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Ischemic stroke continues to have a major impact on the public health of our nation. Ranking among the leading causes of death, stroke is far more disabling than fatal and results in enormous costs measured in both health-care dollars and lost productivity. Once considered untreatable, ischemic stroke has become subject to intensive scrutiny in recent years. Considerable research has led to a better delineation of risk factors, as well as an expanded understanding of pathophysiologic subtypes.
Definitions of TIA and Stroke
Ischemic stroke is characterized by the abrupt or ictal onset of neurologic dysfunction due to inadequate perfusion of the brain. By conventional clinical definitions, if the neurological symptoms continue for more than 24 hours, a person is diagnosed with ischemic stroke. Otherwise, a focal neurological deficit lasting less than 24 hours is defined as a transient ischemic attack (TIA). However, with the advent of more sensitive brain imaging, acute cerebral infarcts have been identified even when symptoms last less than 24 hours.
Definition of the Infarct Subtype
There are multiple mechanisms which may lead to brain ischemia. Hemodynamic infarction originates when there is an impediment to normal perfusion usually caused by a severe arterial stenosis or occlusion due to atherosclerosis and coexisting thrombosis. Embolism occurs When a particle of thrombus originating from a more proximal source (arterial or cardiac) travels through the vascular system and leads to a distal occlusion. Small vessel disease occurs when lipohyalinosis or local atherosclerotic disease leads to an occlusion of a small penetrating artery. Less frequent conditions which lead to reductions in cerebral perfusion and result in infarction are: arterial dissection, primary or secondary vasculitis, hypercoagulable states, vasospasm.
Atherosclerotic Infarction
Atherosclerotic plaque at a bifurcation or curve in one of the larger vessels leads to progressive stenosis with the final large artery occlusion due to thrombosis of the narrowed lumen. Arteriosclerotic plaques may develop at any point along the carotid artery and the vertebral-basilar system, either extracranial or intracranial. The most common sites are the bifurcation of the common carotid artery into the external and internal carotid arteries, the origins of the middle and anterior cerebral arteries, and the origins of the vertebral from the subclavian arteries. The site of infarction depends on the collateral flow, but is usually in the distal fields or border zones. Specifying the degree of stenosis that will lead to perfusion difficulty is dependent on multiple factors and is often not easily defined. Classification schemes have relied on stenoses greater than 70 to 80% as more predictive of impending hemodynamic compromise.
Cardiac Embolism
The most common sources of cardiac embolism include: atrial fibrillation, valvular heart disease (mitral stenosis, mitral regurgitation, rheumatic heart disease); intracardiac thrombus particularly along the left ventricular wall (mural thrombus) after anterior myocardial infarction or in the left atrial appendage in patients with atrial fibrillation; ventricular or septal aneurysm; and cardiomyopathies leading to stagnation of blood flow and an increased propensity for the formation of intracardiac thrombus.
Embolism is inferred when the brain image demonstrates an infarction confined to the cerebral surface territory of a single branch, combinations of infarcts involving branches of different divisions of major cerebral arteries, or hemorrhagic infarction. The difficult problem in arriving at a diagnosis of embolism is the identification of the occluding particle and the source. Mural thrombi and platelet aggregates are remarkably evanescent, as has been inferred by findings on angiography. Embolic fragments are found in over 75% of cases angiogramed within 48 hours.
Small vessel, Lacunar Infarction
These strokes have distinctive clinical syndromes with a small zone of ischemia confined to the territory of a single vessel. They are understood to reflect arterial disease of the vessels penetrating the brain to supply the internal capsule, basal ganglia, thalamus, corona radiata and paramedian regions of the brainstem. There are disagreements about the pathogenesis of lacunar infarcts with some favoring the use of the term "lacune" to describe size and location without indicating a specific pathology. Only a handful have been pathologically studied by serial section and documented a tiny focus of microatheroma or lipohyalinosis stenosing one of the deep penetrating arteries. The arterial damage is usually the result of long-standing hypertension.
Cryptogenic Infarction
Despite efforts to arrive at a diagnosis, the cause of infarction in a discouragingly large number of cases remains undetermined. Some cases may be unexplained because no appropriate laboratory studies are performed, while others are due to the improper timing of the appropriate laboratory studies. The most frequent circumstances are when normal or ambiguous findings are reached despite appropriate laboratory studies performed at the appropriate time. Results from the Stroke Data Bank indicated that large artery atherosclerotic occlusive disease was a less frequent cause.
Identify Stroke Risk Factors
Nonmodifiable stroke risk factors include age, gender, heredity, and ethnicity. There is an exponential increase in incidence of stroke with age, and the majority of strokes occur in persons over 65 years of age. Men have a greater stroke incidence than women, but women often live long enough to experience stroke and, therefore outnumber men in some stroke studies. A history of maternal stroke appears to be another gender-related risk factor. Stroke mortality among African-Americans is double that of white Americans. The incidence of stroke has been found to be greater in African-Americans, but further study is needed to assess the importance of referral and selection biases, confounding risk factors, and differential access to medical care. Little information is available regarding the rapidly growing Hispanic population.
Major reductions in stroke morbidity and mortality are more likely to arise from identification and control of modifiable factors in the stroke-prone individual. Modifiable stroke risk factors include: hypertension, cardiac disease (particularly atrial fibrillation), diabetes, hypercholesterolemia, asymptomatic carotid stenosis, cigarette use, alcohol abuse.
Risk Factor Modification
Risk factor modification may be attempted either through the "high risk approach" which identifies and seeks to modify the degree of risk in individuals with increased risk of disease; or through a "mass" approach which targets modification of risk factors detectable through the screening of large populations. Gorelick has estimated the potential savings, in lives and dollars, associated with either a "mass" or "high risk" prevention program. Based on the estimated prevalence of risk factors and their attributable risks for stroke in the United States, it is estimated that 246,500 strokes could be prevented from the control of hypertension alone and associated with a savings of $12.33 billion. A prevention program aimed at cigarette smoking could prevent over 61,000 strokes with an associated savings of over $3 billion. Even if these programs were only 25% successful in reducing hypertension and smoking, over $3.8 billion may be saved in stroke related care. Treatment of atrial fibrillation and modification of heavy alcohol use could eliminate 47,000 and 23,500 strokes, respectively.
Hypertension Control
There are very few studies which have documented that treatment of hypertension will decrease the risk of stroke occurrence after TIA or stroke recurrence after minor stroke. Numerous prospective studies and clinical trials, however, have consistently shown a decreased risk of stroke with control of mild, moderate, and severe hypertension in all age groups of stroke-free subjects. A meta-analysis of 9 prospective studies including 420,000 individuals followed for 10 years found that stroke risk increased by 46% for every 7.5mm Hg increase in diastolic blood
Carotid Endarterectomy for Asymptomatic Carotid Stenosis
The efficacy of carotid endartectomy in asymptomatic carotid stenosis has been evaluated in three separate clinical trials: CASANOVA (Carotid Artery Stenosis with Asymptomatic Narrowing: Operation Versus Aspirin), Veterans Administration Asymptomatic Carotid Endartectomy Study, and ACASS (Asymptomatic Carotid Artery Surgery Study). While CASANOVA found no confirmatory data to support carotid endartectomy for treatment of asymptomatic carotid disease, this trial excluded all cases with high grade stenosis greater than 90%. The Veterans Administration trial confirmed a decrease in neurological events, specifically transient ischemic attack (outcomes reduced from 20% to 8%), associated with the carotid endartectomy treatment group versus the medical treatment group, but no significant reduction for ipsilateral stroke.