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Concussion is a common injury in the adolescent and young adult populations. Although branched chain amino acid (BCAA) supplementation has shown improvements in neurocognitive and sleep function in pre-clinical animal models of mild-to-moderate traumatic brain injury (TBI), to date, no studies have been performed evaluating the efficacy of BCAAs in concussed adolescents and young adults. The goal of this pilot trial was to determine the efficacy, tolerability, and safety of varied doses of oral BCAA supplementation in a group of concussed adolescents and young adults. The study was conducted as a pilot, double-blind, randomized controlled trial of participants ages 11-34 presenting with concussion to outpatient clinics (sports medicine and primary care), urgent care, and emergency departments of a tertiary care pediatric children's hospital and an urban tertiary care adult hospital, between June 24, 2014 and December 5, 2020. Participants were randomized to one of five study arms (placebo and 15 g, 30 g, 45 g, and 54 g BCAA treatment daily) and followed for 21 days after enrollment. Outcome measures included daily computerized neurocognitive tests (processing speed, the a priori primary outcome; and attention, visual learning, and working memory), symptom score, physical and cognitive activity, sleep/wake alterations, treatment compliance, and adverse events. In total, 42 participants were randomized, 38 of whom provided analyzable data. We found no difference in our primary outcome of processing speed between the arms; however, there was a significant reduction in total symptom score (decrease of 4.4 points on a 0-54 scale for every 500 g of study drug consumed, p value for trend = 0.0036, [uncorrected]) and return to physical activity (increase of 0.503 points on a 0-5 scale for every 500 g of study drug consumed, p value for trend = 0.005 [uncorrected]). There were no serious adverse events. Eight of 38 participants reported a mild (not interfering with daily activity) or moderate (limitation of daily activity) adverse event; there were no differences in adverse events by arm, with only two reported mild adverse events (both gastrointestinal) in the highest (45 g and 54 g) BCAA arms. Although limited by slow enrollment, small sample size, and missing data, this study provides the first demonstration of efficacy, as well as safety and tolerability, of BCAAs in concussed adolescents and young adults; specifically, a dose-response effect in reducing concussion symptoms and a return to baseline physical activity in those treated with higher total doses of BCAAs. These findings provide important preliminary data to inform a larger trial of BCAA therapy to expedite concussion recovery.

Visual and vestibular deficits, as measured by a visio-vestibular examination (VVE), are markers of concussion in youth. Little is known about VVE evolution post-injury, nor influence of age or sex on trajectory. The objective was to describe the time trend of abnormal VVE elements after concussion. Two cohorts, 11-18 years, were enrolled: healthy adolescents ( n  = 171) from a high school with VVE assessment before or immediately after their sport seasons and concussed participants ( n  = 255) from a specialty care concussion program, with initial assessment ≤28 days from injury and VVE repeated throughout recovery during clinical visits. The primary outcome, compared between groups, is the time course of recovery of the VVE examination, defined as the probability of an abnormal VVE (≥2/9 abnormal elements) and modeled as a cubic polynomial of days after injury. We explored whether probability trajectories differed by: age (<14 years vs. 14+ years), sex, concussion history (0 versus 1+), and days from injury to last assessment (≤28 days vs. 29+ days). Overall, abnormal VVE probability peaked at 0.57 at day 8 post-injury, compared with an underlying prevalence of 0.083 for uninjured adolescents. Abnormal VVE probability peaked higher for those 14+ years, female, with a concussion history and whose recovery course was longer than 28 days post-injury, compared with their appropriate strata subgroups. Females and those <14 years demonstrated slower resolution of VVE abnormalities. VVE deficits are common in adolescents after concussion, and the trajectory of resolution varies by age, sex, and concussion history. These data provide insight to clinicians managing concussions on the timing of deficit resolution after injury.