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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, and specific developmental issues require a unique context since findings from adult research do not necessarily directly translate to children. Findings in pediatric cohorts tend to lag behind those in adult samples. This may be due, in part, both 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. 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 of neuroimaging data. 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. With the paucity of research studies examining neuroimaging biomarkers in pediatric patients with TBI and the challenges of recruiting large numbers of participants, collaborating to improve statistical power and to address technical challenges like lesions will significantly advance the field. We conclude with recommendations for future research in this field of study.

BackgroundMethodsResultsConclusionsAbbreviationsDepression, anxiety, and stress are persistent and co-occurring symptoms in survivors of childhood traumatic brain injury (TBI), and often impact on health-related quality of life (HRQoL). This paper explored emotional distress symptom clusters and associated factors in young adults with childhood TBI.We included 54 young adults who sustained mild (n = 14), moderate (n = 27), and severe (n = 13) childhood TBI, at 20 years post-injury. The Depression Anxiety Stress Scale was administered. Cluster group membership was identified using two-step clustering and hierarchical clustering methods, and associated factors were assessed with multiple regression models.Two symptom cluster groups were identified, including a No Distress (n = 66%) and an Elevated Distress (n = 33%) group, with the latter showing significantly higher symptoms of depression, anxiety, and stress (all p < .001). Elevated Distress group membership was linked to tobacco use and poor sleep quality, while poor HRQoL was associated with younger age at injury and Elevated Distress group membership.Using cluster methodology, we showed that one-third of young adults with childhood TBI had elevated emotional distress symptoms. This underscores the complex emotional profile of this subgroup and the need for assessment, analysis, and treatment methods that target a range of symptoms rather than relying on single-diagnostic protocols.ANOVA: Analysis of Variance; CT: Computed Tomography; DASS: Depression Anxiety Stress Scale; GCS: Glasgow Coma Scale; HREC: Human Research Ethics Committee; HRQoL: Health-Related Quality of Life; IBM: International Business Machines Corporation; MRI: Magnetic Resonance Imaging; PTA: Post-Traumatic Amnesia; QoL: Quality of Life; QOLIBRI: Quality of Life after Brain Injury Scale; REDCap: Research Electronic Data Capture; SES: Socioeconomic Status; SPSS: Statistical Package for the Social Sciences; TBI: Traumatic Brain Injury. [ABSTRACT FROM AUTHOR]

This prospective, longitudinal case–control study examined global and domain-specific aspects of self-esteem 6-months following pediatric traumatic brain injury (TBI) and evaluated the contribution of injury-related factors and parent mental health to child self-esteem. Participants included 103 children with mild-severe TBI representing consecutive admissions to the emergency department of the Royal Children's Hospital, Melbourne, Australia. Forty-three age-and-sex matched typically developing controls were recruited for comparison. Information regarding injury characteristics including age at injury and clinical indicators of TBI severity were collected for participants at recruitment, with research magnetic resonance imaging conducted 2–8 weeks later. At 6 months post-injury, children rated their global and domain-specific self-esteem (Harter Self-Perception Profile for Children), and ratings of parent mental health were collected (General Health Questionnaire). Self-esteem for behavioural and academic domains was significantly poorer for children with TBI relative to TD children. In the TBI group, higher child-rated scores of global and domain-specific aspects of self-esteem were associated with more severe TBI, presence of frontal neuropathology, younger age at injury, and lower parental symptoms of anxiety/insomnia. Given the psychological status of parents represents a potentially modifiable risk factor, it may form the target of clinical interventions designed to bolster child self-esteem following pediatric TBI. [ABSTRACT FROM AUTHOR]

Although childhood traumatic brain injury (TBI) has been linked to heightened risk of impaired social skills and behavior, current evidence is weakened by small studies of variable methodological quality. To address these weaknesses, this international multi-cohort study involved synthesis of data from two large observational cohort studies of complicated mild-severe child TBI in Australia and North America. Both studies adopted a unified approach to data collection and coding procedures, providing the opportunity to merge datasets from multiple, well-characterized cohorts for which gold standard measures of social outcomes were collected during the chronic recovery phase. The study involved 218 children, including 33 children with severe TBI, 83 children with complicated mild-moderate TBI, 59 children with orthopedic injury, and 43 age- and sex-matched typically developing control children. All injured children were recruited from academic children's hospitals and underwent direct cognitive assessments including measures of theory of mind (ToM) at least 1-year post- injury. Parents rated their child's social adjustment using standardized measures of social skills, communication and behavior. Results showed a brain-injury specific effect on ToM abilities, such that children with both complicated mild to moderate and severe TBI displayed significantly poorer ToM than children without TBI. In mediator models, poorer ToM predicted poorer parent-rated self-direction and social skills, as well as more frequent behavioral symptoms. The ToM mediated the effect of severe TBI on parent ratings of communication and social skills, as well as on overall behavior symptoms. The findings suggest that deficits in ToM are evident across the spectrum of TBI severity and represent one mechanism linking severe child TBI to long-term social adjustment difficulties. The findings underscore the value of large-scale data harmonization projects to increase the quality of evidence regarding the outcomes of TBI. Clinical and scientific implications are discussed. [ABSTRACT FROM AUTHOR]

This study assessed the consequences of childhood traumatic brain injury (TBI) on sleep, fatigue, depression, and quality of life (QoL) outcomes and explored the relationships between these variables at 20 years following childhood TBI. We followed up 54 young adults with mild, moderate, and severe TBI, and 13 typically developing control (TDC) participants, recruited at the time of TBI. Sleep was assessed with the Pittsburgh Sleep Quality Index and actigraphy. At 20 years postinjury, results showed no significant difference between whole TBI group and TDC participants on subjective sleep quality; however, the moderate TBI group reported significantly poorer subjective sleep quality compared to those with severe TBI. Poorer subjective sleep was associated with increased symptoms of fatigue, depression, and poorer perceptions of General Health in the TBI group. Actigraphic sleep efficiency, fatigue, depression, and QoL outcomes were not significantly different between TBI and TDC or among TBI severity groups. These preliminary findings underscore associations between subjective sleep disturbance, fatigue, depression, and QoL in this TBI sample, and mostly comparable outcomes in sleep, fatigue, depression, and QoL between the TBI and TDC groups. Further research is required to clarify these findings. [ABSTRACT FROM AUTHOR]

Social dysfunction is a common and disabling outcome of childhood traumatic brain injury (TBI); however, the mechanisms that link early brain injury to impaired social behavior are unclear. This longitudinal prospective study involved 129 children, including 86 children with TBI (53 mild, 33 moderate-severe TBI) and 43 age-matched typically developing control (TDC) children. Children with TBI were recruited via consecutive admissions to the emergency department of the Royal Children's Hospital, Melbourne Australia. At 6 months post-injury, all participants were assessed on measures of intellectual functioning, and parents provided ratings of children's self-regulation skills using gold standard measures of everyday executive function. At 12-month follow up, parents rated children's social adjustment using standardized measures of social skills, communication, and behavior. As expected, children with moderate-severe TBI were rated by parents as having greater self-regulation problems, worse social skills, and poorer communication than the mild TBI and TDC groups. In mediation models, greater self-regulation problems at 6 months post-injury were predictive of poorer social skills and worse overall social adjustment at 12-month follow-up. Moreover, self-regulation skills mediated the effect of moderate-severe TBI, but not mild TBI, on social skills and overall social adjustment. Our findings show that, while impaired social adjustment is common at 12 months following moderate-severe child TBI, the impact of TBI on these outcomes is likely mediated by its effect on self-regulation skills. Evidence for robust prospective associations between self-regulation deficits and later social adjustment difficulties have implications for early identification of children at high risk for chronic social problems. [ABSTRACT FROM AUTHOR]

Quality of life (QoL) is commonly affected in children and families living with traumatic brain injury (TBI). Despite the established link between childhood TBI and reduced health-related QoL (HRQoL), there is a dearth of longitudinal, prospective research to determine the prevalence and predictors of impaired HRQoL in the very long term post-injury. We evaluated HRQoL in young adult survivors of paediatric TBI at 15 years post-injury. We aimed to identify the prevalence of impaired HRQoL and the respective contribution of pre-injury, environmental, injury-related, cognitive and mood-based factors to various dimensions of HRQoL at 15 years post-injury. This prospective study involved 52 young adult survivors of mild to severe TBI included from consecutive hospital admissions to the Royal Children's Hospital Melbourne, Australia between 1993 and 1997. Participants underwent neuropsychological evaluation and completed self-report measures of HRQoL, psychological functioning and social communication at 15 years post-injury. As compared with an age-matched Australian normative sample, the TBI group reported significantly poorer physical HRQoL at 15 years post-injury. Although group differences in other HRQoL domains did not reach statistical significance, 52% of the TBI group reported impaired functioning in at least one HRQoL domain. Contrary to expectations, HRQoL was not associated with injury severity, socioeconomic status, or pre-injury functioning. Instead, poorer HRQoL was linked to more severe depression symptoms, greater perceived social communication difficulty and reduced cognitive flexibility at 15 years post-injury. A substantial proportion of young adult survivors of childhood TBI experience poor HRQoL in at least one domain of functioning at 15 years post-injury. These findings suggest that, even in the very long term post-injury, the identification and treatment of modifiable risk factors has potential to improve very-long-term HRQoL outcomes in this vulnerable population. [ABSTRACT FROM AUTHOR]

• Child perceptions of academic competence were lower after traumatic brain injury. • Both demographic and family variables predicted child ratings of self-competence. • Greater family integration and routine may improve children's perceived competence.. Demographic and environmental factors can affect child recovery after traumatic brain injury (TBI); however, little is known about their role in predicting child perceptions of competence (i.e., subjective judgments of ability or a sense of adequacy). This prospective, cohort study examined the contribution of participant sex, age at assessment, socioeconomic status, parent-reported change in academic performance post-injury, and the quality of a child's relationship with their family (i.e., family affective involvement, intimacy, integration, and the nature of family roles) to child perceptions of global and academic competence 12 months after pediatric TBI. Participants included 127 children, 84 with a TBI (53 mild, 31 moderate-severe TBI; injury age: 5-15 years) and 43 age-matched typically developing (TD) controls. Children rated their perceptions of global and academic competence and degree of family intimacy and integration. Parents completed questionnaires measuring socioeconomic status, family affective involvement, and the nature of family roles. Parents also indicated whether they perceived a change in their child's post-injury academic performance. Child perceptions of academic competence were significantly lower for children with moderate-severe TBI relative to TD children. In contrast, child perceptions of global competence were comparable between TBI and TD control groups. Socioeconomic status, age at assessment, parent-reported relative change in academic performance post-TBI, and family roles were associated with child perceptions of academic competence. Degree of family integration was the sole predictor of child perceptions of global competence. Child perceptions of academic competence are vulnerable to the effects of moderate-severe TBI, particularly among older children and those from low socioeconomic backgrounds. Well-defined family roles and greater integration of family units might enhance perceptions of global and academic competence in children with TBI. [ABSTRACT FROM AUTHOR]

Social dysfunction is common after traumatic brain injury (TBI), contributing to reduced quality of life for survivors. Factors which influence the development or persistence of social deficits after injury remain poorly understood, particularly in the context of ongoing brain maturation during childhood and adolescence. Aberrant social interactions have recently been modeled in adult and juvenile rodents after experimental TBI, providing an opportunity to gain new insights into the underlying neurobiology of these behaviors. Here, we review our current understanding of social dysfunction in both humans and rodent models of TBI, with a focus on brain injuries acquired during early development. Modulators of social outcomes are discussed, including injury-related and environmental risk and resilience factors. Disruption of social brain network connectivity and aberrant neuroendocrine function are identified as potential mechanisms of social impairments after pediatric TBI. Throughout, we highlight the overlap and disparities between outcome measures and findings from clinical and experimental approaches, and explore the translational potential of future research to prevent or ameliorate social dysfunction after childhood TBI. [ABSTRACT FROM AUTHOR]

Objectives: To investigate rates of clinically significant externalizing behavior (EB) in young adult survivors of pediatric traumatic brain injury (TBI) and evaluate the contribution of pre- and postinjury risk and resilience factors to EB outcomes 16 years after injury. Setting: Melbourne, Australia. Participants: Fifty-five young adults (mean age = 23.85 years; injury age: 1.0-12 years) admitted to an emergency department following TBI between 1993 and 1997. Design: Longitudinal prospective study with data collected at the acute, 10-year, and 16-year postinjury time points. Main Measures: Severity of TBI, adaptive functioning, family functioning, full-scale IC^ executive functioning, social communication, and symptoms of EB. Results: One of every 4 young people with a history of pediatric TBI demonstrated clinical or subthreshold levels of EB in young adulthood. More frequent EB was associated with poorer preinjury adaptive functioning, lower full-scale IQ^ and more frequent pragmatic communication difficulty. Conclusion: Pediatric TBI is associated with an elevated risk for externalizing disorders in the transition to adulthood. Results underscore the need for screening and assessment of TBI among young offenders and suggest that early and long-term targeted interventions may be required to address risk factors for EB in children and young people with TBI. [ABSTRACT FROM AUTHOR]

Emotion perception (EP) forms an integral part of social communication and is critical to attain developmentally appropriate goals. This skill, which emerges relatively early in development, is driven by increasing connectivity among regions of a distributed sociocognitive neural network and may be vulnerable to disruption from early-childhood traumatic brain injury (TBI). The present study aimed to evaluate the very-long-term effect of childhood TBI on EP, as well as examine the contribution of injury- and non-injury-related risk and resilience factors to variability in sociocognitive outcomes. Thirty-four young adult survivors of early-childhood TBI (mean [M], 20.62 years; M time since injury, 16.55 years) and 16 typically developing controls matched for age, gender, and socioeconomic status were assessed using tasks that required recognition and interpretation of facial and prosodic emotional cues. Survivors of severe childhood TBI were found to have significantly poorer emotion perception than controls and young adults with mild-to-moderate injuries. Further, poorer emotion perception was associated with reduced volume of the posterior corpus callosum, presence of frontal pathology, lower SES, and a less-intimate family environment. Our findings lend support to the vulnerability of the immature 'social brain' network to early disruption and underscore the need for context-sensitive rehabilitation that optimizes early family environments to enhance recovery of EP skills after childhood TBI. [ABSTRACT FROM AUTHOR]

Highlights: [•] We investigate very-long social outcomes in 34 young adult survivors of pediatric TBI, and 16 healthy controls. [•] Results provide evidence for persisting socio-cognitive and communicative dysfunction 16-years post-TBI. [•] Greater social communication difficulty is linked to more frequent externalizing behaviors. [•] Social communication mediates the relationship between emotion perception and externalizing behaviors in the TBI sample. [ABSTRACT FROM AUTHOR]

Recent evidence suggests social cognitive deficits may be among the most profound and disabling consequences of childhood traumatic brain injury (TBI); however, it is only over the last decade that this area has received increasing research attention. This study aims to systematically review all studies reporting on the effects of childhood TBI on social cognition. Meta-analytic techniques were employed to determine the magnitude of social cognitive deficits in childhood TBI. Literature searches were conducted in electronic databases (Medline/PubMed, Scopus, Cochrane, EMBASE, PsycINFO and CINAHL) to retrieve relevant articles on social cognitive outcomes of paediatric TBI published from 2007–2019. The systematic review identified fourteen eligible studies, which examined the effect of paediatric TBI on five dimensions of social cognition, including emotion recognition or perception, theory of Mind (ToM), pragmatic language, moral reasoning, and social problem solving. Of these studies, eleven articles were included in subsequent meta-analyses, which included 482 children with TBI. Meta-analysis using a random-effects model revealed non-significant differences between TBI and typically developing (TD) control groups on measures of emotion perception or recognition. In contrast, children and adolescents with TBI performed significantly worse than control groups on ToM and pragmatic language tasks, with small and medium effect sizes, respectively (Hedge’s g = -0.46; -0.73). Meta-regression indicated that post-injury social cognitive deficits were not moderated by child age. While the effect of time since injury was not statistically significant, poorer social cognitive outcomes are documented soon after injury. Despite relatively intact basic social cognitive skills (i.e. emotion perception or recognition) children and adolescents with TBI are vulnerable to deficits in higher-order aspects of social cognition, including ToM and pragmatic language. These findings underscore the importance of further research, using well-validated, standardised outcome instruments, in larger paediatric TBI samples. Furthermore, longitudinal prospective studies are needed to evaluate the respective contribution of injury and non-injury factors to individual variation in outcome and recovery of social cognition after paediatric TBI. [ABSTRACT FROM AUTHOR]

Despite growing research linking childhood traumatic brain injury (TBI) with reduced wellbeing, self-esteem, and psycho-social health, very few studies have examined self-esteem and its correlates in young adult survivors of childhood TBI. This very-long-term follow-up study evaluated self-esteem in 29 young adults with a history of childhood TBI (M time since injury = 13.84 years; SD = 0.74), and 10 typically developing controls (TDCs). All participants were originally recruited into a larger, longitudinal case-control study between 2007 and 2010. In the current follow-up study, both groups completed well-validated measures of self-esteem and mental health in young adulthood. Although group means for self-esteem did not significantly differ between TBI and TDC groups, a higher proportion of TBI participants rated their self-esteem in the clinical range (TBI group = 17%; TDC group = 0%). While self-esteem was not significantly associated with injury or pre-injury child or family characteristics, lower self-esteem was significantly correlated with greater concurrent feelings of loneliness (p = 0.007) and higher concurrent mood symptoms (p < 0.001).Our results suggest that social isolation and low mood may represent meaningful targets for psycho-social interventions to address poor self-worth in young adults with a history of childhood TBI. [ABSTRACT FROM AUTHOR]

Previous studies in pediatric traumatic brain injury (TBI) have been variable in describing the effects of injury severity on white-matter development. The present study used diffusion tensor imaging to investigate prospective sub-acute and longitudinal relationships between early clinical indicators of injury severity, diffusion metrics, and neuropsychological outcomes. Pediatric patients with TBI underwent magnetic resonance imaging (MRI) ( n = 78, mean [M] = 10.56, standard deviation [SD] = 2.21 years) at the sub-acute stage after injury (M = 5.55, SD = 3.05 weeks), and typically developing children were also included and imaged ( n = 30, M = 10.60, SD = 2.88 years). A sub-set of the patients with TBI ( n = 15) was followed up with MRI 2 years post-injury. Diffusion MRI images were acquired at sub-acute and 2-year follow-up time points and analyzed using Tract-Based Spatial Statistics. At the sub-acute stage, mean diffusivity and axial diffusivity were significantly higher in the TBI group compared with matched controls ( p < 0.05). TBI severity significantly predicted diffusion profiles at the sub-acute and 2-year post-injury MRI. Patients with more severe TBI also exhibited poorer information processing speed at 6-months post-injury, which in turn correlated with their diffusion metrics. These findings highlight that the severity of the injury not only has an impact on white-matter microstructure, it also impacts its recovery over time. Moreover, findings suggest that sub-acute microstructural changes may represent a useful prognostic marker to identify children at elevated risk for longer term deficits. [ABSTRACT FROM AUTHOR]

Abstract Childhood and adolescence represent sensitive developmental periods for brain networks implicated in a range of complex skills, including executive functions (EF; inhibitory control, working memory, and cognitive flexibility). As a consequence, these skills may be particularly vulnerable to injuries sustained during these sensitive developmental periods. The present study investigated 1) whether age at injury differentially affects EF 6 months and 2 years after TBI in children aged 5–15 years, and 2) whether the association between brain lesions and EF depend on age at injury. Children with TBI (n = 105) were categorized into four age-at-injury groups based on previous studies and proposed timing of cerebral maturational spurts: early childhood (5–6 years, n = 14), middle childhood (7–9 years, n = 24), late childhood (10–12 years, n = 52), and adolescence (13–15 years, n = 15). EF were assessed with performance-based tasks and a parent-report of everyday EF. TBI patients' EF scores 6 months and 2 years post-injury were compared to those of typically developing (TD) controls (n = 42). Brain lesions were identified using susceptibility weighted imaging (SWI). Results indicated that inhibitory control performance 2 years post-injury was differentially affected by the impact of TBI depending on age at injury. Follow-up analyses did not reveal significant differences within the age groups, preventing drawing strong conclusions regarding the contribution of age at injury to EF outcome after TBI. Tentatively, large effect sizes suggest that vulnerability is most apparent in early childhood and adolescence. Everyday inhibitory control behaviour was worse for children with TBI than TD children across childhood and adolescence at the 2-year assessment. There was no evidence for impairment in working memory or cognitive flexibility after TBI at the group level. Given small group sizes, findings from analyses into correlations between EF and SWI lesions should be interpreted with caution. Extent, number and volume of brain lesions correlated with adolescent everyday EF behaviour 6 months post-injury. Taken together, the results emphasize the need for long-term follow-up after paediatric TBI during sensitive developmental periods given negative outcomes 2-year post injury. Inhibitory control seems to be particular vulnerable to the impact of TBI. Findings of associations between EF and SWI lesions need to be replicated with larger samples. Highlights • Inhibitory control has been established sensitive to (long-term) consequences of TBI. • SWI is associated with parent-reported EF behaviour of adolescents. • Early childhood and adolescence may be vulnerable periods for TBI impact on EF. [ABSTRACT FROM AUTHOR]

Children with traumatic brain injury (TBI) are at risk for social impairment, but research has yet to document the trajectory of these skills post-injury and factors that may predict social problems. This study addressed these gaps in knowledge, reporting on findings from a prospective, longitudinal follow-up study that investigated social outcomes post-injury and explored factors contributing to these outcomes at two years post-injury. The sample included 113 children, 74 with TBI and 39 typically developing (TD) controls. TBI participants were recruited on presentation to the hospital. Parents rated pre-injury function at that time, and all children underwent magnetic resonance imaging (MRI). Participants were followed up at two years post-injury. Outcomes were social adjustment, social participation, social relationships, and social cognition. Predictors of social outcomes examined included brain lesion characteristics, child cognition (6 months post-TBI), and behavior and environmental factors (pre-injury and two years). Reduced social adjustment ( p = 0.011) and social participation ( p < 0.001) were evident in children with TBI compared with TD controls. Poor social adjustment was predicted by externalizing behavior problems and younger age at injury. Reduced social participation was linked to internalizing behavior problems. Greater lesion volume, lower socioeconomic status, and family burden contributed to poorer social relationships, whereas age at injury predicted social cognition. Within the TBI group, 23% of children exhibited social impairments. Younger age at injury, greater pre-injury, and current behavior problems and family dysfunction, and poorer intelligence quotient (IQ), processing speed, and empathy were linked to impairment. Further follow-up is required to track social recovery and the influences of cognition, brain, and environment over time. [ABSTRACT FROM AUTHOR]