Cerebrovascular disease is the most common cause of neurologic disability in adults and the third most common cause of death in our society. About 500,000 people are disabled or killed by cerebrovascular disease each year in the United States.
Most authorities classify cerebrovascular disease into ischemic and hemorrhagic disorders.
Ischemic Cerebrovascular Disease
As a result of its high metabolic rate and limited energy reserves, the central nervous system (CNS) is uniquely sensitive to ischemia. Ischemia results in rapid depletion of adenosine triphosphate (ATP) stores in the CNS. Because Na+–K+-ATPase function is impaired, K+ accumulates in the extracellular space, which leads to neuronal depolarization (see Chapter 3). According to the excitotoxic hypothesis, within gray matter of the CNS, there is an ensuing avalanche of neurotransmitter release (including inappropriate release of excitatory transmitters such as glutamate). This leads to an influx of calcium via glutamate-gated channels as well as voltage-gated calcium channels that are activated as a result of depolarization. Within white matter of the CNS, where synapses are not present, calcium is carried into nerve cells via other routes, including the Na+–Ca2+ exchanger, a specialized molecule that exchanges calcium for sodium. It is generally thought that increased intracellular calcium represents a "final common pathway" leading to irreversible cell injury (the calcium hypothesis of neuronal cell death) because calcium activates a spectrum of enzymes, including proteases, lipases, and endonucleases that damage the neuronal cytoskeleton and plasma membrane.
Transient ischemia, if brief enough, may produce reversible signs and symptoms of neuronal dysfunction. If ischemia is prolonged, however, death of neurons (infarction) occurs and is usually accompanied by persistent neurologic deficits. Because of this time-dependence, ischemic cerebral disease is a medical emergency.
Surrounding the area of infarction, there is often a penumbra, in which neurons have been metabolically compromised and are electrically silent but are not yet dead. Neurons within the penumbra may be salvageable, and various neuroprotective strategies that interfere with calcium influx are being experimentally studied.
Diseases involving vessels of the brain and its coverings have characteristic clinical profiles and can be classified as follows (Table 12–1).
TABLE 12–1Clinical Profile of Cerebrovascular Disorders. ||Download (.pdf) TABLE 12–1 Clinical Profile of Cerebrovascular Disorders.
|Variable ||Hypertensive Intracerebral Hemorrhage ||Cerebral Infarct (Thrombotic) ||Cerebral Infarct (Embolic) ||Subarachnoid Hemorrhage ||Vascular Malformations (can include bleeding) ||Subdural Hemorrhage ||Epidural Hemorrhage |
|Pathology ||Hemorrhage deep structures (putamen, thalamus, cerebellum, pons) or lobar white matter ||Infarct in territory of large or small artery || |
Infarct in territory of large or medium-sized arteries
May be located at periphery of hemisphere (gray–white matter junction)
Bleeding into subarachnoid space from aneurysm
Hemorrhage into parenchyma may occur
|Bleeding or infarct near AVM; localization variable || |
Hemorrhage into subdural space, often over cerebral convexity
May see rupture of meningeal or bridging vein
Hemorrhage into epidural space
Often seen in association with skull fracture over middle meningeal artery
|Onset and course ||Rapid (minutes to hours) onset of hemiplegia or other signs and symptoms || |
Sudden, gradual, or stepwise onset of focal deficits
Often preceded by TIAs (eg, transient monocular blindness, hemiparesis)
|Sudden onset (usually within seconds or minutes) || |
Sudden severe headache
Possible loss of consciousness
Focal neurologic signs may be present
|Can present with repeated seizures (because of ischemia), or sudden onset of deficit caused by bleed || |
Variable time course
May see slow deterioration
Depressed level of consciousness, sometimes with hemiparesis
Can occur after even trivial trauma
|Rapid deterioration, often after a "lucid interval" following head trauma |
|Blood pressure ||Hypertension ||Hypertension often ||Normal ||Hypertension often ||Normal ||Normal at onset ||Normal at onset |
|Special findings ||Cardiac hypertrophy; hyperten- sive retinopathy ||Arteriosclerotic cardiovascular disease frequently present ||Cardiac arrhythmias or infarction (source of emboli often in heart) ||Subhyaloid (preretinal) hemorrhages; nuchal rigidity ||Subhyaloid hemorrhages and retinal angioma ||Trauma, bruises may be present ||Severe trauma often present |
|CT scan findings || |
Increased density surrounded by hypodensity from edema; may see blood in ventricles
Commonly see mass effect
|Less dense in avascular area ||Less dense in avascular area ||Increased density caused by blood in basal cisterns || |
Abnormal vessels, sometimes with calcifications
Dense cisterns may be seen after bleeding
|Dense (later, lighter) zone (high over convexity) ||Dense segment under skull fracture (low over convexity) |
|MR image || |
MRI very sensitive. May see blood clot
Signal characteristics change with time after bleed
|Decreased density on T1; increased density on T2 ||Decreased density on T1; increased density on T2 || |
Less sensitive than CT for subarachnoid blood
|May see hemorrhage ||May see hemorrhage ||May see hemorrhage |
|CSF ||May be bloody ||Clear ||Clear ||Grossly bloody or xanthochromic ||Bloody if hemorrhage has occurred ||May be bloody or xanthochromic ||Clear |
Occlusive cerebrovascular disorders: These result from arterial or venous thrombosis, or embolism, and can lead to infarction of well-defined parts of the brain. Because each artery irrigates a specific part of the brain, it is often possible, on the basis of the neurologic deficit, to identify the vessel that is occluded.
Transient cerebral ischemia: Transient ischemia, if brief enough, can occur without infarction. Episodes of this type are termed transient ischemic attacks (TIAs). As with occlusive cerebrovascular disease, the neurologic abnormalities often permit the clinician to predict the vessel that is involved.
Hemorrhage: The rupture of a blood vessel is often associated with hypertension or vascular malformations or with trauma.
Vascular malformations and developmental abnormalities: These include aneurysms or arteriovenous malformations (AVMs), which can lead to hemorrhage.
Hypoplasia or absence of vessels occurs in some brains.
Degenerative diseases of the arteries: These can lead to occlusion or to hemorrhage.
Inflammatory diseases of the arteries: Inflammatory diseases, including systemic lupus erythematosus, giant cell arteritis, and syphilitic arteritis, can result in occlusion of cerebral vessels, which, in turn, can produce infarction.
The neurologic deficits in cerebral infarcts or hemorrhages—cerebrovascular accidents (CVAs)—develop rapidly (hence the term "stroke"). Patients have sudden, severe focal disturbances of brain function (ie, hemiplegia, aphasia). The deficits appear rapidly (over minutes) or can develop with a stuttering course, over hours. The term stroke is a general one, and further determination of the site (where is the lesion?) and type of disease (what is the lesion?) are essential for correct diagnosis and treatment.
Occlusive Cerebrovascular Disease
Insufficient blood supply to portions of the brain leads to infarction and swelling with necrosis of brain tissue (Figs 12–11 and 12–12; see Table 12–1). Most infarcts are caused by atherosclerosis of the vessels, leading to narrowing, occlusion, or thrombosis; a cerebral embolism, that is, occlusion caused by an embolus (a plug of tissue or a foreign substance) from outside the brain; or other conditions such as prolonged hypotension, drug action, spasm, or inflammation of the vessels. Venous infarction is less common, but may occur when a venous channel becomes occluded.
A. Computed tomography image of a horizontal section of the head showing an infarct caused by middle cerebral artery occlusion. B. Magnetic resonance image of horizontal section of the head from another patient who also sustained an infarct in the distribution of the left middle cerebral artery. This patient presented with sudden onset of aphasia and right-sided weakness. (Used with permission from Joseph Schindler, M.D., Yale Medical School.)
The extent of an infarct depends on the presence or absence of adequate anastomotic channels. The extent of the infarct will often confirm to the territory supplied by the occluded artery, as shown in Figure 12–12. Capillaries from adjacent vascular territories and corticomeningeal capillaries at the surface may reduce the size of the infarct. When arterial occlusion occurs proximal to the circle of Willis, collateral circulation through the anterior communicating artery and posterior communicating arteries may permit sufficient blood flow to prevent infarction. Similarly, in some cases in which the internal carotid artery is occluded in the neck, anastomotic flow in the retrograde direction via the ophthalmic artery, from the external carotid artery, may provide adequate circulation, thus preventing infarction.
Although sudden occlusion can lead to irreparable damage, slowly developing local ischemia may be compensated for by increased flow through anastomoses involving one or more routes: the circle of Willis, the ophthalmic artery (whose branches communicate with external carotid vessels), or corticomeningeal anastomoses from meningeal vessels.
Atherosclerosis of the Brain
The principal pathologic change in the arteries of the brain occurs in the vasculature of the neck and brain, although similar changes may also be present in other systemic vessels. Hypertension accelerates the progression of atherosclerosis and is a treatable risk factor for stroke.
Atheromatous changes in the arterial system are particularly common in patients with untreated hypertension or with unfavorable lipid profiles. Vessels of all sizes may be affected. A combination of degenerative and proliferative changes can be seen microscopically. The muscularis is the main site of proliferation; the intima may be absent. The areas most often involved are near branchings or confluences of vessels (Fig 12–13). The most common and severe atherosclerotic lesions are in the carotid bifurcation. Others occur at the origin of the vertebral arteries, in the upper and lower parts of the basilar artery, and in the internal carotid artery at its trifurcation, the first third of the middle cerebral artery, and the first part of the posterior cerebral artery.
Distribution of degenerative lesions in large cerebral arteries of the circle of Willis. The severity of the lesions is illustrated by the intensity of the shaded areas; the darkest areas show the most severe lesions.
Computed tomography image of a horizontal section of the head, showing an infarct caused by a right-sided anterior cerebral artery occlusion (arrows). Notice the location of the infarct (compare with Figs 12–6 and 12–7). The patient had weakness and numbness of the left leg.
The sudden occlusion of a brain vessel by a blood clot, a piece of fat, a tumor, a clump of bacteria, or air abruptly interrupts the blood supply to a portion of the brain and can result in infarction. A common cause of cerebral embolism is atrial fibrillation. Other common causes include endocarditis and mural thrombus after myocardial infarction. Atheromatous material can break off from a plaque in the carotid artery and, after being carried distally, occlude smaller arteries.
Transient Cerebral Ischemia
Focal cerebral ischemic attacks, especially in middle- aged and older persons, can be caused by transient occlusion of an already narrow vessel. The cause is thought to be a vasospasm, a small embolus that is later carried away, or thrombosis of a diseased vessel (and subsequent lysis of the clot, or anastomosis). Such TIAs result in reversible ischemic neurologic deficits, such as sudden vertigo or sudden focal weakness, loss of cranial nerve function, or even brief loss of consciousness. These episodes are usually due to ischemia in the territory of an artery within the carotid or vertebrobasilar system. There is usually full recovery from a TIA in less than 24 hours (commonly within 30 minutes). These attacks are considered warning signs of future, or imminent, occlusion and merit a rapid workup as shown in Clinical Illustration 12–1.
CLINICAL ILLUSTRATION 12–1
A 48-year-old hypertensive attorney did not take his blood pressure medications. He was apparently well until 4 days after his birthday, when he had several episodes of blurred vision, "like a shade coming down," involving his left eye. These attacks each lasted less than an hour. He was referred for neurologic evaluation but canceled the appointment because of a busy schedule. Several weeks later, he complained to his wife of a left-sided headache. She found him a half hour later slumped in a chair, apparently confused and paralyzed on the right side. Neurologic examination revealed total paralysis of the right arm and severe weakness of the right face. The leg was only mildly affected. Deep tendon reflexes were initially depressed on the right side but within several days became hyperactive; there was a Babinski response on the right. The patient was globally aphasic; he was unable to produce any intelligible speech and appeared to understand only very simple phrases. A computed tomography (CT) scan revealed an infarct in the territory of the middle cerebral artery of the left side (see Fig 4–3). Angiography revealed occlusion of the internal carotid artery. The patient recovered only minimally.
This case illustrates several points. Although the carotid artery on the left was totally occluded, the patient's cerebral infarct was limited to the territory of the middle cerebral artery. Even though the anterior cerebral artery arises (together with the middle cerebral artery) from the carotid, the anterior cerebral artery's territory was spared, probably as a result of collateral flow from other vessels (eg, via the anterior communicating artery). The patient's functional deficit was nevertheless devastating because much of the motor cortex and the speech areas in the left hemisphere were destroyed by the infarction.
This case reminds us that hypertension represents an important risk factor for stroke, and all patients with hypertension should be carefully evaluated and treated if appropriate. It is not enough to prescribe medication; the physician must follow up and make sure the patient takes the medicine. This patient exhibited several episodes of amaurosis fugax, or transient monocular blindness. These episodes, which are due to ischemia of the retina, often occur in the context of atherosclerotic disease of the carotid artery. Indeed, angiography after this patient's stroke revealed occlusion of the carotid artery. The probability of a stroke appears to be highest in the period after TIA onset. Any patient with TIAs of recent onset should be evaluated on an urgent basis.
The advent of thrombolysis with tPA has made acute stroke a treatble entity if therapy is begun early enough. Strokes, and suspected strokes, should be regarded as "brain attacks," and patients should be transported to the emergency room without delay.
Localization of the Vascular Lesion in Stroke Syndromes
The cerebral vessels tend to irrigate particular, well-defined parts of the brain, in patterns that are reproducible from patient to patient. Thus, it is often possible, in stroke syndromes, to identify the affected blood vessel on the basis of the neurologic signs and symptoms, even before imaging studies are carried out.
Carotid artery disease is often accompanied by contralateral weakness or sensory loss. If the dominant hemisphere is involved, there may be aphasia or apraxia. Transient blurring or loss of vision (amaurosis fugax) may occur if there is retinal ischemia. In practice, after occlusion of the internal carotid artery, ischemia is often limited to the territory of the middle cerebral artery, so that weakness predominantly affects the contralateral face and arm. This is because the anterior and posterior cerebral artery territories are nourished via collateral flow from the contralateral circulation via the anterior communicating and posterior communicating arteries. Clinical Illustration 12–1 provides an example.
As predicted from its position with respect to the motor and sensory homunculi, unilateral occlusion of the anterior cerebral artery results in weakness and sensory loss in the contralateral leg (Fig 12–17). In some patients, after bilateral occlusion of the anterior cerebral arteries, there is damage to the frontal lobes, resulting in a state of akinetic mutism, in which the patient is indifferent and apathetic, moving little, and not speaking even though there is no paralysis of the immobile limbs.
Vertebrobasilar artery disease often presents with vertigo, ataxia (impaired coordination), dysarthria (slurred speech), and dysphasia (impaired swallowing). Vertigo, nausea, and vomiting may be present, and if the oculomotor complex is involved, there may be diplopia (double vision). The brain stem syndromes are discussed in Chapter 7, and those arising from arterial occlusion are summarized in Table 12–2.
TABLE 12–2Brain Stem Syndromes Resulting from Vascular Occlusion. ||Download (.pdf) TABLE 12–2 Brain Stem Syndromes Resulting from Vascular Occlusion.
|Syndrome ||Artery Affected ||Structure Involved ||Clinical Manifestations |
|Medial syndromes |
| Medulla ||Paramedian branches ||Emerging fibers of twelfth nerve ||Ipsilateral hemiparalysis of tongue |
| Inferior pons ||Paramedian branches ||Pontine gaze center, near or in nucleus of sixth nerve ||Paralysis of gaze to side of lesion |
| || ||Emerging fibers of sixth nerve ||Ipsilateral abduction paralysis |
| Superior pons ||Paramedian branches ||Medial longitudinal fasciculus ||Internuclear ophthalmoplegia |
|Lateral syndromes |
| Medulla ||Posterior inferior cerebellar ||Emerging fibers of ninth and tenth nerves ||Dysphagia, hoarseness, ipsilateral paralysis of vocal cord; ipsilateral loss of pharyngeal reflex |
| || ||Vestibular nuclei ||Vertigo, nystagmus |
| || ||Descending tract and nucleus of fifth nerve ||Ipsilateral facial analgesia |
| || ||Solitary nucleus and tract ||Taste loss on ipsilateral half of tongue posteriorly |
| Inferior pons ||Anterior inferior cerebellar ||Emerging fibers of seventh nerve ||Ipsilateral facial paralysis |
| || ||Solitary nucleus and tract ||Taste loss on ipsilateral half of tongue anteriorly |
| || ||Cochlear nuclei ||Deafness, tinnitus |
| Midpons || ||Motor nucleus of fifth nerve ||Ipsilateral jaw weakness |
| || ||Emerging sensory fibers of fifth nerve ||Ipsilateral facial numbness |
Hemorrhagic Cerebrovascular Disease: Hypertensive Hemorrhage
Chronic high blood pressure may result in the formation of small areas of vessel distention—microaneurysms—mostly in small arteries that arise from much larger vessels. A further rise in blood pressure then ruptures these aneurysms, resulting in an intracerebral hemorrhage (see Table 12–2). In order of frequency, the most common sites are the lentiform nucleus, especially the putamen, supplied by the lenticulostriate arteries (Fig 12–15); the thalamus, supplied by posterior perforating arteries off the posterior cerebrobasilar artery bifurcation (Fig 12–16); the white matter of the cerebral hemispheres (lobar hemorrhages); the pons, supplied by small perforating arteries from the basilar artery; and the cerebellum, supplied by branches of the cerebellar arteries. The blood clot compresses and may destroy adjacent brain tissue; cerebellar hemorrhages may compress the underlying fourth ventricle and produce acute hydrocephalus. Intracranial hemorrhages are medical emergencies and require prompt diagnosis and treatment.
Computed tomography image of a horizontal section through the head, showing a hematoma (arrows) in the putamen.
Hemorrhage in the right posterior thalamus and internal capsule in a 64-year-old woman.
Subarachnoid hemorrhages usually derive from ruptured aneurysms or vascular malformations (Figs 12–17, 12–18, 12–19; see Table 12–1). Aneurysms (abnormal distention of local vessels) may be congenital (berry aneurysm) or the result of infection (mycotic aneurysm). One complication of subarachnoid hemorrhage, arterial spasm, can lead to infarcts.
Computed tomography image of a horizontal section through the head, showing high densities, representing a subarachnoid hemorrhage (arrows) in the sulci.
A: Computed tomography image of a horizontal section through the head, showing a large aneurysm of the anterior communicating artery. (Reproduced, with permission, from deGroot J: Correlative Neuroanatomy of Computed Tomography and Magnetic Resonance Imaging. Lea & Febiger, 1984.) B: Corresponding angiogram showing the partially thrombosed aneurysm (arrows).
Magnetic resonance image of a horizontal section through the head, demonstrating an arteriovenous malformation (arrows).
Congenital berry aneurysms are seen most frequently in the circle of Willis or in the middle cerebral trifurcation; they are especially common at sites of arterial branching. Aneurysms are seen infrequently in vessels of the posterior fossa. A ruptured aneurysm generally bleeds into the subarachnoid space or, less frequently, into the brain itself.
Vascular malformations, especially AVMs, often occur in younger persons and are found on the surface of the brain, deep in the brain substance, or in the meninges (dural AVMs). Bleeding from such malformations can be intracerebral, subarachnoid, or subdural.
Tearing of the bridging veins between brain surface and dural sinus is the most frequent cause of subdural hemorrhage (Figs 12–20 and 12–21; see Table 12–1). It can occur as the result of a relatively minor trauma, and some blood may be present in the subarachnoid space. Children (because they have thinner veins) and aged adults with brain atrophy (because they have longer bridging veins) are at greatest risk.
Magnetic resonance image of a horizontal section through the head, showing a left subdural hematoma (arrows) causing a midline shift.
Schematic illustration of a subdural hemorrhage.
Bleeding from a torn meningeal vessel (usually an artery) may lead to an extradural (outside the dura) accumulation of blood that can rapidly compress the brain, progressing to herniation or death if not surgically evacuated. Fracture of the skull can cause this type of epidural, or extradural, hemorrhage (Figs 12–22 and 12–23; see Table 12–1). Uncontrolled arterial bleeding may lead to compression of the brain and subsequent herniation. Immediate diagnosis and surgical drainage are essential.
Schematic illustration of an epidural hemorrhage.
Computed tomography image of a horizontal section through the head, showing an extradural hematoma and intracerebral contrecoup lesion. (Reproduced, with permission, from deGroot J: Correlative Neuroanatomy of Computed Tomography and Magnetic Resonance Imaging. 21st ed. Appleton & Lange, 1991.)
AVMs, in which cerebral arteries and veins form abnormal tangles or webs, can occur as developmental anomalies. Whereas some AVMs are clinically silent, others tend to bleed or cause infarction in nearby parts of the brain. Trauma can also cause the rupture of adjacent vessels, allowing arterial blood to flow into nearby veins. For example, in a carotid-cavernous fistula, the internal carotid drains into the cavernous sinus and jugular vein, causing ischemia in the cerebral arteries. There is often pulsating exophthalmos (forward protrusion of the eye in the orbit), and there may be extraocular palsies because of pressure on the oculomotor, trochlear, and abducens nerves, which run through the cavernous sinus. Interventional methods, which involve inserting a balloon or other instrumentation into the shunt via a catheter or surgery, may correct the problem.
A 44-year-old woman was admitted after a seizure. She was lethargic, with a right facial droop, right hemiparesis, and right hyperreflexia. She complained of headache and a painful neck. A few days later, she seemed slightly more alert and made purposeful movements with her left hand but not her right hand. She was still unresponsive to spoken commands and had a rigid neck. Other findings included papilledema, a right pupil that was smaller than the left, incomplete extraocular movements on the left side (nerve VI function was normal), decreased right corneal reflex, and right nasolabial droop. The right arm was hypertonic and paretic, but the other extremities were normal. Reflexes appeared normal. The right plantar extensor response was equivocal, but the left was normal.
The blood pressure was 120/85; pulse rate, 60; and temperature, 38°C (100.4°F). The white blood count was 11,200/μL, and the erythrocyte sedimentation rate was 30 mm/h.
Where is the lesion? What is the cause of the lesion? What is the differential diagnosis?
A CT scan showed a high-density area in the cisterns, especially on the right side. What is the diagnosis? Would you request a lumbar puncture with analysis of the cerebrospinal fluid?
A 55-year-old salesman exhibiting signs of confusion was brought to the hospital. The history from his landlady indicated that he drank alcohol excessively. His landlady found him lying on the floor, incontinent and appearing bewildered; he had also bitten his lip. The landlady remembered that he had been involved in a bar fight 2 months earlier, and 3 weeks previously he had fractured his wrist falling down stairs.
On examination, the patient was unconcerned and disheveled. Bruises on his head and legs were consistent with recent trauma. The liver was palpable 4 cm below the right costal margin. The patient appeared to fall asleep when left alone. Neurologic examination showed normal optic fundi, normal extraocular movements, and no abnormalities that would result from dysfunction of other cranial nerves. When the left hand was extended, it showed a slow downward drift. The reflexes were normal and symmetric, and there was a left-sided plantar extensor response.
Vital signs, complete blood count, and urinalysis were within normal limits. A lumbar puncture showed an opening pressure of 180 mm H2O, xanthochromia, a protein level of 80 mg/dL, and a glucose level of 70 mg/dL. Cell counts in all tubes showed red blood cells, 800/μL; lymphocytes, 20/μL; and polymorphonuclear neutrophils, 4/mL. A CT scan of the head was obtained.
Over the next 36 hours, the patient became deeply obtunded, and a left-sided hemiparesis seemed to develop.
What is the differential diagnosis? What is the most likely diagnosis?
Questions and answers pertaining to Section IV (Chapters 7, 8, 9, 10, 11, 12) can be found in Appendix D.
Cases are discussed further in Chapter 25.
BOX 12–1 Essentials for the Clinical Neuroanatomist After reading and digesting this chapter, you should know and understand:
Principal arteries of the brain (Fig 12-3)
The circle of Willis
The vertebrobasilar circulation including arterial supply of the brain stem (Fig 12-4)
Carotid territory and anterior, middle, and posterior cerebral arteries (Figs 12-5 and 12-6)
The clinical correlates of occlusion of each of the principal arteries