During the last decade scientists in both basic and clinical research have renew ed their interest in the potential role of thrombolytic therapy in the treatment of acute ischemic stroke. The reevaluation of this approach was kindled by our growing knowledge of the pathogenesis of thrombotic and embolic stroke and by the development of new thrombolytic agents. With no proven therapy for acute ischemic stroke available, the potential value of early pharmacologic recanalization of occluded vessels in the management of acute stroke patients - an approach that has been supported by animal experiments and a limited number of uncontrolled clinical pilot studies - is again under scrutiny. A sym posium on "Thrombolysis in Acute Cerebral Ischemia" was held in Heidel berg, Germany, in May 1990 to summarize and discuss the pathophysiological background for thrombolysis in acute ischemic stroke and the recent ex perimental and clinical experience with the new generation of thrombolytic agents. The editors are fortunate to be able to include authoritative manuscripts from almost all the speakers at the symposium. These include reports of work by the most active investigators in this challenging field. The editors wish to express their gratitude to all the contributors for the additional work they have undertaken. Additionally, we would like to thank Springer-Verlag, Heidelberg, for its generous assistance in the preparation and rapid publication of this volume. Heidelberg, August 1990 WERNER HACKE GREGORY J. DEL ZopPO MATTHIAS HIRSCHBERG Contents I.

I. Acute Cerebral Ischemia and Thrombolysis

Natural History of Atherothromboembolic Occlusion of Cerebral Arteries: Carotid Versus Vertebrobasilar Territories
Fibrinolysis: Thrombolytic Agents, Mechanisms, and New Developments
Fibrinolysis in Myocardial Infarction: Lessons for Cerebrovascular Disease
Reperfusion of Ischemic Brain: Why and Why Not!
Thrombolysis in Stroke: Timing of Recanalization and Its Clinical Consequences
The Ischemic Penumbra: Fact or Fiction?
Hemorrhagic Transformation in the Natural History of Acute Embolic Stroke
Intracranial Hemorrhage After Coronary Thrombolysis with Tissue Plasminogen Activator
Predictive Factors for the Effective Treatment of Acute Stroke with Intravenous Thrombolytic Agents
Invasive Imaging Techniques in the Evaluation of Patient Selection and Cerebrovascular Recanalization
The Role of Noninvasive Imaging Techniques in Cerebrovascular Recanalization
II. Thrombolysis and Stroke Models
Thrombolytic Therapy in Ischemic Stroke: Relevance and Limitations of Animal Models
Update on Animal Model Experience with Recombinant Tissue Plasminogen Activator
III. Clinical Trials
Clinical Trials: Some General Considerations
Intraarterial Urokinase Plasminogen Activator and Streptokinase in Carotid and Vertebrobasilar Territory Stroke: Clinical Outcome
Fibrinolytic Recanalization Therapy in Acute Cerebrovascular Thromboembolism
Intravenous Recombinant Tissue Plasminogen Activator in Acute Thrombotic Stroke: Study Design, Recanalization, and Clinical Outcome
Evaluation of Tissue Plasminogen Activator Early in the Course of Acute Ischemic Stroke
Intravenous Recombinant Tissue Plasminogen Activator in Acute Stroke
Thrombolytic Therapy in Embolic and Thrombotic Cerebral Infarction: A Cooperative Study
IV. Future Directions
Problems in Formulating Therapeutic Trials
Invasive and Noninvasive Vascular Imaging Techniques and Their Role in Clinical Stroke Trials
Strategies for Early Treatment of Acute Cerebral Infarction
V. Open Communications
Topical Intraarterial Urokinase Infusion for Acute Stroke
Local Thrombolytic Therapy in Acute Basilar Artery Occlusion: Experience with 18 Patients
Vertebrobasilar Occlusion: Outcome With and Without Local Intraarterial Fibrinolysis
Recanalization of Acute Middle Cerebral Artery Occlusion Monitored by Transcranial Doppler Sonography
Neuropathological Findings After Thrombolytic Therapy in Acute Ischemic Stroke
How Many Stroke Patients Are Candidates for Thrombolysis?
Spontaneous Recanalization in Middle Cerebral Artery Occlusion
In Vitro Thrombus Lysis by Urokinase in Preparation for Patient Studies
Local Intraarterial Fibrinolysis in Acute Middle Cerebral Artery Occlusion
Treatment of Acute Ischemic Stroke with Recombinant Tissue Plasminogen Activator: Evaluation with Regional Cerebral Blood Flow Single Photon Emission Computed Tomography
Thrombolytic Therapy in Acute Ischemic Stroke: The Copenhagen Multicenter Study
Thrombolytic Therapy in Cerebral Sinus Thrombosis: A Case Report
Basilar Artery Occlusion Associated with Protein C Deficiency: Successful Treatment Using Recombinant Tissue Plasminogen Activator Infusion
Intracerebral Hemorrhage and Infarction Volume Following Recombinant Tissue Plasminogen Activator in an Acute Stroke Model
Prourokinase Therapy in Stroke.