title: Clinical utility of serum levels of ubiquitin C-terminal hydrolase as a biomarker for severe traumatic brain injury.
abstract: 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).
  
  
  CONCLUSIONS
  Serum levels of UCH-L1 appear to have potential clinical utility in diagnosing TBI, including correlating to injury severity and survival outcome.
authors.affiliation: Department of Anesthesiology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA. stm_mondello@hotmail.com
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.forename: Akinyi
authors.initials: A
authors.lastname: Linnet
authors.forename: Andras
authors.initials: A
authors.lastname: Buki
authors.forename: Steven
authors.initials: S
authors.lastname: Robicsek
authors.forename: Andrea
authors.initials: A
authors.lastname: Gabrielli
authors.forename: Joseph
authors.initials: J
authors.lastname: Tepas
authors.forename: Linda
authors.initials: L
authors.lastname: Papa
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Brophy
authors.forename: Frank
authors.initials: F
authors.lastname: Tortella
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000097:blood / Q000175:diagnosis / Q000401:mortality; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015599:Trauma Severity Indices; D043222:Ubiquitin Thiolesterase / Q000097:blood* / Q000134:cerebrospinal fluid; D055815:Young Adult
chemical_list: D015415:Biomarkers; D043222:Ubiquitin Thiolesterase