Association of White Matter Disease With Functional Recovery and 90-Day Outcome After EVT: Beyond Chronological Age

Background: Patients with white matter disease (WMD) - a key marker of cerebral small vessel disease - may have less brain reserve to cope with ischemic injury. The relationship of WMD to functional recovery after endovascular thrombectomy is uncertain. We aim to explore the association between WMD and functional outcome, assessed at multiple time-points postendovascular thrombectomy. Methods: In this post hoc analysis, we analyzed noncontrast computed tomography-imaging from the ESCAPE-NA1 (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial and assessed WMD by using the total Fazekas-score (score range: 0-6). The primary outcome was repeated measurements of the modified Rankin scale (mRS) scores (i.e., day-5/discharge, day-30, and day-90). Secondary outcome measures were the ordinal-mRS at 90-days, 90-day-mRS0-2, and 90-day-mortality. Mixed-linear and binary/ordinal logistic regressions were performed, adjusting for age, sex, baseline National Institutes of Health Stroke Scale, cortical atrophy, chronic infarctions, stroke laterality, follow-up infarct volume, and alteplase-nerinetide interaction. Sensitivity analyses were done including only those patients for whom magnetic resonance imaging was available. Results: We included 1102 patients with noncontrast computed tomography (median age 71, interquartile range: 61-80; median National Institutes of Health Stroke Scale 17, interquartile range: 12-21). The median total Fazekas-score was 1(interquartile range: 0-2). Out of 1202 patients, 566 had follow-up magnetic resonance imaging. We observed heterogeneity in functional recovery with varying degrees of WMD-burden (P<0.001). Patients with Fazekas=3-6 fared worse at every time-point after endovascular thrombectomy, compared with patients with Fazekas=0-1. At 30-days, the adjusted difference of the mean mRS=0.47; 95% CI, 0.22-0.72 and at 90-days: adjusted difference=0.60 (95% CI, 0.36-0.85). Higher WMD-burdens were also associated with worse 90-day mRS (adjusted common odds ratio for Fazekas=3-6 versus 0-1: 1.42; 95% CI, 1.03-1.96). Similar results were found in magnetic resonance imaging-only sensitivity analyses. Conclusion: Patients with more WMD showed worse functional recovery after endovascular thrombectomy, compared with patients without WMD, even after adjusting for age and chronic disease markers like atrophy and chronic infarctions. These data may further help inform treatment expectations and recovery-related planning, by using simple visual ratings on routinely acquired noncontrast computed tomography.