TY - JOUR
T1 - White Matter Disruption in Pediatric Traumatic Brain Injury
T2 - Results From ENIGMA Pediatric Moderate to Severe Traumatic Brain Injury
AU - Dennis, Emily L.
AU - Caeyenberghs, Karen
AU - Hoskinson, Kristen R.
AU - Merkley, Tricia L.
AU - Suskauer, Stacy J.
AU - Asarnow, Robert F.
AU - Babikian, Talin
AU - Bartnik-Olson, Brenda
AU - Bickart, Kevin
AU - Bigler, Erin D.
AU - Ewing-Cobbs, Linda
AU - Figaji, Anthony
AU - Giza, Christopher C.
AU - Goodrich-Hunsaker, Naomi J.
AU - Hodges, Cooper B.
AU - Hovenden, Elizabeth S.
AU - Irimia, Andrei
AU - Königs, Marsh
AU - Levin, Harvey S.
AU - Lindsey, Hannah M.
AU - Max, Jeffrey E.
AU - Newsome, Mary R.
AU - Olsen, Alexander
AU - Ryan, Nicholas P.
AU - Schmidt, Adam T.
AU - Spruiell, Matthew S.
AU - Wade, Benjamin S.C.
AU - Ware, Ashley L.
AU - Watson, Christopher G.
AU - Wheeler, Anne L.
AU - Yeates, Keith Owen
AU - Zielinski, Brandon A.
AU - Kochunov, Peter
AU - Jahanshad, Neda
AU - Thompson, Paul M.
AU - Tate, David F.
AU - Wilde, Elisabeth A.
N1 - Funding Information: P.M.T. received partial research support from Biogen, Inc, for research unrelated to this manuscript. J.E.M. reports medico-legal consultation approximately equally for plaintiffs and defendants at ≈10%. C.C.G. reports consulting for the National Basketball Association, National Football League, National Hockey League Players' Association, and Los Angeles Lakers, serving on the Advisory Board for Highmark Interactive, Novartis, Major League Soccer, National Basketball Association, US Soccer Federation, and medico-legal consultation for 1 to 2 cases annually. D.F.T. and E.D.B. additionally report medico-legal consultation. All other authors report no relevant financial disclosures. Go to Neurology.org/N for full disclosures. Funding Information: Funding provided by K99NS096116 (E.L.D.); R61NS120249 (E.L.D., D.F.T., E.A.W.); R01NS05400 (B.B.-O.); National Health and Medical Research Council Career Development Fellowship (K.C.); NRF SARChI Chair of Clinical Neurosciences (A.F.); UCLA Easton Clinic for Brain Health, Stan and Patty Silver, UCLA Brain Injury Research Center, R01HD061504 (C.C.G.); K01HD083459 (K.R.H.); R01NS100973, Department of Defense contract W81XWH-18-1-0413 and a Hanson-Thorell Research Scholarship (A.I.); R01HD088438 (JEM); K12HD001097, K23HD06161, UL1TR001079, 1S10OD021648 (S.J.S.); U54EB020403, R01MH116147, R56AG058854, P41EB015922, R01MH111671 (P.M.T.); K99MH119314, NARSAD 27786 (B.S.C.W.); and Ronald and Irene Ward Chair in Pediatric Brain Injury, funded by the Alberta Children's Hospital Foundation (K.O.Y.). Publisher Copyright: © American Academy of Neurology.
PY - 2021/7/20
Y1 - 2021/7/20
N2 - ObjectiveOur study addressed aims (1) to test the hypothesis that moderate-severe traumatic brain injury (TBI) in pediatric patients is associated with widespread white matter (WM) disruption, (2) to test the hypothesis that age and sex affect WM organization after injury, and (3) to examine associations between WM organization and neurobehavioral outcomes.MethodsData from 10 previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Pediatric Moderate/Severe TBI (msTBI) working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline.ResultsFive hundred seven children and adolescents (244 with complicated msTBI and 263 controls) were included. Patients were clustered into 3 postinjury intervals: acute/subacute, <2 months; postacute, 2 to 6 months; and chronic, ≥6 months. Outcomes were dMRI metrics and postinjury behavioral problems as indexed by the Child Behavior Checklist. Our analyses revealed altered WM diffusion metrics across multiple tracts and all postinjury intervals (effect sizes range d = -0.5 to -1.3). Injury severity is a significant contributor to the extent of WM alterations but explained less variance in dMRI measures with increasing time after injury. We observed a sex-by-group interaction: female patients with TBI had significantly lower fractional anisotropy in the uncinate fasciculus than controls (β = 0.043), which coincided with more parent-reported behavioral problems (β = -0.0027).ConclusionsWM disruption after msTBI is widespread, persistent, and influenced by demographic and clinical variables. Future work will test techniques for harmonizing neurocognitive data, enabling more advanced analyses to identify symptom clusters and clinically meaningful patient subtypes.
AB - ObjectiveOur study addressed aims (1) to test the hypothesis that moderate-severe traumatic brain injury (TBI) in pediatric patients is associated with widespread white matter (WM) disruption, (2) to test the hypothesis that age and sex affect WM organization after injury, and (3) to examine associations between WM organization and neurobehavioral outcomes.MethodsData from 10 previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Pediatric Moderate/Severe TBI (msTBI) working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline.ResultsFive hundred seven children and adolescents (244 with complicated msTBI and 263 controls) were included. Patients were clustered into 3 postinjury intervals: acute/subacute, <2 months; postacute, 2 to 6 months; and chronic, ≥6 months. Outcomes were dMRI metrics and postinjury behavioral problems as indexed by the Child Behavior Checklist. Our analyses revealed altered WM diffusion metrics across multiple tracts and all postinjury intervals (effect sizes range d = -0.5 to -1.3). Injury severity is a significant contributor to the extent of WM alterations but explained less variance in dMRI measures with increasing time after injury. We observed a sex-by-group interaction: female patients with TBI had significantly lower fractional anisotropy in the uncinate fasciculus than controls (β = 0.043), which coincided with more parent-reported behavioral problems (β = -0.0027).ConclusionsWM disruption after msTBI is widespread, persistent, and influenced by demographic and clinical variables. Future work will test techniques for harmonizing neurocognitive data, enabling more advanced analyses to identify symptom clusters and clinically meaningful patient subtypes.
UR - http://www.scopus.com/inward/record.url?scp=85122354212&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000012222
DO - https://doi.org/10.1212/WNL.0000000000012222
M3 - Article
SN - 0028-3878
VL - 97
SP - E298-E309
JO - Neurology
JF - Neurology
IS - 3
ER -