Neurology_Adams

Neurology_Adams. several hundred and even thousands of patients and conducted simultaneously in dozens of institutions have come to dominate investigative activity in this field. These multicenter trials have yielded highly valuable information about the treatment of a variety of cerebrovascular disorders, both symptomatic and asymptomatic. However, this approach suffers from a number of inherent limitations, the most important of which is that the homogenized data derived from an aggregate of patients is difficult to apply to a specific case at hand or the data is not available to resolve each patient’s particular problem. Most large studies show only modest or marginal differences between treated and control groups and correspondingly give guidance in large populations. These multicenter studies will be critically appraised at appropriate points in the ensuing discussion.


Neurology_Adams

Neurology_Adams. Differentiation of Stroke From Other Neurologic Illnesses


Neurology_Adams

Neurology_Adams. The diagnosis of a vascular lesion therefore rests essentially on recognition of the stroke syndrome; without evidence of this, the diagnosis must always be in doubt. The three criteria by which the stroke is identified should be reemphasized: (1) the temporal profile of the clinical syndrome, (2) evidence of focal brain disease, and (3) the clinical setting, by which we mean potential causes of embolic or other types of stroke, such as atrial fibrillation. Definition of the temporal profile requires a clear history of the premonitory phenomena, the mode of onset, and the evolution of the neurologic disturbance in relation to the patient’s medical status. Here, an inadequate history is the most frequent cause of diagnostic error. If these data are lacking, the stroke profile may still be determined by extending the period of observation for a few days or weeks in order to determine if the temporal pattern is more in keeping with a progressive disorder such as brain tumor, thus


Neurology_Adams

Neurology_Adams. be determined by extending the period of observation for a few days or weeks in order to determine if the temporal pattern is more in keeping with a progressive disorder such as brain tumor, thus invoking the clinical rule that the physician’s best diagnostic tool is a second and third examination.


Neurology_Adams

Neurology_Adams. There are several categories of neurologic disease, the temporal profile of which mimic the cerebrovascular disorders. Migraine may do so, but the history usually provides the diagnosis. A seizure may be followed by a prolonged focal deficit (Todd paralysis) but is rarely the initial event in a stroke; the setting in which these symptoms occur and their subsequent course clarify the clinical situation. Tumor, infection, inflammation, degeneration, and nutritional deficiency are unlikely to manifest themselves precipitously, although rarely a primary or metastatic brain tumor produces a focal deficit of abrupt onset (see later). Trauma, of course, occurs abruptly but usually offers no problem in diagnosis. In multiple sclerosis and other demyelinative diseases, there may be an abrupt onset or exacerbation of symptoms, but for the most part they occur in a different age group and clinical setting. Conversely, a stroke-like onset of cerebral symptoms in a young adult should always raise


Neurology_Adams

Neurology_Adams. or exacerbation of symptoms, but for the most part they occur in a different age group and clinical setting. Conversely, a stroke-like onset of cerebral symptoms in a young adult should always raise a suspicion of demyelinative disease. A stroke developing over a period of several days usually progresses in a stepwise fashion, increments of deficit being added abruptly from time to time. A slow, gradual, downhill course over a period of 2 weeks or more indicates that the lesion is probably not vascular but rather neoplastic, demyelinative, infectious (abscess) or granulomatous, or a subdural hematoma.


Neurology_Adams

Neurology_Adams. In regard to the focal neurologic deficits of cerebrovascular disease, many of the nonvascular diseases may produce symptoms that are much the same, and the diagnosis cannot rest solely on this aspect of the clinical picture. Nonetheless, specific patterns of neurologic signs are so highly characteristic of vascular occlusion—for example, the lateral medullary syndrome—that they mark the disease as a stroke. Conversely, certain disturbances are hardly ever attributable to ischemic stroke—for example, diabetes insipidus, fever, bitemporal hemianopia, parkinsonism, generalized myoclonus, repeated falls, and isolated cranial-nerve palsies—and their presence may be of help in excluding vascular disease. Finally, the diagnosis of cerebrovascular disease should always be made on positive data, not by exclusion.


Neurology_Adams

Neurology_Adams. A few conditions are so often confused with cerebrovascular diseases that they merit further comment. Miscellaneous conditions occasionally taken to be a stroke are migraine; Bell palsy; Stokes-Adams syncopal attacks; a severe attack of labyrinthine vertigo; diabetic ophthalmoplegia; acute ulnar, radial, or peroneal palsy; embolism to a limb; and temporal arteritis associated with blindness all of which are discussed in later parts of this chapter.


Neurology_Adams

Neurology_Adams. A brain tumor, especially a rapidly growing glioblastoma or lymphoma, may produce a severe hemiplegia rapidly. Also, the neurologic deficit caused by cancer metastatic to the cerebrum may evolve rapidly, almost at a stroke-like pace. Moreover, in rare cases of brain tumor, a hemiplegia may be preceded by transitory episodes of neurologic deficit, indistinguishable from TIAs. The presence of the tumor and its effects on the cerebrum may make it difficult for the patient to articulate a clear history. A lack of detailed history may also be responsible for the opposite diagnostic error, that is, mistaking a relatively slowly evolving stroke (usually caused by internal carotid artery or basilar occlusion) for a tumor. CT and MRI usually settle the problem. A brain abscess or inflammatory necrotic lesion—for example, herpes encephalitis or toxoplasmosis—may also develop rapidly.


Neurology_Adams

Neurology_Adams. Contrariwise, certain manifestations of stroke may be incorrectly interpreted as evidence of some other neurologic disorder. Headache, at times severe, often occurs as a prodrome of a thrombotic stroke or subarachnoid hemorrhage; unless this is appreciated, a diagnosis of migraine may be made. Dizzy spells, vertigo, vomiting, or brief intermittent lapses of equilibrium as a result of vascular disease of the brainstem may be ascribed to vestibular neuritis, Ménière disease, Stokes-Adams syncope, or gastroenteritis. A detailed account of the attack will usually avert this error. A strikingly focal monoplegia of cerebral origin, causing only weakness of the hand or arm or foot-drop, is not infrequently misdiagnosed as a peripheral neuropathy or plexopathy. Epidemiology of Stroke


Neurology_Adams

Neurology_Adams. Stroke assumes importance both because of its high rate of mortality and the residual disability that it causes. Stroke, after heart disease, cancer, and accidents is among the most common cause of death in the United States. Every year there are approximately 700,000 cases of stroke in the United States—roughly 600,000 ischemic lesions and 100,000 hemorrhages, intracerebral or subarachnoid—with 175,000 fatalities from these causes combined. Since 1950, coincident with the introduction of effective treatment for hypertension and hyperlipidemia, there has been a substantial reduction in the frequency of stroke. Both sexes have shared in the reduced incidence. During this period, the incidence of coronary artery disease and uncontrolled hypertension also fell significantly. By contrast, there has been no change in the frequency of aneurysmal rupture. In the last two decades, according to the American Heart Association, the mortality rate from stroke has declined by 12 percent, but the


Neurology_Adams

Neurology_Adams. has been no change in the frequency of aneurysmal rupture. In the last two decades, according to the American Heart Association, the mortality rate from stroke has declined by 12 percent, but the total number of strokes may again be rising.


Neurology_Adams

Neurology_Adams. The burden of stroke has far wider implications when viewed from an international perspective. Cerebrovascular disease is estimated to account for 7.8 million deaths yearly throughout the world and represents about 13 percent of all causes of death. In developed countries, stroke mortality is only surpassed by cardiac ischemic diseases and close to equivalent to the cancers collectively (mainly lung cancer) in the Global Burden of Disease study. Stroke remains among the five leading causes of death across every income group in most countries in the last comprehensive review by the World Health Organization. The cumulative lifetime risk for 195 countries between 1990 and 2016 has been estimated to be 18 percent for ischemic stroke and 8 percent for hemorrhagic stroke. Strokes cause significant physical, emotional, and cognitive disabilities among survivors, accounting for 3.6 percent of the total disability-adjusted life years (DALYs) and thus placing stroke within the 10 leading


Neurology_Adams

Neurology_Adams. physical, emotional, and cognitive disabilities among survivors, accounting for 3.6 percent of the total disability-adjusted life years (DALYs) and thus placing stroke within the 10 leading causes of disability irrespective of the development status of countries (The 203 Global Burden of Disease for stroke can be found in the article by Feigen et al).


Neurology_Adams

Neurology_Adams. This is an area of major public health importance in that several modifiable factors are known to increase the liability to stroke. The most important of these are hypertension, atrial fibrillation, diabetes mellitus, cigarette smoking, and hyperlipidemia. Others, such as systemic diseases associated with a hypercoagulable state and the use of contraceptives, also contribute, but only in special circumstances. Hypertension is also the most readily recognized factor in the genesis of primary intracerebral hemorrhage. It appears that the stroke-producing potential of hypertension is as much the product of heightened systolic pressure, as of diastolic pressure (Rabkin et al). The cooperative studies of the Veterans Administration (see Freis et al) and the report by Collins and associates (collating 14 randomized trials of antihypertensive drugs) convincingly demonstrated that the long-term control of hypertension decreased the incidence of both ischemic infarction and intracerebral


Neurology_Adams

Neurology_Adams. (collating 14 randomized trials of antihypertensive drugs) convincingly demonstrated that the long-term control of hypertension decreased the incidence of both ischemic infarction and intracerebral hemorrhage. It has been found that simple measures such as the use of hydrochlorothiazide for blood pressure control may be, overall, the most effective. The presence of congestive heart failure and coronary atherosclerosis also increases the probability of stroke. As for embolic strokes, the most important risk factors are arrhythmias, mostly atrial fibrillation, which increases the incidence of stroke about sixfold. Structural cardiac disease also imparts a risk of stroke and when combined with atrial fibrillation, as was common in the past with rheumatic valvular disease, the stroke risk increased 18-fold over the general population.


Neurology_Adams

Neurology_Adams. Diabetes hastens the atherosclerotic process in both large and small arteries. Weinberger and colleagues and Roehmholdt and coworkers found diabetic patients to be twice as liable to stroke as age-matched nondiabetic groups. The importance of long-duration cigarette smoking in the development of carotid atherosclerosis has long been known and was quantitated by Ingall and colleagues. The interactions between diabetes and hypertension on the one hand, and intracerebral hemorrhage and atherothrombotic infarction on the other, as well as the association of cardiac disease and cerebral embolism, are considered further on in this chapter in relation to each of these categories of cerebrovascular disease. Numerous clinical trials have also shown a marked reduction in stroke incidence with the use of cholesterol-lowering drugs. As in the case of coronary artery disease, the level of low-density lipoprotein (LDL) cholesterol has the most impact on the incidence of stroke but elevated


Neurology_Adams

Neurology_Adams. the use of cholesterol-lowering drugs. As in the case of coronary artery disease, the level of low-density lipoprotein (LDL) cholesterol has the most impact on the incidence of stroke but elevated triglycerides may also confer risk. Subsidiary factors, such as low potassium intake and reduced serum levels of potassium, are associated with an increased stroke rate in several studies, including one in which we participated, but the mechanism of this effect is obscure (Green et al); a detrimental effect on blood pressure is possible. Public health measures designed to detect and reduce the aforementioned risk factors offer the most intelligent long-range approach to the prevention of cerebrovascular disease.


Neurology_Adams

Neurology_Adams. Finally, in keeping with the emerging field of genetic risk factors in human disease, several genetic loci have been found that putatively impart a risk of stroke in various populations. One large study, reported by Ikram and associates, has implicated a polymorphism on chromosome 12, encompassing several genes that have putative connections to vascular disease. However, other groups, such the International Stroke Genetics Consortium, were unable to confirm this. It seems likely that more refined definitions of stroke subtypes and careful genotyping of circumscribed populations will be necessary if genetic risk factors for stroke are to be found that are not simply markers for vasculopathy, inducing diseases such as diabetes, hyperlipidemia, and hypertension. There are of course, genetically determined diseases such as sickle cell anemia and Fabry disease that impart a greatly increased risk of stroke. The Major Causes of Ischemic Stroke


Neurology_Adams

Neurology_Adams. The Major Causes of Ischemic Stroke Two causes of ischemic stroke stand out: atherosclerotic–thrombotic disease of the cerebral or extracerebral vessels, and cerebral embolism. An understanding of the biology of these two processes is essential for the analysis of the clinical, laboratory, and imaging features of stroke and its treatment. All other causes of vascular occlusion taken together, account for far fewer strokes. These alternative causes are also important and they are accorded sections later in the chapter.


Neurology_Adams

Neurology_Adams. This is the most common cause of ischemic strokes and of all the types of stroke, cerebral embolism develops most rapidly, “like a bolt out of the blue.” As a rule, the full-blown picture evolves within seconds, exemplifying the idealized temporal profile of a stroke. Although the abruptness with which the stroke develops and the lack of prodromal symptoms point strongly to embolism, the diagnosis is based on the total clinical circumstance. Embolism always merits careful consideration in young persons, in whom atherosclerosis, discussed below, is less common. Only occasionally does the problem unfold more gradually, over many hours, with some fluctuation of symptoms. Possibly, in these cases the embolus initiates a propagating thrombotic process in the occluded vessel.


Neurology_Adams

Neurology_Adams. In most cases, the embolic material consists of a fragment that has broken away from a thrombus within the heart or independently from the endocardial surface of a cardiac chamber or valve (“cardioembolic”). Somewhat less frequently, the source is intraarterial from the distal end of a thrombus within the lumen of an occluded or severely stenotic carotid or vertebral artery (“artery-to-artery embolus”), or a clot that originates in the systemic venous system and passes through an aperture in the heart walls, for example, patent foramen ovale, or the origin of an embolus may be from large atheromatous plaques in the aorta. Thrombotic or infected material (endocarditis) that adheres to the aortic or mitral heart valves and breaks free are also well-appreciated sources of embolism, as are clots originating on prosthetic heart valves. Embolism caused by fat, tumor cells (atrial myxoma), fibrocartilage, amniotic fluid, or air enters into the differential diagnosis of stroke only in special


Neurology_Adams

Neurology_Adams. originating on prosthetic heart valves. Embolism caused by fat, tumor cells (atrial myxoma), fibrocartilage, amniotic fluid, or air enters into the differential diagnosis of stroke only in special circumstances.


Neurology_Adams

Neurology_Adams. The embolus usually becomes arrested at a bifurcation or other site of natural narrowing of the lumen of an intracranial vessel. The resultant infarction is pale, hemorrhagic, or mixed; hemorrhagic infarction nearly always indicates embolism, as noted originally by Fisher and Adams in an obscure abstract and elaborated in their 1987 chapter in Furlan’s book (although venous occlusion can do the same). Any region of the brain may be affected, the territories of the middle cerebral artery, particularly the superior division, being most frequently involved. The two cerebral hemispheres are approximately equally affected. Large embolic clots can block large vessels, while smaller fragments reach vessels as small as 0.2 mm in diameter, usually with inconsequential effects. The embolic material may remain arrested and plug the lumen solidly, but more often it breaks into fragments that enter smaller vessels so that even careful pathologic examination fails to reveal their final location. In


Neurology_Adams

Neurology_Adams. may remain arrested and plug the lumen solidly, but more often it breaks into fragments that enter smaller vessels so that even careful pathologic examination fails to reveal their final location. In this instance, the clinical effects may abate. Because of the rapidity with which embolic occlusion develops, useful collateral influx does not become established. Thus, sparing of the brain territory distal to the site of occlusion is usually not as evident as in thrombosis that develops more slowly.


Neurology_Adams

Neurology_Adams. According to the Framingham Heart Study, patients with chronic atrial fibrillation are approximately six times more liable to stroke than an age-matched population with normal cardiac rhythm (Wolf et al, 1983) and the risk is considerably higher if there is also rheumatic valvular disease, now far less prevalent than in the past. Furthermore, the risk for stroke conferred by the presence of atrial fibrillation varies with age, being 1 percent per year in persons younger than age 65 years, and as high as 8 percent per year in those older than age 75 years with additional risk factors. These levels of risk are of prime importance in determining the potential benefit of chronic anticoagulation, as discussed later. Embolism may also occur in cases of paroxysmal atrial fibrillation or flutter and various studies have suggested that the risk of stroke is even greater than for the chronic arrhythmia. Even more vexing, intermittent and asymptomatic atrial fibrillation is difficult to detect


Neurology_Adams

Neurology_Adams. and various studies have suggested that the risk of stroke is even greater than for the chronic arrhythmia. Even more vexing, intermittent and asymptomatic atrial fibrillation is difficult to detect except with long periods of rhythm monitoring. For example, in a study of patients with implanted pacemakers or defibrillators but not known to have atrial fibrillation by Healy and colleagues, a substantial number of atrial arrhythmias were uncovered and raised the risk of stroke fivefold. Related studies by Gladstone and coworkers (2014) and by Sanna and colleagues suggest that recording heart rhythm for longer periods with various types of monitoring, not surprisingly, increases the rate of detection of episodic atrial fibrillation to approximately 15 percent, from approximately 3 percent with conventional Holter monitoring. Long-term monitoring has been adopted in routine practice in the evaluation of “cryptogenic” stroke.


Neurology_Adams

Neurology_Adams. Several scoring systems have been developed to gauge the future likelihood of stroke from atrial fibrillation. The CHADS2 and related systems are shorthand methods to quantitate the risk factors that modulate risk for stroke in a patient with atrial fibrillation and no valvular disease. A refinement of this system, CHA2DS2-VASc is purported to improve these predictions but the confidence intervals around the point estimates of predictive values in both scales are considerable and clinical judgment must be exercised in their use. This is reflected in part by the observation that the more extensive score does not confer increased risk of stroke in a continuous fashion with each increment in score. The scores, subject to replacement by future ones, are given in Table 33-3. Furthermore, the goal of most of these systems is to make choices regarding warfarin or similar anticoagulation for the prevention of embolic stroke from the arrhythmia as discussed later in the chapter, or as


Neurology_Adams

Neurology_Adams. the goal of most of these systems is to make choices regarding warfarin or similar anticoagulation for the prevention of embolic stroke from the arrhythmia as discussed later in the chapter, or as pertinently, to identify patients who have such a low risk of stroke that the risks of anticoagulation may not be justified. Epidemiologic and clinical aspects of the protective effects of anticoagulation have their own imprecisions.


Neurology_Adams

Neurology_Adams. The vegetations of infective and noninfective (marantic) endocarditis give rise to several different lesions in the brain as described in Chap. 31. Mural thrombus deposited on the damaged endocardium overlying a myocardial infarct in the left ventricle, particularly if there is an aneurysmal sac, is an important source of cerebral emboli, as is a thrombus associated with severe mitral stenosis without atrial fibrillation, now a far less common circumstance than when rheumatic fever was prevalent. Emboli may occur in the first few weeks after an acute myocardial infarction but Loh and colleagues found that a lesser degree of risk persists for up to 5 years. Cardiac catheterization or surgery, especially valvuloplasty, may disseminate fragments from a thrombus or a calcified valve. Mitral and aortic valve prostheses are, as mentioned, additional important sources of embolism. Subendocardial fibroelastosis, idiopathic myocardial hypertrophy, cardiac myxomas, and myocardial lesions of


Neurology_Adams

Neurology_Adams. and aortic valve prostheses are, as mentioned, additional important sources of embolism. Subendocardial fibroelastosis, idiopathic myocardial hypertrophy, cardiac myxomas, and myocardial lesions of trichinosis are additional rare causes of embolism from a cardiac source.


Neurology_Adams

Neurology_Adams. Another source of embolism is the carotid or vertebral artery, where clot forming on an ulcerated atheromatous plaque may be detached and carried to an intracranial branch (artery-to-artery embolism). A similar phenomenon occurs with arterial dissections, discussed in a later section, “Less-Common Causes of Ischemic Cerebrovascular Disease,” and sometimes with fibromuscular disease of the carotid or vertebral arteries.


Neurology_Adams

Neurology_Adams. Atheromatous plaques in the ascending aorta have been recognized to be a more frequent source of embolism than had been previously appreciated. Amarenco and colleagues reported that as many as 38 percent of a group of patients with no discernible cause for embolic stroke had echogenic atherosclerotic plaques in the aortic arch that were greater than 4 mm in thickness, a size found to be associated on a statistical basis with strokes. Disseminated cholesterol emboli from the aorta are known to occur in the cerebral circulation and may be dispersed to other organs as well; rarely, this is sufficiently severe to cause an encephalopathy and pleocytosis in the spinal fluid.


Neurology_Adams

Neurology_Adams. Also of interest are the symptoms caused by an embolus as it traverses a large vessel. This migrating or traveling embolus syndrome is most evident in cases of posterior cerebral artery occlusion, either from a cardiogenic source or from a thrombus in the proximal vertebral artery (“artery-to-artery” embolism; see Koroshetz and Ropper). Minutes or more before the hemianopia develops, the patient reports fleeting dizziness or vertigo, diplopia, or dysarthria, the result of transient occlusion of the origins of penetrating vessels as the clot material traverses the basilar artery. Small residual areas of infarction within the brainstem or cerebellum can be seen on MRI or found at autopsy, and some of the signs of brainstem infarction may persist. The basilar artery is singularly susceptible to this syndrome because the vertebral arteries are smaller in caliber than the basilar, allowing a clot to slowly traverse the larger vessel; furthermore, a clot in the basilar artery is prone to


Neurology_Adams

Neurology_Adams. to this syndrome because the vertebral arteries are smaller in caliber than the basilar, allowing a clot to slowly traverse the larger vessel; furthermore, a clot in the basilar artery is prone to occlude the small orifices of arteries that supply blood to the brainstem.


Neurology_Adams

Neurology_Adams. Paradoxical embolism occurs when an abnormal communication exists between the right and left sides of the heart (particularly a patent foramen ovale [PFO]) or the alternative route of connection via a pulmonary arteriovenous fistula. Embolic material arising in the veins of the lower extremities or pelvis or elsewhere in the systemic venous circulation bypasses the pulmonary circulation and reaches the cerebral vessels. Pulmonary hypertension (often from previous pulmonary embolism) favors the occurrence of paradoxic embolism, but these strokes occur even in the absence of pulmonary hypertension. Several studies indicate that the presence of a small atrial septal aneurysm adjacent to the patient foramen increases the likelihood of stroke. In the series reported by Mas and colleagues (2001), patients ages 18 to 55 years who had a stroke were followed for 4 years; the risk of second stroke was 2 percent in those with a PFO alone and 15 percent among those with both a PFO and an atrial


Neurology_Adams

Neurology_Adams. patients ages 18 to 55 years who had a stroke were followed for 4 years; the risk of second stroke was 2 percent in those with a PFO alone and 15 percent among those with both a PFO and an atrial septal aneurysm (curiously, the risk among those with neither congenital abnormality was 4 percent—higher than for those with a PFO alone). This mechanism comes into play mainly in considering the causes of stroke in the younger patient, but Handke and colleagues published a series in which there was a slightly increased risk of stroke in patients who were older than age 55 and had PFO. It must be emphasized, however, that about one-third of patients in all age groups will be found to have a PFO, and anticoagulation or repair of these lesions in patients older than 55 has not been tested as means of stroke prevention (see further on for discussion of treatment of PFO).


Neurology_Adams

Neurology_Adams. Mitral valve prolapse, in the past considered a common source of emboli, especially in young patients, is no longer currently thought to be an important origin. The initial impetus for considering this abnormality as a source of embolus came from the study of Barnett and colleagues (1980) of a group of 60 patients who had TIAs or small strokes and were younger than 45 years of age; mitral prolapse was detected (by echocardiography and a characteristic midsystolic click) in 24 patients, but in only 5 of 60 age-matched controls. However, several subsequent large studies (Sandok and Giuliani; Jones et al) found that only a very small proportion of strokes in young patients could be attributed to prolapse; even then, the connection was inferred by the exclusion of other causes of stroke. Indeed, in a study using stringent criteria for the echocardiographic diagnosis of prolapse, Gilon and colleagues were unable to establish a relation to stroke. Usually, when valvular prolapse is


Neurology_Adams

Neurology_Adams. Indeed, in a study using stringent criteria for the echocardiographic diagnosis of prolapse, Gilon and colleagues were unable to establish a relation to stroke. Usually, when valvular prolapse is associated with stroke, it is usually severe with ballooning of the valve and a propensity to accumulate clot behind the valve. Of interest, Rice and colleagues described a family with premature stroke in association with valve prolapse and a similar relationship has been reported in twins; the same may occur in Ehlers-Danlos disease.


Neurology_Adams

Neurology_Adams. The pulmonary veins are a potential, if infrequent, source of cerebral emboli, as reflected by the occurrence of cerebral abscesses in association with pulmonary infectious disease (and by the high incidence of cerebral deposits secondary to pulmonary carcinoma). In Osler-Weber-Rendu disease, pulmonary shunts serve as a conduit for emboli. A rare type of embolism follows thyroidectomy, where thrombosis in the stump of the superior thyroid artery extends proximally until a section of the clot, protruding into the lumen of the carotid artery, is carried into the cerebral circulation.


Neurology_Adams

Neurology_Adams. During cerebral arteriography, emboli may arise from the tip of the catheter, or manipulation of the catheter may dislodge atheromatous material from the aorta or carotid or vertebral arteries and account for some of the strokes during this procedure. Monitoring of the cerebral arteries by transcranial Doppler insonation has suggested that small emboli frequently arise during angiographic procedures. For example, a study by Bendszus and colleagues found that 23 of 100 consecutive patients had new cortical lesions shown on diffusion-weighted MRI just after cerebral arteriography. However, none of these patients was symptomatic, and with good technique, emboli from vascular catheters are infrequent.


Neurology_Adams

Neurology_Adams. Cerebral embolism of special type must always have occurred when secondary metastatic tumor is deposited in the brain but a mass of tumor cells is seldom large enough to occlude a cerebral artery and produce the picture of a stroke. Nevertheless, tumor embolism with stroke is known from cardiac myxoma and fibroelastoma, and occasionally with other tumors, even systemic ones; in some of these cases it is a thrombus in the primary lesion that offers a source of embolism. This syndrome must be distinguished from embolism caused by nonbacterial endocarditis that complicates malignant neoplasms (nonbacterial thrombotic endocarditis is discussed further on). This special source of cerebral embolism is a component of a hypercoagulable state that especially accompanies adenocarcinoma and cachexia.


Neurology_Adams

Neurology_Adams. Diffuse cerebral fat embolism is related to severe bone trauma. As a rule, the emboli are minute and widely dispersed, giving rise first to pulmonary symptoms and then to multiple dermal (anterior axillary fold and elsewhere) and cerebral petechial hemorrhages. Accordingly, the clinical picture is more of an encephalopathy and not strictly focal as it is in a stroke, although in some instances there may be focal features. Cerebral air embolism is a rare complication of abortion, scuba diving, or cranial, cervical, or thoracic operations involving large venous structures or venous catheter insertion; it was formerly encountered as a complication of pneumothorax therapy. Clinically, cerebral air embolism may be difficult to separate from the deficits following hypotension or hypoxia with which it frequently coexists. Hyperbaric treatment may be effective if instituted early.


Neurology_Adams

Neurology_Adams. Despite the large number of established sources of emboli, the point of origin cannot be determined in 20 to 30 percent or more of presumed embolic strokes. In such cases, emboli likely have originated from thrombi in the cardiac chambers or an occult arrhythmia but have left behind no residual clot and may be undetectable even by sophisticated methods, such as transesophageal echocardiography and newer MR techniques. Other cases may be a result of atheromatous material arising from the aorta or paradoxical embolism. If extensive evaluation fails to disclose the origin, the odds still favor a source in the left heart. Often, the diagnosis of cerebral embolism is made at autopsy without finding a source. In these cases, one presumes that the search for a thrombotic nidus may not have been sufficiently thorough and small thrombi in the atrial appendage, endocardium (between the papillary muscles of the heart), the aorta and its branches, or pulmonary veins may have been overlooked.


Neurology_Adams

Neurology_Adams. sufficiently thorough and small thrombi in the atrial appendage, endocardium (between the papillary muscles of the heart), the aorta and its branches, or pulmonary veins may have been overlooked. Nevertheless, the source of embolic material is not revealed in a number of cases.


Neurology_Adams

Neurology_Adams. Atherosclerosis is the usual underlying pathology for local vascular thrombosis. The evolution of clinical phenomena in cerebral thrombosis, both of large intracranial (basilar, carotid) or extracranial (carotid, vertebral) and small vessels (lacunes), is more variable than that of embolism and hemorrhage. In many cases, a thrombus is the final event in the occlusion of a vessel but the stroke that results can be from reduced blood flow through the stenotic or occluded vessel or by a mechanism of embolization from the thrombus to a distal territory. Small and large vessel occlusion can even coincide in that atherosclerosis in a large parent vessel occludes the orifice of a smaller tributary vessel.


Neurology_Adams

Neurology_Adams. In some patients with atherothrombosis the stroke is preceded by minor signs or one or more transient attacks of focal neurologic dysfunction, TIAs, discussed further on. These transient prodromal episodes may herald the oncoming vascular event caused by atherothrombotic stroke. Occasionally embolism is preceded by a transient neurologic disorder but TIAs are generally considered as more closely aligned with atherothrombotic stroke. Nevertheless, it has become appreciated that an embolic stroke may give rise to a transitory neurologic syndrome but it remains the case that repetitive stereotyped TIAs usually signal atherothrombotic vascular disease.


Neurology_Adams

Neurology_Adams. The thrombotic stroke syndrome, which represents the result of low blood flow and related phenomena, develops in one of several ways. There may be a single episode, but typically the whole stroke evolves over a few minutes or hours. Characteristic is a “stuttering” or intermittent progression of neurologic deficits. This is a starkly different profile from the abrupt onset of stroke that characterizes the embolic mechanism discussed earlier in the chapter. In thrombosis, a partial stroke may occur and even recede temporarily for several hours, after which there is rapid progression to the completed deficit—or several fleeting episodes may be followed by a longer one and, hours or a day or two later, by a major stroke. Several parts of the body may be affected at once or only one part, such as a limb or one side of the face, the other parts becoming involved serially in step-like fashion until the stroke is fully developed. Or, spells of weakness or involuntary movement of a hand or


Neurology_Adams

Neurology_Adams. as a limb or one side of the face, the other parts becoming involved serially in step-like fashion until the stroke is fully developed. Or, spells of weakness or involuntary movement of a hand or arm or dimness of vision, lasting 5 to 10 min, occur spontaneously or are brought on by standing or walking. Each of the partial attacks may reproduce the profile of the stroke in miniature. In other words, the principle of intermittency seems to characterize the thrombotic process.


Neurology_Adams

Neurology_Adams. Also somewhat characteristic of atherothrombotic events in many, but not all cases, is the occurrence of the stroke during sleep; the patient awakens paralyzed, either during the night or in the morning. Unaware of any difficulty, he may arise and fall helplessly to the floor with the first step. This is the story given by many patients with thrombotic strokes, as well as by a number with embolic strokes.


Neurology_Adams

Neurology_Adams. Most deceptive are the few instances, in which the neurologic disorder evolves very gradually, over several days or longer (“slow stroke”). One’s first impulse is to make a diagnosis of brain tumor, abscess, or subdural hematoma. Careful analysis of the course of the illness will disclose an uneven, saltatory progression. There are also cases in which the evolution of a thrombotic stroke is evenly progressive over a period of days. It is also likely that the abrupt development of a thrombus on an atherosclerotic plaque can cause a fairly sudden or at least rapid evolution of stroke, thereby simulating embolus but this is not characteristic.


Neurology_Adams

Neurology_Adams. Atheromatous plaques preferentially form at branching points and curves of the cerebral arteries. The most frequent sites are (1) in the internal carotid artery at its origin from the common carotid; (2) in the cervical part of the vertebral arteries or at their origins at the subclavian vessels, and at their junction to form the basilar artery; (3) in the stem or at the main bifurcation of the middle cerebral arteries; (4) in the proximal posterior cerebral arteries as they wind around the midbrain; and (5) in the proximal anterior cerebral arteries as they pass anteriorly and curve over the corpus callosum. The last two sites are far less frequent than the first three. It is less frequent for the cerebral arteries to develop significant plaques that develop into strokes beyond their first major branching after the circle of


Neurology_Adams

Neurology_Adams. Willis. Also, it is unusual for the cerebellar and ophthalmic arteries to show atheromatous involvement. The common carotid and vertebral arteries at their origins are additional frequent sites of atheromatous deposits, but because of abundant collateral arterial pathways, occlusions at these sites are less commonly associated with cerebral ischemia as discussed further on. There is tendency for persons of Asian origin to have intracranial atherosclerosis in contrast to the extracranial variety.


Neurology_Adams

Neurology_Adams. Atherothrombosis may cause cerebral infarction in several ways. The most obvious is that an occlusive plaque or a thrombus formed on a plaque occupies the lumen of a major intracerebral vessel, such as the middle cerebral artery, and stops flow to the areas of the brain supplied by the vessel. A variation of this mechanism is one of occlusion by atherosclerosis of a more proximal vessel, such as the distal carotid artery. This may lead to infarction in the territory between major branches of the internal carotid circulation that are most susceptible to reduced blood flow—termed “borderzone,” or “end-arterial,” or less accurately, “watershed infarction,” depending on the richness of collateral vessels. Or, an atherothrombotic lesion in a proximal vessel may serve as the nidus for the formation of an embolus that manifests itself as a stroke in one of the territories of that vessel—called “artery-to-artery” embolism (cardioembolic stroke is more common). A separate mechanism pertains


Neurology_Adams

Neurology_Adams. of an embolus that manifests itself as a stroke in one of the territories of that vessel—called “artery-to-artery” embolism (cardioembolic stroke is more common). A separate mechanism pertains when an atherosclerotic plaque in a large vessel of the circle of Willis occludes the orifices of small penetrating vessels, most often the lenticulostriate branches of the middle cerebral artery or the thalamostriate vessels of the posterior cerebral artery, and cause small, or more confluent, strokes deep in the brain.


Neurology_Adams

Neurology_Adams. Whether plaque rupture plays a role in vessel occlusion or thrombus formation, as it does in the coronary artery, is not clear. In the carotid artery, Hosseini and coworkers found evidence of intraplaque hemorrhage using special MRI techniques and found these changes to be predictive of stroke in the distal distribution of the artery. Previous work by Fisher and Ojemann, cited in the references, involving the serial sectioning of carotid plaques removed at surgery, suggested otherwise. It is clear that the more severe the focal atheromata, the more likely a thrombotic complication will occur. Whether the complexity of a carotid artery plaque with ulcerations is an important component of stroke risk, for example, by originating small emboli, is not settled. Again, it is the high degree of stenosis, usually above 90 percent of the original lumen compromised, or a residual lumen of less than approximately 2 mm, of the carotid artery that is most likely to be associated with strokes in


Neurology_Adams

Neurology_Adams. stenosis, usually above 90 percent of the original lumen compromised, or a residual lumen of less than approximately 2 mm, of the carotid artery that is most likely to be associated with strokes in the distal territory of the vessel.


Neurology_Adams

Neurology_Adams. Atheromatous lesions may regress to some extent under the influence of diet and lipid-lowering drugs. Hennerici and colleagues followed a series of patients with carotid stenosis for a period of 18 months and observed spontaneous regression in nearly 20 percent of the lesions. In the large majority of cases, however, atherosclerosis is a progressive disease if the underlying risk factors, such as hyperlipidemia, smoking, diabetes, and hypertension, are not addressed.


Neurology_Adams

Neurology_Adams. The hemostatic elements, both clotting factors and platelets, which produce a thrombus within a vessel are complex and have been the object of intense study (see Furie and Furie for a discussion of this field). However, just as in the case of coronary artery disease, it is often the development and enlargement of the thrombus that acts as the final element in cerebral vascular occlusion and an ischemic stroke. It seems plausible, although not adequately studied, that the temporal profile of atherothrombotic stroke reflects this accretion of clot in a vessel. These biologic mechanisms have bearing on the treatment and prevention of stroke.


Neurology_Adams

Neurology_Adams. Transient ischemic attacks are focal neurologic episodes that correspond to a vascular territory, appear abruptly and cease in matter of minutes. Previously, the definition on clinical grounds extended to spells that lasted up to 24 h, then a shorter time frame was adopted but now, an event that leaves no clinical or imaging trace of infarction is considered a TIA. It has been realized as a result of more sophisticated techniques that many TIAs previously attributed to atherothrombosis, are truly embolic strokes that resolve clinically. These episodes can reflect the involvement of virtually any cerebral artery: common or internal carotid; middle, posterior, or anterior cerebral; ophthalmic; vertebral, basilar, or cerebellar; or a penetrating branch to the internal capsule, thalamus, or brainstem. Thus, TIAs may present themselves as transient spells of hemiparesis, aphasia, numbness, or tingling on one side of the body, dysarthria, diplopia, ataxia, obscuration of a visual field, or


Neurology_Adams

Neurology_Adams. Thus, TIAs may present themselves as transient spells of hemiparesis, aphasia, numbness, or tingling on one side of the body, dysarthria, diplopia, ataxia, obscuration of a visual field, or combinations thereof that replicate the stroke syndromes. Even limb shaking can represent a TIA (Yanagihara et al). Although there is little doubt that TIAs are caused by transient focal ischemia, their mechanism is not fully understood.


Neurology_Adams

Neurology_Adams. Transient ischemic episodes must be distinguished from other brief neurologic attacks that are from seizures, migraine, and its variants, transient global amnesia, syncope, vertigo from labyrinthine disease, and psychogenic episodes, as emphasized further on. The differentiation of TIAs from other similar transient spells is not always straightforward and occupies considerable attention from neurologists; these distinctions have serious implications with regard to evaluation and treatment.


Neurology_Adams

Neurology_Adams. In the clinical analysis of TIAs, it is useful to separate a single transient episode from repeated ones that are all of uniform type. The latter are more a warning of impending vascular occlusion, particularly of the internal carotid artery, whereas the former, especially when prolonged, are again often caused by an embolus that leaves no lasting clinical effect. Prolonged, fluctuating TIAs are the most ominous. Approximately 20 percent of infarcts that follow TIAs occur within a month after the first attack, and approximately 50 percent within a year (Whisnant et al). In an attempt to provide a predictive tool, various scales were devised, among them the “ABCD” system devised by Rothwell and colleagues (2005) and derivatives of this scale. Blood pressure, unilateral weakness, speech disturbance, and the duration of symptoms (all less than 1 h) are added to produce a predictive score for stroke within 1 week. Studies subsequent to the original one have given variable sensitivities,


Neurology_Adams

Neurology_Adams. and the duration of symptoms (all less than 1 h) are added to produce a predictive score for stroke within 1 week. Studies subsequent to the original one have given variable sensitivities, for which reason this interesting approach must be considered in clinical context. In the original study, unilateral weakness and duration lasting over an hour were most predictive of stroke. The problem of determining the cause of a prolonged TIA has been alluded to—many of these cases are a result of emboli.


Neurology_Adams

Neurology_Adams. Not surprisingly, the rates of myocardial infarction and other atherosclerotic events such as myocardial infarction are high in patients with TIAs, in some series exceeding the risk of stroke. About two-thirds of all patients with TIAs are men with hypertension, reflecting the higher incidence of atherosclerosis in this group. Occasionally, in younger adults, TIAs may occur as relatively benign phenomena, without recognizable features of atherosclerosis or risk factors for it. Migraine is suspected in such patients (see further on); other such instances are a result of special hematologic disorders such as those that cause excessive viscosity or sludging of blood (polycythemia vera, sickle cell disease, thrombocytosis, leukemia, and hyperglobulinemic states) may also cause TIAs prior to a stroke.


Neurology_Adams

Neurology_Adams. It has been recognized that strokes caused by occlusion of small penetrating vessels of the brain—lacunes—have a propensity to be intermittent (“stuttering”) at their onset and occasionally to allow virtually complete restitution of function between discrete episodes. Whether this constitutes a “lacunar TIA” has been debated, but it seems to us that the more important problem is our inability to distinguish a transitory occlusion of a small vessel from that of a larger vessel. Donnan and colleagues (1993) speak of a “capsular warning syndrome,” which we have seen a number of times, consisting of escalating episodes of weakness in the face, arm, and leg and culminating in a capsular lacunar stroke. Nevertheless, the basic pattern of a small deep stroke remains identifiable in mild form; partial syndromes that simulate cortical TIA are less common. Lacunar stroke is discussed extensively further on.


Neurology_Adams

Neurology_Adams. In the transient ischemic attack of the eye, transient monocular blindness (also called amaurosis fugax or TMB) is the usual symptom. Most of the visual episodes evolve swiftly, over 5 to 30 s, and are described as a horizontal shade falling (or rising) smoothly over the visual field until the eye is completely but painlessly blind. The attack clears slowly and uniformly. Sometimes the attack takes the form of a wedge of visual loss, sudden generalized blurring, or, a gray or bright light obscuring vision. Transient attacks of monocular blindness are usually more stereotyped with repeated episodes than are hemispheric attacks. TIAs consisting of a homonymous hemianopia should suggest a stenosis of the posterior cerebral artery but it is often difficult for the patient to make the distinction from monocular blindness.


Neurology_Adams

Neurology_Adams. The implications of amaurosis fugax have been evaluated by several investigators and found not to be as ominous as those of hemispheral TIAs (such as hemiparesis, hemisensory symptoms, aphasia), particularly in younger patients. As pointed out by Benavente and colleagues, the risk of stroke over the 3 years following an attack is as low as 2 percent if there are no other issues such as diabetes, but it may be as high as 24 percent in older patients with risk factors for atherosclerosis. It is evident that particularly in younger patients a mechanism other than atherosclerosis is operative, such as migraine or an antiphospholipid antibody (discussed further on).


Neurology_Adams

Neurology_Adams. It is perhaps not surprising that the risk of stroke after transient monocular blindness is lower than for cerebral TIAs from carotid atherosclerotic disease. The size of particulate material that occludes the ophthalmic and its branches’ vessels is so small that a similar event in the cerebral hemispheres would be less likely to produce symptoms. Furthermore, ischemia of the retina produces symptoms that are hard for the patient to ignore. While there are other underlying causes of TMB, these notions taken together could explain a large part of the difference in risk between conventional TIA and TMB. Mechanism of Transient Ischemic Attacks


Neurology_Adams

Neurology_Adams. The likely causes of TIA are reduced blood flow or embolic particles. It has become clear that many instances of single transient attacks have an embolic mechanism. In contrast, repetitive TIAs, repeatedly producing the same or similar clinical syndrome are in most cases related to vascular stenosis with reduced blood flow to a limited region of the brain. It is also the case that single TIAs can result from vascular stenosis and, of course, on the occurrence of a first TIA it is generally not possible to determine the source. In support of the concept of embolism as a cause of TIAs, almost one-fifth of anterior circulation (carotid territory) TIAs in the series of Pessin and colleagues (1977), and a somewhat larger proportion of cases reported by Ueda and coworkers, had neither stenosis nor ulceration of the carotid arteries. These ischemic attacks, presumably from the heart or great vessels including the aortic arch, exceeded 1 h in duration, suggesting embolism; but there were also


Neurology_Adams

Neurology_Adams. ulceration of the carotid arteries. These ischemic attacks, presumably from the heart or great vessels including the aortic arch, exceeded 1 h in duration, suggesting embolism; but there were also a small number of brief ischemic attacks that were unexplained even after arteriography.


Neurology_Adams

Neurology_Adams. In general, hemodynamic changes in the retinal or cerebral circulation make their appearance when the lumen of the internal carotid artery is reduced to 2.0 mm or less (normal diameter, 7.0 mm; range, 5 to 10 mm, lower part of this range in women). This corresponds to a reduction in cross-sectional area of the vessel of more than 95 percent compared to the normal cross-sectional area of a more distal part of the carotid artery. The exact degree of stenosis that may cause TIAs and the risk of stroke with mild and moderate degrees of stenosis are controversial and are addressed further on.


Neurology_Adams

Neurology_Adams. In some cases of presumed embolism, the neurologic state fluctuates from normal to abnormal repeatedly for as long as 36 h, giving the appearance of TIAs (“stuttering TIAs”); in others, a deficit of several hours’ duration occurs, fulfilling the traditional (now discarded duration of 24 hours) criterion for TIAs. As already noted, the same sequence of events can precede lacunar infarction and seem far more likely in that instance to be the result of locally reduced blood flow than to recurrent emboli.


Neurology_Adams

Neurology_Adams. Ophthalmoscopic observations of the retinal vessels made during episodes of transient monocular blindness may infrequently show either an arrest of blood flow in the retinal arteries and breaking up of the venous columns to form a “boxcar” pattern or scattered bits of white material temporarily blocking the retinal arteries. These observations indicate that in some cases of ischemic attacks involving the retinal vessels, a temporary, complete, or relatively complete cessation of blood flow occurs locally. Whether this is a result of platelet or fibrin emboli or of platelet aggregation in situ because of decreased perfusion pressure remains unsettled.


Neurology_Adams

Neurology_Adams. TIAs that occur with exercise or the assumption of upright posture are particularly suggestive of stenosis of aortic branches, as occurs in Takayasu disease (see further on) and in dissection of the carotid artery or aortic arch. TIAs induced by hyperventilation are said to be characteristic of moyamoya disease, a progressive stenosis of intracranial vessels discussed in a later section. In states of severe anemia, polycythemia, thrombocythemia, extreme hyperlipidemia, hyperviscosity from macroglobulinemia, sickle cell anemia, and extreme hyperor hypoglycemia, there may be transient neurologic deficits related to rheologic or other changes in blood. In some of these cases, the metabolic or rheologic change appears to have brought out symptoms of stenosis in a large or small vessel but just as often, the vasculature is normal. Patients with antiphospholipid antibodies may have TIAs, the mechanism of which is undefined.


Neurology_Adams

Neurology_Adams. Some cases of TIA that occur after the carotid artery has become occluded are probably due to embolism from the thrombus, usually acute, in the lumen of the vessel distal to the thrombus. In other instances, it has been hypothesized by Barnett and colleagues (1978) that a TIA occurring after the carotid artery has been occluded by thrombus may even arise from the proximal end of the thrombus. In this case, the embolic material is posited to enter the cerebral vessels through the external carotid artery and retrograde through the ophthalmic artery. He called this “stump embolism,” a term which has been often inadvertently used to describe embolism from the distal part of the occluded vessel. Differential Diagnosis of TIA


Neurology_Adams

Neurology_Adams. Transient focal neurologic symptoms are ubiquitous in neurologic practice. They may be a result of seizures, migraine (see the analysis of late life migraine accompaniments by Fisher, 1980), syncope, or other conditions such as transient global amnesia (see Chap. 20), and they occur occasionally in patients with multiple sclerosis and with certain systemic metabolic disorders such as severe hyperglycemia. The clinical setting in which they occur assists in making clear the nature of the attack. Furthermore, transient and reversible episodes of focal cerebral symptoms, indistinguishable from TIAs, are known to occur in patients with meningioma, glioblastoma, metastatic brain tumors situated in or near the cortex, and even with subdural hematoma. Although infrequent, these attacks are important mainly because the use of anticoagulants is relatively contraindicated in some of these circumstances. We have seen these episodes mainly with meningiomas and subdural hematomas; they have


Neurology_Adams

Neurology_Adams. important mainly because the use of anticoagulants is relatively contraindicated in some of these circumstances. We have seen these episodes mainly with meningiomas and subdural hematomas; they have consisted of transient aphasia or speech arrest lasting from 2 min to several hours, but sensory symptoms with or without spread over the body, arm weakness, and hemiparesis have also been reported. Some remarkable cases of meningioma have involved repeated transient attacks for decades. Seizures are always suspected in these cases but are rarely proved. It has been speculated that a local vascular disturbance of some kind is operative, but the mechanism is not understood. As far as we can determine, mass lesions have not caused episodes that simulate posterior circulation TIAs.


Neurology_Adams

Neurology_Adams. The issue of the uncertainty regarding vertigo alone as a manifestation of a TIA referable to the basilar or vertebral artery was addressed in Chap. 14. There are occasional cases in which multiple brief episodes of vertigo, lasting perhaps a minute or less and fluctuating in intensity, may be interspersed with additional signs of brainstem ischemia. Careful questioning of the patient usually settles the question but imaging may be necessary in cases where uncertainty remains. Even then, more instances of vertigo than are justified are attributed to stenosis of the posterior circulation vessels. In some patients, the complaint of non-vertiginous “dizziness” will prove, however infrequently, to be part of a carotid TIA. According to Ross Russell, so-called drop attacks (see Chap. 6) have been recorded in 10 to 15 percent of patients with vertebrobasilar insufficiency but we have never observed such attacks as a recurrent ischemic phenomenon or a manifestation of other forms of


Neurology_Adams

Neurology_Adams. have been recorded in 10 to 15 percent of patients with vertebrobasilar insufficiency but we have never observed such attacks as a recurrent ischemic phenomenon or a manifestation of other forms of cerebrovascular disease and the syndrome has usually been due to syncope, seizure, or has been of obscure origin.


Neurology_Adams

Neurology_Adams. Pathophysiology of Ischemic Infarction Cerebral infarction basically comprises two pathophysiologic processes: one, a loss of the supply of oxygen and glucose secondary to vascular occlusion, and the other, an array of changes in cellular metabolism consequent to the collapse of energy-producing processes, ultimately with disintegration of cell structures and their membranes, a process subsumed under the term necrosis. Of potential therapeutic importance are the observations that some of the cellular processes leading to neuronal death are not irrevocable and may be reversed by early intervention, either through restoration of blood flow, by prevention of the influx of calcium into cells, or by interdicting intermediary processes involved in cell death.


Neurology_Adams

Neurology_Adams. At the center of an ischemic stroke is a zone of infarction. The necrotic tissue swells rapidly, mainly because of excessive intracellular water content (cytotoxic edema). Because anoxia also causes necrosis and swelling of cerebral tissue, oxygen lack must be a factor common to both infarction and anoxic encephalopathy. The effects of ischemia, whether functional and reversible or structural and irreversible, depend on its degree and duration. The margins beyond the infarct are hyperemic, being supplied by meningeal collaterals, and here there is only minimal or no parenchymal damage.


Neurology_Adams

Neurology_Adams. Implicit in discussions of ischemic stroke and its treatment is the existence of a “penumbra” zone that is marginally perfused and contains at-risk but viable neurons. Presumably this zone exists at the margins of an infarction, which at its core has irrevocably damaged tissue that is destined to become necrotic. Using various methods, such a penumbra can be demonstrated in association with some infarctions but not all, and the degree of reversible tissue damage has been difficult to determine but is more recently being demonstrated with imaging techniques. The neurons in the penumbra are considered to be physiologically “stunned” by moderate ischemia and subject to salvage if blood flow is restored in a certain period of time. Olsen and colleagues demonstrated hypoperfused penumbral zones but, interestingly, found that regions just adjacent to them are hyperperfused. These concepts find a parallel in attempts to demonstrate by imaging matching of perfusion and infarction (detected by


Neurology_Adams

Neurology_Adams. but, interestingly, found that regions just adjacent to them are hyperperfused. These concepts find a parallel in attempts to demonstrate by imaging matching of perfusion and infarction (detected by diffusion-weighted images on MRI) in patterns with acute stroke as discussed in the section on treatment. Elevating the systemic blood pressure or improving the rheologic flow properties of blood in small vessels by hemodilution improves flow in the penumbra; however, attempts to use that techniques in clinical work has met with mixed success. Reperfusion of the penumbral area by removal of the occluding clot has, however, been successful in improving outcome after stroke.


Neurology_Adams

Neurology_Adams. The effects of a focal arterial occlusion on brain tissue vary depending on the location of the occlusion and on available collateral and anastomotic channels. In occlusion of the internal carotid artery in the neck, there may be anastomotic flow through the anterior and posterior communicating arteries of the circle of Willis from the external carotid artery through the ophthalmic artery or via other smaller external-internal connections (Fig. 33-1). With blockage of the vertebral artery, the anastomotic flow may be via the deep cervical, thyrocervical, or occipital arteries or retrograde from the other vertebral artery and again through the posterior communicating arteries. If the occlusion is in the stem portion of one of the cerebral arteries, that is, distal to the circle of Willis, a series of meningeal interarterial anastomoses may carry sufficient blood into the compromised territory to lessen ischemic damage (Fig. 33-2). There is also a capillary anastomotic system between


Neurology_Adams

Neurology_Adams. a series of meningeal interarterial anastomoses may carry sufficient blood into the compromised territory to lessen ischemic damage (Fig. 33-2). There is also a capillary anastomotic system between adjacent arterial branches, and although it may reduce the size of an ischemic territory, it is usually not adequate to prevent infarction. Thus, in the event of occlusion of a major arterial trunk, the extent of infarction ranges from none at all to the entire vascular territory of that vessel. Between these two extremes are all degrees of variation in the extent of infarction and its degree of completeness, including a penumbral zone in some cases.


Neurology_Adams

Neurology_Adams. The phenomenon of cerebrovascular autoregulation is appropriately introduced here. Over a range of mean blood pressures of approximately 50 to 150 mm Hg, the small pial vessels are able to dilate and to constrict in order to maintain cerebral blood flow (CBF) in a relatively narrow range. This accommodation eventually fails at the extremes of blood pressure, after which CBF follows systemic pressure passively, either falling precipitously or rising to levels that damage the walls of small vessels. The conditions in which the limits of autoregulation are exceeded are at the extremes of hypertensive encephalopathy at one end and circulatory failure at the other, both of which are discussed in later sections of the chapter.


Neurology_Adams

Neurology_Adams. If brain tissue is observed in experimental circumstances at the time of arterial occlusion, the venous blood is first seen to darken, owing to an increase in deoxygenated hemoglobin. The viscosity of the blood and resistance to flow both increase, and there is sludging of formed blood elements within vessels. The tissue becomes pale. Arteries and arterioles become narrowed. Upon reestablishing flow in the occluded artery, the sequence is reversed and there may be a slight hyperemia.


Neurology_Adams

Neurology_Adams. Many of these factors relating to cerebral blood flow were studied many years ago by Heiss and by Siesjo and by others. The critical threshold of CBF below which functional impairment occur has been determined in several animal species, including macaque monkeys and gerbils. The critical level for infarction is approximately 23 mL/100 g/min (normal is 55 mL/100 g/min); if, after a short period of time, CBF is restored to normal levels, the impairment of function can be reversed. Reduction of CBF below 10 to 12 mL/ 100 g/min causes infarction, almost regardless of its duration. The critical level of hypoperfusion that abolishes function and leads to tissue damage is therefore a CBF between 12 and 23 mL/100 g/min but the likelihood of complete infarction is also dependent on the duration of ischemia. Modern techniques such as CT and MR perfusion imaging are able to give comparable values in clinical stroke work.


Neurology_Adams

Neurology_Adams. At these levels of blood flow the electroencephalogram (EEG) is slowed, and below this level it becomes isoelectric. In the region of marginal perfusion, the K level increases (as a result of efflux from injured depolarized cells) and adenosine triphosphate (ATP) and creatine phosphate are depleted. These biochemical abnormalities are reversible if the circulation is quickly restored to normal. Disturbance of calcium ion homeostasis and accumulation of free fatty acids interfere with full recovery of cells. A CBF of 6 to 8 mL/100 g/min causes marked ATP depletion, increase in extracellular K, increase in intracellular Ca, and cellular acidosis, invariably leading to histologic signs of necrosis. These changes do not become apparent for several hours. Free fatty acids (appearing as phospholipases) are activated and destroy the phospholipids of neuronal membranes. Prostaglandins, leukotrienes, and free radicals accumulate, and intracellular proteins and enzymes are denatured. Cells then


Neurology_Adams

Neurology_Adams. are activated and destroy the phospholipids of neuronal membranes. Prostaglandins, leukotrienes, and free radicals accumulate, and intracellular proteins and enzymes are denatured. Cells then swell, a process called cellular, or cytotoxic, edema (see “Brain Edema” in Chap. 30). Similar abnormalities affect mitochondria even before other cellular changes are evident.


Neurology_Adams

Neurology_Adams. Regarding anoxic damage of the brain, a historically interesting phenomenon was studied by Ames and Nesbett. They found that cells could withstand complete absence of O2 for 20 min and postulated that a long period of tolerance of retinal neurons to complete anoxia in vitro, in comparison to that in vivo, is related to what they called the no-reflow phenomenon (swelling of capillary endothelial cells, which prevents the restoration of circulation as originally described by Ames et al).


Neurology_Adams

Neurology_Adams. One area of interest has focused on the role of excitatory neurotransmitters in stroke, particularly glutamate and aspartate, which are formed from glycolytic intermediates of the Krebs cycle. These neurotransmitters, released by ischemic cells, excite neurons and produce an intracellular influx of Na and Ca. These changes are in part responsible for irreversible cell injury, but this must be an oversimplification. Some current attempts at therapy, for example, are directed at limiting the extent of infarction by blocking the glutamate receptor, particularly the NMDA (N-methyl-d-aspartate) channel—one of several calcium channels that open under conditions of ischemia and set in motion a cascade of cellular events eventuating in neuronal death (apoptosis). However, even complete blockade of the NMDA channels has not prevented cellular death, presumably because dysfunction of several other types of calcium channels continues and allows calcium entry to cells. Additional biochemical


Neurology_Adams

Neurology_Adams. of the NMDA channels has not prevented cellular death, presumably because dysfunction of several other types of calcium channels continues and allows calcium entry to cells. Additional biochemical events must be induced by ischemia, including the production of free radicals, which leads to peroxidation and disruption of the outer cell and mitochondrial membranes. Clearly, the cascade of intracellular events that lead to neuronal death is likely to be more complex than is currently envisioned.


Neurology_Adams

Neurology_Adams. The extent of neural tissue dysfunction is not dictated solely by the activation of these mechanisms in neurons. It is now clear that toxic influences are exerted on oligodendroglial cells in white matter during ischemia and on astrocytic cells that support neurons. Moreover, injury to both neurons and astroyctes is augmented by an inflammatory response that activates endothelial cells to express cell adhesion molecules that attract additional inflammatory cells and upregulate levels of inflammatory proteases (e.g., metalloproteases) and cytokines (e.g., interleukins and chemokines). These events are summarized in the review by Lo and coworkers.


Neurology_Adams

Neurology_Adams. Myers and Yamaguchi showed that monkeys infused with glucose before the induction of cardiac arrest suffered more brain damage than did either fasted or saline-infused animals. They suggested that the high cerebral glucose level under anaerobic conditions led to increased glycolysis during the ischemic episode and that the accumulated lactate was neurotoxic. On the basis of such observations, Plum suggested that scrupulous control of the blood glucose might reduce the size of cerebral infarction in diabetic patients. Clinical implementation of this idea remains to be established but there have been correlations between the degree of hyperglycemia and infarct size and progression. Nonetheless, these multiple molecular pathways for neuronal damage provide opportune points for therapeutic intervention.


Neurology_Adams

Neurology_Adams. The process of thrombosis involves changes in a number of anticoagulant factors such as heparin cofactor 2, antithrombin III, protein C, and protein S. Some of these are extrinsic to the blood vessels and hence may result in thrombosis in one or in multiple sites even without prior vascular injury. These are discussed by Furie and Furie. Protein C is a vitamin K-dependent protease that, in combination with its cofactors protein S and antithrombin III, inhibits coagulation. An inherited deficiency of any of these factors may predispose to in situ thrombosis within either the arterial or venous systems and is a cause of otherwise unexplained strokes in young persons. For example, protein C deficiency (heterozygous in one of every 16,000 individuals) is a cause of thrombosis of both veins and arteries; a resistance to activated protein C has also been described (causing venous thrombosis almost exclusively).


Neurology_Adams

Neurology_Adams. Antiphospholipid antibody is yet another cause of vascular occlusion that is apparently not incited by damage to the vessel wall (see later in chapter). The metabolic disturbances in a number of metabolic diseases such as Fabry disease also favor cerebrovascular clotting. Persons with inflammatory bowel diseases (ulcerative colitis, Crohn disease) are known to be prone to thrombotic strokes. Whether inflammation elsewhere in the body predisposes to cerebral vascular occlusions is an open question. Curiously, the hypercoagulable state induced by certain cancers (Trousseau syndrome) does not often produce in situ arterial occlusion but it does lead to thrombotic vegetations on heart valves that precipitate strokes and it predisposes to cerebral venous thrombosis as discussed further on. Hemoglobinopathies such as sickle cell disease are also to be considered as causes of stroke in affected individuals. To this list could be added numerous other hematologic conditions such as


Neurology_Adams

Neurology_Adams. on. Hemoglobinopathies such as sickle cell disease are also to be considered as causes of stroke in affected individuals. To this list could be added numerous other hematologic conditions such as thrombocytosis, polycythemia (primary or secondary), hyperviscosity from paraproteinemias, and others.


Neurology_Adams

Neurology_Adams. These hematologic factors should be sought when unexplained strokes occur in children or young adults, in families whose members have had frequent strokes, in pregnant or parturient women, and in women who are migraineurs or taking birth control pills. According to Markus and Hambley, whose review of this subject is recommended, screening for lupus anticoagulant, anticardiolipin antibodies, deficiency of proteins C and S, and antithrombin III is probably justified, but mainly in these special circumstances. This special category of vascular thrombosis is taken up in later sections, including the distinctions between arterial or venous clotting.


Neurology_Adams

Neurology_Adams. Technologic advances continue to enhance the clinical study of stroke patients; they allow the demonstration of both the cerebral lesion and the affected blood vessel. CT demonstrates and accurately localizes even small hemorrhages, hemorrhagic infarcts, subarachnoid blood, clots in and around aneurysms, arteriovenous malformations, and established regions of infarction as well as adjacent regions of ischemic (penumbral) tissue.


Neurology_Adams

Neurology_Adams. Magnetic resonance imaging demonstrates flow voids in vessels, hemosiderin and iron pigment, and the alterations resulting from ischemic necrosis and gliosis. MRI is particularly advantageous in demonstrating small lacunar lesions deep in the hemispheres and abnormalities in the brainstem (a region obscured by adjacent bone in CT). Diffusion-weighted magnetic resonance techniques are particularly useful to detect infarction within minutes of the stroke, that is, considerably earlier than CT and other MRI sequences (Fig. 33-3). The various MRI imaging sequences used in the diagnosis and dating of stroke are discussed below and in Chap. 2 and in Table 33-4.


Neurology_Adams

Neurology_Adams. Arteriography, enhanced by digital processing of images, accurately demonstrates stenoses and occlusions of the intracranial and extracranial vessels as well as aneurysms, vascular malformations, and other blood vessel diseases such as arteritis and vasospasm. Conventional contrast angiography has largely been supplanted by magnetic resonance angiography (MRA), venography (MRV), and CT angiography for the visualization of large intracranial arteries and veins (see Fig. 2-2J and K). These techniques have the advantage of relative safety (injection of contrast media is required for CT angiography) but do not give refined images of the smaller blood vessels. MRA depicts the “time of flight” of blood through vessels and is not as accurate as CT angiography in measuring the degree and morphology of changes within a cerebral or intracranial vessel.


Neurology_Adams

Neurology_Adams. Partly as a result of the increased use and availability of endovascular thrombectomy, it has become useful to determine if there is ischemic, but not yet infarcted, region of the brain. The main techniques are CT perfusion and MR perfusion. Both involve the rapid acquisition of images during passage of a contrast agent through tissue. A time-intensity curve is derived and from this curve, images of blood flow, blood volume, and transit time can be displayed (Fig. 33-4). A penumbral-ischemic region is identified by increased transit time (or reduced flow) with relatively maintained blood volume. In comparison, infarcted tissue is identified by reduced blood volume that is below the threshold for irreversible tissue damage; this region should correspond to the findings on diffusion weighted imaging.


Neurology_Adams

Neurology_Adams. Other procedures for the investigation of cerebrovascular disease include Doppler ultrasound flow studies, which demonstrate atheromatous plaques and stenoses of large vessels, particularly of the carotid but also of the vertebrobasilar arteries. The transcranial Doppler technique has reached a degree of precision whereby occlusion or spasm of the main vessels of the circle of Willis can be detected and roughly quantitated. Various methods of measuring regional blood flow with positron emission tomography (PET) and radionuclide imaging find use in special instances discussed in appropriate sections of the chapter.


Neurology_Adams

Neurology_Adams. The electroencephalogram (EEG) and lumbar puncture have lost favor in stroke diagnosis but the former is possibly underused as a readily available means of detecting cortical infarction in the wake of ischemia of a region of one hemisphere. It allows a distinction to be made between occlusion of a small and a large vessel, because focal EEG abnormalities are sparse or absent with a deep lacunar stroke. The technique finds more use in distinguishing between transient alterations in nervous function that are a result of seizures and episodes caused by focal ischemia.


Neurology_Adams

Neurology_Adams. Whereas most cerebral arteries can be evaluated only indirectly, more direct clinical means of physical examination are available for the evaluation of the common and internal carotid arteries in the neck. With severe atherosclerotic stenosis at the level of the carotid sinus auscultation discloses a bruit, best heard with the bell of the stethoscope held against the skin just tightly enough to create a seal (excessive pressure creates a diaphragm of the skin and filters the low-pitched frequencies that are typical of the bruit of carotid stenosis). Occasionally, a bruit at the angle of the jaw is caused by stenosis at the origin of the external carotid artery or is a radiated murmur from the aortic valve and can then be misleading. If the bruit is loudest at the angle of the jaw, the stenosis usually lies at the proximal internal carotid; if heard lower in the neck, it is in the common carotid or subclavian artery and may be radiated from the aortic valve. Rarely, stenosis in


Neurology_Adams

Neurology_Adams. the stenosis usually lies at the proximal internal carotid; if heard lower in the neck, it is in the common carotid or subclavian artery and may be radiated from the aortic valve. Rarely, stenosis in vertebral arteries or vascular malformations at the base of the brain produces bruits that are heard posteriorly in the neck.


Neurology_Adams

Neurology_Adams. The presence of a bruit in the neck is an indication of cerebrovascular disease but its detection is not highly correlated with the presence of severely stenotic lesions as assessed by ultrasonography or angiography. In the past, the physician was almost completely dependent on the details of the nature of the bruit but these details are now of limited interest. An additional though infrequent sign of carotid occlusion is the presence of a bruit over the opposite carotid artery, heard by placing the bell of the stethoscope over the eyeball (ocular bruit). As pointed out by Pessin and colleagues (1983), this murmur is often caused by augmented circulation through the patent vessel but there have been as many instances in our experience when a bruit over the eye instead reflects a stenosis in the intracranial portion of the carotid artery on that side. These and other tests for assessing carotid flow have been supplanted by ultrasound insonation and imaging of the carotid artery, but


Neurology_Adams

Neurology_Adams. in the intracranial portion of the carotid artery on that side. These and other tests for assessing carotid flow have been supplanted by ultrasound insonation and imaging of the carotid artery, but retinal examination remains valuable in that it may demonstrate emboli within retinal arteries, either shiny white or reddish in appearance; this is another important sign of carotid disease (crystalline cholesterol, termed Hollenhorst plaque, is sloughed from an atheromatous ulcer).


Neurology_Adams

Neurology_Adams. The clinical picture that results from an occlusion of any one artery differs in minor ways from one patient to another, but there is sufficient uniformity to justify the assignment of a typical syndrome to each of the major cerebral arteries. The identification of these syndromes by careful examination is one of the cardinal skills of the clinical neurologist. The following descriptions apply particularly to the clinical effects of ischemia and infarction caused by embolism and thrombosis. Although hemorrhage within a specific vascular territory may give rise to many of the same effects, the total clinical picture is different because it usually involves regions supplied by more than one artery and, by its deep extension and pressure effects, causes secondary features of headache, vomiting, and hypertension, as well as a series of falsely localizing signs, as described in Chaps. 16 and 30.


Neurology_Adams

Neurology_Adams. The carotid system consists of three major arteries: the common carotid, internal carotid, and external carotid. As indicated in Fig. 33-1, the right common carotid artery arises at the level of the sternoclavicular notch from the innominate (brachiocephalic) artery, and the left common carotid comes directly from the aortic arch. The common carotid arteries ascend in the neck to the C4 level, just below the angle of the jaw, where each divides into external and internal branches (sometimes the bifurcation is slightly above or below this point). This part of the extracerebral circulation is essential to an understanding of stroke. The carotid vessels are subject to atherosclerotic narrowing, atherothrombotic occlusion, arterial dissection and rarely, other processes such as various forms of vasculitis. There are two ways in which carotid stenosis causes ischemic symptoms; the main one is by the embolization from atherosclerosis and platelet-fibrin material originating in the artery


Neurology_Adams

Neurology_Adams. of vasculitis. There are two ways in which carotid stenosis causes ischemic symptoms; the main one is by the embolization from atherosclerosis and platelet-fibrin material originating in the artery and the less common one is a result of hypoperfusion of the ipsilateral cerebral hemisphere.


Neurology_Adams

Neurology_Adams. Occlusion of the common carotid artery accounts for less than 1 percent of cases of carotid artery syndrome, the remainder being because of disease of the internal carotid artery itself. Nevertheless, the common carotid can be occluded by an atheromatous plaque at its origin in the thorax, more often on the left side. Atherosclerotic stenosis or occlusion of the midportion of the common carotid may also occur years after radiation therapy for laryngeal, thyroid, or other head and neck cancer. If the bifurcation is patent, few if any symptoms may result because retrograde flow from the external carotid maintains internal carotid flow and perfusion of the brain.


Neurology_Adams

Neurology_Adams. The remainder of this discussion is concerned with disease of the internal carotid artery. The territory supplied by this vessel and its main branches is shown in Figs. 33-1 and 33-2. The territory affected by diminished blood flow in the brain in cases of carotid occlusion is highly dependent on the configuration of the circle of Willis. For example, when the anterior communicating artery is very small, the ipsilateral anterior cerebral territory is affected as well. In extreme instances where the circle of Willis provides no communication to the side of an occluded carotid artery, thus isolating the hemisphere from other blood flow, massive infarction involving the anterior two-thirds or all of the cerebral hemisphere results. If the two anterior cerebral arteries arise from a common stem on one side, infarction may occur in the territories of both vessels. The territory supplied by the posterior cerebral artery will also be included if this vessel is supplied by the internal


Neurology_Adams

Neurology_Adams. stem on one side, infarction may occur in the territories of both vessels. The territory supplied by the posterior cerebral artery will also be included if this vessel is supplied by the internal carotid rather than the basilar artery (a configuration that reflects a residual fetal origin of the posterior cerebral artery). The clinical manifestations of atherosclerotic thrombotic disease of this artery are among the most variable of any cerebrovascular syndrome because the internal carotid is not an end vessel. In most individuals, it is in continuity with the vessels of the circle of Willis and those of the orbit, and no part of the brain is completely dependent on it. Therefore, occlusion, which occurs most frequently in the first part of the internal carotid artery immediately beyond the carotid bifurcation, is usually silent.


Neurology_Adams

Neurology_Adams. If one internal carotid artery had been occluded at an earlier time, occlusion of the other may cause bilateral cerebral infarction. The clinical effects in such cases may include coma with quadriplegia and continuous horizontal “metronomic” conjugate eye movements. Occlusion of the distal intracranial portion of the internal carotid artery (the “T”)—for example, by an embolus—produces a clinical picture like that of middle cerebral artery occlusion: contralateral hemiplegia, hemihypesthesia, and aphasia (with involvement of the dominant hemisphere). When the anterior cerebral territory is included, there are additional clinical features of leg paralysis as described further on. Patients with such large infarctions are usually immediately drowsy or stuporous because of an ill-defined effect on the reticular activating system.


Neurology_Adams

Neurology_Adams. Headache, located as a rule above the eyebrow, on the side of the infarction, may occur with thrombosis or embolism of the carotid artery, but cranial pain is not invariable and is usually mild. The headache associated with occlusion of the middle cerebral artery tends to be more lateral, at the temple; that of posterior cerebral occlusion is located in or behind the eye.


Neurology_Adams

Neurology_Adams. When the circulation of one carotid artery has been incompletely compromised, reducing blood flow in both the middle and anterior cerebral territories on that side, the zone of maximal ischemia lies between the two vascular territories (“cortical watershed”) or, alternatively, in the deep portions of the hemisphere between the territories of the lenticulostriate branches and the penetrating vessels from the convexity (“internal” or “deep watershed”). The infarction in the first instance occupies a region in the high parietal and frontal cortex and the adjacent subcortical white matter. Its size depends upon the adequacy of collateral vessels. Weakness tends to involve the shoulder and hip more than the hand and face. With long-standing carotid stenosis, the cortical watershed zone shifts downward toward the perisylvian portions of the middle cerebral artery territory, even to the extent that a stroke may weaken facial movement or cause a nonfluent aphasia. With impaired perfusion of


Neurology_Adams

Neurology_Adams. downward toward the perisylvian portions of the middle cerebral artery territory, even to the extent that a stroke may weaken facial movement or cause a nonfluent aphasia. With impaired perfusion of the deep watershed, infarctions of varying size are situated in the subfrontal and subparietal portions of the centrum semiovale.


Neurology_Adams

Neurology_Adams. The situation can be somewhat different in cases of total circulatory collapse from cardiac arrest, in which perfusion fails not only in the watershed areas between the middle and anterior cerebral arteries but also between the middle and posterior cerebral arteries. Bilateral infarctions are then situated within a zone that extends in a sickle-shaped strip of variable width from the cortical convexity of the frontal lobe through the high parietal lobe, to the occipitoparietal junction. Deeper infarctions also occur, but they more often take the form of contiguous extensions of the just described cortical infarction into the subjacent white matter. There may appear to be several separate infarctions after hypoperfusion states, but these often turn out to be radiographically visible portions of a larger border-zone lesion.


Neurology_Adams

Neurology_Adams. The internal carotid artery also supplies the optic nerve and retina. For this reason, transient monocular blindness occurs prior to the onset of stroke in 10 to 25 percent of cases of symptomatic carotid occlusion. Yet central retinal artery ischemia is a relatively rare manifestation of carotid artery occlusion, presumably because of efficient collateral supply in the globe.


Neurology_Adams

Neurology_Adams. Signs of carotid occlusion include transient monocular blindness or visual loss or dimness of vision with exercise, after exposure to bright light, or on assuming an upright position; retinal atrophy and pigmentation; atrophy of the iris; peripapillary arteriovenous anastomoses in the retinae; and claudication of jaw muscles. However, the cardinal clinical signs of stenoses, ulcerations, and dissections of the internal carotid artery are TIAs. It is a subject of debate whether these are the result of fibrin platelet emboli or a reduction in blood flow. TIAs were discussed earlier, but here it can be stated again that they represent an important risk factor for stroke.


Neurology_Adams

Neurology_Adams. The middle cerebral artery (MCA) has superficial and deep hemispheral branches that together supply the largest portion of the cerebral hemisphere. Through its cortical branches, it supplies the lateral (convexity) part of the cerebral hemisphere (see Figs. 33-2 and 33-5) encompassing (1) the cortex and white matter of the lateral and inferior parts of the frontal lobe—including motor areas 4 and 6, contraversive centers for lateral gaze and the motor speech area of Broca (dominant hemisphere); (2) the cortex and white matter of the parietal lobe, including the primary and secondary sensory cortices and the angular and supramarginal gyri; and (3) the superior parts of the temporal lobe and insula, including the receptive language area of Wernicke. The deep penetrating or lenticulostriate branches of the MCA supply the putamen, a large part of the head and body of the caudate nucleus (shared with the Heubner artery, see further on), the outer globus pallidus, the posterior limb of the


Neurology_Adams

Neurology_Adams. branches of the MCA supply the putamen, a large part of the head and body of the caudate nucleus (shared with the Heubner artery, see further on), the outer globus pallidus, the posterior limb of the internal capsule, and the corona radiata (see Fig. 33-6).


Neurology_Adams

Neurology_Adams. The MCA may be occluded in its longitudinal portion, or the stem, that is proximal to its bifurcation (the term M1 is used to denote this portion of the vessel). An occlusion at this site blocks the flow in the small deep penetrating vessels as well as in superficial cortical branches. An occlusion at the distal end of the stem blocks only the orifices of the divisions of the artery in the sylvian sulcus but leaves unaffected the deep penetrating vessels. The idealized picture of total occlusion of the stem is one of contralateral hemiplegia (involving the face, arm, and leg as a result of infarction of the posterior limb of the internal capsule), hemianesthesia, and can include homonymous visual field deficit (because of infarction of the lateral geniculate body), with deviation of the head and eyes toward the side of the lesion. In addition, there is a variable but usually global aphasia with left hemispheric lesions and anosognosia and amorphosynthesis with right-sided lesions (see


Neurology_Adams

Neurology_Adams. and eyes toward the side of the lesion. In addition, there is a variable but usually global aphasia with left hemispheric lesions and anosognosia and amorphosynthesis with right-sided lesions (see Chap. 21). Partial syndromes encompassing several parts of this ensemble are common. At the onset of the stroke, the patient may be drowsy because of an ill-defined effect of widespread paralysis of neurologic function. If there are adequate collateral vessels over the surface of the hemisphere, only those components of the stroke referable to the deep structures may be evident (mainly hemiplegia encompassing the contralateral limbs and face) as discussed below, the cortical elements of aphasia, agnosia, and apraxia then being absent or mild.


Neurology_Adams

Neurology_Adams. Occlusion of the stem of the MCA is usually caused by embolus and less often by a thrombus superimposed on a local atherosclerotic plaque. In the past, “middle cerebral artery thrombosis” was thought to be the most common cause of stroke, whereas studies over the years have affirmed that most carotid occlusions are thrombotic, whereas most middle cerebral occlusions are embolic (Fisher, 1975; Caplan, 1989). The emboli may lodge in the stem or, more often, drift into the cortical branches as described below; emboli infrequently enter solely the deep penetrating branches of the stem and cause a small deep infarction (lacune).


Neurology_Adams

Neurology_Adams. In the less-common circumstance of stenosis of the MCA with occlusion of the vessel by a superimposed thrombus, the stroke is often preceded by TIAs, producing a picture resembling that of carotid stenosis (see Caplan, 1989). Transient monocular blindness does not occur in this situation because the occlusion is distal to the ophthalmic artery. In epidemiologic studies, certain populations such as Asians are disproportionally affected by this form of intracranial atherosclerosis, as are diabetics.


Neurology_Adams

Neurology_Adams. Striatocapsular infarction A number of interesting syndromes occur with deep lesions in the territory of the penetrating vessels of the MCA, collectively known as lenticulostriate, or penetrating vessels (see Figs. 33-6 and 33-8). Most, as mentioned, are attributable to emboli that lodge in the stem of the main vessel, although imaging studies may show a patent middle cerebral artery, implying that the embolus has moved on. Others are undoubtedly atherothrombotic as mentioned earlier. These lesions in the corona radiata are larger than typical lacunar infarctions (see further on) but probably have a similar pathophysiology.


Neurology_Adams

Neurology_Adams. Although the infarction is centered in the deep white matter, most of the syndromes include a fragment of one of the cortical stroke patterns described further on. The most common type is a large striatocapsular infarction, similar to that described by Weiller and colleagues. All of their patients had a degree of hemiparesis and one-fifth had aphasia or hemineglect. Aphasia, when it occurred, tended to be a limited form of the Broca type and is usually short-lived. With smaller deep strokes, incomplete motor syndromes affecting only the arm and hand, without language disturbance or neglect are common; these are difficult to differentiate from small embolic cortical strokes.


Neurology_Adams

Neurology_Adams. Homonymous hemianopia is an infrequent occurrence with posterior capsular lesions, but when it occurs, is probably a result of damage to the region of the lateral geniculate nucleus and optic radiations, but it is infrequent and must be distinguished from visual hemineglect of contralateral space. Bilateral cerebral infarctions involving mainly the insular–perisylvian (anterior opercular) regions manifest themselves by a diplegia of the face, tongue, and masseters that results in anarthria without aphasia (see Mao et al and Bakar et al). Superior division An embolus entering the middle cerebral artery most often lodges in one of its two main branches, the superior division (supplying the rolandic and prerolandic areas) or the inferior division (supplying the lateral temporal and inferior parietal lobes), sometimes together designated as M2 segments; see Figs. 33-2 and 33-7. Atherothrombotic occlusion of these vessels is infrequent.


Neurology_Adams

Neurology_Adams. Complete infarction in the territory of the superior division causes a dense sensorimotor deficit in the contralateral face, arm, but, to a lesser extent the leg, as well as ipsilateral deviation of the head and eyes; that is, it differs from the MCA stem occlusion syndrome in that the leg and foot are partly spared and less involved with weakness than the arm and face (“brachiofacial,” or “chierobrachial” paralysis); there is no impairment of alertness. Less extensive strokes are more common than this archetype and the deficits are correspondingly milder. If the occlusion is long lasting (not merely transient ischemia with disintegration of the embolus) there will be slow improvement; after a few months, the patient is able to walk with a spastic leg, while the motor deficits of the arm and face may remain. The sensory deficit may be profound, resembling that of a thalamic infarct (as described in Chap. 8) but more often it is less severe than the motor deficit, taking the form of


Neurology_Adams

Neurology_Adams. and face may remain. The sensory deficit may be profound, resembling that of a thalamic infarct (as described in Chap. 8) but more often it is less severe than the motor deficit, taking the form of stereoanesthesia, agraphesthesia, impaired position sense, tactile localization, and two-point discrimination, as well as variable changes in touch, pain, and temperature sense (see Chap. 21). With left-sided lesions there may initially be severe aphasia to the point of mutism, or there is a predominantly nonfluent (Broca’s) aphasia, reflected by effortful, hesitant, grammatically simplified, and dysmelodic speech (see Chap. 22).