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

2021-05-10

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 N

Wouters, Anke

Gerloff, Christian

Thomalla, Götz

Cheng, Bastian

Thrombolysis

Anterior-circulation Stroke

Journal Article

0000-0002-5729-2935

0000-0001-6520-3720

0000-0002-7936-6958

0000-0003-2434-1822

10.1038/s41467-021-22786-w

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.

link

Nature Communications 2021; 12(1): 2590

Nature Communications