# Biofluid-based predictors of post-concussion symptoms: a narrative review of mild traumatic brain injury biomarkers

## TL;DR

This review explores biofluid biomarkers that could predict long-term symptoms after mild traumatic brain injury, aiming to improve personalized care and early interventions.

## Contribution

The paper systematically categorizes biomarkers by symptom type, offering a framework for personalized medicine in post-concussion care.

## Key findings

- Biomarkers like S100B and interleukin-6 are linked to physical symptoms such as headaches and dizziness.
- Inflammatory markers and microRNA are associated with cognitive disturbances following mild traumatic brain injury.
- Brain-derived neurotrophic factor and cortisol may predict mental health disturbances after injury.

## Abstract

Mild traumatic brain injury can disrupt brain function and is associated with high morbidity and healthcare utilization. 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 utilize 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 neurone-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 utilizing such biomarkers, there is capacity to adopt a personalized 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.

Lyons et al. review current evidence on biofluid biomarkers that may predict persistent symptoms following mild traumatic brain injury. They highlight specific markers linked to physical, cognitive and mental health disturbances, suggesting that these could support more personalized care and early intervention strategies in affected individuals.

Graphical Abstract