Elevated markers of brain injury as a result of clinically asymptomatic high-acceleration head impacts in high-school football athletes

Abstract

OBJECTIVE This prospective observational cohort study of high-school football athletes was performed to determine if high-acceleration head impacts (HHIs) that do not result in clinically diagnosed concussion still lead to increases in serum levels of biomarkers indicating traumatic brain injury (TBI) in asymptomatic athletes and to determine the longitudinal profile of these biomarkers over the course of the football season. METHODS Sixteen varsity high-school football athletes underwent baseline neurocognitive testing and blood sampling for the biomarkers tau, ubiquitin C-terminal hydrolase L1 (UCH-L1), neurofilament light protein (NF-L), glial fibrillary acidic protein (GFAP), and spectrin breakdown products (SBDPs). All athletes wore helmet-based accelerometers to measure and record head impact data during all practices and games. At various time points during the season, 6 of these athletes met the criteria for HHI (linear acceleration > 95 g and rotational acceleration > 3760 rad/sec ); in these athletes a second blood sample was drawn at the end of the athletic event during which the HHI occurred. Five athletes who did not meet the criteria for HHI underwent repeat blood sampling following the final game of the season. In a separate analysis, all athletes who did not receive a diagnosis of concussion during the season (n = 12) underwent repeat neurocognitive testing and blood sampling after the end of the season. RESULTS Total tau levels increased 492.6% ± 109.8% from baseline to postsession values in athletes who received an HHI, compared with 164% ± 35% in athletes who did not receive an HHI (p = 0.03). Similarly, UCH-L1 levels increased 738.2% ± 163.3% in athletes following an HHI, compared with 237.7% ± 71.9% in athletes in whom there was no HHI (p = 0.03). At the end of the season, researchers found that tau levels had increased 0.6 ± 0.2 pg/ml (p = 0.003) and UCH-L1 levels had increased 144.3 ± 56 pg/ml (p = 0.002). No significant elevations in serum NF-L, GFAP, or SBDPs were seen between baseline and end-of-athletic event or end-of-season sampling (for all, p> 0.05). CONCLUSIONS In this pilot study on asymptomatic football athletes, an HHI was associated with increased markers of neuronal (UCH-L1) and axonal (tau) injury when compared with values in control athletes. These same markers were also increased in nonconcussed athletes following the football season.

Pupillary changes after clinically asymptomatic high-acceleration head impacts in high school football athletes

“…Clinically asymptomatic HHIs have already been associated with increases in serum tau and UCH-L1, both biomarkers of TBI. 13 Coupled with the QP data, an otherwise asymptomatic HHI potentially meets the criteria proposed for concussion by the CISG based on an objective biomechanical, physiological, and biomarker evaluation. Previous literature has suggested that there is a wide spectrum of mTBIs.…”

“…However, an HHI accounts for only 0.01% of all head impacts experienced by high school athletes. 13 Given this low incidence, an HHI appears to be an actionable entity. Previous studies have suggested that the frequency of high-speed collisions can be regulated out of football and, perhaps, other sports.…”

“…This definition was based on data from a previous investigation in which a correction had been made to the resultant rotational acceleration value. 5,13 All athletes also underwent a midseason assessment that included a neurocognitive evaluation and QP immediately after an athletic event during which the athlete did not sustain an HHI. This midseason assessment was performed approximately 2-2.5 months after the baseline assessment and took place within a 10-day period.…”

“…Furthermore, there is now evidence of brain injury in athletes who are asymptomatic or do not otherwise seek immediate clinical attention. 2,13,22 A rapid, objective, noninvasive method to identify athletes at risk and diagnose concussion would be a major advance.…”

Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

“…Biomarker discovery work in TBI has identified several promising blood protein biomarkers: glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1, neuron specific enolase and S100β (Wang et al, 2018). While these proteins may be useful biomarkers of acute and severe TBI, their use in reliably detecting milder forms of TBI remains to be fully investigated (Adrian et al, 2016;Joseph et al, 2018). At present, there are no blood biomarkers available for PTSD, and only broad inflammatory markers and cerebrospinal fluid (CSF) cortisone levels have been thoroughly examined (Schmidt et al, 2013;Michopoulos et al, 2015).…”