Browsing by Subject "concussion"
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Item Accumulation of high magnitude acceleration events predicts cerebrovascular reactivity changes in female high school soccer athletes(Springer, 2018) Svaldi, Diana O.; Joshi, Chetas; McCuen, Emily C.; Music, Jacob P.; Hannemann, Robert; Leverenz, Larry J.; Nauman, Eric A.; Talavage, Thomas M.; Neurology, School of MedicineMitigating the effects of repetitive exposure to head trauma has become a major concern for the general population, given the growing body of evidence that even asymptomatic exposure to head accelerations is linked with increased risk for negative life outcomes and that risk increases as exposure is prolonged over many years. Among women's sports, soccer currently exhibits the highest growth in participation and reports the largest number of mild traumatic brain injuries annually, making female soccer athletes a relevant population in assessing the effects of repetitive exposure to head trauma. Cerebrovascular biomarkers may be useful in assessing the effects of repetitive head trauma, as these are thought to contribute directly to neurocognitive symptoms associated with mild traumatic brain injury. Here we use fMRI paired with a hypercapnic breath hold task along with monitoring of head acceleration events, to assess the relationship between cerebrovascular brain changes and exposure to repetitive head trauma over a season of play in female high school soccer athletes. We identified longitudinal changes in cerebrovascular reactivity that were significantly associated with prolonged accumulation to high magnitude (> 75th percentile) head acceleration events. Findings argue for active monitoring of athletes during periods of exposure to head acceleration events, illustrate the importance of collecting baseline (i.e., pre-exposure) measurements, and suggest modeling as a means of guiding policy to mitigate the effects of repetitive head trauma.Item Comprehensive Coach Education Reduces Head Impact Exposure in American Youth Football(2015-10) Kerr, Zachary Y.; Yeargin, Susan W.; Valovich McLeod, Tamara C.; Mensch, James; Hayden, Ross; Dompier, Thomas P.BACKGROUND: Despite little evidence that defines a threshold of head impact exposure or that participation in youth sports leads to long-term cognitive impairments, it is prudent to identify methods of reducing the frequency of head impacts. PURPOSE: To compare the mean number of head impacts between youth football players in practice and games between leagues that implemented the Heads Up Football (HUF) educational program and those that did not (NHUF). STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: During the 2014 season, head impact exposure was measured using xPatch accelerometers from 70 youth football players aged 8 to 15 years from 5 leagues. Data were collected during both games and practices. The NHUF group comprised 32 players from 8 teams within 3 leagues. The HUF group comprised 38 players from 7 teams within 2 leagues. Independent-sample t tests evaluated differences in head impact exposure across groups (ie, HUF and NHUF). RESULTS: Players (mean ± SD: age, 11.7 ± 1.4 years; height, 152.2 ± 10.5 cm; weight, 51.6 ± 9.6 kg) experienced a total of 7478 impacts over 10g, of which 4250 (56.8%) and 3228 (43.2%) occurred in practices and games, respectively. The majority of impacts occurred within the NHUF group (62.0%), followed by the HUF group (38.0%). With a 10g impact threshold, the mean number of impacts during practice per individual event was lower in the HUF group (mean ± SD, 5.6 ± 2.9) than in the NHUF group (mean ± SD, 8.9 ± 3.1; difference, 3.4; 95% CI, 2.9-3.9). This difference was attenuated when the threshold was changed to 20g but remained significant (difference, 1.0; 95% CI, 0.7-1.3). At both the 10g and 20g impact thresholds, no differences were found in games. CONCLUSION: Players who participated in HUF leagues accumulated fewer head impacts per practice at both the 10g and 20g thresholds. Youth football leagues should consider the HUF educational program, while exploring additional interventions, to help reduce the number of head impacts in players.Item Concussion and Football: Failures to Respond by the NFL and the Medical Profession(2012) Orentlicher, David; David, William S.The National Football League (NFL) has come under sharp criticism for its approach to the problem of concussion, and many former players have filed a lawsuit against the league. In reviewing the response of NFL to concussion, one can easily think that the league was too slow to worry about the medical consequences of head trauma. Despite concerns being raised for many years about the risk to player health, it took until December 2009 for the NFL to advise its teams that players should not return to play or practice on the same day that they suffer a concussion. But the NFL was not alone in viewing concussion as a relatively mild problem. Physicians also did not worry very much about the medical consequences of concussions. For decades, neurologic experts disagreed as to whether concussions could cause permanent injury, with many attributing patient symptoms to psychological issues or to the incentives created by compensation programs for people with disabling conditions. While the NFL may have responded slowly to problems from concussion, the extent to which its response was unreasonable is unclear. If many medical experts did not worry about concussions, it is difficult to fault the NFL for not worrying either. Still, one can question the NFL’s failure to adopt concussion guidelines in the late 1990’s when they were being issued by medical experts.Item Concussions and Sports: Introduction(2014) Orentlicher, David; Robert H. McKinney School of LawWhile it has become clear that concussion is a serious problem in football and other sports, it is not clear how best to respond to the problem. When athletes suffer concussions — or injuries that might be a concussion — what steps should be taken? More importantly, has the response to concussion focused too much on management of concussive injury and not enough on prevention of harm? This article provides an introduction to a symposium that sheds light on a number of questions about concussions and sports, from both theoretical and empirical perspectives. The papers inform our understanding about the adoption, implementation, and effectiveness of state statutes and other policies designed to reduce the harm from concussions. Ultimately, we must ask whether some sports are so dangerous that they should no longer be played. It is one thing to assume risks to health when there are meaningful benefits to be gained. But there are many ways to exercise, develop teamwork skills, or gain the other benefits of competitive athletics without playing football or other sports that lead to concussion. Ultimately, the social value of violent sports seems to rest heavily on the entertainment they offer to spectators. And that should lead us to ask whether there is any legitimate role for the levels of physical violence that we tolerate in sport.Item Descriptive Analysis of a Baseline Concussion Battery Among U.S. Service Academy Members: Results from the Concussion Assessment, Research, and Education (CARE) Consortium(Oxford, 2018-11) O'Connor, Kathryn L.; Allred, C. Dain; Cameron, Kenneth L.; Campbell, Darren E.; D'Lauro, Christopher J.; Houston, Megan N.; Johnson, Brian R.; Kelly, Tim F.; McGinty, Gerald; O'Donnell, Patrick G.; Peck, Karen Y.; Svoboda, Steven J.; Pasquina, Paul; McAllister, Thomas; McCrea, Michael; Broglio, Steven P.; Psychiatry, School of MedicineIntroduction The prevalence and possible long-term consequences of concussion remain an increasing concern to the U.S. military, particularly as it pertains to maintaining a medically ready force. Baseline testing is being used both in the civilian and military domains to assess concussion injury and recovery. Accurate interpretation of these baseline assessments requires one to consider other influencing factors not related to concussion. To date, there is limited understanding, especially within the military, of what factors influence normative test performance. Given the significant physical and mental demands placed on service academy members (SAM), and their relatively high risk for concussion, it is important to describe demographics and normative profile of SAMs. Furthermore, the absence of available baseline normative data on female and non-varsity SAMs makes interpretation of post-injury assessments challenging. Understanding how individuals perform at baseline, given their unique individual characteristics (e.g., concussion history, sex, competition level), will inform post-concussion assessment and management. Thus, the primary aim of this manuscript is to characterize the SAM population and determine normative values on a concussion baseline testing battery. Materials and Methods All data were collected as part of the Concussion Assessment, Research and Education (CARE) Consortium. The baseline test battery included a post-concussion symptom checklist (Sport Concussion Assessment Tool (SCAT), psychological health screening inventory (Brief Symptom Inventory (BSI-18) and neurocognitive evaluation (ImPACT), Balance Error Scoring System (BESS), and Standardized Assessment of Concussion (SAC). Linear regression models were used to examine differences across sexes, competition levels, and varsity contact levels while controlling for academy, freshman status, race, and previous concussion. Zero inflated negative binomial models estimated symptom scores due to the high frequency of zero scores. Results Significant, but small, sex effects were observed on the ImPACT visual memory task. While, females performed worse than males (p < 0.0001, pη2 = 0.01), these differences were small and not larger than the effects of the covariates. A similar pattern was observed for competition level on the SAC. There was a small, but significant difference across competition level. SAMs participating in varsity athletics did significantly worse on the SAC compared to SAMs participating in club or intramural athletics (all p’s < 0.001, η2 = 0.01). When examining symptom reporting, males were more than two times as likely to report zero symptoms on the SCAT or BSI-18. Intramural SAMs had the highest number of symptoms and severity compared to varsity SAMs (p < 0.0001, Cohen’s d < 0.2). Contact level was not associated with SCAT or BSI-18 symptoms among varsity SAMs. Notably, the significant differences across competition level on SCAT and BSI-18 were sub-clinical and had small effect sizes. Conclusion The current analyses provide the first baseline concussion battery normative data among SAMs. While statistically significant differences may be observed on baseline tests, the effect sizes for competition and contact levels are very small, indicating that differences are likely not clinically meaningful at baseline. Identifying baseline differences and significant covariates is important for future concussion-related analyses to inform concussion evaluations for all athlete levels.Item Investigating Disease Mechanisms and Drug Response Differences in Transcriptomics Sequencing Data(2022-01) Simpson, Edward Ronald Jr.; Liu, Yunlong; Janga, Sarath; Wan, Jun; Wu, Huanmei; Yan, JingwenIn eukaryotes, genetic information is encoded by DNA, transcribed to precursor messenger RNA (pre-mRNA), processed into mature messenger RNA (mRNA), and translated into functional proteins. Splicing of pre-mRNA is an important epigenetic process that alters the function of proteins through modifying the exon structure of mature mRNA transcripts and is known to greatly contribute to diversity of the human proteome. The vast majority of human genes are expressed through multiple transcript isoforms. Expression of genes through splicing of pre-mRNA plays crucial roles in cellular development, identity, and processes. Both the identity of genes selected for transcription and the specific transcript isoforms that are expressed are essential for normal cellular function. Deviations in gene expression or isoform proportion can be an indication or the cause of disease. RNA sequencing (RNAseq) is a high-throughput next-generation sequencing technology that allows for the interrogation of gene expression on a massive scale. RNAseq generates short sequences that reflect pieces of mRNAs present in a sample. RNAseq can therefore be used to explore differences in gene expression, reveal transcript isoform identities and compare changes in isoform proportions. In this dissertation, I design and apply advanced analysis techniques to RNAseq, phenotypic and drug response data to investigate disease mechanisms and drug sensitivity. Research Goals: The work described in this dissertation accomplishes 4 aims. Aim 1) Evaluate the gene expression signature of concussion in collegiate athletes and identify potential biomarkers for response and recovery. Aim 2) Implement a machine-learning algorithm to determine if splicing can predict drug response in cancer cell lines. Aim 3) Design a fast, scalable method to identify differentially spliced events related to cancer drug response. Aim 4) Construct a drug-splicing network and use a systems biology approach to search for similarities in underlying splicing events.Item Prevalence of Potentially Clinically Significant Magnetic Resonance Imaging Findings in Athletes with and without Sport-Related Concussion(Mary Ann Liebert, 2019-05-22) Klein, Andrew P.; Tetzlaff, Julie E.; Bonis, Joshua M.; Nelson, Lindsay D.; Mayer, Andrew R.; Huber, Daniel L.; Harezlak, Jaroslaw; Mathews, Vincent P.; Ulmer, John L.; Sinson, Grant P.; Nencka, Andrew S.; Koch, Kevin M.; Wu, Yu-Chien; Saykin, Andrew J.; DiFiori, John P.; Giza, Christopher C.; Goldman, Joshua; Guskiewicz, Kevin M.; Mihalik, Jason P.; Duma, Stefan M.; Rowson, Steven; Brooks, Alison; Broglio, Steven P.; McAllister, Thomas; McCrea, Michael A.; Meier, Timothy B.; Radiology and Imaging Sciences, School of MedicinePrevious studies have shown that mild traumatic brain injury (mTBI) can cause abnormalities in clinically relevant magnetic resonance imaging (MRI) sequences. No large-scale study, however, has prospectively assessed this in athletes with sport-related concussion (SRC). The aim of the current study was to characterize and compare the prevalence of acute, trauma-related MRI findings and clinically significant, non-specific MRI findings in athletes with and without SRC. College and high-school athletes were prospectively enrolled and participated in scanning sessions between January 2015 through August 2017. Concussed contact sport athletes (n = 138; 14 female [F]; 19.5 ± 1.6 years) completed up to four scanning sessions after SRC. Non-concussed contact (n = 135; 15 F; 19.7 ± 1.6) and non-contact athletes (n = 96; 15 F; 20.0 ± 1.7) completed similar scanning sessions and served as controls. Board-certified neuroradiologists, blinded to SRC status, reviewed T1-weighted and T2-weighted fluid-attenuated inversion recovery and T2*-weighted and T2-weighted images for acute (i.e., injury-related) or non-acute findings that prompted recommendation for clinical follow-up. Concussed athletes were more likely to have MRI findings relative to contact (30.4% vs. 15.6%; odds ratio [OR] = 2.32; p = 0.01) and non-contact control athletes (19.8%; OR = 2.11; p = 0.04). Female athletes were more likely to have MRI findings than males (43.2% vs. 19.4%; OR = 2.62; p = 0.01). One athlete with SRC had an acute, injury-related finding; group differences were largely driven by increased rate of non-specific white matter hyperintensities in concussed athletes. This prospective, large-scale study demonstrates that <1% of SRCs are associated with acute injury findings on qualitative structural MRI, providing empirical support for clinical guidelines that do not recommend use of MRI after SRC.Item Progress and Future Directions of the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium and Mind Matters Challenge at the US Service Academies(Frontiers, 2020-09-24) Houston, Megan N.; O'Donovan, Kevin J.; Trump, Jesse R.; Brodeur, Rachel M.; McGinty, Gerald T.; Wickiser, J. Kenneth; D'Lauro, Christopher J.; Jackson, Jonathan C.; Svoboda, Steven J.; Susmarski, Adam J.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Pasquina, Paul; Cameron, Kenneth L.; Psychiatry, School of MedicineDespite the significant impact that concussion has on military service members, significant gaps remain in our understanding of the optimal diagnostic, management, and return to activity/duty criteria to mitigate the consequences of concussion. In response to these significant knowledge gaps, the US Department of Defense (DoD) and the National Collegiate Athletic Association (NCAA) partnered to form the NCAA-DoD Grand Alliance in 2014. The NCAA-DoD CARE Consortium was established with the aim of creating a national multisite research network to study the clinical and neurobiological natural history of concussion in NCAA athletes and military Service Academy cadets and midshipmen. In addition to the data collected for the larger CARE Consortium effort, the service academies have pursued military-specific lines of research relevant to operational and medical readiness associated with concussion. The purpose of this article is to describe the structure of the NCAA-DoD Grand Alliance efforts at the service academies, as well as discuss military-specific research objectives and provide an overview of progress to date. A secondary objective is to discuss the challenges associated with conducting large-scale studies in the Service Academy environment and highlight future directions for concussion research endeavors across the CARE Service Academy sites.Item Return to play and risk of repeat concussion in collegiate football players: comparative analysis from the NCAA Concussion Study (1999–2001) and CARE Consortium (2014–2017)(BMJ, 2020) McCrea, Michael; Broglio, Steven P.; McAllister, Thomas; Zhou, Wenxian; Zhao, Shi; Katz, Barry P.; Kudela, Maria; Harezlak, Jaroslaw; Nelson, Lindsay D.; Meier, Timothy B.; Marshall, Stephen W.; Guskiewicz, Kevin; Psychiatry, School of MedicineObjective We compared data from the National Collegiate Athletic Association (NCAA) Concussion Study (1999–2001) and the NCAA-Department of Defense Concussion Assessment, Research and Education (CARE) Consortium (2014–2017) to examine how clinical management, return to play (RTP) and risk of repeat concussion in collegiate football players have changed over the past 15 years. Methods We analysed data on reported duration of symptoms, symptom-free waiting period (SFWP), RTP and occurrence of within-season repeat concussion in collegiate football players with diagnosed concussion from the NCAA Study (n=184) and CARE (n=701). Results CARE athletes had significantly longer symptom duration (CARE median=5.92 days, IQR=3.02–9.98 days; NCAA median=2.00 days, IQR=1.00–4.00 days), SFWP (CARE median=6.00 days, IQR=3.49–9.00 days; NCAA median=0.98 days, IQR=0.00–4.00 days) and RTP (CARE median=12.23 days, IQR=8.04–18.92 days; NCAA median=3.00 days, IQR=1.00–8.00 days) than NCAA Study athletes (all p<0.0001). In CARE, there was only one case of repeat concussion within 10 days of initial injury (3.7% of within-season repeat concussions), whereas 92% of repeat concussions occurred within 10 days in the NCAA Study (p<0.001). The average interval between first and repeat concussion in CARE was 56.41 days, compared with 5.59 days in the NCAA Study (M difference=50.82 days; 95% CI 38.37 to 63.27; p<0.0001). Conclusion Our findings indicate that concussion in collegiate football is managed more conservatively than 15 years ago. These changes in clinical management appear to have reduced the risk of repetitive concussion during the critical period of cerebral vulnerability after sport-related concussion (SRC). These data support international guidelines recommending additional time for brain recovery before athletes RTP after SRC.Item Role of Repetitive Head Impact Exposure in the Onset of Concussion: Evidence of a Possible Second Mechanism of Concussion for Contact Sports(International Research Council on the Biomechanics of Injury, 2018-09) Stemper, Brian D.; Shah, Alok S.; Wild, Alexa; Humm, John R.; Pintar, Frank A.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael; Psychiatry, School of Medicine