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Front. Neurol. | doi: 10.3389/fneur.2019.00446

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

 Zoe S. Gan1, Sherman C. Stein2,  Randel L. Swanson II2, 3, Shaobo Guan2, Lizette Garcia2, Devanshi Mehta2 and  Douglas H. Smith2*
  • 1University of North Carolina at Chapel Hill, United States
  • 2Department of Neurosurgery, University of Pennsylvania, United States
  • 3Department of Physical Medicine & Rehabilitation, University of Pennsylvania, United States

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.

Keywords: Traumatic Brain Injury, TBI, concussion, diagnostic, prognostic, biomarker, biomarkers

Received: 04 Feb 2019; Accepted: 12 Apr 2019.

Edited by:

Firas H. Kobeissy, University of Florida, United States

Reviewed by:

Shoji Yokobori, Nippon Medical School, Japan
Donald Stein, Emory University, United States  

Copyright: © 2019 Gan, Stein, Swanson II, Guan, Garcia, Mehta and Smith. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Douglas H. Smith, University of Pennsylvania, Department of Neurosurgery, Philadelphia, 19104, Pennsylvania, United States,