Primer: Stroke

Stroke is a sudden focal neurologic deficit caused by either ischemia (80% to 85% of all strokes) or hemorrhage (15% to 20% of all strokes).


Classification and epidemiology

Stroke is a sudden focal neurologic deficit caused by either ischemia (80% to 85% of all strokes) or hemorrhage (15% to 20% of all strokes). Impaired cerebral blood flow causes ischemic stroke, or cerebral infarction. This condition may be further characterized by the etiologic mechanism. Transient ischemic attack (TIA) is a sudden ischemic focal neurologic deficit that resolves completely. TIAs are classically defined as lasting less than 24 hours, although some have recently advocated that a duration of less than 1 hour should define this condition. Hemorrhagic stroke is classified as either subarachnoid (5% of all strokes) or intracerebral (intraparenchymal) (10% to 15% of all strokes).

Stroke is a leading cause of disability and the third leading cause of death in the U.S. The annual incidence of stroke in the U.S. is estimated to be 700,000 to 750,000, and about 20% of these cases are recurrent strokes. The risk for stroke increases exponentially with age. Furthermore, black patients have an excess stroke burden relative to white patients and have higher stroke mortality.

Overall, the direct costs due to stroke exceed $50 billion annually in the U.S. Hospitalization accounts for approximately 50% of these costs, and rehabilitation and long-term care account for the remainder. The costs of lost productivity for patients, caregivers, and families may be immeasurable.

Pathophysiology of stroke and TIAs

The clinical manifestations of stroke and TIA depend predominantly on the location of the stroke within the central nervous system. Occlusion of the middle cerebral artery or one of its branches is most common, resulting in contralateral hemiparesis and hemisensory and visual field loss, as well as aphasia with left hemispheric stroke and neglect (hemi-inattention) with right hemispheric stroke.

Small, deep penetrating arteries that arise from the larger vessels also may be affected by stroke. Occlusion of these vessels may cause small infarctions with stereotypical clinical “lacunar” syndromes, such as pure motor hemiparesis, pure sensory stroke, clumsy hand-dysarthria syndrome and ataxic hemiparesis. Stroke may occur in the spinal cord as well, but this is quite rare. Of importance, ischemic and hemorrhagic strokes may have identical clinical presentations, though headache, nausea, vomiting and severe hypertension may be more common with hemorrhage.

Emergency evaluation of a patient with acute stroke

Stroke is a time-critical medical emergency. Within the first minutes to hours after the onset of cerebral ischemia, an infarct core, which is an area of brain that is irreversibly damaged, develops. The ischemic penumbra, which is potentially viable brain tissue, surrounds this area and will eventually become part of the infarct core if blood flow is not restored quickly. The time course of this process is poorly defined. Substantial volumes of brain potentially remain viable for up to 24 hours after stroke in extreme cases, but most damage occurs in the first 3 to 6 hours post-stroke. Therefore, the penumbra is the target of acute ischemic stroke therapy.

Patients presenting with the sudden onset of neurologic dysfunction or reporting neurologic signs and symptoms evolving over a few minutes to a few hours most likely have experienced a stroke. Ischemic stroke is more likely in this setting compared with hemorrhagic stroke. However, the differential diagnosis should include stroke mimics.

Evaluation of the patient with suspected stroke or TIA should be efficient and streamlined to minimize the time required. An extensive neurologic examination usually is not necessary for initial assessment. For example, testing of memory, deep tendon reflexes and extensor plantar response is of limited value for differential diagnosis, localization or determination of stroke severity. A more thorough examination may be performed after the acute diagnostic and treatment decisions are made.

The National Institutes of Health Stroke Scale offers rapid clinical assessment of key components of the neurologic examination in less than 5 minutes. (Training is available at asa.trainingcampus.net.) Moreover, use of this tool appears to improve communication among health care providers and may indicate a clinically meaningful change in patient status. The Glasgow Coma Scale is not useful as an assessment tool for the vast majority of stroke patients.

Patients who have a stroke or TIA are at high risk for recurrent vascular events. Most often, the recurrent event will be a stroke. However, these patients also have increased risk for myocardial infarction and vascular-related death. Among patients with TIA, a duration of more than 10 minutes, limb weakness, speech disturbance, age older than 60 years and a history of diabetes have been shown to be associated with a high risk for subsequent stroke. Because the risk for subsequent major vascular events is particularly high even in the first few days after the initial event, urgent evaluation is warranted for all patients with stroke or TIA. In addition, many experts recommend hospitalization for nearly all patients with acute cerebrovascular symptoms.

Before considering specific treatment for stroke, neuroimaging is indicated. Clinical signs and symptoms are not sufficiently accurate to distinguish ischemic from hemorrhagic stroke, and the treatment options for these two conditions are quite different.

Neuroimaging in acute stroke

CT of the brain without radiocontrast is initially indicated for patients with suspicion for stroke. This study reliably distinguishes acute intracerebral hemorrhage from ischemia. CT is relatively insensitive to ischemic changes in the first few hours after stroke, and early CT findings may be subtle, including hyperdense vessels (suggestive of acute intraluminal thrombus), loss of boundaries between gray and white matter and effacement of cerebral sulci. However, these subtle findings are highly specific for ischemic stroke. CT is nearly 100% sensitive for intracerebral hemorrhage and about 90% sensitive for subarachnoid hemorrhage.

MRI also is an option for the evaluation of patients with acute stroke, although this approach is more expensive, usually more time-consuming and less available compared with CT. Therefore, MRI currently is not the standard of care in this setting. Identification of potentially viable ischemic penumbra, which some MRI techniques may achieve, is believed to be clinically relevant because early therapy may salvage substantial brain tissue. Physiologic imaging may detect the presence of penumbra, which may be fairly large, surrounding a smaller core of infarcted tissue.

Diffusion-weighted MRI is extremely sensitive to very early cytotoxic changes and may detect infarction many hours before CT or conventional MRI. However, this technique may slightly overestimate the size of permanently damaged tissue. Quantitative analysis of the calculated apparent diffusion coefficient may more accurately identify permanently infarcted tissue. Perfusion-weighted imaging demonstrates regionally reduced cerebral blood flow. The difference between the perfusion defect and the diffusion defect is believed to represent penumbra.

Additionally, magnetic resonance spectroscopy may identify biochemical markers of the extent of ischemic injury. Similarly, CT may be coupled with inhalation of xenon to create a graphical map of cerebral blood flow, which may be used to surmise areas with profoundly ischemic tissue (analogous to diffusion-weighted MRI) and areas with moderately decreased perfusion (analogous to perfusion-weighted MRI). However, these advanced imaging techniques are not widely available, particularly in community hospitals, and are therefore rarely used for clinical decision making in the acute setting.

Neuroimaging also may characterize the acute vascular lesion. The gold standard for evaluating this condition is conventional angiography, which may demonstrate acute occlusion or an embolus lodged at or near a vascular bifurcation. However, the vasculature may be visualized noninvasively with CT angiography (CTA), magnetic resonance angiography (MRA) or transcranial Doppler ultrasonography. In most instances, however, this information is not critical for initial treatment decisions.