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Serum glial fibrillary acidic protein (GFAP) predicts outcome after intracerebral and subarachnoid hemorrhage

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Abstract

Background and purpose

Intracerebral and subarachnoid hemorrhage are critical conditions with a high mortality, and the outcome for the individual patient is notoriously difficult to predict. Biomarkers that reflect disease severity and predict outcome are therefore warranted.

Methods

Blood samples from 40 patients with intracerebral, 46 patients with subarachnoid hemorrhage, and 70 healthy individuals were collected. Levels of glial fibrillary acidic protein (GFAP) and neuroglobin were measured by ultra-sensitive single molecule array and enzyme-linked immunosorbent assay, respectively. Clinical information including mortality and functional outcome was recorded.

Results

Blood levels of GFAP and neuroglobin in intracerebral and subarachnoid hemorrhage patients were significantly elevated when compared to healthy individuals (all p < 0.0001). GFAP levels were significantly higher in patients dying or with poor functional outcome than in healthy individuals (all p ≤ 0.01). GFAP levels separated survivors from non-survivors with an area under receiver operating characteristics (AUROC) = 0.78 (confidence interval (CI) 0.59–0.98) for intracerebral hemorrhage and 0.82 (CI 0.69–0.94) for subarachnoid hemorrhage patients. The Akaike and Bayesian information criteria (AIC/BIC) for mortality/poor outcome prediction improved when combining GFAP levels with hematoma volume (p = 0.04/p < 0.01), National Institutes of Health Stroke Scale (NIHSS) (p = 0.09/p < 0.01), Hunt-Hess (p < 0.05/p = 0.21), or Fischer score (p < 0.05/p = 0.02).

Conclusions

Elevated GFAP levels at admission to hospital predicted mortality and poor outcome in our cohort of intracerebral and subarachnoid hemorrhage patients. Neuroglobin levels did not provide additional information. Combining GFAP measurements with clinical disease severity scores increased outcome prediction precision. This may suggest that GFAP measurement could improve prognostication in patients with intracerebral or subarachnoid hemorrhage.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to patient confidentiality and local data management laws, but are available from the corresponding author upon reasonable request.

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Funding

The study was graciously funded by Grosserer L.F. Foghts Fond and A.P. Møller Fonden. We also thank CLS Behring and Octapharma for unrestricted financial research support.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark

    Tua Gyldenholm, Anne-Mette Hvas & Claus V. B. Hviid

  2. Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark

    Christine L. Hvas

  3. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Christine L. Hvas & Anne-Mette Hvas

  4. Department of Clinical Biochemistry, Aalborg University Hospital, Hobrovej 18-22, Aalborg, 9100, Denmark

    Claus V. B. Hviid

Authors
  1. Tua Gyldenholm
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  4. Claus V. B. Hviid
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Corresponding author

Correspondence to Claus V. B. Hviid.

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Ethical approval and informed consent

The study was performed in accordance with the Declaration of Helsinki and was approved by the Central Denmark Region Committees on Health Research Ethics (case no. 1–10-72–95-14 and 1–10-72–94-14). The Danish Data Agency (journal no. 2014–41-3416) approved the study before initiation. Informed consent was obtained from the patients when possible. If the cognitive state of the patient made informed consent impossible, consent was obtained from the patients’ next of kin and the patients’ general practitioner.

Conflict of interest

None of the financial donors had any influence on the design, analysis, interpretation of the results, or manuscript writing. None of the authors have any conflicts of interest to disclose regarding the present manuscript.

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Gyldenholm, T., Hvas, C.L., Hvas, AM. et al. Serum glial fibrillary acidic protein (GFAP) predicts outcome after intracerebral and subarachnoid hemorrhage. Neurol Sci 43, 6011–6019 (2022). https://doi.org/10.1007/s10072-022-06274-7

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  • DOI: https://doi.org/10.1007/s10072-022-06274-7

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