title: Severe traumatic brain injury in children elevates glial fibrillary acidic protein in cerebrospinal fluid and serum.
abstract: OBJECTIVE
  1) To determine the levels of glial fibrillary acidic protein (GFAP) in both cerebrospinal fluid and serum; 2) to determine whether serum GFAP levels correlate with functional outcome; and 3) to determine whether therapeutic hypothermia, as compared with normothermia, alters serum GFAP levels in children with severe traumatic brain injury (TBI).
  
  
  METHODS
  Laboratory-based analyses; postrandomized, controlled trial.
  
  
  METHODS
  Four Canadian pediatric intensive care units and a university-affiliated laboratory.
  
  
  METHODS
  Twenty-seven children, aged 2-17 yrs, with severe TBI (Glasgow Coma Scale score of ≤ 8).
  
  
  METHODS
  Hypothermia therapy (32.5°C) for 24 hrs with cooling started within 8 hrs of injury and rewarming at a rate of 0.5°C every 2 hrs or normothermia (37.0°C).
  
  
  RESULTS
  GFAP was measured in cerebrospinal fluid and serum, using enzyme-linked immunosorbent assay. Levels of GFAP were maximal on day 1 post-TBI, with cerebrospinal fluid GFAP (15.5 ± 6.1 ng/mL) 25-fold higher than serum GFAP (0.6 ± 0.2 ng/mL). Cerebrospinal fluid GFAP normalized by day 7, whereas serum GFAP decreased gradually to reach a steady state by day 10. Serum GFAP measured on day 1 correlated with Pediatric Cerebral Performance Category scores determined at 6 months post-TBI (ρ = 0.527; p = .008) but failed to correlate with the injury scoring on admission, physiologic variables, or indices of injury measured on computerized tomography imaging. The areas under the receiver operating characteristic curves for pediatric intensive care unit day 1 serum GFAP in determining good outcome were 0.80 (pediatric cerebral performance category, 1-2; normal-mild disability) and 0.91 (pediatric cerebral performance category, 1-3; normal-moderate disability). For a serum GFAP cutoff level of 0.6 ng/mL, sensitivity and specificity were 88% to 90% and 43% to 71%, respectively. Serum GFAP levels were similar among children randomized to either therapeutic hypothermia or normothermia.
  
  
  CONCLUSIONS
  GFAP was markedly elevated in cerebrospinal fluid and serum in children after severe TBI and serum GFAP measured on pediatric intensive care unit day 1 correlated with functional outcome at 6 months. Hypothermia therapy did not alter serum GFAP levels compared with normothermia after severe TBI in children. Serum GFAP concentration, together with other biomarkers, may have prognostic value after TBI in children.
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, University of Western Ontario, London, ON, Canada. douglas.fraser@lhsc.on.ca
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Fraser
authors.forename: Taylor E
authors.initials: TE
authors.lastname: Close
authors.forename: Keeley L
authors.initials: KL
authors.lastname: Rose
authors.forename: Roxanne
authors.initials: R
authors.lastname: Ward
authors.forename: Martin
authors.initials: M
authors.lastname: Mehl
authors.forename: Catherine
authors.initials: C
authors.lastname: Farrell
authors.forename: Jacques
authors.initials: J
authors.lastname: Lacroix
authors.forename: David
authors.initials: D
authors.lastname: Creery
authors.forename: Murray
authors.initials: M
authors.lastname: Kesselman
authors.forename: Danica
authors.initials: D
authors.lastname: Stanimirovic
authors.forename: James S
authors.initials: JS
authors.lastname: Hutchison
mesh_terms: D000293:Adolescent; D001930:Brain Injuries / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D015600:Glasgow Coma Scale; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid*; D006801:Humans; D015599:Trauma Severity Indices
chemical_list: D005904:Glial Fibrillary Acidic Protein