Advances in Traumatic Brain Injury Biomarkers

Abstract

Traumatic brain injury (TBI) is increasingly a major cause of disability across the globe. The current methods of diagnosis are inadequate at classifying patients and prognosis. TBI is a diagnostic and therapeutic challenge. There is no Food and Drug Administration (FDA)-approved treatment for TBI yet. It took about 16 years of preclinical research to develop accurate and objective diagnostic measures for TBI. Two brain-specific protein biomarkers, namely, ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein, have been extensively characterized. Recently, the two biomarkers were approved by the FDA as the first blood-based biomarker, Brain Trauma Indicator™ (BTI™), via the Breakthrough Devices Program. This scoping review presents (i) TBI diagnosis challenges, (ii) the process behind the FDA approval of biomarkers, and (iii) known unknowns in TBI biomarker biology. The current lag in TBI incidence and hospitalization can be reduced if digital biomarkers such as hard fall detection are standardized and used as a mechanism to alert paramedics to an unresponsive trauma patient.

Keywords: brain trauma indicator; gfap; neurologic prognosis; prognostic biomarkers; serum biomarkers; traumatic brain injury; uchl-1.

Figure 1. Specific biomarker types and their spatiotemporal distribution.

TBI-specific biomarker types and their spatiotemporal distribution. The prevalence of a biomarker in a healthy population (blue) shifts following injury (red thunderbolt) to a new distribution (red) above the baseline (dashed horizontal line) that is not present in 99 percentiles of the uninjured (specific to injury). Such a biomarker can peak acutely (first rectangle), function as a diagnostic biomarker, and in absence of therapy fuel a cascade of secondary injury over days and months (next to rectangles). The subsequent subacute and chronic biomarkers (yellow and brown, respectively) could serve as monitoring/therapeutic response biomarkers. Failure of therapeutic effect can be assessed by increased safety biomarker. These analog biomarkers (black outline) can be augmented with digital biomarkers (black rectangle) to detect injury and alter, especially when an individual is alone and unresponsive following TBI. It is important to reinforce that any biomarker data should be interpreted only in the context of pertinent clinical history. TBI: traumatic brain injury