Title : Serum biomarkers in mild traumatic brain injury: A systematic review on the diagnostic and prognostic performance of GFAP, UCH-L1 and S100B
Abstract:
Background: Mild traumatic brain injury (mTBI) accounts for approximately 80–90% of all traumatic brain injuries evaluated in emergency departments. Although computed tomography (CT) remains the gold standard for detecting acute intracranial lesions, a substantial proportion of CT scans are negative, contributing to unnecessary radiation exposure, increased healthcare costs, and emergency department overcrowding. Blood-based biomarkers have emerged as promising tools to improve early diagnosis and optimize imaging decisions.
Objective: To systematically evaluate the diagnostic and prognostic performance of the serum biomarkers glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and S100 calcium-binding protein B (S100B) in patients with mild traumatic brain injury.
Methods: A systematic review was conducted according to the PRISMA guidelines. PubMed/MEDLINE, Embase, and Scopus were systematically searched for studies evaluating serum biomarkers in adult patients with mTBI. Eligible studies investigated biomarker concentrations in relation to CT findings, neurosurgical intervention, and clinical outcomes. Data regarding study design, patient characteristics, biomarker performance, and diagnostic accuracy were extracted and qualitatively synthesized.
Results: Eight studies involving more than 5,000 patients fulfilled the inclusion criteria. GFAP consistently demonstrated the highest diagnostic accuracy for identifying CT-positive intracranial injuries and remained elevated for up to 72 hours after trauma, supporting its usefulness even in delayed presentations. UCH-L1 showed superior sensitivity during the early post-injury period, particularly within the first hours after trauma. S100B demonstrated prognostic value but exhibited lower specificity because of extracranial expression. Several studies reported improved diagnostic performance when GFAP and UCH-L1 were combined, increasing discrimination between CT-positive and CT-negative patients while potentially reducing unnecessary neuroimaging without compromising patient safety.
Conclusion: Current evidence supports GFAP as the most reliable serum biomarker for detecting clinically significant intracranial injury after mild traumatic brain injury. The combined use of GFAP and UCH-L1 represents a promising strategy to enhance emergency department decision-making, facilitate early risk stratification, and decrease unnecessary CT utilization. Future prospective multicenter studies are needed to establish standardized cutoff values and support routine clinical implementation.
Keywords: Mild traumatic brain injury; GFAP; UCH-L1; S100B; Biomarkers; Neurotrauma; Computed Tomography.
