White matter hyperintensities modify relationships between corticospinal tract damage and motor outcomes after stroke

• Type of Material: Article
• Authors: Jennifer K. Ferris, Simon Fraser University; Bethany P. Lo, University of Southern California; Giuseppe Barisano, Stanford University; Amy Brodtmann, Monash University; Cathrin Buetefisch, Emory University; Adriana B. Conforto, Universidade de São Paulo; Miranda H. Donnelly, University of Southern California; Natalia Egorova-Brumley, University of Melbourne; Kathryn S. Hayward, University of Melbourne; Mohamed Salah Khlif, Monash University; Kate Pirog Revill, Emory University; Artemis Zavaliangos-Petropulu, University of California, Los Angeles; Lara A. Boyd, University of British Columbia; Sook-Lei Liew, University of Southern California, Los Angeles
• Language: English
• Date: 2023-10-30
• Publisher: NIH
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1101/2023.10.29.23297734
• Title of Journal or Parent Work: medRxiv
• Start Page: 23297734
• Grant/Funding Information: JF receives salary support from the Canadian Institutes of Health Research (CIHR) and Michael Smith Health Research BC (HSIF-2022-2990). KSH is supported by a National Health and Medical Research Council of Australia Emerging Leadership Fellowship (2016420) and Heart Foundation Future Leader Fellowship (106607). This research was funded by the following granting agencies: Australian Heart Foundation Future Leader Fellowships (PI Brodtmann: 104748 and 100784), Canadian Institutes of Health Research (PI Boyd: PTJ-148535, MOP-130269, MOP-106651), Hospital Israelita Albert Einstein (PI Conforto: 2250-14), National Health and Medical Research Council (PI Brodtmann: GNT1020526 GNT1094974 GNT1045617), and National Institutes of Health (PI Butefisch: R21HD067906; R01NS090677; PI Conforto: R01NS076348-01; PI Liew: R01NS115845; PI Revill: R01NS090677).
• Keywords: corticospinal tract; CST lesion load; white matter hyperintensities
• Research Categories: Biology, Neuroscience; Health Sciences, Rehabilitation and Therapy

Abstract

Motor outcomes after stroke relate to corticospinal tract (CST) damage. Concurrent damage from white matter hyperintensities (WMHs) might impact neurological capacity for recovery after CST injury. Here, we evaluated if WMHs modulate the relationship between CST damage and post-stroke motor impairment outcome. We included 223 individuals from the ENIGMA Stroke Recovery Working Group. CST damage was indexed with weighted CST lesion load (CST-LL). Mixed effects beta-regression models were fit to test the impact of CST-LL, WMH volume, and their interaction on motor impairment. WMH volume related to motor impairment above and beyond CST-LL (β = 0.178, p = 0.022). We tested if relationships varied by WMH severity (mild vs. moderate-severe). In individuals with mild WMHs, motor impairment related to CST-LL (β = 0.888, p < 0.001) with a CST-LL x WMH interaction (β = −0.211, 0.026). In individuals with moderate-severe WMHs, motor impairment related to WMH volume (β = 0.299, p = 0.044), but did not significantly relate to CST-LL or a CST-LL x WMH interaction. WMH-related damage may be under-recognised in stroke research as a factor contributing to variability in motor outcomes. Our findings emphasize the importance of brain structural reserve in motor outcomes after brain injury.