Serum Biomarkers for Early Prediction of Outcome After Moderate-to-Severe Traumatic Brain Injury
Early Prognostic Biomarkers for TBI
DOI:
https://doi.org/10.69750/dmls.03.06.0216Keywords:
Traumatic brain injury, GFAP, UCH-L1, serum biomarkers, neurological outcome, GCSAbstract
Background: The prognosis following moderate-to-severe traumatic brain injury (TBI) is difficult to predict accurately in the early stage.
Objective: To evaluate the prognostic value of early serum biomarkers in predicting six-month functional outcomes among patients with moderate-to-severe traumatic brain injury.
Methods: This prospective observational study was conducted in the Department of Neurosurgery and Neurocritical Care, Nishtar Hospital, Nishtar Medical University, Multan, Pakistan, from March 2023 to March 2025.Serial GFAP, UCH-L1, NSE, and S100B levels were obtained within 6 hours of admission. At six months, functional outcome was evaluated using the Glasgow Outcome Scale-Extended and divided into favourable and unfavourable outcomes.
Results: A favourable outcome was observed in 72 patients, while 48 had an unfavourable outcome, including 20 deaths. The GFAP, UCH-L1, NSE, and S100B levels were significantly higher for patients with an unfavourable outcome compared to patients with a favourable recovery. GFAP was the best predictor of unfavourable outcome with an AUC of 0.86, followed by UCH-L1 (AUC 0.81). The combined GFAP and UCH-L1 model had better predictive accuracy (AUC 0.89). Multivariable analysis revealed GFAP, UCH-L1, a lower GCS on admission, non-reactive pupils, a higher Marshall CT grade, and higher age to be independent predictors of poor outcome.
Conclusions: The serum assessment of these biomarkers is a valuable prognostic tool following moderate to severe TBI. GFAP and UCH-L1 seem to be the most promising early markers and could potentially be used to help stratify patients clinically.
Downloads
References
Bazarian JJ, Zetterberg H, Buki A, Dengler BA, Diaz-Arrastia R, Korley FK, et al. Blood-based biomarkers for improved characterization of traumatic brain injury: recommendations from the 2024 National Institute of Neurological Disorders and Stroke Traumatic Brain Injury Classification and Nomenclature Initiative Blood-Based Biomarkers Working Group. J Neurotrauma. 2025;42(13-14):1065-1085. doi:10.1089/neu.2024.0581.
Whitehouse DP, Wilson L, Czeiter E, Buki A, Wang KKW, von Steinbüchel N, et al. Association of blood-based biomarkers and 6-month patient-reported outcomes in patients with mild TBI: a CENTER-TBI analysis. Neurology. 2025;104(1):e210040. doi:10.1212/WNL.0000000000210040.
Ma R, Liu Y, Mao Q. Clinical value of serum LINC02446 and S100B in early diagnosis and prognosis assessment of traumatic brain injury. Int J Neurosci. 2025;135(9):998-1005. doi:10.1080/00207454.2024.2341929.
Welch RD, Bazarian JJ, Chen JY, Chandran R, Datwyler SA, McQuiston B, et al. A high-performance core laboratory GFAP/UCH-L1 test for the prediction of intracranial injury after mild traumatic brain injury. Am J Emerg Med. 2025;89:129-134. doi:10.1016/j.ajem.2024.12.005.
Wilson L, Newcombe VFJ, Whitehouse DP, Mondello S, Maas AIR, Menon DK; CENTER-TBI Participants and Investigators. Association of early blood-based biomarkers and six-month functional outcomes in conventional severity categories of traumatic brain injury: capturing the continuous spectrum of injury. EBioMedicine. 2024;107:105298. doi:10.1016/j.ebiom.2024.105298.
Behzadi F, Luy DD, Schaible PA, Zywiciel JF, Puccio AM, Germanwala AV. A systematic review and meta-analysis of major blood protein biomarkers that predict unfavorable outcomes in severe traumatic brain injury. Clin Neurol Neurosurg. 2024;242:108312. doi:10.1016/j.clineuro.2024.108312.
Mathew D, Purohit P, Gadwal A, Anil A, Sharma RK, Meshram VP, et al. Integrated assessment of GFAP and UCH-L1 for their utility in severity assessment and outcome prediction in traumatic brain injury. Int J Legal Med. 2024;138(6):2559-2568. doi:10.1007/s00414-024-03287-z.
Sperry JL, Luther JF, Okonkwo DO, Vincent LE, Agarwal V, Cotton BA, et al. Early GFAP and UCH-L1 point-of-care biomarker measurements for the prediction of traumatic brain injury and progression in patients with polytrauma and hemorrhagic shock. J Neurosurg. 2024. doi:10.3171/2024.1.JNS232569.
Mastandrea P, Mengozzi S, Bernardini S. Systematic review and meta-analysis of observational studies evaluating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 as blood biomarkers of mild acute traumatic brain injury or sport-related concussion in adult subjects. Diagnosis (Berl). 2025;12(1):1-16. doi:10.1515/dx-2024-0078.
Zarei H, Roshdi Dizaji S, Toloui A, Yousefifard M, Esmaeili A. Diagnostic and prognostic values of S100B versus neuron-specific enolase for traumatic brain injury: a systematic review and meta-analysis. Arch Acad Emerg Med. 2024;12(1):e29. doi:10.22037/aaem.v12i1.2222.
Hossain I, Marklund N, Czeiter E, Hutchinson P, Buki A. Blood biomarkers for traumatic brain injury: a narrative review of current evidence. Brain Spine. 2024;4:102735. doi:10.1016/j.bas.2023.102735.
Legramante JM, Minieri M, Belli M, Giovannelli A, Agnoli A, Bajo D, et al. Evaluation of GFAP/UCH-L1 biomarkers for computed tomography exclusion in mild traumatic brain injury. Int J Emerg Med. 2024;17(1):164. doi:10.1186/s12245-024-00708-z.
Kobeissy F, Arja RD, Munoz JC, Shear DA, Gilsdorf J, Zhu J, et al. The game changer: UCH-L1 and GFAP-based blood test as the first marketed in vitro diagnostic test for mild traumatic brain injury. Expert Rev Mol Diagn. 2024;24(1-2):67-77. doi:10.1080/14737159.2024.2306876.
Robba C, Graziano F, Picetti E, Åkerlund C, Addis A, Pastore G, et al. Early systemic insults following traumatic brain injury: association with biomarker profiles, therapy for intracranial hypertension, and neurological outcomes—an analysis of CENTER-TBI data. Intensive Care Med. 2024;50(3):371-384. doi:10.1007/s00134-024-07324-8.
Richter S, Czeiter E, Amrein K, Mikolic A, Verheyden J, Wang K, et al. Prognostic value of serum biomarkers in patients with moderate-severe traumatic brain injury, differentiated by Marshall computed tomography classification. J Neurotrauma. 2023;40(21-22):2297-2310. doi:10.1089/neu.2023.0029.
Castaño-Leon AM, Sánchez Carabias C, Hilario A, Ramos A, Navarro-Main B, Paredes I, et al. Serum assessment of traumatic axonal injury: the correlation of GFAP, t-tau, UCH-L1, and NfL levels with diffusion tensor imaging metrics and its prognosis utility. J Neurosurg. 2023;138(2):454-464. doi:10.3171/2022.5.JNS22638.
Wang KW, Zhan CP, Liu YQ, Fu ZZ, Qiu TW, Yu GF. A prospective observational study on utility of serum mesencephalic astrocyte-derived neurotrophic factor as a promising prognostic biomarker of severe traumatic brain injury in humans. Clin Chim Acta. 2023;545:117370. doi:10.1016/j.cca.2023.117370.
Retel Helmrich IRA, Czeiter E, Amrein K, Buki A, Lingsma HF, Menon DK, et al. Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury: an observational cohort study. Lancet Neurol. 2022;21(9):792-802. doi:10.1016/S1474-4422(22)00218-6.
Korley FK, Jain S, Sun X, Puccio AM, Yue JK, Gardner RC, et al. Prognostic value of day-of-injury plasma GFAP and UCH-L1 concentrations for predicting functional recovery after traumatic brain injury in patients from the US TRACK-TBI cohort: an observational cohort study. Lancet Neurol. 2022;21(9):803-813. doi:10.1016/S1474-4422(22)00256-3.
Czeiter E, Amrein K, Gravesteijn BY, Lecky F, Menon DK, Mondello S, et al. Blood biomarkers on admission in acute traumatic brain injury: relations to severity, CT findings and care path in the CENTER-TBI study. EBioMedicine. 2020;56:102785. doi:10.1016/j.ebiom.2020.102785
Downloads
PlumX Metrics
Published
Issue
Section
License
© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License , which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third-party material in this article are included in the article’s Creative Commons license unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you must obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
How to Cite
