Citation

Diaz-Arrastia R, Wang KK, Papa L, Sorani MD, Yue JK, Puccio AM, McMahon PJ, Inoue T, Yuh EL, Lingsma H, Maas A, Valadka A, Okonkwo DO, Manley GT, Casey SS, Cheong M, Cooper SR, Dams-O'connor K, Gordon W, Hricik AJ, Menon D, Mukherjee P, Schnyer DM, Sinha TK, Vassar MJ. J. Neurotrauma 2014; 31(1): 19-25.

Affiliation

Uniformed Services University of the Health Sciences, Neurology, Center for Neuroscience and Regenerative Medicine, 4301 Jones Bridge Road, Bethesda, Maryland, United States, 20814 ; ramon.diaz-arrastia@usuhs.edu.

Copyright

(Copyright © 2014, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2013.3040

PMID

23865516

Abstract

Biomarkers are important for accurate diagnosis of complex disorders such as traumatic brain injury (TBI). For a complex and multifaceted condition such as TBI, it is likely that a single biomarker will not reflect the full spectrum of the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are among of the most widely studied biomarkers for TBI. Since UCH-L1 and GFAP measure distinct molecular events, we hypothesized that analysis of both biomarkers would be superior to each alone for diagnosis and prognosis of TBI. Serum levels of UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a multicenter observational study (TRACK-TBI). Levels of the two biomarkers were weakly correlated to each other (r = 0.364). Each biomarker in isolation had good sensitivity and sensitivity for discriminating between TBI patients and healthy controls (AUC 0.87 and 0.91 for UCH-L1 and GFAP, respectively). When combined, superior sensitivity and specificity for diagnosing TBI was obtained (AUC 0.94). Both biomarkers discriminated between TBI patients with intracranial lesions on CT scan from those without such lesions, but GFAP measures were significantly more sensitive and specific (AUC 0.88 vs. 0.71 for UCH-L1). For association with outcome 3 months after injury, neither biomarker had adequate sensitivity and specificity (AUC 0.65 - 0.74, for GFAP, and 0.59 - 0.80 for UCH-L1, depending on GOSE threshold used). Our results support a role for multiple biomarker measurements in TBI research.

Language: en