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

Robert D Welch, Syed I Ayaz, Lawrence M Lewis, Johan Unden, James Y Chen, Valerie H Mika, Ben Saville, Joseph A Tyndall, Marshall Nash, Andras Buki, Pal Barzo, Dallas Hack, Frank C Tortella, Kara Schmid, Ronald L Hayes, Arastoo Vossough, Stephen T Sweriduk, Jeffrey J Bazarian, Robert D Welch, Syed I Ayaz, Lawrence M Lewis, Johan Unden, James Y Chen, Valerie H Mika, Ben Saville, Joseph A Tyndall, Marshall Nash, Andras Buki, Pal Barzo, Dallas Hack, Frank C Tortella, Kara Schmid, Ronald L Hayes, Arastoo Vossough, Stephen T Sweriduk, Jeffrey J Bazarian

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.

Trial registration: ClinicalTrials.gov NCT01295346.

Figures

FIG. 1.
FIG. 1.
Flow diagram describing excluded and included patients with mild to moderate traumatic brain injury. CT, computed tomography; UCH-L1, ubiquitin carboxyl-terminal hydrolase-L; GFAP, glial fibrillary acidic protein.
FIG. 2.
FIG. 2.
Scatter plots for glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase-L (UCH-L1), and S100B stratified by computed tomography (CT) results. (A) All biomarker values; (B) biomarker values ≤1200 pg/mL; (C) biomarker values ≤400 pg/mL. Color image is available online at www.liebertpub.com/neu
FIG. 3.
FIG. 3.
Scatter plots for glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase-L (UCH-L1), and S100B stratified by presenting Glasgow Coma Scale (GCS) score (all values ≤400 pg/mL for resolution). (A) GFAP; (B) UCH-L1; (C) S100B. CT, computed tomography. Color image is available online at www.liebertpub.com/neu
FIG. 4.
FIG. 4.
Area under the receiver operating characteristic (ROC) curve comparison for all (A) biomarkers in the model (n = 231) and for each individual marker (n = 251 for glial fibrillary acidic protein [B] and ubiquitin carboxyl-terminal hydrolase-L [C] and n = 231 for S100B [D]). Color image is available online at www.liebertpub.com/neu

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