Objectives: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are considered to be both sensitive and specific for TBI in acute injury diagnostics. The objective of this study is to report the levels of GFAP and UCH-L1 in patients with acute orthopedic injuries without central nervous system involvement and to relate them with the type of extracranial injury, head magnetic resonance imaging (MRI) findings, and GFAP and UCH-L1 levels of patients with mild TBI. Methods: Serum UCH-L1 and GFAP were measured from 74 patients with acute orthopedic trauma without any acute or previous brain injuries or central nervous system diseases and compared with mild TBI patients. In addition, for the patients in whom GFAP and UCH-L1 levels were in the upper quartile on arrival day biomarker levels were compared to those found within patients with mild TBI with negative head computed tomography findings (n=52). The injury types and head MRI findings were recorded from all orthopedic trauma patients. Results: The levels of UCH-L1 were not significantly different in patients with mild TBI and orthopedic trauma. The levels of GFAP were higher in orthopedic trauma patients as compared to patients with mild TBI on arrival day (p = 0.026), but the levels were not significantly different on the following days (Figure 1). Altogether 23 patients with orthopedic trauma (31 %) had elevated levels of GFAP, UCH-L1, or both. The patients with elevated levels of GFAP and UCH-L1 had significantly higher biomarker levels as compared to mild TBI patients (p < 0.001) (Figure 2). The levels of UCH-L1 and GFAP in orthopedic trauma patients correlated significantly on admission, on the day after the injury, and on the follow-up visit 3-6 months after the injury: Spearman rho for arrival 0.744 (p < 0.001), for day 1 0.544 (p = 0.004), and for the follow-up 0.394 (p = 0.005). Eight patients with high UCH-L1 values had injuries in the upper extremity and the majority of them had concurrently high GFAP values. Another eight patients with high GFAP levels had ankle fractures. Fifty three patients with orthopaedic injuries underwent MRI of the brain, and 31 of those were reported as normal. The majority of patients who had high levels of UCH-L1 and GFAP and underwent MRI of the brain had imaging than was reported as normal. 31 out of 53 done had normal MRI findings. Conclusion: Levels of GFAP and UCH-L1 were not able to distinguish mild TBI patients from orthopedic trauma patients. Orthopaedic trauma patients with levels of GFAP and UCH-L1 in the upper quartile for that group had significantly higher biomarker levels than those found in patients with mild TBI. The source of elevated GFAP and UCH-L1 levels in the presented patients remains unknown. Orthopedic trauma patients with high UCH-L1 and GFAP values may interfere with outcome analysis of true TBI patients in the emergency department and predispose them to unwarranted diagnostics and recurrent head imaging.   Figure 1. Levels of GFAP and UCH-L1 in patients with orthopedic injury (C) and mild TBI (mTBI). P-Value is from Mann-Whitney U test.
Figure 2. Levels of GFAP and UCH-L1 in patients with orthopedic injury with biomarker levels in the upper quartile group and mild TBI (mTBI). P-Value from Mann-Whitney U test.