Emerging Science in Brain Health: Biomarkers and Diagnostic Devices for Concussion

Introduction: Concussions can be sustained through exposure to external forces that disrupt normal brain function. Diagnosing a concussion is difficult, as symptom presentation and duration may be heterogeneous in patients with concussion. Further, overt structural damage is usually not visible on conventional computed tomography (CT) imaging for those with a concussion. Thus, it is important to develop assessment capabilities that can objectively and reliably identify concussions to allow for timely and appropriate treatment. Biomarkers and corresponding devices are currently being investigated as potential solutions to address the need for objective diagnostic tools.

Methods: The current available literature was reviewed to identify biomarkers with potential for application to the diagnosis of concussion. Biomarkers were identified in several key domains: molecular, structural, functional, and neurosensory. Corresponding devices used to detect injury-mediated changes in these biomarkers were also identified.

Results: The molecular biomarkers that are currently being evaluated as indicators of concussion include neuronal injury markers, astrocytic markers, and microglial markers. These molecular biomarkers are usually detected through biochemical assays in specialized medical devices. Structural biomarkers have also been identified using structural neuroimaging techniques such as magnetic resonance imaging. Functional biomarkers are evaluated using neuroimaging techniques such as MRS, EEG, MEG, PET, and specialized MRI techniques. Neurosensory biomarkers have also been explored as indicators of injury and are assessed using specialized medical devices. Several medical devices have been cleared by the U.S. Food and Drug Administration to aid clinicians in the assessment of concussion (not as standalone diagnostic devices). Devices designed for use at the point-of-injury to objectively identify concussions are limited, and those methods with potential for application outside of research use are better suited for clinical use.

Discussion: To eventually implement these biomarker measurement/assessment tools as standard clinical practice, several considerations must be addressed. These include end-user training requirements, discerning timing related to stages of injury, feasibility, optimal settings, and the fidelity of the biomarker-based information (i.e., stand-alone vs. information utilized as part of a diagnostic battery). Currently, the use of biomarkers has major limitations. Some biomarkers exhibit variable specificity, reliability, and consistency in indicating changes resulting from TBI across studies. As it relates to devices, the reproducibility of results and standardized, universal threshold limits have not been established.

Conclusion: There is a present need for objective and definitive indicators of concussion. Many studies have sought to establish biomarkers and concurrent diagnostic devices as tools that can identify concussion; however, only a handful of devices have been cleared by the U.S. Food and Drug Administration for use as part of a diagnostic battery for concussion. More research is needed to address limitations and facilitate standardized clinical use of these biomarkers to diagnose concussion.