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Glymphatic Flow after Thrombectomy is Associated with Futile Recanalization in Large Vessel Occlusion Stroke

Finkelstein, A. J.; Sipple, M.; Akkipeddi, S. M. K.; Whyte, R.; Kohli, G. S.; Susa, S. T.; Singh, R.; Romiyo, P.; Zhong, J.; Bhalla, T.; Mattingly, T. K.; Nguyen, V.; Nedergaard, M.; Bender, M. T.; Schartz, D.

2025-01-17 surgery
10.1101/2025.01.16.25320702 medRxiv
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BackgroundStroke 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. In this retrospective study, we utilized glymphatic diffusion tensor analysis on post-thrombectomy MRIs scans to evaluate the association between glymphatic flow, clinical outcomes, and futile recanalization in LVO ischemic stroke. MethodsIn this retrospective study, 133 patients with anterior LVO ischemic stroke and MRI post-thrombectomy were identified. Futile recanalization was defined as a modified Rankin score >2 at 90 days, despite achieving complete or near-complete angiographic recanalization (mTICI 2b-3). We employed diffusion tensor imaging along the perivascular space (DTI-ALPS) to evaluate glymphatic function in individuals with futile recanalization and those with functional independence at 90 days. Spearmans rank correlation was used to examine associations between the ALPS index and clinical variables. Effect sizes were calculated and reported using Cohens d. ResultsIn total, 55 anterior circulation LVO patients (mean age 73.9, 44% male) were included with adequate post-thrombectomy MRIs for analysis. Overall, glymphatic clearance was lower in the infarct side compared to the contralateral side (p = 0.035). Patients with futile recanalization had lower glymphatic flow compared to those with functional independence (p=0.049). Additionally, glymphatic flow was significantly associated with presenting NIHSS (R=-0.46, p = 0.002). ConclusionsThese 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 may facilitate the development of therapeutic adjuncts.

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