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Advanced magnetic resonance imaging (MRI) techniques indicate that concussion (i.e., mild traumatic brain injury) disrupts brain structure and function in children. However, the functional connectivity of brain regions within global and local networks (i.e., functional connectome) is poorly understood in pediatric concussion. This prospective, longitudinal study addressed this gap using data from the largest neuroimaging study of pediatric concussion to date to study the functional connectome longitudinally after concussion as compared with mild orthopedic injury (OI). Children and adolescents ( n  = 967) 8-16.99 years with concussion or mild OI were recruited from pediatric emergency departments within 48 h post-injury. Pre-injury and 1-month post-injury symptom ratings were used to classify concussion with or without persistent symptoms based on reliable change. Subjects completed a post-acute (2-33 days) and chronic (3 or 6 months via random assignment) MRI scan. Graph theory metrics were derived from 918 resting-state functional MRI scans in 585 children (386 concussion/199 OI). Linear mixed-effects modeling was performed to assess group differences over time, correcting for multiple comparisons. Relative to OI, the global clustering coefficient was reduced at 3 months post-injury in older children with concussion and in females with concussion and persistent symptoms. Time post-injury and sex moderated group differences in local (regional) network metrics of several brain regions, including degree centrality, efficiency, and clustering coefficient of the angular gyrus, calcarine fissure, cuneus, and inferior occipital, lingual, middle occipital, post-central, and superior occipital gyrus. Relative to OI, degree centrality and nodal efficiency were reduced post-acutely, and nodal efficiency and clustering coefficient were reduced chronically after concussion (i.e., at 3 and 6 months post-injury in females; at 6 months post-injury in males). Functional network alterations were more robust and widespread chronically as opposed to post-acutely after concussion, and varied by sex, age, and symptom recovery at 1-month post-injury. Local network segregation reductions emerged globally (across the whole brain network) in older children and in females with poor recovery chronically after concussion. Reduced functioning between neighboring regions could negatively disrupt specialized information processing. Local network metric alterations were demonstrated in several posterior regions that are involved in vision and attention after concussion relative to OI. This indicates that functioning of superior parietal and occipital regions could be particularly susceptibile to the effects of concussion. Moreover, those regional alterations were especially apparent at later time periods post-injury, emerging after post-concussive symptoms resolved in most and persisted up to 6 months post-injury, and differed by biological sex. This indicates that neurobiological changes continue to occur up to 6 months after pediatric concussion, although changes emerge earlier in females than in males. Changes could reflect neural compensation mechanisms.

Higher psychological resilience is correlated with less severe post-concussion symptoms (PCS) after mild traumatic brain injury (mTBI) in children, but the directional nature of this relationship remains uncertain. Although traditionally regarded as a stable, trait-like construct, resilience may be malleable and potentially influenced by mTBI and post-concussive symptoms. The current study sought to examine the stability of resilience, elucidate the dynamic nature of the resilience-PCS relation, and determine whether resilience-symptom associations are specific to mTBI or applicable to traumatic injury in general. Participants were children aged 8-16.99 years with either mTBI ( n  = 633) or orthopedic injury (OI; n  = 334) recruited to participate in a prospective cohort study after presenting acutely to five Canadian pediatric emergency departments (EDs). Symptoms and psychological resilience were assessed at 1 week, 3 months, and 6 months post-injury. Group differences in resilience over time were examined using a mixed linear model, and associations between resilience and symptoms over time were examined using random intercepts cross-lagged panel modeling (RI-CLPM). The mTBI group reported significantly lower resilience than the OI group, but the difference was significantly larger 1 week post-injury ( d  = 0.50) than at 3 months ( d  = 0.08) and 6 months ( d  = 0.10). Cross-lagged panel models indicated that resilience had both stable and dynamic aspects, and both affected and was affected by PCS, although their association varied by time post-injury, symptom measure, and reporter (parent vs. child). Higher parent-reported cognitive symptom severity at 1 week was significantly associated with higher resilience at 3 months ( β  = 0.23, p  = 0.001). Higher resilience at 3 months was associated with lower levels of parent-reported somatic symptom severity ( β  = -0.14, p  = 0.004) and fewer total symptoms ( β  = -0.135, p  = 0.029) at 6 months. Higher resilience at 3 months was associated with fewer child-reported symptoms at 6 months ( β  = -0.11, p  = 0.030) and, reciprocally, fewer child-reported symptoms at 3 months were associated with higher resilience at 6 months ( β  = -0.22, p  = 0.001). Notably, injury group was not a significant moderator in cross-lagged models, suggesting that resilience-symptom associations are not specific to mTBI. Psychological resilience and symptoms have bidirectional relationships after injury. Interventions designed to foster resilience have the potential to promote recovery after mTBI specifically and injury more generally.

Pediatric traumatic brain injury (TBI) can lead to adverse emotional, social, and behavioral consequences. However, outcome is difficult to predict due to significant individual variability, likely reflecting a complex interaction between injury- and child-related variables. Among these variables are genetically determined individual differences, which can modulate TBI outcome through their influence on neuroplasticity mechanisms. In this study, we examined the effect of Val66Met, a common polymorphism of the brain-derived neurotrophic factor gene known to be involved in neuroplasticity mechanisms, on behavioral symptoms of mild TBI (mTBI) sustained in early childhood. This work is part of a prospective, longitudinal cohort study of early TBI. The current sample consisted of 145 children between ages 18 and 60 months assigned to one of three participant groups: mild TBI, orthopedic injury, or typically developing children. Participants provided a saliva sample to detect the presence of the Val66Met polymorphism, and the Child Behavior Checklist was used to document the presence of behavioral symptoms at 6- and 18-months post-injury. Contrary to our initial hypothesis, at 6 months post-injury, non-carriers of the Val66Met polymorphism in the mTBI group presented significantly more internalizing symptoms (e.g., anxiety/depression and somatic complaints) than Val66Met carriers, who were similar to orthopedically injured and typically developing children. However, at 18 months post-injury, all children with mTBI presented more internalizing symptoms, independent of genotype. The results of the study provide evidence for a protective effect of the Val66Met polymorphism on internalizing behavior symptoms 6 months after early childhood mTBI.

Given the lack of evidence regarding effective pharmacological and non-pharmacological interventions for pediatric mild traumatic brain injury (mTBI) and the resultant lack of treatment recommendations reflected in consensus guidelines, variation in the management of pediatric mTBI is to be expected. We therefore surveyed practitioners across 15 centers in the United States and Canada who care for children with pediatric mTBI to evaluate common-practice variation in the management of pediatric mTBI. The survey, developed by a panel of pediatric mTBI experts, consisted of a 10-item survey instrument regarding providers' perception of common pediatric mTBI symptoms and mTBI interventions. Surveys were distributed electronically to a convenience sample of local experts at each center. Frequencies and percentages (with confidence intervals [CI]) were determined for survey responses. One hundred and seven respondents (71% response rate) included specialists in pediatric Emergency Medicine, Sports Medicine, Neurology, Neurosurgery, Neuropsychology, Neuropsychiatry, Physical and Occupational Therapy, Physiatry/Rehabilitation, and General Pediatrics. Respondents rated headache as the most prevalently reported symptom after pediatric mTBI, followed by cognitive problems, dizziness, and irritability. Of the 65 (61%; [95% CI: 51,70]) respondents able to prescribe medications, non-steroidal anti-inflammatory medications (55%; [95% CI: 42,68]) and acetaminophen (59%; [95% CI: 46,71]) were most commonly recommended. One in five respondents reported prescribing amitriptyline for headache management after pediatric mTBI, whereas topiramate (8%; [95% CI: 3,17]) was less commonly reported. For cognitive problems, methylphenidate (11%; [95% CI: 4,21]) was used more commonly than amantadine (2%; [95% CI: 0,8]). The most common non-pharmacological interventions were rest ("always" or "often" recommended by 83% [95% CI: 63,92] of the 107 respondents), exercise (59%; [95%CI: 49,69]), vestibular therapy (42% [95%CI: 33,53]) and cervical spine exercises (29% [95%CI: 21,39]). Self-reported utilization for common pediatric mTBI interventions varied widely across our Canadian and United States consortium. Future effectiveness studies for pediatric mTBI are urgently needed to advance the evidence-based care.

The identification of clinical phenotypes may help parse the substantial heterogeneity that characterizes children with concussion. This study used latent class analysis (LCA) to identify discernible phenotypes among children with acute concussion and examine the association between phenotypes and persistent post-concussive symptoms (PPCS) at 4 and 12 weeks post-injury. We conducted LCA of variables representing pre-injury history, clinical presentation, and parent symptom ratings, derived from a prospective cohort, observational study that recruited participants from August 2013 until June 2015 at nine pediatric emergency departments within the Pediatric Emergency Research Canada network. This substudy included 2323 children from the original cohort ages 8.00-17.99 years who had data for at least 80% of all variables included in each LCA. Concussion was defined according to Zurich consensus statement diagnostic criteria. The primary outcome was PPCS at 4 and 12 weeks after enrollment. Participants were 39.5% female and had a mean age of 12.8 years (standard deviation = 2.6). Follow-up was completed by 1980 (85%) at 4 weeks and 1744 (75%) at 12 weeks. LCA identified four groups with discrete pre-injury histories, four groups with discrete clinical presentations, and seven groups with discrete profiles of acute symptoms. Clinical phenotypes based on the profile of group membership across the three LCAs varied significantly in their predicted probability of PPCS at 4 and 12 weeks. The results indicate that children with concussion can be grouped into distinct clinical phenotypes, based on pre-injury history, clinical presentation, and acute symptoms, with markedly different risks of PPCS. With further validation, clinical phenotypes may provide a useful heuristic for clinical assessment and management.

A significant proportion of children and adolescents report psychological distress following concussion, but little is known about the predictors of these problems. The purpose of this study was to examine predictive factors of psychological distress following pediatric concussion. It was hypothesized that the presence of pre-injury psychological distress would be the strongest predictor of psychological distress post-concussion, with other demographic and acute injury factors adding incrementally to prediction. This is a prospective, multi-center cohort. Children and adolescents (6-17 years old; n = 311) who sustained a concussion and were assessed through four pediatric emergency departments. Participants were reassessed at 4-weeks (n = 275) and 12-weeks (n = 190) post-injury. Emergency department (ED) assessment documented injury mechanism, acute symptomatology, acute cognitive functioning, and pre-injury functioning. Psychological distress at 4- and 12-weeks follow-up was categorized as present if one or more psychological scores from the parent-completed measures (Child Behavior Checklist, Strengths and Difficulties Questionnaire) exceeded established cutoffs. The presence of psychological distress at each follow-up was predicted using multi-variable logistic regressions. Psychological distress was reported in 23% of youth at both 4- and 12-weeks post-concussion. A pre-injury diagnosis of anxiety and acutely forgetting recent information were significant predictors of psychological distress at 4 weeks, whereas worse acute orientation assessment in the ED predicted psychological distress at 12 weeks. Nearly one of four youth experienced psychological distress after concussion. Clinicians in acute care settings should screen for the factors (pre-injury anxiety, acute mental status) associated with post-injury psychological distress and consider proactively referring patients for further assistance.

A critical component for accelerating the clinical uptake of research data in the area of pediatric concussion or mild traumatic brain injury (MTBI) pertains to the establishment and utilization of common databases. The objective of the first phase of our CanPedCDE initiative was to agree upon pediatric common data elements (CDEs) that could best characterize children with MTBI over their recovery period. The selection of CDEs for our framework aimed to balance factors such as the comprehensiveness of outcomes collected, their applicability to diverse settings, as well as the costs associated with their use. Selection began by identifying relevant domains of functioning (e.g., post-concussion symptoms, attention, and balance). Two sources were used to make this process more efficient: 1) the World Health Organization International Classification of Functioning (ICF) Traumatic Brain Injury Core Set, and the U.S. National Institute of Neurological Disorders and Stroke Traumatic Brain Injury Common Data Elements, both of which had already suggested relevant domains to include in TBI research. The process was completed in two phases: 1) using an online survey of experts and 2) through an in-person consensus meeting. Measurement tools were also proposed that were best felt to capture these domains. Forty experts in MTBI in children from multiple health-related perspectives (e.g., emergency medicine, pediatrics, neurosurgery, nursing, physiotherapy, and neuroscience), as well as knowledge users, participated in the selection process. The final list of CDEs included 77 distinct areas of functioning, covering all categories of the ICF model. Outcome measures were attached to each element, when applicable. The CanPedCDE initiative addresses a significant limitation in MTBI research to date and may help both researchers and clinicians to organize and standardize their assessment of children and youth post-MTBI in order to move the field in promising directions.

Pediatric traumatic brain injury (TBI) research depends on comparisons of profiles and outcomes between brain-injured individuals and groups consisting either of injured controls (e.g., orthopedic injuries, OI) or uninjured, typically developing children recruited from the community (community controls, CC). Children with OI are thought to provide optimal comparisons for individuals with TBI because they share injury-related experiences and pre-morbid characteristics; however, a study by Mathias and colleagues (2013)1 in adults has called into question the added value of injury control groups in TBI research. The comparability of these control groups has not been established in young children. Seventy-two children with OI and 84 CC aged between 18 and 60 months were compared on a range of demographic variables, developmental and medical history, pre-injury behavioral and adaptive profiles, as well as on measures of adaptive functioning, behavior, family functioning, post-concussive symptoms, and cognition (intellectual functioning, verbal abilities, executive functioning, social cognition) 6 months after the OI. There were no statistically significant differences between the OI and CC groups on any of the variables tested, whether they related to pre-injury or post-injury characteristics. The findings are applicable to studies seeking to identify appropriate control groups in the context of preschool TBI research, and suggest no clear advantage in recruiting OI controls based on the variables studied and the methodology used. However, further work is necessary to verify additional factors and outcomes relevant to pediatric TBI research, as well as to compare outcomes between these two groups at more acute stages (i.e., prior to 6 months post-injury). [ABSTRACT FROM AUTHOR]