Multivariate analysis of traumatic brain injury: development of an assessment score.

John E Buonora,Gregory P Mueller,Lawrence L Latour,Shawn G Rhind,Sandro B Rizoli,Michael Mousseau,Angela M Yarnell,Rachel C Lazarus,Ramon Diaz-Arrastia,Andrew J Baker

doi:10.3389/fneur.2015.00068

Abstract

Important challenges for the diagnosis and monitoring of mild traumatic brain injury (mTBI) include the development of plasma biomarkers for assessing neurologic injury, monitoring pathogenesis, and predicting vulnerability for the development of untoward neurologic outcomes. While several biomarker proteins have shown promise in this regard, used individually, these candidates lack adequate sensitivity and/or specificity for making a definitive diagnosis or identifying those at risk of subsequent pathology. The objective for this study was to evaluate a panel of six recognized and novel biomarker candidates for the assessment of TBI in adult patients. The biomarkers studied were selected on the basis of their relative brain-specificities and potentials to reflect distinct features of TBI mechanisms including (1) neuronal damage assessed by neuron-specific enolase (NSE) and brain derived neurotrophic factor (BDNF); (2) oxidative stress assessed by peroxiredoxin 6 (PRDX6); (3) glial damage and gliosis assessed by glial fibrillary acidic protein and S100 calcium binding protein beta (S100b); (4) immune activation assessed by monocyte chemoattractant protein 1/chemokine (C–C motif) ligand 2 (MCP1/CCL2); and (5) disruption of the intercellular adhesion apparatus assessed by intercellular adhesion protein-5 (ICAM-5). The combined fold-changes in plasma levels of PRDX6, S100b, MCP1, NSE, and BDNF resulted in the formulation of a TBI assessment score that identified mTBI with a receiver operating characteristic (ROC) area under the curve of 0.97, when compared to healthy controls. This research demonstrates that a profile of biomarker responses can be used to formulate a diagnostic score that is sensitive for the detection of mTBI. Ideally, this multivariate assessment strategy will be refined with additional biomarkers that can effectively assess the spectrum of TBI and identify those at particular risk for developing neuropathologies as consequence of a mTBI event.

Highlights

Mild traumatic brain injury is a major problem for civilian and military clinicians alike and is often described as an invisible wound [1]
The findings presented here demonstrate that fold increases in plasma levels of neuron-specific enolase (NSE), peroxiredoxin 6 (PRDX6), S100 calcium binding protein beta (S100b), brain derived neurotrophic factor (BDNF), and MCP1 biomarkers in adult subjects experiencing Mild traumatic brain injury (mTBI) may be formulated to produce an informative TBI assessment score (TBIAS)
The present investigation demonstrates that five of the biomarkers studied here can be used to establish a signature that identifies mTBI with a quantitative assessment score

Summary

Introduction

Mild traumatic brain injury (mTBI) is a major problem for civilian and military clinicians alike and is often described as an invisible wound [1]. Such an injury can precipitate a cascade of intracerebral events that include hypoxia, oxidative stress, necrosis, apoptosis, and chronic inflammation [2,3,4]. These processes may be initiated in the absence of any acute clinical signs [5, 6]. Missed diagnoses are key factors hindering preclinical and clinical TBI investigations [10, 11]

Methods

Results

Conclusion