The n e w e ng l a n d j o u r na l of m e dic i n e

Review article

Current Concepts

Aneurysmal Subarachnoid Hemorrhage

Jose I. Suarez, M.D., Robert W. Tarr, M.D., and Warren R. Selman, M.D.

N
ontraumatic subarachnoid hemorrhage is a neurologic emer- From the Departments of Neurology
gency characterized by the extravasation of blood into the spaces covering (J.I.S.), Radiology (R.W.T.), and Neuro-
surgery (W.R.S.), University Hospitals of
the central nervous system that are filled with cerebrospinal fluid. The Cleveland, Case Western Reserve Univer-
leading cause of nontraumatic subarachnoid hemorrhage is rupture of an intracra- sity, Cleveland. Address reprint requests
nial aneurysm, which accounts for about 80 percent of cases and has a high rate of to Dr. Suarez at the Department of Neu-
rology, Neurosciences Critical Care and
death and complications.1 Nonaneurysmal subarachnoid hemorrhage, including iso- Cerebrovascular Center, University Hos-
lated perimesencephalic subarachnoid hemorrhage, occurs in about 20 percent of pitals of Cleveland, Case Western Reserve
cases and carries a good prognosis with uncommon neurologic complications.2 University, 11100 Euclid Ave., Cleveland,
OH 44106, or at [email protected].
This review focuses on aneurysmal subarachnoid hemorrhage.
As many as 46 percent of survivors of subarachnoid hemorrhage may have N Engl J Med 2006;354:387-96.
Copyright 2006 Massachusetts Medical Society.
long-term cognitive impairment, with an effect on functional status and quality
of life.3,4 The disorder is also associated with a substantial burden on health care
resources, most of which are related to hospitalization.5 Subarachnoid hemorrhage
has distinct demographic characteristics, risk factors, and treatments. It accounts
for 2 to 5 percent of all new strokes and affects 21,000 to 33,000 people each
year in the United States.6-8 The incidence of the disorder has remained stable
over the past 30 years,1 and although it varies from region to region, the aggregate
worldwide incidence is about 10.5 cases per 100,000 person-years.9 The incidence
increases with age, with a mean age at presentation of 55 years.7 The risk for
women is 1.6 times that of men,10 and the risk for blacks is 2.1 times that of
whites.11 The average case fatality rate for subarachnoid hemorrhage is 51 percent,
with approximately one third of survivors needing lifelong care.12 Most deaths
occur within two weeks after the ictus, with 10 percent occurring before the pa-
tient receives medical attention and 25 percent within 24 hours after the event.13
Overall, subarachnoid hemorrhage accounts for 5 percent of deaths from stroke but
for 27 percent of all stroke-related years of potential life lost before the age of 65.14
The major factors associated with poor outcome are the patients level of
consciousness on admission, age, and the amount of blood shown by initial
computed tomography (CT) of the head.15 Several grading systems are used to
assess the initial clinical and radiologic features of subarachnoid hemorrhage16-19
(Table 1). The two most widely used clinical scales are those of Hunt and Hess16
and the World Federation of Neurological Surgeons.17 The latter is currently
preferred since it is based on the sum score of the Glasgow Coma Scale (a very
reliable method for evaluating the level of consciousness) and the presence of focal
neurologic signs. The higher the score, the worse the prognosis. The amount of
blood seen on initial head CT scanning can be easily evaluated.18,19 A thick sub-
arachnoid clot and bilateral ventricular hemorrhage are both predictive of poor
outcome and can be reliably graded on head CT.19
The major identified modifiable risk factors include cigarette smoking, hyper-
tension, cocaine use, and heavy alcohol use.20-22 Patients with a family history of
first-degree relatives with subarachnoid hemorrhage are also at a higher risk.21,23
Heritable connective-tissue disorders associated with the presence of intracranial

n engl j med 354;4 www.nejm.org january 26, 2006 387

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 1. Clinical and Radiologic Grading Scales for Subarachnoid Hemorrhage.

Clinical Grading Scale of the World Federation

of Neurological Surgeons* Head CT Grading Scale
Score on
Glasgow Subarachnoid
Grade Coma Scale Clinical Appearance Grade Hemorrhage Intraventricular Hemorrhage
1 15 No motor deficit 0 Absent Absent
2 1314 No motor deficit 1 Minimal Absent in both lateral ventricles
3 1314 Motor deficit 2 Minimal Present in both lateral ventricles
4 712 With or without motor deficit 3 Thick Absent in both lateral ventricles
5 36 With or without motor deficit 4 Thick Present in both lateral ventricles

* Data are from the Report of the World Federation of Neurological Surgeons.17
Data are from Claassen et al.19
The overall score on the Glasgow Coma Scale is the sum of points for eye opening (4 points), best motor response
(6 points), and best verbal response (5 points).
This designation denotes a hemorrhage filling one or more cisterns or fissures. The 10 cisterns or fissures evaluated in-
clude the frontal interhemispheric fissure, the quadrigeminal cistern, both suprasellar cisterns, both ambient cisterns,
both basal sylvian fissures, and both lateral sylvian fissures.

aneurysm and subarachnoid hemorrhage include usually includes third-nerve palsy (posterior com-
polycystic kidney disease, the EhlersDanlos syn- municating aneurysm), sixth-nerve palsy (increased
drome (type IV), pseudoxanthoma elasticum, and intracranial pressure), bilateral lower-extremity
fibromuscular dysplasia.24 The risk of rupture weakness or abulia (anterior communicating an-
depends on the size and location of the aneu- eurysm), and the combination of hemiparesis and
rysm.25,26 According to an international study of aphasia or visuospatial neglect (middle cerebral-
unruptured intracranial aneurysms,25 in patients artery aneurysm). Retinal hemorrhages should be
with no history of subarachnoid hemorrhage, the differentiated from the preretinal hemorrhages
five-year cumulative rate of rupture of aneurysms of Tersons syndrome,28 which indicates a more
located in the internal carotid artery, anterior abrupt increase in intracranial pressure and in-
communicating artery, anterior cerebral artery, creased mortality.
or middle cerebral artery is zero for aneurysms In the absence of the classic signs and symp-
under 7 mm, 2.6 percent for 7 to 12 mm, 14.5 toms, subarachnoid hemorrhage may be misdi-
percent for 13 to 24 mm, and 40 percent for 25 agnosed.27,29 The frequency of misdiagnosis may
mm or more. This rate is in contrast to rupture be up to 50 percent in patients presenting for
rates of 2.5 percent, 14.5 percent, 18.4 percent, their first visit to a physician. The common in-
and 50 percent, respectively, for the same sizes of correct diagnoses are migraine and tension-type
aneurysms in the posterior circulating and pos- headaches. Failure to obtain the appropriate im-
terior communicating artery. aging study accounts for 73 percent of cases of
misdiagnosis, and failure to perform or correctly
Di agnosis interpret the results of a lumbar puncture ac-
counts for 23 percent. Misdiagnosed patients tend
Subarachnoid hemorrhage should always be sus- to be less ill and have a normal neurologic ex-
pected in patients with a typical presentation amination. However, in such cases, neurologic
(Fig. 1),27 which includes a sudden onset of se- complications occur later in as many as 50 per-
vere headache (frequently described as the worst cent of patients, and these patients have an as-
ever), with nausea, vomiting, neck pain, photo- sociated higher risk of death and disability. Head-
phobia, and loss of consciousness. Physical exami- ache may be the only presenting symptom in up
nation may reveal retinal hemorrhages, menin- to 40 percent of patients and may abate completely
gismus, a diminished level of consciousness, and within minutes or hours30; these are called sen-
localizing neurologic signs. The latter finding tinel or thunderclap headaches or warning leaks.

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 Typical presentation
Severe headache with nausea and vomiting
Meningismus
Diminished level of consciousness
Focalizing neurologic signs
Atypical presentation
Thunderclap headache
Seizure
Confusional state
Associated head trauma

Head CT without contrast material

Subarachnoid hemorrhage No subarachnoid hemorrhage

Lumbar puncture
current concepts

CT angiography or cerebral
Unequivocally abnormal (xantho- Abnormal but equivocal (elevated Normal
angiography
chromia, elevated red-cell count red-cell count without xanthochromia

The New England Journal of Medicine

unchanged from tube 1 to tube 4) or analysis of only 1 tube)

n engl j med 354;4 www.nejm.org january 26, 2006

Stop
CT angiography or cerebral
Aneurysm found Normal
angiography

Copyright 2006 Massachusetts Medical Society. All rights reserved.

Repeat CT angio-
Prompt treatment
graphy in 13 wk
Aneurysm found Normal

Imaging of brain,

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brain stem,
and spinal cord Prompt treatment Stop

Figure 1. Diagnostic Algorithm for Subarachnoid Hemorrhage.

AUTHOR: Suarez RETAKE 1st

ICM
FIGURE: 1 of 3 2nd

389
REG F
3rd
CASE Revised
EMail Line 4-C SIZE
ARTIST: ts H/T H/T
Enon 39p6
 The n e w e ng l a n d j o u r na l of m e dic i n e

Emergency evaluation of sentinel headaches is Di agnos t ic S t udie s

required since patients may have a serious sub-
arachnoid hemorrhage within three weeks.31 In Head CT scanning should be the first study per-
many instances, no reliable clinical features dis- formed in any patient with suspected subarach-
tinguish a sentinel headache from a benign head- noid hemorrhage (Fig. 1). The characteristic ap-
ache. Some patients may not have a severe head- pearance of extravasated blood is hyperdense
ache, or other symptoms, such as seizures or a (Fig. 2). Since small amounts of blood can be
confusional state, may be more prominent. Any missed, all scans should be performed with thin
patients first or worst headache should suggest cuts through the base of the brain.32 A good-
subarachnoid hemorrhage and prompt the or- quality head CT scan will reveal subarachnoid
dering of a CT scan of the head (Fig. 1). hemorrhage in 100 percent of cases within 12

A B C

D E

Figure 2. Subarachnoid Hemorrhage in a 69-Year-Old Woman.

This patient, who had a long-standing history of smoking and hypertension, presented to the emergency room with
severe headache with nausea and vomiting for four hours and had meningismus on physical examination. Initial
computed tomography (CT) of the head ICM revealed
AUTHORa subarachnoid
Suarez hemorrhage,
RETAKEa right
1st frontal hematoma suggestive
of an anterior communicating arteryREG aneurysm,
F FIGURE and hydrocephalus
2a-e (Panel A). An external
2nd ventricular drain was
inserted on arrival. Digital-subtraction
CASEcerebral 3rd
TITLE angiography (oblique view) showed Revised
an aneurysm stemming from
the anterior communicating artery (Panel
EMail B, arrow). Three-dimensional
Line 4-C digital-subtraction angiography clearly
showed the bilobed, irregular natureEnonof theARTIST:
aneurysmmst (Panel C, arrow). The SIZE underwent craniotomy and sur-
patient
H/T H/T
gical clipping of the aneurysm, withFILL Combo Six days after
good postoperative recovery. 33p9admission, the patient had rapid
onset of global aphasia and right hemiparesis. Transcranial
AUTHOR, PLEASEDopplerNOTE:ultrasonography demonstrated a severe eleva-
tion in blood-flow velocities (>200 cm Figure has beeninredrawn
per second) the leftand type has
middle been
and reset. cerebral arteries. Angiography
anterior
showed considerable vasospasm (Panel D) in the Please proximalcheck carefully.
segments of the left anterior arteries (arrowhead) and
middle cerebral arteries (arrow). The patient underwent transluminal balloon angioplasty of the left middle cerebral
JOB: 35404 ISSUE: 1-26-06
artery, and direct vasodilators (papaverine and verapamil) were infused into the left anterior cerebral artery with
good resolution of the vasospasm (Panel E). The patients clinical course evolved favorably, and she was indepen-
dent three months after presentation.

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 current concepts

hours after the onset of symptoms and in more raphy may obviate the need for invasive cerebral
than 93 percent of cases within 24 hours.33 Head angiography and its inherent risks.
CT scanning can also demonstrate intraparen-
chymal hematomas, hydrocephalus, and cerebral T r e atmen t
edema and can help predict the site of aneurysm
rupture, particularly in patients with aneurysms All patients with subarachnoid hemorrhage should
in the anterior cerebral or anterior communicat- be evaluated and treated on an emergency basis
ing arteries (Fig. 2).34 Head CT scanning is also with maintenance of airway and cardiovascular
the most reliable test for predicting cerebral va- function (Table 2). After initial stabilization, pa-
sospasm and poor outcome.35 Because of rapid tients should be transferred to centers with neu-
clearance of blood, delayed head CT scanning rovascular expertise and preferably with a dedi-
may be normal despite a suggestive history, and cated neurologic critical care unit to optimize
sensitivity drops to 50 percent at seven days.23 care.37,38 Once in the critical care setting, the main
Lumbar puncture should be performed in any goals of treatment are the prevention of rebleed-
patient with suspected subarachnoid hemorrhage ing, the prevention and management of vaso-
and negative or equivocal results on head CT scan- spasm, and the treatment of other medical and
ning (Fig. 1). Cerebrospinal fluid should be col- neurologic complications.
lected in four consecutive tubes, with the red-
cell count determined in tubes 1 and 4. Findings General Therapy
consistent with subarachnoid hemorrhage in- Blood pressure should be maintained within nor-
clude an elevated opening pressure, an elevated mal limits, and if necessary, intravenous antihy-
red-cell count that does not diminish from tube pertensive agents such as labetalol and nicardi
1 to tube 4, and xanthochromia (owing to red- pine can be used.23 Once the aneurysm is secured,
cell breakdown detected by spectrophotometry), hypertension is allowed, but there is no agree-
which may require more than 12 hours to de- ment on the range. Analgesia is often required,
velop. In patients with either equivocal or diag- and reversible agents such as narcotics are indi-
nostic lumbar puncture, an imaging study, such as cated. Two important factors that are associated
CT angiography of the head or cerebral angiogra- with poor outcome are hyperglycemia and hyper-
phy, should be the next step (Fig. 1 and 2). Digital- thermia, and both should be corrected.39,40 Pro-
subtraction cerebral angiography has been the phylaxis of deep venous thrombosis should be
gold standard for the detection of cerebral an- instituted early with sequential compressive de-
eurysm, but CT angiography has gained popular- vices, and subcutaneous heparin should be added
ity and is frequently used owing to its noninvasive- after the aneurysm is treated. Calcium antago-
ness and a sensitivity and specificity comparable nists reduce the risk of poor outcome from ische
to that of cerebral angiography.36 mic complications, and oral nimodipine is cur-
In all instances, a careful evaluation of all ce- rently recommended.41 Prolonged administration
rebral vessels should be undertaken, since about of antifibrinolytic agents reduces rebleeding but
15 percent of patients will have multiple aneu- is associated with an increased risk of cerebral
rysms. Patients with a negative imaging study ischemia and systemic thrombotic events.42 Early
should have a repeated study 7 to 14 days after treatment of aneurysms has become the main-
the initial presentation. If the second evaluation stay of rebleeding prevention, but antifibrinolytic
does not reveal an aneurysm, magnetic resonance therapy may be used in the short term before
imaging (MRI) should be performed to uncover aneurysm treatment.
a possible vascular malformation of the brain,
brain stem, or spinal cord. Other imaging tech- Treatment Options for Aneurysms
niques that may be used include MRI of the head Currently, the two main therapeutic options for
to determine the size of the aneurysm (particu- securing a ruptured aneurysm are microvascular
larly in cases of partial thrombosis of the aneu- neurosurgical clipping and endovascular coiling.
rysm) and three-dimensional digital-subtraction Historically, microsurgical clipping has been the
cerebral angiography (which helps delineate the preferred method of treatment. Although the tim-
morphology of the aneurysm) (Fig. 2C). Also, re- ing of surgery has been debated, most neurovas-
cent advances in three-dimensional CT angiog- cular surgeons recommend early operation. Evi-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 2. Treatment Guidelines for Subarachnoid Hemorrhage.*

Management of Condition Recommendations

General measures

Airway and cardiovascular system Monitor closely in intensive care unit or preferably in neurologic critical care unit
Environment Maintain reduced noise level and limit visitors until aneurysm is treated
Pain Administer morphine sulfate (24 mg IV every 24 hr) or codeine (3060 mg IM every 4 hr)
Gastrointestinal prophylaxis Administer ranitidine (150 mg PO twice daily or 50 mg IV every 812 hr) or lansoprazole (30 mg PO
daily)
Deep venous thrombosis prophylaxis Use thigh-high stockings and sequential compression pneumatic devices; administer heparin
(5000 U SC three times daily) after treatment of aneurysm
Blood pressure Keep systolic blood pressure at 90140 mm Hg before aneurysm treatment, then allow hypertension
to keep systolic blood pressure <200 mm Hg
Serum glucose Maintain level at 80120 mg/dl; use sliding scale or continuous infusion of insulin if necessary
Core body temperature Keep at 37.2C; administer acetaminophen (325650 mg PO every 46 hr) and use cooling devices
if necessary
Calcium antagonist Administer nimodipine (60 mg PO every 4 hr for 21 days)
Antifibrinolytic therapy (optional) Administer aminocaproic acid (first 2448 hr, 5 g IV, followed by infusion at 1.5 g/hr)
Anticonvulsants Administer phenytoin (35 mg/kg/day PO or IV) or valproic acid (1545 mg/kg/day PO or IV)
Fluids and hydration Maintain euvolemia (CVP, 58 mm Hg); if cerebral vasospasm is present, maintain hypervolemia
(CVP, 812 mm Hg, or PCWP, 1216 mm Hg)
Nutrition Try oral intake (after evaluation of swallowing); for alternative routes, enteral feeding preferred
Other treatment
Surgical clipping Perform procedure within first 72 hr
Endovascular coiling Perform procedure within first 72 hr
Common complications
Hydrocephalus Insert external ventricular or lumbar drain
Rebleeding Provide supportive care and emergency treatment of aneurysm
Cerebral vasospasm Maintain hypervolemia or induced hypertension with phenylephrine, norepinephrine, or dopamine;
provide endovascular treatment (transluminal angioplasty or direct vasodilators)

Seizures Administer lorazepam (0.1 mg/kg, at a rate of 2 mg/min), followed by phenytoin (20 mg/kg IV bolus
at <50 mg/min, up to 30 mg/kg)
Hyponatremia With SIADH, restrict fluids; with cerebral salt-wasting syndrome, aggressively replace fluids with
0.9% saline or hypertonic saline solution
Myocardial injury and arrhythmias Administer metoprolol (12.5100 mg PO twice daily); evaluate ventricular function; treat arrhythmia
Pulmonary edema Provide supplemental oxygen or mechanical ventilation if necessary; monitor PCWP and ventricular
function; distinguish cardiogenic vs. neurogenic pulmonary edema

Long-term care
Rehabilitation Provide physical, occupational, and speech therapies
Neuropsychological evaluation Perform global and domain-specific testing; provide cognitive rehabilitation
Depression Administer antidepressant medications and provide psychotherapy
Chronic headaches Administer NSAIDs, tricyclic antidepressants, or SSRIs; gabapentin

* Recommendations are based on generally accepted practices and may not be based on controlled trials. IV denotes intravenously, IM intramus-
cularly, PO orally, SC subcutaneously, CVP central venous pressure, PCWP pulmonary-capillary wedge pressure, SIADH syndrome of inappropri-
ate secretion of antidiuretic hormone, NSAIDs nonsteroidal antiinflammatory drugs, and SSRIs selective serotonin-reuptake inhibitors.

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 current concepts

dence from clinical trials suggests that patients neck diameter to that of the largest dome is more
undergoing early surgery have a lower rate of re- than 0.5) tend to be less suitable for endovascu-
bleeding and tend to fare better than those treat- lar coiling. Aneurysms associated with large pa-
ed later.43 Securing the ruptured aneurysm will renchymal hematomas and those that have nor-
also facilitate the treatment of complications such mal branches arising from the base or dome are
as cerebral vasospasm.7 Although many neuro- often more suitable for microsurgical clipping.
vascular surgeons use mild hypothermia during In addition, for aneurysms causing a local mass
microsurgical clipping of aneurysms, it has not effect, surgical therapy may be more efficacious.
proved to be beneficial in patients with lower Owing to the complex analysis of specific vari-
grades of subarachnoid hemorrhages.44 ables among patients and types of aneurysms that
Endovascular treatment of aneurysms has been is needed to determine the most appropriate
available as an alternative to surgical therapy for treatment for individual patients, we recommend
the past 15 years.45 Coils are made of platinum evaluation by practitioners who have detailed
and are attached to a delivery wire. Once proper knowledge of neurovascular surgery, endovascu-
position within the aneurysm is achieved, coils lar techniques, and neurologic critical care.
are detached from the wire. Multiple coils of vari-
ous length and diameter are often packed into Management of Complications
the aneurysm to exclude it from the circulation Neurologic complications are common and in-
(Fig. 3). clude symptomatic vasospasm (46 percent of pa-
The International Subarachnoid Aneurysm Trial tients), hydrocephalus (20 percent), and rebleed-
(ISAT) prospectively examined patients with rup- ing (7 percent).51,52 Patients with rebleeding have
tured aneurysms who were considered equally a high risk of permanent neurologic disability
suitable for either endovascular coiling or micro- and a mortality rate of about 50 percent.23 Re-
surgical clipping.46,47 The authors found that for bleeding can be prevented with early treatment,
this particular subgroup of patients, a favorable since the condition is more common in the ini-
outcome, which was defined as survival free of tial few days (4 percent on the first day and 1.5
disability at one year, occurred significantly more percent per day for the next two weeks).23 Cere-
often in patients treated with endovascular coil- bral vasospasm is most likely an inflammatory
ing than with surgical placement of clips. The risk reaction in the blood-vessel wall and develops be-
of epilepsy was substantially lower in patients who tween days 4 and 12 after subarachnoid hemor-
underwent endovascular coiling, but the risk of rhage. The best predictor of vasospasm is the
rebleeding was higher. Also, in patients who un- amount of blood seen on the initial head CT
derwent follow-up cerebral angiography, the rate scan.15,18,19 Angiographic vasospasm is more com-
of complete occlusion of the aneurysm was greater mon (occurring in about two thirds of patients)
with surgical clipping. than is symptomatic vasospasm (with clinical
ISAT was a landmark study that validated the evidence of cerebral ischemia). Transcranial Dop-
technique of endovascular coiling. However, many pler ultrasonography is performed either daily or
aneurysms are not equally suitable for either every other day to monitor for vasospasm, which
microsurgical clipping or endovascular coiling. is defined as a mean velocity of cerebral blood
In individual cases, several factors such as the flow of more than 120 cm per second in a major
patients age and overall medical condition and vessel. Doppler ultrasonography has a sensitivity
the aneurysms location, morphology, and relation- that is similar to that of cerebral angiography for
ship to adjacent vessels need to be analyzed the detection of narrowed vessels, particularly in
to decide on the most appropriate treatment.48-50 the middle cerebral and internal cerebral arter-
In general, elderly patients or patients in poor ies.53 Once symptomatic vasospasm is evident (with
medical condition are often better suited for en- focal neurologic signs), patients are treated with
dovascular coiling. Aneurysms of the vertebro- hypervolemia and induced hypertension (Table 2).
basilar circulation or aneurysms deep in the skull Patients whose condition does not improve with
base, such as paraophthalmic aneurysms, may be medical therapy undergo emergency cerebral an-
more easily accessed by an endovascular approach. giography and transluminal angioplasty or vaso-
Wide-neck aneurysms (in which the ratio of the dilator infusion when focal vessel narrowing is

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Figure 3. Endovascular Coiling of Ruptured Intracranial

Aneurysm.
Panel A shows a drawing of a platinum coil after deploy-
ment. Panel B shows cerebral angiography of a ruptured
aneurysm at the basilar tip before endovascular coiling
(arrow) and immediately after endovascular coiling
(Panel C).

detected (Fig. 2). Other radiologic evaluation, such

as brain MRI, should also be selectively under-
taken because brain infarctions do not always
have gross clinical manifestations. Symptomatic
hydrocephalus that is caused by diminished ab-
sorption of cerebrospinal fluid may require treat-
ment with temporary external ventricular drainage
or the placement of a permanent shunt. Seizures
occur in up to a third of patients.7 Although the
effectiveness of prophylactic anticonvulsant agents
has not been formally tested, the potentially devas-
tating effects of seizures, which may lead to re-
bleeding, suggest the use of anticonvulsants for
at least one week after the initial bleed (Table 2).
Patients who are in a coma should undergo mon-
itoring with electroencephalography, since the fre-
quency of nonconvulsive seizures can be as high
as 20 percent.54
Potentially preventable medical complications
after subarachnoid hemorrhage may increase mor-
bidity, the length of the hospital stay, and mor-
tality. The vast majority of patients experience a
medical complication, which could be severe in
40 percent of cases.51 The most common medical
complications include pulmonary edema in 23
percent (either cardiogenic or neurogenic with the
acute respiratory distress syndrome), cardiac ar-
rhythmias in 35 percent, and electrolyte distur-
bances in 28 percent of patients. Hyponatremia
can be caused by inappropriate secretion of antidi-
uretic hormone (normal or increased intravascu-
lar volume) or cerebral salt wasting (low intra-
vascular volume).2,4 Treatment of hyponatremia
consists of fluid restriction for the former condi-
tion and aggressive fluid administration for the
latter. In general, patients should be kept eu-
volemic at all times, since hypovolemia is asso-
ciated with cerebral ischemia and a worse out-
come (Table 2).2

Long-term Care
Many survivors of subarachnoid hemorrhage may
have chronically disabling problems.3,4 More than
50 percent of survivors report problems with mem-

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 current concepts

ory, mood, or neuropsychological function. These in well-designed clinical trials include, among
deficits result in an impairment of social roles, others, the use of human albumin for neuropro-
even with an absence of apparent physical dis- tection,55 intracisternal application of thrombo-
ability. Half to two thirds of survivors are able lytic therapy and washing to decrease the blood
to return to work one year after a subarachnoid burden,56 and new radiologic and endovascular
hemorrhage. Prompt physical and neuropsycho- techniques (e.g., biologically active coils and
logical evaluation and treatment should be initi- stents) to improve the treatment of aneurysm
ated (Table 2). and vasospasm.57,58 Other areas to be addressed
are the need for prophylactic anticonvulsants and
F u t ur e R e se a rch the implementation of aggressive preventive mea-
sures, such as hypertension control and smoking
Further epidemiologic studies and new treatments cessation.
are needed to improve the outcome of patients Dr. Tarr reports having received consulting fees from Cordis.
with subarachnoid hemorrhage. Determinants of No other potential conflict of interest relevant to this article was
the growth and rupture of aneurysms need to be reported.
We are indebted to Dr. Robert B. Daroff for reviewing the
studied. Improved prevention and diagnosis of manuscript and to Dr. Daniel Hsu and Elena Dupont for provid-
cerebral vasospasm require more study. Promis- ing technical assistance with the figures.
ing areas of research that warrant further testing

References
1. van Gijn J, Rinkel GJ. Subarachnoid Jones RP. Observer variability in assessing after subarachnoid hemorrhage: the Fish-
haemorrhage: diagnosis, causes and man- the clinical features of subarachnoid er scale revisited. Stroke 2001;32:2012-20.
agement. Brain 2001;124:249-78. hemorrhage. J Neurosurg 1983;58:57-62. 20. Qureshi AI, Suri MF, Yahia AM, et al.
2. Adams HP Jr, Gordon DL. Nonaneu- 11. Broderick JP, Brott T, Tomsick T, Hus- Risk factors for subarachnoid hemor-
rysmal subarachnoid hemorrhage. Ann ter G, Miller R. The risk of subarachnoid rhage. Neurosurgery 2001;49:607-12.
Neurol 1991;29:461-2. and intracerebral hemorrhages in blacks 21. Broderick JP, Viscoli CM, Brott T, et
3. Mayer SA, Kreiter KT, Copeland D, et as compared with whites. N Engl J Med al. Major risk factors for aneurysmal sub-
al. Global and domain-specific cognitive 1992;326:733-6. arachnoid hemorrhage in the young are
impairment and outcome after subarach- 12. Hop JW, Rinkel GJ, Algra A, van Gijn modifiable. Stroke 2003;34:1375-81.
noid hemorrhage. Neurology 2002;59:1750- J. Case-fatality rates and functional out- 22. Teunissen LL, Rinkel GJ, Algra A, van
8. come after subarachnoid hemorrhage: a sys- Gijn J. Risk factors for subarachnoid hem-
4. Hackett ML, Anderson CS. Health tematic review. Stroke 1997;28:660-4. orrhage: a systematic review. Stroke
outcomes 1 year after subarachnoid hem- 13. Broderick JP, Brott TG, Duldner JE, 1996;27:544-9.
orrhage: an international population- Tomsick T, Leach A. Initial and recurrent 23. Bambakidis NC, Selman WR. Sub-
based study. Neurology 2000;55:658-62. bleeding are the major causes of death arachnoid hemorrhage. In: Suarez JI, ed.
5. Roos YB, Dijkgraaf MGW, Albrecht following subarachnoid hemorrhage. Critical care neurology and neurosurgery.
KW, et al. Direct costs of modern treat- Stroke 1994;25:1342-7. Totowa, N.J.: Humana Press, 2004:365-77.
ment of aneurysmal subarachnoid hemor- 14. Johnston SC, Selvin S, Gress DR. The 24. Schievink WI, Michels VV, Piepgras DG.
rhage in the first year after diagnosis. burden, trends, and demographics of mor- Neurovascular manifestations of heritable
Stroke 2002;33:1595-9. tality from subarachnoid hemorrhage. connective tissue disorders: a review. Stroke
6. American Heart Association. Heart Neurology 1998;50:1413-8. 1994;25:889-903.
disease and stroke statistics 2005 up- 15. Hijdra A, van Gijn J, Nagelkerke NJ, 25. Wiebers DO, Whisnant JP, Huston J
date. Dallas: American Heart Association, Vermeulen M, van Crevel H. Prediction of III, et al. Unruptured intracranial aneu-
2005. delayed cerebral ischemia, rebleeding, rysms: natural history, clinical outcome,
7. Mayberg MR, Batjer HH, Dacey R, et and outcome after aneurysmal subarach- and risks of surgical and endovascular
al. Guidelines for the management of noid hemorrhage. Stroke 1988;19:1250-6. treatment. Lancet 2003;362:103-10.
aneurysmal subarachnoid hemorrhage: 16. Hunt WE, Hess RM. Surgical risk as 26. White PM, Wardlaw J. Unruptured in-
astatement for healthcare professionals related to time of intervention in the re- tracranial aneurysms: prospective data
from a special writing group of the Stroke pair of intracranial aneurysms. J Neuro- have arrived. Lancet 2003;362:90-1.
Council, American Heart Association. surg 1968;28:14-20. 27. Edlow JA, Caplan LR. Avoiding pit-
Stroke 1994;25:2315-28. 17. Report of World Federation of Neuro- falls in the diagnosis of subarachnoid
8. Sudlow CL, Warlow CP. Comparable logical Surgeons committee on a univer- hemorrhage. N Engl J Med 2000;342:29-
studies of the incidence of stroke and its sal subarachnoid hemorrhage grading 36.
pathological types: results from an inter- scale. J Neurosurg 1988;68:985-6. 28. McCarron MO, Alberts MJ, McCarron
national collaboration. Stroke 1997;28:491- 18. Fisher CM, Kistler JP, Davis JM. Rela- P. A systematic review of Tersons syn-
9. tion of cerebral vasospasm to subarach- drome: frequency and prognosis after
9. Linn FH, Rinkel GJ, Algra A, van Gijn noid hemorrhage visualized by computed subarachnoid hemorrhage. J Neurol Neu-
J. Incidence of subarachnoid hemorrhage: tomographic scanning. Neurosurgery rosurg Psychiatry 2004;75:491-3.
role of region, year, and rate of computed 1980;6:1-9. 29. Kowalski RG, Claassen J, Kreiter KT,
tomography: a meta-analysis. Stroke 1996; 19. Claassen J, Bernardini GL, Kreiter K, et al. Initial misdiagnosis and outcome
27:625-9. et al. Effect of cisternal and ventricular after subarachnoid hemorrhage. JAMA
10. Lindsay KW, Teasdale GM, Knill- blood on risk of delayed cerebral ischemia 2004;291:866-9.

n engl j med 354;4 www.nejm.org january 26, 2006 395

The New England Journal of Medicine
Downloaded from nejm.org on December 18, 2015. For personal use only. No other uses without permission.
Copyright 2006 Massachusetts Medical Society. All rights reserved.
 current concepts

30. Polmear A. Sentinel headaches in an- tensive care unit. Neurology 2003;60:837- from the Committee on Cerebrovascular
eurysmal subarachnoid hemorrhage: what 41. Imaging of the American Heart Associa-
is the true incidence? A systematic review. 41. Rinkel GJ, Feigin VL, Algra A, van den tion Council on Cardiovascular Radiolo-
Cephalalgia 2003;23:935-41. Bergh WM, Vermeulen M, Gijn J. Calcium gy. Stroke 2002;33:2536-44.
31. Leblanc R. The minor leak preceding antagonists for aneurysmal subarachnoid 50. Lozier AP, Connolly ES Jr, Lavine SD,
subarachnoid hemorrhage. J Neurosurg hemorrhage. Cochrane Database Syst Rev Solomon RA. Guglielmi detachable coil
1987;66:35-9. 2005;1:CD000277. embolization of posterior circulation an-
32. Latchaw RE, Silva P, Falcone SF. The 42. Roos YB, Rinkel GJ, Vermeulen M, Al- eurysms: a systematic review of the litera-
role of CT following aneurysmal rupture. gra A, van Gijn J. Antifibrinolytic therapy ture. Stroke 2002;33:2509-18.
Neuroimaging Clin N Am 1997;7:693- for aneurysmal subarachnoid hemorrhage. 51. Solenski NJ, Haley EC Jr, Kassell NF,
708. Cochrane Database Syst Rev 2003;2: et al. Medical complications of aneurys-
33. Sames TA, Storrow AB, Finkelstein CD001245. mal subarachnoid hemorrhage: a report
JA, Magoon MR. Sensitivity of new-gen- 43. Whitfield PC, Kirkpatrick PJ. Timing of the multicenter, cooperative aneurysm
eration computed tomography in sub- of surgery for aneurysmal subarachnoid study. Crit Care Med 1995;23:1007-17.
arachnoid hemorrhage. Acad Emerg Med hemorrhage. Cochrane Database Syst Rev 52. van Gijn J, Hijdra A, Wijdicks EF, Ver-
1996;3:16-20. 2001;2:CD001697. meulen M, van Crevel H. Acute hydro-
34. van der Jagt M, Hasan D, Bijvoet HW, 44. Todd MM, Hindman BJ, Clarke WR, cephalus after aneurysmal subarachnoid
et al. Validity of prediction of the site of Torner JC. Mild intraoperative hypother- hemorrhage. J Neurosurg 1985;63:355-62.
ruptured intracranial aneurysms with CT. mia during surgery for intracranial aneu- 53. Suarez JI, Qureshi AI, Yahia AB, et al.
Neurology 1999;52:34-9. rysm. N Engl J Med 2005;352:135-45. Symptomatic vasospasm diagnosis after
35. Adams HP Jr, Kassell NF, Torner JC, 45. Guglielmi G, Vinuela F, Dion J, Duck- subarachnoid hemorrhage: evaluation of
Haley EC Jr. Predicting cerebral ischemia wiler G. Electrothrombosis of saccular an- transcranial Doppler ultrasound and ce-
after aneurysmal subarachnoid hemor- eurysms via endovascular approach. Part 2: rebral angiography as related to compro-
rhage: influences of clinical condition, CT preliminary clinical experience. J Neuro- mised vascular distribution. Crit Care Med
results, and antifibrinolytic therapy: a re- surg 1991;75:8-14. 2002;30:1348-55.
port of the Cooperative Aneurysm Study. 46. Molyneux A, Kerr R, Stratton I, et al. 54. Claassen J, Mayer SA, Kowalski RG,
Neurology 1987;37:1586-91. International Subarachnoid Aneurysm Emerson RG, Hirsch LJ. Detection of elec-
36. Jayaraman MV, Mayo-Smith WW, Trial (ISAT) of neurosurgical clipping trographic seizures with continuous EEG
Tung GA, et al. Detection of intracranial versus endovascular coiling in 2143 pa- monitoring in critically ill patients. Neu-
aneurysms: multi-detector row CT angi- tients with ruptured intracranial aneu- rology 2004;62:1743-8.
ography compared with DSA. Radiology rysms: a randomised trial. Lancet 2002;360: 55. Suarez JI, Shannon L, Zaidat OO, et
2004;230:510-8. 1267-74. al. Effect of human albumin administra-
37. Bardach NS, Olson SJ, Elkins JS, 47. Molyneux AJ, Kerr RS, Yu L-M, et al. tion on clinical outcome and hospital cost
Smith WS, Lawton MT, Johnston SC. Re- International Subarachnoid Aneurysm in patients with subarachnoid hemorrhage.
gionalization of treatment for subarach- Trial (ISAT) of neurosurgical clipping ver- J Neurosurg 2004;100:585-90.
noid hemorrhage: a cost-utility analysis. sus endovascular coiling in 2143 patients 56. Amin-Hanjani S, Ogilvy CS, Barker
Circulation 2004;109:2207-12. with ruptured intracranial aneurysms: FG II. Does intracisternal thrombolysis
38. Suarez JI, Zaidat OO, Suri MF, et al. arandomised comparison of effects on prevent vasospasm after aneurysmal sub-
Length of stay and mortality in neuro- survival, dependency, seizures, rebleeding, arachnoid hemorrhage? A meta-analysis.
critically ill patients: impact of a special- subgroups, and aneurysm occlusion. Lan- Neurosurgery 2004;54:326-34.
ized neurocritical care team. Crit Care Med cet 2005;366:809-17. 57. Qureshi AI. Endovascular treatment
2004;32:2311-7. 48. Britz GW. ISAT trial: coiling or clip- of cerebrovascular diseases and intracra-
39. Dorhout Mees SM, van Dijk GW, Algra ping for intracranial aneurysms? Lancet nial neoplasms. Lancet 2004;363:804-13.
A, Kempink DR, Rinkel GJ. Glucose levels 2005;366:783-5. 58. Hoeffner EG, Case I, Jain R, et al. Ce-
and outcome after subarachnoid hemor- 49. Johnston SC, Higashida RT, Barrow DL, rebral perfusion CT: technique and clini-
rhage. Neurology 2003;61:1132-3. et al. Recommendations for the endovascu- cal applications. Radiology 2004;231:632-
40. Commichau C, Scarmeas N, Mayer SA. lar treatment of intracranial aneurysms: 44.
Risk factors for fever in the neurologic in- a statement for healthcare professionals Copyright 2006 Massachusetts Medical Society.

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