Assessment of Long-Term Effects of Sports-Related Concussions: Biological Mechanisms and Exosomal Biomarkers

Ledreux, Aurélie; Pryhoda, Moira K.; Gorgens, Kim A.; Shelburne, Kevin B.; Gilmore, Anah; Linseman, Daniel A.; Fleming, Holly; Koza, Lilia; Campbell, Julie; Wolff, Adam; Kelly, James P.; Margittai, Martin; Davidson, Bradley S.; Granholm, Ann‐Charlotte

doi:10.3389/fnins.2020.00761

Cited by 20 publications

(18 citation statements)

References 207 publications

(307 reference statements)

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“…The potential long-term consequences of SRC and repetitive "subconcussive" head impacts make early detection of any impairment of brain function an important consideration for protection of an athlete's performance capabilities and healthrelated quality of life (Hirad et al, 2019). However, the clinically silent nature of the underlying pathophysiological process, combined with the reluctance of some athletes to report persistent SRC symptoms, may result in an unrecognized vulnerability to repetitive injury and progressive dysfunction (Brett et al, 2020;Ledreux et al, 2020). The ability to rapidly generate appropriate responses to visual cues may facilitate collision avoidance and impact preparation, thereby preventing injury (Kung et al, 2020).…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

A Novel Approach to Assessment of Perceptual-Motor Efficiency and Training-Induced Improvement in the Performance Capabilities of Elite Athletes

Wilkerson

Nabhan

Perry

2021

Front. Sports Act. Living

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Standard clinical assessments of mild traumatic brain injury are inadequate to detect subtle abnormalities that can be revealed by sophisticated diagnostic technology. An association has been observed between sport-related concussion (SRC) and subsequent musculoskeletal injury, but the underlying neurophysiological mechanism is not currently understood. A cohort of 16 elite athletes (10 male, 6 female), which included nine individuals who reported a history of SRC (5 male, 4 female) that occurred between 4 months and 8 years earlier, volunteered to participate in a 12-session program for assessment and training of perceptual-motor efficiency. Performance metrics derived from single- and dual-task whole-body lateral and diagonal reactive movements to virtual reality targets in left and right directions were analyzed separately and combined in various ways to create composite representations of global function. Intra-individual variability across performance domains demonstrated very good SRC history classification accuracy for the earliest 3-session phase of the program (Reaction Time Dispersion AUC = 0.841; Deceleration Dispersion AUC = 0.810; Reaction Time Discrepancy AUC = 0.825, Deceleration Discrepancy AUC = 0.794). Good earliest phase discrimination was also found for Composite Asymmetry between left and right movement directions (AUC = 0.778) and Excursion Average distance beyond the minimal body displacement necessary for virtual target deactivation (AUC = 0.730). Sensitivity derived from Youden's Index for the 6 global factors ranged from 67 to 89% and an identical specificity value of 86% for all of them. Median values demonstrated substantial improvement from the first 3-session phase to the last 3-session phase for Composite Asymmetry and Excursion Average. The results suggest that a Composite Asymmetry value ≥ 0.15 and an Excursion Average value ≥ 7 m, provide reasonable qualitative approximations for clinical identification of suboptimal perceptual-motor performance. Despite acknowledged study limitations, the findings support a hypothesized relationship between whole-body reactive agility performance and functional connectivity among brain networks subserving sensory perception, cognitive decision-making, and motor execution. A complex systems approach appears to perform better than traditional data analysis methods for detection of subtle perceptual-motor impairment, which has the potential to advance both clinical management of SRC and training for performance enhancement.

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Section: Limitations and Future Directionsmentioning

confidence: 99%

A Novel Approach to Assessment of Perceptual-Motor Efficiency and Training-Induced Improvement in the Performance Capabilities of Elite Athletes

Wilkerson

Nabhan

Perry

2021

Front. Sports Act. Living

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“…Although the precise mechanism by which SRC elevates the risk for musculoskeletal injury remains unknown, 28 it may result from the same neuroinflammatory process that is believed to increase brain vulnerability to repeated SRC and neurodegeneration. 5 , 33 Microstructural disruption of connectivity within and between brain networks can variably affect cognition, mood, and motor coordination. 25 , 45 There is evidence that multimodal neuromuscular control training (ie, postural balance, progressive resistance, plyometric, and functional movement exercises) can substantially reduce the incidence of both SRC and musculoskeletal injuries.…”

Section: Discussionmentioning

confidence: 99%

“… 11 , 12 , 17 A key concern is the potential for adverse subacute or long-term outcomes if subtle impairment remains undetected and further brain injury is sustained from sport participation. 5 Repetitive SRC has the potential to exacerbate a chronic neuroinflammatory response within the brain 33 , 50 and further elevate the risk for lower extremity injury. 23 American football presents an exceptionally high risk for occurrence of SRC and musculoskeletal injury, with sprain or strain of anatomic structures in the body core or in the lower extremity being the most common injuries.…”

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confidence: 99%

“…16 A combination of self-reported persisting effects of SRC and musculoskeletal injuries with an objective measurement of perceptual-motor performance may provide a means to accurately classify an individual athlete's level of injury risk as a component of a preparticipation evaluation process. 33 Thus, the objectives of this study were as follows: (1) to acquire preparticipation data believed to be relevant to injury risk; (2) to document injury occurrences from the first practice session to the end of the football season; and (3) to utilize predictive modeling methods to quantify the relative odds for injury occurrence between player groups with differing preparticipation risk profiles. Specifically, we sought (1) to identify factors that can accurately categorize an individual football player's risk for occurrence of core or lower extremity injury (CLEI), (2) to identify factors that can accurately categorize an individual football player's risk for occurrence of SRC, and (3) to identify factors that have a strong association with a football player's self-reported lifetime history of SRC.…”

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confidence: 99%

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Perceptual-Motor Efficiency and Concussion History Are Prospectively Associated With Injury Occurrences Among High School and Collegiate American Football Players

Wilkerson

Bruce

Wilson

et al. 2021

Orthopaedic Journal of Sports Medicine

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Background: After a sport-related concussion (SRC), the risk for lower extremity injury is approximately 2 times greater, and the risk for another SRC may be as much as 3 to 5 times greater. Purpose: To assess the predictive validity of screening methods for identification of individual athletes who possess an elevated risk of SRC. Study Design: Case-control study; Level of evidence, 3. Methods: Metrics derived from a smartphone flanker test software application and self-ratings of both musculoskeletal function and overall wellness were acquired from American high school and college football players before study participation. Occurrences of core or lower extremity injury (CLEI) and SRC were documented for all practice sessions and games for 1 season. Receiver operating characteristic and logistic regression analyses were used to identify variables that provided the greatest predictive accuracy for CLEI or SRC occurrence. Results: Overall, there were 87 high school and 74 American college football players included in this study. At least 1 CLEI was sustained by 45% (39/87) of high school players and 55% (41/74) of college players. Predictors of CLEI included the flanker test conflict effect ≥69 milliseconds (odds ratio [OR], 2.12; 90% CI, 1.24-3.62) and a self-reported lifetime history of SRC (OR, 1.70; 90% CI, 0.90-3.23). Of players with neither risk factor, only 38% (29/77) sustained CLEI compared with 61% (51/84) of players with 1 or both of the risk factors (OR, 2.56; 90% CI, 1.50-4.36). SRC was sustained by 7 high school players and 3 college players. Predictors of SRC included the Overall Wellness Index score ≤78 (OR, 9.83; 90% CI, 3.17-30.50), number of postconcussion symptoms ≥4 (OR, 8.35; 90% CI, 2.71-25.72), the Sport Fitness Index score ≤78 (OR, 5.16; 90% CI, 1.70-15.65), history of SRC (OR, 4.03; 90% CI, 1.35-12.03), and the flanker test inverse efficiency ratio ≥1.7 (OR, 3.19; 90% CI, 1.08-9.47). Conclusion: Survey responses and smartphone flanker test metrics predicted greater injury incidence among individual football players classified as high-risk compared with that for players with a low-risk profile.

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“…Both clinical trials and preclinical studies have focused solely on males; a recent review estimated that 93 % of preclinical studies precluded sex as a variable ( Spani et al., 2018 ). While in young adults traumatic brain injury is more common in males ( Faul and Coronado, 2015 ; Coronadoet al., 2010 ), there is a growing number of cases identified in females ( Ledreuxet al., 2020 ; Gizaet al., 2013 ; Kutcher and Giza, 2014 ). Furthermore, female athletes report more concussions when playing the same sports as males ( Covassin et al., 2016 ), In the elderly population, TBI is more prevalent in females ( Maet al., 2019 ) as well, which makes the individual sex paradigm obsolete.…”

Section: Sex-differences In Traumatic Brain Injurymentioning

confidence: 99%

Short review: The impact of sex on neuroimmune and cognitive outcomes after traumatic brain injury

Krukowski

2021

Brain, Behavior, & Immunity - Health

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Traumatic brain injury (TBI) is an ever growing health concern, with cases increasing in both the US and the world at large. With the improvement of emergency medicine in recent decades, survival from TBI has become more common place, and thus individuals are coping with long-term deleterious outcomes from trauma as a result. Such outcomes include altered cognitive (memory loss/executive function), social (isolation tendencies), and behavioral (risk-taking behavior/anxiety) function. Researchers use preclinical rodent models to investigate cellular and molecular underpinnings of adverse TBI outcomes. One leading mechanism of long-term cognitive changes include alterations of immune function in the brain (termed ‘neuroimmune’). Studies have found that TBI can induce chronic maladaptive neuroimmune responses, which can in turn propagate long-term neurological deficits. Unfortunately, most of the molecular understanding of TBI-induced neuroimmune outcomes is derived from studies performed solely in males. This is especially problematic as sex-dimorphic neuroimmune changes have been identified in healthy individuals. If and how these basal neuroimmune differences influence TBI related outcomes is the focus of this short review. Importantly, understanding these differences could allow for improved therapeutic development for treating the long-term effects of TBI.

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Assessment of Long-Term Effects of Sports-Related Concussions: Biological Mechanisms and Exosomal Biomarkers

Cited by 20 publications

References 207 publications

A Novel Approach to Assessment of Perceptual-Motor Efficiency and Training-Induced Improvement in the Performance Capabilities of Elite Athletes

A Novel Approach to Assessment of Perceptual-Motor Efficiency and Training-Induced Improvement in the Performance Capabilities of Elite Athletes

Perceptual-Motor Efficiency and Concussion History Are Prospectively Associated With Injury Occurrences Among High School and Collegiate American Football Players

Short review: The impact of sex on neuroimmune and cognitive outcomes after traumatic brain injury

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