Written by Alex Clark
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Novel blood-based biomarkers, specifically GFAP, UCH-L1, S100B, and NfL, may be well suited for early classification and triage of patients with acute and subacute minor traumatic brain injury.
Introducing the TBI alphabet soup
Blood-based biomarkers (BBM) have the potential to enhance triage, diagnosis, prognosis, and treatment of patients with acute traumatic brain injury (TBI) presenting to the ED. Current TBI classification systems (eg. Glasgow Coma Scale) rely heavily on clinical and neuroimaging criteria but may not fully capture the clinical heterogeneity of TBI.
This consensus-driven review by the National Institute for Neurological Disorders and Stroke Blood-Based Biomarkers Working Group aimed to revise the GCS-based classification system by evaluating use of BBMs in TBI. Synthesizing both available data and expert opinion, the authors support the use of FDA-approved BBMs glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and S100B for classification of acute TBI (0-24 hours, ED setting), as well as GFAP, S100B, and neurofilament light chain (NfL) for subacute classification (1-30 days, in-hospital or ICU setting). The authors highlight the potential of BBMs to accurately reflect the extent of structural brain injury and provide more nuanced phenotyping of patients with TBI.
Despite impressive sensitivity and NPV approaching 100%, the authors are overall fair in their appraisal of BBMs and include several limitations that restrict widespread clinical adoption: (1) limited evidence at “chronic” time points (>30 days), (2) lack of assay harmonization across testing platforms, (3) lack of standardized age- and sex-specific reference ranges, and (4) concern for lack of CNS tissue-specificity (ie. found in other injured organ systems).
How does this change my practice?
Although these labs are available in my ED, I am currently struggling to find reliable ways to incorporate them into clinical practice. I will continue to scan those with high-risk minor blunt head trauma and rely on validated clinical decision tools (eg. Canadian CT Head Rule) for those in the grey zone until more prospectively validated data is available. However, a brain “troponin” for minor head trauma is still intriguing, and the door appears open to combine physician gestalt, decision tools, and BBMs into a “brain score” similar to the “heart score”.
Source
Blood-Based Biomarkers for Improved Characterization of Traumatic Brain Injury: Recommendations from the 2024 National Institute for Neurological Disorders and Stroke Traumatic Brain Injury Classification and Nomenclature Initiative Blood-Based Biomarkers Working Group. J Neurotrauma. 2025 Jul;42(13-14):1065-1085. doi: 10.1089/neu.2024.0581. Epub 2025 May 20. PMID: 40393505
