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

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...

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Autores principales: Schlemm, Eckhard, Ingwersen, Thies, 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, Wouters, Anke, Gerloff, Christian, Thomalla, Götz, Cheng, Bastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110812/
https://www.ncbi.nlm.nih.gov/pubmed/33972513
http://dx.doi.org/10.1038/s41467-021-22786-w
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author Schlemm, Eckhard
Ingwersen, Thies
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
Wouters, Anke
Gerloff, Christian
Thomalla, Götz
Cheng, Bastian
author_facet Schlemm, Eckhard
Ingwersen, Thies
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
Wouters, Anke
Gerloff, Christian
Thomalla, Götz
Cheng, Bastian
author_sort Schlemm, Eckhard
collection PubMed
description 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.
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spelling pubmed-81108122021-05-14 Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke Schlemm, Eckhard Ingwersen, Thies 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 Wouters, Anke Gerloff, Christian Thomalla, Götz Cheng, Bastian Nat Commun Article 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. Nature Publishing Group UK 2021-05-10 /pmc/articles/PMC8110812/ /pubmed/33972513 http://dx.doi.org/10.1038/s41467-021-22786-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Schlemm, Eckhard
Ingwersen, Thies
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
Wouters, Anke
Gerloff, Christian
Thomalla, Götz
Cheng, Bastian
Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke
title Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke
title_full Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke
title_fullStr Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke
title_full_unstemmed Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke
title_short Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke
title_sort preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110812/
https://www.ncbi.nlm.nih.gov/pubmed/33972513
http://dx.doi.org/10.1038/s41467-021-22786-w
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