Higher early S100B levels were independently associated with worse functional outcome and higher mortality in spontaneous subarachnoid hemorrhage, though its independent association with delayed cerebral ischemia and systemic complications appears limited.
Key Findings
Results
Higher early serum S100B levels were independently associated with worse functional outcomes in spontaneous subarachnoid hemorrhage patients.
Study enrolled 108 consecutive sSAH patients admitted between January 2022 and August 2024
S100B levels were measured at 24 hours (T0), 72 hours (T1), and 7 days (T2) post-admission
Functional outcomes were assessed using the modified Rankin Scale (mRS) at 14 days and 3 months
Association was confirmed by both logistic regression and random forest analyses with repeated cross-validation
S100B at T0 and T1 emerged as the most influential predictors in random forest analyses
Results
Higher early S100B levels were independently associated with higher mortality in sSAH patients.
The association between early S100B and mortality was identified through logistic regression analysis
S100B measurements at 24 hours (T0) and 72 hours (T1) were the most prognostically relevant time points
The prospective observational design included 108 consecutive patients
This association held after multivariable adjustment
Results
S100B at 72 hours (T1) was associated with delayed cerebral ischemia (DCI) in univariate analysis, but this association did not persist after multivariable adjustment for clinical severity.
DCI was recorded as one of the clinical complications tracked in the study
The univariate association between T1 S100B and DCI was not maintained after controlling for clinical severity measures
This suggests that clinical severity scores may account for the apparent S100B-DCI relationship
The authors concluded that S100B's independent association with DCI 'appears limited'
Results
No significant association was found between S100B levels at any time point and systemic complications.
Systemic adverse events were recorded alongside neurological complications
S100B levels at T0, T1, and T2 were all examined for association with systemic complications
The absence of association suggests S100B reflects brain-specific injury rather than systemic stress responses
Authors concluded S100B's predictive value for systemic complications 'appears limited'
Results
Random forest analyses with repeated cross-validation supported the prognostic value of early S100B measurements for functional outcome.
Random forest analysis was used alongside logistic regression as a complementary analytical approach
S100B at T0 (24 hours) and T1 (72 hours) emerged as the most influential predictors in this model
Repeated cross-validation was used to assess robustness of the machine learning findings
Results were consistent with the logistic regression findings, supporting the overall conclusion
Conclusions
The authors concluded that larger validation studies are warranted before biomarker-guided clinical protocols based on S100B can be considered.
The study was a single-center prospective observational study with 108 patients
The authors described S100B as 'a promising early biomarker for predicting mortality and functional outcomes in sSAH'
The call for larger studies indicates the current sample size is insufficient to support clinical protocol development
The study period spanned from January 2022 to August 2024
What This Means
This research suggests that a blood protein called S100B, which is released from brain cells when they are damaged, can help predict how well patients will recover after a spontaneous subarachnoid hemorrhage (a type of brain bleed that occurs when a blood vessel ruptures near the brain's surface). Researchers measured S100B levels in 108 patients at three time points — 1 day, 3 days, and 7 days after admission — and found that patients with higher S100B levels early on were more likely to die or have poor functional outcomes at both 2 weeks and 3 months after their hemorrhage. Both traditional statistical analysis and machine learning approaches pointed to the same conclusion: early S100B measurements, especially at 24 and 72 hours, were among the strongest predictors of outcome.
However, the study also found important limitations to S100B's usefulness. While S100B at 72 hours appeared linked to a serious complication called delayed cerebral ischemia (reduced blood flow to the brain that can occur days after the initial bleed), this link disappeared when researchers accounted for how clinically severe the patients were overall. S100B also showed no meaningful relationship with complications outside the brain, suggesting it specifically reflects brain injury rather than general bodily stress.
This research suggests S100B has real promise as an early warning tool for doctors treating subarachnoid hemorrhage patients, potentially helping identify those most at risk of death or disability before it becomes clinically obvious. However, because this was a single-center study with 108 patients, the authors caution that larger studies across multiple hospitals are needed before S100B measurements could be formally incorporated into treatment decision-making protocols.
Auricchio A, Baroni S, Nichelatti M, Napoli G, Calvanese F, Ceccarelli G, et al.. (2026). Serum S100B and Clinical Outcomes After Spontaneous Subarachnoid Hemorrhage: A Prospective Observational Study.. Molecular neurobiology. https://doi.org/10.1007/s12035-026-06202-2