Introduction: Ubiquitin C-terminal hydrolase (UCH-L1) is a protein highly expressed within neurons and may be a potential biomarker for traumatic brain injury (TBI). It has previously been shown to be elevated in TBI patients compared to uninjured controls. However, its utility as a biomarker in CT-negative concussion has yet to be investigated.
Methods: Patients in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study with GCS of 13-15 on ED admission and negative intracranial findings on acute CT within 24 hours of injury, with blood draw within 24-hours of injury for UCH-L1 analysis and brain MRI at 2-weeks were included in the current analysis.
Results: Overall, acute blood sample and MRI were obtained in 44 CT-negative patients. The presence of intracranial injury on MRI was assessed in all patients. Positive MRI findings included the following: 3 subdural hematoma (SDH), 3 deep shear injury, and 13 cortical shear injury. CT-negative patients with MRI findings of shear or SDH showed significantly elevated UCH-L1 compared to MRI-negative patients. Mean plasma level of UCH-L1 in MRI-positive patients was elevated compared to MRI-negative (0.20 ng/mL vs. 0.13 ng/mL; p=0.031). Patients with deep shear injury had higher mean UCH-L1 than those without (0.23 vs 0.13 ng/mL; p=0.020). Similarly, patient with SDH had higher mean UCH-L1 than those without (0.30 vs 0.15 ng/mL; p=0.020). These findings within the concussion cohort were not replicated with glial fibrillary acidic protein (GFAP), a known marker of astrocyte injury following TBI.
Conclusions: These data suggest that this novel biomarker has the potential to detect occult intracranial injury in TBI patients, specifically those meeting criteria with concussion who have negative head CT imaging. Further studies are necessary to replicate these findings in larger and more diverse samples, and to assess the impact on UCH-L1 levels as a prognosticator for acute and long-term outcomes following TBI.
Patient Care: The use of UCH-L1 as a biomarker for CT-occult MRI findings may have inform the stratification of concussion into more and less severe types. In addition to imaging findings, it may help to diagnose brain injury.
Learning Objectives: 1) Understand the physiologic role of UCH-L1 within neurons and the rationale behind its use as a potential biomarker in TBI.
2) Recognize the potential role of UCH-L1 in prognosticating patients who may suffer higher burden of sequelae after TBI.
3) Understand the emerging role of biomarkers in the detection and prognostication of TBI in combination with standard imaging techniques.