CHAPTER 32 CEREBROVASCULAR DISEASE
Practice of Geriatrics
CHAPTER 32 CEREBROVASCULAR DISEASE*
Linda Ann Hershey, M.D., Ph.D.
Stroke is the third leading cause of death in the developed world. With heart disease and cancer, it ranks among the most costly of all health care problems. Transient ischemic attacks (TIAs) are important predictors of stroke, myocardial infarction, and death. One third of all patients with TIAs have a stroke within 5 years. Strokes may be either hemorrhagic or ischemic, and hemorrhagic strokes carry a higher mortality (30% to 50%) than ischemic infarction (15% to 20%). Seizures at the onset of a stroke are predictive of subsequent epilepsy. Ischemic vascular dementia develops in 10% to 25% of stroke patients, depending upon age and the number of previous strokes. Just as stroke can be prevented by maintaining blood pressure control, ceasing smoking, and initiating antiplatelet or anticoagulant therapy, vascular dementia can be prevented by controlling stroke risk factors. This chapter reviews the epidemiology, pathophysiology, clinical assessment, and management of cerebrovascular disease in the elderly.
Transient Ischemic Attack
TIAs are brief episodes of focal loss of brain function that are due to transient hypoperfusion of a portion of the brain supplied by a specific vessel or group of vessels.1 Most TIAs last less than 24 minutes, but studies usually define them as lasting less than 24 hours. It has been shown by computed tomography (CT) that many TIAs that last longer than 6 to 8 hours are associated with infarction of the brain. Half of all strokes that follow TIAs occur within a year of the last TIA, making TIA an urgent medical condition requiring early evaluation and intervention.2 Some TIAs are better predictors of myocardial ischemia than of stroke. Retinal TIAs, for example, are more likely to be followed by myocardial infarction than by stroke.
Stroke is defined as a focal neurologic deficit of vascular origin that is sudden in onset and lasts longer than 24 hours. Hemorrhages account for only 15% of all strokes, while ischemic infarctions account for 80% to 85%. Infarction is divided into three broad categories based on the most common pathologic mechanisms: atherothrombotic, cardioembolic, and lacunar. Atherothrombotic infarcts are associated with plaques of the carotid arteries, the vertebrobasilar arteries, or the aortic arch.
A history of TIAs and the presence of a cervical bruit are more frequently found in persons with atherothrombotic infarction than in those with other types of stroke.1 In patients who have symptomatic carotid stenosis of 70% or more and no significant cardiac source of emboli, the risk of stroke following a TIA is directly proportional to the percentage of carotid stenosis.3
Ischemic stroke patients who have no significant carotid stenosis, no pattern of lacunar infarction, and no cardiac source of emboli may experience stroke because of embolic material that breaks off an atheromatous plaque in the aortic arch.4 The most common reversible risk factors associated with atheromatous disease of the carotids or the aorta are hypertension and cigarette smoking.
Small Deep Infarction
About 15% of all strokes are due to occlusion of small penetrating vessels in deep structures of the brain, such as the internal capsule, the thalamus, or the brain stem. Over a period of time these small deep infarcts become cystic and filled with fluid, giving rise to the name lacunar because of their resemblance to small lakes.1 Brain imaging with CT may not identify lacunar infarcts, since they are by definition less than 15 mm in diameter. Magnetic resonance imaging (MRI) is a more sensitive tool than CT for documenting their presence. The most prevalent reversible risk factor for small deep infarcts is essential hypertension.5
Cardiac emboli are responsible for about 15% of all strokes. Patients with atrial fibrillation (AF) are five times more likely to have a stroke (5% per year) than age-matched controls (1% per year). AF patients who have had a previous stroke have an even higher risk of recurrence (12% per year). Not only does the risk of AF increase with age, but the risk of stroke in AF patients is also age related.6 Other cardiac sources of embolism besides AF include acute anterior wall myocardial infarction, left atrial thrombus, spontaneous echocardiographic contrast, left ventricular thrombus, dilated cardiomyopathy, mitral stenosis, prosthetic heart valves, mitral annulus calcification, subacute bacterial endocarditis, and atrial septal aneurysm.
Subarachnoid, intracerebral, and subdural hemorrhages account for another 15% of all strokes. Hemorrhage should be the primary diagnostic consideration in patients who appear in the emergency room with early headache, loss of consciousness, stiff neck, vomiting, agitation, or seizures. Subarachnoid hemorrhage (SAH) is more likely to occur in women than in men, and in blacks than in whites.7 Intracerebral hemorrhage (ICH) is also more prevalent in blacks except for those over the age of 65 years; in this group whites are at greater risk. Both SAH and ICH are associated with high cost and high mortality (40% to 50%). The most prevalent risk factor associated with SAH is cigarette smoking, whereas for ICH it is hypertension.8
Cerebrovascular disease accounts for 30% to 50% of all seizures occurring in the elderly. Early seizures are thought to be more common at the onset of hemorrhagic infarction than at the onset of ischemic infarction. Among the various infarct types, early seizures are more likely to be associated with cardioembolic than with atherothrombotic or lacunar strokes.9 Late postinfarction seizures may occur months to years following a stroke. Recurrent seizures (epilepsy) develop in about 15% to 20% of all stroke patients.
Ischemic Vascular Dementia
Vascular dementia is a general term used to describe several subtypes of cognitive decline: multi-infarct dementia, lacunar dementia, Binswanger’s disease (subcortical arteriosclerotic encephalopathy), and single-infarct dementia. Vascular dementia and mixed dementia (a combination of vascular dementia and Alzheimer’s disease) are second only to Alzheimer’s disease as the most prevalent causes of cognitive impairment in the elderly. Epidemiologic studies of large populations have supported the findings of smaller autopsy studies: Vascular and mixed dementia account for 20% to 30% of all patients with severe dementia.10 Hypertension has been shown to be the most important risk factor for both lacunar dementia and Binswanger’s disease.5
Transient Ischemic Attacks
For many years, TIAs were thought to have a hemodynamic basis rather than an embolic one. Cerebral bypass surgery was originally designed to correct what was thought to be a hemodynamic problem in patients with carotid occlusion or high-grade carotid stenosis. Nevertheless, a large randomized trial showed that this type of surgery produced no significant reduction in the number of subsequent strokes in patients with severe carotid disease.11
The embolic hypothesis for TIAs received support on two occasions during the bypass study when surgeons photographed platelet-fibrin material in branches of the middle cerebral artery. Similar platelet-fibrin material had been visualized previously in vessels on the fundi of patients who happened to have been examined during a retinal TIA. Further evidence of a causal link between platelet-fibrin emboli and clinical symptoms is shown by the response of patients with TIAs and small strokes to antiplatelet agents such as aspirin or ticlopidine. Both of these drugs are effective in reducing the frequency and severity of recurrent TIAs and strokes.12
Transcranial Doppler (TCD) ultrasonography is a technique that allows investigators to monitor the frequency of emboli arriving in intracerebral vessels of patients with symptomatic carotid stenosis. One group showed that endarterectomy could reduce or eliminate the number of embolic signals recorded by TCD in the middle cerebral artery distal to a high-grade stenotic lesion of the internal carotid artery.13 This study strengthened the idea that atheromatous plaque could serve as a nidus for platelet-fibrin or cholesterol emboli.
Even though most TIAs are embolic in origin, there are some that are caused by hemodynamic compromise. For example, if there is poor collateral flow through the circle of Willis, a patient with carotid occlusion may experience ischemic symptoms when making rapid postural changes. The phenomenon of unilateral limb-shaking upon standing has been observed in patients with unilateral carotid occlusion. In the extracranial/intracranial (EC/IC) bypass study, there were 74 patients with bilateral carotid occlusion. A few of them experienced focal ischemic events on standing. These symptoms abated after a few months in patients in both the medical and surgical arms of the study. Improvement was probably due to the spontaneous development of collateral circulation.11
Noncardioembolic Ischemic Infarction
Patients with stenosis of 70% or more of a symptomatic carotid artery are at high risk (about 25%) for having an ipsilateral infarct within the first 2 years after their TIA or small stroke. This compares to a stroke risk of 2% in asymptomatic patients with carotid stenosis. Among patients with carotid stenosis assigned to the medical treatment arm of the North American Symptomatic Carotid Endarterectomy Trial (NASCET), stroke risk varied not only as a function of the severity of carotid stenosis but also as a function of the number of vascular risk factors present.3
Hypertension increases the risk of both ischemic infarction and intracerebral hemorrhage. About 40% of all strokes are associated with systolic pressures of over 140 mmHg.8 In patients with chronic hypertension, vascular remodeling results in thickening of the media and narrowing of the lumen of small vessels.5 Normal vessels can dilate to compensate for low perfusion pressures (autoregulation), but as arteriosclerosis progresses, the thickened vessels respond less efficiently to sudden changes in perfusion pressure. As a result, chronically hypertensive individuals who experience acute lowering of systemic blood pressure to normal levels may develop global ischemic symptoms such as dizziness or syncope. Autoregulation is also lost soon after a stroke, which explains why acute lowering of blood pressure in patients with fresh infarcts can cause focal neurologic signs to become worse.
Cautious lowering of blood pressure into the normal range in hypertensive rats can reduce the medial thickness of large cerebral arteries. Similarly, judicious control of blood pressure in patients with chronic hypertension decreases the likelihood of future strokes.5
Cigarette smoking is another important reversible risk factor for ischemic stroke. Women who smoke triple their stroke risk, while men who smoke double theirs. Cigarettes augment stroke risk by facilitating atherogenesis and increasing platelet aggregability and hematocrit and fibrinogen levels. Long-term smokers have reduced cerebral perfusion compared to nonsmokers. Just as the risk of stroke can be reversed in hypertensives if blood pressure is controlled over time, so stroke risk can be reversed in light smokers (less than 20 cigarettes/day) who stop smoking.14 According to a new study, heavy smokers cannot completely reverse their stroke risk by ceasing to smoke, nor can those who switch from cigarettes to cigars or pipes.
Atrial fibrillation associated with rheumatic heart disease and mitral stenosis has long been recognized as a risk factor for stroke. It is now known that chronic AF without valvular heart disease also increases stroke risk.6 Women in their eighties with nonvalvular AF are at particularly high risk for stroke. In general, women are less likely than men to have AF, but the prevalence of AF becomes nearly equal in men and women by the eighth decade. The risk of stroke in patients with AF rises as a function of age, just as it does with other stroke risk factors such as hypertension, congestive heart failure, previous stroke, or echocardiographic evidence of either left atrial enlargement or left ventricular dysfunction.
Patients with SAH are often younger and less likely to have hypertension than those with ICH.1 SAH is usually caused by the rupture of a saccular aneurysm or arteriovenous malformation. The risk of aneurysmal rupture usually depends on the size of the aneurysm, with those less than 3 mm in diameter carrying the lowest risk of hemorrhage and those above 10 mm carrying the highest. The clinical severity of the condition at the initial assessment is usually a good index of short-term prognosis.
Ischemic stroke may develop in patients with SAH as a result of vasospasm, particularly when the brain tissue distal to the site of vasospasm remains hypoperfused for longer than 24 hours. In most cases, vasospasm develops within 3 to 5 days of the hemorrhage and resolves over 2 to 4 weeks. The severity of vasospasm usually varies as a function of the size of the clot. Recurrent hemorrhage, a serious consequence of SAH, is associated with a mortality as high as 70%.
Subdural hemorrhage is due to rupture of the bridging veins that extend from the pia mater to the dura mater. Subdural bleeding is more likely to occur in the elderly because the bridging veins become increasingly fragile with age-related atrophy of the brain. Even minor head injuries in the elderly can result in subdural hemorrhage. Patients who are receiving anticoagulation therapy or are alcoholic, thrombocytopenic, or uremic are particularly vulnerable to this complication of a simple fall.
ICH represents arterial bleeding directly into the brain parenchyma. The most common locations of hypertensive ICH are the basal ganglia, thalamus, cerebellum, and pons.1 Anticoagulated patients with ICH are more likely to die than those with spontaneous hemorrhage because hematomas in patients who are being treated with heparin or warfarin are larger. The active bleeding of a spontaneous ICH usually lasts less than an hour, but that of a hypertensive hemorrhage can continue over several hours if the blood pressure is not promptly brought under control. Small deep vessels of hypertensive patients develop both microaneurysms and lipohyalinosis, which are thought to be related to the development of ICH. This fact explains why hypertensive bleeds occur in the same parts of the brain where small deep infarcts are found.
Hemorrhages associated with either cerebral amyloid angiopathy (CAA) or thrombolytic agents are usually cortical, not deep. Patients with these types of hemorrhage often complain of headache, but they rarely lose consciousness. Patients with ICH resulting from CAA are typically over the age of 60 and are usually normotensive. Many of them have recurrent hemorrhages. Autopsy studies have shown that the prevalence of CAA in the general population increases linearly with age, and CAA affects the cerebral vessels in as many as 40% of those in their eighties. Amyloid deposits in the vessel walls are associated with vasculopathy in patients with CAA. Weakening of the vessel wall is thought to lead to hemorrhage.
Infarcts that produce early seizures are usually larger than those not associated with seizures. Cortical strokes are more likely to produce seizures than subcortical ones. Early seizures and stroke recurrence are both predictors of the development of epilepsy.9 It is not clear what causes an ICH to produce seizures, but seizures associated with SAH are related to the volume of blood in the basal cisterns.
Ischemic Vascular Dementia
The three most important risk factors for vascular dementia are hypertension, advanced age, and recurrent stroke.10 These are the same risk factors that cause changes in the subcortical white matter in the brains of community-dwelling nondemented elderly individuals.
Pathophysiologically, a critical cascade may account for the relationship between subcortical white matter changes and progressive cognitive decline in elderly hypertensive individuals.15 Patients with untreated chronic hypertension have been shown to have hypoperfusion in the deep white matter, presumably because of the narrowing of deep penetrating arteries by lipohyalinosis. Nondemented hypertensive patients may be able to compensate for subcortical hypoperfusion by extracting more oxygen from the blood. White matter changes may develop when compensation is no longer possible. This is likely to occur when viscosity rises in association with high hematocrit, hypercholesterolemia, or hyperfibrinogenemia. Ultimately, dementia develops when a critical mass of white matter has undergone demyelinization and other ischemic changes.
Clinical Symptoms of Brain Ischemia
Symptoms of TIAs and infarction vary according to the vessel that has been occluded, either temporarily or permanently (Table 32-1). Symptoms of small deep infarcts differ from those of atherothrombotic infarcts depending upon the location of the lacunae (Table 32-2). If pure motor hemiparesis is associated with nausea or ataxia, the infarct is more likely to be pontine in location than capsular. If sensory symptoms march up the arm, a focal seizure is more likely than a TIA. If hemianopsia is associated with headache, nausea, and photophobia, complicated migraine is a better clinical diagnosis than TIA.
TABLE 32-1 SYMPTOMS OF BRAIN ISCHEMIA
TABLE 32-2 SYMPTOMS OF SMALL DEEP INFARCTS
Transient vertigo associated with ataxia, diplopia, tinnitus, or nausea is likely to be due to vertebrobasilar insufficiency. Vertigo that develops in a diabetic patient along with tachycardia or tremor may be a symptom of hypoglycemia rather than a TIA. When vertigo is accompanied by bilateral paresthesias and anxiety, it may be a manifestation of hyperventilation or a panic attack.
Emergency Assessment of Brain Ischemia
It is important to order a head CT scan for all patients with symptoms of acute ischemia because tumor, SAH, subdural hematoma, and ICH can all mimic the symptoms of TIA and stroke.1,16 Intravenous contrast medium is not needed for the admission head CT scan because the main purpose is to exclude hemorrhage. Only about 50% of acute ischemic infarcts appear on the first CT scan. Infarcts that are already large on the admission CT scan are more likely to bleed if the patient is anticoagulated. Large infarcts carry a poor prognosis in general because they are likely to be associated with edema and increased intracranial pressure.
An electrocardiogram (ECG) is recommended for every new TIA or stroke in order to identify patients who have AF, acute myocardial infarction, or left ventricular hypertrophy.2,16 If the admission ECG detects serious cardiac abnormalities, telemetry is usually indicated for at least the first 24 hours. A chest radiograph is also needed on admission to look for cardiomegaly and signs of possible aortic dissection. Blood tests needed in acute TIA and stroke patients include a complete blood count, prothrombin time, partial thromboplastin time, creatinine, glucose, and creatine kinase (CK).
Nonemergent Assessment of Ischemia
If the admission CT scan for a stroke patient is normal, a repeat scan without contrast can be done 4 to 7 days later to document the location and to clarify the pathogenesis of the infarct. This scan will help in selecting the proper therapy. Some small cortical infarcts, for example, may produce a pure motor deficit that mimicks a lacunar stroke. After the repeat CT scan has verified a cortical location for the infarct and a carotid source of emboli has been excluded by carotid ultrasound, the clinician is justified in pursuing a cardiac source of emboli (an echocardiogram is recommended at this point).
Carotid ultrasonography should be scheduled within the first week of new ischemic symptoms provided they are in the distribution of the carotid arteries. TCD ultrasound is a noninvasive method of examining the posterior circulation in patients with symptoms of vertebrobasilar insufficiency. If carotid ultrasound suggests high-grade (70% to 99%) stenosis of the symptomatic vessel, cerebral angiography is the next step for patients who are good surgical candidates.3 This technique is needed to rule out the presence of distal disease of the internal carotid that might be more severe than that in the cervical portion of the artery. Transesophageal echocardiography is justified when no lacunar, cardioembolic, or atherothrombotic sources can be identified.4
Sudden onset of severe headache followed by nausea, vomiting, stiff neck, or altered mental state should lead the clinician to suspect SAH. If a noncontrast CT scan shows no evidence of fresh blood in the subarachnoid space, then a lumbar puncture should be done to confirm the diagnosis (10% of SAHs must be diagnosed in this way). If fresh blood is apparent on CT scan, a lumbar puncture is usually contraindicated because changes in hydrostatic pressure could dislodge the clot and facilitate rebleeding. Selective catheter angiography is the next step in localizing the aneurysm or arteriovenous malformation. Nevertheless, 15% to 25% of angiograms performed to detect SAH do not show a source of the hemorrhage. SAH patients with no identifiable aneurysm or arteriovenous malformation on angiography are less likely to experience rebleeding following SAH.
Besides hypertension, anticoagulation, alcohol abuse, and amyloid angiopathy, another cause of ICH is brain tumor. Glioblastoma and metastases from lung, melanoma, or kidney are more likely to bleed than other tumor types. A tumor should be suspected if focal symptoms precede the hemorrhage or if bleeding occurs into unusual sites such as the corpus callosum. If the admission CT scan suggests a tumor, contrast CT or MRI should be scheduled the next day to clarify the diagnosis. Treatment for brain tumor differs considerably from that for acute stroke.
In the emergency room, the condition most commonly mistaken for stroke is seizure. The short-term hemiparesis that follows a partial seizure (Todd’s paralysis) can be clinically indistinguishable from the weakness associated with a small stroke. On the other hand, 5% of all ischemic stroke patients may develop seizures during the acute stages of an infarct.9 Only about 20% of EEGs in patients with postinfarction seizures show paroxysmal activity. The presence of early seizures and recurrent strokes is a better predictor of epilepsy in stroke patients than are focal abnormalities on EEG.9
Ischemic Vascular Dementia
Multi-infarct dementia is usually distinguished from Alzheimer’s dementia by its sudden onset, fluctuating course, focal neurologic signs, and the presence of multiple infarcts as shown by the history or CT.10 In contrast, the cognitive and gait impairments characteristic of Binswanger’s disease may develop subacutely, without cortical infarcts on head CT (which may show only periventricular white matter lucencies and ventricular atrophy). Patients with Binswanger’s disease may come to medical attention with a TIA, seizure, repeated falls, pseudobulbar affect, or acute confusional state.
Transient Ischemic Attacks
Recent changes in the practice of medicine have resulted in more frequent management of TIA patients in the outpatient setting. Nevertheless, patients with a high risk of stroke should still be admitted to the hospital, especially those with a probable cardiac source of emboli and those who have had more than two TIAs within the last 2 weeks.2 Since retinal TIAs carry a lower risk of stroke than hemispheric TIAs, patients with retinal TIAs can usually be evaluated on an outpatient basis.
If cerebral angiography confirms the presence of high-grade stenosis (70% to 99%) of the symptomatic carotid artery, the treatment of choice is endarterectomy and aspirin.3 In a large randomized trial of aspirin alone versus aspirin combined with endarterectomy, TIA patients treated with both surgery and aspirin were found to have a 9% risk of stroke over 2 years, whereas those treated with aspirin alone had a 26% risk. Patients were not permitted to enter that study if they were over the age of 80 years, were mentally incompetent, had more severe siphon stenosis than proximal carotid stenosis, or had a limited life expectancy owing to cancer or organ failure.
If there is no evidence of either significant carotid stenosis or a cardiac source of emboli, antiplatelet therapy with aspirin or ticlopidine is indicated for stroke prophylaxis.12 Dipyridamole is usually reserved for patients who cannot tolerate either aspirin or ticlopidine. Most practitioners start therapy for TIA patients with one aspirin per day (325 mg/day), although some patients with recurrent TIAs may benefit from as many as four tablets per day (1300 mg/day). If TIA or stroke patients are intolerant of aspirin or if they continue to have strokes while taking aspirin, ticlopidine is indicated for stroke prophylaxis (250 mg bid). Hematologic monitoring is required during the first 3 months of ticlopidine therapy because about 1% of patients treated with this drug develop severe (rarely fatal) neutropenia during the first 12 weeks of therapy.
There is good evidence from clinical trials that TIA patients with nonvalvular AF should receive anticoagulation with warfarin, especially if they are women over the age of 75 or if they have other thromboembolic risk factors such as left ventricular dysfunction, hypertension, or prior stroke. Aspirin may be preferred, however, for AF patients who are at high risk for falls, have poorly controlled hypertension, or are unlikely to comply with close monitoring of coagulation parameters.
Acute Ischemic Infarction
New data are now appearing in the literature suggesting that thrombolytic agents can improve the functional outcome of survivors of acute ischemic stroke regardless of cause (atherothrombotic, cardioembolic, or lacunar). The most promising agent is tissue plasminogen-activating factor (tPA).17
The key to successful use of thrombolytic agents is administration of the drugs within the first 3 hours after the onset of symptoms. Despite the tenfold increase in cerebral hemorrhage, patients receiving tPA were at least 30% more likely to have a good functional outcome at 3 months. Current studies with tPA are examining ways of predicting in advance who might benefit the most and who is at highest risk of hemorrhage.
There is general agreement that most patients with acute ischemic stroke should not be treated with antihypertensive agents unless their calculated mean blood pressure is greater than 130 mmHg.16 The other exceptions include patients with acute myocardial infarction, acute renal failure, dissection of the thoracic aorta, or hemorrhagic transformation of a cerebral infarction. The best parenteral drugs for treating hypertension in patients with acute stroke are labetalol and nitroprusside.
Early mobilization of stroke patients should aid in preventing pneumonia and other complications. Corticosteroids should be avoided in those with acute ischemic stroke because their use is more detrimental than beneficial (more infections). If there are signs of increased intracranial pressure in a patient with an acute stroke, a trial of hyperventilation is recommended. Surgical intervention is necessary on the rare occasions when hydrocephalus develops or when a large cerebellar infarction is found. Use of heparin in acute stroke cannot be justified by scientific studies, but it is the standard of care in some communities.16 Prophylactic heparin, on the other hand, is strongly recommended for stroke patients who are immobilized.
The treatment of SAH depends on the patient’s neurologic status. Patients who are asymptomatic except for headache or a stiff neck should have early angiography with the goal of performing early surgical clipping of the aneurysm. During close monitoring prior to surgery, these patients need strict bed rest, oral nimodipine, and prophylaxis for deep vein thrombosis. Patients who are drowsy or obtunded may have to be intubated to protect the airway. SAH patients whose condition deteriorates rapidly may be taken to surgery for immediate clot removal and clipping of the aneurysm.
If CT of an ICH patient shows no evidence of midline shift and the patient is alert and awake, management on a general medical floor is feasible provided the nurses are given guidelines about the treatment of hypertension, headache, and changes in mental state. If the patient’s condition deteriorates, transfer to an intensive care unit is indicated. Families should be made aware of the high mortality rate in patients with ICH. There is general agreement that patients with cerebellar hemorrhages that cause signs of brain stem compression should receive mannitol and surgical decompression.16
Ischemic Vascular Dementia
There is good evidence that risk factor management is useful in treating patients with vascular dementia just as it is in those with TIA and small strokes.10 Occasionally these patients deteriorate if their blood pressure has been reduced excessively, so the goal should be to keep the systolic pressure in the range of 135 to 150 mmHg. Antiplatelet agents have been shown to be beneficial not only for stroke prevention but also for cognitive benefit in patients with vascular dementia. In a double-blind placebo-controlled trial, pentoxifylline produced improvement in cognitive function in patients with vascular dementia who had CT evidence of ischemic changes. The multiple mechanisms of action of this drug probably explain its therapeutic effect. It increases red cell deformability, inhibits plate-let aggregation, lowers plasma fibrinogen levels, and decreases the viscosity of whole blood.
We must communicate to our patients that 40% of all strokes can be prevented with better management of reversible risk factors such as smoking and hypertension. Patients also must learn that stroke is an emergency and that beneficial treatment of acute stroke can only be achieved in those who seek treatment within the first few hours of symptom onset. In addition to thrombolytic agents that dissolve the clots causing acute ischemic stroke, new protective agents are being developed to reduce the size of the infarct. Similar agents are being tested in patients with SAH to prevent infarcts from developing in association with vasospasm. If strokes can be prevented by reducing risk factors, we should see fewer patients with postinfarction epilepsy and vascular dementia. Patient education is the key.
Whisnant JP, Basford JR, Bernstein EF, et al: Classification of cerebrovascular disease III. Stroke 1990;21:637–676.
Brown RD, Evans BA, Weibers DO, Petty GW, Meissner I, Dale AJD: Transient ischemic attack and minor ischemic stroke. Mayo Clin Proc 1994;69:1027–1039.
North American Symptomatic Carotid Endarterectomy Trial Collaborators: Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445–453.
Amarenco P, Cohen A, Tzourio C, et al: Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. N Engl J Med 1994;331:1474–1479.
Strandgaard S, Paulson OB: Cerebrovascular consequences of hypertension. Lancet 1994;344:519–521.
Wolf PA, Abbott RD, Kannel WB: Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke 1991;22:983–988.
Broderick JP, Brott T, Tomsick T, Huster G, Miller R: The risk of subarachnoid hemorrhage and intracerebral hemorrhage in blacks compared to whites. N Engl J Med 1992;326:733–736.
Marmot MG, Poulter NR: Primary prevention of stroke. Lancet 1992;339:344–347.
So EL, Annegers JF, Hauser WA, O’Brien PC, Whisnant JP: Population-based study of seizure disorders after cerebral infarction. Neurology 1996;46:350–355.
Hershey LA, Olszewski WA: Ischemic vascular dementia. In Morris JC (ed): Handbook of Dementing Illnesses. New York, Marcel Dekker, 1994, pp. 335–351.
The EC/IC Bypass Study Group: Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. N Engl J Med 1985;313:1191–1200.
Hass WK, Easton JD, Adams HP, et al: A randomized trial comparing ticlopidine with aspirin for prevention of stroke. N Engl J Med 1989;321:501–507.
Siebler M, Sitzer M, Rose G, Bendfeldt D, Steinmetz H: Silent cerebral embolism caused by symptomatic high-grade carotid stenosis. Brain 1993;116:1005–1015.
Wannamethee SG, Shaper AG, Whincup PH, Walker M: Smoking cessation and the risk of stroke in middle-aged men. JAMA 1995;274:155–160.
Yao H, Sadoshima S, Ibayashi S, et al: Leukoaraiosis and dementia in hypertensive patients. Stroke 1992;23:1673–1677.
Adams HP, Brott TG, Crowell RM, et al: Guidelines for the management of patients with acute ischemic stroke. Stroke 1994;25:1901–1914.
NINDS Stroke Study Group: Tissue plasminogen activator for acute stroke. N Engl J Med 1995;333:1581–1587.
*All material in this chapter is in the public domain, with the exception of any borrowed figures or tables.