Browsing by Author "McAllister, Thomas"
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Item Acute Sport Concussion Assessment Optimization: A Prospective Assessment from the CARE Consortium(Springer, 2019) Broglio, Steven P.; Harezlak, Jaroslaw; Katz, Barry; Zhao, Shi; McAllister, Thomas; McCrea, Michael; Biostatistics, School of Public HealthBackground Numerous medical organizations recommend a multifaceted approach to the assessment of concussion occurring during sporting events. A number of tools are available to clinicians, with a wide breadth of sensitivity and specificity; however, little work has been done to evaluate the combined efficiency of these tools in concussed male and female athletes from a broad array of collegiate sports and with variable time from the pre-season baseline evaluation. Objective The aim of this study was to optimize the concussion assessment battery for application within the first 72 h of injury, and to identify the necessary baseline retesting frequency. Methods Between 2014 and 2017, a total of 1458 National Collegiate Athletic Association (NCAA) athletes sustaining 1640 diagnosed concussions completed a baseline assessment each year of the investigation and were evaluated up to three times within the first 72 h of injury using a standardized assessment protocol. Classification and regression tree analyses were implemented to identify the most efficient multifaceted assessment pathway to quantify concussion-related outcomes. Results were optimized for assessments occurring within 1 h post-injury, 1–24 h post-injury, and 24–72 h post-injury when using the raw post-injury assessment performance, difference scores from baseline evaluations occurring in the same year, and difference scores from baseline evaluations occurring the year prior. Results At each of the assessment time points, the analyses indicated that alone or in combination, a symptom evaluation, Balance Error Scoring System (BESS) scores collected on the firm surface, and Standardized Assessment of Concussion (SAC) total score offered the best overall performance when compared with pre-morbid performance captured in the same season. Optimized sensitivity of the multifaceted approach was 61% within 1 h of injury, 67% at the 1–24 h interval, and 55% at the 24–72 h interval when difference scores from the same-season baseline were available. Conclusions This investigation identified key concussion assessments in quantifying post-concussion performance among student athletes, that were maximized when same-season pre-morbid evaluations were available. Consistent with clinical recommendations, medical professionals should continue to focus on symptom reporting, postural control, and neurocognitive screening to support the clinical examination when making a concussion diagnosis.Item Baseline Performance of NCAA Athletes on a Concussion Assessment Battery: A Report from the CARE Consortium(Springer, 2018-08) Katz, Barry P.; Kudela, Maria; Harezlak, Jaroslaw; McCrea, Michael; McAllister, Thomas; Broglio, Steven P.; Biostatistics, School of Public HealthBackground Sport-related concussion and repetitive head impact exposure in contact sports continue to receive increased attention in public and medical spheres. The Concussion Assessment, Research and Education (CARE) Consortium, a multicenter cooperative, was established to study the natural history of concussion in National Collegiate Athletic Association (NCAA) collegiate student-athletes across 29 colleges and universities in the United States. The purpose of this investigation is to provide normative data from the CARE Consortium and evaluate for differences between sport categories. Methods NCAA student-athletes were evaluated annually for general demographics and sport-specific characteristics before the start of the competitive season. We collected demographic and medical history information and evaluated each student-athlete’s neurocognitive function, neurological status, postural stability, and self-reported symptoms. Sports were categorized by the amount of contact typically associated with the sport (i.e., contact, limited contact, non-contact). Comparisons between the three sport categories for the evaluated variables were made using linear or zero inflated negative binomial regression models adjusted for gender, concussion history, and household income. Results Over a 2-year period (August 2014–July 2016), 15,681 NCAA athletes completed preseason evaluations. Overall, 53% of the athletes were in the contact sport group, 31% were in the limited contact group and 17% were in the non-contact group. After adjusting for covariates, there were statistically significant differences found between athlete groups, although the differences and effect sizes were small and not clinically significant. The contact sport group had better scores on Immediate Post-Concussion Assessment Testing (ImPACT®) visual and verbal memory, Sport Concussion Assessment Tool (SCAT) symptom checklist, and Brief Symptom Inventory–18 (BSI-18), but slower ImPACT reaction time and worse scores on Standardized Assessment of Concussion (SAC). Further, the data indicate that some ImPACT score distributions were noticeably different from those presented in the technical manual. Conclusions In this large, racially and socio-economically diverse cohort of male and female college athletes, we found no evidence that student-athletes participating in contact sports have clinically meaningful deficits in pre-season cognitive and balance testing. They also did not report significantly more symptoms of psychological distress when compared with student-athletes in non-contact or limited contact sports. In addition, the data suggest potential limitations when using published ImPACT norms when evaluating injured athletes.Item A cohort study to identify and evaluate concussion risk factors across multiple injury settings: findings from the CARE Consortium(Biomed Central, 2019-01-14) Van Pelt, Kathryn L.; Allred, Dain; Cameron, Kenneth L.; Campbell, Darren E.; D’Lauro, Christopher J.; He, Xuming; Houston, Megan N.; Johnson, Brian R.; Kelly, Tim F.; McGinty, Gerald; Meehan, Sean; O’Donnell, Patrick G.; Peck, Karen Y.; Svoboda, Steven J.; Pasquina, Paul; McAllister, Thomas; McCrea, Michael; Broglio, Steven P.; Medicine, School of MedicineBACKGROUND: Concussion, or mild traumatic brain injury, is a major public health concern affecting 42 million individuals globally each year. However, little is known regarding concussion risk factors across all concussion settings as most concussion research has focused on only sport-related or military-related concussive injuries. METHODS: The current study is part of the Concussion, Assessment, Research, and Education (CARE) Consortium, a multi-site investigation on the natural history of concussion. Cadets at three participating service academies completed annual baseline assessments, which included demographics, medical history, and concussion history, along with the Sport Concussion Assessment Tool (SCAT) symptom checklist and Brief Symptom Inventory (BSI-18). Clinical and research staff recorded the date and injury setting at time of concussion. Generalized mixed models estimated concussion risk with service academy as a random effect. Since concussion was a rare event, the odds ratios were assumed to approximate relative risk. RESULTS: Beginning in 2014, 10,604 (n = 2421, 22.83% female) cadets enrolled over 3 years. A total of 738 (6.96%) cadets experienced a concussion, 301 (2.84%) concussed cadets were female. Female sex and previous concussion were the most consistent estimators of concussion risk across all concussion settings. Compared to males, females had 2.02 (95% CI: 1.70-2.40) times the risk of a concussion regardless of injury setting, and greater relative risk when the concussion occurred during sport (Odds Ratio (OR): 1.38 95% CI: 1.07-1.78). Previous concussion was associated with 1.98 (95% CI: 1.65-2.37) times increased risk for any incident concussion, and the magnitude was relatively stable across all concussion settings (OR: 1.73 to 2.01). Freshman status was also associated with increased overall concussion risk, but was driven by increased risk for academy training-related concussions (OR: 8.17 95% CI: 5.87-11.37). Medical history of headaches in the past 3 months, diagnosed ADD/ADHD, and BSI-18 Somatization symptoms increased overall concussion risk. CONCLUSIONS: Various demographic and medical history factors are associated with increased concussion risk. While certain factors (e.g. sex and previous concussion) are consistently associated with increased concussion risk, regardless of concussion injury setting, other factors significantly influence concussion risk within specific injury settings. Further research is required to determine whether these risk factors may aid in concussion risk reduction or prevention.Item Correction to: Test-Retest Reliability and Interpretation of Common Concussion Assessment Tools: Findings from the NCAA-DoD CARE Consortium(Springer, 2018-07) Broglio, Steven P.; Katz, Barry P.; Zhao, Shi; McCrea, Michael; McAllister, Thomas; CARE Consortium Investigators; Biostatistics, School of Public HealthItem 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 A National Study on the Effects of Concussion in Collegiate Athletes and US Military Service Academy Members: The NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium Structure and Methods(Springer, 2017-07) Broglio, Steven P.; McCrea, Michael; McAllister, Thomas; Harezlak, Jaroslaw; Katz, Barry; Hack, Dallas; Hainline, Brian; CARE Consortium Investigators; Psychiatry, School of MedicineBACKGROUND: The natural history of mild traumatic brain injury (TBI) or concussion remains poorly defined and no objective biomarker of physiological recovery exists for clinical use. The National Collegiate Athletic Association (NCAA) and the US Department of Defense (DoD) established the Concussion Assessment, Research and Education (CARE) Consortium to study the natural history of clinical and neurobiological recovery after concussion in the service of improved injury prevention, safety and medical care for student-athletes and military personnel. OBJECTIVES: The objectives of this paper were to (i) describe the background and driving rationale for the CARE Consortium; (ii) outline the infrastructure of the Consortium policies, procedures, and governance; (iii) describe the longitudinal 6-month clinical and neurobiological study methodology; and (iv) characterize special considerations in the design and implementation of a multicenter trial. METHODS: Beginning Fall 2014, CARE Consortium institutions have recruited and enrolled 23,533 student-athletes and military service academy students (approximately 90% of eligible student-athletes and cadets; 64.6% male, 35.4% female). A total of 1174 concussions have been diagnosed in participating subjects, with both concussion and baseline cases deposited in the Federal Interagency Traumatic Brain Injury Research (FITBIR) database. CONCLUSIONS: Challenges have included coordinating regulatory issues across civilian and military institutions, operationalizing study procedures, neuroimaging protocol harmonization across sites and platforms, construction and maintenance of a relational database, and data quality and integrity monitoring. The NCAA-DoD CARE Consortium represents a comprehensive investigation of concussion in student-athletes and military service academy students. The richly characterized study sample and multidimensional approach provide an opportunity to advance the field of concussion science, not only among student athletes but in all populations at risk for mild TBI.Item Orbitofrontal Cortex and Social Processing in Rodent Models(2019-05) Andrews, Katharine DiAnn; Xu, Xiao-Ming; Lamb, Bruce; McAllister, Thomas; McDonald, Brenna; Truitt, William; Wu, Yu-ChienSocial processing is the reception, interpretation, and reciprocation of social information and is critical for mental health. The neural structures, circuits, and substrates regulating these complex mechanisms are not well understood. Social processing in the form of social safety learning, as measured by a rat model of social familiarity-induced anxiolysis (SoFiA), was impaired following mild blast traumatic brain injury (mbTBI). Initial findings indicated that mbTBI altered resting state network activity in the orbitofrontal cortex (OFC) and was associated with accumulation of neurotoxin marker, acrolein, in lateral prefrontal cortex (PFC) (including OFC), indicating OFC as a brain region of interest that may contribute to social processing. Measuring GABA and Glutamate-related gene expression in OFC of mbTBI or sham-exposed rat brain revealed specific elevations of metabotropic glutamate receptor type 1 and 5 (mGluR1/5) expression in mbTBI but not sham OFC. Exposure-naïve rats intracranially injected with mGluR1/5 agonist demonstrated attenuated SoFiA, and this coincided with an impairment of social recognition (SR) behavior. Additionally, inactivation of OFC by local intracranial injection of GABAA agonist, muscimol, impaired two different measures of SR in which two conspecifics, or members of the same species, one novel and one familiar, were presented and required discrimination. Novelty seeking, decision-making, memory, and gregariousness were tested in isolation to determine OFC contributions to these specific behavioral contributions to SR test performance. OFC inactivation did not impair novelty seeking, non-social decision-making, or non-social memory as measured by novel object recognition (NOR) test, or gregariousness or social decision-making as measure by social preference (SP) test. When measuring SR behavior via consecutive presentation of two different conspecifics, OFC inactivation did not impact SR. Therefore, OFC is not directly responsible for social recognition, but rather the discrimination or ability to act upon discrimination of two simultaneously present conspecifics. These data suggest a novel role for OFC in high order processing or execution of action based on social information.Item Plasma Biomarker Concentrations Associated With Return to Sport Following Sport-Related Concussion in Collegiate Athletes—A Concussion Assessment, Research, and Education (CARE) Consortium Study(American Medical Association, 2020-08-27) Pattinson, Cassandra L.; Meier, Timothy B.; Guedes, Vivian A.; Lai, Chen; Devoto, Christina; Haight, Thaddeus; Broglio, Steven P.; McAllister, Thomas; Giza, Christopher; Huber, Daniel; Harezlak, Jaroslaw; Cameron, Kenneth; McGinty, Gerald; Jackson, Jonathan; Guskiewicz, Kevin; Mihalik, Jason; Brooks, Alison; Duma, Stefan; Rowson, Steven; Nelson, Lindsay D.; Pasquina, Paul; McCrea, Michael; Gill, Jessica M.; CARE Consortium Investigators; Psychiatry, School of MedicineImportance Identifying plasma biomarkers associated with the amount of time an athlete may need before they return to sport (RTS) following a sport-related concussion (SRC) is important because it may help to improve the health and safety of athletes. Objective To examine whether plasma biomarkers can differentiate collegiate athletes who RTS in less than 14 days or 14 days or more following SRC. Design, Setting, and Participants This multicenter prospective diagnostic study, conducted by the National Collegiate Athletics Association–Department of Defense Concussion Assessment, Research, and Education Consortium, included 127 male and female athletes who had sustained an SRC while enrolled at 6 Concussion Assessment, Research, and Education Consortium Advanced Research Core sites as well as 2 partial–Advanced Research Core military service academies. Data were collected between February 2015 and May 2018. Athletes with SRC completed clinical testing and blood collection at preseason (baseline), postinjury (0-21 hours), 24 to 48 hours postinjury, time of symptom resolution, and 7 days after unrestricted RTS. Main Outcomes and Measures A total of 3 plasma biomarkers (ie, total tau protein, glial fibrillary acidic protein [GFAP], and neurofilament light chain protein [Nf-L]) were measured using an ultrasensitive single molecule array technology and were included in the final analysis. RTS was examined between athletes who took less than 14 days vs those who took 14 days or more to RTS following SRC. Linear mixed models were used to identify significant interactions between period by RTS group. Area under the receiver operating characteristic curve analyses were conducted to examine whether these plasma biomarkers could discriminate between RTS groups. Results The 127 participants had a mean (SD) age of 18.9 (1.3) years, and 97 (76.4%) were men; 65 (51.2%) took less than 14 days to RTS, and 62 (48.8%) took 14 days or more to RTS. Linear mixed models identified significant associations for both mean (SE) plasma total tau (24-48 hours postinjury, <14 days RTS vs ≥14 days RTS: −0.65 [0.12] pg/mL vs −0.14 [0.14] pg/mL; P = .008) and GFAP (postinjury, 14 days RTS vs ≥14 days RTS: 4.72 [0.12] pg/mL vs 4.39 [0.11] pg/mL; P = .04). Total tau at the time of symptom resolution had acceptable discrimination power (area under the receiver operating characteristic curve, 0.75; 95% CI, 0.63-0.86; P < .001). We also examined a combined plasma biomarker panel that incorporated Nf-L, GFAP, and total tau at each period to discriminate RTS groups. Although the analyses did reach significance at each time period when combined, results indicated that they were poor at distinguishing the groups (area under the receiver operating characteristic curve, <0.7). Conclusions and Relevance The findings of this study suggest that measures of total tau and GFAP may identify athletes who will require more time to RTS. However, further research is needed to improve our ability to determine recovery following an SRC.Item Plasma Biomarker Concentrations Associated With Return to Sport Following Sport-Related Concussion in Collegiate Athletes—A Concussion Assessment, Research, and Education (CARE) Consortium Study(American Medical Association, 2020-08-27) Pattinson, Cassandra L.; Meier, Timothy B.; Guedes, Vivian A.; Lai, Chen; Devoto, Christina; Haight, Thaddeus; Broglio, Steven P.; McAllister, Thomas; Giza, Christopher; Huber, Daniel; Harezlak, Jaroslaw; Cameron, Kenneth; McGinty, Gerald; Jackson, Jonathan; Guskiewicz, Kevin; Mihalik, Jason; Brooks, Alison; Duma, Stefan; Rowson, Steven; Nelson, Lindsay D.; Pasquina, Paul; McCrea, Michael; Gill, Jessica M.; Investigators for the CARE Consortium; Psychiatry, School of MedicineImportance: Identifying plasma biomarkers associated with the amount of time an athlete may need before they return to sport (RTS) following a sport-related concussion (SRC) is important because it may help to improve the health and safety of athletes. Objective: To examine whether plasma biomarkers can differentiate collegiate athletes who RTS in less than 14 days or 14 days or more following SRC. Design, Setting, and Participants: This multicenter prospective diagnostic study, conducted by the National Collegiate Athletics Association–Department of Defense Concussion Assessment, Research, and Education Consortium, included 127 male and female athletes who had sustained an SRC while enrolled at 6 Concussion Assessment, Research, and Education Consortium Advanced Research Core sites as well as 2 partial–Advanced Research Core military service academies. Data were collected between February 2015 and May 2018. Athletes with SRC completed clinical testing and blood collection at preseason (baseline), postinjury (0-21 hours), 24 to 48 hours postinjury, time of symptom resolution, and 7 days after unrestricted RTS. Main Outcomes and Measures: A total of 3 plasma biomarkers (ie, total tau protein, glial fibrillary acidic protein [GFAP], and neurofilament light chain protein [Nf-L]) were measured using an ultrasensitive single molecule array technology and were included in the final analysis. RTS was examined between athletes who took less than 14 days vs those who took 14 days or more to RTS following SRC. Linear mixed models were used to identify significant interactions between period by RTS group. Area under the receiver operating characteristic curve analyses were conducted to examine whether these plasma biomarkers could discriminate between RTS groups. Results: The 127 participants had a mean (SD) age of 18.9 (1.3) years, and 97 (76.4%) were men; 65 (51.2%) took less than 14 days to RTS, and 62 (48.8%) took 14 days or more to RTS. Linear mixed models identified significant associations for both mean (SE) plasma total tau (24-48 hours postinjury, <14 days RTS vs ≥14 days RTS: −0.65 [0.12] pg/mL vs −0.14 [0.14] pg/mL; P = .008) and GFAP (postinjury, 14 days RTS vs ≥14 days RTS: 4.72 [0.12] pg/mL vs 4.39 [0.11] pg/mL; P = .04). Total tau at the time of symptom resolution had acceptable discrimination power (area under the receiver operating characteristic curve, 0.75; 95% CI, 0.63-0.86; P < .001). We also examined a combined plasma biomarker panel that incorporated Nf-L, GFAP, and total tau at each period to discriminate RTS groups. Although the analyses did reach significance at each time period when combined, results indicated that they were poor at distinguishing the groups (area under the receiver operating characteristic curve, <0.7). Conclusions and Relevance: The findings of this study suggest that measures of total tau and GFAP may identify athletes who will require more time to RTS. However, further research is needed to improve our ability to determine recovery following an SRC.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.