Browsing by Subject "Concussion"

Now showing 1 - 10 of 25
  • Thumbnail Image
    Item
    Are EPB41 and alpha-synuclein diagnostic biomarkers of sport-related concussion? Findings from the NCAA and Department of Defense CARE Consortium
    (Elsevier, 2023) Vorn, Rany; Devoto, Christina; Meier, Timothy B.; Lai, Chen; Yun, Sijung; Broglio, Steven P.; Mithani, Sara; McAllister, Thomas W.; Giza, Christopher C.; Kim, Hyung-Suk; Huber, Daniel; Harezlak, Jaroslaw; Cameron, Kenneth L.; McGinty, Gerald; Jackson, Jonathan; Guskiewicz, Kevin M.; Mihalik, Jason P.; Brooks, Alison; Duma, Stefan; Rowson, Steven; Nelson, Lindsay D.; Pasquina, Paul; McCrea, Michael A.; Gill, Jessica M.; CARE Consortium Investigators; Psychiatry, School of Medicine
    Background: Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion. Therefore, more accurate diagnostic markers are needed for sport-related concussion. Methods: This was a multicenter, prospective, case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research, and Education Consortium conducted between 2015 and 2019. The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints. Athletes with concussion were divided into 6 h post-injury (0-6 h post-injury) and after 6 h post-injury (7-48 h post-injury) groups. We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305 proteins in plasma samples from athletes with and without sport-related concussion. Results: A total of 140 athletes with concussion (79.3% males; aged 18.71 ± 1.10 years, mean ± SD) and 21 non-concussed athletes (76.2% males; 19.14 ± 1.10 years) were included in this study. We identified 338 plasma proteins that significantly differed in abundance (319 upregulated and 19 downregulated) in concussed athletes compared to non-concussed athletes. The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve (AUC) of 0.954 (95% confidence interval: 0.922‒0.986). Specifically, after 6 h of injury, the individual AUC of plasma erythrocyte membrane protein band 4.1 (EPB41) and alpha-synuclein (SNCA) were 0.956 and 0.875, respectively. The combination of EPB41 and SNCA provided the best AUC (1.000), which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury. Conclusion: Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.
  • Thumbnail Image
    Item
    Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players: A Pilot Study
    (Frontiers Media, 2020-11-16) Kawata, Keisuke; Steinfeldt, Jesse A.; Huibregtse, Megan E.; Nowak, Madeleine K.; Macy, Jonathan T.; Kercher, Kyle; Rettke, Devin J.; Shin, Andrea; Chen, Zhongxue; Ejima, Keisuke; Newman, Sharlene D.; Cheng, Hu; Medicine, School of Medicine
    While neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts.
  • Thumbnail Image
    Item
    Association of Alzheimer’s disease polygenic risk score with concussion severity and recovery metrics
    (Wiley, 2025-01-09) Dybing, Kaitlyn M.; McAllister, Thomas W.; Wu, Yu-Chien; McDonald, Brenna C.; McCrea, Michael A.; Broglio, Steven P.; Pasquina, Paul F.; Brooks, M. Alison; Mihalik, Jason P.; Guskiewicz, Kevin M.; Giza, Christopher C.; Goldman, Joshua; Duma, Stefan; Rowson, Steve; Svoboda, Steven; Cameron, Kenneth L.; Houston, Megan N.; Campbell, Darren E.; McGinty, Gerald; Jackson, Jonathan; Risacher, Shannon L.; Saykin, Andrew J.; Nudelman, Kelly N.; Radiology and Imaging Sciences, School of Medicine
    Background: Shared genetic risk between Alzheimer’s disease (AD) and concussion may help explain the association between concussion and elevated risk for dementia. However, there has been little investigation into whether AD risk genes also associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate associations between AD genetic risk and concussion severity/recovery in the NCAA‐DoD Grand Alliance CARE Consortium (CARE) dataset. Method: There were 1,917 injuries in the dataset upon project initiation. After removing repeated injuries, related participants, and those without genetic/outcome data, we had 931 participants. Outcomes were number of days to return to play (RTP) as a recovery measure, and four severity measures (scores on SAC and BESS, SCAT symptom severity and total number of symptoms). We calculated PRS using a published score (de Rojas et al., 2021) and performed a linear regression (MLR) of RTP by PRS in normal (<24 days) and long (>24 days) RTP subgroups. We then compared severity measures by PRS using MLR. Next, we used t‐tests to examine outcomes by APOE genotype in military and civilian subgroups. We also performed chi‐squared tests of RTP category (normal vs. long) by APOE genotype. Finally, we analyzed outcomes by PRS in European or African genetic ancestry subgroups using MLR. Result: Higher PRS was associated with longer injury to RTP interval in the normal RTP (<24 days) subgroup (estimate = 0.0412, SE = 0.182, p = 0.0237). 1 SD increase in PRS resulted in a 0.412 day (9.89 hours) increase to the interval. This may be clinically meaningful in the collegiate athlete environment. We did not identify any other significant differences. Conclusion: Our preliminary results provide limited evidence for an impact of AD PRS on concussion recovery, though the pattern was inconsistent and its clinical significance is uncertain. Future studies should attempt to replicate these findings in larger samples with longer follow‐up using PRS calculated from multiple/diverse populations, which will be especially relevant for diverse datasets like CARE.
  • Thumbnail Image
    Item
    Association of Premorbid Anxiety and Depression Symptoms in Concussion Recovery in Collegiate Student-Athletes
    (Sage, 2024-06-04) Sawlani, Sabrina P.; Goldman, Joshua T.; Babikian, Talin; McArthur, David L.; Polster, Douglas; McCrea, Michael; McAllister, Thomas; Giza, Christopher C.; CARE Consortium; CARE Consortium Investigators; Ortega, Justus D.; Port, Nicholas; Putukian, Margot; McDevitt, Jane; Giza, Christopher C.; Goldman, Joshua T.; Benjamin, Holly J.; Buckley, Thomas; Kaminski, Thomas W.; Clugston, James R.; Feigenbaum, Luis A.; Eckner, James T.; Mihalik, Jason P.; Anderson, Scott; Master, Christina L.; Kontos, Anthony P.; Chrisman, Sara P. O.; Cameron, Kenneth; Duma, Stefan; Miles, Christopher M.; Psychiatry, School of Medicine
    Background: Mental health disorders are linked to prolonged concussion symptoms. However, the association of premorbid anxiety/depression symptoms with postconcussion return-to-play timelines and total symptom burden is unclear. Objective: To examine the association of self-reported premorbid anxiety/depression symptoms in collegiate student-athletes with (1) recovery times until asymptomatic, (2) return-to-play, and (3) postconcussion symptom burden. Study design: Athletes in the Concussion Assessment, Research and Education Consortium completed baseline concussion assessments (Sport Concussion Assessment Tool [SCAT3] and Brief Symptom Inventory-18 [BSI-18]). Athletes were tested postinjury at <6 hours, 24 to 48 hours, time of asymptomatic and start of return-to-play protocol, unrestricted return-to-play, and 6 months after injury. Injured athletes were categorized into 4 groups based on BSI-18 scores: (1) B-ANX, elevated anxiety symptoms only; (2) B-DEP, elevated depression symptoms only; (3) B-ANX&DEP, elevated anxiety and depression symptoms; and (4) B-NEITHER, no elevated anxiety or depression symptoms. Relationship between age, sex, BSI-18 group, SCAT3 total symptom and severity scores, and time to asymptomatic status and return-to-play was assessed with Pearson's chi-squared test and robust analysis of variance. Level of evidence: Level 3. Results: Among 1329 athletes with 1352 concussions, no respondents had a self-reported premorbid diagnosis of anxiety/depression. There was no difference in time until asymptomatic or time until return-to-play between BSI-18 groups (P = 0.15 and P = 0.11, respectively). B-ANX, B-DEP, and B-ANX&DEP groups did not have higher total symptom or severity scores postinjury compared with the B-NEITHER group. Conclusion: Baseline anxiety/depression symptoms in collegiate student-athletes without a mental health diagnosis are not associated with longer recovery times until asymptomatic, longer time to return-to-play, or higher postconcussion total symptom and severity scores compared with athletes without baseline symptoms. Clinical relevance: Anxiety and depression symptoms without a clear mental health diagnosis should be considered differently from other comorbidities when discussing prolonged recovery in collegiate student-athletes.
  • Thumbnail Image
    Item
    Associations between repetitive head impact exposure and midlife mental health wellbeing in former amateur athletes
    (Frontiers Media, 2024-05-28) Buddenbaum, Claire V.; Recht, Grace O.; Rodriguez, Adriana K.; Newman, Sharlene D.; Kawata, Keisuke; Pediatrics, School of Medicine
    Introduction: Repetitive head impacts (RHI) have been suggested to increase the risk of developing a neurodegenerative disease, and many of these individuals develop a preceding mental health diagnosis. Given the lack of studies among amateur athletes, this study aimed to examine mental health outcomes in middle-aged amateur athletes who have been exposed to RHI through contact sport participation. Methods: This is a single site, cohort study involving former amateur athletes aged between 30 and 60 with at least 10 years of organized contact or non-contact sport participation. All participants completed demographic and mental health questionnaires. Mental health outcomes included symptoms related to depression, anxiety, post-traumatic stress disorder (PTSD), attention deficit hyperactive disorder (ADHD), and aggression. Self-reported data on mental health diagnoses and associated prescription were elicited and used to estimate odds ratios (OR). Results: Data from 41 contact athletes and 22 age/sex-matched non-contact athletes were available for analysis. The contact group exhibited a 2.25-fold higher likelihood of being diagnosed with mental health disorders and 1.29-fold higher likelihood of using associated medications compared to the non-contact group. The contact group reported significantly higher PTSD-related symptoms [4.61 (0.03,9.2), p=0.05] compared to the non-contact control group. While not statistically significant, the contact group showed increased depressive [2.37 (0.05, 4.79), p=0.07] and ADHD symptoms [4.53 (0.51, 9.57), p=0.08] compared to controls. In a secondary analysis, a distinct trend emerged within the contact group, revealing pronounced elevations in mental health symptoms among individuals with lower socioeconomic status (<$50,000/year) compared to higher income subgroups, and these symptoms decreased as income levels rose [depression: -3.08 (-4.47, -1.7), p<0.001; anxiety: -1.95 (-3.15, -0.76), p=0.002; ADHD: -4.99 (-8.28, -1.69), p=0.004; PTSD: -4.42 (-7.28, -1.57), p=0.003; aggression: -6.19 (-11.02, -1.36), p=0.01]. This trend was absent in the non-contact control group. Discussion: Our data suggest that even individuals at the amateur level of contact sports have an increased likelihood of being diagnosed with mental health disorders or experiencing mental health symptoms compared to non-contact athletes. Our findings indicate that socioeconomic status may have an interactive effect on individuals' mental health, particularly among those with a long history of RHI exposure.
  • Thumbnail Image
    Item
    Cerebral blood flow in acute concussion: preliminary ASL findings from the NCAA-DoD CARE consortium
    (Springer, 2019-10-01) Wang, Yang; Nencka, Andrew S.; Meier, Timothy B.; Guskiewicz, Kevin; Mihalik, Jason P.; Alison Brooks, M.; Saykin, Andrew J.; Koch, Kevin M.; Wu, Yu-Chien; Nelson, Lindsay D.; McAllister, Thomas W.; Broglio, Steven P.; McCrea, Michael A.; Radiology and Imaging Sciences, School of Medicine
    Sport-related concussion (SRC) has become a major health problem, affecting millions of athletes each year. Despite the increasing occurrence and prevalence of SRC, its underlying mechanism and recovery course have yet to be fully elucidated. The National Collegiate Athletic Association–Department of Defense Grand Alliance: Concussion Assessment, Research and Education (CARE) Consortium is a large-scale, multisite study of the natural history of concussion across multiple sports. The Advanced Research Core (ARC) of CARE is focused on the advanced biomarker assessment of a reduced subject cohort. This paper reports findings from two ARC sites to evaluate cerebral blood flow (CBF) changes in acute SRC, as measured using advanced arterial spin labeling (ASL) magnetic resonance imaging (MRI). We compared relative CBF maps assessed in 24 concussed contact sport athletes obtained at 24–48 h after injury to those of a control group of 24 matched contact sport players. Significantly less CBF was detected in several brain regions in concussed athletes, while clinical assessments also indicated clinical symptom and performance impairments in SRC patients. Correlations were found between decreased CBF in acute SRC and clinical assessments, including Balance Error Scoring System total score and Immediate Post-Concussion Assessment and Cognitive Test memory composite and impulse control composite scores, as well as days from injury to asymptomatic. Although using different ASL MRI sequences, our preliminary results from two sites are consistent with previous reports and suggest that advanced ASL MRI methods might be useful for detecting acute neurobiological changes in acute SRC.
  • Thumbnail Image
    Item
    Clinical Reaction-Time Performance Factors in Healthy Collegiate Athletes
    (Allen Press, 2020-06-23) Caccese, Jaclyn B.; Eckner, James T.; Franco-MacKendrick, Lea; Hazzard, Joseph B.; Ni, Meng; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael; Buckley, Thomas A.; Psychiatry, School of Medicine
    Context: In the absence of baseline testing, normative data may be used to interpret postconcussion scores on the clinical reaction-time test (RTclin). However, to provide normative data, we must understand the performance factors associated with baseline testing. Objective: To explore performance factors associated with baseline RTclin from among candidate variables representing demographics, medical and concussion history, self-reported symptoms, sleep, and sport-related features. Design: Cross-sectional study. Setting: Clinical setting (eg, athletic training room). Patients or other participants: A total of 2584 National Collegiate Athletic Association student-athletes (n = 1206 females [47%], 1377 males [53%], and 1 unreported (<0.1%); mass = 76.7 ± 18.7 kg; height = 176.7 ± 11.3 cm; age = 19.0 ± 1.3 years) from 3 institutions participated in this study as part of the Concussion Assessment, Research and Education Consortium. Main outcome measure(s): Potential performance factors were sex; race; ethnicity; dominant hand; sport type; number of prior concussions; presence of anxiety, learning disability, attention-deficit disorder or attention-deficit/hyperactivity disorder, depression, or migraine headache; self-reported sleep the night before the test; mass; height; age; total number of symptoms; and total symptom burden at baseline. The primary study outcome measure was mean baseline RTclin. Results: The overall RTclin was 202.0 ± 25.0 milliseconds. Female sex (parameter estimate [B] = 8.6 milliseconds, P < .001, Cohen d = 0.54 relative to male sex), black or African American race (B = 5.3 milliseconds, P = .001, Cohen d = 0.08 relative to white race), and limited-contact (B = 4.2 milliseconds, P < .001, Cohen d = 0.30 relative to contact) or noncontact (B = 5.9 milliseconds, P < .001, Cohen d = 0.38 relative to contact) sport participation were associated with slower RTclin. Being taller was associated with a faster RTclin, although this association was weak (B = -0.7 milliseconds, P < .001). No other predictors were significant. When adjustments are made for sex and sport type, the following normative data may be considered (mean ± standard deviation): female, noncontact (211.5 ± 25.8 milliseconds), limited contact (212.1 ± 24.3 milliseconds), contact (203.7 ± 21.5 milliseconds); male, noncontact (199.4 ± 26.7 milliseconds), limited contact (196.3 ± 23.9 milliseconds), contact (195.0 ± 23.8 milliseconds). Conclusions: Potentially clinically relevant differences existed in RTclin for sex and sport type. These results provide normative data adjusting for these performance factors.
  • Thumbnail Image
    Item
    Comparison of Psychological Response between Concussion and Musculoskeletal Injury in Collegiate Athletes
    (American Psychological Association, 2017) Turner, Samantha; Langdon, Jody; Shaver, George; Graham, Victoria; Naugle, Kelly; Buckley, Thomas; Kinesiology, School of Physical Education and Tourism Management
    The psychological response to musculoskeletal injuries has been well documented, however, research on the psychological response to concussion is limited. The Profile of Mood States (POMS) and the State-Trait Anxiety Inventory (STAI) have recently been used to assess the psychological recovery of concussions. Although some studies indicate that psychological response is different for musculoskeletal injuries and concussion, there is currently not enough information to indicate this difference occurs at specific clinical milestones. The purpose of this study was to compare the psychological responses of student-athletes who have been diagnosed with a concussion to those of athletes diagnosed with musculoskeletal injuries with similar recovery duration. Fifteen collegiate athletes who sustained a musculoskeletal injury were recruited and matched with 15 previously collected concussion participants. The main outcome measures were the scores of POMS constructs: tension-anxiety, anger-hostility, fatigue-inertia, depression-dejection, vigor-activity, confusion-bewilderment, and total mood disturbance and STAI (state anxiety only). Two-way MANOVAs was run to determine the effects of group and time on POMS and STAI constructs. There were no significant interactions identified, but follow-up ANOVAs identified a main effect for time for most POMS subscales, with POMS scores improving over time in both groups. Analyses also revealed that tension-anxiety, vigor-activity and the STAI were not affected by time or group. The findings of this study, that both groups' psychological response to injury improves over time and at similar clinical milestones suggests reduction in sports and team related activities may play a substantial role in the psychological response to either concussion or musculoskeletal injury.
  • Thumbnail Image
    Item
    Diffusion Tensor Imaging Reveals Elevated Diffusivity of White Matter Microstructure that Is Independently Associated with Long-Term Outcome after Mild Traumatic Brain Injury: A TRACK-TBI Study
    (Mary Ann Liebert, 2022) Palacios, Eva M.; Yuh, Esther L.; Mac Donald, Christine L.; Bourla, Ioanna; Wren-Jarvis, Jamie; Sun, Xiaoying; Vassar, Mary J.; Diaz-Arrastia, Ramon; Giacino, Joseph T.; Okonkwo, David O.; Robertson, Claudia S.; Stein, Murray B.; Temkin, Nancy; McCrea, Michael A.; Levin, Harvey S.; Markowitz, Amy J.; Jain, Sonia; Manley, Geoffrey T.; Mukherjee, Pratik; TRACK-TBI Investigators; Psychiatry, School of Medicine
    Diffusion tensor imaging (DTI) literature on single-center studies contains conflicting results regarding acute effects of mild traumatic brain injury (mTBI) on white matter (WM) microstructure and the prognostic significance. This larger-scale multi-center DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a cohort study at 11 United States level 1 trauma centers, a total of 391 patients with acute mTBI ages 17 to 60 years were included and studied at two weeks and six months post-injury. Demographically matched friends or family of the participants were the control group (n = 148). Axial diffusivity (AD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were the measures of WM microstructure. The primary outcome was the Glasgow Outcome Scale Extended (GOSE) score of injury-related functional limitations across broad life domains at six months post-injury. The AD, MD, and RD were higher and FA was lower in mTBI versus friend control (FC) at both two weeks and six months post-injury throughout most major WM tracts of the cerebral hemispheres. In the mTBI group, AD and, to a lesser extent, MD decreased in WM from two weeks to six months post-injury. At two weeks post-injury, global WM AD and MD were both independently associated with six-month incomplete recovery (GOSE <8 vs = 8) even after accounting for demographic, clinical, and other imaging factors. DTI provides reliable imaging biomarkers of dynamic WM microstructural changes after mTBI that have utility for patient selection and treatment response in clinical trials. Continued technological advances in the sensitivity, specificity, and precision of diffusion magnetic resonance imaging hold promise for routine clinical application in mTBI.
  • Thumbnail Image
    Item
    Head impact accelerations for brain strain-related responses in contact sports: a model-based investigation
    (Springer, 2014-10) Ji, Songbai; Zhao, Wei; Li, Zhigang; McAllister, Thomas W.; Psychiatry, School of Medicine
    Both linear (alin) and rotational (arot) accelerations contribute to head impacts on the field in contact sports; however, they are often isolated in injury studies. It is critical to evaluate the feasibility of estimating brain responses using isolated instead of full degrees-of-freedom (DOFs) accelerations. In this study, we investigated the sensitivities of regional brain strain-related responses to resultant alin and arot as well as the relative contributions of these acceleration components to the responses via random sampling and linear regression using parameterized, triangulated head impacts with kinematic variable values based on on-field measurements. Two independently established and validated finite element models of the human head were employed to evaluate model consistency and dependency in results: the Dartmouth Head Injury Model (DHIM) and Simulated Injury Monitor (SIMon). For the majority of the brain, volume-weighted regional peak strain, strain rate, and von Mises stress accumulated from the simulation significantly correlated to the product of the magnitude and duration of arot, or effectively, the rotational velocity, but not to alin. Responses from arot-only were comparable to the full-DOFs counterparts especially when normalized by injury-causing thresholds (e.g., volume fractions of large differences virtually diminished (i.e., <1%) at typical difference percentage levels of 1–4% on average). These model-consistent results support the inclusion of both rotational acceleration magnitude and duration into kinematics-based injury metrics, and demonstrate the feasibility of estimating strain-related responses from isolated arot for analyses of strain-induced injury relevant to contact sports without significant loss of accuracy, especially for the cerebrum.