Biofluid-Based Predictors of Post-Concussion Symptoms: A Narrative Review of Mild Traumatic Brain Injury Biomarkers

Mild traumatic brain injury can disrupt brain function and is associated with high morbidity and healthcare utilisation. While many individuals recover from mild traumatic brain injury, a significant proportion experience long-term sequelae, collectively known as post-concussion syndrome. Symptoms of post-concussion syndrome include headache, dizziness, insomnia, cognitive processing difficulties, and mental health disturbances. The disease burden is augmented by the current lack of objective measures to accurately predict long-term symptoms and deficits, providing an opportunity to utilise biomarkers in biofluids. A large proportion of available diagnostic clinical tools are subjective symptom scores. This review aims to explore current fluid biomarkers, grouped by clinical symptoms. With the available literature, we have discovered a wide range of fluid biomarkers that have been investigated for predicting post-traumatic headache, including neuropeptides; sleep disturbances, such as cortisol and melatonin; vestibular disturbances, including interleukin-6 and neuron-specific enolase; and vomiting, such as S100B. Along with physical symptoms, biomarkers investigated for predicting cognitive disturbances include inflammatory markers, S100B, neurofilament light chain, tau, microRNA, and hormones. Biomarkers to predict mental health disturbances may include brain-derived neurotrophic factor, tau, and cortisol. By utilising such biomarkers, there is capacity to adopt a personalised medicine approach to facilitate early interventions for those most in need, while also identifying individuals with a favourable prognosis who can safely return to their normal activities.