Quantified Brain Atrophy and Risk of Severe Mass Effect in Acute Ischemic Stroke

Large middle cerebral artery (MCA) infarctions can result in life-threatening cerebral edema. Quantitative brain atrophy may improve risk stratification for severe edema. We examined whether quantitative brain atrophy is associated with severe midline shift after large ischemic stroke and whether incorporating atrophy improves prediction beyond established clinical and radiographic predictors.

This was a retrospective observational cohort study of patients with ≥½ MCA ischemic infarction, presentation within 24 hours of last known well, and at least one follow-up head CT, admitted to two academic hospitals with comprehensive stroke centers between 2006 and 2024. The study was approved by the institutional review boards of both centers. Brain atrophy was quantified as the inverse of standardized brain volume on admission head CT. The primary outcome was severe radiographic mass effect, defined as midline shift ≥5 mm on follow-up CT. The secondary outcome was in-hospital mortality. Multivariable regression models assessed associations between quantified atrophy and outcomes. Incremental prognostic value was evaluated by comparing models with and without atrophy using measures of goodness of fit, calibration, and discrimination.

Among 565 patients (mean age 67.5±15.7 years; 49.9% female), 223 (39.5%) developed severe mass effect. Greater atrophy was associated with lower odds of midline shift ≥5 mm (OR 0.44, 95% CI 0.34-0.58), but not with in-hospital mortality. Incorporation of atrophy significantly improved prediction of severe mass effect compared to the baseline model (likelihood ratio test χ² (1) = 41, p <0.001; AIC 703 vs. 741; BIC 733 vs. 767; AUC 0.68 vs. 0.60).

Quantified brain atrophy is independently associated with a reduced risk of severe mass effect after large MCA stroke and improved the performance of established predictive models. Incorporation of this imaging biomarker may enhance early risk stratification, monitoring, and intervention planning for patients at risk of life-threatening cerebral edema.