Neurovascular Disorders

 

Historical Background

Overview of Strokes

Ischemia

Atherothrombosis

Embolism

Systemic hypoperfusion

Hemorrhage

Stroke Incidence and Prevalence

Risk Factors for Stroke

Transient Ischemic Attacks and Strokes

Diagnosis

Diseases That Cause Strokes

Atherothrombotic Disease

Occlusive Disease of Small Penetrating Arteries

Brain Embolism

Systemic Hypotenstion (Border Zone Infarction)

Selected Non-Atherosclerotic Occlusive Diseases

Noninflammatory vascular diseases

Cerebrovascular diseases related especially to pregnancy

Inflammatory vascular disorder

Migraine related stroke

Coagulation Disorders

Immunological Abnormalities

Hemorrhagic Cerebrovascular Diseases

Primary Intracranial Hemorrhage

Subarachnoid Hemorrhage

Arteriovenous Malformations

Traumatic Cerebrovascular Diseases

Carotid-Cavernous Sinus Fistulas

Subdural Hematomas

Epidural Hematomas

Spinal Cord Strokes

Strokes in the Young

HISTORICAL BACKGROUND

During the seventeenth and eighteenth centuries, physicians and morphologists (Wepfer, Willis, Morgagni, Cheyne, and others) recognized that the brains of patients who died of apoplexy often contained hemorrhages and softenings and that brain damage could result from either bleeding or deprivation of the vital blood supply.During the nineteenth and early twentieth centuries, physicians became interested in correlating the neurological symptoms and signs found in stroke patients during life with the anatomical region of damage in the brain found after death. Various eponymic syndromes such as those of Wallenberg, Babinski-Nageotte, Weber, Millard Gubler, among others, described the neurological findings in patients with lesions at various brain stem sites. Anatomical-clinical correlations culminated in the work of Charles Foix and his Paris colleagues who, in the mid-1920s, defined the territories of supply of the various vessels within the anterior and posterior brain circulations and noted the findings in patients with infarcts in the territories of the various arteries.

During the middle years of the twentieth century, clinicians became interested in the clinical findings in patients with brain hemorrhages and infarcts. In 1935, Aring and Merritt analyzed the clinical findings in patients who died at the Boston City Hospital from large strokes and tried to separate the signs of embolism, thrombosis, and brain hemorrhage.Kubik and Adams, in 1946, reported the first detailed clinicopathological analysis of a stroke syndrome--occlusion of the basilar artery.In 1951, Miller Fisher described the clinical findings in patients who had internal carotid artery occlusions in the neck.Fisher emphasized that warning spells, which he dubbed transient ischemic attacks (TIAs), often preceded strokes in his patients and that the causative vascular disease was located in the neck, where it could theoretically be repaired by surgeons, rather than intracranially in the middle cerebral arteries (MCAs), where most of the prior literature had indicated that the usual vascular lesions were located. Shortly thereafter, Hutchinson and Yates showed that patients with posterior circulation infarcts and TIAs also often had occlusive disease in the neck,at the origins of the extracranial vertebral arteries, rather than in the head. Wallenberg and Kubik and Adams had identified the vascular pathology. In 1961, Miller Fisher described the clinical findings in patients with large fatal brain hemorrhages located in the putamen, thalamus, pons, and cerebellum.

Stimulated by these seminal reports and their own clinical experiences, physicians became more interested in the clinical features of stroke, brain ischemia, and cerebrovascular disease. Unfortunately, during the third quarter of the twentieth century (1951-1975), few neurologists had much interest in stroke, and most patients were cared for by non-neurologists. Furthermore, few investigations were available that could be performed safely during life and could also clarify the nature, location, and extent of strokerelated brain damage or the causative cardiac and cerebrovascular lesions. Physicians during this era turned to classifications based solely on the temporal features of symptoms. The terms TIAs, reversible ischemic neurological deficit (RIND), stroke-in-evolution, progressing stroke, and completed stroke became popular and were used as a basis for treatment. These terms were arbitrarily and variously defined and proved unpredictive of the presence of brain infarction, prognosis, and stroke mechanism; they are now obsolete and of historical interest only. , TIA is the only term that remains useful, mainly for ease in communication but not as a guide to diagnosis or treatment.

During the last quarter of the twentieth century, an explosion of technical advances in brain imaging (computed tomography CT and later magnetic resonance imaging MRI) and technology occurred that could give information about the cervicocranial arteries (subtraction angiography, magnetic resonance angiography MRA, computed tomography angiography CTA, and extracranial and transcranial ultrasound). Knowledge of the role of blood cells and coagulation factors in causing or contributing to thromboembolism also advanced. During this time, potential treatments also proliferated; these included agents that modify platelet functions; standard anticoagulants including heparin, heparinoids, low-molecular-weight heparins, and warfarin (Coumadin); endarterectomy and surgical bypass of stenotic or occluded arteries; thrombolytic treatment; angioplasty; and neuroprotective drugs aimed at increasing the brain's tolerance of ischemia. Treatment should now be based mainly on the nature, location, and severity of the causative cardiac, vascular, and hematological disorder; the pathogenesis of the stroke; and the state of the brain (normal, stunned, infarcted, or containing a hematoma). The newer available diagnostic technologies now make it possible to collect these data safely and quickly in most stroke patients.

OVERVIEW OF STROKES

Ischemia

Brain ischemia results from the occlusion of cervicocranial vessels or hypoperfusion to the brain caused by various processes: atherothrombosis, embolism, or hemodynamic abnormalities.

ATHEROTHROMBOSIS

Atherothrombosis occurs in the large cervicocranial arteries in the neck and head and small penetrating arteries. In this condition, a localized thrombus is formed in situ on an atherosclerotic arterial narrowing; it impedes distal blood flow and causes ischemia and ensuing infarction of the brain tissue supplied by the artery. The neurological symptoms and signs depend on the location of the brain vessel affected.

EMBOLISM

In brain embolism, a brain artery is suddenly blocked by embolic material, which is usually a thrombus that developed more proximally in the heart (cardiogenic), aorta, proximal arteries (intra-arterial), or venous system (paradoxical). These donor sites give rise to various types of particulate matter (white platelet-fibrin and red erythrocyte-fibrin thrombi, cholesterol crystals, fragments of atherosclerotic plaques, calcific fragments of valves and plaques, air, fat, myxomatous tumor fragments, bacterial vegetations), which then travel within the cervicocranial arteries to reach a recipient site. If the embolic material lodges for very long at a recipient site, the resulting hypoperfusion causes an infarct that often becomes hemorrhagic when the embolus moves or fragments and reperfusion occurs. The clinical findings depend on the location of the recipient brain artery affected.

SYSTEMIC HYPOPERFUSION

Critically lowered blood flow to the brain (too severe to be compensated by cerebral autoregulation mechanisms) caused by cardiac pump failure or hypovolemia causes a global decrease in cerebral blood flow. During such episodes, most patients are hypotensive. This condition causes infarction in the border zones between the major cerebral arteries (so-called watershed infarction) as well as widespread bilateral cerebral dysfunction. The major zones of damage are between the anterior and middle cerebral arteries, and between the middle and posterior cerebral arteries in the parieto-occipital regions of the cerebral hemispheres. Loss of vision, decreased alertness, and weakness affecting predominantly the shoulder, hand, and thigh result.

Hemorrhage

Rupture of a brain vessel causes leakage of blood into the brain parenchyma, cerebrospinal fluid (CSF) spaces around the brain, or both. Bleeding injures the neighboring tissues by interrupting and cutting vital brain pathways, by exerting local pressure on the surrounding brain structures, and by causing ischemia of tissues adjacent to the hematoma. Further increase in intracranial pressure (ICP) causes shifts and herniations of brain tissues and may compress the brain stem. There are two large subcategories of spontaneous intracranial hemorrhages. Intracerebral hemorrhage (ICH) is bleeding in the brain parenchyma itself, and subarachnoid hemorrhage (SAH) refers to bleeding around the brain into the subarachnoid spaces and CSF. These two types of hemorrhages have different etiologies, clinical courses, and outcomes and thus require different management strategies.

Stroke Incidence and Prevalence

Stroke is a major public health problem, ranking among the top three causes of death in most countries. It affects the brains of almost a half million people every year, causing 150,000 deaths, and there are now approximately 3 million stroke survivors in the United States. Overall, ageadjusted incidence rates range between 100 and 300 per 100,000 population per year. Stroke is the major cause of serious disability in adults and is responsible for $20 billion in annual costs per year in lost wages in the United States. Stroke incidence rates declined during the 1950s and 1960s but increased during the 1980s. This increase may be due to increased recognition related to advances in neuroimaging technology, increased survival of patients with ischemic heart disease, better detection of milder cases of stroke, and other undefined factors during the past 10 years. ,

Stroke accounts for about 10 percent of all deaths in most industrialized countries, and the great majority of deaths are among persons over age 65. The average age-adjusted mortality rate is 50 to 100 per 100,000 population per year in the United States. Stroke mortality rises exponentially with age, virtually doubling every 5 years. Stroke death rates are higher among blacks. The stroke mortality rate has steadily declined in the United States since 1915; the decline in black mortality rates has exceeded that of whites and spans all age groups. Improved survival after stroke contributes to this trend most significantly.

Ischemic stroke accounts for more than 80 percent of all strokes. ICH usually accounts for 10 to 30 percent of cases depending on the origin of the patient, with greater relative frequencies reported in Asians and blacks. Frequency of SAH is usually a third to a half of that of ICH. Among patients with brain ischemia, cardioembolism accounts for 20 to 30 percent of cases, atherothrombotic infarction accounts for 14 to 40 percent, and small deep infarcts due to penetrating artery disease (lacunes) account for 15 to 30 percent of cases.

There are major sex and racial differences in the distribution of occlusive cerebrovascular lesions. Extracranial occlusive diseases usually affect white men, are located at the origins of the internal carotid and vertebral arteries in the neck, occur twice as often in men, and are strongly associated with coronary and peripheral vascular occlusive disease, systolic hypertension, and hyperlipidemia. Compared with white men, blacks, persons of Asian origin, and women have more severe diseases of the intracranial arteries and their perforating branches. Intracranial stenosis is usually less frequently associated with coronary and peripheral vascular disease.

Risk Factors for Stroke

Knowledge of stroke risk factors has advanced substantially during the past several decades and exceeds that of many other major neurological diseases. Important stroke risk factors include advanced age, systolic hypertension, diabetes mellitus, hypercholesterolemia, carotid artery stenosis, TIAs, cigarette smoking, lack of exercise, cardiovascular disease, atrial fibrillation, and left ventricular hypertrophy (LVH) on electrocardiography (ECG). , Based on epidemiological data, a risk profile table can be used to estimate a person's 10-year probability of stroke occurrence. Stroke rates increase dramatically with age. About two thirds of all strokes occur after the age of 65. In the Framingham study the mean age of stroke patients was 65.4 years for men and 66.1 years for women. As the population ages, the burden of stroke becomes greater.

Hypertension is the most significant modifiable risk factor for stroke, and stroke incidence is proportional to the level of the blood pressure. This is particularly true in blacks because of higher prevalence, earlier onset, greater severity, and poorer control of hypertension in this population. Decreasing systolic blood pressure by about 10 mm Hg reduces the relative risk of stroke by 35 to 40 percent. Improved control of hypertension has resulted in a recent dramatic decline in stroke frequency, most notably in black women. The combination of hypertension, diabetes, and cigarette smoking is particularly risky and requires aggressive interventions. Diabetes mellitus is also a significant risk factor and is present in about 10 percent of stroke patients. It is common among blacks and particularly contributes to the development of intracranial atherosclerosis.

Cigarette smoking is a very important preventable cause of stroke, and about 30 percent of stroke patients do smoke. Heavy cigarette smoking (more than a pack per day) carries 11 times the ischemic stroke risk and four times the SAH risk of people who do not smoke. Smoking has an especially toxic effect on women taking oral contraceptives, in whom it carries 22 times the risk of developing stroke than occurs in nonsmoking women who use other forms of birth control. With cessation of cigarette smoking, the risk of stroke declines after 2 to 5 years. A J-shaped relationship exists between alcohol and stroke. The relative risk of stroke increases with moderate to heavy alcohol consumption and decreases with light drinking compared with nondrinkers. Heart diseases are clearly associated with increased risk of ischemic stroke, particularly atrial fibrillation, valvular heart disease, myocardial infarction, coronary artery disease, congestive heart failure, LVH on ECG, and mitral valve prolapse. Atrial fibrillation, which alone carries a fivefold increased risk of stroke, is particularly important in the elderly and among those with coronary heart disease or heart failure or valvular heart disease. Ascending aorta and aortic arch atheromas are an important independent risk factor for brain infarction. Abnormal serum lipid levels are regarded as risk factors, more for coronary artery disease than stroke, and are more closely related to the progression of carotid stenosis. Sex also has an influence on stroke incidence; the stroke incidence rate is greater in men than in women.

Transient Ischemic Attacks and Strokes

Miller Fisher first described the phenomenology of TIAs as "prodromal fleeting attacks of paralysis, numbness, tingling, speechlessness, unilateral blindness or dizziness," which nearly always preceded cerebral infarction in patients with occlusion of the internal carotid artery (ICA). TIA is a strong indicator of a subsequent stroke. The first year after a TIA carries the greatest stroke risk (5 percent). TIA is arbitrarily defined as a focal neurological deficit lasting less than 24 hours, but attacks are usually shorter, most episodes clearing within 1 hour. , If neurological deficits last 4 hours or longer, patients often have infarcts in the locations corresponding to the transient symptoms. The clinical features of TIAs are usually similar to those of infarctions located in the arteries affected except for the transient nature of the clinical episodes.

Because TIAs are a manifestation of underlying cardiovascular or blood diseases, the underlying cardiac, hematological, and cerebrovascular diseases that potentially cause TIAs should be thoroughly investigated to manage the patients optimally. For accurate diagnosis and management, detailed clinical information is essential and helps to predict the underlying cause. Data should include the duration of the neurological deficit, heterogeneity or stereotypy, time from first TIA and from last TIA, number of spells, and nature of symptoms (motor, sensory, visual, motor and sensory, distribution on the body). There are many laboratory tests that are helpful in defining the most probable causative mechanisms of TIAs, but they should be selected and ordered on the basis of judicious interpretation of clinical data.

Management of patients with TIAs should be directed toward specific vascular lesions and underlying causative diseases. , Further details are discussed later in relation to the individual disease entities.

Diagnosis

To determine the stroke mechanism or mechanisms, the following clinical bedside data should be obtained through careful history taking: (1) ecology--past and present personal and family illnesses; (2) the presence and nature of past strokes and TIAs; (3) the time of onset of the symptoms; (4) activity at onset; (5) the temporal course and progression of the findings; and (6) accompanying symptoms. A general physical examination should then be done to add more data that can be used for diagnosis of the stroke mechanism. Elevated blood pressure, cardiac enlargement or murmurs, bruits in the carotid and supraclavicular region, and symmetry of blood pressure and pulses in the arms are important check points during physical examination of stroke patients.

The presence of some findings, such as headache, vomiting, loss of consciousness, and seizures, is helpful in diagnosing subtypes of strokes. Headache at onset is an invariable feature of SAH and is also common in patients with large ICHs and large cerebral infarcts due to large artery occlusive disease and brain embolism. Headache unusual for the patient is rare in patients with lacunar infarction due to penetrating artery disease. Some patients with large artery occlusive disease and those with severe hypertension often have unaccustomed headaches in the days and weeks preceding a stroke or TIA.

Vomiting is very common in patients with SAH and ICH and in those with brain stem and cerebellar infarcts. Vomiting is very rare in patients with hemispherical brain infarction due to large artery occlusive disease or embolism. Seizures at or shortly after the onset of the stroke are relatively common in patients with lobar hemorrhages and those with brain embolism, but do not occur in patients with lacunar infarcts. Loss of consciousness at onset is common in patients with large SAHs and in those with embolism to the basilar artery but is rare in strokes due to other mechanisms. Patients with large ICHs often have headache, vomiting, and progressive loss of alertness as the hematoma enlarges and intracranial pressure rises.

Neuroimaging studies include CT scan, MRI, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). CT and MRI scans image brain structure. CT scans are best for differentiating ischemic stroke from hemorrhagic stroke. MRI can detect an acute ischemic stroke earlier than CT and is the preferred technique for identifying brain stem and cerebellar infarctions. SPECT and PET scans image the perfusion and metabolic state of the brain and can quantify cerebrovascular reserve capacity.

Vascular imaging can be divided into noninvasive and invasive studies. Four commonly used noninvasive tests are Duplex scans (B-mode and Doppler combined), transcranial Doppler ultrasonography (TCD), MRA, and CTA. Duplex scans show an accurate image of the extracranial carotid and subclavian arteries. TCD is useful for the evaluation of the intracranial cerebral arteries by measuring flow velocities and directions. MRA and CTA are also noninvasive methods for the evaluation of intracranial and extracranial large arteries. Combined use of these noninvasive tests is usually adequate for evaluation of most stroke patients. MR venography is now a very useful diagnostic tool for showing cerebral venous sinus thrombosis and has largely replaced invasive conventional cerebral angiography. When there is any suspicion of significant vascular lesions such as severe intra- or extracranial stenosis, aneurysm, arteriovenous malformation (AVM), or vasculitides, standard femoral artery catheterization and angiography are usually done to further define and characterize the lesions and, when possible, to intervene to treat vascular lesions at the same time. Important laboratory tests for stroke patients are listed in Table 45-1 .

 

 

TABLE 45-1 -- LABORATORY STUDIES FOR STROKE PATIENTS

Neuroimaging

Structural imaging

Computed tomography (CT)

Magnetic resonance imaging (MRI)

Functional imaging

Single-photon emission tomography (SPECT)

Positron emission tomography (PET)

Magnetic resonance spectroscopy (MRS)

Diffusion and perfusion MRI

Vascular Imaging

Noninvasive

B-mode ultrasound

Continuous wave and pulsed Doppler (Duplex)

Transcranial Doppler ultrasound (TCD)

Magnetic resonance angiography (MRA)

Invasive

Digital subtraction angiography (DSA)

Conventional angiography

Heart Studies

Echocardiography: transthoracic, transesophageal

24-hour ambulatory cardiac monitoring

Cardiac nuclear scanning

Blood Tests

Coagulation and platelet function tests

 

DISEASES THAT CAUSE BRAIN ISCHEMIA

Atherothrombotic Disease

Pathogenesis and Pathophysiology. Atherothrombosis implies a reduction or occlusion of blood flow caused by a localized thrombotic process in one or more atherosclerotic cervicocranial arteries. Branching points of arteries are the predilection sites of development of atherosclerosis (Fig. 45-3 (Figure Not Available) ). In atherosclerosis, fibrous and muscular tissues of the vessel wall overgrow in the subintima, and fatty materials form plaques that can encroach on the lumen. Platelets adhere to the crevices in the plaques and form clumps that serve as nidi for the deposition of fibrin, thrombin, and clot. Plaques and ulcers are associated with denudation of the endothelium and decreased release of endothelium-releasing factors including nitric oxide. Endothelins can promote platelet activation and thrombus formation. Intraluminal thrombi are of different types: so-called "white clots," which are mainly composed of platelets and fibrin, and "red thrombi," which are red blood cells enmeshed in fibrin. White platelet clumps form most often in fast-moving streams, adhering to crevices and irregularities along the intimal surface. Fibrin-dependent red thrombi develop in slow-moving streams, for example, arteries with severe luminal narrowing. Narrowing of arteries decreases blood flow, leading to stagnation of the blood column and activation of clotting factors. Clot and fibrin-platelet clumps form and break off, blocking distal arteries and further impeding flow in the affected parent artery (see Fig. 45-3 (Figure Not Available) ).

Epidemiology and Risk Factors. Atherosclerosis affects chiefly the large extracranial and intracranial arteries, but there are important sex and racial differences in the distribution and incidence of lesions at these sites. White men have more severe disease of the extracranial arteries, whereas in blacks, persons of Asian origin, and women there is a predilection for narrowing of the intracranial arteries.

Patients with extracranial large artery disease also have a high incidence of coronary artery disease (angina pectoris and myocardial infarction), peripheral vascular occlusive disease (claudication), hypertension, and hypercholesterolemia. Death is more often due to fatal coronary artery disease than stroke.

Clinical Features and Associated Disorders. Development of neurological deficits preceded by brief, frequent shotgun-like TIAs in the same vascular territory usually suggests atherothrombosis as the vascular mechanism. Stroke caused by a thrombotic process often develops during or just after sleep. Atherothrombotic infarctions are usually characterized by postural sensitivity of symptoms, occlusion or severe stenosis of a large artery, absence of distal embolus by angiography, infarct on CT or MRI near the border zone territory of the affected artery, and the presence of risk factors for atherosclerosis such as hypertension, diabetes mellitus, and smoking. The neurological symptoms and signs depend on the vessels involved and the regions of brain ischemia.

Differential Diagnosis and Evaluation. The diagnosis of large artery occlusive disease is based on the demographic and epidemiological situation of the patient, analysis of the time course of the brain ischemia, physical examination of the heart and neck vessels, and tests that define the anatomy and function of the cervicocranial arteries. Brain imaging (by CT or MRI) is usually important to define the presence, location, and size of any infarction and may show unexpected ("silent") infarcts not predicted from the history and physical examination. Ultrasound has now become the cornerstone of noninvasive vascular diagnosis. Duplex scans of the carotid and vertebral artery origins combined with color-flow Doppler ultrasound can define and quantify most extracranial carotid and vertebral artery (VA) lesions. TCD can detect many intracranial occlusive lesions, especially those involving the MCAs, intracranial VAs, and the posterior cerebral arteries (PCAs). TCD also yields information about the impact of occlusive extracranial lesions on intracranial blood flow. MRA and CTA are also helpful in imaging the large extracranial and intracranial arteries. When ultrasound and MRA or CTA are concordant and define the occlusive vascular lesions, catheter angiography is usually not necessary.

Management. The very basic goal of management of ischemic stroke patients in the acute phase is protection of the so-called penumbra zone. This zone comprises the brain tissues at risk of irreversible ischemic damage. Brain tissues adjacent to the ischemic core are often impaired functionally ("stunned"), but ischemia is potentially reversible if the circulation is restored soon enough. To achieve this goal, several therapies can be used: (1) occluded vessels can be recanalized (thrombolytic therapy) if possible, (2) blood volume and cerebral blood flow can be maximized and blood viscosity can be reduced, (3) perfusion pressure must be maintained sufficiently (by careful control of blood pressure, reduction of cerebral edema, and lowering of intracranial pressure), and (4) the progression of occlusive processes should be blocked using anticoagulants and agents that alter platelet function in some instances. All these measures should be guided by the severity and reversibility of the lesion, the nature, location, and severity of the underlying stroke mechanism, and the viscosity and coagulability of the blood. Recanalization is usually performed by thrombolysis and will be discussed later in this chapter. Hemodilution therapy decreases blood viscosity by lowering the hematocrit level. Blood pressure should not be aggressively lowered during the acute phase, since this decreases pressure in the collateral channels and may extend the infarct. Various neuroprotective agents are presently under study.

For prevention of recurrence of ischemia in the future, prophylactic treatment should be guided by the mechanism of the stroke. Theoretically, red clots would respond more to warfarin anticoagulants and heparin, and white clots would be better prevented with platelet antiaggregants, such as aspirin. Surgery (endarterectomy), angioplasty, or warfarin may be indicated for patients with tight stenotic lesions and important tissue at risk for further ischemia. The choice of warfarin versus surgery or angioplasty depends on the accessibility of the lesions to treatment, the risk of surgery and angioplasty, the patient's wishes, the likelihood of the patient's compliance with anticoagulant usage, and any contraindication to the use of anticoagulants. Heparin may be used for as long as 2 to 3 weeks to prevent propagation and embolization of clot. Long-term warfarin use is usually not needed after the clot organizes and adheres to the vessel wall in atherothrombotic stroke (usually 3 to 4 weeks). Aspirin, 325 mg or more per day, can prevent platelet-fibrin emboli in patients with minor or moderate stenosis. An increase in the dose of aspirin (especially if an in vitro aspirin effect is not shown at the lower dose) or use of ticlopidine should be tried if symptoms recur. Ticlopidine hydrochloride, a thienopyridine derivative, is another effective antiplatelet agent that has been recently introduced into clinical practice. The recommended dosage is 250 mg twice a day. Its side effects are gastrointestinal symptoms, skin rash, and leukopenia, which require careful monitoring of clinical findings and blood tests during the first 3 months. Neither warfarin nor surgery is recommended in patients with slight to moderate stenosis. If the patient has a primary coagulopathy, polycythemia, or thrombocytosis, these disorders should be treated more specifically.

Prognosis and Future Perspectives. In patients with large artery occlusions, the risk of infarction is maximal in the days after occlusion. After the first week, the likelihood of further infarction is much less. Prognosis depends on whether the initial thrombus propagates distally or embolizes to intracranial arteries and the extent of collateral circulation that develops. Optimization of blood pressure and blood volume during the time when the collateral circulation is developing helps to augment blood flow to the penumbral zones and thus limits the extent of infarction. Of course, patients with large artery atherostenosis are at risk during the subsequent months and years of narrowing and occlusion of other arteries, so preventive measures instituted at the time of the initial symptoms may help in preventing or delaying further strokes. The effectiveness of surgery and angioplasty for various occlusive lesions is now under study in large trials. At times, thrombolysis and angioplasty may be used together because patients with thrombi superimposed on severe atherosclerotic occlusive disease often experience reocclusion of the artery after thrombolysis unless the atherostenosis is repaired. The optimal thrombolytic agent, portal of delivery, dose, timing, and target population for thrombolysis are now being studied. Many trials now are trying to define the usefulness of a variety of neuroprotective agents.

Occlusive Disease of Small Penetrating Arteries

The small penetrating arteries deep within the brain parenchyma are the sites of various occlusive processes that are different from those of the larger arteries.

Pathogenesis and Pathophysiology. Lipohyalinosis, a destructive vasculopathy linked to severe hypertension, affects arteries 40 to 200 m in diameter. The arterial lumen is compromised not by an intimal process but by thickening of the vessel wall itself. Subintimal lipid-laden foam cells and pink-staining fibrinoid material thicken the arterial walls, sometimes compressing the lumen. In places, the arteries are replaced by tangles and wisps of connective tissue that obliterate the usual vascular layers. The small, deep infarcts that result from occlusion of these arteries are usually called lacunes. , , Small, deep infarcts can also result from miniature atheromas (microatheromas) that form at the origin of penetrating arteries, as well as by plaques within the parent arteries that obstruct or extend into the branches (junctional plaques). Rarely, they are occluded by microemboli (Fig. 45-5 (Figure Not Available) ). Vascular lesions involving the mouths of penetrating arteries are called intracranial branch atheromatous disease.

A recently recognized entity named CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a familial arterial disease of the brain that begins in early adult life. Its gene is mapped to chromosome 19. The CADASIL vasculopathy affects the media of leptomeningeal and perforating arteries of the brain. The media is thickened by an eosinophilic granular material of unknown origin. Clinically, patients present with recurrent subcortical infarcts, progressive or stepwise dementia, migraine with aura, and depression. Usually, there is no hypertension or other vascular risk factors. Prominent subcortical white matter and basal ganglia hyperintensities are noted on T2-weighted MRI. Vascular studies are usually not helpful diagnostically.

Epidemiology and Risk Factors. Hypertension is the most significant risk factor for small vessel occlusive diseases and is responsible for about 80 to 90 percent of lacunar infarctions. In addition to hypertension, diabetes mellitus and smoking are also significantly associated with small vessel occlusive disease, particularly with branch atheromatous disease. Blacks and Asians, races with a predilection for hypertension, also have a higher frequency of penetrating artery disease and lacunar infarction than whites.

Clinical Features and Associated Disorders. The arteries commonly affected are the lenticulostriate branches of the MCAs, the thalamogeniculate and thalamoperforant branches of the PCAs, and midline and paramedian penetrating branches of the vertebral and basilar arteries. Infarcts do not involve the cerebral cortex but usually affect the subcortical structures such as the basal ganglia, thalamus, internal capsule, subcortical white matter, and brain stem. Clinical findings are characteristically less severe, neurological dysfunctions are restricted within a few systems, and cognitive and behavioral abnormalities are less common. Lacunar infarcts present diverse clinical syndromes.

Deep infarcts in some regions such as the caudate nucleus, anterior thalamus, and genu of the internal capsule can produce apathy, inertia, and reduced interest in the environment. Bilateral extensive lacunar infarcts are often associated with white matter damage and clinical dementia. Neurological deficits in patients with lacunar infarction can progress gradually or stepwise for 1 to 7 days.

Differential Diagnosis and Evaluation. The major differential diagnostic considerations are restricted cortical and brain stem infarcts due to large artery occlusive disease or embolism and small ICHs. The diagnosis of penetrating artery disease is based on (1) the presence of risk factors, especially present or past hypertension, and diabetes; (2) clinical neurological symptoms and signs typical for or compatible with occlusion of a single perforating artery; and (3) CT or MRI showing a lacunar cerebral infarct or a brain stem infarct in the territory of a single penetrator, or at least no cortical infarct. In uncertain cases, vascular and cardiac imaging may be needed to clarify the diagnosis of penetrating versus large artery occlusive disease.

Management. Treatment consists primarily of controlling the underlying causative process--hypertension. Antiplatelet agents have not been shown to be effective in this condition but are frequently prescribed. Heparin and warfarin anticoagulants are probably ineffective. No specific treatment is currently available for CADASIL.

Prognosis and Future Perspectives. Recovery from lacunar infarctions or branch atheromatous diseases is usually better than that from cortical infarctions. However, many patients develop recurrent lacunar infarcts and white matter ischemia. Dementia, pseudobulbar dysarthria and dysphagia, gait abnormalities, and parkinsonian-like stiffness are common features in patients with extensive brain damage caused by penetrating artery disease.

To date, there have been no controlled trials of patients with acute lacunar infarcts, but these are badly needed in the future. Also badly needed are studies of prevention of further brain damage in patients who already have lacunar infarcts and white matter damage.

Brain Embolism

Pathogenesis and Pathophysiology. There are three major types of embolism--cardiogenic, intra-arterial, and paradoxical. Emboli from any source tend to be arrested in a recipient artery, depending on the location of branch points and the size of the embolic material. Once lodged, embolic matter often migrates distally within 48 hours, allowing reperfusion of the previously ischemic zone. This reperfusion frequently causes extravasation of blood through the disintegrated endothelial linings and hemorrhagic conversion of the ischemic lesions, so-called hemorrhagic infarction.

Recent advances in technology have improved the identification of previously unrecognized potential cardiogenic embolic sources and have documented the fact that a higher proportion of ischemic strokes than previously suspected are embolic in origin. Arrhythmias, especially atrial fibrillation and sick sinus syndrome, are important causes of brain embolism. Valvular disease--rheumatic, congenital, calcific, and bacterial and nonbacterial vegetations--is another very important donor source for embolism. Thrombi also form within the heart in patients with myocardial infarcts, myocardiopathies, ventricular aneurysms, and other diseases that cause endocardial and myocardial damage.

Atherosclerotic stenosis of the ICA or VA causes intraarterial thromboembolism when the thrombus formed on the ulcerative plaque dislodges and travels up to a distal intracranial cerebral artery. Usually emboli are composed of clot, platelet clumps, or fragments of plaques. Embolism is especially apt to occur just after a clot is formed, before it becomes organized and adheres to the arterial wall. Cholesterol crystals, fat, tumor, and foreign body material, particularly talc and cornstarch injected by drug abusers, are less frequent intra-arterial embolic materials. Another important source of intra-arterial embolism is atheromatous aortic plaques. Transesophageal echocardiographic studies have shown that protruding, often mobile and pedunculated, atheromas and clots can be found in the thoracic aorta and are a relatively common source of embolism. Angiography and cardiac surgery with clamping of the aorta promote embolism from aortic lesions.

A less common form of embolism, paradoxical embolism, occurs when the heart serves as a conduit for emboli arising from blood clots in the peripheral veins; these clots pass through septal defects, a patent foramen ovale (PFO), or pulmonary arteriovenous (AV) fistulas to reach the brain and systemic circulation. Because PFOs usually open during exertion, stroke frequently occurs during Valsalva maneuvers, exertion, and sexual intercourse.

Epidemiology and Risk Factors. At least 30 percent of ischemic strokes are caused by cardiogenic embolism. The lesions with the highest risk are probably atrial fibrillation, acute myocardial infarction with mural thrombosis, ventricular aneurysms, prosthetic heart valves, rheumatic heart disease with atrial enlargement, myocardiopathies, and bacterial and marantic endocarditis. Cardiac surgery now also poses an important risk of embolism from the heart and aorta.

Clinical Features and Associated Disorders. Brain embolism usually presents abruptly with clinical abnormalities. Fluctuations or worsening symptoms and sudden improvements are common during the first 24 to 48 hours, probably because of emboli passing distally. Usually embolic infarcts are large, and deficits are more severe in patients with emboli than with in situ occlusions. Single or infrequent but longer lasting TIAs may precede embolic infarctions. Embolic events often occur during activity or sudden straining, coughing, or sneezing. Infarcts may involve multiple vascular territories and are mixed in age. Early angiographic or TCD studies may show the presence of distal intra-arterial emboli. Hemorrhagic conversion of infarcted areas is commonly noted on CT and MRI scans. Infarcts are often wedge-shaped and involve the cerebral cortical surface.

Intra-arterial sources of cerebral embolism are usually atheromatous plaques at the carotid bifurcation, but occasionally responsible proximal vascular lesions are detected at the originating sites of the common carotid arteries or vertebral arteries from the subclavian arteries or aorta. Cardiac sources of emboli are listed in Table 45-2 .

Differential Diagnosis and Evaluation. Embolic strokes are often difficult to separate from in situ thrombosis engrafted on stenotic lesions and intracerebral hemorrhage. Patients with brain hematomas more often develop signs gradually, whereas embolic strokes often begin instantly and in about 80 percent of patients reach their maximum intensity at or near onset. Decreased consciousness, headache, and vomiting are more common acutely in patients with hematomas than in those with embolic infarction. Still, CT is most often needed to differentiate hematomas from ischemia.

In patients with pre-existing arterial stenotic lesions and superimposed acute thrombosis, preceding TIAs are common and may occur several times over a period of weeks or months. The region of ischemia is also smaller than it is in patients with embolism, and the signs tend to accumulate over a longer period of time, producing frequent fluctuations and stepwise changes in neurological signs.

Angiography performed in the first 12 hours shows emboli in a high percentage of cases, but after 48 hours most emboli are no longer detectable. The most common recipient arteries are the MCAs and ACAs in the anterior circulation and the VAs, distal basilar artery (BA), and PCAs in the posterior circulation. The clinical signs and imaging findings are the same as those described in the discussion of these vessels in the section on thrombotic stroke. In patients in whom brain embolism is suspected, the possible embolic sources should be evaluated to prevent further strokes. Evaluation of cardiac and aortic sources usually involves transesophageal echocardiography (TEE) and sometimes cardiac rhythm monitoring. Noninvasive vascular tests (ultrasound, MRA, CTA) can be used to evaluate arterial sources. TCD monitoring for embolic signals can help identify the presence of embolism and may suggest the source.

Management. Treatment of cerebral embolism consists of two major strategies: acute thrombolytic therapy to lyse the embolus and long-term prophylactic therapy to prevent recurrence of embolic stroke.

Thrombolytic therapy has usually been tried in patients with acute embolic stroke to recanalize the occluded artery, restore cerebral blood flow, reduce ischemia, and limit neurological disability. Recanalization may assist the recovery of reversibly ischemic tissue. Several thrombolytic agents have been tested in uncontrolled trials (urokinase, recombinant tissue plasminogen activator rt-PA, streptokinase) using either intra-arterial or intravenous administration. , So far the efficacy and safety of thrombolytic therapy have not been confirmed, but timely recanalization may benefit patients with acute thromboembolic stroke if it is started early enough. Two recent placebo-controlled studies using intravenous rt-PA have shown that thrombolytic therapy may be effective and relatively safe when it is started within 3 to 6 hours. , The most feared complication of this therapy is severe intracranial hemorrhage.

After an acute stroke the goal of treatment is to prevent the next embolus, using anticoagulation or removal of embolic sources. Cardiac sources may be corrected surgically. Usually intravenous heparin is used, followed by oral warfarin. Because it has been generally accepted that hemorrhagic complications are common in patients with large infarctions, early anticoagulation should be carefully monitored in such patients.

If a tightly stenotic carotid artery is present, either surgery (if feasible) or longer-term warfarin is indicated. When stenosis is not as severe, antiplatelet agents such as aspirin or ticlopidine may be used. Warfarin is effective in preventing embolism in patients with nonrheumatic atrial fibrillation. Warfarin also decreases the incidence of embolism in patients with rheumatic mitral stenosis and in those with mechanical heart valves. When warfarin anticoagulation is used, it is advisable to keep the international normalized ratios at around 3. , In older patients, long-term anticoagulation poses important risks and problems. Aspirin may be useful for prophylaxis in some patients with cardiac lesions of low embolic potential and in patients with absolute or relative contraindications to warfarin use.

Carotid artery stenosis is a very common source of intra-arterial embolism. Carotid endarterectomy has been used as a method of stroke prophylaxis, but there has been controversy about its safety and efficacy. Recent studies suggest that symptomatic carotid stenosis of 70 percent or more and asymptomatic carotid stenosis of 60 percent or more may be indications for carotid endarterectomy.

Prognosis and Future Perspectives. Prognosis depends on the nature of the potential embolic sources and the effectiveness of prophylaxis. The advent of monitoring for emboli with TCD technology has opened new diagnostic possibilities. Further advances in this technology with the use of multiple concurrent channels (such as EEG) will allow better recognition of the source and of the nature and frequency of release of embolic material.

 

TABLE 45-2 -- COMMON CARDIAC SOURCES OF EMBOLI

Coronary Artery Diseases

Myocardial infarcts

Ventricular aneurysms

Mural thrombi

Hypokinetic segments (focal and global)

Cardiomyopathies and Endocardiopathies

Endocardial fibroclastosis

Alcoholic cardiomyopathy

Cocaine cardiomyopathy

Myocardibs

Sareoidosis

Amyloidosis

Valvular Diseases

Mitral stenosis, rheumatic

Aortic stenosis, rheumatic

Bicuspid aortic valve

Mitral annulus calcification (MAC)

Calcific aortic stenosis

Mitral valve prolapse (MVP)

Bacterial endocarditis

Nonbacterial thrombotic (marantic) endocarditis--systemic lupus erythematosus (SLE)

Prosthetic valves

Arrhythmias

Atrial fibrillation and flutter

Sick sinus syndrome

Intracardiac Lesions, Defects, and Shunts

Myxomas

Fibroelastomas

Malignant cardiac tumors

Metastatic tumors

Ball-valve thrombi

Cardiac Chamber Abnormalities

Atrial and ventricular thrombi

Spontaneous contrast on echocardiography

Septal Abnormalities for Paradoxical Embolism

Atrial septal defects

Patent foramen ovale

Atrial septal aneurysms

Pulmonary arteriovenous fistulas

Modified from Caplan LR: Stroke. A Clinical Approach, 2nd ed. Boston, Butterworth-Heinemann, 1993.


Systemic Hypotension (Border Zone Infarction)

 

Pathogenesis and Pathophysiology. Inadequate pumping of the heart results in a lack of blood flow to the brain. This occurs when there is too little blood in the system (shock, hypovolemia), when the pump itself fails (myocardial failure or severe arrhythmia), or when systemic hypotension is present. Collateral blood flow is affected first by a generalized lowering of blood pressure. In contrast to thromboembolic stroke, hypoperfusion is global and causes so-called border zone or watershed infarcts in the areas between the major regions of vascular supply (see Fig. 45-1 (Figure Not Available) ). Infarcts are usually bilateral but may also occur unilaterally when there is severe stenosis of the ipsilateral proximal carotid or other large arteries. The most common area of border zone ischemia is in the temporoparietal region between the MCA and PCA supply regions.

Epidemiology and Risk Factors. Causes of stroke due to cerebral hypoperfusion include orthostatic hypotension (due to diabetic dysautonomia or antihypertensive therapy), orthostatic brain ischemia (without hypotension), perioperative complications (especially cardiac surgery), myocardial ischemia, cardiac arrhythmias, severe carotid stenosis or occlusion, or combinations of these.

Clinical Features and Associated Features. Faintness, pallor, dim vision, dim hearing and lightheadedness, dizziness, and lack of thought clarity are commonly noticed. The patient is worse when sitting or standing, and the blood pressure is low. Profuse sweating is common. Temporoparietal border zone ischemia most often causes visual abnormalities. Balint's syndrome is common and consists of asimultagnosia (difficulty in seeing multiple objects at one time), optic ataxia (abnormal hand-eye coordination in one or both visual hemifields), and apraxia of gaze (difficulty in directing the eyes where willed) . Ischemia in the anterior border zone between the anterior and middle cerebral arteries affects mostly the convexal surface of the precentral and postcentral gyri and causes arm and thigh weakness, usually with sparing of the face, feet, and often the hands. Occasionally patients have ischemia in the cerebellar border zones between the posteroinferior, anterior, and superior cerebellar arteries and have some gait and limb ataxia.

Differential Diagnosis and Evaluation. Frequently watershed infarction is diagnosed on the basis of one or more of the following: documented hypotension, a history of syncope or near-syncope preceding the event, and characteristic patterns of infarction on CT or MRI.

Orthostatic hypotension is defined as a persistent decline of greater than 20 mm Hg in systolic pressure from the supine to the standing position. Hypotension due to other causes is defined as systolic blood pressure of 90 mm Hg or less or at least a 25 percent drop from pre-existing levels. Symptoms of syncope, near-syncope, or cardiac arrhythmia should be sought. Laboratory tests include (1) systemic blood tests including CBC, blood urea nitrogen, and electrolytes; (2) cardiac studies--ECG, echocardiography, and Holter monitoring; and (3) neuroimaging--CT, MRI, and SPECT.

Management. Correction of underlying disorders is essential. Care should be taken when performing interventional procedures such as carotid endarterectomy or cardiac surgery. Excessive use of antihypertensive drugs should be avoided. Recurrences are common and, if not treated early, the outlook is poor. The mortality rate is around 10 percent, and there is a high incidence of myocardial infarction.

Selected Nonatherosclerotic Occlusive Diseases

NONINFLAMMATORY VASCULAR DISEASES

Fibromuscular dysplasia (FMD) is a rare condition that affects any or all of the three layers in the arterial walls of both extracranial and intracranial arteries, particularly those of the bilateral ICAs. FMD causes fibrous dysplastic tissue and proliferating smooth muscle cells in the media, presenting as constricting bands and a string-of-beads appearance on arteriography. ,

FMD is commonly found in middle-aged women and is most often asymptomatic. Because of its frequent association with cerebral aneurysms, FMD is often found during the evaluation of SAH. FMD also causes arterial dissections, producing ischemic stroke syndromes, but it may present as a TIA or stroke without any evident compromise of the vascular lumen, possibly due to functional constriction. The stroke recurrence rate is quite low, even with no therapy. If the patient is hypertensive, the renal arteries should be studied.

Moyamoya disease is defined as progressive occlusion of the intracranial ICAs at their intracranial bifurcations and formation of collateral channels through the basal penetrating branches of the cerebral arteries. Pathologically, this condition is characterized by endothelial hyperplasia and fibrosis with intimal thickening and abnormalities of the internal elastic laminas and arterial walls of the perforating arteries, probably due to greatly increased flow through these small vessels. Inflammatory changes are absent. Moyamoya vessels are also found in patients with sickle cell disease, neurofibromatosis, and FMD, and in young women (especially those who smoke cigarettes and take oral contraceptives).

Although the disease was first described in young Asians, it has subsequently been found to be widespread and is not limited to Asians. Clinically, children under 15 years of age usually present with transient episodes of hemiparesis, headache, seizures, or other focal neurological deficits, often precipitated by physical exercise or hyperventilation. In contrast, adults usually present with brain hemorrhages--usually in the thalamus, basal ganglia, or deep white matter. Occasionally the hemorrhages are SAH.

Cerebral angiography, the standard method of diagnosis, shows progressive abnormalities in the intracranial ICAs bilaterally. MCA and ACA branches are also frequently involved. Collateral vessels appear as a cloud of smoke. Recently, MRA has been used as a noninvasive alternative to conventional angiography in typical moyamoya disease.

Some patients with moyamoya disease stabilize clinically, often after they have developed disabilities. The best treatment is not known. A variety of surgical revascularization procedures called encephaloduro-arteriosynangiosis (EDAS) have been used, but whether they improve the outcome is now uncertain.

CEREBROVASCULAR DISEASES ESPECIALLY RELATED TO PREGNANCY

Oral contraceptive pills can be associated with stroke. Although the incidence of ischemic stroke is not much increased during pregnancy and the early puerperium, pregnancy does increase the risk of cerebral hemorrhage. The incidence rates for ischemic stroke associated with pregnancy vary from 5 to 210 per 100,000 deliveries. Ischemic strokes seem to be most common in the puerperal period and third trimester, with few cases occurring in the first trimester. Hypertension contributes independently to the risk of pregnancy-related stroke, especially in older women with chronic hypertension. Eclampsia is the main cause of both ischemic and hemorrhagic stroke. Eclampsia accounts for about half of ischemic strokes, and eclampsia-related ICH carries a poor prognosis. Stroke was responsible for 4.3 percent of maternal deaths in one major American study. Up to one third of pregnancy-related brain infarcts may be due to intracranial venous thrombosis. This condition is more frequent in the early postpartum period and in the third trimester. Dehydration, infection, and sepsis may contribute to venous thrombosis.

Patients with eclampsia present with focal neurological deficits of sudden onset in addition to headaches, seizures, or altered consciousness. These symptoms and signs usually resolve in several days. The precise pathogenesis of these short-lasting focal deficits associated with eclampsia is still poorly understood. Premature atheroma is causative in a quarter of strokes in pregnancy, but there are many other uncommon causes of ischemic stroke during pregnancy: amniotic embolism, choriocarcinoma, reversible postpartum cerebral angiopathy, arterial dissection, postpartum cardiomyopathy, paradoxical embolism, border zone infarction, use of ergot, pregnancy-related cardiac diseases, hematological disorders, antiphospholipid antibody syndrome, and homocystinuria. MRI and CT can confirm the location and nature of the brain lesions. For vascular imaging, MRA or ultrasound techniques are recommended. Prognosis is worse than in nonpregnant women or men of the same age.

Cerebral venous sinus thrombi are rich in red blood cells and fibrin but poor in platelets ("red thrombus") and are then replaced by fibrous tissue with time. Occlusion of a dural sinus often results in severe brain edema, venous infarction in the cortex, and adjacent white matter, while deep cerebral vein thrombosis causes venous infarcts in the basal ganglia, thalamus, or both. , The venous hypertension caused by blockage of blood draining from the skull can also lead to brain hemorrhages. Brain edema, ischemia, and hemorrhages result from extensive thromboses. The sagittal sinus is involved most often, followed by the lateral sinuses and the cavernous sinus.

Cerebral venous thrombosis (CVT) is an uncommon condition. Basic mechanisms of CVT include venous stasis, increased clotting tendency, and traumatic or infective changes in the venous walls. Various endocrine, hematological, immunological, vasculitic, infective, and neoplastic diseases may be associated with CVT. In neonates and children, regional infections (otitis media and mastoiditis), neonatal asphyxia, severe dehydrations, and congenital heart diseases are common associated diseases. In young women, pregnancy, puerperium, oral contraceptive pills, and various connective tissue diseases like systemic lupus erythematosus are the major causes. Other causes include malignancies, antithrombin III protein C and protein S deficiencies, and Behcalet's disease. ,

CVT has a variable mode of onset and usually has a favorable outcome. The most common symptom is headache. Head pain can be severe and persistent and is often due to increased intracranial pressure. Vomiting also results from increased pressure. Seizures and focal neurological symptoms and signs result from brain ischemia, edema, or hemorrhage. Clinical patterns include (1) isolated intracranial hypertension mimicking pseudotumor cerebri and presenting with headache, papilledema, and sixth nerve palsy; (2) focal neurological signs simulating arterial strokes or seizure attacks; and (3) a cavernous sinus syndrome. These syndromes usually resolve spontaneously. The dural venous sinuses may become recanalized after antithrombotic therapy. Poor prognostic factors include rapid evolution of thrombosis, coma, infancy or old age, involvement of deep veins and cerebellar veins, and septic thrombi.

Differential diagnoses include benign intracranial hypertension ("pseudotumor cerebri"), migraine, meningitis, encephalitis, cerebral infarction (arterial), ICH, brain abscess, brain tumor, and eclampsia. Diagnosis is based on clinical data, CT or MRI, and conventional and MRI venographic findings. Venous infarcts appear as unilateral or bilateral or single or multifocal on CT or MRI. Hemorrhagic infarction and small hematoma are commonly found because of the increased pressure in draining veins.

Management of patients with CVT includes reducing ICP and administering anticoagulant therapy, thrombolytic therapy, and antibiotics in case of an infected thrombus. Intravenous heparin followed by warfarin is indicated. Steroids and osmotic diuretics are used in patients with brain edema or increased intracranial pressure. Anticonvulsants are given for seizures due to venous infarcts. Review of the published experience of patients with dural sinus thrombosis shows a clear and definite improvement in outcome in patients treated with anticoagulants. , Even in patients who had hemorrhagic infarction of hematomas before treatment, anticoagulation led to fewer new hemorrhages and better outcomes than occurred in patients not given anticoagulant treatment. Thrombolytic treatment given by inserting a catheter into or adjacent to the occluded sinus has also been successful, but often high doses are needed for a prolonged period of time.

If left untreated, CVT is potentially life-threatening. Recent reports attributed better outcomes to greater awareness of CVT, noninvasive imaging techniques, and a relative decline of infective etiologies. Among survivors only a minority develop a permanent deficit such as focal limb weakness, epilepsy, or optic atrophy.

Arterial dissection, especially spontaneous dissection of the cervicocranial arteries, is an important cause of ischemic strokes, especially in young people. The pharyngeal portion of the extracranial ICA and the first and third segments of the VA are more mobile and thus more vulnerable to trauma and mechanical stress. ,

, , Congenital changes in the media or elastic layer of the arteries and edema of the arterial wall also promote dissection.

A tear within the arterial wall leads to bleeding, which dissects along the longitudinal course of the artery. The dissection can also produce an intimal tear, allowing the blood clot within the media to reenter the lumen. The expanded arterial wall encroaches on the lumen. Clot formed in the lumen is usually loosely adherent to the intima and can readily embolize distally and cause brain infarction. The intraluminal clot is absorbed within several weeks, and the lumen usually returns to its normal size. Aneurysmal pouches may remain as a mark of the healed lesion. When dissections extend between the media and the adventitia, both aneurysms and tears through the adventitia may lead to SAH or aneurysmal masses, presenting as space-occupying lesions that compress adjacent cranial nerves or brain parenchyma.

Dissections usually occur in young people, although they can develop at any age. Individuals with inherited disorders of connective tissue such as Marfan's disease, Ehlers-Danlos syndrome, and pseudoxanthoma elasticum are susceptible. Migraine and fibromuscular dysplasia also make the vascular walls more susceptible to tearing. Chiropractic manipulation of the neck and sports and other activities that involve sudden neck stretching or, alternatively, prolonged holding of the neck in an eccentric position promote dissections.

Carotid dissection usually causes ipsilateral throbbing headache; local sharp pain in the neck, jaw, pharynx, or face; or an ipsilateral Horner's syndrome. TIAs are common and are probably due to luminal compromise with distal hypoperfusion, but most patients with severe strokes have evidence of embolization of blood clot to the MCA from thrombus at the site of dissection. In carotid dissections, strokes usually occur within the first few days after the ICA dissection. At times, both carotid arteries and even the VAs are dissected at the same time. Recurrent dissection is rare.

Pain in the neck and head are important symptoms in patients with dissections that help to separate this entity from other causes of brain ischemia. Subarachnoid hemorrhage also is a consideration in some patients.

CT and MRI can directly visualize the intramural bleeding and expansion, confirming the diagnosis. Conventional angiography, MRA, and ultrasound testing are reliable noninvasive diagnostic and monitoring tools for the detection of arterial dissections. ,

, MRA is a reliable noninvasive method for use in diagnosis and follow-up of extracranial ICA dissections, but conventional angiography is more useful for VA dissections. Angiography may show regions of severe narrowing ("string sign"), or the ICA may be totally occluded, beginning more than 2 cm distal to the ICA origin, sparing the siphon, and having a gradually tapering segment. Localized aneurysmal sacs or outpouchings may be seen. B-mode ultrasound testing can show tapering of the ICA lumen, an irregular membrane crossing the lumen, and true and false lumens. Duplex scans of the VAs in the neck can show increased arterial diameter, decreased pulsatility, intravascular abnormal echoes, and hemodynamic evidence of decreased flow. TCD demonstrates the effect of the neck pathology on the poststenotic intracranial circulation, including collateral blood flow. TCD may show diminished intracranial velocities in the ICA siphon and the MCAs or the ICVAs. When this occurs in young patients without risk factors for atherosclerosis or embolism who have normal ICA bifurcations in the neck, the diagnosis of dissection is quite likely.

Most extracranial dissections heal spontaneously with time. Their location high in the neck usually makes surgical repair difficult or impossible. When complete occlusion has occurred, the arteries often do not recanalize, and they remain occluded. Arteries that retain some residual lumen invariably heal and become normal. Intracranial dissections can be repaired surgically in those patients with SAH. Although there have been no controlled trials of medical therapy, prevention of embolization of clot at or shortly after the dissection should prevent stroke. Anticoagulants do not seem to increase the extent of the dissection. Because the risk of embolization exists only during the acute period, intravenous administration of heparin followed by warfarin may be effective and is continued until the lumen is not severely compromised.

Most patients with dissections who will develop strokes do so shortly after the onset of symptoms. Late strokes are unusual. Recurrence is also rare, occurring in only about 7 percent of patients with dissection. Most research on vascular disease has concerned intimal and endothelial abnormalities such as atherosclerosis, and the media of vessels has been given very scanty attention. Subtle abnormalities of connective tissue including smooth muscle, elastic tissue, and collagen may predispose to dissection. Further research on vascular connective tissue and muscle will help in gaining a better understanding of arterial dissections and fibromuscular dysplasia, two conditions that sometimes coexist.

INFLAMMATORY VASCULAR DISORDERS

Table 45-3 outlines some of the important vasculitides and their key features.

 

 

TABLE 45-3 -- SOME IMPORTANT VASCULITIDES

Condition

Demography

Pathology Vessel Type

Clinical Environment

Other Features

Polyarteritis nodosa

1:2.5 f/m ratio; 30 to 50 years old

Necrotizing, small-medium muscular arteries

Strokes; kidney, peripheral nerves

Fever, hypertension, circulating immune

Churg-Strauss syndrome

1:1.4 f/m ratio; 10 to 50 years old

Fibrinoid necrosis with eosinophils; small-medium arteries, veins, capillaries

Asthma; skin, kidney, encephalopathy, peripheral nerves

Eosinophilia, fever, rhematoid factor

Hypersensitivity vasculitis

Any age and sex

Leukocytoclastic vasculitis, postcapillary venules

Peripheral nerves and plexus, encephalopathy, palpable purpura

Drug-induced cryoglobulins, circulating immune complexes

Wegener's granulomatosis

1:1.2 f/m ratio; any age

Granulomas in organs, necrotizing arteritis

Sinuses, respiratory tract, kidneys, cranial and peripheral nerves

cANCA-positive; upper and lower respiratory tract involvement

Sarcoidosis

20 to 30 years old; no sex predilection, blacks > whites

Perivenous, granulomas

Peripheral nerves, muscle, eyes, lungs, skin, lymph nodes, brain granulomas

Granulomas in skin, muscle, liver, nodes

Temporal arteritis

1:2 to 1:3 f/m ratio; >50 years

Segmental granulomatous, external carotid, and aortic branches

Eyes, peripheral nerves, occasional strokes

High ESR, jaw claudication, scalp tender

Isolated CNS angiitis

1:2 f/m ratio any age

Mononuclear perivascular cell, granulomas

Brain only, seizures, confusion

High CSF protein, no systemic symptoms

Takayasu's arteritis

9:1 f/m ratio; Asians; age range 15-40 yr

Acute inflammatory giant cell; large arteries of aortic arch

Syncope, light-headedness, headache, absent arm pulses (strokes rare)

Systemic symptoms, hypertension

Behcets disease

1:9 f/m ratio; Japan and Mediterranean heritage

Perivascular cell loss and demyelinization, perivascular plasma cells and lymphocytes

Aphthous oral ulcers, genital ulcers, eye inflammation, meningitis, brain stem lesions

Strokes and meningoencephalitis with focal brain stem lesions

Cogan's disease

Young adults

Arteritis of small and medium-sized arteries

Interstitial keratitis of eye, uveitis, ear involvement

Vertigo, tinnitus, decreased hearing, cornea opacification

Eales' disease

Mostly young men, aged 20 to 30 years old; middle East and Indian heritage

Inflammation of retinal arteries and veins

Retinal and vitreous hemorrhages, meningitis, occasional brain and spinal cord infarcts

Characteristic sheathing of retinal arteries and veins and vitreous hemorrhages

Microangiopathy of the brain, retina, ear

Almost always women, 15 to 30 years old

Obliterative, noninflammatory arteries and arterioles

Retina, ear, brain

High CSF protein

Kohlmeier-Degos syndrome

Young adults 15 to 30 years old

Fibrous vascular proliferation, rare inflammation

Small yellow-raised skin lesions, GI tract, brain infarcts

Skin, GI, and brain infarcts

Sneddon's disease

Females > males; age 30 to 50

Proliferative thrombo-occlusive disease of skin and brain and small arteries and arterioles

Livedo reticularis of skin and brain infarcts

Antiphospholipid antibodies common

cANCA, Classic antineutrophil cytoplasmic antibody; CSF, cerebrospinal fluid; ESR, erythrocyte sedimentation rate; f/m, female-to-male; GI, gastrointestinal.

 

DRUG-RELATED VASCULOPATHIES

Illicit drug use and abuse has unfortunately become an important cause of stroke, especially in young individuals. Table 45-4 outlines the common drugs implicated and some features of the strokes that they cause.

MIGRAINE-RELATED STROKE

Stroke is a rare but potentially devastating complication of migraine. , Infarction is thought to be due to prolonged intense vasospasm associated with migraines. Intense vasospasm can impede flow, promoting thrombosis. Platelets are activated during migraine and the vasoconstrictive process itself may stimulate the endothelium to release factors that promote thrombosis. Severe vasoconstriction and thrombi have been demonstrated in patients with migraine who have PCA and basilar artery territory infarcts. ,

To complicate matters, atherosclerotic lesions in the coronary arteries of humans--and in the extracranial and retinal arteries of experimental animals--seem to predispose them to superimposed vasoconstriction. Thus, vasoconstriction can complicate atherostenosis. TCD shows promise of identifying vasoconstriction by showing high velocities that change with time and with various pharmacological treatments.

Hemorrhage can occasionally complicate a severe migraine attack. Intense vasoconstriction leads to ischemia of a local brain region, accompanied by edema and ischemia of the small vessels perfused by the constricted artery. Then, when vasoconstriction abates, blood flow to the region is augmented, and the reperfusion can cause hemorrhage from the damaged arteries and arterioles. The mechanism is the same as that found in hemorrhage after carotid endarterectomy and in reperfusion after brain embolization.

Prophylactic agents (most often calcium channel blockers, cyproheptadine, or methysergide) should be maintained as well as agents that modify platelet function and coagulation. Aspirin may be prescribed, but warfarin can be used in patients with prior infarcts.

 

 

TABLE 45-4 -- DRUG ABUSE AND STROKES

Drug

Route

Ischemia

Hemorrhage

Other Features

Heroin

IV

Strokes--brain and spinal cord

No

Increased gamma globulins

Amphetamines

Oral, IV

No ischemic strokes

SAH, ICH; aneurysms and AVMs rare

Hypertension

Cocaine HCI

Nasal, IV

Ischemic strokes

SAH and ICH; aneurysms and AVMs common

Hypertension

Crack cocaine

Nasal, IV

Ischemic strokes very common

SAH and ICH; aneurysms and AVMs common

Hypertension

Mashed pills

IV

Ischemic strokes

No

Tale particles in eyes and lungs

SAH, Subarachnoid hemorrhage; ICH, intracerebral hemorrhage; AVM, arteriovenous malformation.


Coagulation Disorders

Brain ischemia and hemorrhage often result from hematological disorders.

Changes in the formed cellular constituents of the blood may be quantitative or qualitative. Polycythemia increases blood viscosity, decreases cerebral blood flow, and increases the risk of thrombosis. Sickle-cell disease and sickle-cell hemoglobin-C disease are examples of qualitative red blood cell abnormalities that affect blood flow. Sickle-cell disease causes occlusive changes in large intracranial arteries and small penetrating vessels. Subcortical, cortical, and borderzone infarcts are often found on CT and MRI.

Increased platelet counts, especially those over 1 million, are associated with hypercoagulability. Thrombocytosis can be primary (so-called essential thrombocythemia), can be associated with other myeloproliferation, or less often, can be secondary to systemic disease. Essential thrombocythemia is associated with strokes and digital arterial occlusions. There are also qualitative abnormalities of platelet function. In some patients, increased coagulability has been attributed to increased adhesion and aggregation of platelets (so-called sticky platelets) in the absence of thrombocytosis.

Leukemia is complicated occasionally by brain hemorrhages and microinfarcts. When the white blood cell count is very high (increased leukocrit), the white blood cells can pack capillaries, leading to microinfarcts and vascular rupture with small hemorrhages in the brain. Larger intraparenchymatous hemorrhages and SAHs are most often related to thrombocytopenia, due to replacement of the bone marrow with leukocyte precursors.

Abnormalities of the coagulation cascade can also cause hypercoagulability and lead to venous and arterial occlusions and brain infarction. Table 45-5 lists some of the most common abnormalities.

Immunological Abnormalities

Circulating antibodies, like lupus anticoagulant (LA) and anticardiolipin antibodies, may be related to stroke. The LA is a phospholipid antibody that interferes with the formation of the prothrombin activator. In the laboratory, there is a prolonged activated partial thromboplastin time (PTT). Some patients with LA have SLE, but most do not. When antiphospholipids of the IgG, IgM, or IgA classes are found in the absence of a known systemic illness, and patients present with an increased incidence of spontaneous abortions, thrombophlebitis, pulmonary embolism, and large- and small-artery occlusions, the disorder is now referred to as primary antiphospholipid lupus anticoagulant (APLA) syndrome. The APLA-associated stroke syndrome is characterized by its younger age at onset, predominance in women, and high risk of recurrent thrombo-occlusive events. Some patients have mitral and aortic valve vegetations and ocular ischemia. In addition to the presence of LA or anticardiolipins, or both, laboratory abnormalities include false-positive Venereal Disease Research Laboratory (VDRL), thrombocytopenia, antinuclear antibodies, and prolonged activated PTT. The risk of recurrent thrombosis in patients with the antiphospholipid-antibody syndrome is high. More than one-half of the patients have at least one recurrent thrombo-occlusive stroke, most occurring within the first year. Long-term anticoagulation therapy is recommended, maintaining the international normalized ratio at or above 3.

Disseminated intravascular coagulation occurs when a primary disorder leads to local or diffuse clotting and the coagulation cascade is activated, with generation of excess intravascular thrombin. The coagulation system then is activated further, fibrin is deposited into the microcirculation, hemostatic elements have a shortened survival, and the fibrinolytic system is activated. The most common disorders inciting disseminated intravascular coagulation are infections, obstetric and vascular emergencies, cancer, nonbacterial thrombotic endocarditis, head trauma, SAH, brain tumors, and vascular malformations. The laboratory findings usually include thrombocytopenia, reduced fibrinogen levels, prolongation of prothrombin time (PT) and PTT, and increased levels of fibrin split products. Neurological findings are frequent and include an encephalopathy with multifocal signs and frank thrombotic and embolic infarcts. Bleeding can also occur. ,

Whole blood viscosity is one of the major determinants of cerebral blood flow, especially in the microcirculation. Whole blood viscosity is very dependent on the hematocrit and fibrinogen levels, and these are often elevated in patients with stroke. Hyperviscosity also is probably pathogenetically related to Binswanger's disease (subcortical arteriosclerotic encephalopathy). Less often, viscosity is increased by high levels of globulins as in Waldenstrom's macroglobulinemia or in other disorders with abnormal proteins or cryoglobulins, such as multiple myeloma, or by very high levels of serum lipids, especially chylomicron.

Thrombotic thrombocytopenic purpura is characterized clinically by fever, renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. Transient focal neurological signs and a more diffuse encephalopathy are common, but occasionally, persistent neurological deficits due to occlusion of medium-sized arteries or brain hemorrhages occur. Plasma exchange can be an effective treatment.

 

TABLE 45-5 -- SOME COMMON COAGULATION DISORDERS CAUSING HYPERCOAGULABILITY

1. Deficiencies of natural coagulation inhibitors

Antithrombin III

Protein C

Protein S

2. Resistance to activated protein C

3. Increased levels of serine protein coagulation factors (can occur in patients with inflammatory diseases), factors V, VII, and VIII

4. Cancer, especially mucinous adenocarcinomas

5. Abnormalities of the normal fibrinolytic system

Tissue plasminogen activator (t-PA)

Plasminogen activator inhibitor (PAI)

6. Dysfibrinogenemias including increased levels of fibrinogen

 

 

HEMORRHAGIC CEREBROVASCULAR DISEASE

Primary Intracerebral Hemorrhage

Pathogenesis and Pathophysiology. Chronic hypertension causes fibrinoid necrosis in the penetrating and subcortical arteries, weakening of the arterial walls, and formation of small aneurysmal outpouchings, so-called Charcot-Bouchard microaneurysms, that predispose the patient to spontaneous ICH. Bleeding usually arises from the deep penetrating arteries of the circle of Willis, including the lenticulostriate, thalamogeniculate, and thalamoperforating arteries and perforators of the basilar artery. Acute rises in blood pressure and blood flow can also precipitate ICH even in the absence of preexisting severe hypertension. A ruptured vascular malformation is the second most common cause of ICH.

Bleeding is limited by the resistance of tissue pressure in the surrounding brain structures. If a hematoma is large, distortion of structures and increased intracranial pressure (ICP) cause headache, vomiting, and decreased alertness. Because the cranial cavity is a closed system, enlargement of hematoma or development of severe edema may shift brain tissues into another compartment, so-called herniation, and cause deterioration in the clinical condition.

Epidemiology and Risk Factors. ICH is a major cause of morbidity and death and accounts for 10 to 15 percent of all strokes in whites and about 30 percent in blacks and individuals of Asian origin. Pregnancy may increase the risk of ICH. Eclampsia accounts for more than 40 percent of ICHs in pregnancy and is a common cause of death from eclampsia. Locations of hypertensive ICHs are putamen (40 percent), lobar (22 percent), thalamus (15 percent), pons (8 percent), cerebellum (8 percent), and caudate (7 percent).

Spontaneous ICH can also occur in association with bleeding diatheses, especially the prescription of anticoagulants, primary or metastatic brain tumors or granulomas, and use of sympatheticomimetic drugs. Aneurysms rarely bleed only into the brain, causing a local hematoma near the brain surface.

Clinical Features and Associated Disorders. Hematomas are often classified as putaminal, thalamic, caudate, lobar, pontine, or cerebellar, and each has its specific neurological features in addition to the symptoms and signs of sudden increased ICP. Even hematomas arising in the same anatomical location may present different clinical features and prognosis because they differ in size, intraregional location, direction of intraparenchymal extensions, and presence of ventricular hemorrhage.

The earliest signs relate to blood issuing into parenchymatous structures. For example, a hematoma in the left putamen and internal capsule would first cause weakness of the right limbs while a cerebellar hematoma would cause gait ataxia. As the hematomas enlarge the focal symptoms increase. If the hematoma becomes large enough to raise intracranial pressure, then headache, vomiting, and decreased alertness develop. Some hematomas remain small and the only symptoms relate to the focal collection of blood. Table 45-6 notes the most important features of hematomas at the most common sites. This material is discussed in detail elsewhere and in another section of this book.

Differential Diagnosis and Evaluation. Diagnostic considerations include infarcts in similar regions and subdural and epidural hematomas. Rarely, brain tumors and abscesses can have a rapid onset mimicking ICH.

It is very important to identify the cause of the hemorrhage. Hypertension, bleeding diatheses (especially as a result of iatrogenic prescription of coumadin), trauma, and amyloid angiopathy are the most frequent causes. In young normotensive patients, especially those with lobar and intraventricular hemorrhages, vascular malformations are the most likely source of bleeding. Aneurysms can also rarely bleed directly into brain parenchyma. Some primary and metastatic brain tumors, especially renal carcinoma and choriocarcinoma, have a propensity to develop hemorrhages within the tumor, thus causing an abrupt onset or worsening of neurological symptoms.

During the initial evaluation, blood samples for basic laboratory studies including CBC, chemistries, coagulation studies (prothrombin time, PTT, bleeding time, and platelet count), arterial blood gas analysis, toxicology screen, and arterial blood gases are obtained.

The CT scan is an essential tool for diagnosis, management, and follow-up of ICH. It accurately documents the size and location of the hematoma, the presence and extent of any mass effect, and the presence of hydrocephalus and intraventricular hemorrhage. CT scans should be performed immediately in patients suspected of having an ICH. Follow-up CT scans are requested when there is a change in clinical signs or state of alertness in order to monitor changes in the size of the lesion and ventricular system and to detect important pressure shifts. If the clinical syndrome and CT findings are typical of hypertensive

hemorrhage in the basal ganglia, caudate nucleus, thalamus, pons, or cerebellum, angiography is usually not necessary. If the hemorrhage is in an atypical location or the patient is young and not hypertensive, angiography is indicated to exclude an AVM, aneurysm, vasculitis, or tumor. Patients who have ICH after cocaine use have a high likelihood of vascular malformations and aneurysms and need angiography.

Management. Prompt and careful management of patients with ICH may be life saving and is important even in those who will later undergo surgical intervention. Adequate airway and respiratory support should be established. Blood gases should be measured in patients with reduced alertness. Endotracheal intubation is performed for patients presenting in coma, for those who are unable to protect their airway, and for those who have respiratory failure. Wide swings in blood pressure, especially hypertension, are common in the initial period following hemorrhage. Intravenous labetalol or sodium nitroprusside with concomitant intra-arterial pressure monitoring is an effective method of controlling such elevations. Continuous cardiac monitoring for arrhythmias is important. Hypotension, however, from cardiac or other etiologies can be devastating due to the impact on cerebral perfusion pressure. Control of local tissue pressure and intracranial pressure (ICP) is also important to guarantee adequate cerebral perfusion pressure. The available medical and surgical treatment modalities are outlined in Table 45-7 . They are not competitive, but a combined approach utilizing both medical and surgical modalities will often yield satisfactory results. ,

Emergency surgical treatments have been tried for several decades. Early studies showed that there was no value in surgical removal of hematomas over standard medical management. More recent studies of hematoma removal have shown promise for open surgical decompression, but only if it is accomplished early after the onset of symptoms. The best candidates for surgery may be patients with moderate to large hematomas who are still awake. Recent advances in neuroimaging techniques have made it possible to drain hematomas percutaneously, using stereotactic surgery.

A burr hole is made, and the drainage instrument is guided stereotactically, using CT, to the core of the hematoma, which is then evacuated. Fibrinolytic agents also can be instilled to soften and lyse coagulated hematomas. As yet, there is too little experience to allow comparison of open versus stereotactic drainage of hematomas although stereotactic surgical aspiration of ICH is probably safe and is promising. ,

Prognosis and Future Perspectives. Survival depends on the size and rapidity of development of the hematoma. ICHs are at first soft and dissect along white matter fiber tracts. If the patient survives the initial changes in ICP, blood is absorbed and a cavity or slit forms that may disconnect brain pathways. Patients with small hematomas located deep and near midline structures often suffer from secondary herniation and mass effect, and these patients have a high mortality rate. Survivors invariably have severe neurological deficits. In patients with medium-sized hematomas, the deficit varies with the location and size of the hematomas. Most patients survive with some residual neurological signs.

Recent studies show that ischemic pressure damage develops around the hematomas in ICH. This finding implies the necessity of new treatment strategies in the future. The recent development of stereotactic surgical aspiration is promising.

 

TABLE 45-6 -- SIGNS IN PATIENTS WITH INTRACEREBRAL HEMORRHAGES AT VARIOUS SITES

Location

Motor/Sensory

Eye Movements

Pupils

Other Signs

Putamen or internal capsule

Contralateral hemiparesis and hemisensory loss

Ipsilateral conjugate deviation

Normal

Left: aphasia

Right: left-sided neglect

Thalamus

Contralateral hemisensory loss

Down and in upgaze palsy

Small, react poorly

Somnolence, decreased alertness; left: aphasia

Lobar

 

 

 

 

Frontal

Contralateral limb weakness

Ipsilateral conjugate gaze

Normal

Abulia

Temporal

None

None

Hemianopia

Left: aphasia

Occipital

None

None

 

Hemianopia

Parietal

Slight contralateral hemiparesis and hemisensory loss

 

 

Hemianopia; left: aphasia; right: left neglect; poor drawing and copying

Caudate

None or slight contralateral hemiparesis

None

Normal

Abulia, agitation, poor memory

Pons

Quadriparesis

Bilateral horizontal gaze paresis,

Small; reactive ocular bobbing

Coma

Cerebellar

Gait ataxia, ipsilateral limb hypotonia

Ipsilateral gaze or sixth nerve paresis

Small

Vomiting, inability to walk, tilt when sitting


 

TABLE 45-7 -- TREATMENT OF INTRACEREBRAL HEMORRHAGE

Medical

Medical decompression for increased intracranial pressure

Intubation and mechanical hyperventilation

Dexamethasone (Decadron), 4 mg every 6 hours

Mannitol, 0.5 to 1 g/kg every 4 hours intravenously (IV)

Glycerol, 1 to 1.5 ounces orally every 6 hours

Furosemide (Lasix), 40 mg (4 mg/min) IV*

Control of hypertension

Labetalol, 10 mg IV, followed by 10-mg doses as needed

Trimethaphan camsylate (Arfonad), 0.5 to l mg/min IV by drip

Nitroprusside sodium, 15 to 200 mug/min

Hydralazine hydrochloride (Apresoline), 50 to 100 mg twice daily orally

Reversal of bleeding diathesis

Fresh frozen plasma

Antihemophilic factor

Phytonadione (vitamin K, AquaMEPHYTON) 20 to 40 mg IV

Platelet transfusion

Fresh blood transfusion

Surgical

Drainage of hematoma--stereotactic drainage or surgical evacuation

Ventricular drainage or shunt

Removal of bleeding arteriovenous malformation or tumor

Repair of aneurysm

*FDA approved for this indication.

Modified from Chung C-S, Caplan LR: Parenchymatous brain hemorrhage. In Rakel RE (ed): Conn's Current Therapy Philadelphia, WB Saunders. 1995, p 794.



Subarachnoid Hemorrhage (SAH)

SAH is a common and often devastating condition. Despite considerable advances in diagnostic, surgical, and anesthetic techniques and perioperative management, the outcome for patients with SAH remains poor.

Pathogenesis and Pathophysiology. SAH is most often caused by leakage of blood from abnormal blood vessels on the surface of the brain resulting in aneurysms and vascular malformations. Aneurysms, often referred to as berry or congenital, are outpouchings on arteries probably caused by a combination of congenital defects in the vascular wall and degenerative changes. Aneurysms usually occur at branching sites on the large arteries of the circle of Willis at the base of the brain. When an aneurysm ruptures, blood is released under arterial pressure into the subarachnoid space and quickly spreads through the CSF around the brain and spinal cord. Aneurysms are less often caused by arterial dissection through the adventitia of arterial walls, embolism of infected or myxomatous material to the vasa vasorum of distal cerebral arteries (mycotic aneurysms), and degenerative elongation and tortuosity of arteries (dolichoectasia).

Vascular malformations (AVMs) are the second most common identifiable cause of nontraumatic SAH, accounting for approximately 10 percent of SAHs. Rupture of AVMs often causes ICH and SAH. Bleeding of AVMs is usually less vigorous and under less pressure than aneurysmal bleeding. Other less frequent causes of SAH include bleeding diatheses, trauma, bleeding into meningeal tumors, and the use of sympathomimetic drugs such as methamphetamine and cocaine. Amyloid angiopathy is an important cause of SAH during the geriatric years.

Epidemiology and Risk Factors. SAH is a significant cause of worldwide morbidity and mortality, predominantly among young adults of both sexes. Population-based incidence rates for SAH vary from 6 to 16 per 100,000, with the highest rates reported in Finland and Japan. The annual prevalence of aneurysmal SAH in the United States probably exceeds 30,000 persons. Unlike other stroke types, the incidence of SAH has not declined over time.

The incidence of SAH increases with age (mean age of approximately 50 years) and is higher in women than in men. Blacks are at higher risk than whites. Population-based mortality rates for SAH have progressively declined, and the survival rate after SAH has improved since the 1970s. The risk of SAH is increased during the third trimester of pregnancy. SAH due to aneurysm rupture is a leading cause of maternal mortality, contributing to between 6 and 25 percent of maternal deaths. Significant risk factors for SAH include smoking, hypertension, and heavy alcohol use. Use of oral contraceptives, hormone replacement therapy, hypercholesterolemia, and physical activity are not significantly related. During pregnancy, there is also a greater risk of AVM rupture ,

Clinical Features and Associated Disorders. A sudden increase in ICP and meningeal irritation cause sudden severe headache, cessation of physical and intellectual activity, vomiting, and alteration of consciousness. Drowsiness, restlessness, and agitation are especially common. Severe focal neurological signs such as hemiplegia and hemianopia are absent at onset unless the aneurysm also bleeds into the brain. Expanding aneurysms or focal surrounding collections of blood within the cisterns and sub-arachnoid space can affect the cranial nerves and adjacent brain structures, causing characteristic focal features that depend on the location of the aneurysm. Table 45-8 lists these common focal signs. SAH commonly causes various complications, which are discussed later in association with the management of patients with SAH.

Patients with fibromuscular dysplasia, polycystic kidney disease, and connective tissue diseases have a higher incidence of aneurysms. Embolization of bacteria, fungi, and tumor tissue to the adventitia of cranial arteries can cause mycotic aneurysms. Endocarditis and cardiac myxomas are the usual causes. About one fifth of patients with aneurysms have more than one vascular anomaly or other aneurysms.

Differential Diagnosis and Evaluation. Severe migraine and meningitis are the major differential diagnostic considerations. Sometimes only lumbar puncture can settle separation of these three disorders.

History taking and neurological examination are the essential core of the diagnosis of SAH and of grading the clinical status. A CT scan that is performed within the first 24 hours shows approximately 95 percent of all SAH cases and is also useful in detecting increased intracerebral density in large AVMs. When the diagnosis of SAH is highly likely clinically but the CT scan is normal, a lumbar puncture to detect blood in the CSF is necessary. After the diagnosis of SAH has been made, cerebral angiography is performed to define and localize aneurysm(s).

Management. Management of patients with SAH is directed to prevent and manage relatively common complications of SAH, such as rebleeding, vasospasm, hydrocephalus, hyponatremia, and seizures.

Rebleeding may be related to variations or changes in blood pressure rather than to absolute blood pressure. Bed rest, analgesics to relieve headache, and stable maintenance of blood pressure using antihypertensive medications in hypertensive patients are generally recommended. Because antifibrinolytic therapy has been found to be associated with a higher risk of brain ischemia and no benefits in overall outcome, use of antifibrinolytic agents is usually recommended only in certain clinical situations, for example, patients with low risk of vasospasm or a beneficial effect of delaying surgery. Early surgical clipping of the aneurysm is the method of choice, but interventional endovascular occlusive procedures are occasionally used for surgically unclippable aneurysms.

Cerebral vasospasm is the delayed narrowing of large capacitance arteries at the base of the brain after SAH, which is often associated with radiographic or cerebral blood flow evidence of diminished brain perfusion in the territory of the constricted arteries. About one half of patients with SAH have vasospasm, which may resolve or progress to cerebral infarction, and 15 to 20 percent of such patients die from vasospasm despite maximal therapy. Angiographic vasospasm has a typical temporal course: onset between 3 to 5 days after hemorrhage, maximal narrowing at 5 to 14 days, and gradual resolution over 2 to 4 weeks. Oral nimodipine is recommended to reduce poor outcome related to vasospasm. Other calcium antagonists administered orally or intravenously are of uncertain value. So-called triple H therapy composed of hypertension, hypervolemia, and hemodilution is recommended. Aneurysms should be clipped when possible, and patients receiving this therapy should be closely monitored in an intensive care setting for hemodynamic function using TCD. The value of intracisternal fibrinolysis and antioxidant and anti-inflammatory agents are uncertain. Transluminal angioplasty is recommended for treatment of vasospasm in patients in whom conventional therapy has failed.

Acute obstructive hydrocephalus after SAH complicates about 20 percent of cases. Ventriculostomy is recommended in severe cases, although there may be associated increased rebleeding and infection. Chronic communicating hydrocephalus also occurs frequently. Temporary or permanent CSF diversion is recommended in symptomatic patients. In many patients, hydrocephalus and increased subarachnoid fluid can be managed by repeated lumbar punctures.

Hyponatremia occurs in 10 to 34 percent of cases after SAH. Hypotonic fluids should be avoided, and fluid restriction should not be instituted to treat hyponatremia. Volume should be maintained using isotonic solutions.

Seizure-like episodes occur in 25 percent of patients after SAH. Because of the potential risk of rebleeding, some recommend the administration of prophylactic anticonvulsants. The long-term use of anticonvulsants is not routinely recommended for patients with no seizure episodes and should be considered only for patients with risk factors such as prior seizure, hematoma, infarcts, or middle cerebral artery aneurysms.

During pregnancy, the management options after SAH are early clipping or delivery (spontaneous or by cesarean section), with a possible risk of rebleeding during delivery when aneurysms are unclipped. Cesarean section may be appropriate for patients with an acute hemorrhage who are near term, but management is otherwise similar to nonpregnant patients. Craniotomy and clipping have been successfully archived at all stages of pregnancy. No difference is present in prognosis between pregnant and nonpregnant patients with SAH.

Reduction of exposure to the risk factors for SAH might result in a decreased incidence of SAH. Treatment of hypertension with antihypertensive medication, cessation of smoking, and moderation of alcohol use reduces the risk of SAH. Screening of certain high-risk populations for unruptured aneurysms is of uncertain value. Advances in MRA may facilitate screening in the future. In patients with acceptable surgical risk, clipping of unruptured aneurysms larger than 5 to 7 mm is often recommended.

Prognosis and Future Perspectives. At times, the initial bleeding is so severe that death or irreversible brain damage occurs. If the bleeding is limited, the patient survives but is at risk for rebleeding in the days and weeks after the initial SAH. For untreated, ruptured aneurysms, there is a 3- to 4-percent risk of rebleeding in the first 24 hours, 1- to 2-percent per day risk in the first month, and a long-term risk of 3 percent per year after 3 months. Urgent evaluation and treatment of patients with suspected SAH is strongly recommended.

Many recent advances in endovascular treatment of aneurysms and AVMs may improve the outcome in patients with lesions that are inaccessible to surgery. The major problem is early recognition and referral to neurological centers for early definitive treatment.

 

TABLE 45-8 -- FOCAL SIGNS IN PATIENTS WITH ANEURYSMS AT VARIOUS SITES

Site of Aneurysms

Clinical Finding

Internal carotid--post communicating

Third nerve palsy

Middle cerebral artery

Contralateral face or hand paresis

Aphasia (left side)

Contralateral visual neglect (right side)

Anterior communicating

Bilateral leg paresis

Bilateral Babinski's signs

Basilar artery apex

Vertical gaze paresis

Coma

Intracranial vertebral artery/posterior inferior cerebellar artery

Vertigo

Elements of lateral medullary syndrome



Arteriovenous Malformations

Pathogenesis and Pathophysiology. Vascular malformations are congenital in origin. They are classified into several subtypes according to the predominant vasculature. The most common type is venous angiomas, which are composed of anomalous veins without any direct feeding artery. The next most common is telangiectasia, usually found deep within the brain, particularly in the brain stem. It is composed of vessels morphologically resembling capillaries but slightly larger and often found at necropsy. Another less common vascular abnormality, which also rarely causes symptoms, is the venous varix. Two other common symptomatic angiomas are AVMs and cavernous angiomas. ,

, AVMs are composed of clusters of abnormal arteries and veins of varying size, without intervening capillaries.

Epidemiology and Risk Factors. Vascular malformations are the second most common cause of nontraumatic SAH and ICH. Vascular malformations are one tenth as common as aneurysms; an estimated 1000 new cases are identified in the United States each year. They rupture most commonly during the second and third decades of life. Hemorrhage from malformation is most common during early pregnancy or delivery.

Clinical Features and Associated Disorders. As AVMs enlarge, symptoms are related to a number of mechanisms. They can cause bleeding, seizures, vascular headache, and chronic ischemia. Bleeding is most likely due to fragility of the abnormal vessels. The angiomas that most frequently rupture are of the AV type. Symptoms and signs depend on the location of hemorrhage. There are usually signs of meningeal irritation due to bleeding into the CSF. Not all ruptures are symptomatic but evidence of previous bleeding is often observed at necropsy. About one half of the patients present with epilepsy. Progressive neurological signs may develop secondary to a mechanism called intracerebral steal or compression of adjacent brain tissue by the pulsating blood vessels. Chronic migrainous headaches are also a frequent complaint in patients with vascular malformations. Patients with unruptured AVMs may present with increased ICP and papilledema. Angiomas in the brain stem may cause serious bleeding or progressive neurological deficits, which may be fluctuating in clinical course and may simulate multiple sclerosis. Rarely, angiomas, particularly aneurysms of the vein of Galen, present with hydrocephalus by disrupting the normal flow of CSF. Bruits may be audible either to the patient or to the examiner. If there is enough shunting through a large AVM, high-output congestive heart failure may develop, especially in children. In spinal AVMs, the patients may present with back pain, myelopathic symptoms, and root dysfunction. However, headache often accompanies spinal AVM rupture, mimicking aneurysmal SAH. A number of patients with spinal AVMs have intracranial symptoms, including headache, mental status changes, loss of consciousness, papilledema, decreased vision, nystagmus, diplopia, seizures, sixth nerve palsy, and oculomotor paresis.

Some cavernous angiomas are familial. Patients with hereditary hemorrhagic telangiectasias (Osler-Weber-Rendu syndrome) have a higher than normal incidence of vascular malformations.

Differential Diagnosis and Evaluation. Diagnostic considerations include aneurysms and brain infarcts and tumors. Diagnosis of AVMs can be suspected clinically when young patients present with intracerebral hemorrhage, seizures, or frequent unilateral headaches. CT scan, MRI, MRA, and transcranial Doppler ultrasonography are helpful noninvasive tests. However, a confirmative diagnosis is made using angiography, through which therapeutic embolization can sometimes be performed at the same time. On angiography, a typical AVM shows large feeding arteries; a central tangle of vessels; enlarged, tortuous draining veins; and rapid arterial-to-venous shunting of blood.

Management. Direct surgical excision of AVMs has been improved with the use of the operating microscope and often can be carried out with low rates of morbidity and mortality. The major complications of surgical excision are loss of normal brain tissue, with additional loss of neurological function, and the so-called breakthrough phenomenon. This term describes massive brain swelling and ICH occurring postoperatively, which is caused by redirection of the large volume of blood into small vessels that are unable to handle the large volume of blood that previously flowed into the AVM.

Endovascular treatment of AVMs using embolization techniques can be used alone, before surgery, or at the time of surgery. It is particularly useful in treating lesions that are not surgically accessible and as an adjunct to surgical removal. Complications include hemorrhage, ischemic stroke, and angionecrosis due to toxicity of the embolic materials.

Radiotherapy of AVMs with high energy x-rays, gamma rays, and protons induces subendothelial deposition of collagen and hyaline substances, which narrow the lumen of small vessels and shrink the nidus of the malformations by progressive occlusion of vessels during the months after treatment. Recent techniques focus the radiation beam on small regions. An example is the so-called gamma knife, a system that uses a cobalt source to generate highly collimated gamma rays that converge on a focal point. Modified linear accelerators can now deliver radiation to a defined volume of tissue with very good accuracy. Complications include radionecrosis of normal brain, bleeding, hydrocephalus, immediate post-therapy seizures, loss of body temperature regulation, and possibly long-term cognitive function deficits.

Forms of medical management include strict control of blood pressure and avoidance of anticoagulants and antiplatelet drugs. Because pregnancy increases risk of bleeding, appropriate contraception may be recommended in fertile women with an AVM.

Prognosis and Future Perspectives. In the short term, the prognosis of ruptured AVMs and cavernous angiomas is better than that of aneurysms. The rebleeding rate is low during the first few months. Only 6 percent of patients rebleed during the first year, and vasospasm occurs only rarely. Mortality from the first hemorrhage is low, only about 10 percent. However, in the long term, the prognosis of AVMs is not as good. With subsequent hemorrhages, the mortality rate is higher, about 20 percent. With each recurrence, the chances of additional bleeding increase.

Improved noninvasive diagnosis using MRI and MRA and improved methods of treatment (endovascular and radiotherapy) promise to help reduce the rates of morbidity and mortality of this serious vascular condition.

TRAUMATIC NEUROVASCULAR DISEASES

Carotid-Cavernous Sinus Fistulas

A carotid-cavernous sinus fistula (CCF) is an abnormal communication between the cavernous sinus and the carotid arterial system. CCFs usually develop after head trauma but can occur spontaneously. CCFs are classified into direct and dural types. The most common type is the direct type (70 to 90 percent) in which there is a direct connection between the intracavernous portion of the ICA and the cavernous sinus. This is a high-flow type often caused by a traumatic tear of the arterial wall. The other dural types are communications between the cavernous sinus and meningeal arterial branches of the ICA, of the external carotid artery, or of both. They develop spontaneously or in the setting of atherosclerosis, systemic hypertension, collagen vascular disease, and during and after childbirth. These fistulas usually are of the low-flow type and almost always produce symptoms and signs spontaneously without antecedent trauma.

Patients with a direct CCF may develop monocular visual loss and abnormalities of the oculomotor nerves (III, IV, VI) ipsilaterally or bilaterally. Ocular manifestations include diplopia, proptosis, ocular bruit, chemosis, ocular pulsation, dilatation of retinal veins, optic disc swelling, visual loss, and potentially glaucoma. There are often signs of intracranial hypertension. Trigeminal nerve dysfunction is the most common cranial nerve abnormality. Dural types usually occur in middle-aged or elderly women. They present similar clinical symptoms and signs but are less severe than those of the direct type.

If a CCF is suspected, CT or MRI and ocular ultrasonography are performed and often show enlarged extraocular muscles, dilated superior ophthalmic veins, and an enlarged affected cavernous sinus. The ultimate diagnostic test is cerebral arteriography of both the bilateral internal and external carotid arteries.

Urgent treatment is indicated in patients who have rapidly deteriorating vision, hemorrhage, and intracranial hypertension. Surgical repair of the damaged portion of the intracavernous ICA is only rarely used these days. Endovascular occlusion using detachable balloons has a success rate of 90 to 100 percent with low complication rates (2 to 5 percent). The recurrence rate is 1 to 3.9 percent, and recurrence often responds to second balloon treatment. Early complications include migration of balloons and thromboembolism resulting in stroke; delayed complications are pseudoaneurysm formation and persistent ophthalmoplegias. If the condition is left untreated, almost all patients have progressive ocular problems, including increasing proptosis, chemosis, and visual loss. The most feared complications are central retinal vein occlusion and secondary glaucoma. Endovascular techniques have greatly improved the prognosis of CCFs. Most symptoms and signs usually disappear within days after treatment or at least improve with this procedure, but complete resolution may take weeks to months.

Subdural Hematomas

Pathogenesis and Pathophysiology. A subdural hematoma (SDH) results from venous bleeding after blunt head trauma, which causes brain motion within the skull, shearing off the bridging veins between the surface of the brain and adjacent dural venous sinuses. The blood leaks and collects slowly, forming a hematoma in the subdural space. An SDH may be absorbed spontaneously or may form an encapsulated and liquefied hematoma. After about 2 weeks, membranes form around the hematoma. The outer membrane is thicker and more vascular than the inner membrane. The center of the encapsulated SDH liquefies and may enlarge due to repeated bleeding from the vascular outer membrane, assuming a progressively larger biconvex lens shape.

Epidemiology and Risk Factors. Acute SDHs develop after severe head trauma and carry a poor prognosis. The mortality rate of a treated acute SDH is roughly 50 percent. A chronic SDH usually develops after minor trauma, typically in an elderly person under anticoagulation or in an alcoholic individual with some degree of brain atrophy. Because an atrophic brain cannot tamponade a beginning hematoma, bleeding frequently continues, causing headaches, behavioral changes, altered level of consciousness, or a focal neurological deficit such as hemiparesis. At times, subdural hematomas develop without a history of trauma. Patients treated with anticoagulants and those with bleeding disorders may develop spontaneous subdural bleeding. Occasionally, subdural collections develop after lumbar puncture. In other patients head trauma is forgotten or considered too inconsequential to mention. In many instances, a fall causes retrograde amnesia and the patient may not have been fully aware of the injury.

Clinical Features and Associated Disorders. The three most common findings in patients with subdural hematomas are headache, decreased level of alertness, and abnormalities of cortical function. Headache is usually ipsilateral to the hematoma and may be worse at night. Drowsiness and decreased alertness reflect an increase in intracranial pressure. There is often slight weakness, hyperreflexia, and Babinski sign contralateral to the hematoma. Slight aphasia may develop in patients with left-sided hematomas and neglect of the right side of space occurs in patients with right subdural hematomas. Usually, the neurological abnormalities are soft and seldom are as profound deficits as those that occur in patients with large hemisphere infarcts or intracerebral hematomas. Seizures may occur and probably indicate some contusion of the underlying brain tissue as the hematoma enlarges, headache worsens, and the level of consciousness often decreases. An ipsilateral Babinski sign or elements of an ipsilateral third nerve palsy, or both, may develop and indicate midbrain compression.

Differential Diagnosis and Evaluation. The diagnosis is usually obvious in patients with head injury. The insidious development of symptoms, especially in patients who provide no history of trauma can readily mimic brain tumor or abscess. Brain infarcts and hematomas usually present with more acute onset symptoms and signs and more severe focal deficits. Neuroimaging is now indispensable for accurate diagnosis. On a CT scan, an acute SDH appears as a sickle-shaped, hyperdense lesion over the outer surface of the brain lying against the inner surface of the skull and dura. A subacute SDH appears isodense in relation to the brain, making diagnosis difficult. During this acute period, a T1-weighted MRI is very helpful and shows a high signal intensity lesion in the subdural space. A chronic SDH appears hypodense on CT scans.

Management. If an SDH is not recognized and is left untreated, it may cause a severe neurological deficit or death. SDHs should be surgically evacuated. The prognosis is good and primarily related to the degree of associated brain injury. In older patients and in those with brain atrophy, re-expansion of the compressed brain may be delayed. Because subdural bleeding may recur, a drain must be left in for days and the patient must be watched carefully for continued bleeding.

Prognosis and Future Perspectives. Recovery is usually excellent in patients in whom subdural hematomas are recognized and treated. Small subdural hematomas probably are more common than recognized and may heal spontaneously without medical treatment. Because subdural hematomas represent a very treatable cause of mental abnormalities and neurological signs in elderly populations prone to falls, improved screening of these patients would be an important public health advance.

Epidural Hematomas

Pathogenesis and Pathophysiology. An epidural hematoma (EDH) develops when blood collects between the skull and the dura mater as the result of a severe head injury causing a fracture of the squamous portion of the temporal bone and producing a tear in the middle meningeal artery. Blood escaping under arterial pressure dissects the dura inward away from the bone and forms a hematoma. The most common location of EDH is along the lateral wall of the middle cranial fossa. The underlying brain is displaced inward, and brain herniation may follow. Occasionally, epidural hematomas can develop in patients with tumors involving those that have spread into the epidural space.

Epidemiology and Risk Factors. Epidural hematomas are rare when compared with subdural hematomas. They usually develop only in patients with severe head trauma. They may be an important cause of death in patients with severe head injury. Subdural, intracerebral, and subarachnoid hemorrhage often co-exists.

Clinical Features and Associated Disorders. Classically, the patient often has a lucid interval just after head trauma and then often has a progressive reduction in the level of consciousness as the hematoma enlarges. The lucid interval is explained as follows: The initial injury causes brain concussion and loss of consciousness from which the patient awakens and may have some headache but seems otherwise to have recovered. The acute development of epidural bleeding causes pressure on the ipsilateral cerebral hemisphere and headache, reduction in consciousness, and abnormalities of function of the ipsilateral hemisphere. Downward transtentorial herniation may develop rapidly, causing dilatation of the ipsilateral pupil due to third nerve compression and an ipsilateral hemiparesis due to compression of the contralateral cerebral peduncle of the midbrain against the contralateral tentorial edge.

Rarely, an EDH may be venous in origin due to laceration of the middle meningeal vein or a dural venous sinus. The time course is more protracted, evolving over several days. Altered mental status and hemiparesis develop before signs of brain herniation.

Differential Diagnosis and Evaluation. Diagnosis is made by CT. The hematoma typically appears as a biconvex lens-shaped hyperdense lesion. There is an underlying skull fracture. However, if the patient's condition is rapidly deteriorating, the diagnosis is better made by taking the patient directly to the operating room for a procedure that is both diagnostic and therapeutic.

Management. Epidural hematomas should be surgically evacuated as soon as possible. There is no place for conservative management of epidural hematomas. Rapid drainage can be life saving.

Prognosis and Future Perspectives. The outcome is usually excellent when epidural hematomas are rapidly diagnosed and treated surgically. Death usually results from unrecognized epidural hematomas. After effective treatment, there are usually no residual neurological deficits.

Spinal Cord Strokes

Pathogenesis and Pathophysiology. Spinal cord infarcts are most often caused by interruption of the blood flow in one or more of the arteries that feed into the anterior spinal arterial system. A large anterior spinal artery runs in the ventral midline from the medullospinal junction rostrally to the conus medullaris and the filum terminale caudally. This anterior spinal artery system is supplied by five to 10 single radicular arteries. The cervical region is supplied by the anterior spinal artery branch of the intracranial vertebral artery and inferiorly by branches of the thyrocervical and costocervical branches of the subclavian arteries. The thoracic and lumbar spinal cord segments are fed by radicular arterial branches of the deep cervical and intercostal arteries and branches of the aorta. The lower thoracic cord is supplied by direct branches from the aorta, the largest of which is the artery of Adamkiewicz, which most often enters between T12 and L2. The sacral cord and cauda equina are supplied by branches of the hypogastric and obturator arteries. This anterior system is vulnerable to interruption of flow through any one of the feeding arteries. Resulting infarcts usually affect the anterior horns and the lateral and ventral white matter columns.

In contrast to the anterior spinal artery system, there are paired posterior spinal arteries, which are fed by small posterior radicular arteries and which enter along nerve roots at every level from both sides. The posterior spinal arteries form a rete of communicating vessels that supply the posterior columns and posterior gray horns of the spinal cord. Because of the multiple feeding channels, this system is very resistant to interruption of its blood supply.

Interruption of blood flow in anterior spinal branches is probably most often due to disease within the aorta. Aortic aneurysms, surgery on the aorta, aortic dissections, and emboli from atheromatous aortic plaques can result in obstruction to flow in feeding arteries. Disc cartilage can also fragment and enter spinal arteries and veins and lead to infarction.

AV fistulas are also an important cause of spinal cord infarction. These lesions are most common in older men. Direct communications develop between radicular arteries and veins outside the dura mater. This greatly increases pressure in the venous system, and large drainage veins develop on the surface of the spinal cord. At the same time, shunting of blood decreases flow to the spinal cord from the feeding artery. In order to maintain adequate spinal perfusion, the pressure of blood in the arterial system must exceed venous pressure. The spinal-dural AV fistula often creates a situation in which intermittently venous pressure exceeds arterial pressure, and ischemia develops. At first, ischemia can be intermittent, and spinal cord TIAs can result.

Spinal infarcts can also develop in relation to infections in the meninges and parasitic invasion of the spinal arteries. Syphilis, tuberculosis, and lyme borreliosis can involve the spinal arteries. Adhesive arachnoiditis can also cause obliteration of spinal arteries and lead to cord ischemia, especially in the central portion of the spinal cord. Schistosomiasis can involve feeding spinal arteries. Hypoxic-ischemic injury to the spinal cord also develops in patients with severe systemic hypotension and shock. In these patients, brain damage usually is more severe than spinal injury and makes it difficult to identify the spinal pathology clinically.

Spinal cord hemorrhage most often results from trauma. Bleeding diathesis, especially anticoagulation, is another important cause. Aneurysms of intradural arteries and intradural AVMs and cavernous angiomas are other causes of spinal cord hemorrhages.

Epidemiology and Risk Factors. Spinal strokes are very rare in comparison to strokes that involve the brain. The rarity of spinal cord strokes and the inaccessibility of the spinal cord vascular system to imaging during life have greatly limited knowledge about the causes and pathophysiology of spinal strokes. In addition, the spinal cord and its vascular system are seldom examined in detail during postmortem examinations. The major risk factor for spinal strokes is disease of the aorta and aortic surgery. In older individuals, aortic disease and dural fistulas account for the bulk of cases. In younger persons, trauma, cartilaginous emboli, and congenital vascular malformations and bleeding diatheses account for most instances of spinal strokes.

Clinical Features and Associated Disorders. Spinal cord infarcts usually develop abruptly. Most spinal strokes are thoracic or lumbar, so that the lower extremities are selectively involved. The most common signs are motor and include both lower motor neuron and upper motor neuron abnormalities within the lower limbs. Paraplegia is usually symmetrical. There may be a pain and temperature level along the thorax. Sphincter function is most often lost. Posterior column functions (vibration and position sense) are usually spared. The findings are most often roughly symmetrical. When the lesion is asymmetrical or unilateral, sensory dissociation occurs, producing a Brown-Sequard-like pattern. In patients with spinal-dural AV fistulas, TIAs and steplike development of deficits are common.

Differential Diagnosis. Almost always, the symptoms and signs allow recognition that the lesion is spinal. Occasionally, medullary and pontine infarction can be a consideration. Tumors, abscesses, and syrinxes usually cause symptoms that develop gradually, but hemorrhage into a spinal cord tumor, most often an ependymoma, can be an important consideration. Spinal cord compression caused by cancer, epidural and subdural infections, and hematomas are other considerations.

Almost all compressive spinal cord lesions involve the vertebral column. Plain bone x-ray studies and CT, MRI, and bone scans can yield information about osseous lesions that could compress the spinal cord. MRI is the best method to visualize the spinal cord, dura mater, and overlying bony structures. MRI can show spinal hemorrhages and infarcts and can identify the presence of spinal cord compression. MRI is not very sensitive for the detection of spinal-dural AV fistulas. Myelography may be needed to show the characteristic dilated veins that course on the surface of the spinal cord. Lumbar puncture is helpful in identifying spinal hemorrhage and infection. Spinal angiography is often necessary to characterize spinal vascular malformations and fistulas.

Management. There is little information about treatment of patients with spinal cord infarcts. Definitive treatment depends, as it does in the brain, on identification of the etiology in the individual patient. Hemorrhage, infection, and infarction can be separated by MRI and lumbar puncture. Identification of spinal-dural AV fistulas is very important because obliteration of the abnormalities can prevent further spinal cord damage. Rehabilitation and management of sphincter functions is similar to that pursued in other diseases of the spinal cord.

Prognosis and Future Perspectives. Outcome depends almost entirely on the cause of the spinal cord vascular damage. In the future, we need to develop more accurate ways to study the aortic blood supply to the spinal cord. Intravascular ultrasound is promising. Perhaps further development of MRA and venography will be helpful and obviate the need for spinal angiography, which can be hazardous. Basic research on spinal cord protection may help limit damage in patients with vascular spinal cord insults.

STROKES IN THE YOUNG

Strokes in children younger 15 are often different from those found in adults. Brain infarcts tend to be limited more to the deeper regions of the cerebral hemispheres, especially the striatocapsular areas. Vascular occlusive lesions are more often intracranial and affect mostly the intracranial carotid and the middle cerebral and basilar arteries. Extracranial lesions are less common; when they occur, they usually involve the pharyngeal portions of the carotid and vertebral arteries rather than the arterial origins that are involved more commonly in adults. Vasoconstriction, dissection, fibromuscular dysplasia, trauma, and contiguous infection are the major diseases that affect the extracranial arteries of children. When the vascular occlusive process or embolism involves the middle cerebral artery, vascular compromise is maximal in the territory of the lenticulostriate branches. Because of the invariable absence of severe occlusive disease, collateral circulation over the convexities is abundant. This explains the striatocapsular localization of infarcts. Because atherosclerosis is very rare in youth, the types of vasculopathies that cause brain ischemia in children is much more diverse than in adults, and the differential diagnosis is very broad. Congenital cardiac disease is an important cause of stroke in children. Table 45-9 lists the most important causes of brain ischemia in children younger than age 15 years.

Brain and subarachnoid hemorrhages, especially from aneurysms and vascular malformations, comprise a much higher percentage of strokes in children than they do in adults.

In young adults, premature atherosclerosis and stroke risk factors are much more important than in youths. Cardiac disease and hematological diseases and cancer provide a higher proportion of infarcts in young adults than during the geriatric years. Table 45-10 lists the major differential considerations of brain ischemia in persons 15 to 40 years of age.

 

TABLE 45-9 -- DIFFERENTIAL DIAGNOSIS OF PEDIATRIC BRAIN ISCHEMIA (1-15 YEARS)

Migraine

Trauma: Dissection and other vascular injuries; abuse including whiplash-shake injuries; oral foreign body trauma to the internal carotid artery

Cardiac: Congenital heart disease with right-to-left shunts; tetralogy of Fallot; transposition of great vessels; tricuspid atresia; atrial and ventricular septal defects; cardiomyopathies; endocarditis; pulmonary arteriovenous fistula

Drugs: Especially cocaine and heroin

Infections: Bacterial meningitis, especially Hemophilus influenzae, pneumococci, and streptococci; facial, otitic, and sinus infections; AIDS; dural sinus occlusion and infection; tuberculous meningitis

Genetic and metabolic: Neurofibromatosis; hereditary disorders of connective tissue (Marfan's and Ehlers-Danlos syndromes, pseudoxanthoma elasticum); homocystinuria; Menkes' kinky hair syndrome; hypoalphalipoproteinemia; familial hyperlipidemias; methylmalonic aciduria; MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, strokes)

Hematological and neoplastic: Sickle cell anemia; purpuras; leukemia; L-asparaginase and aminocaproic acid (Amicar) treatment; radiation vasculopathy; hypercoagulable states (e.g., caused by decrease in natural inhibitors such as antithrombin III)

Arteritis: Collagen vascular disease; local infections; Takayasu's disease; Behcet's disease

Venous sinus thrombosis: Head and neck infections; dehydration; coagulopathy; paroxysmal nocturnal hemoglobinuria; puerperal or pregnancy-related

Systemic disease: Rheumatic; gastrointestinal; renal; hepatic; pulmonary

Moyamoya disease

From Caplan LR, Estol CE: Strokes in youths. In Adams HP (ed): Cerebrovascular Disease. New York, Marcel Dekker, 1993, pp 233-254.



 

TABLE 45-10 -- DIFFERENTIAL DIAGNOSIS OF ISCHEMIA IN YOUNG ADULTS (15-40 YEARS)

Migraine

Arterial dissection

Drugs, especially cocaine and heroine

Premature atherosclerosis, hyperlipidemias, hypertension, diabetes, smoking, homocystinuria

Female hormone-related (oral contraceptives, pregnancy, puerperium): eclampsia; dural sinus occlusion; arterial and venous infarcts; peripartum cardiomyopathy

Hematological: Deficiency of antithrombin III, protein C, protein S; fibrinolytic system disorders; deficiency of plasminogen activator; antiphospholipid antibody syndrome; increased factor VIII; cancer; thrombocytosis; polycythemia; thrombotic thrombocytopenic purpura; disseminated intravascular coagulation

Rheumatic and inflammatory: Systemic lupus erythematosus; rheumatoid arthritis; sarcoidosis; Sjogrens syndrome; scleroderma; polyarteritis nodosa; cryoglobulinemia; Crohn's disease; ulcerative colitis

Cardiac: Interatrial septal defect; patent foramen ovale; mitral valve prolapse; mitral annulus calcification; myocardiopathies; arrhythmias; endocarditis

Penetrating artery disease (lacunes); hypertension, diabetes

Others: Moyamoya disease; Behcets disease; neurosyphilis; Takayasus disease; Sneddon's disease; fibromuscular dysplasia; Fabry's disease; Cogan's disease

From Caplan LR, Estol CE: Strokes in youths. In Adams HP (ed): Cerebrovascular Disease. New York, Marcel Dekker, 1993, pp 233-254.

 

Hosted by uCoz