Challenges and Opportunities for Neuroimaging in Young Patients with Traumatic Brain Injury: a Coordinated Effort towards Advancing Discovery from the ENIGMA Pediatric Moderate/Severe TBI Group

Abstract

Traumatic brain injury (TBI) is a major cause of death and disability in children in both developed and developing nations. Children and adolescents suffer from TBI at a higher rate than the general population; however, research in this population lags behind research in adults. This may be due, in part, to the smaller number of investigators engaged in research with this population and may also be related to changes in safety laws and clinical practice that have altered length of hospital stays, treatment, and access to this population. Specific developmental issues also warrant attention in studies of children, and the ever-changing context of childhood and adolescence may require larger sample sizes than are commonly available to adequately address remaining questions related to TBI. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric Moderate-Severe TBI (msTBI) group aims to advance research in this area through global collaborative meta-analysis. In this paper we discuss important challenges in pediatric TBI research and opportunities that we believe the ENIGMA Pediatric msTBI group can provide to address them. We conclude with recommendations for future research in this field of study.

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

“…ENIGMA's Brain Injury WG 111 combines data from 72 centers, and is organized into ten separate subgroups that focus on (1) acute mild traumatic brain injury (TBI), (2) adult moderate/severe TBI 112 , (3) pediatric moderate/ severe TBI 113,114 , (4) military-related brain injury [115][116][117][118] , (5) sports-related concussion 119 , (6) intimate partner violence 120 , (7) MR spectroscopy 121 , (8) arterial spin labeling, (9) resting state fMRI, and (10) cognitive endpoints. These groups have recently started-up compared to other ENIGMA WGs, but are rapidly expanding in membership and focus.…”

“…Another limitation of this type of data is that the depth of phenotyping varies across centers, which can lead to a limited set of clinical and other scales shared by all centers. As we discuss below, ENIGMA is now beginning to address these limitations with a series of newly funded and planned studies 111,112,114,[118][119][120][121] . The paucity of longitudinal data in the literature is also reflected within ENIGMA, which includes a limited number of longitudinal studies.…”

Longitudinal Neuroimaging in Pediatric Traumatic Brain Injury: Current State and Consideration of Factors That Influence Recovery

“…Additionally, the longitudinal neuroimaging studies that have been published to date are limited to investigations of pediatric TBI populations with injuries sustained no earlier than the early childhood stage of development (ages 4-6), which is likely due to difficulties associated with scanning infants and toddlers. The literature would greatly benefit from investigations of children who sustained accidental injuries at younger ages, however, and current efforts to develop multi-step procedures that ensure the comfort of young children in the MRI environment [see (170)]. The body of literature in this area is small but becomes even smaller when we consider how many individual cohorts have been examined: the tables included in this review indicate that 20 articles on 13 longitudinal cohorts have been published to date.…”

Longitudinal fixel-based analysis reveals restoration of white matter alterations following balance training in young brain-injured patients

“…An important limitation is the relatively small sample size, which hindered our ability to test specific hypotheses regarding the role of specific demographic variables (e.g., age) and injury-related variables (such as age at injury and time since injury) on the gross motor performance changes and training-related structural plasticity changes. Through the ENIGMA pediatric moderate/severe TBI group ( Dennis et al, 2020a , Dennis et al, 2020b ), we aim to improve statistical power to address these open questions (for a paper in preprint, see Dennis et al, 2020a , Dennis et al, 2020b ). Another limitation, which is shared with other current FBA studies, is the heterogeneous nature of TBI lesions.…”