Abstract

Introduction: As a radiographic signature of end-stage small vessel disease, white matter hyperintensity (WMH) burden impacts recovery and outcomes after acute ischemic stroke (AIS). In this study, we sought to investigate the effect of WMH volume (WMHv) on stroke severity and functional outcomes independent of the infarct size and topography. Methods: We analyzed 503 AIS patients with MRI data obtained on admission for index stroke enrolled in the multi-center MRI-GENIE study (cohort 1), followed by validation of the findings in an independent single-site study of 555 AIS patients (cohort 2). Stroke severity (NIHSS score) at index stroke and the long-term outcome (3-6 months mRS score) were modeled via Bayesian linear regression. Models included WMHv, age, sex, a 10-dimensional spatial ischemic lesion representation, acute infarct (DWI) volume, and common vascular risk factors (hypertension, diabetes mellitus, atrial fibrillation, coronary artery disease). Results: Cohorts did not differ significantly in major clinical characteristics [cohort 1: age: 65.0±14.6, 41% female, NIHSS: 5.5±5.4, mRS: 1(iqr 2); cohort 2: age: 65.0±14.8, 38% female, NIHSS: 5.0±6.0, mRS: 1(iqr 3), p >0.05 for all comparisons]. WMHv did not substantially affect AIS severity ( Fig A ); in contrast, it emerged as an independent predictor of functional outcome in both datasets ( Fig B ). Conclusions: When accounted for AIS lesion topography and stroke volume, total WMH lesion burden did not appear to modulate initial stroke severity but was associated with worse functional post-stroke outcomes. Future studies are needed to explore potential origins of these detrimental effects of pre-existing WMH burden on recovery after AIS.

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