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Stroke Drug May Have Wider Window of Opportunity

Study suggests some may benefit six hours after symptoms

FRIDAY, Jan. 25, 2002 (HealthDayNews) -- A new study suggests certain stroke patients may benefit from clot-busting drugs up to six hours after symptoms start, instead of the three hours previously thought.

The researchers also found magnetic resonance imaging (MRI), rather than computed tomography (CT), may be a better way to determine which patients will benefit from the therapy. Their work appears in the January issue of the Annals of Neurology.

Ischemic stroke, the most common type of stroke, occurs when a blood clot or clots block arteries to the brain, disrupting blood flow. Victims can end up with paralysis, loss of speech or memory impairment. Recovery from this or any type of stroke depends on whether the affected brain tissue lives or dies. This, in turn, is dependent on how long and how severe the disruption to blood flow is.

It's fairly easy to measure the time involved in a stroke, but not so easy to measure the severity, experts say. Even if an artery is blocked, other arteries may provide enough blood to keep the brain tissue alive for some time. The clot-busting drug rt-PA, approved by the U.S. Food and Drug Administration in 1996, has been shown to "rescue" brain tissue that lives through the early stages of an ischemic stroke. Standard practice has been to administer the drug within three hours of the onset of stroke symptoms, which means only a fraction of stroke victims receive the treatment.

"Our work and that of others does indicate that MRI can help us define patients who will have the greatest potential to respond to rt-PA and possibly other therapies beyond clinical time windows," says Dr. Stephen Davis, co-author and professor of neurology at Royal Melbourne Hospital and at the University of Melbourne in Australia.

"It is without a doubt a hopeful sign," says Dr. Don B. Smith, director of the Stroke Program at the Colorado Neurological Institute in Denver. "It means that there is hope for some patients beyond the three-hour window. We may be able to reliably identify them, and effectively treat them.

"Stroke specialists are well aware that some strokes can be treated beyond the three-hour time window, with excellent benefit," Smith explains. "The trouble is, we haven't had a good way to identify those patients who will benefit because we can't reliably tell how much salvageable tissue is present."

MRI technology may be the key to figuring out how much tissue can be saved -- and thereby determining who should get this or other treatments. In this study, the researchers looked at two different imaging tests done with MRI. One is diffusion-weighted imaging (DWI), which shows the area of the brain that has been permanently damaged. The other is perfusion-weighted imaging (PWI), which shows a larger area, some of which may be salvageable.

Researchers predicted that, when the PWI showed a larger area than the DWI, stroke drugs might help beyond the conventional three-hour limit.

To test the hypothesis, 16 patients with stroke symptoms were given MRIs and determined to show this "mismatch" between PWI and DWI. The patients were then given rt-PA an average of four hours after onset of symptoms, and their progress was monitored. The researchers then compared these patients to 16 patients who had suffered similar strokes, but were not treated with rt-PA. All the information was gleaned from medical files. Brain damage was reduced in the patients who received the clot-busting drug, even if it was after the three-hour mark.

That's not to say stroke victims should delay getting help.

"Timing is still critical," says Smith. "For acute stroke, earlier treatment will always be better than the same treatment given later."

The study has some limitations: It was small, non-randomized and non-blinded, which are hallmark features of studies that carry more weight among doctors.

MRI is also not as quick or easy to use as CT scans: They take about 20 minutes and the patient has to be still; CT scans take about five minutes, even on a restless patient.

The Australian researchers are moving ahead with a prospective, randomized study called EPITHET (Echoplanar Imaging Thrombolytic Evaluation Trial) involving 50 rt-PA patients and 50 controls.

"MRI is likely to predict treatment responders to rt-PA beyond the currently accepted three-hour time window, but the EPITHET trial is required to confirm this hypothesis," says Davis.

What To Do

According to the National Stroke Association, stroke is the nation's third-leading cause of death, killing 160,000 people every year. Every year, more than 750,000 Americans have a stroke.

If you have any of these symptoms, call 911 right away. Every minute counts, even if the window for the stroke drug may be wider.

The National Institute of Neurological Disorders and Stroke has more about brain attacks.

SOURCES: Interviews with Stephen Davis, M.D., professor, neurology, Royal Melbourne Hospital and University of Melbourne, Australia; Don B. Smith, M.D., director, Stroke Program, Colorado Neurological Institute, Denver; January 2002 Annals of Neurology
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