Blood-Based Biomarkers in Traumatic Brain Injury: A Narrative Review With Implications for the Legal System

Abstract

Traumatic brain injury (TBI) is an increasingly recognized diagnosis with significant, and often costly, associated consequences. Yet, despite their increased recognition, TBIs remain underdiagnosed. This issue is especially prominent in the context of mild TBI (mTBI), where there often exists little to no objective evidence of brain injury. In recent years, considerable effort has been made to better define and interpret known objective markers of TBI, as well as identify and explore new ones. An area of particular interest has focused on research related to blood-based biomarkers of TBI. Advancements in our understanding of TBI-related biomarkers can make it possible to characterize the severity of TBI with greater accuracy, improve our understanding of staging within both the injury process and the recovery process, and help us develop quantifiable metrics representative of reversal and recovery from a brain injury following trauma. Proteomic and non-proteomic blood-based biomarkers are being studied extensively and have shown promise for these purposes. Developments in this realm have significant implications not only for clinical care but also for legislation, as well as civil and criminal litigation. Despite their substantial potential, most of these biomarkers are not yet ready for use within the clinical setting, and therefore, are not appropriate for use within the legal or policy-making systems at this time. Given that existing standardization for the accurate and reliable use of TBI biomarkers is currently insufficient for use within either the clinical or legal realms, such data can be vulnerable to misuse and can even result in the abuse of the legal system for unwarranted gain. Courts will need to carefully evaluate the information presented in their role as gatekeepers of the admissibility of scientific evidence within the legal process. Ultimately, the development of biomarkers should lead to improved clinical care following TBI exposure, coherent and informed laws surrounding TBI, and more accurate and just results in litigation surrounding TBI-related sequelae.

Immunohistochemical Detection of Axonal Injury in Chimpanzee (Pan troglodytes) with Traumatic and Fatal Brain Injury

“…Measuring cerebral biomarkers is crucial for developing new wildlife forensics methods to estimate post-traumatic survival time and time since death, particularly in demographic studies or pathological investigations of epidemic diseases in a specific geographical area. To date, no wildlife forensic studies have examined Traumatic axonal injury (TAI)-related biomarkers within the brain tissues of wildlife species (2,3).…”

Raman Spectroscopy Spectral Fingerprints of Biomarkers of Traumatic Brain Injury

“…Mild TBI (mTBI) is often underdiagnosed if not identified rapidly at the point of injury, with 90% of acute cases undetected and not admitted to ED [2,14,15]. Therefore, development of successful TBI biomarker diagnostics from blood [16], or other biofluids, i.e., cerebrospinal fluid (CSF) [8], saliva [17], urine [18], and tears [19], would lead to improved triage of severe and high-risk injuries and improve outcomes, whilst appropriate classification of low-risk and mTBI patients would allow for the focusing of resources on those who need it the most. Furthermore, reduced resource demand would mitigate the relatively low costs of the investigation in comparison to ED assessment, CT imaging and hospital admission, and have distinct yet complementary use cases.…”