The impact of the DWI-FLAIR-mismatch in the ECASS-4 trial - A post hoc analysis

Johannes Ar Pfaff; Martin Bendszus; Geoffrey Donnan; Carlos Molina; Didier Leys; Peter D Schellinger; Stefan Schwab; Danilo Toni; Nils Wahlgren; Werner Hacke; Peter Arthur Ringleb

doi:10.1177/2396987320920114

The impact of the DWI-FLAIR-mismatch in the ECASS-4 trial - A post hoc analysis

Eur Stroke J. 2020 Dec;5(4):370-373. doi: 10.1177/2396987320920114. Epub 2020 Apr 23.

Authors

Affiliations

¹ Heidelberg University Hospital, Department of Neuroradiology, Heidelberg, Germany.
² National Stroke Research Institute, Neurosciences Bldg, Heidelberg Heights, Australia.
³ Hospital Universitari Vall d'Hebron, Department of Neurosciences, Barcelona, Spain.
⁴ Hopital Roger Salengro, Service de neurologie et pathologie neurovasculaire, Lille Cedex, France.
⁵ University Hospital Erlangen, Department of Neurology, Erlangen, Germany.
⁶ Hospital Policlinico Umberto I, Emergency Department Stroke Unit, Rome, Italy.
⁷ Karolinska Institutet, Department of Clinical Neurosciences, Stockholm, Sweden.
⁸ Heidelberg University Hospital, Department of Neurology, Heidelberg, Germany.

Abstract

Introduction: To investigate the impact of a mismatch between diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) on functional outcome in patients with acute stroke in a prolonged time window or unknown time of symptom onset randomized to intravenous thrombolysis or placebo.

Patients and methods: We performed a post-hoc analysis of the European Cooperative Acute Stroke Study-4 (ECASS-4) trial. ECASS-4 was an investigator driven, phase 3, multi-center, double-blind, placebo-controlled study which randomized ischemic stroke patients presenting within 4.5 and 9h of stroke onset or unknown time-window to either rt-PA or placebo after MR-imaging. Two subgroups "no mismatch" (nMM) and "any mismatch" (aMM) were created by applying a DWI-FLAIR-mismatch criterion. We calculated frequency of nMM and aMM and performed a univariate analysis (Fisher's Test) for excellent clinical outcome (mRS 0-1) and mortality (mRS=6).

Results: MR-Imaging of n=111/119 (93.2%) patients was suitable for this analysis. DWI-FLAIR mismatch was found in 49 patients (44.1%). Proportions of mismatch nMM and aMM were comparable in treatment-groups (aMM: Placebo 46.3%, Alteplase 42.1%; p=0.70). Patients with nMM showed no benefit of rt-PA-treatment (OR (95%CI) mRS 0-1: 0.95 (0.29-3.17)). Patients with aMM showed a point estimate of the odds ratio in favour of a treatment benefit of rt-PA (mRS 0-1: OR (95%CI) 2.62 (0.68-11.1)). Mortality within 90 days was not different in patients treated with rt-PA if nMM (15.2%) or aMM (12.5%) was present.

Discussion: In this analysis no significant evidence, but subtle indication towards patients treated with rt-PA in a prolonged time window reaching an excellent clinical outcome if a DWI-FLAIR-mismatch is present on initial stroke MR-imaging.

Conclusion: A DWI-FLAIR mismatch in the region of ischemia as imaging based surrogate parameter for patient selection for i.v. rt-PA should be strongly pursued.

Keywords: DWI-FLAIR-mismatch; European Cooperative Acute Stroke Study-4; Thrombolysis; acute ischemic stroke; diffusion-weighted imaging; fluid-attenuated inversion recovery; magnetic resonance imaging.