Estimated Effect of Early Neurological Deterioration on Mortality and Poor Functional Outcome After Intracerebral Hemorrhage: A Causal Inference Analysis

Background: Early neurological deterioration (END) after intracerebral hemorrhage (ICH) is associated with poor prognosis, but its independent contribution to mortality and disability beyond baseline severity remains undetermined. Using causal inference methods, we estimated the effect of END on 3-month outcomes and the population-level impact of preventing END. Methods: Consecutive patients with acute ICH presenting within 12 h of symptom onset at a comprehensive stroke center (2014–2023) were retrospectively analyzed. END was defined as a ≥4-point increase in National Institutes of Health Stroke Scale (NIHSS) score or a ≥2-point decrease in Glasgow Coma Scale (GCS) score within 24 h. Multivariable logistic regression identified baseline predictors of END. The average treatment effect (ATE) of END on the 3-month mortality rate and poor functional outcome rate (mRS of 4–6) was estimated using G-computation, inverse probability weighting, and targeted maximum likelihood estimation (TMLE; primary), adjusting for baseline severity and clinical confounders. TMLE-based counterfactual analyses estimated the population-level impact of preventing END. Results: Among 690 patients (median age of 71 [interquartile: 60–81] years; 308 (44.6%) female), 273 (39.6%) developed END. Across the estimators, END increased the absolute risk of 3-month mortality by 23.1–23.9% and poor functional outcomes by 20.2–22.8%, with no significant effect on disability among the survivors. Counterfactual analyses projected that preventing END would reduce the mortality rate from 31.6% to 21.3% (population attributable fraction of 32.5%) and poor functional outcomes from 56.8% to 48.8% (population attributable fraction of 14.2%). Conclusions: In this single-center cohort, END was associated with a substantially higher 3-month mortality rate and poor functional outcomes, independent of measured baseline severity and other clinical confounders. If this is causal, then END is a potential target for early intervention and a candidate early efficacy endpoint for ICH trials; whether preventing END improves outcomes requires prospective evaluation.