The term stroke denotes a wide variety of nontraumatic cerebrovascular accidents of abrupt onset. So defined, stroke has many causes (Table 64-1; Figure 64-3); cerebral thrombosis with infarction is responsible for about 90% of cases. Stroke is one of the leading causes of death and morbidity in developed countries, accounting for approximately 200,000 deaths per year in the United States and 80,000 in Great Britain. Five percent of persons over 65 years in the United States suffer a stroke, and over 400,000 persons per year are released from hospitals after surviving a stroke.
Ischemic Strokes (Cerebral Infarction)
Atherosclerosis and Thrombosis
Cerebral thrombosis resulting from atherosclerotic arterial disease is responsible for most cases of cerebral infarction. Atherosclerosis tends to involve the large arteries (Figure 64-4). Sites of arterial branching (such as the carotid bifurcation) and curvature (the carotid siphon in the petrous temporal bone) tend to show severe atherosclerosis. Small arteries on the surface of the brain are rarely affected.
Distribution of atherosclerosis, berry aneurysms, and microaneurysms in cerebral vessels.
The circle of Willis at the base of the brain is a highly effective anastomotic system between the carotid and vertebrobasilar arteries. Occlusions proximal to the circle of Willis are usually compensated for by the collaterals in the circle. Arteries distal to the circle are functionally end arteries, and their occlusion usually results in cerebral infarction.
Atherosclerosis may have several consequences: (1) narrowing in excess of 75% causes a significant decrease in blood flow; (2) thrombosis may occlude the artery—the most common site for thrombosis is at the carotid sinus and bifurcation; and (3) ulceration of an atherosclerotic plaque releases emboli into the distal circulation. These emboli are commonly composed of cholesterol or small platelet aggregates and may give rise to transient ischemic attacks (see below). Infarction follows any of the above if the blood supply falls below critical levels for a sufficiently long time.
Small cerebral emboli are difficult to identify during life or at autopsy; they may be responsible for many cases of “nonocclusive” infarction. Recognizable emboli occur (1) after myocardial infarction due to detachment of mural thrombi; (2) with infective endocarditis due to detachment of valvular vegetations; (3) with prosthetic cardiac valves; (4) with mitral stenosis and atrial fibrillation; and (5) with atherosclerotic disease in the aortic arch, carotids, or circle of Willis.
Prolonged hypoxia, usually secondary to hypotensive shock, results in cerebral necrosis. This may be widespread in severe hypoxia, producing extensive autolysis of brain in patients whose lives are maintained artificially (respirator brain). With lesser degrees of hypoxia, selective necrosis of the most susceptible cells—neurons in the deep cortical gray matter—results. This necrosis of a layer of neurons in the cortex is called laminar necrosis. A similar lesion complicates severe hypoglycemia.
Rarely, cerebral ischemia is the result of vasculitides such as polyarteritis nodosa and giant cell arteritis affecting cerebral arteries (Table 64-1). Cerebral venous occlusion is a rare cause of stroke but an important one because it occurs in hypercoagulable states or in severe dehydration and is treatable if diagnosed early.
The earliest gross change after infarction occurs at about 6 hours and is a softening of the brain with loss of the normal demarcation between gray and white matter (Figure 64-5). Microscopically, the neurons show nuclear pyknosis, cytoplasmic eosinophilia, and liquefaction. Glial cells disappear, and the myelin sheaths and axis cylinders in the white matter disintegrate.
Cerebral infarction, showing clinical and pathologic changes observed at different stages.
At 48–72 hours the cerebral infarct is fully formed, appearing as a pale, soft area composed of liquefied necrotic cells. The surrounding brain shows edema. Ten to 20 percent of cerebral infarcts are hemorrhagic, due possibly to restoration of blood supply to the infarcted area, either by fibrinolysis or by fragmentation of the thrombus.
After a transient phase of neutrophil infiltration, macrophages appear in large numbers (Chapter 1: Cell Degeneration & Necrosis). They phagocytose the dead tissue, becoming converted to large cells with abundant pale foamy cytoplasm called gitter cells or compound granular corpuscles.
After about 3 weeks, the debris has been cleared, producing a cystic fluid-filled cavity (Figure 64-6) surrounded by a zone of reactive gliosis.
Cerebral infarct, showing a cystic space (which collapsed when the brain was cut) associated with loss of cerebral substance in the distribution of the middle cerebral artery. This is the typical appearance of an old infarct.
Cerebral infarction is characterized by a sudden loss of neurologic function corresponding to the area involved (Table 64-2). The onset may be acute but is usually not as explosive as in cerebral hemorrhage. In many cases the neurologic deficit progresses over several hours to days. Infarction secondary to thrombosis has a slower onset than that caused by embolism.
Localizing Signs Associated with Occlusion of Major Cerebral Arteries.
Localizing Signs Associated with Occlusion of Major Cerebral Arteries.
Anterior cerebral artery
Motor and sensory cortex (leg area)
Contralateral weakness, maximal in leg; cortical–type sensory loss, maximal in leg
Middle cerebral artery
Lateral surface of hemisphere
Contralateral hemiparesis, face > leg; contralateral cortical–type sensory loss
Speech area (if dominant hemisphere)
Posterior cerebral artery
Cortical–type visual loss
Intention tremor, incoordination, hypotonia
Contralateral hemiparesis and sensory loss; ipsilateral cranial nerve palsies
Most patients with infarction also show evidence of increased intracranial pressure due to the presence of edema around the infarct. The edema may cause additional neurologic deficits that are reversible—unlike the deficit produced by the infarct itself.
Treatment is supportive. In the acute phase, corticosteroids and diuretics such as furosemide and mannitol are used to decrease cerebral edema and intracranial pressure.
The overall prognosis for recovery of neurologic function after cerebral infarction is reasonably good. Even in patients in whom the initial deficit is severe, considerable improvement may occur, with reversal of cerebral edema and recovery of function by ischemic but not necrotic neurons.
Transient Ischemic Attacks
Transient ischemic attacks are caused by (1) low flow states in patients with widespread atherosclerotic narrowing of cerebral arteries, and (2) platelet or cholesterol emboli originating from ulcerative atherosclerotic plaques in the carotid arteries or even the aorta. The neurologic dysfunction depends on the area of brain affected. Attacks last a few seconds to a few minutes; by definition, recovery occurs within 24 hours. The frequency of attacks varies from several times a day (common in low flow states) to once in several months (typical of embolic episodes). In patients with embolic episodes, the diagnosis may be established by observing the embolic fragments in the vessels of the optic fundus. Cholesterol emboli have a bronze appearance, whereas platelet emboli are white. The brain shows no pathologic changes.
The occurrence of transient ischemic attacks indicates the presence of severe atherosclerosis in the cerebral arteries. Thirty percent of such patients will suffer cerebral infarction within 5 years; conversely, 30% of patients with cerebral infarction give a history of transient ischemic attacks. Patients with transient ischemic attacks should therefore be evaluated for surgically correctable vascular disease or for anticoagulant therapy. Aspirin has been used with some success in the treatment of transient ischemic attacks.
Hypertensive encephalopathy results from cerebral ischemia due to arterial spasm precipitated by extremely high blood pressure, usually in patients with malignant hypertension. Spasm is temporary and results in cerebral edema, usually with minimal or no necrosis.
Patients develop acute transient neurologic dysfunction, convulsions, and increased intracranial pressure. The condition requires immediate treatment to reduce blood pressure and decrease cerebral edema; recovery is then the rule.
Several factors may contribute to cerebral hemorrhage (Table 64-1). The site of the bleeding distinguishes intracerebral hemorrhages (small arteries deep in the brain substance, eg, lenticulostriate arteries) from subarachnoid hemorrhage (larger arteries traversing the subarachnoid space). In practice, the bleeding site may not be identifiable in large hemorrhages that involve both subarachnoid space and brain substance, and the distinction is then somewhat arbitrary.
Spontaneous Intracerebral Hemorrhage
Cerebral hemorrhage is responsible for about 10% of strokes. Over 80% of intracerebral hemorrhages are secondary to hypertension. Most occur after age 40 years, and the most common site is around the basal ganglia and internal capsule from rupture of the lenticulostriate arteries (Figure 64-4).
Less commonly, intracerebral hemorrhage may result from rupture of arteriovenous malformations, particularly important as a cause in patients under 40 years of age. Rupture of a mycotic aneurysm complicating infective endocarditis, acute bleeding into a cerebral neoplasm, and bleeding diatheses such as thrombocytopenia and coagulation disorders are rare causes of intracerebral hemorrhage (Table 64-1).
The site of rupture is frequently a microaneurysm (Charcot-Bouchard aneurysm) in the lenticulostriate arteries. Multiple microaneurysms occur at this location in a significant number (70%) of hypertensive patients (Figure 64-4). Rupture is commonly precipitated by a sudden increase in blood pressure. The rapidly expanding blood clot dissects and destroys brain tissue and may rupture into the ventricular system or subarachnoid space. Blood in the cerebrospinal fluid causes meningeal irritation.
The expanding hematoma (Figure 64-7) acts like a space-occupying lesion, causing rapid and marked increase in intracranial pressure and displacing brain substance. Tentorial herniation is common and may cause death by compressing the brain stem.
Intracerebral hematoma involving the region of the basal ganglia. This is the typical location of a hypertensive intracerebral hemorrhage caused by rupture of microaneurysms involving the lenticulostriate arteries.
Recovery from intracerebral hemorrhage is followed by breakdown of the blood and necrotic brain tissue, leading to an area of gliosis and cystic change that appears brown because of the numerous hemosiderin-laden macrophages.
Intracerebral hemorrhage results in abrupt onset of headache, dense neurologic deficit, papilledema, and loss of consciousness (cerebral apoplexy). Because bleeding is commonly in the region of the basal ganglia, hemiplegia from pyramidal tract involvement in the internal capsule is the most common neurologic deficit. Cerebral hemorrhage is associated with a high mortality rate.
Spontaneous Subarachnoid Hemorrhage
Spontaneous subarachnoid hemorrhage is less common than spontaneous intracerebral hemorrhage and usually (95% of cases) results from rupture of a berry aneurysm (saccular aneurysm) of the cerebral arteries.
Berry aneurysms are also called congenital aneurysms, although they are not present at birth. There is, however, a congenital defect of the media of the artery, which becomes the site of the aneurysm in later life. Berry aneurysms are commonly located in the circle of Willis. The common sites are the anterior communicating artery (30%), the junction of the posterior communicating and internal carotid arteries (30%), the middle cerebral artery (10%), and the basilar artery (10%). In 10–20% of cases, multiple berry aneurysms are present (Figure 64-4).
Rupture of a berry aneurysm may occur at any time but is rare in childhood. The frequency of rupture increases with age. Hypertension and atherosclerosis result in further weakening of the aneurysm and predispose to rupture. Actual rupture of an aneurysm may be precipitated by exercise (one of the recognized complications of jogging) and sexual intercourse. Many aneurysms never rupture and are found incidentally at autopsy.
When aneurysms rupture, they usually cause rapid bleeding into the subarachnoid space (Figure 64-8). Many aneurysms leak a little blood before they burst, leading to adhesions between the wall of the aneurysm and adjacent structures. If such adhesions tether the aneurysm to the brain surface, final rupture of the aneurysm may occur into the substance of the brain, presenting as an intracerebral hemorrhage rather than a subarachnoid hemorrhage.
Subarachnoid hemorrhage, showing extensive bleeding into the subarachnoid space in a patient with a ruptured berry aneurysm.
Intact berry aneurysms may become large enough to cause focal symptoms, eg, third nerve paralysis due to compression by a large posterior communicating artery aneurysm.
Subarachnoid hemorrhage presents with sudden onset of severe “bursting” headache associated with vomiting, pain in the neck, and rapid loss of consciousness. Marked neck stiffness is present as a result of the meningeal irritation caused by the blood. Increased intracranial pressure with papilledema is common. Blood courses along the subarachnoid sheath around the optic nerve and may be visible ophthalmoscopically as an area of hemorrhage in the retina below the optic disk.
The diagnosis is made clinically. Computerized tomography and magnetic resonance imaging are useful in demonstrating the blood as well as the aneurysm in many cases. Lumbar puncture, which may be performed after the presence of a mass lesion in the brain has been excluded, shows the presence of blood in cerebrospinal fluid.
Death may occur rapidly. In patients who recover, there is a high risk of recurrence, and surgical correction is urgent.
Occlusion of cerebral veins and venous sinuses is an uncommon cause of cerebrovascular accident. In general, venous drainage of the brain has many collaterals, and occlusion of a large vein is necessary before clinical effects are produced.
Superior sagittal sinus thrombosis may occur in severely malnourished or chronically sick individuals. It is characterized by edema, hemorrhage, and infarction involving both cerebral hemispheres.
Thrombophlebitis of the cortical cerebral veins occurs rarely in women after childbirth or abortion. When extensive, it causes fever, convulsions, and infarction of the cerebral hemisphere.
Thrombosis of the vein of Galen (internal cerebral vein) leads to hemorrhagic infarction of the thalamic region and deep white matter.
Cavernous sinus thrombophlebitis may result from spread of infection from the face and orbit and is associated with high fever, leukocytosis, orbital edema, congestion, and hemorrhage. This disorder presents with marked proptosis with pain and can result in blindness.
Lateral sinus thrombophlebitis may occur as a complication of suppurative otitis media. It is accompanied by severe bacteremia and associated with high fever and pain in the back of the head.