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DOI: 10.1055/s-0046-1815951
Clinical Effectiveness of a Blood-Based Biomarker in Patients with Mild Traumatic Brain Injury
Authors
Abstract
Objectives
Mild traumatic brain injury (mTBI) is among the most prevalent neurological conditions worldwide. Its diagnosis predominantly depends on computed tomography (CT) imaging, despite the majority of scans yielding negative results, leading to unnecessary resource utilization and avoidable radiation exposure. This study aims to investigate the potential of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) as serum biomarkers for ruling out clinically significant intracranial injuries.
Materials and Methods
This prospective cohort study enrolled adult patients (aged >18 years) presenting to the emergency department with nonpenetrating mTBI between October 2023 and October 2024. All participants underwent brain CT imaging and venous blood sampling for quantification of GFAP and UCH-L1. Diagnostic performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, were calculated to assess biomarker accuracy in detecting intracranial abnormalities.
Results
A total of 123 patients were enrolled, with a mean age of 70 years. The predominant mechanism of injury was a ground-level fall. The combined use of GFAP and UCH-L1 demonstrated excellent sensitivity (100%; 95% CI: 89.1–100%) and negative predictive value (100%; 95% CI: 76.8–100%) for detecting intracranial injury. However, specificity was low (15.4%; 95% CI: 8.7–24.5%), indicating limited ability to rule in pathology based on biomarker elevation alone.
Conclusion
This study demonstrates the high sensitivity and negative predictive value of GFAP and UCH-L1 as a combined biomarker test for evaluating moderate- and high-risk mTBI. Patients with a negative biomarker result may safely forgo head CT, thereby reducing unnecessary radiation exposure and avoiding unwarranted CT utilization. Nevertheless, practical challenges remain before routine clinical adoption is feasible. Future cost analyses will be essential to determine the economic viability of these biomarkers, particularly in resource-limited settings.
Keywords
traumatic brain injury - mild traumatic brain injury - serum biomarkers - head CT scan - ubiquitin C-terminal hydrolase-L1 - glial fibrillary acidic proteinAuthors' Contributions
K.L. contributed to conceptualization, methodology, data curation, formal analysis, project administration, and resources, and was responsible for writing the original draft as well as writing, reviewing, and editing the manuscript, including review of the submitted version. K.M. contributed to conceptualization, methodology, data curation, project administration, and resources, and reviewed the submitted version. K.B. contributed to conceptualization, supervision, formal analysis, and project administration, and was involved in writing, reviewing, and editing the manuscript, as well as reviewing the submitted version.
Ethical Approval
The Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, has approved this study in compliance with the international guidelines for human research protection as Declaration of Helsinki, The Belmont Report, CIOMS Guideline, and International Conference on Harmonization in Good Clinical Practice (ICH-GCP) with IRB number 0246/66, COA 615/2023, 599/2024.
Publication History
Article published online:
03 February 2026
© 2026. Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References
- 1 Damkliang J, Considine J, Kent B. Thai emergency nurses' management of patients with severe traumatic brain injury: comparison of knowledge and clinical management with best available evidence. Australas Emerg Nurs J 2013; 16 (04) 127-135
- 2 Ratanalert S, Kornsilp T, Chintragoolpradub N, Kongchoochouy S. The impacts and outcomes of implementing head injury guidelines: clinical experience in Thailand. Emerg Med J 2007; 24 (01) 25-30
- 3 Tunthanathip T, Phuenpathom N, Jongjit A. Prognostic factors and clinical nomogram for in-hospital mortality in traumatic brain injury. Am J Emerg Med 2024; 77: 194-202
- 4 Hall EJ, Brenner DJ. Cancer risks from diagnostic radiology. Br J Radiol 2008; 81 (965) 362-378
- 5 Smith-Bindman R. Is computed tomography safe?. N Engl J Med 2010; 363 (01) 1-4
- 6 af Geijerstam JL, Britton M. Mild head injury - mortality and complication rate: meta-analysis of findings in a systematic literature review. Acta Neurochir (Wien) 2003; 145 (10) 843-850 , discussion 850
- 7 Easter JS, Haukoos JS, Meehan WP, Novack V, Edlow JA. Will neuroimaging reveal a severe intracranial injury in this adult with minor head trauma?: The rational clinical examination systematic review. JAMA 2015; 314 (24) 2672-2681
- 8 Smits M, Dippel DW, de Haan GG. et al. External validation of the Canadian CT Head Rule and the New Orleans Criteria for CT scanning in patients with minor head injury. JAMA 2005; 294 (12) 1519-1525
- 9 Jagoda AS, Bazarian JJ, Bruns Jr JJ. et al; American College of Emergency Physicians, Centers for Disease Control and Prevention. Clinical policy: neuroimaging and decision making in adult mild traumatic brain injury in the acute setting. Ann Emerg Med 2008; 52 (06) 714-748
- 10 Pelinka LE, Kroepfl A, Schmidhammer R. et al. Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J Trauma 2004; 57 (05) 1006-1012
- 11 Undén J, Romner B. Can low serum levels of S100B predict normal CT findings after minor head injury in adults?: an evidence-based review and meta-analysis. J Head Trauma Rehabil 2010; 25 (04) 228-240
- 12 Bazarian JJ, Biberthaler P, Welch RD. et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol 2018; 17 (09) 782-789
- 13 Papa L, McKinley WI, Valadka AB. et al. Diagnostic performance of GFAP, UCH-L1, and MAP-2 within 30 and 60 minutes of traumatic brain injury. JAMA Netw Open 2024; 7 (09) e2431115
- 14 Bazarian JJ, Welch RD, Caudle K. et al. Accuracy of a rapid glial fibrillary acidic protein/ubiquitin carboxyl-terminal hydrolase L1 test for the prediction of intracranial injuries on head computed tomography after mild traumatic brain injury. Acad Emerg Med 2021; 28 (11) 1308-1317
- 15 Wichmann TO, Babaee A, Duch K. et al. A head-to-head comparison of S100B and GFAP/UCH-L1 for detection of traumatic intracranial lesions in a Scandinavian trauma cohort. Scand J Trauma Resusc Emerg Med 2025; 33 (01) 52
- 16 GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18 (01) 56-87
- 17 Maas AIR, Menon DK, Adelson PD. et al; InTBIR Participants and Investigators. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol 2017; 16 (12) 987-1048
- 18 Roozenbeek B, Maas AI, Menon DK. Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol 2013; 9 (04) 231-236
- 19 Steyerberg EW, Wiegers E, Sewalt C. et al; CENTER-TBI Participants and Investigators. Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study. Lancet Neurol 2019; 18 (10) 923-934
- 20 Haydel MJ, Preston CA, Mills TJ, Luber S, Blaudeau E, DeBlieux PM. Indications for computed tomography in patients with minor head injury. N Engl J Med 2000; 343 (02) 100-105
- 21 Stiell IG, Wells GA, Vandemheen K. et al. The Canadian CT head rule for patients with minor head injury. Lancet 2001; 357 (9266): 1391-1396
- 22 Jeret JS, Mandell M, Anziska B. et al. Clinical predictors of abnormality disclosed by computed tomography after mild head trauma. Neurosurgery 1993; 32 (01) 9-15 , discussion 15–16
- 23 Seno S, Tomura S, Ono K, Tanaka Y, Ikeuchi H, Saitoh D. Poor prognostic factors in elderly patients aged 75 years old or older with mild traumatic brain injury. J Clin Neurosci 2019; 67: 124-128
- 24 Nagurney JT, Borczuk P, Thomas SH. Elder patients with closed head trauma: a comparison with nonelder patients. Acad Emerg Med 1998; 5 (07) 678-684
- 25 Borczuk P. Predictors of intracranial injury in patients with mild head trauma. Ann Emerg Med 1995; 25 (06) 731-736
- 26 Czeiter E, Amrein K, Gravesteijn BY. et al; CENTER-TBI Participants and Investigators. 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
- 27 Diaz-Arrastia R, Wang KK, Papa L. et al; TRACK-TBI Investigators. Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. J Neurotrauma 2014; 31 (01) 19-25
- 28 Papa L, Zonfrillo MR, Welch RD. et al. Evaluating glial and neuronal blood biomarkers GFAP and UCH-L1 as gradients of brain injury in concussive, subconcussive and non-concussive trauma: a prospective cohort study. BMJ Paediatr Open 2019; 3 (01) e000473
- 29 Papa L, Brophy GM, Welch RD. et al. Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury. JAMA Neurol 2016; 73 (05) 551-560
- 30 Michelson EA, Huff JS, Loparo M. et al. Emergency department time course for mild traumatic brain injury workup. West J Emerg Med 2018; 19 (04) 635-640
- 31 Rogg JG, Huckman R, Lev M, Raja A, Chang Y, White BA. Describing wait time bottlenecks for ED patients undergoing head CT. Am J Emerg Med 2017; 35 (10) 1510-1513
