Lauranne Scheldeman1,2,3, Anke Wouters1,2,3, Florent Boutitie4,5, Patrick Dupont6, Soren Christensen7, Bastian Cheng8, Martin Ebinger9,10, Matthias Endres9,11,12,13, Jochen B Fiebach9, Christian Gerloff8, Keith W Muir14, Norbert Nighoghossian15, Salvador Pedraza16, Claus Z Simonsen17, Vincent Thijs18,19, Götz Thomalla8, Robin Lemmens1,2,3. 1. Department of Neurology, University Hospitals Leuven, Leuven, Belgium. 2. Department of Neurosciences, Experimental Neurology, KU Leuven-University of Leuven, Leuven, Belgium. 3. Center for Brain & Disease Research, Laboratory of Neurobiology, Flanders Institute for Biotechnology, Leuven, Belgium. 4. Hospices Civils de Lyon, Service de Biostatistique, F-69003 Lyon, France; Université Lyon 1, F-69100, Villeurbanne, France. 5. Centre national de la recherche scientifique, unité mixte de recherche 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France. 6. Department of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven-University of Leuven, Leuven, Belgium. 7. GrayNumber Analytics, Lomma, Sweden. 8. Department of Neurology, Head and Neurocenter, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 9. Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany. 10. Neurology Clinic, Medical Park Berlin Humboldtmühle, Berlin, Germany. 11. Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany. 12. German Center for Cardiovascular Research, Berlin, Germany. 13. German Center for Neurodegenerative Diseases, Berlin, Germany. 14. Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, United Kingdom. 15. Department of Stroke Medicine, Claude Bernard University Lyon 1, CREATIS National Center for Scientific Research Mixed Unit of Research 5220-National Institute of Health and Medical Research U1206, National Institute of Applied Sciences of Lyon, Lyon Civil Hospices, Lyon, France. 16. Department of Radiology, Institute of Diagnostic Imaging, Dr Josep Trueta Hospital, Girona Institute of Biomedical Research, Marti and Julia de Salt Hospital Park - Building M2, Girona, Spain. 17. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. 18. Stroke Theme, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia. 19. Department of Neurology, Austin Health, Heidelberg, Victoria, Australia.
Abstract
OBJECTIVE: To explore the prevalence of the perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch and response to intravenous thrombolysis in the WAKE-UP trial. METHODS: We performed a prespecified post hoc analysis of ischemic stroke patients screened for DWI-fluid-attenuated inversion recovery (FLAIR) mismatch in WAKE-UP who underwent PWI. We defined PWI-DWI mismatch as ischemic core volume < 70ml, mismatch volume > 10ml, and mismatch ratio > 1.2. Primary efficacy end point was a modified Rankin Scale score of 0-1 at 90 days, adjusted for age and symptom severity. RESULTS: Of 1,362 magnetic resonance imaging-screened patients, 431 underwent PWI. Of these, 57 (13%) had a double mismatch, 151 (35%) only a DWI-FLAIR mismatch, and 54 (13%) only a PWI-DWI mismatch. DWI-FLAIR mismatch was more prevalent than PWI-DWI mismatch (48%, 95% confidence interval [CI] = 43-53% vs 26%, 95% CI = 22-30%; p < 0.0001). Screening for either one of the mismatch profiles resulted in a yield of 61% (95% CI = 56-65%). Prevalence of PWI-DWI mismatch was similar in patients with (27%) or without (24%) DWI-FLAIR mismatch (p = 0.52). In an exploratory analysis in the small subgroup of 208 randomized patients with PWI, PWI-DWI mismatch status did not modify the treatment response (p for interaction = 0.73). INTERPRETATION: Evaluating both the DWI-FLAIR and PWI-DWI mismatch patterns in patients with unknown time of stroke onset will result in the highest yield of thrombolysis treatment. The treatment benefit of alteplase in patients with a DWI-FLAIR mismatch seems to be driven not merely by the presence of a PWI-DWI mismatch, although this analysis was underpowered. ANN NEUROL 2020;87:931-938.
RCT Entities:
OBJECTIVE: To explore the prevalence of the perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch and response to intravenous thrombolysis in the WAKE-UP trial. METHODS: We performed a prespecified post hoc analysis of ischemic strokepatients screened for DWI-fluid-attenuated inversion recovery (FLAIR) mismatch in WAKE-UP who underwent PWI. We defined PWI-DWI mismatch as ischemic core volume < 70ml, mismatch volume > 10ml, and mismatch ratio > 1.2. Primary efficacy end point was a modified Rankin Scale score of 0-1 at 90 days, adjusted for age and symptom severity. RESULTS: Of 1,362 magnetic resonance imaging-screened patients, 431 underwent PWI. Of these, 57 (13%) had a double mismatch, 151 (35%) only a DWI-FLAIR mismatch, and 54 (13%) only a PWI-DWI mismatch. DWI-FLAIR mismatch was more prevalent than PWI-DWI mismatch (48%, 95% confidence interval [CI] = 43-53% vs 26%, 95% CI = 22-30%; p < 0.0001). Screening for either one of the mismatch profiles resulted in a yield of 61% (95% CI = 56-65%). Prevalence of PWI-DWI mismatch was similar in patients with (27%) or without (24%) DWI-FLAIR mismatch (p = 0.52). In an exploratory analysis in the small subgroup of 208 randomized patients with PWI, PWI-DWI mismatch status did not modify the treatment response (p for interaction = 0.73). INTERPRETATION: Evaluating both the DWI-FLAIR and PWI-DWI mismatch patterns in patients with unknown time of stroke onset will result in the highest yield of thrombolysis treatment. The treatment benefit of alteplase in patients with a DWI-FLAIR mismatch seems to be driven not merely by the presence of a PWI-DWI mismatch, although this analysis was underpowered. ANN NEUROL 2020;87:931-938.
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Authors: Kamil Zeleňák; Antonín Krajina; Lukas Meyer; Jens Fiehler; Daniel Behme; Deniz Bulja; Jildaz Caroff; Amar Ajay Chotai; Valerio Da Ros; Jean-Christophe Gentric; Jeremy Hofmeister; Omar Kass-Hout; Özcan Kocatürk; Jeremy Lynch; Ernesto Pearson; Ivan Vukasinovic Journal: Life (Basel) Date: 2021-05-27