Browsing by Author "Giza, Christopher C."

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    Acute White-Matter Abnormalities in Sports-Related Concussion: A Diffusion Tensor Imaging Study from the NCAA-DoD CARE Consortium
    (Mary Ann Liebert, 2018-11-15) Mustafi, Sourajit Mitra; Harezlak, Jaroslaw; Koch, Kevin M.; Nencka, Andrew S.; Meier, Timothy B.; West, John D.; Giza, Christopher C.; DiFiori, John P.; Guskiewicz, Kevin M.; Mihalik, Jason P.; LaConte, Stephen M.; Duma, Stefan M.; Broglio, Steven P.; Saykin, Andrew J.; McCrea, Michael; McAllister, Thomas W.; Wu, Yu-Chien; Radiology and Imaging Sciences, School of Medicine
    Sports-related concussion (SRC) is an important public health issue. Although standardized assessment tools are useful in the clinical management of acute concussion, the underlying pathophysiology of SRC and the time course of physiological recovery after injury remain unclear. In this study, we used diffusion tensor imaging (DTI) to detect white matter alterations in football players within 48 h after SRC. As part of the NCAA-DoD CARE Consortium study of SRC, 30 American football players diagnosed with acute concussion and 28 matched controls received clinical assessments and underwent advanced magnetic resonance imaging scans. To avoid selection bias and partial volume effects, whole-brain skeletonized white matter was examined by tract-based spatial statistics to investigate between-group differences in DTI metrics and their associations with clinical outcome measures. Mean diffusivity was significantly higher in brain white matter of concussed athletes, particularly in frontal and subfrontal long white matter tracts. In the concussed group, axial diffusivity was significantly correlated with the Brief Symptom Inventory and there was a similar trend with the symptom severity score of the Sport Concussion Assessment Tool. In addition, concussed athletes with higher fractional anisotropy performed better on the cognitive component of the Standardized Assessment of Concussion. Overall, the results of this study are consistent with the hypothesis that SRC is associated with changes in white matter tracts shortly after injury, and these differences are correlated clinically with acute symptoms and functional impairments.
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    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.
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    Assessment of Blood Biomarker Profile After Acute Concussion During Combative Training Among US Military Cadets
    (JAMA, 2021-02) Giza, Christopher C.; McCrea, Michael; Huber, Daniel; Cameron, Kenneth L.; Houston, Megan N.; Jackson, Jonathan C.; McGinty, Gerald; Pasquina, Paul; Broglio, Steven P.; Brooks, Alison; DiFiori, John; Duma, Stefan; Harezlak, Jaroslaw; Goldman, Joshua; Guskiewicz, Kevin; McAllister, Thomas W.; McArthur, David; Meier, Timothy B.; Mihalik, Jason P.; Nelson, Lindsay D.; Rowson, Steven; Gill, Jessica; Foroud, Tatiana; Katz, Barry; Saykin, Andrew; Campbell, Darren E.; Svoboda, Steven; Psychiatry, School of Medicine
    Importance: Validation of protein biomarkers for concussion diagnosis and management in military combative training is important, as these injuries occur outside of traditional health care settings and are generally difficult to diagnose. Objective: To investigate acute blood protein levels in military cadets after combative training-associated concussions. Design, setting, and participants: This multicenter prospective case-control study was part of a larger cohort study conducted by the National Collegiate Athletic Association and the US Department of Defense Concussion Assessment Research and Education (CARE) Consortium from February 20, 2015, to May 31, 2018. The study was performed among cadets from 2 CARE Consortium Advanced Research Core sites: the US Military Academy at West Point and the US Air Force Academy. Cadets who incurred concussions during combative training (concussion group) were compared with cadets who participated in the same combative training exercises but did not incur concussions (contact-control group). Clinical measures and blood sample collection occurred at baseline, the acute postinjury point (<6 hours), the 24- to 48-hour postinjury point, the asymptomatic postinjury point (defined as the point at which the cadet reported being asymptomatic and began the return-to-activity protocol), and 7 days after return to activity. Biomarker levels and estimated mean differences in biomarker levels were natural log (ln) transformed to decrease the skewness of their distributions. Data were collected from August 1, 2016, to May 31, 2018, and analyses were conducted from March 1, 2019, to January 14, 2020. Exposure: Concussion incurred during combative training. Main outcomes and measures: Proteins examined included glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, neurofilament light chain, and tau. Quantification was conducted using a multiplex assay (Simoa; Quanterix Corp). Clinical measures included the Sport Concussion Assessment Tool-Third Edition symptom severity evaluation, the Standardized Assessment of Concussion, the Balance Error Scoring System, and the 18-item Brief Symptom Inventory. Results: Among 103 military service academy cadets, 67 cadets incurred concussions during combative training, and 36 matched cadets who engaged in the same training exercises did not incur concussions. The mean (SD) age of cadets in the concussion group was 18.6 (1.3) years, and 40 cadets (59.7%) were male. The mean (SD) age of matched cadets in the contact-control group was 19.5 (1.3) years, and 25 cadets (69.4%) were male. Compared with cadets in the contact-control group, those in the concussion group had significant increases in glial fibrillary acidic protein (mean difference in ln values, 0.34; 95% CI, 0.18-0.50; P < .001) and ubiquitin C-terminal hydrolase-L1 (mean difference in ln values, 0.97; 95% CI, 0.44-1.50; P < .001) levels at the acute postinjury point. The glial fibrillary acidic protein level remained high in the concussion group compared with the contact-control group at the 24- to 48-hour postinjury point (mean difference in ln values, 0.22; 95% CI, 0.06-0.38; P = .007) and the asymptomatic postinjury point (mean difference in ln values, 0.21; 95% CI, 0.05-0.36; P = .01). The area under the curve for all biomarkers combined, which was used to differentiate cadets in the concussion and contact-control groups, was 0.80 (95% CI, 0.68-0.93; P < .001) at the acute postinjury point. Conclusions and relevance: This study's findings indicate that blood biomarkers have potential for use as research tools to better understand the pathobiological changes associated with concussion and to assist with injury identification and recovery from combative training-associated concussions among military service academy cadets. These results extend the previous findings of studies of collegiate athletes with sport-associated concussions.
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    The Association Between Persistent White-Matter Abnormalities and Repeat Injury After Sport-Related Concussion
    (Frontiers Media, 2020-01-21) Brett, Benjamin L.; Wu, Yu-Chien; Mustafi, Sourajit M.; Saykin, Andrew J.; Koch, Kevin M.; Nencka, Andrew S.; Giza, Christopher C.; Goldman, Joshua; Guskiewicz, Kevin M.; Mihalik, Jason P.; Duma, Stefan M.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Meier, Timothy B.; Radiology and Imaging Sciences, School of Medicine
    Objective: A recent systematic review determined that the physiological effects of concussion may persist beyond clinical recovery. Preclinical models suggest that ongoing physiological effects are accompanied by increased cerebral vulnerability that is associated with risk for subsequent, more severe injury. This study examined the association between signal alterations on diffusion tensor imaging following clinical recovery of sport-related concussion in athletes with and without a subsequent second concussion. Methods: Average mean diffusivity (MD) was calculated in a region of interest (ROI) in which concussed athletes (n = 82) showed significantly elevated MD acutely after injury (<48 h), at an asymptomatic time point, 7 days post-return to play (RTP), and 6 months relative to controls (n = 69). The relationship between MD in the identified ROI and likelihood of sustaining a subsequent concussion over a 1-year period was examined with a binary logistic regression (re-injured, yes/no). Results: Eleven of 82 concussed athletes (13.4%) sustained a second concussion within 12 months of initial injury. Mean MD at 7 days post-RTP was significantly higher in those athletes who went on to sustain a repeat concussion within 1 year of initial injury than those who did not (p = 0.048; d = 0.75). In this underpowered sample, the relationship between MD at 7 days post-RTP and likelihood of sustaining a secondary injury approached significance [χ2 (1) = 4.17, p = 0.057; B = 0.03, SE = 0.017; OR = 1.03, CI = 0.99, 1.07]. Conclusions: These preliminary findings raise the hypothesis that persistent signal abnormalities in diffusion imaging metrics at RTP following concussion may be predictive of a repeat concussion. This may reflect a window of cerebral vulnerability or increased susceptibility following concussion, though understanding the clinical significance of these findings requires further study.
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    Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium
    (JAMA Network, 2020-01-03) McCrea, Michael; Broglio, Steven P.; McAllister, Thomas W.; Gill, Jessica; Giza, Christopher C.; Huber, Daniel L.; Harezlak, Jaroslaw; Cameron, Kenneth L.; Houston, Megan N.; McGinty, Gerald; Jackson, Jonathan C.; Guskiewicz, Kevin; Mihalik, Jason; Brooks, M. Alison; Duma, Stephan; Rowson, Steven; Nelson, Lindsay D.; Pasquina, Paul; Meier, Timothy B.; CARE Consortium Investigators; Foroud, Tatiana; Katz, Barry P.; Saykin, Andrew J.; Campbell, Darren E.; Svoboda, Steven J.; Goldman, Joshua; DiFiori, Jon; Psychiatry, School of Medicine
    Importance: There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective: To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants: This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures: Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results: A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group × visit) was found for GFAP (F7,1507.36 = 16.18, P < .001), UCH-L1 (F7,1153.09 = 5.71, P < .001), and tau (F7,1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F7,1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (β = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (β = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance: The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC.
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    Comparison of Head Impact Exposure Between Concussed Football Athletes and Matched Controls: Evidence for a Possible Second Mechanism of Sport-Related Concussion
    (Springer, 2018) Stemper, Brian D.; Shah, Alok S.; Harezlak, Jaroslaw; Rowson, Steven; Mihalik, Jason P.; Duma, Stefan M.; Riggen, Larry D.; Brooks, Alison; Cameron, Kenneth L.; Campbell, Darren; DiFiori, John P.; Giza, Christopher C.; Guskiewicz, Kevin M.; Jackson, Jonathan; McGinty, Gerald T.; Svoboda, Steven J.; McAllister, Thomas W.; Broglio, Steven P.; McCrea, Michael; Psychiatry, School of Medicine
    Studies of football athletes have implicated repetitive head impact exposure in the onset of cognitive and brain structural changes, even in the absence of diagnosed concussion. Those studies imply accumulating damage from successive head impacts reduces tolerance and increases risk for concussion. Support for this premise is that biomechanics of head impacts resulting in concussion are often not remarkable when compared to impacts sustained by athletes without diagnosed concussion. Accordingly, this analysis quantified repetitive head impact exposure in a cohort of 50 concussed NCAA Division I FBS college football athletes compared to controls that were matched for team and position group. The analysis quantified the number of head impacts and risk weighted exposure both on the day of injury and for the season to the date of injury. 43% of concussed athletes had the most severe head impact exposure on the day of injury compared to their matched control group and 46% of concussed athletes had the most severe head impact exposure for the season to the date of injury compared to their matched control group. When accounting for date of injury or season to date of injury, 72% of all concussed athletes had the most or second most severe head impact exposure compared to their matched control group. These trends associating cumulative head impact exposure with concussion onset were stronger for athletes that participated in a greater number of contact activities. For example, 77% of athletes that participated in ten or more days of contact activities had greater head impact exposure than their matched control group. This unique analysis provided further evidence for the role of repetitive head impact exposure as a predisposing factor for the onset of concussion. The clinical implication of these findings supports contemporary trends of limiting head impact exposure for college football athletes during practice activities in an effort to also reduce risk of concussive injury.
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    Effects of White-Matter Tract Length in Sport-Related Concussion: A Tractography Study from the NCAA-DoD CARE Consortium
    (Mary Ann Liebert, Inc., 2022-11) Mustafi, Sourajit M.; Yang, Ho-Ching; Harezlak, Jaroslaw; Meier, Timothy B.; Brett, Benjamin L.; Giza, Christopher C.; Goldman, Joshua; Guskiewicz, Kevin M.; Mihalik, Jason P.; LaConte, Stephen M.; Duma, Stefan M.; Broglio, Steven P.; McCrea, Michael A.; McAllister, Thomas W.; Wu, Yu-Chien; Psychiatry, School of Medicine
    Sport-related concussion (SRC) is an important public health issue. White-matter alterations after SRC are widely studied by neuroimaging approaches, such as diffusion magnetic resonance imaging (MRI). Although the exact anatomical location of the alterations may differ, significant white-matter alterations are commonly observed in long fiber tracts, but are never proven. In the present study, we performed streamline tractography to characterize the association between tract length and white-matter microstructural alterations after SRC. Sixty-eight collegiate athletes diagnosed with acute concussion (24–48 h post-injury) and 64 matched contact-sport controls were included in this study. The athletes underwent diffusion tensor imaging (DTI) in 3.0 T MRI scanners across three study sites. DTI metrics were used for tract-based spatial statistics to map white-matter regions-of-interest (ROIs) with significant group differences. Whole-brain white-mater streamline tractography was performed to extract “affected” white-matter streamlines (i.e., streamlines passing through the identified ROIs). In the concussed athletes, streamline counts and DTI metrics of the affected white-matter fiber tracts were summarized and compared with unaffected white-matter tracts across tract length in the same participant. The affected white-matter tracts had a high streamline count at length of 80–100 mm and high length-adjusted affected ratio for streamline length longer than 80 mm. DTI mean diffusivity was higher in the affected streamlines longer than 100 mm with significant associations with the Brief Symptom Inventory score. Our findings suggest that long fibers in the brains of collegiate athletes are more vulnerable to acute SRC with higher mean diffusivity and a higher affected ratio compared with the whole distribution.
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    Effects of White-Matter Tract Length in Sport-Related Concussion: A Tractography Study from the NCAA-DoD CARE Consortium
    (Mary Ann Liebert, 2022) Mustafi, Sourajit M.; Yang, Ho-Ching; Harezlak, Jaroslaw; Meier, Timothy B.; Brett, Benjamin L.; Giza, Christopher C.; Goldman, Joshua; Guskiewicz, Kevin M.; Mihalik, Jason P.; LaConte, Stephen M.; Duma, Stefan M.; Broglio, Steven P.; McCrea, Michael A.; McAllister, Thomas W.; Wu, Yu-Chien; Radiology and Imaging Sciences, School of Medicine
    Sport-related concussion (SRC) is an important public health issue. White-matter alterations after SRC are widely studied by neuroimaging approaches, such as diffusion magnetic resonance imaging (MRI). Although the exact anatomical location of the alterations may differ, significant white-matter alterations are commonly observed in long fiber tracts, but are never proven. In the present study, we performed streamline tractography to characterize the association between tract length and white-matter microstructural alterations after SRC. Sixty-eight collegiate athletes diagnosed with acute concussion (24–48 h post-injury) and 64 matched contact-sport controls were included in this study. The athletes underwent diffusion tensor imaging (DTI) in 3.0 T MRI scanners across three study sites. DTI metrics were used for tract-based spatial statistics to map white-matter regions-of-interest (ROIs) with significant group differences. Whole-brain white-mater streamline tractography was performed to extract “affected” white-matter streamlines (i.e., streamlines passing through the identified ROIs). In the concussed athletes, streamline counts and DTI metrics of the affected white-matter fiber tracts were summarized and compared with unaffected white-matter tracts across tract length in the same participant. The affected white-matter tracts had a high streamline count at length of 80–100 mm and high length-adjusted affected ratio for streamline length longer than 80 mm. DTI mean diffusivity was higher in the affected streamlines longer than 100 mm with significant associations with the Brief Symptom Inventory score. Our findings suggest that long fibers in the brains of collegiate athletes are more vulnerable to acute SRC with higher mean diffusivity and a higher affected ratio compared with the whole distribution.
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    Estimated age of first exposure to American football and outcome from concussion
    (Wolters Kluwer, 2020-11-24) Caccese, Jaclyn B.; Houck, Zac; Kaminski, Thomas W.; Clugston, James R.; Iverson, Grant L.; Bryk, Kelsey N.; Oldham, Jessie R.; Pasquina, Paul F.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael; Reed Hoy, April Marie; Hazzard, Joseph B., Jr.; Kelly, Louise A.; Ortega, Justus D.; Port, Nicholas; Putukian, Margot; Langford, T. Dianne; Giza, Christopher C.; Goldman, Joshua T.; Benjamin, Holly J.; Schmidt, Julianne D.; Feigenbaum, Luis A.; Eckner, James T.; Mihalik, Jason P.; Dysart Miles, Jessica; Anderson, Scott; Master, Christina L.; Collins, Micky W.; Kontos, Anthony P.; Chrisman, Sara P.D.; Brooks, Alison; Jackson, Jonathan C.; McGinty, Gerald; Cameron, Kenneth L.; Susmarski, Adam; O'Donnell, Patrick G.; Duma, Stefan; Rowson, Steve; Miles, Christopher M.; Bullers, Christopher T.; Dykhuizen, Brian H.; Lintner, Laura; Buckley, Thomas A.; Psychiatry, School of Medicine
    Objective: To examine the association between estimated age at first exposure (eAFE) to American football and clinical measures throughout recovery following concussion. Methods: Participants were recruited across 30 colleges and universities as part of the National Collegiate Athletic Association (NCAA)-Department of Defense Concussion Assessment, Research and Education Consortium. There were 294 NCAA American football players (age 19 ± 1 years) evaluated 24-48 hours following concussion with valid baseline data and 327 (age 19 ± 1 years) evaluated at the time they were asymptomatic with valid baseline data. Participants sustained a medically diagnosed concussion between baseline testing and postconcussion assessments. Outcome measures included the number of days until asymptomatic, Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) composite scores, Balance Error Scoring System (BESS) total score, and Brief Symptom Inventory 18 (BSI-18) subscores. The eAFE was defined as participant's age at the time of assessment minus self-reported number of years playing football. Results: In unadjusted regression models, younger eAFE was associated with lower (worse) ImPACT Visual Motor Speed (R 2 = 0.031, p = 0.012) at 24-48 hours following injury and lower (better) BSI-18 Somatization subscores (R 2 = 0.014, p = 0.038) when the athletes were asymptomatic. The effect sizes were very small. The eAFE was not associated with the number of days until asymptomatic, other ImPACT composite scores, BESS total score, or other BSI-18 subscores. Conclusion: Earlier eAFE to American football was not associated with longer symptom recovery, worse balance, worse cognitive performance, or greater psychological distress following concussion. In these NCAA football players, longer duration of exposure to football during childhood and adolescence appears to be unrelated to clinical recovery following concussion.
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    Flying After Concussion and Symptom Recovery in College Athletes and Military Cadets
    (AMA, 2020-11-02) Sharma, Tara L.; Kerrigan, Julia Morrow; McArthur, David L.; Bickart, Kevin; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael; Giza, Christopher C.; Psychiatry, School of Medicine
    Importance: Concussions are a common occurrence in young athletes. Hypobaric hypoxemia, such as that experienced during airplane travel, can potentially cause alterations to cerebral blood flow and increased neuroinflammatory response. It remains unknown whether flying early after a concussion may influence the clinical course of injury. Objective: To determine whether there is an association between concussion recovery and airplane travel in collegiate athletes and military cadets. Design, Setting, and Participants: This cohort study was conducted by the National Collegiate Athletic Association and US Department of Defense Concussion Assessment, Research, and Education Consortium from August 3, 2014, to September 13, 2018. Participant groups were categorized by those who flew within 72 hours of injury and those who did not fly. All participants included in the final analyses had complete data of interest and only 1 injury during the study. Data analysis was performed from September 2018 to March 2020. Main Outcomes and Measures: Recovery outcome measures were defined as time (in days) from injury to return to activity, school, and baseline symptoms. Symptom and headache severity scores were derived from the Sports Concussion Assessment Tool-Third Edition. Scores for both groups were taken at baseline and a median of 2 days after injury. Results: A total of 92 participants who flew (mean [SD] age, 19.1 [1.2] years; 55 male [59.8%]) and 1383 participants who did not fly (mean [SD] age, 18.9 [1.3] years; 809 male [58.5%]) were included in the analysis of symptom recovery outcomes (analysis 1). Similarly, 100 participants who flew (mean [SD] age, 19.2 [1.2] years; 63 male [63.0%]) and 1577 participants who did not fly (mean [SD] age, 18.9 [1.3] years; 916 male [58.1%]) were included in the analysis of symptom severity outcomes (analysis 2). No significant group differences were found regarding recovery outcome measures. Likewise, there were no group differences in symptom (estimated mean difference, 0.029; 95% CI, -0.083 to 0.144; P = .67) or headache (estimated mean difference, -0.007; 95% CI, -0.094 to 0.081; P = .91) severity scores. Conclusions and Relevance: Airplane travel early after concussion was not associated with recovery or severity of concussion symptoms. These findings may help guide future recommendations on flight travel after concussion in athletes.