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A prospective observational study was conducted on 108 consecutive sSAH patients admitted between January 2022 and August 2024. Serum S100B levels were measured at 24\u00a0h (T0), 72\u00a0h (T1), and 7\u00a0days (T2) post-admission. Clinical outcomes, including the modified Rankin Scale (mRS) at 14\u00a0days and 3\u00a0months, as well as complications such as delayed cerebral ischemia (DCI) and systemic adverse events, were recorded. Associations were analyzed using logistic regression and explored using random forest with repeated cross-validation. Higher early S100B levels were independently associated with worse functional outcome and higher mortality. S100B at T1 was associated with delayed cerebral ischemia (DCI) in univariate analysis, but this association did not persist after multivariable adjustment for clinical severity. Random forest analyses supported the prognostic value of early S100B measurements for functional outcome; S100B at T0 and T1 emerged as the most influential predictors. No significant association was found between S100B levels and systemic complications. S100B is a promising early biomarker for predicting mortality and functional outcomes in sSAH, whereas its independent association with DCI and its predictive value for systemic complications appear limited. Larger validation studies are warranted before biomarker-guided clinical protocols can be considered.<\/jats:p>","DOI":"10.1007\/s12035-026-06202-2","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:45:33Z","timestamp":1789969533000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum S100B and Clinical Outcomes After Spontaneous Subarachnoid Hemorrhage: A Prospective Observational Study"],"prefix":"10.1007","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-4476","authenticated-orcid":false,"given":"Anna Maria","family":"Auricchio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Baroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Nichelatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Napoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Calvanese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Maria","family":"Ceccarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Martinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Menna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Obersnel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Scarcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Alexandre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anselmo","family":"Caricato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo Lucio","family":"Sturiale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Albanese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Marchese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Doglietto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Olivi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Maria Della","family":"Pepa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"6202_CR1","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1161\/STR.0b013e3182587839","volume":"43","author":"ES Connolly","year":"2012","unstructured":"Connolly ES, Rabinstein AA, Carhuapoma JR et al (2012) Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association\/American Stroke Association. 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Institutional Review Board approval was obtained (ID FPG\/6185).The objective was to evaluate and diagnose patients according to the facility\u2019s standard procedures, without introducing any new treatments.A prospective observational study to monitor the predictive role of blood serum biomarkers for sSAH was launched. (clinicaltrials.gov NCT06218654, 2024-01-15).","order":1,"name":"Ethics","label":"Ethics Approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","label":"Consent for Publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"913"}}