Abstract
Background: Endovascular thrombectomy (EVT) improves long-term outcome in patients presenting with large ischemic core but is associated with early neurological worsening (ENW), potentially related to cerebral edema post-reperfusion. We investigated whether EVT increases edema development, and the relationship between edema and ENW in a secondary analysis of the SELECT2 trial. Methods: SELECT 2 tested the efficacy and safety of EVT versus medical therapy in patients with large ischemic core (ASPECTS 3-5 or core volume ≥50ml on CT Perfusion[CTP]/MR diffusion). Core volume was defined as the larger of the CTP-CBF relative cerebral blood flow <30% or the visible hypodensity on non-contrast CT. Cerebral edema was measured as the maximum midline shift (MLS) on 24h follow-up MRI or CT. ENW was defined as >=4 point worsening in NIHSS at 24h compared to baseline. Probabilistic index model was used in multivariable analyses to assess ≥1 point improvement on modified Rankin Scale at 90-days. Results: After exclusion of 10 patients with hemicraniectomy, the median MLS in 327 patients was 2.75mm (IQR 0-5.85) in EVT and 0mm (IQR 0-4.02) in control patients (p=0.005). EVT was independently associated with greater MLS (adjusted odds ratio, aOR 1.50, 95%CI 1.17-1.92, p=0.0012) after adjusting for age and core volume. There was no interaction between EVT and core volume on the association with MLS (p>0.79). Patient with ENW had greater MLS (5.05mm [IQR2.06-10.2] vs 0mm [IQR0-3.94, p<0.001]) MLS was associated with development of ENW (aOR 1.22, 95%CI 1.13-1.32, p<0.001), and lower likelihood of long-term functional improvement (adjusted generalized OR 0.96, 95%CI 0.92-0.97, p<0.001, adjusted for core volume, EVT, age and baseline NIHSS). Sensitivity analysis testing alternative definitions of core volume (CTP core volume only and Hypodensity on non-contrast only) showed concordant results. Conclusion: In patients presenting with large ischemic core, EVT was associated with increased cerebral edema at 24h which, in turn, was associated with ENW. Despite overall benefit of EVT, EVT-related edema is independently associated with neurological deterioration and long-term disability and is therefore a potential treatment target to improve EVT outcomes.
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