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Critical Care Medicine:
doi: 10.1097/CCM.0b013e3181b788ab
Clinical Investigations

Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury*

Papa, Linda MDCM, MSc; Akinyi, Linnet MS; Liu, Ming Cheng PhD; Pineda, Jose A. MD; Tepas, Joseph J. III MD; Oli, Monika W. PhD; Zheng, Wenrong PhD; Robinson, Gillian PhD; Robicsek, Steven A. MD; Gabrielli, Andrea MD; Heaton, Shelley C. PhD; Hannay, H Julia PhD; Demery, Jason A. PhD; Brophy, Gretchen M. PharmD; Layon, Joe MD; Robertson, Claudia S. MD; Hayes, Ronald L. PhD; Wang, Kevin K. W. PhD

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Abstract

Objective: Ubiquitin C-terminal hydrolase (UCH-L1), also called neuronal-specific protein gene product (PGP 9.3), is highly abundant in neurons. To assess the reliability of UCH-L1 as a potential biomarker for traumatic brain injury (TBI) this study compared cerebrospinal fluid (CSF) levels of UCH-L1 from adult patients with severe TBI to uninjured controls; and examined the relationship between levels with severity of injury, complications and functional outcome.

Design: This study was designed as prospective case control study.

Patients: This study enrolled 66 patients, 41 with severe TBI, defined by a Glasgow coma scale (GCS) score of ≤8, who underwent intraventricular intracranial pressure monitoring and 25 controls without TBI requiring CSF drainage for other medical reasons.

Setting: Two hospital system level I trauma centers.

Measurements and Main Results: Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, 120, 144, and 168 hrs following TBI and analyzed for UCH-L1. Injury severity was assessed by the GCS score, Marshall Classification on computed tomography and a complicated postinjury course. Mortality was assessed at 6 wks and long-term outcome was assessed using the Glasgow outcome score 6 months after injury. TBI patients had significantly elevated CSF levels of UCH-L1 at each time point after injury compared to uninjured controls. Overall mean levels of UCH-L1 in TBI patients was 44.2 ng/mL (±7.9) compared with 2.7 ng/mL (±0.7) in controls (p <.001). There were significantly higher levels of UCH-L1 in patients with a lower GCS score at 24 hrs, in those with postinjury complications, in those with 6-wk mortality, and in those with a poor 6-month dichotomized Glasgow outcome score.

Conclusions: These data suggest that this novel biomarker has the potential to determine injury severity in TBI patients. Further studies are needed to validate these findings in a larger sample.

© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

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