Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy.

Zoe S Gan,Lizette Garcia,Sherman C Stein,Randel Swanson,Shaobo Guan,Devanshi Mehta,Douglas H Smith

doi:10.3389/fneur.2019.00446

Abstract

Blood biomarkers have been explored for their potential to provide objective measures in the assessment of traumatic brain injury (TBI). However, it is not clear which biomarkers are best for diagnosis and prognosis in different severities of TBI. Here, we compare existing studies on the discriminative abilities of serum biomarkers for four commonly studied clinical situations: detecting concussion, predicting intracranial damage after mild TBI (mTBI), predicting delayed recovery after mTBI, and predicting adverse outcome after severe TBI (sTBI). We conducted a literature search of publications on biomarkers in TBI published up until July 2018. Operating characteristics were pooled for each biomarker for comparison. For detecting concussion, 4 biomarker panels and creatine kinase B type had excellent discriminative ability. For detecting intracranial injury and the need for a head CT scan after mTBI, 2 biomarker panels, and hyperphosphorylated tau had excellent operating characteristics. For predicting delayed recovery after mTBI, top candidates included calpain-derived αII-spectrin N-terminal fragment, tau A, neurofilament light, and ghrelin. For predicting adverse outcome following sTBI, no biomarker had excellent performance, but several had good performance, including markers of coagulation and inflammation, structural proteins in the brain, and proteins involved in homeostasis. The highest-performing biomarkers in each of these categories may provide insight into the pathophysiologies underlying mild and severe TBI. With further study, these biomarkers have the potential to be used alongside clinical and radiological data to improve TBI diagnostics, prognostics, and evidence-based medical management.

Highlights

Traumatic brain injury (TBI) is a common cause of disability and mortality in the US [1] and worldwide [2]
Excluded were 162 case series limited to tissue other than blood (CSF, brain tissue, etc.), 40 reports containing fewer than 10 observations and 346 reports not relevant to the four outlined scenarios or from which operating characteristics could not be calculated
While the current study shows that operating characteristics were good for GFAP and its breakdown products and poor for UCH-L1, the use of both biomarkers in combination had excellent discriminative ability for identifying computed tomography (CT)-positive mild TBI (mTBI)

Summary

Introduction

Traumatic brain injury (TBI) is a common cause of disability and mortality in the US [1] and worldwide [2]. To inform future guideline formulation, it is critical to distinguish between different clinical situations for biomarker use in TBI, such as detection of concussion, prediction of positive and negative head computed tomography (CT) findings, and prediction of outcome for different TBI severities.

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Discussion

Conclusion