Serum biomarkers as early indicators of outcomes in spontaneous subarachnoid hemorrhage

Abstract Objectives Spontaneous subarachnoid hemorrhage (sSAH) is a life-threatening neurological event with high morbidity and mortality. Predicting patient outcomes remains challenging, necessitating novel prognostic tools. This study evaluates the prognostic value of central and systemic serum biomarkers, including S100, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCHL-1), soluble suppression of tumorigenicity 2 (sST2), and soluble urokinase plasminogen activator receptor (suPAR) in acute sSAH. Methods A prospective observational study was conducted on 91 sSAH patients admitted to the Emergency Department. Biomarkers were measured 24 h post-admission and correlated with clinical severity using the modified Rankin Scale (mRS) at 24 h and 3 months. Statistical analyses included correlation tests, receiver operating characteristic (ROC) curves, and partial least squares discriminant analysis with 10-fold cross-validation (PLS-DA) to assess predictive accuracy. Results Patients with unfavorable outcomes (mRS 3–6) exhibited significantly higher median levels of all biomarkers. GFAP (ρ=0.74, p<0.0001) and S100 (ρ=0.65, p<0.0001) strongly correlated with hemorrhage volume. ROC analysis confirmed GFAP and S100 as the most effective central biomarkers (AUC=0.951), while sST2 demonstrated the highest prognostic sensitivity (97.1 %). PLS-DA further validated the prognostic relevance of sST2, GFAP, and S100. Conclusions Early biomarker assessment enhances sSAH prognosis, complementing neuroimaging. GFAP and S100 strongly correlate with brain injury severity, while sST2 predicts 3-months outcomes. Integrating these biomarkers into routine practice may improve early risk stratification and patient management.