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CEREBROVASCULAR DISEASE
Classification of Stroke: Stroke, in lay terms is "a sudden neurologic affliction".
Stroke represents a heterogeneous collection of disorders that affect the vasculature of
the brain. There are two major subtypes of stroke: ischemia (lack of blood supply) and
hemorrhage (leakage of blood outside the normal vessels). are vastly different problems.
Hemorrhagic stroke represent, 20% of strokes and ischemic stroke 80%. The two groups are
further differentiated by the location and causes of the hemorrhage/ischemia.
Stroke is a very important public health problem. It is the third leading cause of
death in the. U.S. In 1985, 500,000 Americans had a stroke and 152,700 died of a stroke.
Ischemic strokes can be subdivided into different mechanisms: systemic hypoperfusion,
embolism, and thrombosis.
In systemic hypoperfusion, there is central failure of blood pumping due to hemorrhage, shock,
cardiac arrest, or severe hypovolemia. Patients are cold, clammy, and pale and may have low
blood pressure. They feel faint, dizzy and complain of lightheadedness, dim vision, and distant
hearing. Focal neurological signs are unusual.
Embolic stroke is caused by blockage of an artery supplying the brain by a plug of material
formed downstream in the proximal vascular system or in the heart. The sudden onset of focal
neurological signs is seen usually in patients with heart disease or occlusive disease of the
extracranial arteries. The most common cause of ischemic stroke is embolic.
Thrombosis is a term traditionally applied to local decreased perfusion due to a
lesion formed in-situ in an artery, usually at the site of an atherosclerotic plaque. It is
often associated with focal neurological signs that fluctuate. Clinically, it is often difficult to
distinguish embolism from thrombosis. The evaluation and management of these patients are
often similar.
Hemorrhage is further subdivided into subarachnoid hemorrhage and intracerebral hemorrhage
Subarachnoid hemorrhage is usually caused by the rupture of an intracranial
aneurysm or arteriovenous malformation into the CSF spaces. The patient, who is often young
and without risk factors for arteriosclerosis, develops sudden severe headache, nausea, and
emesis. A lumbar puncture will demonstrate blood in the spinal fluid and CT or MR scans will
show blood around the brain surface.
Intracerebral hemorrhage occurs most often from rupture of small arteries
damaged by hypertension. It can be caused by rupture of an aneurysm or AVM. The
patient develops focal neurological signs, such as hemiparesis or aphasia, depending on the
location of the clot, that progressively worsen in minutes or hours. Headache, vomiting, and
reduced level of consciousness occur. Imaging studies show hematoma within the brain.
ISCHEMIC STROKE
Atherosclerosis, the primary cause of vascular occlusion, is most prevalent at the
bifurcations of blood vessels. The origin of the internal carotid artery, just distal to the
bifurcation of the common carotid artery, is a common place for atherosclerosis to occur.
Transient Ischemic Attacks (TIA): An episode of focal brain ischemia of loss
than 24 hours is called a transient ischemic attack or TIA.
Diagnosis of TIA: Clinical concept based on the sudden development and clearing of
neurological symptoms presumably resulting from a vascular occlusive process. Non-focal
symptoms occurring in isolation are not TIAs. These include isolated vertigo,
wooziness, lightheadedness, and syncope.
Focal ischemia is not the only cause of sudden focal neurological deficits. Simple
partial (focal) seizures, migraine syndromes, tumors and chronic subdural hematoma may
mimic TIAs. Focal seizures may not be associated with a change in level of
consciousness. Focal migraine may not have associated headache.
The key to the diagnosis of focal seizures and migraines, rather than TIA, is the
marching evolution of the neurological symptoms. With seizures, the march is rapid,
lasting seconds. With migraines, the march lasts several minutes. Other clues to
migraine include visual scintillations and normal results of vascular imaging studies. On
the other hand, focal ischemia occasionally produces marching, clonic, or positive
symptoms suggestive of seizures or migraines. Focal clonic limb shaking has been
associated with severe carotid stenosis or occlusion (hemodynamic insufficiency), and patients
with vertebro-basilar system atherosclerosis may have visual symptoms due to occipital lobe
ischemia.
Vascular distribution of TIAs
Carotid vs. vertebro-basilar: Unilateral symptoms suggest carotid ischemia,
while bilateral symptoms suggest vertebro-basilar ischemia, especially when combined with
symptoms like vertigo, dysarthria, or dysphagia.
Recurrent, stereotyped hemi-motor or hermi-sensory symptoms suggest carotid occlusive
disease.
Alternating neurological symptoms suggest vertebro basilar disease, cardiac
embolism, or diffuse vascular disease.
Carotid artery ischemia
Amaurosis fugax: Transient monocular blindness. The patients classically describe descending
or ascending "shade" in vision. Less than half of patients have 75% or greater stenosis of the
internal carotid artery.
Cortical deficits: Contralateral hemiparesis and hemisensory loss, dysphasia with dominant
cerebral hemisphere involvement, dysarthria with non-dominant cerebral hemisphere
involvement, and contralateral homonymous hemianopsia may be seen in varying combinations
in carotid artery territory ischemia.
Vertebro-basilar ischemia: Homonymous field defect, diplopia, vertigo, dysarthria, gait
ataxia, brief loss of consciousness, unilateral or bilateral hemiparesis or hemisensory loss.
Bilateral visual loss is posterior circulation ischemia. Description of visual loss moving
medially or laterally is suspicious for hemianopsia arid therefore posterior circulation ischemia.
Mechanism of TIAs: Embolus: atherosclerotic plaque, lipohyaliosis of arterioles.
Hemodynamic basis: postural, exercise induced, after introduction of antihypertensive
medications.
Epidemiology and natural history of TIAs: A prevalence of 116 per 100,000
was seen in the Framingham, MA study and a prevalence of 139 per 100,000 was found
in the 1970 age-adjusted Rochester, MN study. Less than halt of brain infarctions are
preceded by warning TIAs. The period of highest risk for stroke is in the first several
months to the first year after TIA occurrence. There is an 8% risk of stroke in the first
month, 5% per year risk for the next three years and a 3% risk per year thereafter. The
overall 5 year risk of stroke following the onset of TIAs is 33%, but the numbers may be
diluted by including younger patients, non-focal symptoms, etc., in these series. The
long-term stroke rate for carotid or vertero-basliar TIAs, is not significantly different. The
frequency, duration, and number of TIAs are not consistently related to stroke risk, but
this is not proven. "Crescendo" TIAs are thought to have greater stroke risk, but this is not
proven. A single TIA also carries significant risk. The annual risk of MI is 5% in TIA patients,
which is equivalent to that of patients with angina pectoris or triple vessel coronary disease.
There is a high prevalence of asymptomatic coronary artery disease in TIA patients. Carotid
bruit is a better marker for coronary artery disease
than for stroke. It is important to incorporate an evaluation of the coronary circulation the workup of patients with cerebrovascular symptoms.
Cerebral Infarction: There is risk of further infarction after the initial occurrence of infarction.
A 7.9% risk of recurrent infarction within 30 days was seen in patients with an atherosclerotic
cerebral infarct entered into the Stroke Data Bank Study. Transient monocular blindness, TIA,
minor stroke and major stroke form a hierarchy of increasingly severe symptoms that mirror an
increasing risk for stroke. The available evidence indicates that stroke risk correlates with the
degree of carotid stenosis.
Lacunar Infarction: Lacunes are small infarcts resulting from the thrombosis of
small perforating blood vessels. These infarcts are associated with hypertensive vascular
disease and may produce certain well-defined neurological syndromes.
Pure motor hemiparesis. Pure motor weakness without other associated
neurological deficits are often associated with small lacunes in the pons or internal capsule.
Pure sensory stroke. Sensory loss without other associated neurological deficits is often due
to a small lesion within the thalamus.
Leg paresis and ataxia. This unusual combination of weakness and difficulty with
coordination can be seen with lesions in the pons or internal capsule.
Clumsy hand dysarthria syndrome. This combination of neurological findings is seen with
lesions in the upper third of the pons.
Prevention of Stroke: Risk factors for cerebral atherosclerotic TIA and stroke include: age,
hypertension, diabetes, family history, cigarette smoking, lipid disorders.
Cardiac pathologies, such as dilated cardiomyopathies, certain valvular disease, and atrial
fibrillation may lead to intracardiac thrombus formation and cerebral embolism.
Risk factor modification, smoking cessation, anti-hypertensive agents, and lipid lowering
agents all decrease the risk for stroke as well as for myocardial infarction. The widespread
treatment of hypertension is the most important reason for the decline in the stroke rate in the
U.S. over the past 40 years. No studies have shown a benefit of anti-platelet therapy in the
general population and for asymptomatic cerebrovascular lesions.
Evaluation of patients
Medical history and examination: The history should focus on atherosclerotic risk factors,
cardiac disease, and vascular disease in patients under age of 45, non-atherosclerotic causes of
cerebral ischemia are more prevalent. Question patients re: use of oral contraceptives and the
use of cocaine. A history of spontaneous abortions and deep vein thrombosis may suggest a
hypercoagulable state, such as the anticardiolipin syndrome.
Neurovascular exam: Blood pressure in both arms, lying and standing. This is
particularly important in patients suspected of having vertebro-basilar ischemia to detect a
subclavian steal syndrome.
Cardiac auscultation and rhythm check
Auscultation of head and neck for bruits: Absence of bruit does not rule out
severe carotid stenosis. Conversely, only 50% of cervical bruits are associated with significant
underlying carotid stenosis.
Palpation of neck, facial, and radial pulses: Unless the carotid pulse is absent, palpation of
the carotid pulse is not much help in establishing a diagnosis.
Funduscopic exam for platelet or fibrin, cholesterol or calcific emboli.
Laboratory evaluation is often normal in stroke patients. Diabetes mellitus and
lipid disorders need to be ruled out. In younger patients, tests for vasculitis and
hypercoagulable states need to be performed. Cardiac studies give the best results in
patients under age 45. In patients with unexplained events, or in patients with cardiac
symptoms and signs, transesophageal echocardiography is superior to transthoracic
echocardiography in potential sources of cerebral emboli. Transthoracic echocardiography is
less expensive and more convenient and is usually used for initial screening. Holter monitoring
may detect occult cardiac rhythm disturbances associated with cerebral ischemia.
Imaging studies
Brain imaging studies: A CTor MR scan should be obtained to rule out tumor, vascular
malformations, and other nonocclusive causes of neurological symptoms, intracranial
hemorrhage, and to demonstrate infarction. An MR scan is more likely to show acute changes
in patients with cerebral infarction, compared to a CT scan. A CT scan may begin to
demonstrate low-density areas as early as 12 hours after the occurrence of an infarct. The lowdensity of infarction seen on CT scan may take several days to become maximal. The lowdensity of cerebral infarction does not stop at the border between gray and white matter, as is
seen with cerebral edema. Contrast enhancement of the infarct may be seen after several days
and may persist for weeks. In one study of patients with TIA or amaurosis fugax, 42% of CT
scans had focal changes, half of which correlated with the patient's symptoms. MR scans
showed abnormalities in 84% of patients, with 80% of abnormalities ipsilateral to the
presenting symptoms. An MR scan is more expensive and loss readily available. A CT scan is
adequate to rule out intracranial hemorrhage, which is the major concern in initial management.
Ultrasound studies: Duplex carotid ultrasonography has supplanted a large battery of noninvasive tests for the detection of extracranial carotid artery occlusive disease. In experienced
hands duplex scanning for lesions of the carotid artery have shown an overall 91% to 99%
sensitivity and 84% to 90% specificity. Ultrasound studies may not be able to distinguish severe
stenosis from complete occlusion of the internal carotid artery. It is most accurate for detecting
stenosis exceeding 70%, Duplex scanning is also useful for studying carotid plaque
morphology. The extra-cranial vertebral artery can be studied with ultrasound technique. If the
patient is a reasonable surgical risk for carotid endarterectomy, there is little indication for
ultrasound studies. The patient should have cerebral angiography carried out.
Conventional cerebral angiography is still the "gold standard". It permits assessment of
the intracranial circulation and collateral pathways. It defines the extent of extra cranial
occlusive disease. The indications for angiography in vertebra-basilar disease are more
controversial.
MR angiography continues to be refined. It has proven to be a good screening procedure
for extra cranial carotid occlusive disease with accuracy comparable to duplex carotid
ultrasonography. Some studies are not technically adequate and its accuracy in determining the
degree of stenosis is not as good as conventional angiography. It sometimes has difficulty
distinguishing severe stenosis from complete occlusion of the carotid artery.
Medical treatment of ischemic stroke
Cardiac disorders: Anticoagulation with warfarin decreases the incidence of stroke in
patients with recent MI, prosthetic valves, and non-rheumatic atrial fibrillation. Four
randomized, controlled clinical trials have compared warfarin or aspirin with placebo for
primary prevention of stroke in patients with atrial fibrillation. Control patients had stroke event
rates 4.5% per year (3%-7%) compared to 1.7% per year (0.2%-3.4%) in patients treated with
warfarin. The annual rates of bleeding in patients; on warfarin was less than 2%. The proper
dose of warfarin is unclear, but significant risk reduction is achieved with the prothrombin time
at 1.3-1.5 times control.
Large artery atherosclerotic occlusive disease
Warfarin anticoagulation: There is no indication for warfarin in carotid artery disease.
There is some evidence for warfarin anticoagulation in vertebra-basilar artery disease; but- this
is not entirely clear.
Antiplatelet therapy: Aspirin (ASA) therapy is standard for virtually all patients
since publication of the American and Canadian aspirin trials in the late 1970s. A metaanalysis of 25 completed studies involving 29,000 patients with angina, MI, TIA, or stroke
indicates that ASA reduces the risk of nonfatal stroke, MI or vascular death by 25%. The
risk of nonfatal stroke in TIA patients is reduced by about 22%. Aspirin is thought to work
by inhibiting the cyclooxygenase pathway of the arachidonic acid cascade. The
ineffectiveness of ASA in women may be due to the small number of women included in
published studies. The European Stroke Prevention Study showed that the combination
of ASA and dipyridamole was effective in men as well as women. The optimal dose of
ASA is problematic. Low and high doses of A SA were equivalent in the UK-TIA ASA trial.
Dipyridamole and sulfinpyrazone are no better than ASA alone.
Ticlopidine is a newer antiplatelet agent. The mechanism of action of this agent is unclear. It
does not inhibit cyclooxygenase. It may irreversibly affect platelet membrane function. It is
moderately superior to ASA in stroke prevention. In the Ticlopidine Aspirin Stroke Study
(TASS), the overall risk reduction for nonfatal or fatal stroke by ticlopidine was 21% and was
observed in both men and women. Compared with placebo, ticlopidine reduces the rate of
recurrence in patients who have had a major stroke by 33% in one year. Side effects of
ticlopidine are severe neutropenia (0.8%}. This usually occurs in the first 90 days of therapy
and is reversible. The CBC must be monitored every two weeks for three months. It also causes
diarrhea and GI upset. Ticlopidine is currently recommended for stroke prevention in patients
with symptomatic atherothrombotic cerebrovascular disease who cannot tolerate ASA or who
have events while on ASA. It is a very expensive drug.
Clopidogrel (Plavix) is a new antiplatelet drug. It has not been shown to be any more effective
than ASA in the secondary prevention of stroke.
No studies have shown a benefit for antiplatelet therapy as a primary prevention for stroke in
the general population or in asymptomatic patients with vascular risk factors or carotid artery
stenosis.
Surgical Treatment of Ischemic Stroke
Carotid endarterectomy involves opening the carotid artery at the carotid
bifurcation and dissecting out and removing the atheromatous plaque. Three major
randomized studies of symptomatic patients comparing medical vs. surgical therapy were
recently completed. All patients were on ASA and hypertension was treated. Some
medical patients were on warfarin. The patients had amaurosis, hemispheric TIAs, or mild
strokes.

North American Symptomatic Carotid Endarterectomy Trial (N.Eng.J.Med. 325:445453,1991, N Eng J Med 339:1415-1425, 1998).

MRC European Carotid Surgery Trial (Lancet 337:1235-1243. 1991).

VA Cooperative Study (JAMA 266:3289-3294, 1991)
Surgery significantly benefits patients under 80 years of age with appropriate angiographically
defined carotid stenosis of 70%-99%. There is a small but significant benefit of surgery in
symptomatic patients with 50% to 69% stenosis of the carotid artery.
The benefit is greatest in males, with only a marginal benefit of surgery in females. The
benefit of carotid endarterectomy in this group of patients is much less than that seen in
patients with carotid stenosis of 70% or more. No benefit for carotid stenosis of 50% or
less.
Extracranial-intracranial arterial bypass for atherosclerotic lesions not
accessible by conventional extra cranial surgical techniques. No benefit of surgery vs. medical
therapy was found in a large randomized study.
Interventional neuroradiology treatment: Balloon angioplasty and stenting are
being performed for carotid artery stenosis. Distal emboli following angioplasty is a major
risk, but has not been a significant problem. Good initial results for carotid artery stenosis
have been reported. Good results have been reported for balloon angioplasty of vertebral
artery origin stenosis. Some good results have been reported for balloon angioplasty of
intracranial stenosis, but a significant number of severe arterial complications have
occurred with this procedure when performed in intracranial vessels.
Intra-arterial thrombolytic agents have been used in some centers to treat acutely
thrombosed cerebral arteries.
Asymptomatic carotid artery stenosis: Prevalence of neck bruits and carotid
artery stenosis. Neck bruits in Framingham study: 3.5% incidence <54 years of age,
7.0% incidence 65-79 years of age. Ultrasound screening for carotid stenosis (45-84 years of
aye): 2.4% incidence in men, 30% incidence in men 75-84 years of age.
The risk of perioperative stroke are future stroke are two separate problems in
patients with asymptomatic carotid artery stenosis. The risk of perioperative stroke is
known and is very low. The risk of future stroke is less clear. In a large long-term followup study using carotid ultrasound to investigate patients with asymptomatic cerebral
artery disease, patients with less than 75% stenosis of the internal carotid artery had an
annual ipsilateral ischemic stroke rate of 1.3%. With greater than 75% stenosis of the
internal carotid artery, the annual ipsilateral stroke rate was 2.5%.
Carotid endarterectomy: A large randomized trial of surgical vs medical treatment
of asymptomatic carotid stenosis of 60% or greater showed a significant benefit of carotid
endarterectomy, with a reduction of an annual ipsilateral stroke risk of 2.2% to 1.0%. The
benefit occurred mostly in men with only a marginal benefit for surgery in women.
HEMORRHAGIC CEREBROVASCULAR DISEASE
The two most frequent types of hemorrhagic strokes are subarachnoid
hemorrhage (SAH) and spontaneous intracerebral hemorrhage. Each of those occurs with an
incidence of approximately 10-14 per 100,000 population per year and represents an important
cause of neurological morbidity and mortality. Hemorrhagic strokes may either result in
devastating neurological deficits and death, or relatively minor symptoms.
Subarachnoid hemorrhage
Epidemiology: Depending on the population studied, trauma is probably the most common
cause of subarachnoid hemorrhage. In general, and for the purposes of this syllabus,
subarachnoid hemorrhage of non-traumatic (spontaneous) etiology will be considered. Ruptured
intracranial aneurysms account for approximately 80% of subarachnoid hemorrhages.
Arteriovenous malformations lying adjacent to the subarachnoid space account for
approximately 15 %.
A variety of other less frequent causes, including tumor and vasculitis, cause the remaining
cases of subarachnoid hemorrhage. As many as 20% of patients who sustain a subarachnoid
hemorrhage, after a complete neuroradiological evaluation, will not have a definable cause for
their hemorrhage,
Intracranial aneurysms are present in approximately 2% of the population. The risk of
rupture has been quantified by the ISUIA study. The 5 year rupture rate for aneurysms in the
anterior circulation aneurysms by size are: 0% for <7mm, 2.6% for 7-12 mm, 14.5% for 13-24
mm, and 40% for >2.5 cm. For posterior circulation aneurysm, the risks are higher: 2.6% for
<7mm, 14.5% for 7-12 mm, 18% for 13-24 mm, and 50% for .2.5 cm.
Certain families appear to have a higher prevalence of intracranial aneurysm. There are welldocumented cases where multiple family members have had subarachnoid hemorrhages. Most
data suggest that families with more than one close relative with an intracranial aneurysm or
subarachnoid hemorrhage have a prevalence of intracranial aneurysms of about 7% to 8%, or
approximately three times the risk for the general population.
About one-third of patients will have a subarachnoid hemorrhage that occurs
during sleep. A significant number of other patients will be participating in strenuous
activity, such as exercise or sexual intercourse, at the time of their hemorrhage. An
important entity in the differential diagnosis is benign orgasmic cephalalgia which is a
condition of uncertain cause characterized by recurrent headaches that occur during
orgasm. Subarachnoid hemorrhage is not infrequently associated with extension of the
hemorrhage into the cerebral hemisphere or into the ventricles. It rarely involves the subdural
space.
A number of risk factors have been identified for subarachnoid hemorrhage.
These include hypertension, cigarette smoking in women, alcohol consumption and
possibly oral contraceptives. Subarachnoid hemorrhage can occur during pregnancy
and parturition, but there is controversy about whether the risk of intracranial
hemorrhage is increased in either of these conditions. The relationship between the
occurrence of systemic arterial hypertension and intracranial hemorrhage is also
uncertain. Hypertension does appear to be related to the development of intracranial
aneurysms, but is not clearly related to their rupture once they have developed.
Some patients with defects of Type 3 collagen and certain connective tissue diseases also
appear to be at an increased risk for the development of cerebral aneurysms. Patients with
polycystic kidney disease and coarctation of the aorta are also at increased risk, although the
precise cause of this, whether it relates to hypertension, is not entirely clear.
About 28,000 patients will sustain a subarachnoid hemorrhage each year. A significant
number of patients (between 10%- 20/%), will die either with the initial hemorrhage or during
the first few days. The overall early mortality is approximately 5O% and about half of the
survivors of subarachnoid hemorrhage have a significant neurological disability.
Clinical Aspects: Subarachnoid hemorrhage is characterized by the abrupt onset of a severe
headache. Patients frequently describe this headache as being the worst headache of their life.
Other patients will describe a feeling like "being hit in the back of the neck with a 2 by 4".
Patients will frequently describe neck pain, especially in the suboccipital region, as the initial
manifestation of their hemorrhage. A generalized headache may later develop. Neck stiffness
and symptoms of focal crania nerve deficits may also occur. About 30%-50% of patients with
subarachnoid hemorrhage will sustain a loss of consciousness. Warning hemorrhage may occur
in up to 50% of patients with subarachnoid hemorrhage. This is usually a headache of less
severe character or occasionally a mild neurological deficit such as diplopia. It is important that
these warning symptoms be recognized and evaluated, although they are often very subtle and
may be difficult to distinguish from other transient neurological symptoms.
Physical Examination: Patients may have an altered level of consciousness and they are
described by the variety of classification schemes for subarachnoid hemorrhage. The commonly
used scheme is that described by Hunt and Hess as indicated in the following table.
Cerebrovascular Disease
Grade
1
2
3
Clinical Description
Asymptomatic or very mild headache or meningismus
Cranial nerve palsy, moderate to severe headache or severe
nuchal rigidity
Mild to moderate focal neurological deficit, lethargy or confusion
4
Stupor (Localize)
5
Coma (Posture)
One grade is added for serious medical illnesses such as coronary artery disease, diabetes
mellitus or chronic obstructive pulmonary disease.
Nuchal rigidity usually develops after the patient’s initial symptoms. When the
thigh is flexed and the knee is extended, Kernig's sign may be elicited with pain in
the posterior aspect of the upper legs. Brudzinski's sign is elicited when the patient's
neck is flexed and they involuntarily flex their hips. A third nerve palsy may be
present especially with aneurysms arising at the posterior communicating artery,
superior cerebellar, or basilar artery. Subhyaloid hemorrhages may occur on
fundus examination and are characterized as a bright red accumulation of blood
near the optic disc.
Diagnosis of Subarachnoid Hemorrhage: The history and physical exam
findings should suggest the diagnosis of SAH. Laboratory and imaging studies are
used to confirm the diagnosis. The first confirmatory diagnostic study that should be
applied in a patient with a suspected subarachnoid hemorrhage is a non-contrast CT
scan. Greater than 95% of patients with a subarachnoid hemorrhage, scanned
within 48 hours of the onset of their symptoms, will have detectable blood in the
subarachnoid cisterns or cerebral ventricles. The CT scan may also show the
presence of a significant increase in ventricular size, the presence of a hematoma
and may the useful in predicting the location or the aneurysms If the CT scan is
positive, it is usually not necessary to further confirm the diagnosis by doing a lumbar puncture,
In patients who are suspected of having a subarachnoid hemorrhage and in whom the CT
scan is negative, a CSF examination should be performed. Bloody fluid will indicate that a
subarachnoid hemorrhage has occurred. If the fluid is bloody because o a traumatic tap, the cell
count in sequential tubes will decrease. Xanthochromia of the fluid will often be present and
should be looked for in a specimen of the fluid after centrifugation. MR scans are generally not
useful in making the diagnosis of a subarachnoid hemorrhage from an intracranial aneurysm. It
may be helpful if other entities cause the hemorrhage, such as an arteriovenous malformation.
Usually, however, MR scanning is not necessary.
Once the diagnosis of subarachnoid hemorrhage has been confirmed by a CT scan
or lumbar puncture, a cerebral angiogram should be performed. In 80% to 85%
of patients, an aneurysm or other cause for the hemorrhage will be identified. The
most common sites for the occurrence of an aneurysm in a patient with a
subarachnoid hemorrhage are the internal carotid artery at its junction with the
posterior communicating artery, the anterior communicating artery, the bifurcation of the
middle cerebral artery in the Sylvian fissure, and the basilar artery apex. Less frequent sites
include the ophthalmic artery, the termination of the carotid artery, and arteries distributed
along the vertebral and lower trunk of the basilar artery. Twenty per cent of patients will have
multiple intracranial aneurysms and it is important that complete cerebral angiography be
accomplished so that all potential sites of aneurysms have been identified.
Management of Subarachnoid Hemorrhage: The main objectives in the
management of aneurysmal subarachnoid hemorrhage are to prevent rebleeding,
treat vasospasm and hydrocephalus, and avoid the medical complications of
subarachnoid hemorrhage. Re-hemorrhage is avoided by securing the aneurysm or resecting the
arteriovenous malformation which has caused the hemorrhage.
Surgical and Endovascular Management: To prevent rebleeding, cerebral aneurysms
should be either clipped or coiled. Clipping the aneurysm is a time-tested standard therapy
which requires a craniotomy and microsurgical.dissection of the arteries and the application of a
small aneurysm clip. Recently, techniques have been developed to treat cerebral aneurysms by
endovascular techniques. The most commonly applied technique is the use of a detachable
platinum coil. In this technique, a cerebral angiograrn is performed and a small platinum wire
is placed into the aneurysm to form a coil in the shape of a basket, which leads to the eventual
thrombosis and obliteration of the aneurysm in successful cases. The coil is then detached from
the delivery mechanism. Aneurysms with small necks relative to the overall dimensions of the
fundus of the aneurysm, are the lesion most optimally treated by endovascular means. In most
large medical centers, a decision regarding the appropriate type of treatment is made by a
combined team neurosurgeons and endovascular therapists.
The surgical management of subarachnoid hemorrhage is usually initiated
within the first two days after the hemorrhage. If the diagnosis has been delayed for some
reason and the patient is within the 10-14 day post subarachnoid hemorrhage period, surgery is
usually delayed so that the patient will not be at increased risk for the development of
postoperative vasospasm. Early surgery in the treatment of subarachnoid hemorrhage is usually
a superior approach because it markedly reduces the risk of rebleeding which occurs frequently
in the first few days following subarachnoid hemorrhage. It also may allow vasospasm to be
more effectively treated by having the aneurysm secured prior to manipulations which may
elevate the transmural pressure of the aneurysm.
The frequent sites for the occurrence of cerebral aneurysms can he reached
via a pterional craniotomy. In this approach, an incision is made behind the hairline
and a flap of bone is removed, centered on the pterion in the anterior temporal and
inferior frontal region. This allows access to the basal subarachnoid cisterns by a
path that parallels the greater sphenoid wing. The anterior communicating artery,
posterior communicating artery, middle cerebral artery and basilar apex may all be
accessed through this approach. A more posterior subtemporal approach is sometimes used for
aneurysms of the basilar apex.
Surgery on intracranial aneurysms is greatly facilitated by the use of the
operating microscope. These sophisticated devices allow magnification and..brilliant
illumination of the subarachnoid space. Precisely manufactured spring-loaded clips
can then be manipulated across the neck of an aneurysm, separating the aneurysm
from the circulation while maintaining normal blood flow through the parent vessel and
important perforators in the region of the fundus of the aneurysm.
The surgical morbidity and mortality for the management of vertebrobasilar
aneurysms, and large and giant aneurysms (aneurysms having a maximum
dimension exceeding 25mn) is generally higher than that for smaller anterior
circulation aneurysms.
Peri-operative Management: Patients who have sustained a subarachnoid
hemorrhage are vulnerable to a number of complications. The most frequent and
serious complications are: rebleeding of the aneurysm, cerebral vasospasm with the
development of delayed cerebral ischemia, hydrocephalus, fluid and electrolyte
problems.
Cerebral Vasospasm
Incidence and pathophysiology: Cerebral vasospasrn is an incompletely
understood complication of subarachnoid hemorrhage in which progressive arterial
narrowing occurs-usually 4-10 days after the initial hemorrhage. If this progressive
arterial narrowing is severe enough, cerebral ischemia will develop in the distribution
of the affected arteries.
The pathogenesis and etiology of cerebral vasospasm are not completely
understood. Most evidence points to oxy-hemoglobin accumulating in the
subarachnoid space on the adventitial surface of the vessel as the main causative
agent. A loss of endothelial dependent relaxation, inflammation and free oxygen
radicals all appeal to play a role in the ultimate pathological consequences of
cerebral vasospasm which is a critical narrowing of cerebral arteries with resultant cerebral
ischemia.
Clinical characteristics of cerebral vasospasm: About one-third of patients
with aneurysmal subarachrroid hemorrhage will develop some evidence of
symptomatic cerebral vasospasm. Many patients will have radiographic evidence of
some vasospasm without developing clinical symptoms. The onset of spasm is
usually 6-8 days after subarachnoid hemorrhage, but may occur somewhat earlier
and later than this. Cerebral vasospasm appears to be much more likely in patients
with thick subarachnoid clot. A grading system proposed by Fisher describes
patients at increased risk. There also appears to be a relationship between the initial
Hunt and Hess grade and the incidence of clinical vasospasm. Patients with poor
neurological function are at higher risk for the development of vasospasm.
The initial symptoms and signs of cerebral vasospasm after a subarachnoid hemorrhage
include increasing lethargy, fever and the development of focal neurological deficits such as
hemiparesis or dysphasia. The recognition of subtle neurological deficits in this setting is
important for the early escalation of treatment for cerebral vasospasm.
Treatment of cerebral vasospasm
Calcium channel blockers: Cerebral arteries are extremely dependent upon
the mobilization of calcium from extracellular stores to induce vasoconstriction. For
this reason, calcium channel blockers have proven to be effective in the
management and prophylaxis of cerebral vasospasm. Nimodipine has been shown
in a randomized perspective double blind clinical trial to improve outcome after
aneurysmal subarachnoid hemorrhage by lessening the severity of delayed cerebral
ischemia. It must be given PO or by an NG tube at a dose of 60mg every four hours.
It can be associated with hypotension or cardiac dysrhythmias and therefore must be
administered in lesser doses in patients who develop one of these complications.
Hypervolemic therapy for cerebral vasospasm: Patients with symptomatic
cerebral vasospasm are extremely sensitive to reduced blood volume. This
observation led to the development of hypervolomic therapy for cerebral vasospasm.
Patients with symptomatic cerebral vasospasm are monitored with an arterial line, a
Foley catheter and usually a Swan-Ganz catheter. Cardiac output and pulmonary
capillary wedge pressure are monitored and continuously recorded. The CVP is
elevated to approximately 10-12mm of mercury and tine pulmonary capillary wedge
between 14 -20mm of mercury. The systolic blood pressure may be allowed to rise to
levels up to 240mm of mercury in patients with clipped aneurysms and mean blood
pressure levels less than 150mm of mercury. Patients with unclipped aneurysms
should have their systolic blood pressure maintained below 150mm of mercury.
Volume expansion to induce hypervolemia is usually accomplished by the
administration of colloids including plasma, albumin or hetastarch. Packed red cells or whole
blood is given, depending upon the hematocrit which should be maintained between 30-33%.
Pressors, such as Dopamine or phenylephrine, may be administered. Patients will often develop
a brisk diuresis in this situation and high volumes of crystalloid may need to be given.
Occasionally, vasopressin can be administered to diminish the volume of such a diuresis as long
as the serum sodium is carefully monitored.
Additional treatments for cerebral vasospasm: Recently it has become
possible to treat cerebral vasospasm by an endovascular route. Balloon catheters
are placed within the artery and are used to gently dilate the constricted vessels.
Papavorine many be administered interarterially and has been reported to be effective
in the treatment of cerebral vasospasm. These treatments are used for patients who
do not respond to hypervolemic therapy and calcium antagonists.
Hydrocephalus: Hydrocephalus develops after subarachnoid hemorrhage in about 15% of
patients. Patients with intraventricular hemorrhage and severe subarachnoid hemorrhage are
more likely to develop hydrocephalus.
Hydrocephalus is an important differential consideration in evaluating the new onset of
lethargy in a patient after subarachnoid hemorrhage and therefore a CT scan may often have to
be performed to detect this condition. Hydrocephalus, in the setting of. subarachnoid
hemorrhage, is usually managed initially with a placement of an intraventricular catheter via a
frontal twist drill craniotomy if the hydrocephalus does not resolve after a week to 10 days of
external ventricular drainage, then a ventriculo-peritoneal shunt may need to be placed.
Hyponatremia and other fluid and electrolyte problems: Hyponatremia
occurs frequently in patients with subarachnoid hemorrhage. The etiology of the
hyponatremia in these patients is complex, but is not the simple development of
inappropriate secretion of ADH (SIADH). There appears to be a significant component of
hypovolemia and total body sodium depletion which occurs in these patients. A variety of
naturetic factors have been implicated in the pathogenesis of this syndrome, but it is
incompletely understood. It is crucial that patients with hyponatremia not be treated with fluid
restriction. This will only worsen the vasospasm that will likely develop in this circumstance.
Patients should either be managed with isotonic or occasionally hypertonic saline with careful
attention to central filling pressures. The management of hyponatremia in the setting of
subarachnoid hemorrhage can be extremely difficult.
Vascular malformations which cause intracranial hemorrhage: There are
three important types of vascular malformations: arteriovenous malformations
(AVMs), cavernous angiomas or cavernous malformations, and venous angiomas.
Arteriovenous malformations: Arteriovenous malformations are congenital lesions
lesions characterized by direct shunting of arterial blood into the cerebral venous system. These
lesions may vary in size from a few millimeters up to 10-20 centimeters and may occupy an
entire hemisphere. They have a tendency to enlarge after their formation in the fetus and the
progressive enlargement of the arterial and venous components may constitute a mass lesion,
cause seizures or alter cerebral hemodynamics in a way that may precipitate cerebral ischemia.
Clinical characteristics of arteriovenous malformations: Most often become apparent
during the 2nd, 3rd or 4th decade of life. Arteriovenous malformations may present as an
intracerebral or subarachnoid hemorrhage, seizures, headaches or other neurological deficits.
Hemorrhage occurs in 30-50% arteriorvenous malformations and seizures occur with a similar
frequency.
Natural history of arteriovenous malformations: Arteriovenous malformations, which
present with an initial hemorrhage, rehemorrhage at a rate of approximately 4% per year.
AVMs that present with other manifestations such as a seizure or headaches appear to bleed at a
rate of 1% to 2% per year. Younger patients are more likely to develop epilepsy as a
complication of an existing arteriovenous malformation.
Evaluation of arteriovenous malformations: CT scans will often demonstrate an
enhancing mass of abnormal vessels. MR scans are extremely useful in the evaluation of
cerebral arteriovenous malformations since it allows assessment of the contiguity of functional
brain structures around the arteriovenous malformation. Assessment of the feeding vessels and
venous components of an arteriovenous malformation can only be done by cerebral
angiography. Arteriovenous malformations are graded based on their size, the eloquence of
adjacent brain and the pattern of venous drainage. The outcome of treatment on the
Spetzler grading system is directly related to the grade of AVM.
Treatment of arteriovenous malformations: The decision to treat an arteriovenous
malformation must be based on an assessment of the location and vascular characteristics of the
lesion as well as the proximity of the lesion to eloquent cortex. In general, arteriovenous
malformations of moderate size which are not in eloquent areas of brain should be removed in
younger patients since they are likely to cause a hemorrhage at some point in the patient’s life.
The decision to treat other lesions must be individualized.
There are several methods of treating arteriovenous malformations: microsurgical removal,
endovascular treatment with embolization therapy and stereotactic radiosurgery.
Microsurgical removal involves the performance of a craniotomy usually after embolization
therapy has been performed. The arterial feeders of the malformation are isolated and the lesion
is progressively separated from the surrounding brain. Eventually the lesion is isolated on its
venous pedicle and it is removed. Intraoperative angiography can often be helpful in the
management of these lesions.
Stereotactic radiosurgery is another useful treatment for arteriovenous malformations.
Lesions with diameters of less than 3-4cm are suitable for stereotactic radiosurgery. The
radiation administered in this form of treatment causes a progressive obliteration of the arterial
and venous components of the lesion, making it not visible on angiography, in approximately
85% of patients at two years after treatment. A disadvantage of stereotactic radiosurgery is that
there is a latency period between the administration of the treatment and the effect of
obliteration of the lesion, which may be up to two years. About 15-20% of lesions so treated
will not be completely obliterated.
Cavernous malformations are lesions composed primarily of large venous channels
without a clear-cut arterial component. These lesions are difficult to visualize on angiography
and are not characterized by the very high blood flows seen in arteriovenous malformations.
These lesions are readily identified by their typical appearance on the MR scan consisting of a
heterogeneous lesion with bright and dark signal areas on the T1 and T2 weighted images
consistent with blood products in various degrees of resolution. They constitute about 5-10% of
vascular malformations and may occur at any site in the brain. They usually present with
seizures, but may sometimes cause an intracerebral hemorrhage.
Accessible cavernous malformations which cause symptoms should be surgically excised.
Asymptomatic lesions or lesions at inaccessible sites are often not treated surgically unless they
cause recurrent and repeated hemorrhages.
Venous malformations seldom need any type of treatment. They are often identified
incidentally.
Intracerebral Hemorrhage
Epidemiology: Intracerebral hemorrhage occurs with a frequency of about 8-14 cases per
100,000 per year. The incidence of intracerebral hemorrhage is highest in the 6th, 7th and 8th
decades of life and occurs somewhat later than the peak incidence for aneurysmal subarachnoid
hemorrhage. The cause of many intracerebral hemorrhages is unknown. Hypertension has been
implicated as a cause, but there is not a clear-cut relationship between the presence of systemic
arterial hypertension and the development of an intracerebral hemorrhage. Brain tumors,
vascular malformations and cocaine abuse are all associated with the development of
intracerebral hemorrhage.
The most common sites for intracerebral hemorrhage are in the basal ganglia
and occur in the putamen, globus pallidus or thalamus. Pontine and cerebellar
hemorrhages each account for 10% of all intracerebral hemorrhages, respectively.
Hemorrhages occurring in the frontal, temporal or occipital lobes are described as lobar
hemorrhages.
Clinical characteristics of intracerebral hemorrhage: Lesions occurring in
the putamen most often cause a contralateral hemiparesis or hemiplegia and may
progress to produce coma of death. Headaches may be present at the onset of the
hemorrhage but are frequently not noted. Patients with thalamic hemorrhages are
somewhat more likely to initially have a hemisonsory loss and then develop a
hemiparesis. Gaze disturbances are also frequently noted. A progressive or gradual
deterioration to a maximum neurological deficit characterizes the development of an
intracerebral hemorrhage and usually distinguishes it from arterial occlusion due to
embolus or thrombosis.
Management of intracerebral hemorrhage: Patients with small intracerebral
hemorrhages may be managed conservatively and observed for neurological
deterioration. If there is no significant neurological deficit or if the maximum
neurological deficit is not severe, no specific treatment other than anti-hypertensive
treatment may be required. For patients who have more profound neurological
deficits, hypertension should be treated cautiously and anti-convulsants and steroids should be
administered.
An extremely lethargic or comatose patient should be intubated to protect the airway.
Angiograms may be performed on intracerebral hemorrhages that occur in unusual locations or
associated with hemorrhage in the subarachnoid space, since an aneurysm or AVM may cause
an intracerebral hemorrhage. A lobar hemorrhage in a young patient may be more suggestive of
all underlying tumor or vascular malformation and therefore angiograms will frequently be
indicated.
Surgical treatment: Patients with accessible lobar hemorrhages who are deteriorating
neurologically will often improve with surgery. Large dominant hemisphere basal ganglia
lesions in elderly patients are probably not suitable candidates for surgery. The decision to
operate depends on the patient's neurological deficit, evidence of progression of the deficit, the
location of the hemorrhage and an assessment of the neurological prognosis, given all these
factors, by the treating physicians. A craniotomy is usually performed over the most superficial
aspect of the hemorrhage. The hemorrhage cavity is entered and the hematoma is aspirated and
removed. Biopsies of the wall of the hemorrhage cavity are always done to determine if a tumor
or vascular malformation may be present and causative. Many patients with intracerebellar
hemorrhage may require a ventriculostomy to manage concomitant hydrocephalus.