Abstract
Mild traumatic brain injury is a relatively common event in contact sports and there is increasing interest in the long-term neurocognitive effects. The diagnosis largely relies on symptom reporting and there is a need for objective tools to aid diagnosis and prognosis. There are recent reports that blood biomarkers could potentially help triage patients with suspected injury and normal CT findings. We have measured plasma concentrations of glial and neuronal proteins and explored their potential in the assessment of mild traumatic brain injury in contact sport. We recruited a prospective cohort of active male rugby players, who had pre-season baseline plasma sampling. From this prospective cohort, we recruited 25 players diagnosed with mild traumatic brain injury. We sampled post-match rugby players without head injuries as post-match controls. We measured plasma neurofilament light chain, tau and glial fibrillary acidic protein levels using ultrasensitive single molecule array technology. The data were analysed at the group and individual player level. Plasma glial fibrillary acidic protein concentration was significantly increased 1-h post-injury in mild traumatic brain injury cases compared to the non-injured group (P = 0.017). Pairwise comparison also showed that glial fibrillary acidic protein levels were higher in players after a head injury in comparison to their pre-season levels at both 1-h and 3- to 10-day post-injury time points (P = 0.039 and 0.040, respectively). There was also an increase in neurofilament light chain concentration in brain injury cases compared to the pre-season levels within the same individual at both time points (P = 0.023 and 0.002, respectively). Tau was elevated in both the non-injured control group and the 1-h post-injury group compared to pre-season levels (P = 0.007 and 0.015, respectively). Furthermore, receiver operating characteristic analysis showed that glial fibrillary acidic protein and neurofilament light chain can separate head injury cases from control players. The highest diagnostic power was detected when biomarkers were combined in differentiating 1-h post-match control players from 1-h post-head injury players (area under curve 0.90, 95% confidence interval 0.79–1.00, P < 0.0002). The brain astrocytic marker glial fibrillary acidic protein is elevated in blood 1 h after mild traumatic brain injury and in combination with neurofilament light chain displayed the potential as a reliable biomarker for brain injury evaluation. Plasma total tau is elevated following competitive rugby with and without a head injury, perhaps related to peripheral nerve trauma and therefore total tau does not appear to be suitable as a blood biomarker.
Highlights
Concussion, known as mild traumatic brain injury, accounts for >80% of the estimated 1.4 million TBI cases seen in hospitals in the UK annually and affects 1.6–3.8 million individuals in the USA each year (Cancelliere et al, 2014; Levin and Diaz-Arrastia, 2015)
There was no difference in age or years of play between the players with mild traumatic brain injury (mTBI) and the non-mTBI post-match controls (P 1⁄4 > 0.7 for all) and no significant difference in the baseline biomarker levels between those who went on to have an mTBI and those who did not (Supplementary Fig. 1)
No blood biomarker is in clinical use as an independent objective tool in the assessment of mTBI
Summary
Concussion, known as mild traumatic brain injury (mTBI), accounts for >80% of the estimated 1.4 million TBI cases seen in hospitals in the UK annually and affects 1.6–3.8 million individuals in the USA each year (Cancelliere et al, 2014; Levin and Diaz-Arrastia, 2015). Management guidelines in sports have been prepared largely from recognized consensus processes, and the need for more objective diagnostic tools, including fluid biomarkers, has been recognized as a priority (McCrory et al, 2017). The key elements of the 10-min off-field World Rugby Head Injury Assessment 1 include review of game footage for presence of signs, memory and gait assessments and an mTBI symptom check (Raftery et al, 2016; McCrory et al, 2017). Athletes are known to under report symptoms and this can affect diagnosis (Meier et al, 2015). The clinical evaluation remains limited as the relationship between extent of injury to the brain, the microstructural changes that result from mTBI, and immediate clinical symptoms is uncertain. A variety of methods, including diffusion tensor imaging, have shown physiological changes that may persists longer than functional clinical recovery (Kamins et al, 2017)
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