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Longitudinal white matter microstructural changes in pediatric mild traumatic brain injury: An A‐CAP study
Abstract
In the largest sample studied to date, white matter microstructural trajectories and their relation to persistent symptoms were examined after pediatric mild traumatic brain injury (mTBI). This prospective, longitudinal cohort study recruited children aged 8–16.99 years with mTBI or mild orthopedic injury (OI) from five pediatric emergency departments. Children's pre‐injury and 1‐month post‐injury symptom ratings were used to classify mTBI with or without persistent symptoms. Children completed diffusion‐weighted imaging at post‐acute (2–33 days post‐injury) and chronic (3 or 6 months via random assignment) post‐injury assessments. Mean diffusivity (MD) and fractional anisotropy (FA) were derived for 18 white matter tracts in 560 children (362 mTBI/198 OI), 407 with longitudinal data. Superior longitudinal fasciculus FA was higher in mTBI without persistent symptoms relative to OI,d(95% confidence interval) = 0.31 to 0.37 (0.02, 0.68), across time. In younger children, MD of the anterior thalamic radiations was higher in mTBI with persistent symptoms relative to both mTBI without persistent symptoms, 1.43 (0.59, 2.27), and OI, 1.94 (1.07, 2.81). MD of the arcuate fasciculus, −0.58 (−1.04, −0.11), and superior longitudinal fasciculus, −0.49 (−0.90, −0.09) was lower in mTBI without persistent symptoms relative to OI at 6 months post‐injury. White matter microstructural changes suggesting neuroinflammation and axonal swelling occurred chronically and continued 6 months post injury in children with mTBI, especially in younger children with persistent symptoms, relative to OI. White matter microstructure appears more organized in children without persistent symptoms, consistent with their better clinical outcomes.
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“and another demonstrating time-dependent microstructural changes in anterior thalamic radiations among younger children with persistent symptoms (Ware et al., 2022)”
From A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury (2026) · cites this paper as Ware et al., 2022
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“In addition, 4 studies applied graph theoretical approaches, with 3 studies reporting altered network topology characterized by reduced global efficiency and disrupted hub connectivity in regions associated with executive control and salience networks, including the superior frontal gyrus, middle frontal gyrus, insula, and fusiform gyrus (Chung et al., 2019; Yuan et al., 2014; Ware et al., 2022;”
From A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury (2026) · cites this paper as Ware et al., 2022
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“disrupted hub connectivity in executive and salience networks”
From A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury (2026) · cites this paper as Ware et al., 2022
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“alongside reduced global network efficiency”
From A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury (2026) · cites this paper as Ware et al., 2022
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Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know
Gupte, R. P., Brooks, W. M., Vukas, R. R., Pierce, J. D., & Harris, J. L. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.6171 · Cited by 533
Diffusion tensor imaging of acute mild traumatic brain injury in adolescents
Wilde, E. A., McCauley, S. R., Hunter, J. V., Bigler, E. D., Chu, Z., Wang, Z. J., Hanten, G. R., Troyanskaya, M., Yallampalli, R., Li, X., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000305961.68029.54 · Cited by 525
Natural Progression of Symptom Change and Recovery From Concussion in a Pediatric Population
Ledoux, A.-A., Tang, K., Yeates, K. O., Pusic, M. V., Boutis, K., Craig, W. R., Gravel, J., Freedman, S. B., Gagnon, I., Gioia, G. A., et al. (2019) · JAMA Pediatrics · doi:10.1001/jamapediatrics.2018.3820 · Cited by 188
Self-citationSchilling, K. G., Rheault, F., Petit, L., Hansen, C. B., Nath, V., Yeh, F.-C., Girard, G., Barakovic, M., Rafael-Patino, J., Yu, T., et al. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118502 · Cited by 182
Self-citationAdelson, P. D., Pineda, J., Bell, M. J., Abend, N. S., Berger, R. P., Giza, C. C., Hotz, G., & Wainwright, M. S. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2011.1952 · Cited by 93
Fakhran, S., Yaeger, K., Collins, M., & Alhilali, L. (2014) · Radiology · doi:10.1148/radiol.14132512 · Cited by 83
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Cited by
Xu, H., Wu, S., Zhan, H., Xu, G., Zhao, J., & Yin, B. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1879109
Metadata
- Authors
- Ware, A. L., Yeates, K. O., Tang, K., Shukla, A., Onicas, A. I., Guo, S., Goodrich‐Hunsaker, N., Abdeen, N., Beauchamp, M. H., Beaulieu, C., Bjornson, B., Craig, W., Dehaes, M., Doan, Q., Deschenes, S., Freedman, S. B., Goodyear, B. G., Gravel, J., Ledoux, A., Zemek, R., Lebel, C., & Pediatric Emergency Research Canada A‐CAP Study Team
- Affiliations
- Department of Psychology, Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada
- Independent Statistical Consulting Richmond British Columbia Canada
- Department of Radiology, Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada
- Department of Neurology University of Utah Salt Lake City Utah USA
- Department of Radiology University of Ottawa, Children's Hospital of Eastern Ontario Research Institute Ottawa Ontario Canada
- Department of Psychology University of Montreal & CHU Sainte‐Justine Hospital Research Center Montréal Québec Canada
- Department of Biomedical Engineering University of Alberta Edmonton Alberta Canada
- Division of Neurology, Department of Pediatrics University of British Columbia, Vancouver, BC, Canada; 2. BC Children's Hospital Research Institute Vancouver British Columbia Canada
- University of Alberta and Stollery Children's Hospital Edmonton Alberta Canada
- Department of Radiology, Radio‐oncology and Nuclear Medicine, Institute of Biomedical Engineering University of Montreal; CHU Sainte‐Justine Research Center Montréal Québec Canada
- Department of Pediatrics, University of British Columbia BC Children's Hospital Research Institute Vancouver British Columbia Canada
- CHU Sainte‐Justine Research Center; Department of Radiology, Radio‐oncology and Nuclear Medicine University of Montreal Montréal Québec Canada
- Department of Emergency Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada
- Department of Pediatric Emergency Medicine, Department of Pediatrics CHU Sainte‐Justine, University of Montréal Montréal Québec Canada
- Department of Cellular and Molecular Medicine University of Ottawa, & Children's Hospital of Eastern Ontario Research Institute Ottawa Ontario Canada
- Department of Pediatrics and Emergency Medicine University of Ottawa, Children's Hospital of Eastern Ontario Research Institute Ottawa Ontario Canada
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2022-04-25
- Volume
- 43
- Issue
- 12
- Pages
- 3809-3823
- ISSN
- 1065-9471
- 1097-0193
- Cited by
- 36
- References
- 6
- Language
- en
- Funders
- Canadian Institutes of Health Research (FDN143304)
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