Role of post-thrombectomy glymphatic flow in futile recanalization in large-vessel occlusion ischemic stroke

OBJECTIVE: Stroke is a leading cause of global death and disability, with mechanical thrombectomy remaining the optimal treatment approach for large-vessel occlusion (LVO) ischemic stroke. Despite endovascular recanalization, nearly half of patients experience poor functional outcomes, a phenomenon termed "futile recanalization." The cerebral glymphatic system has emerged as a potential, yet underexplored, therapeutic target. The aim of this study was to use glymphatic diffusion tensor analysis on post-thrombectomy MRI to evaluate the association between glymphatic flow, clinical outcomes, and futile recanalization in patients with LVO ischemic stroke. METHODS: In this retrospective study, 133 patients with anterior LVO ischemic stroke and available post-thrombectomy MRI at a single center from 2017 to 2021 were identified. Futile recanalization was defined by a modified Rankin Scale score > 2 at 90 days despite achieving complete or near-complete angiographic recanalization (modified thrombolysis in cerebral infarction grades 2b-3). Diffusion tensor imaging along the perivascular space was used to evaluate glymphatic function in patients with futile recanalization and patients with functional independence at 90 days. Spearman's rank correlation was used to examine associations between the along the perivascular space index and clinical variables. Effect sizes were calculated and reported using Cohen's d. RESULTS: Fifty-five patients (24 male, mean age 73.9 years) with anterior circulation LVO ischemic stroke and adequate post-thrombectomy MRI were included for analysis. Overall, glymphatic clearance was lower on the infarcted side compared with the contralateral side (p = 0.035). Patients with futile recanalization had lower glymphatic flow compared with those with functional independence at 90 days (p = 0.049). Additionally, glymphatic flow was significantly associated with the presenting National Institutes of Health Stroke Scale score (ρ = -0.46, p = 0.002). CONCLUSIONS: These findings suggest that patients with futile recanalization have comparatively worse glymphatic clearance. Further research is required to clarify the relationship between futile recanalization and the glymphatic system, which could facilitate the development of therapeutic adjuncts.