Association of Acute Increase in Plasma Neurofilament Light with Repetitive Subconcussive Head Impacts: A Pilot Randomized Control Trial

The purpose of the study was to examine an association of repetitive subconcussive head impacts with changes in plasma neurofilament light (NF-L) levels following 10 bouts of controlled soccer heading. In this randomized control trial, 37 healthy adult soccer players were randomly assigned into either a heading (n=19) or kicking-control group (n=18). The heading group executed 10 headers with soccer balls projected at a velocity of 25mph over 10min. Plasma samples were obtained at pre-heading baseline, 0h, 2h, and 24h post-heading. The kicking-control group followed the same protocol with 10 kicks. Plasma NF-L was measured using ultrasensitive single-molecule array technology. Data from 34 subjects were eligible for analysis (heading n=18 and kicking n=16). Ten subconcussive head impacts induced a gradual increase in plasma NF-L expression for the heading group (=0.0297, standard error [SE]=0.01, p=0.0049), whereas there was no significant time effect for the kicking-control group. A follow-up analysis revealed that a significant difference appeared at 24h post-heading (3.68 +/- 0.30pg/mL) compared with pre-heading (3.12 +/- 0.29pg/mL, p=0.0013; Cohen's d=1.898). At the 24h post-heading time-point, the plasma NF-L level for the heading group was significantly higher than that of the kicking-control group with an estimated mean difference of 0.66pg/mL (SE=0.22, p=0.0025). The data suggest that the increased level of plasma NF-L was driven by repetitive subconcussive head impacts and required longer than 2h after the head impacts for the increase to be detected. Plasma NF-L levels may serve as an objective marker to monitor acute axonal burden from subconcussive head impacts.