Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome.

Abstract

To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways. MR neuroimaging and National Institutes of Health Stroke Scale data at index stroke, as well as modified Rankin Scale (mRS) at 3-6 months post-stroke were obtained from the MRI-GENIE study of acute ischemic stroke (AIS) patients. Individual WMH volume was automatically derived from FLAIR-images. Stroke lesions were automatically segmented from DWI-images, parcellated into atlas-defined brain regions and further condensed to ten lesion patterns via machine-learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS>2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high versus 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. A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8(14.5), 40% women), 698 patients to long-term functional outcome analyses (age: 65.9(14.7), 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 temporo-parietal regions had more pronounced effects on stroke severity in case of high compared to 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. Higher 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 temporo-parietal 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.