Stroke. Revolution in therapy.

Stroke remains the third leading cause of death in this country, although recent advances in both clinical and basic science research have revolutionized the concept of stroke. Studies of primary and secondary stroke prevention have now documented the means to prevent thousands of cases of stroke each year. Three distinct strategies are evolving for intervention in the acute stroke process. Evidence is clear that ischemia leads to a toxic accumulation of intracellular calcium, in part mediated by excitatory neurotransmitters such as glutamate. Glutamate antagonists have shown clear benefit in experimental stroke models, and early clinical trials are underway. Acute revascularization to restore perfusion is also feasible and may minimize the extent of infarction. Studies of fibrinolytic agents are promising, with randomized clinical studies being done. While reperfusion is desired, it may be associated with additional neuronal injury. The development of anaerobic metabolism followed by reperfusion and aerobic conditions favors oxidation and free-radical formation. This mechanism of injury can be decreased by agents known to scavenge free radicals, and clinical trials are also testing this. This revolution in the understanding of ischemia, as well as the outpouring of new pharmacologic agents, is making stroke a true neurologic emergency requiring immediate intervention.