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

Joseph JR, Swallow JS, Willsey K, Lapointe AP, Khalatbari S, Korley FK,  Oppenlander ME, Park P, Szerlip NJ, Broglio SP. Elevated markers of brain injury as a result of clinically asymptomatic high-acceleration head impacts in high-school football athletes. J Neurosurg. 2018 Jul 3:1-7.

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 2 ); 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.
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"While we do see increases in TBI biomarkers in these athletes, we do not yet know whether these changes are clinically significant or whether they can cause long-term issues," Dr. Joseph said.

Dr. Thomas Talavage from the Concussion Neuroimaging Consortium, Purdue University, West Lafayette, Indiana, who has published extensively on brain changes after head injury in athletes, told Reuters Health, "I was pleased to see that they are also now finding that larger-magnitude events seem to have a greater immediate effect, as we have recently been publishing neuroimaging work, that supports this hypothesis, as well."

"While the manuscript caveats use circular logic to continue to argue that a neuropsychologist is the best identifier of a 'concussion' (which is, truthfully, defined by traditional neuropsychological measures), I would argue that these results are further evidence that clinicians need to be more open to what is and is not 'clinically relevant.' If athletes are experiencing statistically-significant changes in biomarkers known to be associated with brain damage, even 'non-clinical' levels are almost certainly not good for the athletes, and the medical community must become more engaged with prevention of 'clinically-relevant' levels of these biomarkers."

"While the study involves a small sample size, and the presentation of the data groupings is less than clear, the growing body of literature in the neuroimaging domain that argues for meaningful changes in brain physiology associated with histories of head accelerations leads me to believe that there are extremely rapid increases in blood serum levels for several of the biomarkers they examined, and that it is possible that more biomarkers would exhibit changes and a clearer picture of the contributing factors would be obtained, had the sample size been larger," Dr. Talavage said. 

"For example," he said, "the non-HHI group shows increases in tau and UCH-L1 after the season that might achieve significance with a larger group. Such a finding would argue that the used criteria for an HHI were over-strict, and that a (far) greater percentage of head impacts should be
monitored. (Again, our data suggest the linear component of this threshold is closer to 50g than to 100g.)"

https://www.medscape.com/viewarticle/899117?