Longitudinal white-matter abnormalities in sports-related concussion

Wu, Yu-Chien; Harezlak, Jaroslaw; Elsaid, Nahla M. H.; Lin, Zikai; Wen, Qiuting; Mustafi, Sourajit M.; Riggen, Larry; Koch, Kevin M.; Nencka, Andrew S.; Meier, Timothy B.; Mayer, Andrew R.; Wang, Yan; 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.

doi:10.1212/wnl.0000000000009930

Cited by 57 publications

(66 citation statements)

References 47 publications

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“…Neuroimaging and clinical data were collected at the 24-48 h, asymptomatic, post-RTP, and 6-month visits (10). Athletes were followed over multiple years of sport participation, which allowed tracking of re-injury incidence.…”

Section: Participants and Proceduresmentioning

confidence: 99%

“…MRI protocols/processing have been previously described (10). Scans were acquired on Siemens MAGNETOM 3T Tim Trio or Prisma scanners at Virginia Tech, University of North Carolina at Chapel Hill, and University of California, Los Angeles.…”

Section: Participants and Proceduresmentioning

confidence: 99%

“…Voxels were deemed significant if p < 0.05 after being adjusted for multiple comparisons by controlling family-wise error rate (FWER) within the white matter skeleton. The regression models used in TBSS controlled for pertinent demographic factors (i.e., age and sex), as well as site and scanner differences, as previously described (10).…”

Section: Participants and Proceduresmentioning

confidence: 99%

“…Regardless of the observed direction, studies have shown that early diffusion metrics correlate with traditional clinical measures following concussion [e.g., inventory of concussion-related symptoms, inventory of psychological symptoms of distress, and time to RTP; (10)]. Other studies have shown that persistent signal alterations remain even after symptom resolution and RTP (2,7,11).…”

Section: Introductionmentioning

confidence: 99%

“…The National Collegiate Athletic Association (NCAA) and the US Department of Defense (DoD) Grand Alliance Concussion Assessment, Research and Education (CARE) Consortium is a multi-center study conducted over multiple years that provides a unique opportunity to address this hypothesis. Recent work from the CARE Consortium observed persistent elevations in MD in concussed athletes in the corpus callosum acutely following injury (i.e., 24-48 h), as well as at three additional time points after clinical recovery: following resolution of symptoms (asymptomatic), 7 days following unrestricted RTP (post-RTP), and 6 months post-injury (10). The current study investigated whether persistent DTI signal (i.e., elevations in MD) in these previously identified regions were different among athletes with and without a subsequent re-injury within the following 1year period.…”

Section: Introductionmentioning

confidence: 99%

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The Association Between Persistent White-Matter Abnormalities and Repeat Injury After Sport-Related Concussion

Brett

Mustafi

et al. 2020

Front. Neurol.

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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 [χ 2 (1) = 4.17, p = 0.057; B = 0.03, SE = 0.017; OR = 1.03, CI = 0.99, 1.07]. Brett et al. Re-injury and DTI 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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Section: Participants and Proceduresmentioning

confidence: 99%

Section: Participants and Proceduresmentioning

confidence: 99%

Section: Participants and Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Association Between Persistent White-Matter Abnormalities and Repeat Injury After Sport-Related Concussion

Brett

Mustafi

et al. 2020

Front. Neurol.

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Associations of prior concussion severity with brain microstructure using mean apparent propagator magnetic resonance imaging

Goeckner,

Brett,

Mayer

et al. 2023

Human Brain Mapping

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Magnetic resonance imaging (MRI) diffusion studies have shown chronic microstructural tissue abnormalities in athletes with history of concussion, but with inconsistent findings. Concussions with post‐traumatic amnesia (PTA) and/or loss of consciousness (LOC) have been connected to greater physiological injury. The novel mean apparent propagator (MAP) MRI is expected to be more sensitive to such tissue injury than the conventional diffusion tensor imaging. This study examined effects of prior concussion severity on microstructure with MAP‐MRI. Collegiate‐aged athletes (N = 111, 38 females; ≥6 months since most recent concussion, if present) completed semistructured interviews to determine the presence of prior concussion and associated injury characteristics, including PTA and LOC. MAP‐MRI metrics (mean non‐Gaussian diffusion [NG Mean], return‐to‐origin probability [RTOP], and mean square displacement [MSD]) were calculated from multi‐shell diffusion data, then evaluated for associations with concussion severity through group comparisons in a primary model (athletes with/without prior concussion) and two secondary models (athletes with/without prior concussion with PTA and/or LOC, and athletes with/without prior concussion with LOC only). Bayesian multilevel modeling estimated models in regions of interest (ROI) in white matter and subcortical gray matter, separately. In gray matter, the primary model showed decreased NG Mean and RTOP in the bilateral pallidum and decreased NG Mean in the left putamen with prior concussion. In white matter, lower NG Mean with prior concussion was present in all ROI across all models and was further decreased with LOC. However, only prior concussion with LOC was associated with decreased RTOP and increased MSD across ROI. Exploratory analyses conducted separately in male and female athletes indicate associations in the primary model may differ by sex. Results suggest microstructural measures in gray matter are associated with a general history of concussion, while a severity‐dependent association of prior concussion may exist in white matter.

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