acute stroke'.) 

Elevation of serum brain type natriuretic peptide (BNP) has been noted after SAH [100,108,109], 

although the source of this elevation is unclear. BNP is present in the brain and in the heart; serum 

BNP elevation occurs with heart failure. (See "Brain natriuretic peptide measurement in left 

ventricular dysfunction and other cardiac diseases".) In a prospective cohort of 57 subjects with 

SAH, elevated BNP levels were associated with the presence of cardiac regional wall motion 

abnormalities, diastolic dysfunction, pulmonary edema, elevated cardiac troponin I, and left 

ventricular ejection fraction


Head CT scan — The cornerstone of SAH diagnosis is the noncontrast head CT scan [117,118]. 

Clot is demonstrated in the subarachnoid space in 92 percent of cases if the scan is performed 

within 24 hours of the bleed [118]. Intracerebral extension is present in 20 to 40 percent of 

patients and intraventricular and subdural blood may be seen in 15 to 35 and 2 to 5 percent, 

respectively. The head CT scan should be performed with thin cuts through the base of the brain to 

increase the sensitivity to small amounts of blood [119]. 

The distribution of blood on CT (performed within 72 hours after the bleed) is a poor predictor of 

the site of an aneurysm except in patients with ruptured anterior cerebral artery or anterior 

communicating artery aneurysms and in patients with a parenchymal hematoma [18]. 

The sensitivity of head CT for detecting SAH is highest in the first 12 hours after SAH (nearly 100 

percent) and then progressively declines over time to about 58 percent at day five [118,120-122]. 

The sensitivity of head CT is also reduced with more minor bleeds. In one study, for example, a 

minor SAH was not diagnosed by CT scan in 55 percent of patients; lumbar puncture was positive in 

all cases [123]. 

Lumbar puncture — Lumbar puncture is mandatory if there is a strong suspicion of SAH despite a 

normal head CT [117]. The classic findings are an elevated opening pressure and an elevated red 

blood cell (RBC) count that does not diminish from CSF tube one to tube four. Immediate 

centrifugation of the CSF can help differentiate bleeding in SAH from that due to a traumatic spinal 

tap. 

Clearing of blood — Clearing of blood (a declining RBC count with successive collection tubes) is 

purported to be a useful way of distinguishing a traumatic LP from SAH. However, this is an 

unreliable sign of a traumatic tap, since a decrease in the number of RBCs in later tubes can occur 

in SAH. This method can reliably exclude SAH only if the late or final collection tube is normal. (See 

"Cerebrospinal fluid: Physiology and utility of an examination in disease states", section on 

'Traumatic tap'.) 

Xanthochromia — Xanthochromia (pink or yellow tint) represents hemoglobin degradation 

products. An otherwise unexplained xanthochromic supernatant in CSF is highly suggestive of SAH. 

Xanthochromia may be visually detected by comparing a vial of CSF with a vial of plain water held 

side by side against a white background in bright light [124]. 

The utility of xanthochromia and CSF red cell counts is illustrated by a retrospective study of 117 

adults with no known history of aneurysm or previous SAH who presented with thunderclap 

headache in the absence of trauma [125]. All had a negative noncontrast head CT followed by LP. 

Xanthochromic CSF was found by visual inspection in 18 patients (15 percent). Those patients then 

had four-vessel catheter angiography, which detected a ruptured cerebral aneurysm in 13 (72 

percent). One patient with no xanthochromia had an elevated red blood cell count (≥20,000/microL) 

in four successive collection tubes and a ruptured aneurysm by angiography. Xanthochromia for the 

detection of cerebral aneurysms had a sensitivity and specificity of 93 and 95 percent. 

The presence of xanthochromia indicates that blood has been in the CSF for at least two hours; 

lumbar puncture performed before this time may not reveal xanthochromia. Xanthochromia can last 

for two weeks or more [126,127]. 

Xanthochromia can also occur with increased CSF concentrations of protein (150 mg/dL), systemic 

hyperbilirubinemia (serum bilirubin >10 to 15 mg/dL), and traumatic lumbar puncture with more than 

100,000 red blood cells/microL. 

Spectrophotometry — Spectrophotometry detects blood breakdown products as they progress 

from oxyhemoglobin to methemoglobin and finally to bilirubin [45,126,128]. Bilirubin concentration 

peaks about 48 hours after SAH onset, and it may last as long as four weeks after major SAH [129]. 



The sample of CSF to be tested by spectrophotometry should be the one that contains the least 

amount of blood staining. It should be protected from light and sent immediately to the laboratory 

for analysis [126,129]. 

Spectrophotometry for detection of bilirubin is highly sensitive (>95 percent) when LP is done at 

least 12 hours after SAH [127]. Although xanthochromia is generally confirmed by visual inspection, 

laboratory confirmation with CSF spectrophotometry is more sensitive and, if available, is 

rec ommended by some expert s [126,129-132]. This point is illustrated by a study that involved 11 

analysts who compared xanthochromic CSF samples using visual and spectrophotometric analysis 

[131]. The spectrophotometric detection of bilirubin was significantly higher than visual detection in 

conditions where CSF samples were contaminated by presence of hemolyzed blood, or when CSF 

samples contained low levels of bilirubin. 

Despite a higher sensitivity than visual inspection for the detection of xanthochromia, CSF 

spectrophotometry has only a low to moderate specificity for the diagnosis of SAH [133]. 

It should be noted that CSF spectrophotometry is not universally recommended. As a practical 

matter, spectrophotometry is rarely available in North American hospitals. 

Brain MRI — Limited data suggest that proton density and FLAIR sequences on brain MRI may be 

as sensitive as head CT for the acute detection of SAH [134]. In addition, FLAIR and T2* 

sequences on MRI have a high sensitivity in patients with a subacute presentation of SAH (eg, >4 

days from the bleed) [135]. 

Misdiagnosis — Misdiagnosis of SAH is not infrequent, and usually results from three common 

errors [136]: 

Failure to appreciate the spectrum of clinical presentation associated with SAH (see 'Clinical 

manifest at ions' above) 

Failure to obtain a head CT scan or to understand its limitations in diagnosing SAH (see 'Head CT 

scan' above) 

Failure to perform a lumbar puncture and correctly interpret the results (see 'Lumbar 

puncture' above) 

In a hospital-based series of 482 patients admitted with SAH, initial misdiagnosis occurred in 12 

percent [137]. Misdiagnosis was independently associated with small SAH volume, normal mental 

status at presentation, and right-sided aneurysm location. Failure to obtain a head CT scan at 

initial contact was the most common error, occurring in 73 percent of misdiagnosed patients. Among 

SAH patients with normal mental status at first contact (45 percent), the misdiagnosis rate rose to 

20 percent and was associated with a nearly four-fold increase in mortality at 12 months as well as 

increased morbidity among survivors. 

Delays in diagnosis of SAH are also common, even in patients with a characteristic history [138], 

leading to delays in treatment in 25 percent of patients [117] that can worsen outcome. 

IDENTIFYING THE ETIOLOGY — Once a diagnosis of SAH has been made, the etiology of the 

hemorrhage must be determined with angiographic studies. Of the available tests, digital subtraction 

angiography (DSA) is believed to have the highest resolution to detect intracranial aneurysms and 

define their anatomic features and remains the gold standard test for this indication [36]. 

No angiographic cause of SAH is evident in 14 to 22 percent of cases. It is critical to repeat the 

angiogram in 4 to 14 days if the initial angiogram is negative, since lesions may be hidden in cisterns 



packed with fresh hemorrhage. A third angiogram at a period of two to three months is advocated 

by some, but is probably not necessary. (See "Nonaneurysmal subarachnoid hemorrhage".) 

Digital subtraction angiography — Most responsible lesions can be readily identified using 

standard cross-sectional imaging techniques coupled with DSA that includes injections of the 

external carotid circulation and deep cervical branches, which may supply a cryptic dural 

arteriovenous fistula. Angiographic demonstration of key branch points, including the proximal 

posterior circulation, is essential to definitively rule out aneurysm. 

The morbidity of DSA in patients with SAH is relatively low. In a meta-analysis of three prospective 

studies, for example, the combined risk of permanent and transient neurologic complications was 

significantly lower in patients with SAH compared with those with a TIA or stroke (1.8 versus 3.7 

percent) [139]. 

CT and MR angiography — CT angiography (CTA) and magnetic resonance angiography (MRA) are 

noninvasive tests that are useful for screening and presurgical planning. Both CTA and MRA can 

identify aneurysms 3 to 5 mm or larger with a high degree of sensitivity [140], but they do not 

achieve the resolution of conventional angiography. 

The sensitivity of CTA for the detection of ruptured aneurysms, using conventional angiography or 

digital subtraction angiography as the gold standard, is 83 to 98 percent [141-146]. The addition of 

transcranial Doppler ultrasound to either CTA or MRA improves diagnostic performance, but small 

aneurysms may not be reliably identified [147]. 

The utility of CTA is continuously improving [47]. A major advantage of CTA over conventional 

angiography is the speed and ease by which it can be obtained, often immediately after the 

diagnosis of SAH is made by head CT when the patient is still in the scanner. CTA is increasingly 

used as an alternative to angiography in many patients with SAH, thereby avoiding the need for 

conventional angiography [148,149], and is particularly useful in the acute setting in a rapidly 

declining patient who needs emergent craniotomy for hematoma evacuation. Furthermore, CTA 

offers a more practical approach to acute diagnosis than MRA, given the constraints of acute 

patient management. 

Perimesencephalic hemorrhage — Some patients with an initially negative angiogram have blood 

in the cisterns around the midbrain, which reflects a perimesencephalic (nonaneurysmal) pattern of 

hemorrhage (picture 1) [150-152]. Perimesencephalic hemorrhage accounts for about 10 percent of 

all cases of SAH. 

This pattern is associated with a more favorable prognosis as illustrated in a study of 65 patients 

with perimesencephalic SAH; no patient rebled, none had delayed cerebral ischemia (compared to 4 

of 49 with aneurysmal SAH), and only three (5 percent) developed clinical signs of acute 

hydrocephalus [151]. All had a good outcome after three months with none having died or been 

disabled. 

It is believed that this nonaneurysmal pattern of hemorrhage is the result of rupture of a small pial 

fistula or prepontine vein. In support of a venous origin of bleeding, a study involving 55 patients 

with perimesencephalic SAH found that these patients were more likely than patients with 

aneurysmal SAH to have a primitive venous drainage directly into the dural sinuses instead of the 

vein of Galen [153]. 

Repeat angiography is probably not necessary in patients with perimesencephalic hemorrhage [152]. 

One study suggested that angiography may be avoided altogether if CT angiography excludes the 

presence of a vertebrobasilar aneurysm in patients with a perimesencephalic pattern of hemorrhage 

on unenhanced CT [154]. A decision analysis supported omitting invasive angiography in these 

individuals [155]. 



Perimesencephalic hemorrhage is discussed in detail separately. (See "Perimesencephalic 

nonaneurysmal subarachnoid hemorrhage".) 

Other tests — A minority of SAH is nonaneurysmal. The causes of these hemorrhages are diverse. 

This topic is discussed separately. (See "Nonaneurysmal subarachnoid hemorrhage".) 

INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. 

(See "Patient information: Stroke symptoms and diagnosis" and "Patient information: Hemorrhagic 

stroke treatment".) We encourage you to print or e-mail these topics, or to refer patients to our 

public web site www.uptodate.com/patients, which includes these and other topics. 

Use of UpToDate is subject to the Subscription and License Agreement. 

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GRAPHICS 



Light alcohol consumption reduces the risk of stroke 

The relationship between stroke of various etiologies and 

alcohol consumption was evaluated in 26,556 male 

cigarette smokers; relative risks were adjusted for age, 

body mass index, serum total cholesterol, number of 

cigarettes smoked daily, history of diabetes, history of 

heart disease, education, leisure-time activity, and 

supplementation with an antioxidant. Systolic blood 

pressure (SBP) and HDL cholesterol (HDLC) were added 

separately. Light alcohol intake reduced the risk of a 

stroke, while moderate and heavy consumption increased 

the risk. 

Data from Leppala, JM, Paunio, M, Virtamo, J, et al, Circulation 

1999; 100:1209. 



Headache and vomiting in stroke subtypes 

The frequency of sentinel headache, onset headache, and 

vomiting in three subtypes of stroke: subarachnoid 

hemorrhage (SAH), intraparenchymal (intracerebral) 

hemorrhage (IPH), and ischemic stroke (IS). Onset 

headache was present in virtually all patients with SAH and 

about one-half of those with IPH; all of these symptoms 

were infrequent in patients with IS. 

Data from Gorelick, PB, Hier, DB, Caplan, LR, et al, Neurology 

1986; 36:1445. 



Fisher grade of cerebral vasospasm risk in subarachnoid hemorrhage 

Group 

Appearance of blood on head CT scan 

1 No blood detected 

2 Diffuse deposition or thin layer with all vertical layers (in interhemispheric fissure, 

insular cistern, ambient cistern) less than 1 mm thick 

3 Localized clot and/or vertical layers 1 mm or more in thickness 

4 Intracerebral or intraventricular clot with diffuse or no subarachnoid blood 

Fisher, CM, Kistler, JP, Davis, JM. Relation of cerebral vasospasm to subarachnoid 

hemorrhage visualized by CT scanning. Neurosurgery 1980; 6:1. 



Claassen subarachnoid hemorrhage CT rating scale 

Grade 

Head CT criteria 

1 No SAH or IVH 

2 Minimal SAH and no IVH 

3 Minimal SAH with bilateral IVH 

4 Thick SAH (completely filling one or more cistern or fissure) without bilateral IVH 

5 Thick SAH (completely filling one or more cistern or fissure) with bilateral IVH 

SAH: subarachnoid hemorrhage; IVH: intraventricular hemorrhage. 

From: Claassen, J, Bernardini, GL, Kreiter, K, et al. Effect of cisternal and ventricular blood 

on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale 

revisited. Stroke 2001; 32:2012. 



Hunt and Hess grading system for patients with subarachnoid hemnorrhage 

Grade 

Neurologic status 

1 Asymptomatic or mild headache and slight nuchal rigidity 

2 Severe headache, stiff neck, no neurologic deficit except cranial nerve palsy 

3 Drowsy or confused, mild focal neurologic deficit 

4 Stuporous, moderate or severe hemiparesis 

5 Coma, decerebrate posturing 

Based upon initial neurologic examination; adapted from Hunt, W, Hess, R, J Neurosurg 1968; 

28:14. 



Perimesencephalic subarachnoid hemorrhage 

CT scan demonstrates the typical findings of a 

nonaneurysmal perimesencephalic subarachnoid 

hemorrhage. Note the predominance of hemorrhage in the 

interpeduncular fossa (arrow). 

Courtesy of Guy Rordorf, MD. 

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