Use of Blood Biomarkers in the Assessment of Sports-Related Concussion—A Systematic Review in the Context of Their Biological Significance

Abstract

At present, blood biomarkers have only a limited role in the evaluation and management of concussion. Although several biomarkers of brain injury have been identified, continued research is required. S100B holds promise as the most clinically useful diagnostic biomarker. Blood biomarkers, in combination with other clinical data, such as head computed tomography, would maximize the diagnostic accuracy. The methodological limitations evident in blood biomarker research results in the need for the clinical utility of blood biomarker use in concussion to be further explored.

Management of Concussion and Mild Traumatic Brain Injury: A Synthesis of Practice Guidelines

“…Many novel biomarkers for mTBI are under development, but none have yet been validated for diagnostic purposes. 25,[58][59][60][61] A clinical interview based on patient selfreport (and corroborated with medical records, when available) with physical examination remains the criterion standard for diagnosing mTBI in primary care.…”

The role and diagnostic significance of cellular barriers after concussive head trauma

“…An emerging alternative for clinical diagnostics is the testing of serum for brain-derived biomarkers in the acute postinjury phase. Among the candidate biomarkers for such testing is S100B, whose serum levels have been proven to reflect the presence of a damaged BBB, and may predict or rule out brain injury [ 15 , 16 ]. Most importantly, S100B presents a quantifiable increase after an mTBI characterized by computed tomography (CT) changes consistent with intracranial events.…”

“…In studies where S100B serum levels were compared with CT-based diagnosis of mTBI, a negative predictive value (NPV) of >95% was reported for this biomarker [ 17 , 18 ]. Approaches for on-site detection of blood biomarker levels indicative of brain health are currently being pursued [ 14 , 15 ], however blood-based biomarker testing is met with its own set of limiting factors. Principal among these complications is the need for invasive retrieval of the blood sample, preprocessing/filtration of blood cells and mitigation of nonspecific binding entities.…”

The anatomy of concussion and chronic traumatic encephalopathy: A comprehensive review

“…GFAP's sensitivity in detecting intracranial lesions on CT ranges between 94% and 100% (Papa et al, ; Papa et al, ), and its performance in detecting brain injury is better in trauma patients who present to the emergency department with mild TBI compared to studies performed on athletes, likely because of the different timing of the blood draws (Papa, ). Like other biomarkers, such as NSE, S‐100β, and tau, GFAP's role as a diagnostic and prognostic biomarker in SRC is inconclusive at this time and requires further validation (O'Connell et al, ).…”