Insular infarction synergistically amplifies malignant cerebral edema risk in anterior circulation large vessel occlusion

PURPOSE: Malignant cerebral edema (MCE) is a life-threatening complication following reperfusion therapy for anterior circulation large vessel occlusion stroke. This study evaluate the association between individual Alberta Stroke Program Early CT Score (ASPECTS) territories and MCE development and to quantify the synergistic risk amplification when a key territory co-occurs with ASPECTS, the National Institutes of Health Stroke Scale (NIHSS) score, and onset-to-CT time. METHODS: This multicenter retrospective study of 523 patients used multivariable logistic regression to identify independent MCE predictors. Generalized linear models and stratified analyses evaluated synergistic effects. RESULTS: MCE occurred in 22.2 % of the cohort. Insular infarction (odds ratio [OR] = 2.93; 95 % confidence interval [CI], 1.51-5.70), higher NIHSS (per point OR = 1.11; 95 % CI, 1.07-1.16), and elevated blood glucose (per mmol/L OR = 1.13; 95 % CI, 1.05-1.22) were factors independently associated with MCE. A critical synergistic effect was observed: coexisting insular infarction and ASPECTS < 6 yielded the highest risk, with 46 % of patients developing MCE (risk ratio [RR] = 4.41; 95 % CI, 2.94-7.42). Insular infarction also amplified MCE risk in patients presenting within 4.5 hours of stroke onset (RR = 5.43; 95 % CI, 3.21-12.43; interaction P = 0.006) and in those with NIHSS scores > 14 (RR = 12.89; 95 % CI, 5.85-58.86). Trend tests confirmed a dose-dependent risk escalation (P < 0.01). CONCLUSION: Insular infarction is a potent risk multiplier, synergistically amplifying MCE risk when combined with extensive early ischemia (ASPECTS < 6) or severe deficits (NIHSS score > 14), particularly during the hyperacute phase.