Abstract

BackgroundBiomarkers that can objectively guide the diagnosis of sports-related concussion, and consequent return-to-play decisions, are urgently needed. In this study, we aimed to determine the temporal profile and diagnostic ability of serum levels of neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), glial fibrillary acidic protein (GFAP), and tau in concussed male and female Australian footballers.MethodsBlood was collected from 28 Australian rules footballers (20 males, 8 females) at 2-, 6-, and 13-days after a diagnosed concussion for comparison to their levels at baseline (i.e. pre-season), and with 27 control players (19 males, 8 females) without a diagnosis of concussion. Serum concentrations of protein markers associated with damage to neurons (UCHL1), axons (NfL, tau), and astrocytes (GFAP) were quantified using a Simoa HD-X Analyzer. Biomarker levels for concussed players were compared over time and between sex using generalised linear mixed effect models, and diagnostic performance was assessed using area under the receiver operating characteristic curve (AUROC) analysis.ResultsSerum NfL was increased from baseline in male footballers at 6- and 13-days post-concussion. GFAP and tau were increased in male footballers with concussion at 2- and 13-days respectively. NfL concentrations discriminated between concussed and non-concussed male footballers at all time-points (AUROC: 2d = 0.73, 6d = 0.85, 13d = 0.79), with tau also demonstrating utility at 13d (AUROC = 0.72). No biomarker differences were observed in female footballers after concussion.ConclusionsSerum NfL may be a useful biomarker for the acute and sub-acute diagnosis of concussion in males, and could inform neurobiological recovery and return-to-play decisions. Future adequately powered studies are still needed to investigate biomarker changes in concussed females.

Highlights

  • Biomarkers that can objectively guide the diagnosis of sports-related concussion, and consequent return-to-play decisions, are urgently needed

  • Post-hoc analyses of results among male players revealed an increase in symptom number and severity at 2-days post-sports-related concussion (SRC) when compared to baseline, with no differences from baseline found at 6- and 13-days

  • Post-hoc analyses of results among female players revealed a significant decrease in Standardized concussion assessment (SAC) score at 2-days post-SRC when compared to baseline, but no differences from baseline found at 6- and 13-days

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Summary

Introduction

Biomarkers that can objectively guide the diagnosis of sports-related concussion, and consequent return-to-play decisions, are urgently needed. We aimed to determine the temporal profile and diagnostic ability of serum levels of neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), glial fibrillary acidic protein (GFAP), and tau in concussed male and female Australian footballers. This is an important knowledge gap, as many athletes with suspected concussion do not immediately seek medical attention [13, 14]. As studies to date have primarily focused on male athletes, little is known about how biological sex may affect biomarker profiles This prospective current study of male and female Australian footballers aimed to compare serum concentrations of NfL, tau, ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and GFAP at 2-, 6-, and 13-days after SRC with levels at baseline and with control footballers without SRC

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