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[Preprint]. 2023 Oct 30:2023.10.29.23297734.

doi: 10.1101/2023.10.29.23297734.

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

Jennifer K Ferris^{1

2}, Bethany P Lo³, Giuseppe Barisano⁴, Amy Brodtmann^{5

6}, Cathrin M Buetefisch^{7

8

9}, Adriana B Conforto^{10

11}, Miranda H Donnelly³, Natalia Egorova-Brumley¹², Kathryn S Hayward¹³, Mohamed Salah Khlif⁵, Kate P Revill¹⁴, Artemis Zavaliangos-Petropulu¹⁵, Lara A Boyd², Sook-Lei Liew^{3

16}

Affiliations

¹ Gerontology Research Centre, Simon Fraser University, Vancouver, British Columbia, Canada.
² Department of Physical Therapy and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.
³ Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, California, USA.
⁴ Department of Neurosurgery, Stanford School of Medicine, Stanford University, California, USA.
⁵ Central Clinical School, Monash University, Melbourne, Victoria, Australia.
⁶ Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
⁷ Department of Neurology, Emory University, Atlanta, Georgia, USA.
⁸ Department of Rehabilitation Medicine, Emory University, Atlanta, Georgia, USA.
⁹ Department of Radiology, Emory University, Atlanta, Georgia, USA.
¹⁰ Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
¹¹ Hospital Israelita Albert Einstein, São Paulo, Brazil.
¹² Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia.
¹³ Departments of Physiotherapy, Medicine (RMH) & The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia.
¹⁴ Facility for Education and Research in Neuroscience, Emory University, Atlanta, Georgia, USA.
¹⁵ Brain Mapping Center, Department of Neurology, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
¹⁶ Mark and Mary Stevens Neuroimaging and Informatics Institute and Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

PMID: 37961329
PMCID: PMC10635227
DOI: 10.1101/2023.10.29.23297734

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

Jennifer K Ferris et al. medRxiv. 2023.

[Preprint]. 2023 Oct 30:2023.10.29.23297734.

doi: 10.1101/2023.10.29.23297734.

Authors

Affiliations

¹ Gerontology Research Centre, Simon Fraser University, Vancouver, British Columbia, Canada.
² Department of Physical Therapy and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.
³ Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, California, USA.
⁴ Department of Neurosurgery, Stanford School of Medicine, Stanford University, California, USA.
⁵ Central Clinical School, Monash University, Melbourne, Victoria, Australia.
⁶ Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
⁷ Department of Neurology, Emory University, Atlanta, Georgia, USA.
⁸ Department of Rehabilitation Medicine, Emory University, Atlanta, Georgia, USA.
⁹ Department of Radiology, Emory University, Atlanta, Georgia, USA.
¹⁰ Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
¹¹ Hospital Israelita Albert Einstein, São Paulo, Brazil.
¹² Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia.
¹³ Departments of Physiotherapy, Medicine (RMH) & The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia.
¹⁴ Facility for Education and Research in Neuroscience, Emory University, Atlanta, Georgia, USA.
¹⁵ Brain Mapping Center, Department of Neurology, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
¹⁶ Mark and Mary Stevens Neuroimaging and Informatics Institute and Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

PMID: 37961329
PMCID: PMC10635227
DOI: 10.1101/2023.10.29.23297734

Update in

Modulation of the Association Between Corticospinal Tract Damage and Outcome After Stroke by White Matter Hyperintensities.
Ferris JK, Lo BP, Barisano G, Brodtmann A, Buetefisch CM, Conforto AB, Donnelly MR, Egorova-Brumley N, Hayward KS, Khlif MS, Revill KP, Zavaliangos-Petropulu A, Boyd L, Liew SL. Ferris JK, et al. Neurology. 2024 May 28;102(10):e209387. doi: 10.1212/WNL.0000000000209387. Epub 2024 May 3. Neurology. 2024. PMID: 38701386 Free PMC article.

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.

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Conflict of interest statement

Competing Interests A.C. was a consultant for Boehringer Ingelheim in 2021.

Figures

**Figure 1:**
Relationships between motor impairment and stroke/WMHs Motor impairment by CST Lesion Load (left panel) or WMH volumes (in mL; right panel). Plots present beta regression line (solid), standard error (shaded), and parameter eatimates (text)

**Figure 2:**
Relationships between motor impairment and CST Lesion Load stratified by WMH severity Motor impairment by CST Lesion Load, stratified by WMH severity (light blue = mild WMHs, dark blue = moderate-severe WMHs). Plots present beta regression line (solid), standard error (shaded), and parameter eatimates (text) for stratifeid models

See this image and copyright information in PMC

References

1. Andersson JLR, Jenkinson M, Smith S. Non-linear registration aka spatial normalisation; FMRIB Technical Report TR07JA2 [Internet]. 2007Available from: http://fmrib.medsci.ox.ac.uk/analysis/techrep/tr07ja2/tr07ja2.pdf
1. Auriat AM, Ferris JK, Peters S, Ramirez J, Black SE, Jacova C, et al. The Impact of Covert Lacunar Infarcts and White Matter Hyperintensities on Cognitive and Motor Outcomes After Stroke. J Stroke Cerebrovasc Dis 2019; 28: 381–388. - PubMed
1. Bernhardt J, Hayward KS, Kwakkel G, Ward NS, Wolf SL, Borschmann K, et al. Agreed definitions and a shared vision for new standards in stroke recovery research: The Stroke Recovery and Rehabilitation Roundtable taskforce. Int J Stroke 2017; 12: 444–450. - PubMed
1. Boyd LA, Hayward KS, Ward NS, Stinear CM, Rosso C, Fisher RJ, et al. Biomarkers of Stroke Recovery: Consensus-Based Core Recommendations from the Stroke Recovery and Rehabilitation Roundtable. Int J Stroke 2017; 12: 480–493. - PMC - PubMed
1. Brooks ME, Kristensen K, van Benthem KJ, Magnusson A, Berg CW, Nielsen A, et al. glmmTMB balances speed and flexibility among packages for zero-inflated generalized linear mixed modeling. R J 2017; 9: 378–400.

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This is a preprint.

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

Affiliations

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

Authors

Affiliations

Update in

Abstract

Conflict of interest statement

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References

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