Hyperacute stroke diffusion- and perfusion-weighted MRI distinguishes t-PA responders
Background: There is an urgent need to better select candidates for t-PA based on knowledge of cerebral pathophysiology rather than a rigid time window. Methods: We therefore studied 14 consecutive patients with acute hemispheric stroke with diffusion- (DWI) and perfusion-weighted imaging (PWI) prioe to 3 hours of stroke onset, and again at days 3 and 90. Seven patients received intravenous t-PA, 6 were imaged prior to t-PA. The 7 patients that did not receive t-PA were used as a control group as they each fulfilled clinical criteria for t-PA administration. Results: 12/14 patients had PWI > DWI mismatch, 5/7 in the t-PA group and all 7 in the control group. One of the 2 exceptions was the only patient who received t-PA prior to imaging. The second DWI > PWI patient was treated with t-PA, but died due to hemorrhagic transformation. Of the PWI > DWI mismatch patients, there was no major infarct expansion in 4/5 of the t-PA group, whilst all 7 patients not receiving t-PA had major infarct expansion (chi squared = 7.2, p=0.01). In addition, the extent of acutely hypoperfused tisse salvaged from infarction was greater in the t-PA group (mean 64% vs mean 29%; p=0.02). All 7 of the t-PA patients had major reperfusion, as opposed to 3/7 control patients (chi squared = 4.9, p = 0.03). Conclusions: Patients with PWI > DWI mismatch treated with t-PA had attenuation of infarct expansion and greater salvage of acutely hypoperfused tissue from infarction. This is best explained by thrombolysis-enhanced reperfusion. This study suggests that patients with PWI > DWI mismatch have the greatest potential to benefit from thrombolytic therapy. As 75% of patients still have PWI > DWI mismatch at 6 hours after stroke onset, we postulate that patients with this pattern may still have salvageable tissue with t-PA beyond the currently accepted 3 hour window. We aim to further test this hypothesis in a multicentre, randomised, placebo-controlled trial in acute stroke patients presenting 3–6 hours after symptom onset.