Thrombectomy improves functional outcome in large core stroke partly by preventing severe cerebral edema: a real-world mediation analysis

Abstract

Endovascular thrombectomy (EVT) is effective in large infarct core (LIC) stroke, but mortality and severe disability remain high when cerebral edema (CED) develops. We assessed the effect of EVT on CED and outcomes in LIC patients within 24 h of stroke onset. In a prospective observational cohort study, we enrolled patients with large-vessel occlusion in the anterior circulation, National Institutes of Health Stroke Scale (NIHSS) score ≥ 6, Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5, and admission within 24 h of onset. The primary outcome was mass effect (ME) due to severe cerebral edema, defined as a maximum midline shift (MLS) ≥ 5 mm on follow-up imaging within 72 h. The secondary outcome was favorable outcome, defined as modified Rankin Scale (mRS) score of 0–3 at 90 days. Safety outcomes were determined by death at 90 days, symptomatic intracranial hemorrhage (sICH) according to SITS-MOST criteria. Treatment effects were estimated using inverse probability of treatment weighting (IPTW) with doubly robust adjustment. Mediation analysis assessed whether ME contributed to the association between EVT and favorable outcome. Of 202 patients (EVT group: 119; medical management group: 83), after IPTW adjustment, EVT was associated with lower odds of ME [31.1% vs. 51.8%; IPTW-adjusted odds ratio (aOR), 0.28; 95% CI, 0.12–0.67], higher odds of favorable outcome (aOR, 2.32; 95% CI, 1.01–5.31), and lower mortality (aOR 0.45; 95% CI, 0.21–0.97) with no excess sICH. ME independently predicted poor outcome (aOR for mRS 4–6, 7.7; 95% CI, 3.01–19.69), and approximately 29.5% of the association between EVT and favorable outcome was statistically mediated by ME attenuation. Two admission variables—lower baseline ASPECTS and higher admission glucose—independently predicted ME (optimism-corrected AUC 0.82). In large-core stroke, EVT was associated with better functional outcome and lower odds of mass effect. Approximately one-third of EVT's functional benefit was statistically mediated by attenuation of severe CED. ME independently predicted poor outcome, whereas lower ASPECTS and higher admission glucose identified patients at greater risk of severe swelling, supporting bedside risk stratification to guide intensified monitoring and edema-targeted management. ClinicalTrials.gov , Identifier [NCT06016348].