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

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Listed:
  • 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
    Université Lyon 1
    CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé)

  • Martin Ebinger

    (Charité - Universitätsmedizin Berlin, Campus Mitte
    Klinik für Neurologie, Medical Park Berlin Humboldtmühle)

  • Matthias Endres

    (Charité - Universitätsmedizin Berlin, Campus Mitte
    Charité-Universitätsmedizin Berlin, Campus Mitte
    German Center for Neurodegenerative Diseases (DZNE)
    German Centre for Cardiovascular Research (DZHK))

  • 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
    KU Leuven – University of Leuven, Department of Neurosciences, Experimental Neurology
    VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Campus Gasthuisberg)

  • 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
    Austin Health, Department of Neurology)

  • Anke Wouters

    (University Hospitals Leuven
    KU Leuven – University of Leuven, Department of Neurosciences, Experimental Neurology
    VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Campus Gasthuisberg)

  • Christian Gerloff

    (University Medical Center Hamburg-Eppendorf)

  • Götz Thomalla

    (University Medical Center Hamburg-Eppendorf)

  • Bastian Cheng

    (University Medical Center Hamburg-Eppendorf)

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.

Suggested Citation

  • Eckhard Schlemm & Thies Ingwersen & Alina Königsberg & Florent Boutitie & Martin Ebinger & Matthias Endres & Jochen B. Fiebach & Jens Fiehler & Ivana Galinovic & Robin Lemmens & Keith W. Muir & Norber, 2021. "Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22786-w
    DOI: 10.1038/s41467-021-22786-w
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