Orthopedic trauma is associated with higher serum concentrations of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 in mild traumatic brain injury with negative head computed tomography

Introduction: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) are increasingly used biomarkers in the evaluation of mild traumatic brain injury (mTBI), primarily to reduce the frequent overuse of head computed tomography (head CT). However, their specificity may be compromised by orthopedic trauma, which commonly accompanies mTBI. The aim of this study was to assess whether orthopedic trauma is associated with higher serum concentrations of GFAP and UCH-L1 in CT-negative mTBI patients, thereby potentially reducing their specificity for detecting CT-positive mTBI. Materials and methods: This prospective observational study included 67 CT-negative mTBI patients, of whom 29 (0.43) had orthopedic trauma and 38 (0.57) had none. Blood samples were obtained within 12 hours of injury and serum concentrations of GFAP and UCH-L1 were measured using a chemiluminescent microparticle immunoassay (CMIA) on the Alinity analyzer, following the manufacturer’s instructions. Statistical analysis included Mann-Whitney U test, chi-square test, Kruskal-Wallis test, post-hoc Dunn’s test and logistic regression analysis with P < 0.05 considered significant. Results: Serum GFAP concentrations were significantly higher in patients with orthopedic injuries (median (IQR): 70.0 (30.8 to 226.5) pg/mL) than in those without (24.95 (5.52 to 49.15) pg/mL; P < 0.001). Similarly, UCH-L1 concentrations were higher in the orthopedic injury group (median (IQR): 2494.3 (670.1 to 5708.1) pg/mL) compared with those without trauma (262.8 (153.8-595.3) pg/mL; P < 0.001). Conclusions: Orthopedic trauma is associated with higher serum concentrations of GFAP and UCH-L1 in CT-negative mTBI patients, which may reduce the specificity of these biomarkers for ruling out intracranial injury.