White Matter Hyperintensities on Admission CT are Associated with Worse Outcomes But Not Cerebral Edema or Hemorrhagic Transformation After Large Vessel Occlusion Stroke

INTRODUCTION: White matter hyperintensities (WMH) are key radiographic biomarkers of cerebral small vessel disease (CSVD) and have been associated with worse outcomes after stroke. Since CSVD may involve blood-brain barrier disruption, we hypothesized that worse outcomes in those with WMH may be mediated through more severe cerebral edema and hemorrhagic transformation (HT). METHODS: In this retrospective multicenter cohort study, we studied patients from four multinational stroke cohorts who presented within 12 h of anterior circulation large vessel occlusion (LVO) stroke and received at least one follow-up computed tomography (CT) between 12 and 48 h. WMH were rated on baseline CTs using a Fazekas-derived system, with a subset also assessed with Fazekas grading on magnetic resonance imaging (MRI). Automated image analysis measured cerebrospinal fluid displacement (ΔCSF) and lesional-to-contralateral hemispheric CSF volumes (CSF-ratio) as quantitative edema biomarkers. We analyzed the association between WMH presence and edema severity, hemorrhagic transformation, and poor functional outcome (mRS 3-6), adjusting for key covariates, overall and in the subgroup undergoing thrombectomy and those with successful reperfusion. RESULTS: Of 1290 patients with LVO, 782 were eligible for analysis. Of these, 19% had WMH on CT. Patients with WMH were older, more often female, and had a history of hypertension and higher presenting systolic blood pressure and glucose levels. WMH presence was associated with worse functional outcome, adjusting for age and additional covariates [OR 1.84 (1.06-3.22), p = 0.04] but lower risk of any HT [OR 0.48 (0.25-0.88), p = 0.03]. However, WMH presence by CT or MRI was not associated with edema (ΔCSF, CSF ratio, or midline shift) in the whole population or thrombectomy/reperfusion subgroups. Reperfusion was associated with less edema and improved recovery. CONCLUSIONS: Presence of CT-graded WMH was associated with worse outcome after LVO stroke, independent of age and other factors. However, this risk appears not to be mediated through greater risk of HT or cerebral edema formation.