OBJECTIVE: The goal was to analyze the progression of cerebral edema post-endovascular thrombectomy (EVT) in large infarcts and its association with functional outcomes. METHODS: A secondary analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core trial was conducted in patients with large ischemic cores randomized to receive either EVT or medical management (MM) alone. Patients who had follow-up imaging within 7 days post-randomization were involved. The primary outcome was midline shift (MLS). Mediation analysis was performed with EVT as the independent variable, MLS as the mediator, and modified Rankin scale scores at 90 days served as the endpoint. An exploratory analysis was conducted on the progression of net water uptake (ΔNWU). RESULTS: Of 434 patients, median age was 66.0 years (standard deviation [SD], 9.9), with 61.3% (266) being males. EVT was associated with an early increase in MLS at 24 (±12) hours after randomization (mean [SD], 3.0 [4.2] vs 2.4 [3.6]mm
p = 0.03) compared with the MM group, partially mediating poorer functional outcomes post-EVT (mediation proportion, -25%
95% CI, -46.54 to -4.10), but did not negate the overall efficacy of thrombectomy. The progression of NWU remained slower after EVT throughout 7 days, inconsistent with MLS. INTERPRETATION: In patients with large infarct cores, EVT was associated with an early increased mass effect compared with MM, potentially mediating poorer functional outcomes. Despite the evident overall benefits from thrombectomy, accurate prediction and effective anti-edema interventions for the early mass effect post-EVT may further improve outcomes. The complex relationship between NWU and cerebral edema progression warrants further investigation. ANN NEUROL 2025.