Longitudinal Serum and Cerebrospinal Fluid S100B Concentrations After Aneurysmal Subarachnoid Hemorrhage: An Exploratory Comparison of Historical Cohorts With and Without Cerebrolysin Exposure

Background/Objectives: Cerebrolysin (CBL) has been proposed to exert neuroprotective and neurotrophic effects, but its biological effects after aneurysmal subarachnoid hemorrhage (aSAH) remain uncertain. We investigated longitudinal serum and cerebrospinal fluid (CSF) S100 calcium-binding protein B (S100B) profiles according to CBL exposure. Methods: This retrospective, single-center exploratory cohort study included 67 patients with aSAH (CBL, n = 26; non-CBL, n = 41). S100B was measured in serum and, when CSF access was clinically available, in CSF on days 1, 3, 5, 7, and 10. In the CBL cohort, treatment was initiated before the first study sample, which was obtained approximately 12 h after the first dose on average. Accordingly, day 1 was considered an early post-exposure measurement rather than a pre-treatment baseline. Longitudinal serum and CSF S100B concentrations were analyzed using linear mixed-effects models with patient-specific random intercepts, including CBL exposure, study day, and their interaction. A sensitivity analysis was performed after exclusion of day 1. Results: A significant overall between-cohort difference in serum S100B was observed across the study period (geometric mean ratio [GMR] 0.028, 95% CI 0.013–0.057; p < 0.001), with no significant CBL-by-day interaction (p = 0.218). The association persisted after exclusion of day 1 (GMR 0.023, 95% CI 0.011–0.049; p < 0.001). No significant overall between-cohort difference was observed for CSF S100B (GMR 0.542, 95% CI 0.185–1.584; p = 0.263). The CSF-to-serum ratio was higher in the CBL cohort on days 1, 3, 5, and 7 but not on day 10. No significant between-group differences were observed in delayed cerebral ischemia (DCI), TCD-detected cerebral vasospasm, mortality, or functional outcomes. Conclusions: CBL exposure was associated with persistently lower serum S100B concentrations, whereas no corresponding overall between-cohort difference was observed in CSF. These findings indicate a differential association of CBL exposure with serum and CSF S100B profiles; however, because CBL exposure was completely confounded by treatment era, the observed associations cannot establish a causal treatment effect. Prospective, contemporaneous controlled studies are required to determine whether CBL directly influences S100B dynamics after aSAH.