title: Measurement of the glial fibrillary acidic protein and its breakdown products GFAP-BDP biomarker for the detection of traumatic brain injury compared to computed tomography and magnetic resonance imaging.
abstract: Glial fibrillary acidic protein and its breakdown products (GFAP-BDP) are brain-specific proteins released into serum as part of the pathophysiological response after traumatic brain injury (TBI). We performed a multi-center trial to validate and characterize the use of GFAP-BDP levels in the diagnosis of intracranial injury in a broad population of patients with a positive clinical screen for head injury. This multi-center, prospective, cohort study included patients 16-93 years of age presenting to three level 1 trauma centers with suspected TBI (loss of consciousness, post-trauma amnesia, and so on). Serum GFAP-BDP levels were drawn within 24 h and analyzed, in a blinded fashion, using sandwich enzyme-linked immunosorbent assay. The ability of GFAP-BDP to predict intracranial injury on admission computed tomography (CT) as well as delayed magnetic resonance imaging was analyzed by multiple regression and assessed by the area under the receiver operating characteristic curve (AUC). Utility of GFAP-BDP to predict injury and reduce unnecessary CT scans was assessed utilizing decision curve analysis. A total of 215 patients were included, of which 83% suffered mild TBI, 4% moderate, and 12% severe; mean age was 42.1±18 years. Evidence of intracranial injury was present in 51% of the sample (median Rotterdam Score, 2; interquartile range, 2). GFAP-BDP demonstrated very good predictive ability (AUC=0.87) and demonstrated significant discrimination of injury severity (odds ratio, 1.45; 95% confidence interval, 1.29-1.64). Use of GFAP-BDP yielded a net benefit above clinical screening alone and a net reduction in unnecessary scans by 12-30%. Used in conjunction with other clinical information, rapid measurement of GFAP-BDP is useful in establishing or excluding the diagnosis of radiographically apparent intracranial injury throughout the spectrum of TBI. As an adjunct to current screening practices, GFAP-BDP may help avoid unnecessary CT scans without sacrificing sensitivity (Registry: ClinicalTrials.gov Identifier: NCT01565551).
authors.affiliation: 1 Department of Neurological Surgery, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McMahon
authors.forename: David M
authors.initials: DM
authors.lastname: Panczykowski
authors.forename: John K
authors.initials: JK
authors.lastname: Yue
authors.forename: Ava M
authors.initials: AM
authors.lastname: Puccio
authors.forename: Tomoo
authors.initials: T
authors.lastname: Inoue
authors.forename: Marco D
authors.initials: MD
authors.lastname: Sorani
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: Esther L
authors.initials: EL
authors.lastname: Yuh
authors.forename: Pratik
authors.initials: P
authors.lastname: Mukherjee
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Manley
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001930:Brain Injuries / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging; D002648:Child; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D016037:Single-Blind Method; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein
keywords: biomarkers; imaging; traumatic brain injury