Journal Article

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

Aarhus University Hospital, Nighoghossian, N, Ingwersen, T, Gerloff, C, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Simonsen, C. Z, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Wouters, A, Schlemm, E, Universitair Ziekenhuis Leuven = University Hospital of Leuven = Hopital universitaire de Louvain (UZ Leuven), Fiebach, J. B, Neuroscience Research Center and Cluster of Excellence NeuroCure, Thomalla, G, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon) ; Université de Lyon-Institut National

2021

Overview

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% (CI(95%) [-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% (CI(95%) [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.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK,Nature Portfolio
• Subject: 59/57 / 631/378/116/1925 / 631/378/1689/534 / Aged / Blood flow / Brain - diagnostic imaging / Brain - drug effects / Brain - pathology / Brain Ischemia - diagnostic imaging / Brain Ischemia - drug therapy / Brain Ischemia - pathology / Clinical trials / Damage prevention / Disease Progression / Fibrinolytic Agents - therapeutic use / Humanities and Social Sciences / Humans / Ischemia / Life Sciences / Magnetic Resonance Imaging / Mediation / Middle Aged / multidisciplinary / Nerve Net - drug effects / Nerve Net - pathology / Neural networks / Neuroimaging / Randomized Controlled Trials as Topic / Science / Science (multidisciplinary) / Secondary analysis / Severity of Illness Index / Stroke / Stroke - physiopathology / t-Plasminogen activator / Therapeutic applications / Thrombolysis / Thrombolytic drugs / Thrombolytic Therapy - adverse effects / Thrombolytic Therapy - methods / Time Factors / Tissue Plasminogen Activator - therapeutic use