title: GFAP-BDP as an acute diagnostic marker in traumatic brain injury: results from the prospective transforming research and clinical knowledge in traumatic brain injury study.
abstract: Reliable diagnosis of traumatic brain injury (TBI) is a major public health need. Glial fibrillary acidic protein (GFAP) is expressed in the central nervous system, and breakdown products (GFAP-BDP) are released following parenchymal brain injury. Here, we evaluate the diagnostic accuracy of elevated levels of plasma GFAP-BDP in TBI. Participants were identified as part of the prospective Transforming Research And Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study. Acute plasma samples (<24 h post-injury) were collected from patients presenting with brain injury who had CT imaging. The ability of GFAP-BDP level to discriminate patients with demonstrable traumatic lesions on CT, and with failure to return to pre-injury baseline at 6 months, was evaluated by the area under the receiver operating characteristic curve (AUC). Of the 215 patients included for analysis, 83% had mild, 4% had moderate, and 13% had severe TBI; 54% had acute traumatic lesions on CT. The ability of GFAP-BDP level to discriminate patients with traumatic lesions on CT as evaluated by AUC was 0.88 (95% confidence interval [CI], 0.84-0.93). The optimal cutoff of 0.68 ng/mL for plasma GFAP-BDP level was associated with a 21.61 odds ratio for traumatic findings on head CT. Discriminatory ability of unfavorable 6 month outcome was lower, AUC 0.65 (95% CI, 0.55-0.74), with a 2.07 odds ratio. GFAP-BDP levels reliably distinguish the presence and severity of CT scan findings in TBI patients. Although these findings confirm and extend prior studies, a larger prospective trial is still needed to validate the use of GFAP-BDP as a routine diagnostic biomarker for patient care and clinical research. The term "mild" continues to be a misnomer for this patient population, and underscores the need for evolving classification strategies for TBI targeted therapy. (ClinicalTrials.gov number NCT01565551; NIH Grant 1RC2 NS069409).
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. okonkwodo@upmc.edu
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.forename: John K
authors.initials: JK
authors.lastname: Yue
authors.forename: Ava M
authors.initials: AM
authors.lastname: Puccio
authors.forename: David M
authors.initials: DM
authors.lastname: Panczykowski
authors.forename: Tomoo
authors.initials: T
authors.lastname: Inoue
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McMahon
authors.forename: Marco D
authors.initials: MD
authors.lastname: Sorani
authors.forename: Esther L
authors.initials: EL
authors.lastname: Yuh
authors.forename: Hester F
authors.initials: HF
authors.lastname: Lingsma
authors.forename: Andrew I R
authors.initials: AI
authors.lastname: Maas
authors.forename: Alex B
authors.initials: AB
authors.lastname: Valadka
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Manley
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001930:Brain Injuries / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein