title: Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury.
abstract: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice.
  
  
  
  To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention.
  
  
  
  This prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury.
  
  
  
  Diagnosis of MMTBI, presence of traumatic intracranial lesions on head CT scan, and neurosurgical intervention.
  
  
  
  A total of 1831 blood samples were drawn from 584 patients (mean [SD] age, 40 [16] years; 62.0% [362 of 584] male) over 7 days. Both GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at 8 hours after injury and declined rapidly over 48 hours. Over the course of 1 week, GFAP demonstrated a diagnostic range of areas under the curve for detecting MMTBI of 0.73 (95% CI, 0.69-0.77) to 0.94 (95% CI, 0.78-1.00), and UCH-L1 demonstrated a diagnostic range of 0.30 (95% CI, 0.02-0.50) to 0.67 (95% CI, 0.53-0.81). For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 (95% CI, 0.67-0.92) to 0.97 (95% CI, 0.93-1.00)for GFAP and 0.31 (95% CI, 0-0.63) to 0.77 (95% CI, 0.68-0.85) for UCH-L1. For distinguishing patients with and without a neurosurgical intervention, the range for GFAP was 0.91 (95% CI, 0.79-1.00) to 1.00 (95% CI, 1.00-1.00), and the range for UCH-L1 was 0.50 (95% CI, 0-1.00) to 0.92 (95% CI, 0.83-1.00).
  
  
  
  GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical intervention across 7 days. UCH-L1 performed best in the early postinjury period.
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
authors.forename: Linda
authors.initials: L
authors.lastname: Papa
authors.affiliation: Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond3Department of Neurosurgery, Virginia Commonwealth University, Richmond.
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Brophy
authors.affiliation: Division of Emergency Medicine, Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Welch
authors.affiliation: Division of Emergency Medicine, Washington University School of Medicine in St Louis, Missouri.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Lewis
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
authors.forename: Carolina F
authors.initials: CF
authors.lastname: Braga
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
authors.forename: Ciara N
authors.initials: CN
authors.lastname: Tan
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
authors.forename: Neema J
authors.initials: NJ
authors.lastname: Ameli
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Lopez
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
authors.forename: Crystal A
authors.initials: CA
authors.lastname: Haeussler
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
authors.forename: Diego I
authors.initials: DI
authors.lastname: Mendez Giordano
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Silvestri
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
authors.forename: Philip
authors.initials: P
authors.lastname: Giordano
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
authors.forename: Kurt D
authors.initials: KD
authors.lastname: Weber
authors.affiliation: US Department of Defense, Silver Springs, Maryland.
authors.forename: Crystal
authors.initials: C
authors.lastname: Hill-Pryor
authors.affiliation: Brain Health, Harpers Ferry, West Virginia.
authors.forename: Dallas C
authors.initials: DC
authors.lastname: Hack
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001924:Brain Concussion / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging* / Q000601:surgery; D015331:Cohort Studies; D004636:Emergency Service, Hospital; D005260:Female; D023261:Glasgow Outcome Scale; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D043222:Ubiquitin Thiolesterase / Q000097:blood*; D014947:Wounds and Injuries / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging* / Q000601:surgery; D055815:Young Adult
chemical_list: D005904:Glial Fibrillary Acidic Protein; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase