P. N. Sylaja, MD, Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, AB.
Philip A. Barber, MD, MRCP (UK), FRCPC, Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, AB.

The very old represent the fastest-growing segment of the population in developed and developing countries and, in view of the increased incidence of stroke with advancing age, stroke-related disability is expected to increase in the population. Although patients more than 80 years of age account for 30% of the patients with strokes, the role of intravenous thrombolysis in this age group is insufficiently defined. There are no randomized trials that focus specifically on older patients with acute ischemic stroke. Recently, several case series on the use of intravenous tissue plasminogen activator (tPA) in older adults in clinical practice have shown that the outcome of older patients after stroke is poor, but the risk of symptomatic intracerebral hemorrhage (SICH) after tPA has been variable, ranging from 4.4-13%. Current evidence suggests that, by careful selection, tPA may be safely given to older adults without increased risk of SICH within the three-hour time window. Further randomized data from trials will allow more definitive conclusions on the use of tPA in the older population.
Key words: thrombolytic therapy, acute stroke, cerebral ischemia, tissue plasminogen activator, symptomatic intracerebral hemorrhage.

Dr. Denis DeSilvey
Associate Professor of Clinical Internal Medicine,
Department of Internal Medicine,
Division of Cardiovascular Medicine,
University of Virginia,
Charlottesville, VA.

Thrombolytic therapy for the management of acute myocardial infarction is one of the major advances in cardiovascular medicine in the last fifteen years. Beginning in the mid 1980s, an increasing body of literature supported the concept of the early administration of a thrombolytic agent, either streptokinase or tissue plasminogen activator (TPA), to salvage ischemic myocardium. The concept that 'time is muscle' took hold and has dominated our thinking about the management of acute ST segment elevation injury.

The guidelines of the American Heart Association and the American College of Cardiology¹ as well as the review in the Fibrinolytic Therapy Trialists' Collaborative,² show that fibrinolytic therapy reduces mortality for 18-30% of patients with acute myocardial infarction when given within 6 to 12 hours of the onset of pain. These excellent results were supported by subsequent studies such as the Second International Study of Infarct Survival (ISIS-2)³ and the Gruppo Italiano per lo Studio dell Streptochinasi nell'Infaarcto Miocardico (GISSI).⁴

Joyce So, BSc

While thrombolytic therapy has become an established part of treatment for acute ischemic heart disease, the controversy continues regarding its potential and practical use in acute ischemic stroke. In a situation where time is of the essence, is thrombolysis the best available solution?

Acute ischemic stroke (AIS), or "brain infarction", is most commonly a result of intracerebral artery occlusion due to embolism from proximal sites such as the internal carotid arteries, heart or aorta. Unlike cardiac arrest, where brain viability is measured in minutes, AIS presents with a mixture of salvageable tissue, allowing for a therapeutic window that can last several hours. While the definitive time frame has yet to be pinned down, the generally accepted mantra "Time is Brain" reflects the notion that prognosis is improved by early intervention. The question now is whether there is a role for thrombolytic therapy in the management of AIS.

The two most prominent candidates for use in thrombolytic AIS therapy are streptokinase and recombinant tissue plasminogen activator (rtPA), both serine proteases that catalyze the conversion of plasminogen to plasmin, which digests fibrin clots.