Our next speaker will actually be our 2017 Kodma Neurotrauma Research Award winner, Jacob Raul Rajiv Joseph. Thank you, everyone. Thanks to the section for supporting our research. My name is Jacob Joseph. I'm a PGY-6 at the University of Michigan, and our study was looking at elevated markers of brain injury as a result of clinically asymptomatic high-acceleration head impacts in high school football athletes. These are disclosures, a grant from Kodman and from Blue Cross Blue Shield. So high-speed collision sports continue to be extremely popular in adolescents, though the adolescent brain is thought to be particularly sensitive to mild traumatic brain injury or concussion. While the long-term effects of concussion are controversial, the short-term effects are really not. There's a marked decrease in school and job performance immediately following a concussion. However, only about 50% of athletes report their symptoms of concussion to medical professionals, the reasons of which are varied. There are currently no objective tools truly for the diagnosis of concussion, and it remains a clinical diagnosis. Previous investigations have shown that there's a subset of athletes who do not have clinically diagnosed concussion, but do have evidence of neurocognitive deficits along with fMRI changes. The question becomes, who are these athletes, and can we identify them? One theory is that this group may represent subconcussion, which is linked to the prevailing theory that repetitive subconcussive hits may be the driver behind chronic traumatic encephalopathy. However, the current literature has assumed that, one, all hits are subconcussive, and, two, all hits are the same. If we look at concussion impact magnitude, however, looking at helmet accelerometry, what we see is that that's not really the case. The hits that are associated with concussion are actually quite high impact, with mean linear translational accelerations in excess of 100 Gs of force, and radial acceleration in excess of 5,000 radians per second squared. The objective of this study was primarily to determine if non-concussive, high-acceleration head impacts lead to increases in serum levels of TBI biomarkers in asymptomatic athletes. Secondarily, we determined the longitudinal profile of these biomarkers over the course of the season. It was a single season. We did a prospective observational cohort study looking at varsity high school football athletes. The five biomarkers we elected to study were tau protein, neurofilament light chain, gliofibrily acidic protein, and ubiquitin carboxy terminal hydrolase L1, and spectrum breakdown products. All of these have been studied in TBI separately. This is an overview of our study design. Briefly, prior to the season beginning, prior to any head impact exposure, the athletes were assented and consented. We performed a concussion battery of tests, including SCAT-3, King-Devick tests, the AxonSport computerized cognitive assessment tool, and then we also collected based on serum on all of these athletes. During the season, athletes were continuously monitored at all practices and games with helmet accelerometer using the Rydell HIT system. If an athlete met criteria for a high acceleration head impact, a repeat concussion battery and a serum analysis was performed at the end of the game, immediately following the competition. If an athlete had no high acceleration head impact throughout the course of the season, they were similarly tested at the end of the final game of the season. I should mention that the high acceleration head impact was defined by our group as a linear acceleration of greater than 95 Gs and rotational acceleration of greater than 3,700 rads per second squared. That's based on previous studies by our group, which defined this as being a high-risk hit. In the post-season, approximately one week after the conclusion of the season, we again repeated the concussion battery and serum analysis. All serum was sent to commercial labs, including Quanterix and Banyan biomarkers for analysis. This was a study population, 16 athletes, basically the standard high school varsity football player, about 17 years old, 183 centimeters, 95 kilograms, with seven years of previous football experience. Interestingly, 37.5 percent of them reported a previous diagnosis of concussion previously. For our primary analysis, we had 11 athletes eligible at the end of the season, looking at high-impact versus non-high-impact athletes. There was no difference in baseline values of biomarkers between these two groups. So in our high-acceleration head impact group, which we had six athletes, the linear and rotational acceleration met on the day of testing was 114 Gs of linear force and over 5,000 radians per second squared of rotational force. Our non-high-impact, high-acceleration head impact group also experienced significant force on the day of testing, although they don't meet criteria to be considered an HHI. These were hits that averaged about 63 Gs in linear force and 2,300 in rotational force. The time to blood draw between, so the time of the maximal impact to the time of the venipuncture was about 90 minutes in the high-impact group and about 100 minutes in the non-high-impact group. So looking at our primary analysis again, high-acceleration head impact versus non-high-acceleration head impact, what we see is that in tau protein, serum tau rose about 493 percent after high-acceleration head impact compared to about 164 percent in the control group. Similarly, in UCHL1, we saw a 740 percent rise after high-acceleration head impact compared to 240 percent in control. NFL, GFAP, and SBDP did not have significant differences between groups. Also, neurocognitive testing was unchanged between these two groups. In our secondary analysis, which is a longitudinal study looking at these athletes, there were 12 athletes that remained eligible at the end of the season, and a total of approximately 8,000 head impacts that were captured throughout the course of the season. Of note, only 11 of these were classified as a high-acceleration head impact. The mean number of head impacts was about 470 per athlete for the course of the season, and these were the mean cumulative and rotational acceleration experienced by each athlete. At the end of the season, compared to each athlete's individual baseline, there was about a 64 percent increase in tau and a 62 percent increase in UCHL1, and those were both statistically significant. The other markers, including NFL, GFAP, and SBDP, did not have significant differences. Importantly, none of these changes at the end of the season correlated with any of the accelerometry metrics. There was no correlation to the total number of head impacts or the total force experienced by the helmet over the course of the season. There was also, again, no significant decreases in neurocognitive testing. So the study, what we found was that high school football athletes have evidence of neuronal and axonal injury after nonconcussive HHI. This represents the first evidence of a link between the magnitude of a biomechanical force and a brain injury in humans. Accelerometry is previously shown to be ineffective to diagnose concussion. However, these results suggest that accelerometry may still have a role to define those at risk for short or long-term injury. HHI is not necessarily manifested as clinical symptoms of concussion, and clinical symptoms may in fact not be the most important predictor of long-term dysfunction. In our secondary analysis, there was also evidence of neuronal and axonal injury over the course of a single season. These changes do not appear to be related to the cumulative impact burden. This suggests that other factors may be at play in determining the risk of collision sports. In summation, just a pilot study looking at and showing that there appears to be a relationship between impact magnitude and brain injury in high school football, with also some evidence that after a season of routine high school football play without a diagnosed concussion, there may be some evidence of injury. Importantly, the short and long-term clinical significance of these findings is as yet unclear. Thank you.

brain injury

high school football athletes

mild traumatic brain injury

concussion

neuronal and axonal injury