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

Schlemm, E. et al. (2021) Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke. Nature Communications, 12, 2590. (doi: 10.1038/s41467-021-22786-w) (PMID:33972513) (PMCID:PMC8110812)

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.

• Item Type: Articles
• Additional Information: This work was supported by a grant (278276) from the European Union Seventh Framework Program, and by a grant from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) Sonderforschungsbereich (SFB) 936, Project C1 (CG) and C2 (BC, GT). Dr Endres received funding from Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanys Excellence Strategy-EXC-2049-390688087 and from Bundesministerium für Bildung und Forschung (BMBF; German Ministry for Education and Research) for the Center for Stroke Research Berlin. C.G. also acknowledges funding from SPP 2041 Computational Connectomics, project Ge 844/5-1.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muir, Professor Keith and Schlemm, Dr Eckhard
• Authors: Schlemm, E., Ingwersen, T., Königsberg, A., Boutitie, F., Ebinger, M., Endres, M., Fiebach, J. B., Fiehler, J., Galinovic, I., Lemmens, R., Muir, K. W., Nighoghossian, N., Pedraza, S., Puig, J., Simonsen, C. Z., Thijs, V., Wouters, A., Gerloff, C., Thomalla, G., and Cheng, B.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Nature Communications 12: 2590
• Publisher Policy: Reproduced under a Creative Commons License