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Background and ObjectivesTo examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern–specific ways.MethodsMR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3–6 months after stroke were obtained from the MRI–Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning–based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts.ResultsA total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location–specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location.DiscussionHigher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.

ObjectiveTo test the hypothesis that cognitive demands influence motor performance during recovery from acute stroke, we tested patients with acute stroke on 2 motor tasks with different cognitive demands and related task performance to cognitive impairment and neuroanatomic injury.MethodsWe assessed the contralesional and ipsilesional upper extremities of a cohort of 50 patients with weakness after unilateral acute ischemic stroke at 3 time points with 2 tasks: the Box & Blocks Test, a task with greater cognitive demand, and Grip Strength, a simple and ballistic motor task. We compared performance on the 2 tasks, related motor performance to cognitive dysfunction, and used voxel-based lesion symptom mapping to determine neuroanatomic sites associated with motor performance.ResultsConsistent across contralesional and ipsilesional upper extremities and most pronounced immediately after stroke, Box & Blocks scores were significantly more impaired than Grip Strength scores. The presence of cognitive dysfunction significantly explained up to 33% of variance in Box & Blocks performance but was not associated with Grip Strength performance. While Grip Strength performance was associated with injury largely restricted to sensorimotor regions, Box & Blocks performance was associated with broad injury outside sensorimotor structures, particularly the dorsal anterior insula, a region known to be important for complex cognitive function.ConclusionsTogether, these results suggest that cognitive demands influence upper extremity motor performance during recovery from acute stroke. Our findings emphasize the integrated nature of motor and cognitive systems and suggest that it is critical to consider cognitive demands during motor testing and neurorehabilitation after stroke.