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Title: | Early effect of thrombolysis on structural brain network organisation after anterior-circulation stroke in the randomized WAKE-UP trial. | Austin Authors: | Schlemm, Eckhard;Jensen, Märit;Kuceyeski, Amy;Jamison, Keith;Ingwersen, Thies;Mayer, Carola;Königsberg, Alina;Boutitie, Florent;Ebinger, Martin;Endres, Matthias;Fiebach, Jochen B;Fiehler, Jens;Galinovic, Ivana;Lemmens, Robin;Muir, Keith W;Nighoghossian, Norbert;Pedraza, Salvador;Puig, Josep;Simonsen, Claus Z;Thijs, Vincent N ;Wouters, Anke;Gerloff, Christian;Thomalla, Götz;Cheng, Bastian | Affiliation: | Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, UK Neurology Department of Radiology, Weill Cornell Medicine, New York, New York, USA Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.. The Florey Institute of Neuroscience and Mental Health Hospices Civils de Lyon, Service de Biostatistique, Lyon, France.. Université Lyon 1, Villeurbanne, France.. CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France.. Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.. Centrum für Schlaganfallforschung Berlin (CSB), Charité - Universitätsmedizin Berlin, Berlin, Germany.. Klinik für Neurologie, Medical Park Berlin Humboldtmühle, Berlin, Germany.. Department of Diagnostic and Interventional Neuroradiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.. Department of Neurology, University Hospitals Leuven, Leuven, Belgium.. Department of Neurosciences Division of Experimental Neurology, KU Leuven-University of Leuven, Leuven, Belgium.. VIB, Centre for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium.. Department of Stroke Medicine, Université Claude Bernard Lyon 1, CREATIS CNRS UMR 5220-INSERM U1206, INSA-Lyon, Lyon, France.. Department of Radiology, Institut de Diagnostic per la Image (IDI), Hospital Dr Josep Trueta, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain.. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.. Department of Neurology, University Hospitals Leuven, Leuven, Belgium.. Department of Neurosciences Division of Experimental Neurology, KU Leuven-University of Leuven, Leuven, Belgium.. VIB, Centre for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium.. Department of Neurology Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.. Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.. |
Issue Date: | 14-Sep-2022 | Date: | 2022 | Publication information: | Human Brain Mapping 2022; 43(16): 5053-5065 | Abstract: | The symptoms of acute ischemic stroke can be attributed to disruption of the brain network architecture. Systemic thrombolysis is an effective treatment that preserves structural connectivity in the first days after the event. Its effect on the evolution of global network organisation is, however, not well understood. We present a secondary analysis of 269 patients from the randomized WAKE-UP trial, comparing 127 imaging-selected patients treated with alteplase with 142 controls who received placebo. We used indirect network mapping to quantify the impact of ischemic lesions on structural brain network organisation in terms of both global parameters of segregation and integration, and local disruption of individual connections. Network damage was estimated before randomization and again 22 to 36 h after administration of either alteplase or placebo. Evolution of structural network organisation was characterised by a loss in integration and gain in segregation, and this trajectory was attenuated by the administration of alteplase. Preserved brain network organization was associated with excellent functional outcome. Furthermore, the protective effect of alteplase was spatio-topologically nonuniform, concentrating on a subnetwork of high centrality supported in the salvageable white matter surrounding the ischemic cores. This interplay between the location of the lesion, the pathophysiology of the ischemic penumbra, and the spatial embedding of the brain network explains the observed potential of thrombolysis to attenuate topological network damage early after stroke. Our findings might, in the future, lead to new brain network-informed imaging biomarkers and improved prognostication in ischemic stroke. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/30902 | DOI: | 10.1002/hbm.26073 | ORCID: | https://orcid.org/0000-0002-5729-2935 https://orcid.org/0000-0001-7793-0941 https://orcid.org/0000-0002-5050-8342 https://orcid.org/0000-0003-2434-1822 |
Journal: | Human Brain Mapping | PubMed URL: | 36102287 | Type: | Journal Article | Subjects: | ischemic stroke network neuroscience structural connectivity systemic thrombolysis |
Appears in Collections: | Journal articles |
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