Modulation of the Association Between Corticospinal Tract Damage and Outcome After Stroke by White Matter
Jennifer K Ferris1, Bethany P Lo1, Giuseppe Barisano1
1From the Gerontology Research Centre (J.K.F.), Simon Fraser University; Department of Physical Therapy and Djavad Mowafaghian Centre for Brain Health (J.K.F.), University of British Columbia, Vancouver, Canada; Chan Division of Occupational Science and Occupational Therapy (B.P.L., M.R.D., S.-L.L.), University of Southern California, Los Angeles; Department of Neurosurgery (G.B.), Stanford School of Medicine, Stanford University, CA; Central Clinical School (A.B., M.S.K.), Monash University, Melbourne, Victoria, Australia; Department of Medicine (A.B.), Royal Melbourne Hospital, University of Melbourne, Victoria, Australia; Department of Neurology (C.M.B.), Department of Rehabilitation Medicine (C.M.B.), and Department of Radiology (C.M.B.), Emory University, Atlanta, GA; Hospital das Clinicas HCFMUSP (A.B.C.), Faculdade de Medicina, Universidade de São Paulo; Hospital Israelita Albert Einstein (A.B.C.), São Paulo, Brazil; Melbourne School of Psychological Sciences (N.E.-B.), University of Melbourne; Departments of Physiotherapy, Medicine (RMH) & The Florey Institute of Neuroscience and Mental Health (K.S.H.), University of Melbourne, Victoria, Australia; Facility for Education and Research in Neuroscience (K.P.R.), Emory University, Atlanta, GA; Brain Mapping Center (A.Z.-P.), Department of Neurology, Geffen School of Medicine, University of California Los Angeles; and Mark and Mary Stevens Neuroimaging and Informatics Institute and Keck School of Medicine (L.B., S.-L.L.), University of Southern California, Los Angeles.
Background And Objectives:
Motor outcomes after stroke relate to corticospinal tract (CST) damage. The brain leverages surviving neural pathways to compensate for CST damage and mediate motor recovery. Thus, concurrent age-related damage from white matter hyperintensities (WMHs) might affect neurologic capacity for recovery after CST injury. The role of WMHs in post-stroke motor outcomes is unclear. In this study, we evaluated whether WMHs modulate the relationship between CST damage and post-stroke motor outcomes.
Methods:
We used data from the multisite ENIGMA Stroke Recovery Working Group with T1 and T2/fluid-attenuated inversion recovery imaging. CST damage was indexed with weighted CST lesion load (CST-LL). WMH volumes were extracted with Freesurfer's SAMSEG. Mixed-effects beta-regression models were fit to test the impact of CST-LL, WMH volume, and their interaction on motor impairment, controlling for age, days after stroke, and stroke volume.
Results:
A total of 223 individuals were included. WMH volume related to motor impairment above and beyond CST-LL (β = 0.178, 95% CI 0.025-0.331, p = 0.022). Relationships varied by WMH severity (mild vs moderate-severe). In individuals with mild WMHs, motor impairment related to CST-LL (β = 0.888, 95% CI 0.604-1.172, p < 0.001) with a CST-LL × WMH interaction (β = -0.211, 95% CI -0.340 to -0.026, p = 0.026). In individuals with moderate-severe WMHs, motor impairment related to WMH volume (β = 0.299, 95% CI 0.008-0.590, p = 0.044), but did not significantly relate to CST-LL or a CST-LL × WMH interaction.
Discussion:
WMHs relate to motor outcomes after stroke and modify relationships between motor impairment and CST damage. WMH-related damage may be under-recognized 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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