Brain frailty on penumbral salvage following successful reperfusion in MeVO stroke via collateral impairment

Abstract

Whether endovascular thrombectomy (EVT) benefits medium vessel occlusion (MeVO) stroke remains uncertain. Brain frailty, reflecting chronic small-vessel disease and neurodegeneration, may indicate weaken collateral circulation and limit tissue salvage. We retrospectively studied 227 MeVO patients who achieved successful reperfusion (mTICI 2b–3). Baseline multimodal CT (NCCT + CTP) and follow-up MRI/CT were used to quantify the penumbral salvage index (PSI). Brain frailty was categorized on NCCT as absent (n = 66), mild (n = 88), or moderate-to-severe (n = 73) based on white matter hyperintensities, atrophy, and vascular lesions. Mediation analysis tested the indirect effect through collateral status. Greater frailty severity was associated with progressively lower PSI (0.81 vs 0.70 vs 0.63, p < 0.001). In multivariable models, higher frailty independently predicted lower PSI (β = −0.19, p = 0.003). Collateral dysfunction mediated 38% of the frailty–PSI association. Correspondingly, rates of excellent outcome (mRS 0–1) and functional independence (mRS 0–2) at 90 days declined with increasing frailty severity (both p < 0.001). These findings identify brain frailty as an independent predictor of impaired penumbral salvage for MeVO after EVT and links it to worse 90-day outcomes. The effect appears substantially mediated by collateral failure. Incorporating brain frailty into acute assessment may improve prognostic stratification among patients who achieve successful reperfusion.