Porth's Essentials of Pathophysiology, 4e

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Disorders of Brain Function

C h a p t e r 3 7

large artery atherosclerotic disease (both thrombosis and arterial emboli); 25% small vessel or penetrating artery disease (so-called lacunar stroke); 20% cardio- genic embolism; 30% cryptogenic stroke (undetermined cause); and 5% other causes (i.e., migraine, vessel dissec- tion, coagulopathy). 7 Ischemic Penumbra in Evolving Stroke. During the evolution of a stroke, there usually is a central core of dead or dying cells, surrounded by an ischemic band or area of minimally perfused cells called the penumbra (“halo”). Brain cells of the penumbra receive marginal blood flow, and their metabolic activities are impaired. Although the area undergoes an “electrical failure,” the structural integrity of the brain cells is maintained. 4,23 Reversal of the penumbral injury depends on the suc- cessful and timely return of adequate circulation, the volume of toxic products released by the neighboring dying cells, the degree of cerebral edema, and alterations in local blood flow. If the toxic products result in addi- tional death of cells in the penumbra, the core of dead or dying tissue enlarges, and the volume of surrounding ischemic tissue increases. Transient Ischemic Attacks. Transient ischemic attacks (TIAs) are brief episodes of neurologic dysfunction result- ing from focal cerebral ischemia not associated with infarction. 18,24–26 A TIA or “ministroke” is equivalent to “brain angina” and reflects a temporary disturbance in cerebral blood flow, which reverses before infarction occurs, analogous to angina in relation to heart attack. The traditional definition of TIAs as a neurologic deficit resolving within 24 hours was developed before the mech- anisms of ischemic cell damage and the penumbra were known and before the newer, more advanced methods of neuroimaging became available. A more accurate defini- tion now is a transient deficit without time limits, best described as a zone of penumbra without central infarc- tion. 20 The causes of TIAs are the same as those of isch- emic stroke and include atherosclerotic disease of cerebral vessels and emboli. Transient ischemic attacks are impor- tant because they may provide warning of impending stroke. In fact, the risk for stroke is 15% in the 3 months following a TIA. 20 Diagnosis of TIA before a stroke may permit surgical or medical intervention that prevents an eventual stroke and associated neurologic deficits. Large Vessel (Thrombotic) Stroke. Thrombi are the most common cause of ischemic strokes, usually occur- ring in atherosclerotic blood vessels. 1,4 In the cerebral circulation, atherosclerotic plaques are most commonly found at arterial bifurcations of large arteries. Common sites of plaque formation include the origins of the inter- nal carotid and vertebral arteries, and junctions of the basilar and vertebral arteries. Cerebral infarction can result from an acute local thrombosis and occlusion at the site of chronic atherosclerosis, with or without embolization of the plaque material distally, or from critical perfusion failure distal to a stenosis (water- shed). These infarcts often affect the cortex, causing aphasia or hemineglect, visual field defects, or transient

TABLE 37-4 Modifiable and Unmodifiable Risk Factors for Stroke Modifiable Factors Unmodifiable Factors

• Hypertension • Hyperlipidemia

• Age

• Gender

• Smoking • Diabetes

• Race

• Heredity

• Heart disease

Atrial fibrillation Wall motion defects

• Carotid artery disease • Coagulation disorders • Obesity/inactivity • Heavy alcohol use • Cocaine use

stroke are family history of ischemic stroke, hyperten- sion, cigarette smoking, overweight and obesity, high blood cholesterol and other lipids, diabetes mellitus, disorders of cardiac rhythm (e.g., atrial fibrillation), and chronic kidney disease 21 (Table 37-4). The incidence of stroke increases with age, and varies by sex and ethnic- ity. Men have higher rates in the younger age groups, though women catch up after menopause and live lon- ger, resulting in higher rates of death among women. African Americans have almost twice the risk of first-ever strokes as whites. Blood pressure is a powerful determi- nant of stroke risk. Individuals with a blood pressure less than 120/80 mm Hg have about half the lifetime risk of stroke compared with persons with hyperten- sion. Heart disease, particularly atrial fibrillation and other conditions that predispose to clot formation on the wall of the heart or valve leaflets, or to paradoxical embolism through right-to-left shunting, predisposes to cardioembolic stroke. Polycythemia, sickle cell disease (during sickle cell crisis), and blood disorders predispose to clot formation in the cerebral vessels. Other, less well-documented risk factors include obe- sity, physical inactivity, alcohol and drug abuse, hyper- coagulability disorders, hormone replacement therapy, and oral contraceptive use. Clinical trial data indicate that estrogen plus progestin, as well as estrogen alone, increase stroke risk in postmenopausal, generally healthy women, and provide no protection for women with established heart disease. Although extensively used in the past, the use of hormone therapy is no longer recom- mended (see Chapter 40). Heavy alcohol consumption can lead to hypertension, hypercoagulability of blood, reduction of cerebral blood flow, and greater likeli- hood of atrial fibrillation. Cocaine use causes both isch- emic and hemorrhagic strokes by inducing vasospasm, enhanced platelet activity, and increased blood pressure, heart rate, body temperature, and metabolic rate. 22 Classification. Various methods have been used to clas- sify ischemic cerebrovascular disease. A common clas- sification system identifies the five main mechanisms of stroke as stroke subtypes and their frequency: 20%