Session 3: Thrombolytic Therapy for Acute Stroke

One of the paradoxes of modem thrombolytic therapy is the investigation of cerebral thrombolysis for acute stroke at a time when we recognize recent cerebral infarction as a contraindication to coronary thrombolytic therapy and when intracranial hemorrhage is one of the most feared complications of thrombolysis. While acute cerebral infarc- tion is generally a thrombotic event that should respond to thrombolysis, there are factors involved in cerebral throm- botic events that must be better understood prior to en- dorsement of thrombolytic therapy for acute thromboem- bolic cerebral infarction.

There are similarities between the use of thrombolytic therapy for myocardial infarction and its use for acute thromboembol ic stroke. Both myocardial and cerebral tissues have a tinre-dependent ability to recover from ische- mia. Both tissues appear sensitive to reperfusion injury. Vas- cular thromboses in both vascular beds appear responsive in part to thrombolytic agents. While the similarities are im- portant, considerable differences also exist. For example, while coronary thrombotic lesions are commonly found at the site of a prior stenosis, cerebral thromboses commonly embolize. The potential for reperfusion hemorrhage also appears greater in cerebral than in coronary vessels.

At the present s thrombolytic therapy for acute throm- boembolic stroke is investigational. This therapy must first undergo careful study in acute interventional stroke center trials. The multidisciplinary approach needed to efficiently identify and enroll patients in this new form of therapy was reflected in the diverse backgrounds and clinical practice areas of the panelists for this session. William G Barsan, MD, an emergency physician, addresses the initial patient assessment and enrollment approach needed in interven- tional stroke therapy. Gregory J del Zoppo, MD, a hema- tologist, addresses the process of acute cerebral thrombosis and therapeutic lysis. Thomas G Brott, MD, a neurologist, addresses the heterogeneity of cerebral thromboembolic stroke and the time dependency of neurologic function.

Dr Barsan has been the emergency medicine liaison for the multidisciplinary acute stroke research team at the Uni- versity of Cincinnati for several years. Through his par- ticipation as a coinvestigator on three major stroke studies, he has emphasized the role of the emergency physician in the care of stroke patients. The emergency physician must help identify candidates for acute interventional stroke therapy and expedite enrollment of patients in the study. This often requires public education, prehospital care pro- vider training, emergency department protocol development and implementation, and collaboration with other stroke

team members. Dr Barsan emphasizes these factors and the experience at the University of Cincinnati. As other prom- ising acute stroke therapies become available, emergency physicians will need to build on this experience if they are to participate in the multidisciplinary team needed to deliv- er modem stroke therapies.

Dr del Zoppo is the principal investigator of the multi- center tPA in Acute Stroke Study Group investigation. This multicenter study is fashioned in a manner similar to early myocardial tPA trials. His patients receive both a cranial CT scan and cerebral angiography prior to thrombolysis. Re- peat CT scan and cerebral angiography are used to docu- ment the response to therapy. As noted by Dr del Zoppo, cerebral angiographic studies of acute cerebral thromboses have been relatively limited. The recanalization response to cerebral thrombolytic therapy also is largely unknown. Studies such as these are needed to correlate neurologic def- icits with vascular occlusion sites, determine the dose-re- sponse to thrombolytic agents, assess neurologic response to documented thrombolysis, and evaluate the risk of hem- orrhagic complications as a function of vascular occlusion site.

Dr Brott is the University of Cincinnati principal investi- gator in the current NIH-funded multicenter tPA in Acute Stroke investigation. This study mandates a rapid (90-min- ute} enrollment time from stroke ictus to therapy and uses neurologic function and serial CT scans rather than an- giography to assess a response to therapy. This ongoing study, which evaluates the safety of early thrombolytic ther- apy for acute stroke, is limited by the absence of control patients to document functional neurological improvement in comparison with standard stroke therapy.

Dr Brott also emphasizes the limits of our knowledge about the composition of cerebral thromboemboli and their location at the time of a stroke and its subsequent evolu- tion. Perhaps newer scanning modalities such as cranial magnetic resonance scanning, when available with a more rapid scanning capability, will permit on-line evaluation of the response to thrombolytic therapy. Nonetheless, the knowledge obtained from the ongoing stroke study Dr Brott describes will help refine the team approach used for rapid patient enrollment and help delineate the appropriate dos- age of tPA for acute stroke and thus will guide future con- trolled studies.

Hence, the papers on this investigational therapy for acute thromboembolic stroke are reminiscent of the early papers on coronary thrombolysis reported five years ago. The authors of this session's papers are truly leaders in in-

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terventional stroke therapy. Five years from now, other new therapies for thromboembolic stroke may be under investi- gation, but such therapies undoubtedly will be based on the work of these researchers.

]erris R Hedges, MD, FACEP Division of Emergency Medicine Oregon Health Sciences University Portland, Oregon

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