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Lawrence Wechsler
Tudor G. Jovin

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Better Stroke Treatment May Come from Physiological Determinations Rather than Time Frame, According to University of Pittsburgh Study

PITTSBURGH, October 28, 2003 Determining the type of treatment for acute stroke caused by blockage of large vessels in the brain can best be decided by measuring both the amount of brain tissue that is threatened but not yet dead (ischemic penumbra) and the amount of brain that is already dead (ischemic core), according to groundbreaking University of Pittsburgh research published in the October issue of Stroke, a journal of the American Heart Association.

This view challenges the currently used selection methods for acute stroke therapy, which utilize time after onset of stroke as the main selection criteria.

The study supports the theory that patient selection for acute stroke therapy based on physiology rather than on time may lead to expansion of the therapeutic window, improved outcomes and fewer side effects than currently achieved. This approach requires early determination of both irreversible ischemic core and reversible penumbra in acute stroke.

The study was led by Tudor Jovin, M.D., assistant professor of neurology at the University of Pittsburgh School of Medicine and a member of the University of Pittsburgh Medical Center Stroke Institute. Researchers used xenon-enhanced CT scans, one of the few technologies that allows accurate quantitative cerebral blood flow measurement in human stroke, to evaluate 36 patients with middle cerebral artery (MCA) occlusion who were studied within six hours of symptom onset. They found that patient outcomes were correlated to core and penumbra and not to the time between stroke onset and the point in time at which they were studied.

The results indicated that doctors might be better able to treat patients with stroke if they know how much tissue is damaged beyond repair and how much might be salvageable. Currently most guidelines for treatment using recanalization, or re-opening blocked blood vessels, use time as the primary factor.

Treatment options in acute stroke include drugs or devices that aim to unblock occluded arteries (thrombolysis), interventions aimed at enhancing blood flow in the affected area through collateral channels and drugs or interventions aimed at lessening the damage produced by blocked vessels through neuroprotection. This can even include brain bypass surgery, a novel approach developed at the University of Pittsburgh.

The goal in acute stroke therapy is to salvage the penumbra, or brain tissue that is threatened to progress to irreversible damage, but is not irreversibly compromised at the time of treatment. We measured the amount of already dead brain tissue, ischemic core, and the threatened brain tissue, the ischemic penumbra, and found that, irrespective of the point in time relative to symptoms onset, the penumbra is relatively constant, while the extent of core varies greatly, Dr. Jovin said.

One implication of our findings is that selection of patients for acute stroke therapy based on determination of these parameters, especially on the extent of ischemic core, may be better than the currently used selection based on time, he said.

The hypothesis remains to be proven in prospective studies using imaging technologies that will allow accurate identification of core and penumbra in acute stroke patients, he added.

Also participating in the study from the University of Pittsburgh were Howard Yonas, M.D., professor of neurosurgery; James M. Gebel, M.D., assistant professor of neurology, Lawrence R. Wechsler, M.D., professor of neurology and director of the UPMC Stroke Institute and Emanuel Kanal, M.D., professor of radiology.

Stroke is the third most common cause of death and a leading cause of chronic disability in North America, with more than 750,000 new cases occurring annually.

The UPMC Stroke Institute is dedicated to the treatment and prevention of stroke. At the Institute, UPMC doctors with a wide variety of specialties join together to offer the very latest techniques of stroke diagnosis and treatment. Multispecialty care allows institute physicians to treat stroke patients and patients at risk of stroke who also suffer from heart disease, diabetes and other serious illnesses. Institute physicians also participate in clinical studies of new stroke treatments that promise to limit or prevent stroke disability.

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