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(Stroke. 2009;40:2572.)
© 2009 American Heart Association, Inc.

Research Letters

Clinical–Diffusion Mismatch and Benefit From Thrombolysis 3 to 6 Hours After Acute Stroke

Martin Ebinger, MD, PhD; Takeshi Iwanaga, MD; Jane F. Prosser, FRACP; Deidre A. De Silva, MD; Soren Christensen, MMSc; Marnie Collins, BCom, BSc; Mark W. Parsons, PhD, FRACP; Christopher R. Levi, FRACP; Christopher F. Bladin, PhD, FRACP; P. Alan Barber, PhD, FRACP; Geoffrey A. Donnan, MD, FRACP; Stephen M. Davis, MD, FRACP for the EPITHET Investigators

From the Department of Neurology (M.E., J.F.P., D.A.D.S., S.C., S.M.D.), The Royal Melbourne Hospital, Parkville, Australia; the Statistical Consulting Centre (M.C.), University of Melbourne, Parkville, Australia; the Department of Neurology (M.W.P., C.R.L.), Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Australia; the Department of Neurology (C.F.B.), Box Hill Hospital, Melbourne, Australia; the Department of Neurology (P.A.B.), Auckland Hospital, New Zealand; and the Department of Neurology (T.I., G.A.D.), Austin Hospital, Melbourne, Australia.

Correspondence to Prof Stephen M. Davis, Department of Neurology, Royal Melbourne Hospital, Grattan Street, 3050 Parkville, Australia. E-mail Stephen.Davis{at}mh.org.au

Background and Purpose— The clinical-diffusion mismatch (CDM) model has been proposed as a simpler tool than perfusion-diffusion mismatch (PDM) to select acute ischemic stroke patients for thrombolytic therapy. We hypothesized that in the 3- to 6-hour time window, the effect of tPA was significantly greater in patients with CDM than in patients without CDM.

Methods— This is a substudy of EPITHET, a double-blind multi-center study of 100 patients randomized to tPA or placebo 3 to 6 hours after stroke onset. MRI was obtained before treatment, and at 3 to 5 days and 90 days after treatment. Presence of PDM (perfusion deficit/DWI_volume >1.2 and perfusion deficit at least 10 mL>DWI_volume) and CDM (NIHSS 8 and DWI_volume 25 mL) was determined for each patient. We assessed lesion growth and neurological improvement (decrease in NIHSS 8 points between baseline and 90 days, or a 90-day NIHSS 1).

Results— 86% of the patients had PDM, but only 41% had CDM. CDM detected PDM with a sensitivity of 46% and a specificity of 86%. We found statistically significant effects of reperfusion on the rate of neurological improvement (OR 9.92, 95% CI 1.91 to 51.64; P<0.01) and on absolute growth (difference: –59.60 mL, 95% CI –95.40 mL to –23.81 mL; P<0.01). Neither treatment with tPA nor reperfusion had a significantly different impact on lesion growth or clinical course in CDM patients compared to patients without CDM.

Conclusions— There was no increased benefit from tPA in patients with CDM. The beneficial effects of reperfusion were similar in patients with and without CDM.

Key Words: MRI • stroke • tPA • clinical-diffusion mismatch