Circulating inflammasome biomarkers provide independent prognostic value beyond clinical scores in aneurysmal subarachnoid hemorrhage

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor functional outcome, driven in part by neuroinflammatory mechanisms. Inflammasome activation has emerged as a key contributor to early brain injury and delayed cerebral ischemia (DCI), yet the prognostic value of circulating inflammasome-related biomarkers remains incompletely defined. This study aimed to evaluate the temporal dynamics and clinical relevance of serum interleukin-18 (IL-18), caspase-1 p20, and gasdermin D N-terminal (GSDMN) in aSAH, and to determine their incremental prognostic value beyond established clinical severity scores. METHODS: In this single-center prospective observational cohort study, 183 patients with aSAH were enrolled. Serum levels of IL-18, caspase-1 p20, and GSDMN were measured on days 1, 5, and 9 after ictus using ELISA. Clinical severity was assessed using WFNS and modified Fisher scores. The primary outcome was 3-month functional status (modified Rankin Scale). Associations were analyzed using mixed-effects models and multivariable logistic regression adjusted for clinical covariates. Model performance was evaluated using ROC analysis. RESULTS: Caspase-1 p20 levels were significantly elevated in patients and consistently higher in those with unfavorable outcome across all time points. In multivariable analyses, caspase-1 p20 (day 1 and day 5) independently predicted poor outcome and DCI, improving model performance beyond clinical variables (AUC increase from 0.880 to 0.919). IL-18 showed time-dependent changes but lacked independent prognostic significance, while GSDMN levels did not differentiate outcome groups. Longitudinal analyses revealed distinct biomarker trajectories, with significant time-outcome interactions for caspase-1 p20 only. CONCLUSION: Circulating caspase-1 p20 is a robust and independent biomarker of inflammasome activation with significant prognostic value in aSAH. Its integration into clinical models enhances outcome prediction, supporting its potential role in risk stratification and biomarker-guided therapeutic strategies.