PWI/DWI brain mismatch widens stroke window

Results of a multicenter international trial indicate MRI perfusion-diffusion mismatch can add a crucial three extra hours for safe administration of tissue plasminogen activator to treat qualified acute stroke patients.

The phase II Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) involved 101 patients with acute ischemic stroke at 15 sites in Australia, New Zealand, Belgium, and Scotland. They all arrived in the emergency room more than three hours after symptom onset, which would usually disqualify them for clot-busing tPA treatment. Under these experimental conditions, however, 52 patients with DWI/PWI mismatch were randomly selected to receive tPA up to six hours after symptom onset. Another 49 with mismatch were given a placebo.

Investigators found that tPA can restore cerebral blood flow and improve clinical outcomes in these patients. "Although we did not find a statistically significant difference in functional outcome, there was a strong trend to improved outcome in the tPA group," said principal investigator Dr. Stephen M. Davis, a professor of neurology at the University of Melbourne in Australia.

He reported a 7.7% rate of symptomatic intracranial hemorrhage among patients who received tPA in the three to six-hour time frame and no instances of ICH for patients who received the placebo. The findings were consistent with rates reported in previous studies for sub-three hour tPA administration, he said.

"The results add weight to the idea that these are responders to tPA and possibly other reperfusion techniques beyond the current time window of three hours," Davis said. "Still, further studies should be done to confirm the clinical benefits beyond three hours."

Findings were announced at the American Stroke Association's 2008 International Conference in New Orleans.

-By H.A. Abella