Edema Reduction versus Penumbra Salvage: Investigating Treatment Effects of Mechanical Thrombectomy in Ischemic Stroke

Objective Mechanical thrombectomy (MT) is of benefit to patients with ischemic stroke; however, the effect of recanalization on lesion pathophysiology is not yet well understood. The aim of this study was to quantitatively assess how the effect of vessel recanalization on clinical outcome is mediated by edema reduction versus penumbra salvage. Methods Consecutive analysis was made of anterior circulation ischemic stroke patients triaged by multimodal computed tomography (CT) undergoing MT. Edema reduction was defined using the difference of quantitative net water uptake (NWU) determined on baseline and follow‐up CT (∆NWU). Penumbra salvage volume (PSV) was defined as the difference between admission penumbra and net infarct growth volumes to follow‐up. Mediation analyses were performed with vessel recanalization as independent variable (modified Thrombolysis in Cerebral Infarction ≥ 2b) and ∆NWU/PSV as mediator variables. Modified Rankin Scale scores at 90 days served as endpoint. Results Of 422 included patients, 321 (76%) achieved successful recanalization. The median ∆NWU was 6.8% (interquartile range [IQR] = 3.9–10.4), and the median PSV was 66ml (IQR = 8–124). ∆NWU, PSV, and recanalization were significantly associated with functional outcome in logistic regression analysis. ∆NWU and PSV partially mediated the relationship between recanalization and outcome. Sixty‐six percent of the relationship between recanalization and functional outcome could be explained by treatment‐induced edema reduction, whereas 22% was mediated by PSV ( p < 0.0001). Interpretation Compared to penumbra salvage, edema reduction was a stronger mediator of the effect of recanalization on functional outcome. Given the current trials on adjuvant neuroprotectants also targeting ischemic edema formation, combining reperfusion with antiedematous neuroprotectants may have synergistic effects resulting in better outcomes in patients with ischemic stroke. ANN NEUROL 2024;95:137–145