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Serum biomarkers as early indicators of outcomes in spontaneous subarachnoid hemorrhage

  • Anna Maria Auricchio ORCID logo EMAIL logo , Giulia Napoli , Giovanni Maria Ceccarelli , Renata Martinelli , Grazia Menna , Marco Obersnel , Luca Scarcia , Andrea Urbani , Alessandro Olivi , Giuseppe Maria Della Pepa and Silvia Baroni
Published/Copyright: May 28, 2025
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 10

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.

Keywords: immunoassay; biomarkers; neurological disorders; chemiluminescence
Corresponding author: Anna Maria Auricchio, MD, PhD Student, Neurosurgery, 18654 University Hospital Foundation A. Gemelli IRCCS, Catholic University of the Sacred Heart, , Rome, Italy, E-mail:
Anna Maria Auricchio and Giulia Napoli contributed equally to this work.

  1. Research ethics: IRB approval obtained (FPG/ID 6185).

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Upon reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0309).

Received: 2025-03-13
Accepted: 2025-05-14
Published Online: 2025-05-28
Published in Print: 2025-09-25

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2025-0309
Keywords for this article
immunoassay; biomarkers; neurological disorders; chemiluminescence

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Quality indicators: an evolving target for laboratory medicine
  4. Reviews
  5. Regulating the future of laboratory medicine: European regulatory landscape of AI-driven medical device software in laboratory medicine
  6. The spectrum of nuclear patterns with stained metaphase chromosome plate: morphology nuances, immunological associations, and clinical relevance
  7. Opinion Papers
  8. Comprehensive assessment of medical laboratory performance: a 4D model of quality, economics, velocity, and productivity indicators
  9. Detecting cardiac injury: the next generation of high-sensitivity cardiac troponins improving diagnostic outcomes
  10. Perspectives
  11. Can Theranos resurrect from its ashes?
  12. Guidelines and Recommendations
  13. Australasian guideline for the performance of sweat chloride testing 3rd edition: to support cystic fibrosis screening, diagnosis and monitoring
  14. General Clinical Chemistry and Laboratory Medicine
  15. Recommendations for the integration of standardized quality indicators for glucose point-of-care testing
  16. A cost-effective assessment for the combination of indirect immunofluorescence and solid-phase assay in ANA-screening
  17. Assessment of measurement uncertainty of immunoassays and LC-MS/MS methods for serum 25-hydroxyvitamin D
  18. A novel immunoprecipitation-based targeted liquid chromatography-tandem mass spectrometry analysis for accurate determination for copeptin in human serum
  19. Histamine metabolite to basal serum tryptase ratios in systemic mastocytosis and hereditary alpha tryptasemia using a validated LC-MS/MS approach
  20. Machine learning algorithms with body fluid parameters: an interpretable framework for malignant cell screening in cerebrospinal fluid
  21. Impact of analytical bias on machine learning models for sepsis prediction using laboratory data
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  24. High myoglobin plasma samples risk being reported as falsely low due to antigen excess – follow up after a 2-year period of using a mitigating procedure
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  26. Commutability evaluation of glycated albumin candidate EQA materials
  27. Reference Values and Biological Variations
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  30. Practical handling of hemolytic, icteric and lipemic samples for coagulation testing in European laboratories. A collaborative survey from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM)
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  32. Assessment of atypical cells in detecting bladder cancer in female patients
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