The Clinical Use of Serum Biomarkers in Traumatic Brain Injury: A Systematic Review Stratified by Injury Severity

Background: Serum biomarkers have gained significant popularity as an adjunctive measure in the evaluation and prognostication of traumatic brain injury (TBI). However, a concise and clinically oriented report of the major markers in function of TBI severity is lacking. This systematic review aims to report current data on the diagnostic and prognostic utility of blood-based biomarkers across the spectrum of TBI. Methods: A literature search of the PubMed/Medline electronic database was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We excluded systematic reviews and meta-analyses that did not provide novel data. The American College of Cardiology/American Heart Association criteria were used to assess levels of evidence. Results: An initial 1463 studies were identified. In total, 115 full-text articles reporting on 94 distinct biomarkers met the inclusion criteria. Glasgow Coma Scale scores, computed tomography/magnetic resonance imaging abnormalities, and injury severity scores were the most used clinical diagnostic variables. Glasgow Outcome Scores and 1-, 3-, and 6-month mortality were the most used clinical prognostic variables. Several biomarkers significantly correlated with these variables and had statistically significant different levels in TBI subjects when compared with healthy, orthopedic, and polytrauma controls. The biomarkers also displayed significant variability across mild, moderate, and severe TBI categories, as well as in concussion cases. Conclusions: This review summarizes existing high-quality evidence that supports the use of severity-specific biomarkers in the diagnostic and prognostic evaluation of TBI. These data can be used as a launching platform for the validation of upcoming clinical studies.