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Traumatic brain injury (TBI) is one of the most common causes of emergency room visits in children, and it is a leading cause of death in juveniles in the United States. Similarly, a high proportion of this population consumes diets that are high in saturated fats, and millions of children are overweight or obese. The goal of the present study was to assess the relationship between diet and TBI on cognitive and cerebrovascular outcomes in juvenile rats. In the current study, groups of juvenile male Long Evans rats were subjected to either mild TBI via the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA) or underwent sham procedures. The animals were provided with either a combination of high-fat diet and a mixture of high-fructose corn syrup (HFD/HFCS) or a standard chow diet (CH) for 9 days prior to injury. Prior to injury, the animals were trained on the Morris water maze for three consecutive days, and they underwent a post-injury trial on the day of the injury. Immediately after TBI, the animals' righting reflexes were tested. Four days post-injury, the animals were euthanized, and brain samples and blood plasma were collected for qRT-PCR, immunohistochemistry, and triglyceride assays. Additional subsets of animals were used to investigate cerebrovascular perfusion using Laser Speckle and perform immunohistochemistry for endothelial cell marker RECA. Following TBI, the righting reflex was significantly increased in TBI rats, irrespective of diet. The TBI worsened the rats' performance in the post-injury trial of the water maze at 3 h, p(injury) < 0.05, but not at 4 days post-injury. Reduced cerebrovascular blood flow using Laser Speckle was demonstrated in the cerebellum, p(injury) < 0.05, but not foci of the cerebral cortices or superior sagittal sinus. Immunoreactive staining for RECA in the cortex and corpus callosum was significantly reduced in HFD/HFCS TBI rats, p < 0.05. qRT-PCR showed significant increases in APOE, CREB1, FCGR2B, IL1B, and IL6, particularly in the hippocampus. The results from this study offer robust evidence that HFD/HFCS negatively influences TBI outcomes with respect to cognition and cerebrovascular perfusion of relevant brain regions in the juvenile rat.

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AIM: To systematically review the prevalence, risk factors and timing of onset of hip displacement in children with a post-neonatal (PNN) brain injury with regards to hip surveillance recommendations. METHOD: A search of PubMed, MEDLINE, Embase, CINAHL and Web of Science was conducted on 22nd February 2022. Studies were included if they reported presence of, and risk factors for, hip displacement in children with PNN brain injury. Data was extracted on patient characteristics, and analyzed in terms of risk factors of interest and timing of development of hip displacement. RESULTS: Six studies met the inclusion criteria (n = 408 participants). All were cohort studies: five retrospective and one prospective. Rates of hip displacement ranged from 1% to 100%, and were higher in children with diffuse brain injury at an early age, who were non-ambulant and had spastic quadriplegia. Hip displacement and hip dislocation were first identified at one and three months respectively following PNN brain injury. INTERPRETATION: Evidence on hip displacement in children with PNN brain injury is sparse and low quality. Children who remain non-ambulant after diffuse PNN brain injury before five years of age appear most at risk of developing progressive hip displacement and earlier hip surveillance is recommended.

As for children with cerebral palsy (CP), children with a post-neonatal (PNN) brain injury who are non-ambulant are most at risk of progressive hip displacement.Children with a diffuse brain injury before five years of age appear to be at greater risk.Hip displacement can occur very early and progress rapidly following PNN brain injury.

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Emerging evidence suggests that advanced neuroimaging modalities such as arterial spin labelling (ASL) might have prognostic utility for pediatric concussion. This study aimed to: 1) examine group differences in global and regional brain perfusion in youth with concussion or orthopedic injury (OI) at 72 h and 4 weeks post-injury; 2) examine patterns of abnormal brain perfusion within both groups and their recovery; 3) investigate the association between perfusion and symptom burden within concussed and OI youths at both time-points; and 4) explore perfusion between symptomatic and asymptomatic concussed and OI youths. Youths ages 10.00-17.99 years presenting to the emergency department with an acute concussion or OI were enrolled. ASL-magnetic resonance imaging scans were conducted at 72 h and 4 weeks post-injury to measure brain perfusion, along with completion of the Health Behavior Inventory (HBI) to measure symptoms. Abnormal perfusion clusters were identified using voxel-based z-score analysis at each visit. First, mixed analyses of covariance (ANCOVAs) investigated the Group*Time interaction on global and regional perfusion. Post hoc region of interest (ROI) analyses were performed on significant regions. Second, within-group generalized estimating equations investigated the recovery of abnormal perfusion at an individual level. Third, multiple regressions at each time-point examined the association between HBI and regional perfusion, and between HBI and abnormal perfusion volumes within the concussion group. Fourth, whole-brain one-way ANCOVAs explored differences in regional and abnormal perfusion based on symptomatic status (symptomatic vs. asymptomatic) and OIs at each time-point. A total of 70 youths with a concussion [median age (interquartile range; IQR) = 12.70 (11.67-14.35), 47.1% female] and 29 with an OI [median age (IQR) = 12.05 (11.18-13.89), 41.4% female] were included. Although no Group effect was found in global perfusion, the concussion group showed greater adjusted perfusion within the anterior cingulate cortex/middle frontal gyrus (MFG) and right MFG compared with the OI group across time-points (ps ≤ 0.004). The concussion group showed lower perfusion within the right superior temporal gyrus at both time-points and bilateral occipital gyrus at 4 weeks, (ps ≤ 0.006). The number of hypoperfused clusters was increased at 72 h compared with 4 weeks in the concussion youths (p < 0.001), but not in the OIs. Moreover, Group moderated the HBI-perfusion association within the left precuneus and superior frontal gyrus at both time-points, (ps ≤ 0.001). No association was found between HBI and abnormal perfusion volume within the concussion group at any visits. At 4 weeks, the symptomatic sub-group (n = 10) showed lower adjusted perfusion within the right cerebellum and lingual gyrus, while the asymptomatic sub-group (n = 59) showed lower adjusted perfusion within the left calcarine, but greater perfusion within the left medial orbitofrontal cortex, right middle frontal gyrus, and bilateral caudate compared with OIs. Yet, no group differences were observed in the number of abnormal perfusion clusters or volumes at any visit. The present study suggests that symptoms may be associated with changes in regional perfusion, but not abnormal perfusion levels.

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Aim In response to the coronavirus 2019 disease (COVID-19) pandemic, governments worldwide implemented measures to prevent infection, resulting in restricted school activities, restricted children's freedom of movement, and increased risk of violence and injuries at home, including traumatic brain injury (TBI), among children. In Brazil, the consequences of the COVID-19 pandemic on the causes, severity, and mortality of pediatric TBI have not yet been investigated. Thus, our study aimed to determine whether the COVID-19 pandemic has affected the epidemiology of pediatric TBI among Brazilian children. Materials and methods We investigated the patients with TBI aged <18 years who visited a tertiary trauma center in Brazil in 2019 and 2020. TBI-related variables, such as classification, mechanism, clinical manifestations, need for intervention, morbidity, and mortality, were recorded. Furthermore, we used a nationwide databank to collect information on mortality from external causes of trauma and violence in the pediatric population in 2019 and 2020. The Mann-Whitney test was used to compare quantitative variables related to the mechanisms and severity of TBI in both periods in order to determine the impact of the COVID-19 pandemic. Results Of the patients with traumatic brain injury, 1371 visited the trauma center in 2019 and 1052 in 2020. No difference was noted in the incidence rate of abusive head trauma between these periods (p=0.142) or in mortality from violence in Brazil. Recreational causes of pediatric TBI increased during the first year of the COVID-19 pandemic in Brazil and falls from bicycles significantly increased during the pandemic (p<0.001). Conclusion A global reduction in pediatric admissions to emergency rooms as well as no impact on mortality and severity of pediatric TBI were observed during the COVID-19 pandemic in Brazil. Additionally, a public education program regarding child safety during recreational activities, particularly how to avoid falls from bicycles was recommended.

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The field of pediatric neurocritical care (PNCC) has expanded and evolved over the last three decades. As mortality from pediatric critical care illness has declined, morbidity from neurodevelopmental disorders has expanded. PNCC clinicians have adopted a multidisciplinary approach to rapidly identify neurological injury, implement neuroprotective therapies, minimize secondary neurological insults, and establish transitions of care, all with the goal of improving neurocognitive outcomes for their patients. Although there are many aspects of PNCC and adult neurocritical care (NCC) medicine that are similar, elemental difference between adult and pediatric medicine has contributed to a divergent evolution of the respective fields. The low incidence of pediatric critical care illness, the heterogeneity of neurological insults, and the limited availability of resources all shape the need for a PNCC clinical care model that is distinct from the established paradigm adopted by the adult neurocritical care community at large. Considerations of neurodevelopment are fundamental in pediatrics. When neurological injury occurs in a child, the neurodevelopmental stage at the time of insult alters the impact of the neurological disease. Developmental variables contribute to a range of outcomes for seemingly similar injuries. Despite the relative infancy of the field of PNCC, early reports have shown that implementation of a specialized PNCC service elevates the quality and safety of care, promotes education and communication, and improves outcomes for children with acute neurological injuries. The multidisciplinary approach of PNCC clinicians and researchers also promotes a culture that emphasizes the importance of quality improvement and education initiatives, as well as development of and adherence to evidence-based guidelines and family-focused care models.

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Background: To investigate the clinical significance of the disturbance coefficient (DC) and regional cerebral oxygen saturation (rSO2) as obtained through the use of electrical bioimpedance and near-infrared spectroscopy (NIRS) in pediatric neurocritical care. Participants and methods: We enrolled 45 pediatric patients as the injury group and 70 healthy children as the control group. DC was derived from impedance analysis of 0.1 mA-50 kHz current via temporal electrodes. rSO2 was the percentage of oxyhemoglobin measured from reflected NIR light on the forehead. DC and rSO2 were obtained at 6, 12, 24, 48 and 72 h after surgery for the injury group and during the health screening clinic visit for the control group. We compared DC and rSO2 between the groups, their changes over time within the injury group and their correlation with intracranial pressure (ICP), cerebral perfusion pressure (CPP), Glasgow coma scale (GCS) score, Glasgow outcome scale (GOS) score, and their ability to diagnose postoperative cerebral edema and predict poor prognosis. Results: DC and rSO2 were significantly lower in the injury group than in the control group. In the injury group, ICP increased over the monitoring period, while DC, CPP and rSO2 decreased. DC was negatively correlated with ICP and positively correlated with GCS score and GOS score. Additionally, lower DC values were observed in patients with signs of cerebral edema, with a DC value of 86.5 or below suggesting the presence of brain edema in patients aged 6-16 years. On the other hand, rSO2 was positively correlated with CPP, GCS score, and GOS score, with a value of 64.4% or below indicating a poor prognosis. Decreased CPP is an independent risk factor for decreased rSO2. Conclusion: DC and rSO2 monitoring based on electrical bioimpedance and near-infrared spectroscopy not only reflect the degree of brain edema and oxygenation, but also reflect the severity of the disease and predict the prognosis of the patients. This approach offers a real-time, bedside, and accurate method for assessing brain function and detecting postoperative cerebral edema and poor prognosis.

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BACKGROUND: Early-onset ventilator-associated pneumonia (VAP) is associated with poor outcomes in patients with severe traumatic brain injury (TBI). The primary aim of this study was to describe VAP, including the microbiology of VAP and differences in frequency of VAP when various definitions are applied. The secondary aim was to determine the clinical variables associated with the development of VAP in children with severe TBI. METHODS: This is a retrospective cohort study at a quaternary referral children's hospital with a level I trauma center designation. Inclusion criteria were patients aged 0-18 years admitted to the pediatric intensive care unit between 2015 and 2020 with severe TBI requiring at least 2 days of invasive ventilation. VAP was defined by using Center of Disease Control (CDC) definition or clinical VAP, based on physician diagnosis. We compared general demographics, reviewed trauma and injury data, and outcomes to assess any differences between patients with VAP and non-VAP patients. Associations were tested with regression models. RESULTS: After applying all inclusion and exclusion criteria, 90 patients were included in the analysis. Patients with VAP were older (8.5 vs. 5.6 years, P = 0.03). Patients with VAP were less likely to have suffered from abusive head trauma (P = 0.01). Patients who received continuous neuromuscular blockade or targeted temperature management did not have different frequencies of VAP. CDC-defined VAP was diagnosed in 27% of patients. Number of patients with VAP increased to 41% for physician-diagnosed or clinical VAP. Methicillin-sensitive Staphylococcus aureus was the most common isolate grown, followed by Hemophilus influenza, with most VAP occurring on days 2-5 of intubation. VAP was not associated with mortality but was associated with worse functional status scale in patients who survived to discharge (8 vs. 7.5, P = 0.048). Over a cumulative period of days, nebulized 3% and albuterol were associated with decreased incidence of VAP. CONCLUSIONS: Ventilator-associated pneumonia occurs commonly in children with severe TBI, with rates of 27-41%, depending on CDC-defined VAP or clinical VAP. The discrepancy between clinical VAP and CDC-defined VAP further illustrates the need for a standardized definition for VAP. Although most interventions were not associated with VAP, nebulized 3% saline and albuterol were associated with reduced incidence of VAP; future investigation is needed to determine whether mucolytic agents can decrease the rate of VAP in children with severe TBI.

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The current study is a feasibility study of a randomized controlled trial (RCT): the Child in Context Intervention (CICI). The CICI study is an individualized, goal-oriented and home-based intervention conducted mainly through videoconference. It targets children with ongoing challenges (physical, cognitive, behavioral, social and/or psychological) after acquired brain injury (ABI) and their families at least one year post injury. The CICI feasibility study included six children aged 11-16 years with verified ABI-diagnosis, their families and their schools. The aim was to evaluate the feasibility of the intervention components, child and parent perceptions of usefulness and relevance of the intervention as well as the assessment protocol through a priori defined criteria. Overall, the families and therapists rated the intervention as feasible and acceptable, including the videoconference treatment delivery. However, the burden of assessment was too high. The SMART-goal approach was rated as useful, and goal attainment was high. The parents' ratings of acceptability of the intervention were somewhat higher than the children's. In conclusion, the CICI protocol proved feasible and acceptable to families, schools and therapists. The assessment burden was reduced, and adjustments in primary outcomes were made for the definitive RCT.

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BACKGROUND: Pediatric acquired brain injury (pABI) is associated with long-term cognitive, behavioral, social, and emotional problems, which may affect the quality of life, school, and family functioning. Yet, there is a lack of evidence-based community-centered rehabilitation programs for chronic pABI and these children do not systematically receive comprehensive rehabilitation. The Child In Context Intervention (CICI) study is a pragmatic randomized controlled trial (RCT) for children with chronic pABI, which aims to evaluate the effectiveness of an individualized and goal-oriented intervention targeting everyday functioning of the child and family. METHODS: Children aged 6-16 years with MRI/CT-verified intracranial abnormalities will be included in the CICI study if they have persistent self- or parent-reported cognitive, emotional, and/or behavioral challenges 1 year or more after insult and attend school regularly. A total of 70 families will be randomized 1:1 to an intervention or a control group. The intervention consists of seven family sessions, one parent seminar, and four school sessions delivered over approximately 6 months. The parent seminar will be held in person, and the other sessions will mainly be video based. The children's and families' self-reported major challenges in everyday life will be targeted using SMART goals. Evidence-based strategies, when available, will be applied to achieve the goals, combined with psychoeducation. Goal attainment scaling (GAS) will be used to evaluate goal attainment. Data is collected at baseline and after approximately 6 and 9 months. External assessors are blinded to group allocation. Primary outcomes are parent-reported brain injury symptoms in children and parenting self-efficacy at 9 months of follow-up. Secondary outcomes include child-reported brain injury symptoms, quality of life, executive functioning in daily life, parent emotional symptoms, family functioning, and unmet family health care needs. A process evaluation will be conducted. DISCUSSION: The current study provides an innovative approach to rehabilitation for children in the chronic phase of ABI and their families. This complex intervention may contribute to the development of evidence-based, high-quality rehabilitation for a large patient group, which is underrepresented in clinical research. It may also improve collaboration between specialized rehabilitation facilities, schools, and local health care services. Inclusion for the trial started in April 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT04798859 . Registered on March 15, 2021.

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Increased sensitivity to light is common after concussion. Viewing a flickering light can also produce uncomfortable somatic sensations like nausea or headache. We examined effects evoked by viewing a patterned, flickering screen in a cohort of 81 uninjured youth athletes and 84 concussed youth. We used Multiple correspondence analysis and identified two primary dimensions of variation: the presence or absence of visually evoked effects and variation in the tendency to manifest effects that localized to the eyes (e.g., eye watering) versus more generalized neurological effects (e.g., headache). Based on these two primary dimensions, we grouped participants into three categories of evoked symptomatology: no effects, eye-predominant effects, and brain-predominant effects. A similar proportion of participants reported eye-predominant effects in the uninjured (33.3%) and concussed (32.1%) groups. By contrast, participants who experienced brain-predominant effects were almost entirely from the concussed group (1.2% of uninjured, 35.7% of concussed). The presence of brain-predominant effects was associated with a higher concussion symptom burden and reduced performance on visio-vestibular tasks. Our findings indicate that the experience of negative constitutional, somatic sensations in response to a dynamic visual stimulus is a salient marker of concussion and is indicative of more severe concussion symptomatology. We speculate that differences in visually evoked effects reflect varying levels of activation of the trigeminal nociceptive system.

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OBJECTIVE: While prior studies have found parental socioeconomic status (SES) affects the outcomes of pediatric traumatic brain injury (TBI), the longitudinal trajectory of this effect is not well understood. METHODS: This prospective cohort study included children 8-18 years of age admitted to six sites with a complicated mild (n = 123) or moderate-severe TBI (n = 47). We used caregiver education and household poverty level as predictors, and multiple quality of life and health behavior domains as outcomes. Differences at 6, 12, and 24 months from baseline ratings of pre-injury functioning were compared by SES. We examined the association between measures of SES and domains of functioning over the 24 months post-injury in children with a complicated mild or moderate- severe TBI, and determined how this association varied over time. RESULTS: Parental education was associated with recovery among children with complicated mild TBI; outcomes at 6, 12, and 24 months were substantially poorer than at baseline for children with the least educated parents. After moderate-severe TBI, children in households with lower incomes had poorer outcomes compared to baseline across time. IMPLICATIONS: Parental education and household income were associated with recovery trajectories for children with TBI of varying severity.

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OBJECTIVE: This retrospective study aimed to describe the volume, severity, and injury mechanism of all hospital-admitted pediatric traumatic brain injury (pTBI) at Oslo University Hospital (OUH), emphasizing consequences for prevention and factors indicating a need for follow-up programs. METHOD: Data were extracted from the OUH Trauma registry on 176 children, 0-15 years old, admitted to OUH in 2015 and 2016 with a pTBI diagnosis. The dataset contains demographic data, injury mechanism, type, and severity (Glasgow coma scale, GCS; abbreviated injury scale, AIS; injury severity score, ISS), ICD-10 diagnosis codes, level of treatment, and destination of discharge. RESULTS: 79.5% had mild, 9% moderate, and 11.4% severe TBI. The incidence of hospital-treated pTBI in Oslo was 29 per 100,000 per year. The boy: girl ratio was 1.9:1, but in the young teenage group (14-15 years), the ratio was 1:1. Intracranial injury (ICI) identified on CT/MRI was associated with extended hospital stays, with a median of 6 days compared to 1 day for patients without ICI. 27% of the patients assessed as mild TBI at admission had ICI. Children below eight years of age had a higher incidence of moderate and severe ICI from trauma (53% v.s. 28% in children ≥ eight years). CONCLUSION: The injury characteristics of hospital-treated pTBI are in line with other European countries, but we find the boy-girl ratio different as young teenage girls seem to be catching up with the boys. ICI and length of stay should be considered when deciding which patients need follow-up and rehabilitation.

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Understanding the long-term medical and developmental outcomes for children who survive abusive head trauma (AHT) is important to ensure necessary supports and services are available. This study examined the retrospective global and specific medical and developmental outcomes of 55 children with AHT who were treated at The Children's Hospital at Westmead. Global outcomes were assessed using the Kings Outcome Scale of Childhood Head Injury (KOSCHI). Five years post-injury, one child had died and two had made a complete recovery. Forty-five children (81.8%) had a moderate or severe disability, an increase from 64.5% at acute discharge. At follow-up, the main impairments were behavioral problems (53%), vision impairment (44%), fine motor difficulties (26%), gross motor problems (26%), communication problems (24%) and 16% had seizures. A Spearman's Rank correlation revealed that only 41% of variance in KOSCHI scores five years post-injury could be accounted for KOSCHI scores at the time of acute discharge (rs(55) = 0.638, p < .001), and many children's presentation was worse at follow-up. Therefore, all children presenting with AHT need long term follow up regardless of early indications of good recovery.

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Sleep disturbances are commonly reported in children with persistent post-concussion symptoms (PPCS). Melatonin treatment is often recommended, yet supporting evidence is scarce. We aimed to evaluate the efficacy of treatment with melatonin for sleep disturbance in youth with PPCS following mild traumatic brain injury (mTBI). This article is a secondary analysis of a clinical trial of melatonin compared with placebo to treat PPCS. Youth (8-18 years of age) with PPCS and significant sleep-related problems (SRPs) at 4-6 weeks post-injury were eligible. Exclusion criteria: significant medical/psychiatric history; previous concussion/mTBI within 3 months. Treatment groups were: placebo, melatonin 3 mg, or melatonin 10 mg. Primary outcome was change in SRPs measured using the Post-Concussion Symptom Inventory (PCSI) after 2 weeks of treatment. Secondary outcomes included change in actigraphy sleep efficiency, duration, onset latency, and wake-after-sleep-onset. Behavior was measured using Behaviour Assessment for Children (2nd edition). Seventy-two participants (mean age 14.0, standard deviation [SD] = 2.6) years; 60% female) with PPCS and significant sleep disturbance were included in the secondary analysis: placebo (n = 22); melatonin 3 mg (n = 25); melatonin 10 mg (n = 25). Sixty-four participants had actigraphy data. SRPs decreased across all groups over time with a significant effect of melatonin 3 mg (3.7; 95% confidence interval [CI]: 2.1, 5.4) compared with placebo (7.4; 95% CI: 4.2, 10.6) and melatonin 10 mg (6.4; 95% CI: 3.6, 9.2). Sleep duration increased in the melatonin 3 mg (43 min; 95% CI: 6, 93) and melatonin 10 mg groups (55 min; 95% CI: 5, 104) compared with placebo. A per protocol analysis demonstrated improved sleep efficiency in the melatonin 10 mg group (p = 0.029). No serious adverse events were reported. Depressive symptoms significantly decreased with melatonin 3 mg (-4.7; 95% CI: -9.2, -.2) but not with melatonin 10 mg (-1.4, 95% CI: -5.9, 3.2) treatment compared with placebo. Changes in cognition or behavior were otherwise not significantly different between treatment groups. Short-term melatonin is a well-tolerated treatment for sleep disturbance in youth with PPCS following mTBI. In this context, it may also be associated with a reduction in depressive symptoms.

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(1) Background: Memory deficits are common sequelae of pediatric Acquired Brain Injury (ABI). Only methods for non-focused cognitive remediation are available to the pediatric field. The aims of this feasibility trial are the description, implementation, and test of an intensive program specific to the training and re-adaptation of memory function in children, called Intensive Memory-Focused Training Program (IM-FTP); (2) Methods: Eleven children and adolescents with ABI (mean age at injury = 12.2 years, brain tumor survivors excluded) were clinically assessed and rehabilitated over 1-month through IM-FTP, including physio-kinesis/occupational, speech, and neuropsychology treatments. Each patient received a psychometric evaluation and a brain functional MRI at enrollment and at discharge. Ten pediatric controls with ABI (mean age at injury = 13.8 years) were clinically assessed, and rehabilitated through a standard program; (3) Results: After treatment, both groups had marked improvement in both immediate and delayed recall. IM-FTP was associated with better learning of semantically related and unrelated words, and larger improvement in immediate recall in prose memory. Imaging showed functional modification in the left frontal inferior cortex; (4) Conclusions: We described an age-independent reproducible multidisciplinary memory-focused rehabilitation protocol, which can be adapted to single patients while preserving inter-subject comparability, and is applicable up to a few months after injury. IM-FTP will now be employed in a powered clinical trial.

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Traumatic brain injury is the leading cause of death in children. Children with severe TBI are in need of neurointensive care where the goal is to prevent secondary brain injury by avoiding secondary insults. Monitoring of cerebral blood flow (CBF) and autoregulation in the injured brain is crucial. However, there are limited studies performed in children to investigate this. Current studies report on age dependent increase in CBF with narrow age range. Low initial CBF following TBI has been correlated to poor outcome and may be more prevalent than hyperemia as previously suggested. Impaired cerebral pressure autoregulation is also detected and correlated with poor outcome but it remains to be elucidated if there is a causal relationship. Current studies are few and mainly based on small number of patients between the age of 0-18 years. Considering the changes of CBF and cerebral pressure autoregulation with increasing age, larger studies with more narrow age ranges and multimodality monitoring are required in order to generate data that can optimize the therapy and clinical management of children suffering TBI.

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The present study aimed to: (a) characterize the emergence to a conscious state (CS) in a sample of children and adolescents with severe brain injury during the post-acute rehabilitation and through two different neuropsychological assessment tools: the Rappaport Coma/Near Coma Scale (CNCS) and Level of Cognitive Functioning Assessment Scale (LOCFAS); (b) compare the evolution in patients with brain lesions due to traumatic and non-traumatic etiologies; and (c) describe the relationship between the emergence to a CS and some relevant clinical variables. In this observational prospective longitudinal study, 92 consecutive patients were recruited. Inclusion criteria were severe disorders of consciousness (DOC), Glasgow Coma Scale (GCS) score ≤8 at insult, age 0 to 18 years, and direct admission to inpatient rehabilitation from acute care. The main outcome measures were CNCS and LOCFAS, both administered three and six months after injury. The cohort globally shifted towards milder DOC over time, moving from overall 'moderate/near coma' at three months to 'near/no coma' at six months post-injury. The shift was captured by both CNCS and LOCFAS. CNCS differentiated levels of coma at best, while LOCFAS was superior in characterizing the emergence from coma. Agreement between scales was fair, and reduced negative findings at less than 10%. Patients with traumatic brain injury (TBI) vs. non-traumatic brain injury (NTBI) were older and had neurosurgical intervention more frequently. No relation between age and the level of consciousness was found overall. Concurrent administration of CNCS and LOCFAS reduced the rate of false negatives and better detected signs of arousal and awareness. This provides indication to administer both tools to increase measurement precision.

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The addition of genetic factors to prognostic models of neurobehavioral recovery following pediatric traumatic brain injury (TBI) may account for unexplained heterogeneity in outcomes. The present study examined the cumulative influence of candidate genes involved in the inflammatory response on long-term neurobehavioral recovery in children with early childhood TBI relative to children with orthopedic injuries (OI). Participants were drawn from a prospective, longitudinal study evaluating outcomes of children who sustained TBI (n = 67) or OI (n = 68) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at an average of 6.8 years after injury. Exploratory unweighted and weighted polygenic risk scores (PRS) were constructed from single nucleotide polymorphisms (SNPs) across candidate inflammatory response genes (i.e., angiotensin converting enzyme [ACE], brain-derived neurotrophic factor [BDNF], interleukin-1 receptor antagonist [IL1RN], and 5'-ectonucleotidase [NT5E]) that showed nominal (p ≤ 0.20) associations with outcomes in the TBI group. Linear regression models tested the PRS × injury group (TBI vs. OI) interaction term and post-hoc analyses examined the effect of PRS within each injury group. Higher inflammatory response PRS were associated with more executive dysfunction and behavior problems in children with TBI but not in children with OI. The cumulative influence of inflammatory response genes as measured by PRS explained additional variance in long-term neurobehavioral outcomes, over and above well-established predictors and single candidate SNPs tested individually. The results suggest that some of the unexplained heterogeneity in long-term neurobehavioral outcomes following pediatric TBI may be attributable to a child's genetic predisposition to a greater or lesser inflammatory response to TBI.

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