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Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study

Stefania Mondello12*, Linda Papa3, Andras Buki4, M Ross Bullock5, Endre Czeiter4, Frank C Tortella6, Kevin K Wang78 and Ronald L Hayes19

Author Affiliations

1 Department of Anesthesiology, University of Florida, 1600 S.W. Archer Road, Gainesville, FL 32610-0254, USA

2 Clinical Department, Center of Innovative Research, Banyan Biomarkers, Inc., 13400 Progress Blvd, Alachua, FL 32615, USA

3 Department of Emergency Medicine, Orlando Regional Medical Center, 86 W. Underwood Street, S-200, Orlando, FL 32806, USA

4 Department of Neurosurgery University of Pecs, 2 Rét street, H- 7624 Pecs, Hungary

5 Department of Neurosurgery University of Miami, 1095 NW 14th Ter, Miami, FL 33136-1060, USA

6 Department of Applied Neurobiology, Division of Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910-7500, USA

7 Diagnostic Research and Development Department, Center of Innovative Research, Banyan Biomarkers, Inc., 12085 Research Drive, Alachua, FL 32615, USA

8 Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, McKnight Brain Institute, University of Florida, 100 S. Newell Drive Bldg. 59, Gainesville, FL 32611, USA

9 Department of Clinical Programs, Center of Innovative Research, Banyan Biomarkers Inc., 13400 Progress Blvd, Alachua, FL 32615, USA

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Critical Care 2011, 15:R156  doi:10.1186/cc10286


See related commentary by Vos, http://ccforum.com/content/15/4/183

Published: 24 June 2011

Abstract

Introduction

Authors of several studies have studied biomarkers and computed tomography (CT) findings in the acute phase after severe traumatic brain injury (TBI). However, the correlation between structural damage as assessed by neuroimaging and biomarkers has not been elucidated. The aim of this study was to investigate the relationships among neuronal (Ubiquitin carboxy-terminal hydrolase L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels in serum, neuroradiological findings and outcomes after severe TBI.

Methods

The study recruited patients from four neurotrauma centers. Serum samples for UCH-L1 and GFAP were obtained at the time of hospital admission and every 6 hours thereafter. CT scans of the brain were obtained within 24hrs of injury. Outcome was assessed by Glasgow Outcome Scale (GOS) at discharge and at 6 months.

Results

81 severe TBI patients and 167 controls were enrolled. The mean serum levels of UCH-L1 and GFAP were higher (p < 0.001) in TBI patients compared to controls. UCH-L1 and GFAP serum levels correlated significantly with Glasgow Coma Scale (GCS) and CT findings. GFAP levels were higher in patients with mass lesions than in those with diffuse injury (2.95 ± 0.48 ng/ml versus 0.74 ± 0.11 ng/ml) while UCH-L1 levels were higher in patients with diffuse injury (1.55 ± 0.18 ng/ml versus 1.21 ± 0.15 ng/ml, p = 0.0031 and 0.0103, respectively). A multivariate logistic regression showed that UCH-L1 was the only independent predictor of death at discharge [adjusted odds ratios 2.95; 95% confidence interval, 1.46-5.97], but both UCH-L1 and GFAP levels strongly predicted death 6 months post-injury.

Conclusions

Relationships between structural changes detected by neuroimaging and biomarkers indicate each biomarker may reflect a different injury pathway. These results suggest that protein biomarkers could provide better characterization of subjects at risk for specific types of cellular damage than that obtained with neuroimaging alone, as well as provide valuable information about injury severity and outcome after severe TBI.

Keywords:
Traumatic Brain Injury; Biomarkers; Diagnostic; Outcome; Computed tomography