Subconcussive head impact, defined as an impact to the head that does not induce clinical symptoms of concussion, has emerged as a complex public health issue. Every year, approximately 2.5 million high school and college athletes engage in contact sports, such as US football, soccer, ice hockey, and rugby,¹ in which they can endure several hundred to nearly a thousand subconcussive head impacts in a single season.² Long-term exposure to these head impacts is suggested to increase risk for developing chronic traumatic encephalopathy.^3-5

The purpose of the study was to test the utility of unique panel of blood biomarkers as a means to reflect one’s recovery process after sport-related neurotrauma. We established a panel of biomarkers that reacted positive with CD81 (extracellular vesicle marker) and various neuron- and glia-specific antigens [e.g., neurofilament light polypeptide (NF-L), tau, synaptosome-associated protein 25 (SNAP25), glial fibrillary acidic protein, and myelin basic protein]. We first evaluated test–retest reliabilities of brain-derived exosome markers, followed by an application of these markers in eight professional ice hockey players to detect cumulative neuronal burden from a single ice hockey season. During the season, two players were diagnosed with concussions by team physician based on an exhibition of symptoms as well as abnormality in balance and ocular motor testing. One player reached symptom-free status 7 days after the concussion, while the other player required 36 days for symptoms to completely resolve. Blood samples and clinical assessments including balance error scoring system and near point of convergence throughout recovery process were obtained. Biomarkers indicative of axonal damage, neuronal inflammation, and glial activation showed excellent test–retest reliabilities (intraclass correlation coefficient: 0.713–0.998, p’s < 0.01). There was a statistically significant increase in the NF-L marker at post-season follow-up compared to pre-season baseline (Z = −2.100, P = 0.036); however the statistical significance did not withstand Bonferroni correction for multiple comparisons. In concussion cases, neuronal and microglia markers notably increased after concussions, with the unique expression patterns being similar to that of concussion recovery process. These longitudinal data coupled with excellent test–retest reliabilities of novel array of blood biomarkers potentially reflect the damage in neural cell structures and metabolic crisis due to concussion. However, future studies with larger sample size and appropriate control groups to evaluate sensitivity and specificity of these markers are needed. This preliminary case report suggests the potential utility of multimodal blood biomarkers for concussion prognosis and recovery assessment.

Astrocyte-enriched marker, S100B, shows promise for gauging the severity of acute brain trauma, and understanding subconcussive effects will advance its utility in tracking real-time acute brain damage. The aim of the study was to investigate whether serum S100B elevations were associated with frequency and magnitude of subconcussive head impacts in adolescents. This prospective cohort study of 17 high-school football players consisted of the following 12 time points: pre-season baseline, 5 in-season pre-post games, and post-season. A sensor-installed mouthguard recorded the number of head impacts, peak linear (PLA) and peak rotational (PRA) head accelerations from every practice and game. During the 5 games, players wore chest-strap heart-rate monitors to estimate players' excess post-exercise oxygen consumption (EPOC), accounting for physical exertion effects. At each time point, blood samples were obtained and assessed for S100B and creatine kinase levels to account for astrocyte damage/activation and muscle damage, respectively. Using k-means clustering on the impact data, players were categorized into high- or low-impact group. Two players withdrew during the first month of the study. A total of 156 blood samples from 15 players were assessed for S100B and creatine kinase levels and included in the analysis. A median value of 596 head impacts from 15 players were recorded during all practices and games in a season. S100B levels were significantly elevated in all post-game measures compared with the respective pre-game values (median-increase, 0.022 μg/L; interquartile-range, 0.011–0.043 μg/L, p < 0.05 for all games). Greater acute S100B increases were significantly associated with greater impact frequency, sum of PLA and PRA, with negligible contributions from physical exertion and muscle damage effects. The high-impact group exhibited greater increases in serum S100B levels at post-games than the low-impact group (high vs. low, 0.043 ± 0.035 μg/L vs. 0.019 ± 0.017 μg/L, p = 0.002). The degree of acute S100B increases was correlated with subconcussive head impact exposure, suggesting that acute astrocyte damage may be induced in an impact-dependent manner. Acute changes in serum S100B levels may become a useful tool in monitoring real-time brain damage in sports.

Repetitive head impacts observed in youth sports are becoming a major public health concern.¹ These subconcussive head impacts, which rarely elicit clinical symptoms of concussion,² may result in long-term neurological deficits if sustained repetitively.³ The near point of convergence (NPC), which measures the closest point of focus before diplopia occurs,⁴ has shown to detect subclinical neuronal damage.

While awareness and understanding of concussion have improved drastically, post-concussion management in academic settings is still at its infancy. The aim of the study was to examine to what extent concussion influences academic performance and to whether there would be a difference in concussion effects on academic performance between high school and college students. This cross-sectional survey study included students, who were between 14 and 24 years old and sustained a sport-related concussion within the previous year. The study used a modified chain-referral sampling method, by distributing a questionnaire link to 3,000 randomly stratified athletic trainers, who worked in high school or college settings. These athletic trainers were then asked to forward the questionnaire link to students in their team, who have sustained a concussion within the previous year. The questionnaire recorded responses regarding demographics (age, sex, race/ethnicity, number of previous concussions); 22 concussion-related symptoms in a binary scale (presence/absence); perception of difficulties in math, reading, writing, computer use, and attention in a 5-point Likert scale; and asymptomatic duration of academic engagement in a 7-point Likert scale. There were 130 respondents with a history of concussion in the past year (n = 59 high school, n = 71 college). While recovering from concussion, significantly more college students (84.5%) reported “difficulty concentrating” than high school students (68.6%: p = 0.049). High -school students experienced more difficulty with math than college students (p = 0.002), whereas college students experienced more difficulty with reading (p = 0.013) and computer use (p = 0.026) than high school students. Asymptomatic duration of cognitive activity was influenced by age (p = 0.0004), where younger students were less tolerant in performing academic tasks after a concussion than older students. Our data indicate that concussions can induce negative symptoms in the academic setting regardless of age. The post-concussion difficulties in academic performance may be a grade-dependent manner, where concussions triggered difficulty in math among high school students and in reading and computer use among college students. It is clear that there is a need for guidelines and accommodations to support students with concussion in academic settings, and the guideline should reflect the age-dependent response to concussions.