title: Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury.
abstract: Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70-0.88) for GFAP, 0.80 (0.71-0.89) for UCH-L1, and 0.75 (0.65-0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.
authors.affiliation: 1 Department of Emergency Medicine, Wayne State University , Detroit, Michigan.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Welch
authors.affiliation: 1 Department of Emergency Medicine, Wayne State University , Detroit, Michigan.
authors.forename: Syed I
authors.initials: SI
authors.lastname: Ayaz
authors.affiliation: 2 Department of Emergency Medicine, Washington University , St. Louis, Missouri.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Lewis
authors.affiliation: 3 Department of Anesthesiology and Intensive Care, Clinical Sciences in Malmo , Malmo, Sweden .
authors.forename: Johan
authors.initials: J
authors.lastname: Unden
authors.affiliation: 4 Department of Radiology, University of California San Diego Health System , San Diego, California.
authors.forename: James Y
authors.initials: JY
authors.lastname: Chen
authors.affiliation: 1 Department of Emergency Medicine, Wayne State University , Detroit, Michigan.
authors.forename: Valerie H
authors.initials: VH
authors.lastname: Mika
authors.affiliation: 5 Berry Consultants , Austin, Texas.
authors.forename: Ben
authors.initials: B
authors.lastname: Saville
authors.affiliation: 6 Department of Emergency Medicine, University of Florida , Gainesville, Florida.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Tyndall
authors.affiliation: 7 Neurostudies.net , Decatur, Georgia .
authors.forename: Marshall
authors.initials: M
authors.lastname: Nash
authors.affiliation: 8 Department of Neurosurgery, Pecs University , Pecs, Hungary .
authors.forename: Andras
authors.initials: A
authors.lastname: Buki
authors.affiliation: 9 Department of Neurosurgery, University of Szeged , Szeged, Hungary .
authors.forename: Pal
authors.initials: P
authors.lastname: Barzo
authors.affiliation: 10 U.S. Army Medical Research and Materiel Command , Fort Detrick, Maryland.
authors.forename: Dallas
authors.initials: D
authors.lastname: Hack
authors.affiliation: 11 Applied Neurobiology, Silver Spring, Maryland.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Tortella
authors.affiliation: 12 Center for Military Psychiatry and Neuroscience Walter Reed Army Institute of Research , Silver Spring, Maryland.
authors.forename: Kara
authors.initials: K
authors.lastname: Schmid
authors.affiliation: 13 Center of Innovative Research, Banyan Biomarkers, Inc. , Alachua, Florida.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.affiliation: 14 Department of Radiology, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Arastoo
authors.initials: A
authors.lastname: Vossough
authors.affiliation: 15 Department of Radiology, Shields Health Care Group , Brockton, Massachusetts.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Sweriduk
authors.affiliation: 16 Department of Emergency Medicine, University of Rochester School of Medicine , Rochester, New York.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Bazarian
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001930:Brain Injuries / Q000097:blood* / Q000000981:diagnostic imaging*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood*; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed / Q000592:standards*; D043222:Ubiquitin Thiolesterase / Q000097:blood*
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase