Effective treatment of acute ischemic stroke requires rapid assessment and early intervention. Currently, the only effective therapy is thrombolysis with tissue plasminogen activator (tPA) within three hours after the onset of stroke. However, a number of potential delays make early diagnosis and treatment difficult. Kasner and Grotta review the pathophysiology of cerebral ischemia and the implications for treatment, identify some of the potential delays that commonly occur in diagnosing stroke and offer ways to expedite diagnosis and treatment.
Stroke occurs as a result of a specific sequence of events that happen after abrupt interruption of blood flow to the brain. The level of brain injury depends on the severity and duration of ischemia. In the hours after stroke, cytokines and cell adhesion molecules stimulate local inflammation, which further impairs blood flow. Reperfusion must occur within three hours of the onset of symptoms to preserve a substantial portion of the brain tissue at risk.
Treatment of acute stroke focuses on restoring cerebral perfusion and protecting neural tissue. Thrombolysis with tPA has demonstrated a positive effect on reperfusion since tPA converts plasminogen to plasmin, which causes cleavage of fibrin and ultimately results in rapid lysis of the clot. At this time, neuro-protective therapies and streptokinase are not effective in the treatment of acute stroke. For tPA to be effective, however, early diagnosis and rapid intervention are essential; patients targeted for tPA intervention must meet very specific inclusion and exclusion criteria to reduce the risk of hemorrhage (see accompanying table). In addition, careful analysis of the initial computed tomographic (CT) scan also appears to be critical in reducing the risk of intracranial hemorrhage. During the first 24 hours, patients given tPA cannot take anticoagulant and antiplatelet agents.
Delays in recognition and treatment can be summarized by using the four D's: door (time until treatment), data (obtaining an electrocardiogram), decision (choice of therapy with thrombolysis) and drug (choice of agent). Education among health care providers at all levels and among the public as well is needed to expedite stroke treatment. Within the hospital, the use of a “stroke team” composed of neurologists, emergency physicians and nurses, along with radiologists and pharmacists, is appropriate to streamline diagnostic testing and emergency care of patients with signs and symptoms of stroke. If the criteria for thrombolysis are met, tPA infusion should be initiated in the emergency department, and the patient should be monitored closely for 24 hours.
The authors conclude that time is the most critical element in the successful treatment of an acute ischemic stroke. Since neural tissue is extremely sensitive to ischemic injury, thrombolysis with tPA should occur within three hours of the onset of symptoms if the patient meets the criteria for this therapy. Care of acute stroke must parallel that of acute myocardial infarction in ensuring early diagnosis and rapid intervention. A door-to-drug interval of 60 minutes is recommended as part of successful management.