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Clinical Utility of Serum Levels of Ubiquitin C-Terminal Hydrolase as a Biomarker for Severe Traumatic Brain Injury

Mondello, Stefania MD*,‡; Linnet, Akinyi MS§; Buki, Andras MD; Robicsek, Steven MD, PhD*; Gabrielli, Andrea MD*; Tepas, Joseph MD; Papa, Linda MD#; Brophy, Gretchen M. PharmD**; Tortella, Frank PhD‡‡; Hayes, Ronald L. PhD*,‡; Wang, Kevin K. PhD§§,‖‖

doi: 10.1227/NEU.0b013e318236a809
Research-Human-Clinical Studies

BACKGROUND: Brain damage markers released in cerebrospinal fluid (CSF) and blood may provide valuable information about diagnosis and outcome prediction after traumatic brain injury (TBI).

OBJECTIVE: To examine the concentrations of ubiquitin C-terminal hydrolase-L1 (UCH-L1), a novel brain injury biomarker, in CSF and serum of severe TBI patients and their association with clinical characteristics and outcome.

METHODS: This case-control study enrolled 95 severe TBI subjects (Glasgow Coma Scale [GCS] score, 8). Using sensitive UCH-L1 sandwich ELISA, we studied the temporal profile of CSF and serum UCH-L1 levels over 7 days for severe TBI patients.

RESULTS: Comparison of serum and CSF levels of UCH-L1 in TBI patients and control subjects shows a robust and significant elevation of UCH-L1 in the acute phase and over the 7-day study period. Serum and CSF UCH-L1 receiver-operating characteristic curves further confirm strong specificity and selectivity for diagnosing severe TBI vs controls, with area under the curve values in serum and CSF statistically significant at all time points up to 24 hours (P < .001). The first 12-hour levels of both serum and CSF UCH-L1 in patients with GCS score of 3 to 5 were also significantly higher than those with GCS score of 6 to 8. Furthermore, UCH-L1 levels in CSF and serum appear to distinguish severe TBI survivors from nonsurvivors within the study, with nonsurvivors having significantly higher and more persistent levels of serum and CSF UCH-L1. Cumulative serum UCH-L1 levels > 5.22 ng/mL predicted death (odds ratio, 4.8).

CONCLUSION: Serum levels of UCH-L1 appear to have potential clinical utility in diagnosing TBI, including correlating to injury severity and survival outcome.

*Department of Anesthesiology

‖‖Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, Florida

Clinical Department, Center of Innovative Research

§Diagnostic Research and Development Department

§§Center of Innovative Research, Diagnostic Research and Development Department, Banyan Biomarkers, Inc, Alachua, Florida

Department of Neurosurgery, University of Pecs, Pecs, Hungary

Department of Neurosurgery, University of Florida, Jacksonville, Florida

#Orlando Regional Medical Center, Emergency Medicine, Orlando, Florida

**Virginia Commonwealth University, Pharmacotherapy & Outcomes Sciences and Neurosurgery, Richmond, Virginia

‡‡Department of Applied Neurobiology, Division of Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland

Correspondence: Stefania Mondello, MD, Department of Clinical Programs and Center of Innovative Research, Banyan Biomarkers, Inc, 13400 Progress Blvd, Alachua, FL 32615. E-mail:,

Received February 16, 2011

Accepted July 28, 2011

Copyright © by the Congress of Neurological Surgeons