Modulation of the Association Between Corticospinal Tract Damage and Outcome After Stroke by White Matter Hyperintensities

Abstract

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.