Pediatric cognitive reserve moderates the effect of brain structure in attention-deficit/hyperactivity disorder: Evidence for an optimized residual approach.

OBJECTIVE: To validate a residual-based cognitive reserve (CR) index optimized for a pediatric sample with attention-deficit/hyperactivity disorder (ADHD). METHOD: Participants were N = 115 children aged 9.5-13 years at baseline (Mage = 10.48 years, SDage = 0.61), and n = 43 (37.4%) met criteria for ADHD. Elastic-net regularized linear regression was used to generate baseline and longitudinal CR indices by maximally residualizing variance in fluid intelligence for demographics and brain structure. Academic and diagnostic outcomes were regressed onto CR indices, and interactions with brain integrity were assessed. RESULTS: Baseline CR predicted baseline math computation (estimate = 0.10, SE = 0.02, p < .001), while change in CR predicted change in word reading ability (estimate = 0.08, SE = 0.02, p < .001). Further, when grey matter volume tended to be lower, higher CR was associated with higher word reading score (estimate = -0.05, SE = 0.02, p = .019) and lower ADHD symptom severity (estimate = 0.04, SE = 0.02, p = .047) compared to lower CR, at baseline. Similarly, when longitudinal change in white matter hypointensity volume tended to be greater, higher change in CR resulted in more favorable word reading trajectory (estimate = 0.03, SE = 0.02, p = .048). CONCLUSIONS: A data-driven residual approach to operationalizing pediatric CR shows better evidence of construct validity over previous methods, with our index showing a novel ability to moderate the deleterious effects of lower grey matter on outcomes in ADHD. This approach may benefit future research aiming to study the early development of CR. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Developmental patterns of inhibition and fronto-basal-ganglia white matter organisation in healthy children and children with attention-deficit/hyperactivity disorder.

There is robust evidence implicating inhibitory deficits as a fundamental behavioural phenotype in children with attention-deficit/hyperactivity disorder (ADHD). However, prior studies have not directly investigated the role in which white matter properties within the fronto-basal-ganglia circuit may play in the development of inhibitory control deficits in this group. Combining recent advancements in brain-behavioural modelling, we mapped the development of stop-signal task (SST) performance and fronto-basal-ganglia maturation in a longitudinal sample of children aged 9-14 with and without ADHD. In a large sample of 135 ADHD and 138 non-ADHD children, we found that the ADHD group had poorer inhibitory control (i.e., longer stop-signal reaction times) across age compared to non-ADHD controls. When applying the novel parametric race model, this group effect was driven by higher within-subject variability (sigma) and higher number of extreme responses (tau) on stop trials. The ADHD group also displayed higher within-subject variability on correct responses to go stimuli. Moreover, we observed the ADHD group committing more task-based failures such as responding on stop trials (trigger failures) and omissions on go trials (go failures) compared to non-ADHD controls, suggesting the contribution of attentional lapses to poorer response inhibition performance. In contrast, longitudinal modelling of fixel-based analysis measures revealed no significant group differences in the maturation of fronto-basal-ganglia fibre cross-section in a subsample (74 ADHD and 73 non-ADHD children). Finally, brain-behavioural models revealed that age-related changes in fronto-basal-ganglia morphology (fibre cross-section) were significantly associated with reductions in the variability of the correct go-trial responses (sigma.true) and skew of the stop-trial distribution (tauS). However, this effect did not differ between ADHD and typically developing children. Overall, our findings support the growing consensus suggesting that attentional deficits subserve ADHD-related inhibitory dysfunction. Furthermore, we show novel evidence suggesting that while children with ADHD are consistently performing worse on the SST than their non-affected peers, they appear to have comparable rates of neurocognitive maturation across this period.

Early Childhood Concussion.

The unconsolidated motor and cognitive skills that are typical of the early childhood period place infants, toddlers, and preschoolers at risk for a variety of traumatic injuries. Such injuries may include mild traumatic brain injury or concussion. Knowledge regarding the risk, diagnosis, outcomes, and management of early childhood concussion is limited, especially compared with what is known about concussion in school-age children, adolescents, and adults. This state-of-the-art review aims to provide current knowledge on the epidemiology, physical signs, behavior, and clinical outcomes associated with early childhood concussion. Research on this condition has been challenged by the need to adapt methods to the unique physical, behavioral, and developmental characteristics of young children. We provide information on observable symptoms associated with concussion, recommended approaches to care, and suggestions for overcoming barriers to research in this area. Developmentally appropriate efforts are needed to improve our ability to identify, evaluate, and treat early childhood concussion.

Network analysis of structural MRI predicts executive function in paediatric traumatic brain injury.

INTRO: Paediatric traumatic brain injury (pTBI) is likely to result in cognitive impairment, specifically executive dysfunction. Evidence of the neuroanatomical correlates of this executive function (EF) impairment is derived from studies that treat morphometry of brain regions as distinct, independent features, rather than as a complex network of interrelationships. Morphometric similarity captures the meso-scale organisation of the cortex as the interrelatedness of multiple macro-architectural features and presents a novel tool with which to investigate the brain post pTBI. METHODS: In a retrospective sample (83 pTBI patients, 33 controls), we estimate morphometric similarity from structural MRI by correlating morphometric features between cortical regions. We compared the meso-scale organisation of the cortex between groups then, using partial least squares regression, assessed the predictive validity of morphometric similarity in understanding later executive functioning, two years post-injury. RESULTS: We found that patients and controls did not differ in terms of the overall magnitude of morphometric similarity. However, a pattern of ROI-level morphometric similarity was predictive of day-to-day EF difficulties reported by parents two years post-injury. This prediction was validated using a leave-one-out, and 20-fold cross-validation approach. Prediction was driven by regions of the prefrontal cortex, typically important for healthy maturation of EF skills in childhood. The meso-scale organisation of the cortex also produced more accurate predictions than any one morphometric feature (i.e. cortical thickness or folding index) alone. CONCLUSION: We conclude that these methodologies show utility in predicting later executive functioning in this population.

Feasibility of Concussion Essentials: A multimodal intervention for persisting post-concussion symptoms among children and adolescents.

This study examined the feasibility of "Concussion Essentials" (CE), an individualized, multimodal intervention for persisting post-concussion symptoms (pPCS). Thirteen 6-18 year-olds with pPCS at 1-month post-concussion, as determined by the Post Concussion Symptom Inventory - Parent Report (PCSI-P), completed education, physiotherapy, and psychology modules, for up to 8-weeks or until pPCS resolved. Intervention participants were matched to a longitudinal observational cohort who received usual care (n = 13). The study enrolled 70% of participants symptomatic on screening and the dropout rate was <30% between baseline and post-programme assessments (4-weeks to 3-months post-injury). Symptoms improved for 100% of CE participants, with the number of symptomatic items on the PCSI-P reducing from 4-weeks, Median (IQR) = 14.0 (8.0-19.0) to 3-months, Median (IQR) = 1.0 (0.0-5.0). Comparatively, symptoms improved for approximately half of matched usual care participants. CE participants (n = 8) and their parents (n = 11) completed acceptability questionnaires. Most parents (91%) agreed CE was acceptable for children with concussion. All participants agreed CE was appropriate for concussion, while approximately 88% agreed they enjoyed the intervention and would recommend CE to others. Findings suggest CE is a feasible and acceptable treatment for paediatric pPCS. Further investigation within a larger scale randomized clinical trial is warranted.

Exploring emotional distress symptom clusters in young adults with childhood traumatic brain injury.

BACKGROUND: Depression, 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. ABBREVIATIONS: 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.

White matter fiber morphology in persisting postconcussive symptoms and posttraumatic headache after pediatric concussion: a fixel-based analysis.

OBJECTIVE: Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion. METHODS: This prospective longitudinal study recruited children aged 5-18 years who presented to the emergency department of a tertiary pediatric hospital with a concussion sustained within the previous 48 hours. Participants underwent diffusion-weighted MRI at 2 weeks postinjury. Whole-brain white matter statistical analysis was performed at the level of each individual fiber population within an image voxel (fixel) to compute FD, FC, and a combined metric (FD and bundle cross-section [FDC]) using connectivity-based fixel enhancement. Tract-based Bayesian analysis was performed to examine FD in 23 major white matter tracts. RESULTS: Comparisons of 1) recovered (n = 27) and symptomatic (n = 16) children, and those with 2) PTH (n = 13) and non-PTH (n = 30; overall mean age 12.99 ± 2.70 years, 74% male) found no fiber-specific white matter microstructural differences in FD, FC, or FDC at 2 weeks postconcussion, when adjusting for age and sex (family-wise error rate corrected p value > 0.05). Tract-based Bayesian analysis showed evidence of no effect of PTH on FD in 10 major white matter tracts, and evidence of no effect of recovery group on FD in 3 white matter tracts (Bayes factor < 1/3). CONCLUSIONS: Using whole-brain fixel-wise and tract-based analyses, these findings indicate that fiber-specific properties of white matter microstructure are not different between children with persisting PCSs compared with recovered children 2 weeks after concussion. These data extend the limited research on white matter fiber-specific morphology while overcoming limitations inherent to traditional diffusion models. Further validation of our findings with a large-scale cohort is warranted.

Language and communication functioning in children and adolescents with agenesis of the corpus callosum.

The corpus callosum, the largest white matter inter-hemispheric pathway, is involved in language and communication. In a cohort of 15 children and adolescents (8-15 years) with developmental absence of the corpus callosum (AgCC), this study aimed to describe language and everyday communication functioning, and explored the role of anatomical factors, social risk, and non-verbal IQ in these outcomes. Standardised measures of language and everyday communication functioning, intellectual ability and social risk were used. AgCC classification and anterior commissure volume, a potential alternative pathway, were extracted from T1-weighted images. Participants with AgCC showed reduced receptive and expressive language compared with test norms, and high rates of language and communication impairments. Complete AgCC, higher social risk and lower non-verbal IQ were associated with communication difficulties. Anterior commissure volume was not associated with language and communication. Recognising heterogeneity in language and communication functioning enhances our understanding and suggests specific focuses for potential interventions.

Pediatric sport and nonsport concussions presenting to emergency departments: injury circumstances, characteristics, and clinical management.

OBJECTIVE: The aim of this study was to compare injury circumstances, characteristics, and clinical management of emergency department (ED) presentations for sports-related concussion (SRC) and non-SRC. METHODS: This multicenter prospective observational study identified patients 5-17 years old who presented to EDs within 24 hours of head injury, with one or more signs or symptoms of concussion. Participants had a Glasgow Coma Scale score of 13-15 and no abnormalities on CT (if performed). Data were stratified by age: young children (5-8 years), older children (9-12 years), and adolescents (13-17 years). RESULTS: Of 4709 patients meeting the concussion criteria, non-SRC accounted for 56.3% of overall concussions, including 80.9% of younger child, 51.1% of older child, and 37.0% of adolescent concussions. The most common mechanism of non-SRC was falls for all ages. The most common activity accounting for SRC was bike riding for younger children, and rugby for older children and adolescents. Concussions occurring in sports areas, home, and educational settings accounted for 26.2%, 21.8%, and 19.0% of overall concussions. Concussions occurring in a sports area increased with age, while occurrences in home and educational settings decreased with age. The presence of amnesia significantly differed for SRC and non-SRC for all age groups, while vomiting and disorientation differed for older children and adolescents. Adolescents with non-SRC were admitted to a ward and underwent CT at higher proportions than those with SRC. CONCLUSIONS: Non-SRC more commonly presented to EDs overall, with SRC more common with increasing age. These data provide important information to inform public health policies, guidelines, and prevention efforts.

Long-term outcomes of early exposure to repeated general anaesthesia in children with cystic fibrosis (CF-GAIN): a multicentre, open-label, randomised controlled phase 4 trial.

BACKGROUND: Long-term effects of early, recurrent human exposure to general anaesthesia remain unknown. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial provided an opportunity to examine this issue in children randomly assigned in infancy to either repeated bronchoalveolar-lavage (BAL)-directed therapy with general anaesthesia or standard care with no planned lavages up to 5 years of age when all children received BAL-directed therapy under general anaesthesia. METHODS: This multicentre, randomised, open-label phase 4 trial (CF-GAIN) used the original ACFBAL trial randomisation at 3·6 months (SD 1·6) to BAL-directed therapy or standard-care groups to assess the impact of general anaesthesia exposures over early childhood. Children who completed the ACFBAL trial, with a mean age of 5·1 (SD 0·18) years, received standardised neurobehavioural and health-related-quality-of-life assessment and brain MRI scans between Oct 8, 2013, and June 30, 2017, at a mean age of 12·8 (SD 1·7) years at three hospitals in Australia and one hospital in New Zealand. The primary outcome was a composite score of performance on a standardised, computer-based assessment of child attention, processing speed, and response inhibition skills (Conners Continuous Performance test, second edition). Secondary outcomes included intellectual function, other neurobehavioural measures, and brain imaging as an exploratory outcome. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12613000057785) and is completed. FINDINGS: At 2 years, the BAL-directed therapy group (n=52) and standard-care group (n=45) had a median of 2·0 (IQR 1·0-3·0) and 0·0 (0·0-0·0) exposures, respectively. At completion of the ACFBAL trial, the BAL-directed therapy group had a median of 6·0 (4·0-9·5) exposures and the standard-care group 2·0 (1·0-4·0) exposures. At CF-GAIN completion, the BAL-directed therapy group had a median of 10·0 (IQR 6·5-14·5) exposures and the standard-care group 4·0 (3·0-7·0) exposures. Cumulative general anaesthesia exposure time was not prospectively collected but, for those with complete cumulative exposure time data to the end of the ACFBAL trial, the median cumulative exposure time for the BAL-directed therapy group (n=29) was 180 (IQR 140-285) min and for the standard-care group (n=32) was 48 (30-122) min. The mean Conners Continuous Performance test, second edition composite score was 51 (SD 8·1) in BAL-directed therapy group and 53 (8·8) in the standard-care group; difference -1·7 (95% CI -5·2 to 1·7; p=0·32) with similar performance on other neurobehavioural measures, including measures of executive function, intellectual quotient scores, and brain imaging. INTERPRETATION: Our findings suggest that repeated general anaesthesia exposure in young children with cystic fibrosis is not related to functional impairment in attention, intellectual quotient, executive function, or brain structure compared with a group with fewer and shorter cumulative anaesthesia durations. FUNDING: National Health and Medical Research Council Australia, Queensland Government Health Service and Clinical Innovation Fellowship, and the Children's Hospital Foundation Queensland.

Longitudinal neurocognitive trajectories and risk factors in the first three months following pediatric concussion.

OBJECTIVE: To identify differential trajectories of neurocognitive outcomes following pediatric concussion and investigate predictors associated with patterns of recovery up to 3 months. METHODS: 74 participants aged 8-17 years completed attention/working memory, processing speed, and executive function measures at 2 weeks, 1 month, and 3 months post-injury. We used principal component analysis to generate a composite of information processing. Group-based trajectory modeling identified latent trajectories. Multinominal logistic regression was used to examine associations between risk factors and trajectory groups. RESULTS: We identified three trajectories of neurocognitive outcomes. The medium (54.6%) and high improving groups (35.8%) showed ongoing increase in information processing, while the low persistent group showed limited change 3 months post-injury. This group recorded below average scores on Digit Span Forward and Backward at 3 months. History of pre-injury headache was significantly associated with the persistent low scoring group, relative to the medium improving (p = 0.03) but not the high improving group (p = 0.09). CONCLUSIONS: This study indicates variability in neurocognitive outcomes according to three differential trajectories, with groups partially distinguished by preexisting child factors (history of frequent headaches). Modelling that accounts for heterogeneity in individual outcomes is essential to identify clinically meaningful indices that are indicative of children requiring intervention.

Understanding factors that influence goal setting in rehabilitation for paediatric acquired brain injury: a qualitative study using the Theoretical Domains Framework.

Background While goal setting with children and their families is considered best practice during rehabilitation following acquired brain injury, its successful implementation in an interdisciplinary team is not straightforward. This paper describes the application of a theoretical framework to understand factors influencing goal setting with children and their families in a large interdisciplinary rehabilitation team. Methods A semi-structured focus group was conducted with rehabilitation clinicians and those with lived experience of paediatric acquired brain injury (ABI). The 90-min focus group was audio-recorded and transcribed verbatim. Data were thematically coded and mapped against the Theoretical Domains Framework (TDF) to understand influencing factors, which were then linked to the Capability, Opportunity, Motivation - Behaviour (COM-B) model. Results A total of 11 participants (nine paediatric rehabilitation clinicians, one parent and one young person with lived experience of paediatric ABI) participated in the focus group. Factors influencing collaborative goal setting mapped to the COM-B and six domains of the TDF: Capabilities (Skills, Knowledge, Beliefs about capabilities, and Behavioural regulation), Opportunities (Environmental context and resources), and Motivation (Social/professional role and identity). Results suggest that a multifaceted intervention is needed to enhance rehabilitation clinicians' and families' skills and knowledge of goal setting, restructure the goal communication processes, and clarify the roles clinicians play in goal setting within the interdisciplinary team. Conclusion The use of the TDF and COM-B enabled a systematic approach to understanding the factors influencing goal setting for children with acquired brain injury in a large interdisciplinary rehabilitation team, and develop a targeted, multifaceted intervention for clinical use. These represent important considerations for the improvement of collaborative goal setting in paediatric rehabilitation services to ensure that best practice approaches to goal setting are implemented effectively in clinical practice.

Discovery of Alpha-1-Antichymotrypsin as a Marker of Delayed Recovery from Concussion in Children.

Of the four million children who experience a concussion each year, 30-50% of children will experience delayed recovery, where they will continue to experience symptoms more than two weeks after their injury. Delayed recovery from concussion encompasses emotional, behavioral, physical, and cognitive symptoms, and as such, there is an increased focus on developing an objective tool to determine risk of delayed recovery. This study aimed to identify a blood protein signature predictive of delayed recovery from concussion in children. Plasma samples were collected from children who presented to the Emergency Department at the Royal Children's Hospital, Melbourne, within 48h post-concussion. This study involved a discovery and validation phase. For the discovery phase, untargeted proteomics analysis was performed using single window acquisition of all theoretical mass spectra to identify blood proteins differentially abundant in samples from children with and without delayed recovery from concussion. A subset of these proteins was then validated in a separate participant cohort using multiple reaction monitoring and enzyme linked immunosorbent assay. A blood protein signature predictive of delayed recovery from concussion was modeled using a Support Vector Machine, a machine learning approach. In the discovery phase, 22 blood proteins were differentially abundant in age- and sex-matched samples from children with (n = 9) and without (n = 9) delayed recovery from concussion, six of whom were chosen for validation. In the validation phase, alpha-1-ACT was shown to be significantly lower in children with delayed recovery (n = 12) compared with those without delayed recovery (n = 28), those with orthopedic injuries (n = 7) and healthy controls (n = 33). A model consisting of alpha-1-ACT concentration stratified children based on recovery from concussion with an 0.88 area under the curve. We have identified that alpha-1-ACT differentiates between children at risk of delayed recovery from those without delayed recovery from concussion. To our knowledge, this is the first study to identify alpha-1-ACT as a potential marker of delayed recovery from concussion in children. Multi-site studies are required to further validate this finding before use in a clinical setting.

Reducing Temperature of Fused Deposition Modelling 3D Printing for Linalool Fast Dissolving Oral Films by Increasing Printer Nozzle Diameter.

Oral thrush and throat infections can occur in a wide range of patients. Treatments are available; however, resistance to drugs is a major problem for treating oral and throat infections. Three-dimensional printing (3DP) of fast dissolving oral films (FDFs) of linalool oil may provide an alternative solution. Linalool oil FDFs were printed by fused deposition modelling across 1-18 % w/w linalool content range with nozzle diameters of 0.4 or 1 mm at the temperature range of 150 °C-185 °C. The FDFs were evaluated for physicochemical and mechanical properties. Increasing the printer nozzle diameter to 1 mm allowed reducing the printing temperature from 185 °C to 150 °C; consequently, more linalool was quantified in the films with improved content uniformity. The higher linalool content in the films increased the film disintegration time and mechanical strength. FDFs containing 10% w/w linalool showed clear antifungal activity against Candida albicans. Raman spectroscopy suggested linalool separation from excipients at higher temperature printing. Viscoelastic measurements indicated that to achieve printing; the elastic modulus of molten filament needed to be higher than the loss modulus at low angular frequencies. In conclusion, increasing the printing nozzle diameter may avoid loss of the active ingredient by reducing the temperature of the 3DP process.

Rehabilitation of Executive Function in Pediatric Traumatic Brain Injury (REPeaT): Outcomes of a pilot randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of Cogmed Working Memory Training (Cogmed) in improving working memory (WM) and decision making (DM) in childhood traumatic brain injury (TBI), and any associated increases in functional outcomes such as academic achievement in mathematics, behavior, social skills, and quality of life. METHOD: A randomized controlled trial of the Cogmed (RM version) intervention for children with TBI. A total of 69 children post-TBI were screened for WM impairments, of which 31 eligible participants (Mage: 10.6 years; male n = 21) were recruited and randomized to either the treatment group (Cogmed, n = 16) or the active-control group (Lexia Reading Core5, n = 15). Both groups completed computerized training for 5 weeks with clinician support via an online video platform. Immediately posttraining and at 6 months follow-up, primary (WM and DM) and secondary functional outcomes were assessed. RESULTS: Immediately postintervention, significant improvement was found in one primary outcome (WM verbal component) for the Cogmed group, but this was not maintained at the 6 months follow-up. No immediate improvements or maintenance gains (small effect sizes) in other primary outcomes of visuospatial WM or DM were reported in the Cogmed group. No other significant group differences were detected for other functional outcomes. CONCLUSIONS: Despite the limited benefits observed in this small randomized controlled trial, it will be beneficial to investigate Cogmed's efficacy in a case-series methodology, to further determine its effectiveness in a pediatric TBI population. Furthermore, a cautious approach in clinical implementation of Cogmed is advised. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Psychological Predictors of Mental Health Difficulties After Pediatric Concussion.

Children often experience mental health difficulties after a concussion. Yet, the extent to which a concussion precipitates or exacerbates mental health difficulties remains unclear. This study aimed to examine psychological predictors of mental health difficulties after pediatric concussion. Children (5 to <18 years of age, M = 11.7, SD = 3.3) with concussion were recruited in a single-site longitudinal prospective cohort study conducted at a tertiary children's hospital (n = 115, 73.9% male). The primary outcomes included internalizing (anxious, depressed, withdrawn behaviors), externalizing (risk-taking, aggression, attention difficulties), and total mental health problems, as measured by the Child Behavior Checklist at 2 weeks (acute) and 3 months (post-acute) after concussion. Predictors included parents' retrospective reports of premorbid concussive symptoms (Post-Concussion Symptom Inventory; PCSI), the child and their family's psychiatric history, child-rated perfectionism (Adaptive-Maladaptive Perfectionism Scale), and child-rated resilience (Youth Resilience Measure). Higher premorbid PCSI ratings consistently predicted acute and post-acute mental health difficulties. This relationship was significantly moderated by child psychiatric history. Furthermore, pre-injury learning difficulties, child psychiatric diagnoses, family psychiatric history, lower resilience, previous concussions, female sex, and older age at injury were associated with greater mental health difficulties after concussion. Pre-injury factors accounted for 23.4-39.9% of acute mental health outcomes, and 32.3-37.8% of post-acute mental health outcomes. When acute mental health was factored into the model, a total of 47.0-68.8% of variance was explained by the model. Overall, in this sample of children, several pre-injury demographic and psychological factors were observed to predict mental health difficulties after a concussion. These findings need to be validated in future research involving larger, multi-site studies that include a broader cohort of children after concussion.

Nature and correlates of self-esteem in young adult survivors of childhood traumatic brain injury.

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.

Family involvement in rehabilitation programmes for children and adolescents with acquired brain injury: A scoping literature review.

Paediatric acquired brain injury (ABI) can adversely impact families, and it is widely accepted that families should be involved in the rehabilitation of children/adolescents with ABI. However, there is limited guidance about how to best involve families in paediatric ABI rehabilitation. Several programmes involving the families of children/adolescents with ABI have been developed, but there are no published reviews outlining their characteristics. This scoping literature review aimed to synthesize information about these programmes and develop an understanding of how families are involved in them. Four databases were systematically searched to identify sources of evidence that described programmes in paediatric ABI rehabilitation that involve family members. One hundred and eight sources of evidence describing 42 programmes were included. Programmes were categorized as: service coordination (n = 11), psychosocial (n = 17), support groups (n = 4), training/instruction (n = 9), and education (n = 1). Families' involvement in these programmes varied across programme development, delivery, and evaluation stages. The findings of this scoping literature review outline how families can be involved in paediatric ABI rehabilitation. While this review outlines many approaches to supporting families, it also highlights the need for models of family-centred care to better articulate how clinicians and services can involve families in paediatric ABI rehabilitation.

Capillary blood protein markers of posttraumatic headache in children after concussion.

OBJECTIVE: Posttraumatic headache (PTH) represents the most common acute and persistent symptom in children after concussion, yet there is no blood protein signature to stratify the risk of PTH after concussion to facilitate early intervention. This discovery study aimed to identify capillary blood protein markers, at emergency department (ED) presentation within 48 hours of concussion, to predict children at risk of persisting PTH at 2 weeks postinjury. METHODS: Capillary blood was collected using the Mitra Clamshell device from children aged 8-17 years who presented to the ED of the Royal Children's Hospital, Melbourne, Australia, within 48 hours of sustaining a concussion. Participants were followed up at 2 weeks postinjury to determine PTH status. PTH was defined per clinical guidelines as a new or worsened headache compared with preinjury. An untargeted proteomics analysis using data-independent acquisition (DIA) was performed. Principal component analysis and hierarchical clustering were used to reduce the dimensionality of the protein dataset. RESULTS: A total of 907 proteins were reproducibly identified from 82 children within 48 hours of concussion. The mean participant age was 12.78 years (SD 2.54 years, range 8-17 years); 70% of patients were male. Eighty percent met criteria for acute PTH in the ED, while one-third of participants with follow-up experienced PTH at 2 weeks postinjury (range 8-16 days). Hemoglobin subunit zeta (HBZ), cystatin B (CSTB), beta-ala-his dipeptidase (CNDP1), hemoglobin subunit gamma-1 (HBG1), and zyxin (ZYX) were weakly associated with PTH at 2 weeks postinjury based on up to a 7% increase in the PTH group despite nonsignificant Benjamini-Hochberg adjusted p values. CONCLUSIONS: This discovery study determined that no capillary blood protein markers, measured at ED presentation within 48 hours of concussion, can predict children at risk of persisting PTH at 2 weeks postinjury. While HBZ, CSTB, CNDP1, HBG1, and ZYX were weakly associated with PTH at 2 weeks postinjury, there was no specific blood protein signature predictor of PTH in children after concussion. There is an urgent need to discover new blood biomarkers associated with PTH to facilitate risk stratification and improve clinical management of pediatric concussion.

Biopsychosocial correlates of fatigue in young adult survivors of childhood traumatic brain injury: A prospective cohort study.

This prospective cohort study aimed to evaluate the potential role of injury, socio-demographic and individual psychological factors in predicting long-term fatigue outcomes in young adult survivors of childhood TBI at 16-years post-injury. The study included 51 young adults diagnosed with childhood TBI from 2-12 years of age. Twenty age-and-sex-matched controls were included for comparison. Findings showed that almost one-in-four TBI participants (24%) endorsed clinically elevated fatigue at 16-years post-injury. Despite the relatively large proportion of TBI participants endorsing clinically significant fatigue, group comparisons revealed that the TBI and control groups did not significantly differ on fatigue symptom severity or rates of clinically elevated fatigue. For the TBI group, post-injury fatigue was significantly associated with socio-demographic and psychological factors, including lower educational level, higher depression symptom severity, and more frequent substance use. Higher fatigue was also associated with lower self-reported quality of life (QoL) in the physical, psychological, and environmental domains, even after controlling for depressive symptom severity, socio-demographic, and injury-related factors. Overall, findings show that a substantial proportion of young adults with a history of childhood TBI experience clinically elevated fatigue at 16-years post-injury. Identification and treatment of modifiable risk-factors (e.g. depression symptoms, substance use) has potential to reduce fatigue.