Multimodal Analysis of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury.

Journal: JAMA network open

Volume: 6

Issue: 11

Year of Publication: 2023

Affiliated Institutions:  TBI and Concussion Center, Department of Neurology, University of Utah School of Medicine, Salt Lake City. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia. Institute of Neuropharmacology, Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran. Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles. Department of Radiology, Loma Linda University Medical Center, Loma Linda, California. Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Victoria, Australia. Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, New York. Children's Learning Institute, Department of Pediatrics, University of Texas Health Science Center at Houston. Steve Tisch BrainSPORT Program, University of California, Los Angeles. Department of Psychology, Brigham Young University, Provo, Utah. Center for Biobehavioral Health, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio. Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles. Emma Neuroscience Group, Emma Children's Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. Department of Psychiatry, University of California, San Diego, La Jolla. H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas. Department of Psychology, Norwegian University of Science and Technology, Trondheim, Norway. Department of Psychological Sciences, Texas Tech University, Lubbock. South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Cape Town University, Cape Town, South Africa. Kennedy Krieger Institute, Baltimore, Maryland. Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada. Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey.

Abstract summary 

Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning.To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function.This retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or healthy controls (some with orthopedic injury) were recruited from trauma centers, clinics, and institutional trauma registries, some of which were followed longitudinally over a period of 0.7 to 1.9 years. Healthy controls were recruited from the surrounding community. Data analysis occurred from October to December 2022.Accidental mild complicated-severe TBI (msTBI) for those in the TBI group. Some controls received a diagnosis of orthopedic injury.Volume of 18 cerebellar lobules and vermal regions were estimated from 3-dimensional T1-weighted magnetic resonance imaging (MRI) scans. White matter organization in 28 regions of interest was assessed with diffusion tensor MRI. Executive function was measured by parent-reported scores from the Behavior Rating Inventory of Executive Functioning.A total of 598 children and adolescents (mean [SD] age, 14.05 [3.06] years; range, 5.45-19.70 years; 386 male participants [64.5%]; 212 female participants [35.5%]) were included in the study, with 314 participants in the msTBI group, and 284 participants in the non-TBI group (133 healthy individuals and 151 orthopedically injured individuals). Significantly smaller total cerebellum volume (d = -0.37; 95% CI, -0.52 to -0.22; P < .001) and subregional cerebellum volumes (eg, corpus medullare; d = -0.43; 95% CI, -0.58 to -0.28; P < .001) were observed in the msTBI group. These alterations were primarily seen in participants in the chronic phase (ie, >6 months postinjury) of injury (total cerebellar volume, d = -0.55; 95% CI, -0.75 to -0.35; P < .001). Smaller cerebellum volumes were associated with higher scores on the Behavior Rating Inventory of Executive Functioning Global Executive Composite score (β = -208.9 mm3; 95% CI, -319.0 to -98.0 mm3; P = .008) and Metacognition Index score (β = -202.5 mm3; 95% CI, -319.0 to -85.0 mm3; P = .02). In a subset of 185 participants with longitudinal data, younger msTBI participants exhibited cerebellum volume reductions (β = 0.0052 mm3; 95% CI, 0.0013 to 0.0090 mm3; P = .01), and older participants slower growth rates. Poorer white matter organization in the first months postinjury was associated with decreases in cerebellum volume over time (β=0.52 mm3; 95% CI, 0.19 to 0.84 mm3; P = .005).In this cohort study of pediatric msTBI, our results demonstrated robust cerebellar volume alterations associated with pediatric TBI, localized to the posterior lobe. Furthermore, longitudinal cerebellum changes were associated with baseline diffusion tensor MRI metrics, suggesting secondary cerebellar atrophy. These results provide further understanding of secondary injury mechanisms and may point to new opportunities for intervention.

Authors & Co-authors:  Keleher Finian F Lindsey Hannah M HM Kerestes Rebecca R Amiri Houshang H Asarnow Robert F RF Babikian Talin T Bartnik-Olson Brenda B Bigler Erin D ED Caeyenberghs Karen K Esopenko Carrie C Ewing-Cobbs Linda L Giza Christopher C CC Goodrich-Hunsaker Naomi J NJ Hodges Cooper B CB Hoskinson Kristen R KR Irimia Andrei A Königs Marsh M Max Jeffrey E JE Newsome Mary R MR Olsen Alexander A Ryan Nicholas P NP Schmidt Adam T AT Stein Dan J DJ Suskauer Stacy J SJ Ware Ashley L AL Wheeler Anne L AL Zielinski Brandon A BA Thompson Paul M PM Harding Ian H IH Tate David F DF Wilde Elisabeth A EA Dennis Emily L EL

Study Outcome 

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Statistics
Citations :  Schneier AJ, Shields BJ, Hostetler SG, Xiang H, Smith GA. Incidence of pediatric traumatic brain injury and associated hospital resource utilization in the United States. Pediatrics. 2006;118(2):483-492. doi:10.1542/peds.2005-2588
Authors :  32
Identifiers
Doi : e2343410
SSN : 2574-3805
Study Population
Male,Female
Mesh Terms
Adolescent
Other Terms
Study Design
Cohort Study,Longitudinal Study,Cross Sectional Study
Study Approach
Country of Study
Publication Country
United States