Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke

Eckhard Schlemm (), Thies Ingwersen, Alina Königsberg, Florent Boutitie, Martin Ebinger, Matthias Endres, Jochen B. Fiebach, Jens Fiehler, Ivana Galinovic, Robin Lemmens, Keith W. Muir, Norbert Nighoghossian, Salvador Pedraza, Josep Puig, Claus Z. Simonsen, Vincent Thijs, Anke Wouters, Christian Gerloff, Götz Thomalla and Bastian Cheng ()
Additional contact information
Eckhard Schlemm: University Medical Center Hamburg-Eppendorf
Thies Ingwersen: University Medical Center Hamburg-Eppendorf
Alina Königsberg: University Medical Center Hamburg-Eppendorf
Florent Boutitie: Hospices Civils de Lyon, Service de Biostatistique
Martin Ebinger: Charité - Universitätsmedizin Berlin, Campus Mitte
Matthias Endres: Charité - Universitätsmedizin Berlin, Campus Mitte
Jochen B. Fiebach: Charité - Universitätsmedizin Berlin, Campus Mitte
Jens Fiehler: University Medical Center Hamburg-Eppendorf
Ivana Galinovic: Charité - Universitätsmedizin Berlin, Campus Mitte
Robin Lemmens: University Hospitals Leuven
Keith W. Muir: University of Glasgow
Norbert Nighoghossian: Université Claude Bernard Lyon 1, CREATIS CNRS UMR 5220-INSERM U1206
Salvador Pedraza: Institut de Diagnostic per la Image (IDI), Hospital Dr Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI)
Josep Puig: Institut de Diagnostic per la Image (IDI), Hospital Dr Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI)
Claus Z. Simonsen: Aarhus University Hospital
Vincent Thijs: University of Melbourne
Anke Wouters: University Hospitals Leuven
Christian Gerloff: University Medical Center Hamburg-Eppendorf
Götz Thomalla: University Medical Center Hamburg-Eppendorf
Bastian Cheng: University Medical Center Hamburg-Eppendorf

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke aims to restore compromised blood flow and prevent further neuronal damage. Despite the proven clinical efficacy of this treatment, little is known about the short-term effects of systemic thrombolysis on structural brain connectivity. In this secondary analysis of the WAKE-UP trial, we used MRI-derived measures of infarct size and estimated structural network disruption to establish that thrombolysis is associated not only with less infarct growth, but also with reduced loss of large-scale connectivity between grey-matter areas after stroke. In a causal mediation analysis, infarct growth mediated a non-significant 8.3% (CI95% [−8.0, 32.6]%) of the clinical effect of thrombolysis on functional outcome. The proportion mediated jointly through infarct growth and change of structural connectivity, especially in the border zone around the infarct core, however, was as high as 33.4% (CI95% [8.8, 77.4]%). Preservation of structural connectivity is thus an important determinant of treatment success and favourable functional outcome in addition to lesion volume. It might, in the future, serve as an imaging endpoint in clinical trials or as a target for therapeutic interventions.

Date: 2021
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DOI: 10.1038/s41467-021-22786-w

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