3350 PART 13 Neurologic Disorders

Thalamic hemorrhages also produce a contralateral hemiplegia or

hemiparesis from pressure on, or dissection into, the adjacent internal

capsule. A prominent sensory deficit involving all modalities is usually

present. Aphasia, often with preserved verbal repetition, may occur

after hemorrhage into the dominant thalamus, and constructional

apraxia or mutism occurs in some cases of nondominant hemorrhage. There may also be a homonymous visual field defect. Thalamic

hemorrhages cause several typical ocular disturbances by extension

inferiorly into the upper midbrain. These include deviation of the eyes

downward and inward so that they appear to be looking at the nose,

unequal pupils with absence of light reaction, skew deviation with the

eye opposite the hemorrhage displaced downward and medially, ipsilateral Horner’s syndrome, absence of convergence, paralysis of vertical

gaze, and retraction nystagmus. Patients may later develop a chronic,

contralateral pain syndrome (Déjérine-Roussy syndrome).

In pontine hemorrhages, deep coma with quadriplegia often occurs

over a few minutes. Typically, there is prominent decerebrate rigidity

and “pinpoint” (1 mm) pupils that react to light. There is impairment

of reflex horizontal eye movements evoked by head turning (doll’shead or oculocephalic maneuver) or by irrigation of the ears with ice

water (Chap. 28). Hyperpnea, severe hypertension, and hyperhidrosis

are common. Most patients with deep coma from pontine hemorrhage

ultimately die or develop a locked-in state, but small hemorrhages are

compatible with survival and significant recovery.

Cerebellar hemorrhages usually develop over several hours and are

characterized by occipital headache, repeated vomiting, and ataxia of

gait. In mild cases, there may be no other neurologic signs except for

gait ataxia. Dizziness or vertigo may be prominent. There is often paresis of conjugate lateral gaze toward the side of the hemorrhage, forced

deviation of the eyes to the opposite side, or an ipsilateral sixth nerve

palsy. Less frequent ocular signs include blepharospasm, involuntary

closure of one eye, ocular bobbing, and skew deviation. Dysarthria and

dysphagia may occur. As the hours pass, the patient often becomes stuporous and then comatose from brainstem compression or obstructive

hydrocephalus; immediate surgical evacuation before severe brainstem

compression occurs may be lifesaving. Hydrocephalus from fourth

ventricle compression can be relieved by external ventricular drainage;

however, in this situation, definitive hematoma evacuation is recommended rather than treatment with ventricular drainage alone. If the

deep cerebellar nuclei are spared, full recovery is common.

Lobar Hemorrhage The major neurologic deficit with an occipital hemorrhage is hemianopsia; with a left temporal hemorrhage,

aphasia and delirium; with a parietal hemorrhage, hemisensory loss;

and with frontal hemorrhage, arm weakness. Large hemorrhages may

be associated with stupor or coma if they compress the thalamus or

midbrain. Most patients with lobar hemorrhages have focal headaches,

and more than one-half vomit or are drowsy. Stiff neck and seizures

are uncommon.

Other Causes of ICH CAA is a disease of the elderly in which

arteriolar degeneration occurs and amyloid is deposited in the walls

of the cerebral arteries. Amyloid angiopathy causes both single and

recurrent lobar hemorrhages and is probably the most common cause

of lobar hemorrhage in the elderly. It accounts for some intracranial

hemorrhages associated with IV thrombolysis given for myocardial

infarction. This disorder can be suspected in patients who present with

multiple hemorrhages (and infarcts) over several months or years or in

patients with “microbleeds” in the cortex, seen on brain MRI sequences

sensitive for hemosiderin (iron-sensitive imaging), but it is definitively diagnosed by pathologic demonstration of Congo red staining

of amyloid in cerebral vessels. The ε2 and ε4 allelic variations of the

apolipoprotein E gene are associated with increased risk of recurrent

lobar hemorrhage and may therefore be markers of amyloid angiopathy. Positron emission tomography imaging can image amyloid-beta

deposits in CAA using specific antibody labels and may be helpful in

diagnosing CAA noninvasively. Although cerebral biopsy is the most

definitive method of diagnosis, evidence of inflammation on lumbar

puncture should prompt consideration of CAA-associated vasculitis

as an underlying cause, and oral glucocorticoids may be beneficial.

Noninflammatory CAA has no specific treatment. Oral anticoagulants

are typically avoided.

Cocaine and methamphetamine are frequent causes of stroke in

young (age <45 years) patients. ICH, ischemic stroke, and subarachnoid hemorrhage (SAH) are all associated with stimulant use. Angiographic findings vary from completely normal arteries to large-vessel

occlusion or stenosis, vasospasm, or changes consistent with vasculopathy. The mechanism of sympathomimetic-related stroke is not known,

but cocaine enhances sympathetic activity causing acute, sometimes

severe, hypertension, and this may lead to hemorrhage. Slightly

more than one-half of stimulant-related intracranial hemorrhages are

intracerebral and the rest are subarachnoid. In cases of SAH, a saccular

aneurysm is usually identified. Presumably, acute hypertension causes

aneurysmal rupture.

Head injury often causes intracranial bleeding. The common sites

are intraparenchymal (especially temporal and inferior frontal lobes)

and into the subarachnoid, subdural, and epidural spaces. Trauma

must be considered in any patient with an unexplained acute neurologic deficit (hemiparesis, stupor, or confusion), particularly if the

deficit occurred in the context of a fall (Chap. 443).

Intracranial hemorrhages associated with anticoagulant therapy

can occur at any location; they are often lobar or subdural. Anticoagulant-related ICHs may continue to evolve over 24–48 h, especially if

coagulopathy is insufficiently reversed. Coagulopathy and thrombocytopenia should be reversed rapidly, as discussed below. ICH associated

with hematologic disorders (leukemia, aplastic anemia, thrombocytopenic purpura) can occur at any site and may present as multiple

ICHs. Skin and mucous membrane bleeding may be evident and offers

a diagnostic clue.

Hemorrhage into a brain tumor may be the first manifestation of

neoplasm. Choriocarcinoma, malignant melanoma, renal cell carcinoma, and bronchogenic carcinoma are among the most common

metastatic tumors associated with ICH. Glioblastoma multiforme in

adults and medulloblastoma in children may also have areas of ICH.

Hypertensive encephalopathy is a complication of malignant hypertension. In this acute syndrome, severe hypertension is associated with

headache, nausea, vomiting, convulsions, confusion, stupor, and coma.

Focal or lateralizing neurologic signs, either transitory or permanent,

may occur but are infrequent and therefore suggest some other vascular disease (hemorrhage, embolism, or atherosclerotic thrombosis).

There are retinal hemorrhages, exudates, papilledema (hypertensive

retinopathy), and evidence of renal and cardiac disease. In most cases,

ICP and CSF protein levels are elevated. MRI brain imaging shows a

pattern of typically posterior (occipital > frontal) brain edema that is

reversible and termed reversible posterior leukoencephalopathy. The

hypertension may be essential or due to chronic renal disease, acute

glomerulonephritis, acute toxemia of pregnancy, pheochromocytoma,

or other causes. Lowering the blood pressure reverses the process, but

stroke can occur, especially if blood pressure is lowered too rapidly.

Neuropathologic examination reveals multifocal to diffuse cerebral

edema and hemorrhages of various sizes from petechial to massive.

Microscopically, there is necrosis of arterioles, minute cerebral infarcts,

and hemorrhages. The term hypertensive encephalopathy should be

reserved for this syndrome and not for chronic recurrent headaches,

dizziness, recurrent transient ischemic attacks, or small strokes that

often occur in association with high blood pressure. Distinguishing

hypertensive encephalopathy with ICH from hypertensive ICH is

important since aggressive lowering of SBP to 140–180 mmHg acutely

is usually considered in hypertensive ICH, but less aggressive measures

should be used in hypertensive encephalopathy. Having no alteration

in mental status or other prodrome prior to the ICH favors hypertensive ICH as the disease.

Primary intraventricular hemorrhage is rare and should prompt

investigation for an underlying vascular anomaly. Sometimes bleeding begins within the periventricular substance of the brain and

dissects into the ventricular system without leaving signs of intraparenchymal hemorrhage. Alternatively, bleeding can arise from

periependymal veins. Vasculitis, usually polyarteritis nodosa or lupus

3351 Intracranial Hemorrhage CHAPTER 428

erythematosus, can produce hemorrhage in any region of the central

nervous system; most hemorrhages are associated with hypertension,

but the arteritis itself may cause bleeding by disrupting the vessel

wall. Nearly one-half of patients with primary intraventricular hemorrhage have identifiable bleeding sources seen using conventional

angiography.

Venous sinus thrombosis (Chap. 427) causes cortical vein hypertension, cerebral edema, and venous infarction. This may progress to

cause ICH surrounding the region of the occluded cerebral venous

sinus or within the drainage region of the vein of Labbé, producing a

posterior temporal inferior parietal hematoma. Despite the presence of

hemorrhage, IV anticoagulation is helpful to reduce the venous hypertension and limit venous ischemia and further ICH.

Sepsis can cause small petechial hemorrhages throughout the cerebral white matter. Moyamoya disease (Chap. 427), mainly an occlusive

arterial disease that causes ischemic symptoms, may on occasion

produce ICH, particularly in the young. Hemorrhages into the spinal

cord are usually the result of an AVM, cavernous malformation, or

metastatic tumor. Epidural spinal hemorrhage produces a rapidly evolving syndrome of spinal cord or nerve root compression (Chap. 442).

Spinal hemorrhages usually present with sudden back pain and some

manifestation of myelopathy.

Laboratory and Imaging Evaluation Patients should have routine blood chemistries and hematologic studies. Specific attention to

the platelet count, prothrombin time, partial thromboplastin time, and

international normalized ratio is important to identify coagulopathy.

CT imaging reliably detects acute focal hemorrhages in the supratentorial space. Rarely, very small pontine or medullary hemorrhages may

not be well delineated because of motion and bone-induced artifact

that obscure structures in the posterior fossa. After the first 2 weeks,

x-ray attenuation values of clotted blood diminish until they become

isodense with surrounding brain. Mass effect and edema may remain.

In some cases, a surrounding rim of contrast enhancement appears

after 2–4 weeks and may persist for months. MRI, although more sensitive for delineating posterior fossa lesions, is generally not necessary for

primary diagnosis. Images of flowing blood on MRI scan may identify

AVMs as the cause of the hemorrhage. MRI, CT angiography (CTA),

and conventional x-ray angiography are used when the cause of intracranial hemorrhage is uncertain, particularly if the patient is young

or not hypertensive and the hematoma is not in one of the usual sites

for hypertensive hemorrhage. CTA or postcontrast CT imaging may

reveal one or more small areas of enhancement within a hematoma;

this “spot sign” is thought to represent ongoing bleeding. The presence

of a spot sign is associated with an increased risk of hematoma expansion, increased mortality, and lower likelihood of favorable functional

outcome. Because patients typically have focal neurologic signs and

obtundation and often show signs of increased ICP, a lumbar puncture

is generally unnecessary and should usually be avoided because it may

induce cerebral herniation.

TREATMENT

Intracerebral Hemorrhage

ACUTE MANAGEMENT

After immediate attention to blood pressure and airway protection

(see above), focus can switch to medical and surgical management.

Approximately 40% of patients with a hypertensive ICH die, but

survivors can have a good to complete recovery. The ICH Score

(Table 428-2) is a validated clinical grading scale that is useful for

stratification of mortality risk and clinical outcome. However, a specific ICH clinical grading scale should not be used to precisely prognosticate outcome because of the concern of creating a self-fulfilling

prophecy of poor outcome if early aggressive care is withheld. Any

identified coagulopathy should be corrected as soon as possible. For

patients taking vitamin K antagonists (VKAs), rapid correction of

coagulopathy can be achieved by infusing prothrombin complex concentrates (PCCs), which can be administered quickly, with vitamin

K administered concurrently. Fresh frozen plasma (FFP) is an alternative, but since it requires larger fluid volumes and longer time to

achieve adequate reversal than PCC, it is not recommended if PCC

is available. Idarucizumab is a monoclonal antibody to dabigatran,

and the administration of two doses reverses the anticoagulation

effect of dabigatran quickly. The oral Xa inhibitors apixaban and

rivaroxaban can be reversed with andexanet alfa. PCC may partially

reverse the effects of oral factor Xa inhibitors and are reasonable to

administer if andexanet alfa is not available. When ICH is associated

with thrombocytopenia (platelet count <50,000/μL), transfusion of

fresh platelets is indicated. A clinical trial of platelet transfusions in

patients with ICH and without thrombocytopenia who were taking

antiplatelet drugs showed no benefit and possible harm.

Hematomas may expand for several hours following the initial

hemorrhage, even in patients without coagulopathy. The precise

mechanism is unclear. A phase 3 trial of treatment with recombinant factor VIIa reduced hematoma expansion; however, clinical

outcomes were not improved, so use of this drug is not recommended. Blood pressure lowering has been considered due to the

theoretical risk of acutely elevated blood pressure on hematoma

expansion, although clinical trials did not find a difference in

hematoma expansion between the SBP targets of 140–180 mmHg.

In deep hemorrhages that involve the basal ganglia, more intensive

blood pressure lowering reduced hematoma expansion but had no

effect on functional outcome.

Evacuation of supratentorial hematomas does not appear to

improve outcome for most patients. The International Surgical

Trial in Intracerebral Haemorrhage (STICH) randomized patients

with supratentorial ICH to either early surgical evacuation or

initial medical management. No benefit was found in the early

surgery arm, although analysis was complicated by the fact that

26% of patients in the initial medical management group ultimately

had surgery for neurologic deterioration. The follow-up study,

STICH-II, found that surgery within 24 h of lobar supratentorial

hemorrhage did not improve overall outcome but might have a role

in select severely affected patients. Therefore, existing data do not

support routine surgical evacuation of supratentorial hemorrhages

in stable patients. However, many centers still consider surgery for

patients deemed salvageable and who are experiencing progressive

neurologic deterioration due to herniation. Surgical techniques

continue to evolve. A minimally invasive endoscopic hematoma

evacuation followed by thrombolysis with the aim of decreasing clot

TABLE 428-2 The ICH Score

CLINICAL OR IMAGING FACTOR POINT SCORE

Age

<80 years 0

≥80 years 1

Hematoma Volume

<30 cc 0

≥30 cc 1

Intraventricular Hemorrhage Present

No 0

Yes 1

Infratentorial Origin of Hemorrhage

No 0

Yes 1

Glasgow Coma Scale Score

13–15 0

5–12 1

3–4 2

Total Score 0–6 Sum of each category above

Source: Reproduced with permission from JC Hemphill 3rd et al: The ICH score:

A simple, reliable grading scale for intracerebral hemorrhage. Stroke 32:891,

2001.

3352 PART 13 Neurologic Disorders

size has not been shown to improve outcome in clinical trials. The

administration of tranexamic acid was not found to alter outcome

in a large randomized trial.

For cerebellar hemorrhages, a neurosurgeon should be consulted

immediately to assist with the evaluation; most cerebellar hematomas >3 cm in diameter will require surgical evacuation. If the

patient is alert without focal brainstem signs and if the hematoma is

<1 cm in diameter, surgical removal is usually unnecessary. Patients

with hematomas between 1 and 3 cm require careful observation

for signs of impaired consciousness, progressive hydrocephalus,

and precipitous respiratory failure. Hydrocephalus due to cerebellar

hematoma requires surgical evacuation and should not be treated

solely with ventricular drainage.

Tissue surrounding hematomas is displaced and compressed but

not necessarily infarcted. Hence, in survivors, major improvement

commonly occurs as the hematoma is reabsorbed and the adjacent

tissue regains its function. Careful management of the patient

during the acute phase of the hemorrhage can lead to considerable

recovery.

Surprisingly, ICP is often normal even with large ICHs. However,

if the hematoma causes marked midline shift of structures with

consequent obtundation, coma, or hydrocephalus, osmotic agents

can be instituted in preparation for placement of a ventriculostomy

or parenchymal ICP monitor (Chap. 307). Once ICP is recorded,

CSF drainage (if available), osmotic therapy, and blood pressure

management can be tailored to maintain cerebral perfusion pressure (MAP minus ICP) at least 50–70 mmHg. For example, if ICP

is found to be high, CSF can be drained from the ventricular space

and osmotic therapy continued; persistent or progressive elevation

in ICP may prompt surgical evacuation of the clot. Alternately,

if ICP is normal or only mildly elevated, interventions such as

osmotic therapy may be tapered. Because hyperventilation may

actually produce ischemia by cerebral vasoconstriction, induced

hyperventilation should be limited to acute resuscitation of the

patient with presumptive high ICP and eliminated once other

treatments (osmotic therapy or surgical treatments) have been

instituted. Glucocorticoids are not helpful for the edema from

intracerebral hematoma.

PREVENTION

Hypertension is the leading cause of primary ICH. Prevention is

aimed at reducing chronic hypertension, eliminating excessive

alcohol use, and discontinuing use of illicit drugs such as cocaine

and amphetamines. Current guidelines recommend that patients

with CAA should generally avoid oral anticoagulant medications,

but antiplatelet agents may be administered if there is an indication

based on atherothrombotic vascular disease.

VASCULAR ANOMALIES

Vascular anomalies can be divided into congenital vascular malformations and acquired vascular lesions.

■ CONGENITAL VASCULAR MALFORMATIONS

True AVMs, venous anomalies, and capillary telangiectasias are lesions

that usually remain clinically silent through life. AVMs are probably

congenital, but cases of acquired lesions have been reported.

True AVMs are congenital shunts between the arterial and venous

systems that may present with headache, seizures, and intracranial

hemorrhage. AVMs consist of a tangle of abnormal vessels across the

cortical surface or deep within the brain substance. AVMs vary in size

from a small blemish a few millimeters in diameter to a large mass

of tortuous channels composing an arteriovenous shunt of sufficient

magnitude to raise cardiac output and precipitate heart failure. Blood

vessels forming the tangle interposed between arteries and veins are

usually abnormally thin and histologically resemble both arteries and

veins. AVMs occur in all parts of the cerebral hemispheres, brainstem,

and spinal cord, but the largest ones are most frequently located in the

posterior half of the hemispheres, commonly forming a wedge-shaped

lesion extending from the cortex to the ventricle.

Bleeding, headache, and seizures are most common between the

ages of 10 and 30, occasionally as late as the fifties. AVMs are more

frequent in men, and rare familial cases have been described. Familial

AVM may be a part of the autosomal dominant syndrome of hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber) syndrome due

to mutations in either endoglin or activin receptor-like kinase 1,

both involved in transforming growth factor (TGF) signaling and

angiogenesis.

Headache (without bleeding) may be hemicranial and throbbing,

like migraine, or diffuse. Focal seizures, with or without generalization, occur in ~30% of cases. One-half of AVMs become evident

as ICHs. In most, the hemorrhage is mainly intraparenchymal with

extension into the subarachnoid space in some cases. Unlike primary SAHs (Chap. 429), blood from a ruptured AVM is usually not

deposited in the basal cisterns, and symptomatic cerebral vasospasm

is rare. The risk of AVM rupture is strongly influenced by a history of

prior rupture. Although unruptured AVMs have a hemorrhage rate of

~2–4% per year, previously ruptured AVMs may have a rate as high

as 17% a year, at least for the first year. Hemorrhages may be massive,

leading to death, or may be as small as 1 cm in diameter, leading to

minor focal symptoms or no deficit. The AVM may be large enough

to steal blood away from adjacent normal brain tissue or to increase

venous pressure significantly to produce venous ischemia locally and

in remote areas of the brain. This is seen most often with large AVMs

in the territory of the middle cerebral artery.

Large AVMs of the anterior circulation may be associated with a systolic and diastolic bruit (sometimes self-audible) over the eye, forehead,

or neck and a bounding carotid pulse. Headache at the onset of AVM

rupture is generally not as explosive as with aneurysmal rupture. MRI

is better than CT for diagnosis, although noncontrast CT scanning

sometimes detects calcification of the AVM and contrast may demonstrate the abnormal blood vessels. Once identified, conventional x-ray

angiography is the gold standard for evaluating the precise anatomy of

the AVM.

Surgical treatment of AVMs presenting with hemorrhage, often

done in conjunction with preoperative embolization to reduce operative bleeding, is usually indicated for accessible lesions. Stereotactic

radiosurgery, an alternative to conventional surgery, can produce a

slow sclerosis of the AVM over 2–3 years.

Several angiographic features can be used to help predict future

bleeding risk. Paradoxically, smaller lesions seem to have a higher

hemorrhage rate. The presence of deep venous drainage, venous outflow stenosis, and intranidal aneurysms may increase rupture risk.

Because of the relatively low annual rate of hemorrhage and the risk

of complications due to surgical or endovascular treatment, the indications for surgery in asymptomatic AVMs are uncertain. The ARUBA

(A Randomized Trial of Unruptured Brain Arteriovenous Malformations) trial randomized patients to medical management versus intervention (surgery, endovascular embolization, combination

embolization and surgery, or gamma-knife). The trial was stopped

prematurely for harm, with the medical arm achieving the combined

endpoint of death or symptomatic stroke in 10% of patients compared to 31% in the intervention group at a mean follow-up time of

33 months. This highly significant finding argues against routine intervention for patients presenting without hemorrhage, although debate

ensues regarding the generalizability of these results.

Venous anomalies are the result of development of anomalous cerebral, cerebellar, or brainstem venous drainage. These structures, unlike

AVMs, are functional venous channels. They are of little clinical significance and should be ignored if found incidentally on brain imaging

studies. Surgical resection of these anomalies may result in venous

infarction and hemorrhage. Venous anomalies may be associated with

cavernous malformations (see below), which do carry some bleeding

risk.

3353 Subarachnoid Hemorrhage CHAPTER 429

Capillary telangiectasias are true capillary malformations that often

form extensive vascular networks through an otherwise normal

brain structure. The pons and deep cerebral white matter are typical

locations, and these capillary malformations can be seen in patients

with hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber) syndrome. If bleeding does occur, it rarely produces mass effect or significant symptoms. No treatment options exist.

■ ACQUIRED VASCULAR LESIONS

Cavernous angiomas (cavernous malformations) are tufts of capillary

sinusoids that form within the deep hemispheric white matter and

brainstem with no normal intervening neural structures. The pathogenesis is unclear. Familial cavernous angiomas have been mapped to

several different genes: KRIT1, CCM2, and PDCD10. Both KRIT1 and

CCM2 have roles in blood vessel formation, whereas PDCD10 is an

apoptotic gene. Cavernous angiomas are typically <1 cm in diameter

and are often associated with a venous anomaly. Bleeding is usually of

small volume, causing slight mass effect only. The bleeding risk for single cavernous malformations is 0.7–1.5% per year and may be higher

for patients with prior clinical hemorrhage or multiple malformations.

Seizures may occur if the malformation is located near the cerebral

cortex. Surgical resection eliminates bleeding risk and may reduce seizure risk, but it is usually reserved for those malformations that form

near the brain surface. Radiation treatment has not been shown to be

of benefit. Recent retrospective data show that intracranial hemorrhage

from cavernous malformations is likely not increased with administration of antiplatelet and anticoagulant medications prescribed for other

medical conditions.

Dural arteriovenous fistulas are acquired connections usually

from a dural artery to a dural sinus. Patients may complain of a

pulse-synchronous cephalic bruit (“pulsatile tinnitus”) and headache.

Depending on the magnitude of the shunt, venous pressures may rise

high enough to cause cortical ischemia or venous hypertension and

hemorrhage, particularly SAH. Surgical and endovascular techniques

are usually curative. These fistulas may form because of trauma, but

most are idiopathic. There is an association between fistulas and dural

sinus thrombosis. Fistulas have been observed to appear months to

years following venous sinus thrombosis, suggesting that angiogenesis

factors elaborated from the thrombotic process may cause these anomalous connections to form. Alternatively, dural arteriovenous fistulas

can produce venous sinus occlusion over time, perhaps from the high

pressure and high flow through a venous structure.

■ FURTHER READING

Anderson CS et al: Rapid blood-pressure lowering in patients with

acute intracerebral hemorrhage. N Engl J Med 368:2355, 2013.

Christensen H et al: European stroke organization guideline on

reversal of oral anticoagulants in acute intracerebral hemorrhage.

Euro Stroke J 4:294, 2019.

Frontera J et al: Guideline for reversal of antithrombotics in intracranial hemorrhage. A statement for healthcare professionals from

the Neurocritical Care Society and Society of Critical Care Medicine.

Neurocrit Care 24:6, 2016.

Hemphill JC et al: Guidelines for the management of spontaneous

intracerebral hemorrhage: A guideline for healthcare professionals

from the American Heart Association/American Stroke Association.

Stroke 46:2032, 2015.

Mohr JP et al: Medical management with or without interventional therapy for unruptured brain arteriovenous malformations

(ARUBA): A multicentre, non-blinded, randomised trial. Lancet

383:614, 2014.

Steiner T et al: European Stroke Organisation (ESO) guidelines for

the management of spontaneous intracerebral hemorrhage. Int J

Stroke 9:840, 2014.

Subarachnoid hemorrhage (SAH) renders the brain critically ill from

both primary and secondary brain insults. Excluding head trauma, the

most common cause of SAH is rupture of a saccular aneurysm. Other

causes include bleeding from a vascular malformation (arteriovenous

malformation or dural arteriovenous fistula) and extension into the

subarachnoid space from a primary intracerebral hemorrhage. Some

idiopathic SAHs are localized to the perimesencephalic cisterns and

are benign; they probably have a venous or capillary source, and angiography is unrevealing.

■ SACCULAR (“BERRY”) ANEURYSM

Autopsy and angiography studies have found that ~2% of adults harbor

intracranial aneurysms, for a prevalence of 4 million persons in the

United States; the aneurysm will rupture, producing SAH, in 25,000–

30,000 cases per year. The overall mortality rate for aneurysmal SAH is

~35%, with around one-third of these patients dying immediately and

prior to hospital admission. Of those who survive, more than half are

left with clinically significant neurologic deficits as a result of the initial

hemorrhage, cerebral vasospasm with infarction, or hydrocephalus.

If the patient survives but the aneurysm is not obliterated, the rate of

rebleeding is ~20% in the first 2 weeks, 30% in the first month, and

~3% per year afterward. Given these alarming figures, the major therapeutic emphasis is on preventing the predictable early complications

of the SAH.

Unruptured, asymptomatic aneurysms are much less dangerous

than a recently ruptured aneurysm. The annual risk of rupture for

aneurysms <10 mm in size is ~0.1%, and for aneurysms ≥10 mm in size

is ~0.5–1%; the surgical morbidity rate far exceeds these percentages.

Aneurysm location may also factor into risk, with basilar bifurcation

aneurysms appearing to have a somewhat higher rupture risk. Because

of the longer length of exposure to risk of rupture, younger patients with

aneurysms >10 mm in size may benefit from prophylactic treatment. As

with the treatment of asymptomatic carotid stenosis, this risk-benefit

ratio strongly depends on the complication rate of treatment.

Giant aneurysms, those >2.5 cm in diameter, occur at the same

sites (see below) as small aneurysms, and account for 5% of cases. The

three most common locations are the terminal internal carotid artery,

middle cerebral artery (MCA) bifurcation, and top of the basilar artery.

Their risk of rupture is ~6% in the first year after identification and

may remain high indefinitely. They often cause symptoms by compressing the adjacent brain or cranial nerves.

Mycotic aneurysms are usually located distal to the first bifurcation of major arteries of the circle of Willis. Most result from infected

emboli due to bacterial endocarditis causing septic degeneration of

arteries and subsequent dilation and rupture. Whether these lesions

should be sought and repaired prior to rupture or left to heal spontaneously with antibiotic treatment remains controversial.

Pathophysiology Saccular aneurysms occur at the bifurcations

of the large- to medium-sized intracranial arteries; rupture is into

the subarachnoid space in the basal cisterns and sometimes into the

parenchyma of the adjacent brain. Approximately 85% of aneurysms

occur in the anterior circulation, mostly on the circle of Willis. About

20% of patients have multiple aneurysms, many at mirror sites bilaterally. As an aneurysm develops, it typically forms a neck with a dome.

The length of the neck and the size of the dome vary greatly and are

important factors in planning neurosurgical obliteration or endovascular embolization. The arterial internal elastic lamina disappears at

the base of the neck. The media thins, and connective tissue replaces

smooth-muscle cells. At the site of rupture (most often the dome), the

wall thins, and the tear that allows bleeding is often ≤0.5 mm long.

429 Subarachnoid Hemorrhage

J. Claude Hemphill, III,

Wade S. Smith, Daryl R. Gress