Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children.

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17 years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were completed by 48 h post-injury. A Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between two doses. Primary end points were quantitative brain volumes using MRI and microstructural integrity of the corpus callosum (diffusivity and oedema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring days and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo [decrease of 19 891 versus 40 491, respectively; mean difference of -20 600, 95% confidence interval (CI): -35 868 to -5332; P = 0.01], and the number of corpus callosum streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved corpus callosum connectivity in the treated groups (-431 streamlines placebo versus -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 h after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to: (i) shorter intensive care duration and decreased ICU intensity; (ii) white matter structural preservation; and (iii) enhanced corpus callosum connectivity and improved microstructural metrics.

Bayesian varying-effects vector autoregressive models for inference of brain connectivity networks and covariate effects in pediatric traumatic brain injury.

In this article, we develop an analytical approach for estimating brain connectivity networks that accounts for subject heterogeneity. More specifically, we consider a novel extension of a multi-subject Bayesian vector autoregressive model that estimates group-specific directed brain connectivity networks and accounts for the effects of covariates on the network edges. We adopt a flexible approach, allowing for (possibly) nonlinear effects of the covariates on edge strength via a novel Bayesian nonparametric prior that employs a weighted mixture of Gaussian processes. For posterior inference, we achieve computational scalability by implementing a variational Bayes scheme. Our approach enables simultaneous estimation of group-specific networks and selection of relevant covariate effects. We show improved performance over competing two-stage approaches on simulated data. We apply our method on resting-state functional magnetic resonance imaging data from children with a history of traumatic brain injury (TBI) and healthy controls to estimate the effects of age and sex on the group-level connectivities. Our results highlight differences in the distribution of parent nodes. They also suggest alteration in the relation of age, with peak edge strength in children with TBI, and differences in effective connectivity strength between males and females.

Novel Oppositional Defiant Disorder or Conduct Disorder 24 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The authors sought to identify predictive factors of new-onset or novel oppositional defiant disorder or conduct disorder assessed 24 months after traumatic brain injury (TBI). METHODS: Children ages 5 to 14 years who had experienced TBI were recruited from consecutive hospital admissions. Soon after injury, participants were assessed for preinjury characteristics, including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, and family function, and the presence and location of lesions were documented by MRI. Psychiatric outcomes, including novel oppositional defiant disorder or conduct disorder, were assessed 24 months after injury. RESULTS: Of the children without preinjury oppositional defiant disorder, conduct disorder, or disruptive behavior disorder not otherwise specified who were recruited in this study, 165 were included in this sample; 95 of these children returned for the 24-month assessment. Multiple imputation was used to address attrition. The prevalence of novel oppositional defiant disorder or conduct disorder was 23.7 out of 165 (14%). In univariable analyses, novel oppositional defiant disorder or conduct disorder was significantly associated with psychosocial adversity (p=0.049) and frontal white matter lesions (p=0.016) and was marginally but not significantly associated with SES. In the final multipredictor model, frontal white matter lesions were significantly associated with novel oppositional defiant disorder or conduct disorder (p=0.021), and psychosocial adversity score was marginally but not significantly associated with the outcome. The odds ratio of novel oppositional defiant disorder or conduct disorder among the children with versus those without novel depressive disorder was significantly higher for girls than boys (p=0.025), and the odds ratio of novel oppositional defiant disorder or conduct disorder among the children with versus those without novel attention-deficit hyperactivity disorder (ADHD) was significantly higher for boys than girls (p=0.006). CONCLUSION: Approximately 14% of children with TBI developed oppositional defiant disorder or conduct disorder. The risk for novel oppositional defiant disorder or conduct disorder can be understood from a biopsychosocial perspective. Sex differences were evident for comorbid novel depressive disorder and comorbid novel ADHD.

Further recommendations of the International Paediatric Brain Injury Society (IPBIS) for the post-acute rehabilitation of children with acquired brain injury.

BACKGROUND: Paediatric acquired brain injury is a life-long condition which impacts on all facets of the individual's lived experience. The existing evidence base continues to expand and new fields of enquiry are established as clinicians and researchers uncover the extent of these impacts. PRIMARY OBJECTIVE: To add to recommendations described in the International Paediatric Brain Injury Society's 2016 paper on post-acute care for children with acquired brain injury and highlight new areas of enquiry. REVIEW OF INFORMATION: Recommendations were made based on the opinions of a group of experienced international clinicians and researchers who are current or past members of the board of directors of the International Paediatric Brain Injury Society. The importance of each recommendation was agreed upon by means of group consensus. OUTCOMES: This update gives new consideration to areas of study including injuries which occur in pre-school children, young people in the military, medical referral, young offenders and the use of technology in rehabilitation.

Novel Psychiatric Disorder 6 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: To investigate the factors predictive of novel psychiatric disorders in the interval 0-6 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years consecutively hospitalized for mild to severe TBI at five hospitals were recruited. Participants were evaluated at baseline (soon after injury) for pre-injury characteristics including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, family function, family psychiatric history, and adaptive function. In addition to the psychosocial variables, injury severity and lesion location detected with acquisition of a research MRI were measured to develop a biopsychosocial predictive model for development of novel psychiatric disorders. Psychiatric outcome, including occurrence of a novel psychiatric disorder, was assessed 6 months after the injury. RESULTS: The recruited sample numbered 177 children, and 141 children (80%) returned for the six-month assessment. Of the 141 children, 58 (41%) developed a novel psychiatric disorder. In univariable analyses, novel psychiatric disorder was significantly associated with lower SES, higher psychosocial adversity, and lesions in frontal lobe locations, such as frontal white matter, superior frontal gyrus, inferior frontal gyrus, and orbital gyrus. Multivariable analyses found that novel psychiatric disorder was independently and significantly associated with frontal-lobe white matter, superior frontal gyrus, and orbital gyrus lesions. CONCLUSION: The results demonstrate that occurrence of novel psychiatric disorders following pediatric TBI requiring hospitalization is common and has identifiable psychosocial and specific biological predictors. However, only the lesion predictors were independently related to this adverse psychiatric outcome.

Long-term Participation and Functional Status in Children Who Experience Traumatic Brain Injury.

OBJECTIVE: To evaluate the effect of child and family factors on children's participation outcomes 2 to 3 years following traumatic brain injury (TBI). SETTING: Two level 1 pediatric trauma centers. PARTICIPANTS: Children aged 0 to 15 years with TBI at all severity levels or an orthopedic injury. DESIGN: Prospective cohort. MAIN MEASURES: Caregivers completed the Child and Adolescent Scale of Participation (CASP) at 2- and 3-year follow-ups. The CASP was categorized as more than 90 or 90 or less on a 100-point scale, with 90 or less representing the 10th percentile and below in this sample. Modified Poisson regression models were used to describe relative risk of the CASP at 90 or less at 2 to 3 years postinjury, adjusting for preinjury family environment variables and injury group. A secondary analysis only included children who were 31 months or older at injury (n = 441) to determine whether changes in functional outcome (Pediatric Injury Functional Outcome Scale, PIFOS) and executive functions (Behavior Rating Inventory of Executive Function, BRIEF) from preinjury to 1 year after injury predicted CASP scores at the 2- or 3-year follow-up. RESULTS: Seventy-eight percent (596/769) of children who had a completed preinjury survey had a completed CASP. In the adjusted model, children with severe TBI had a nearly 3 times higher risk (RR = 2.90; 95% CI, 1.43-5.87) of reduced participation than children with an orthopedic injury. In the secondary analysis, lower functional skills (5-point increase in 1-year postinjury PIFOS score) (RR = 1.36; 95% CI, 1.18-1.57) and less favorable family function (RR = 1.46; 95% CI, 1.02-2.10) were associated with reduced participation in both girls and boys. CONCLUSION: Participation in home, school, and community activities after TBI is related to multiple biopsychosocial factors. Participation-focused interventions are needed to reduce barriers to involvement and assist children and families to close the participation gap across settings.

Effective connectivity in the default mode network after paediatric traumatic brain injury.

Children who experience a traumatic brain injury (TBI) are at elevated risk for a range of negative cognitive and neuropsychological outcomes. Identifying which children are at greatest risk for negative outcomes can be difficult due to the heterogeneity of TBI. To address this barrier, the current study applied a novel method of characterizing brain connectivity networks, Bayesian multi-subject vector autoregressive modelling (BVAR-connect), which used white matter integrity as priors to evaluate effective connectivity-the time-dependent relationship in functional magnetic resonance imaging (fMRI) activity between two brain regions-within the default mode network (DMN). In a prospective longitudinal study, children ages 8-15 years with mild to severe TBI underwent diffusion tensor imaging and resting state fMRI 7 weeks after injury; post-concussion and anxiety symptoms were assessed 7 months after injury. The goals of this study were to (1) characterize differences in positive effective connectivity of resting-state DMN circuitry between healthy controls and children with TBI, (2) determine if severity of TBI was associated with differences in DMN connectivity and (3) evaluate whether patterns of DMN effective connectivity predicted persistent post-concussion symptoms and anxiety. Healthy controls had unique positive connectivity that mostly emerged from the inferior temporal lobes. In contrast, children with TBI had unique effective connectivity among orbitofrontal and parietal regions. These positive orbitofrontal-parietal DMN effective connectivity patterns also differed by TBI severity and were associated with persisting behavioural outcomes. Effective connectivity may be a sensitive neuroimaging marker of TBI severity as well as a predictor of chronic post-concussion symptoms and anxiety.

Novel Oppositional Defiant Disorder 12 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The investigators examined the factors predictive of novel oppositional defiant disorder in the 6-12 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years old who experienced a TBI were recruited from consecutive admissions to five hospitals. Participants were evaluated soon after injury (baseline) for preinjury characteristics, including psychiatric disorders, adaptive function, family function, psychosocial adversity, family psychiatric history, socioeconomic status, and injury severity, to develop a biopsychosocial predictive model for development of novel oppositional defiant disorder. MRI analyses were conducted to examine potential brain lesions. Psychiatric outcome, including that of novel oppositional defiant disorder, was assessed 12 months after injury. RESULTS: Although 177 children were recruited for the study, 120 children without preinjury oppositional defiant disorder, conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) returned for the 12-month assessment. Of these 120 children, seven (5.8%) exhibited novel oppositional defiant disorder, and none developed conduct disorder or DBD NOS in the 6-12 months postinjury. Novel oppositional defiant disorder was significantly associated with lower socioeconomic status, higher psychosocial adversity, and lower preinjury adaptive functioning. CONCLUSIONS: These results demonstrate that novel oppositional defiant disorder following TBI selectively and negatively affects an identifiable group of children. Both proximal (preinjury adaptive function) and distal (socioeconomic status and psychosocial adversity) psychosocial variables significantly increase risk for this outcome.

Novel Oppositional Defiant Disorder 6 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The investigators aimed to assess predictive factors of novel oppositional defiant disorder (ODD) among children and adolescents in the first 6 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years who experienced a TBI were recruited from consecutive admissions to five hospitals. Testing of a biopsychosocial model that may elucidate the development of novel ODD included assessment soon after injury (baseline) of preinjury characteristics, including psychiatric disorders, adaptive function, family function, psychosocial adversity, family psychiatric history, socioeconomic status, injury severity, and postinjury processing speed (which may be a proxy for brain injury). MRI analyses were also conducted to examine potential brain lesions. Psychiatric outcome, including that of novel ODD, was assessed 6 months after the injury. RESULTS: A total of 177 children and adolescents were recruited for the study, and 134 who were without preinjury ODD, conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) returned for the 6-month assessment. Of those who returned 6 months postinjury, 11 (8.2%) developed novel ODD, and none developed novel conduct disorder or DBD NOS. Novel ODD was significantly associated with socioeconomic status, preinjury family functioning, psychosocial adversity, and processing speed. CONCLUSIONS: These findings show that an important minority of children with TBI developed ODD. Psychosocial and injury-related variables, including socioeconomic status, lower family function, psychosocial adversity, and processing speed, significantly increase risk for this outcome.

Randomized Controlled Trial of Bovine Lactoferrin for Prevention of Sepsis and Neurodevelopment Impairment in Infants Weighing Less Than 2000 Grams.

OBJECTIVES: To determine the effect of bovine lactoferrin on prevention of late-onset sepsis (LOS) and neurodevelopment delay. STUDY DESIGN: Randomized, double-blind, controlled trial in neonates with a birth weight of 500-2000 g in 3 neonatal units in Lima, Peru, comparing bovine lactoferrin 200 mg/kg/day with placebo administered for 8 weeks. The primary outcome was the first episode of culture-proven LOS or sepsis-associated death. Neurodevelopment delay was assessed by the Mullen Scales at 24 months corrected age. RESULTS: Of the 414 infants enrolled, 209 received bovine lactoferrin and 205 received placebo. LOS or sepsis-associated death occurred in 22 infants (10.5%) in the bovine lactoferrin group vs 30 (14.6%) in the placebo group; there was no difference after adjusting for hospital and birth weight; hazard ratio 0.73 (95% CI, 0.42-1.26). For infants with birth weights of <1500 g the hazard ratio was 0.69 (95% CI, 0.39-1.25). The mean age-adjusted normalized Mullen composite score at 24 months was 83.3 ± 13.6 in the bovine lactoferrin group vs 82.6 ± 13.1 in the placebo group. Growth outcomes and rehospitalization rates during the 2-year follow-up were similar in both groups, except for significantly less bronchiolitis in the bovine lactoferrin group (rate ratio, 0.34; 95% CI, 0.14-0.86). CONCLUSIONS: Supplementation with bovine lactoferrin did not decrease the incidence of sepsis in infants with birth weights of <2000 g. Growth and neurodevelopment outcomes at 24 months of age were similar. Neonatal bovine lactoferrin supplementation had no adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01525316.

Changing Healthcare and School Needs in the First Year After Traumatic Brain Injury.

OBJECTIVE: To examine children's unmet and unrecognized healthcare and school needs following traumatic brain injury (TBI). SETTING: Two pediatric trauma centers. PARTICIPANTS: Children with all severity of TBI aged 4 to 15 years. DESIGN: Prospective cohort. MAIN MEASURES: Caregivers provided child health and school service use 3 and 12 months postinjury. Unmet and unrecognized needs were categorized compared with norms on standardized physical, cognitive, socioemotional health, or academic competence measures in conjunction with caregiver report of needs and services. Modified Poisson models examined child and family predictors of unmet and unrecognized needs. RESULTS: Of 322 children, 28% had unmet or unrecognized healthcare or school needs at 3 months, decreasing to 24% at 12 months. Unmet healthcare needs changed from primarily physical (79%) at 3 months to cognitive (47%) and/or socioemotional needs (68%) at 12 months. At 3 months, low social capital, preexisting psychological diagnoses, and 6 to 11 years of age predicted higher healthcare needs and severe TBI predicted higher school needs. Twelve months postinjury, prior inpatient rehabilitation, low income, and preexisting psychological diagnoses were associated with higher healthcare needs; family function was important for school and healthcare needs. CONCLUSIONS: Targeted interventions to provide family supports may increase children's access to services.

Healthcare Utilization and Missed Workdays for Parents of Children With Traumatic Brain Injury.

BACKGROUND: We enrolled patients in a prospective study in which we obtained estimates of the direct and indirect burden for families of children with traumatic brain injury (TBI) relative to a control group of families of children with orthopedic injury (OI). METHODS: Parents were surveyed at 3 time points following injury: 3, 6, and 12 months. At each follow-up contact, we asked parents to list the number of workdays missed, number of miles traveled, amount of travel-related costs, and whether their child had an emergency department (ED) visit, hospital admission, any over-the-counter (OTC) medications, and any prescription medications during that time period. We assessed the difference in these outcomes between the TBI and OI groups using multivariable logistic and 2-part regression models to account for high concentrations of zero values. RESULTS: Children with TBI had significantly greater odds of having an ED visit (3.04; 95% CI, 1.12-8.24), OTC medications (1.98; 95% CI, 1.34-2.94), and prescription medications (2.34; 95% CI, 1.19-4.59) than those with OI. In addition, parents of children with TBI missed significantly more days of work (19.91 days; 95% CI, 11.64-28.17) overall during the 12 months following injury than their OI counterparts. CONCLUSION: Extrapolating our results to the entire country, we estimate that pediatric TBI is associated with more than 670 000 lost workdays annually over the 12 months following injury, which translates into more than $150 million in lost productivity. These missed workdays and lost productivity may be prevented through safety efforts to reduce pediatric TBI.

Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells.

Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood-brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design. Adults with severe traumatic brain injury (Glasgow Coma Scale 5-8) and without signs of irreversible brain injury were evaluated for entry into the trial. A dose escalation format was performed in 25 patients: 5 controls, followed 5 patients in each dosing cohort (6, 9, 12 ×106 cells/kg body weight), then 5 more controls. Bone marrow harvest, cell processing to isolate the mononuclear fraction, and re-infusion occurred within 48 hours after injury. Patients were monitored for harvest-related hemodynamic changes, infusional toxicity, and adverse events. Outcome measures included magnetic resonance imaging-based measurements of supratentorial and corpus callosal volumes as well as diffusion tensor imaging-based measurements of fractional anisotropy and mean diffusivity of the corpus callosum and the corticospinal tract at the level of the brainstem at 1 month and 6 months postinjury. Functional and neurocognitive outcomes were measured and correlated with imaging data. Inflammatory cytokine arrays were measured in the plasma pretreatment, posttreatment, and at 1 and 6 month follow-up. There were no serious adverse events. There was a mild pulmonary toxicity of the highest dose that was not clinically significant. Despite the treatment group having greater injury severity, there was structural preservation of critical regions of interest that correlated with functional outcomes. Key inflammatory cytokines were downregulated. Treatment of severe, adult traumatic brain injury using an intravenously delivered autologous bone marrow mononuclear cell infusion is safe and logistically feasible. There appears to be a treatment signal as evidenced by central nervous system structural preservation, consistent with previous pediatric trial data. Inflammatory biomarkers are downregulated after cell infusion. Stem Cells 2016 Video Highlight: https://youtu.be/UiCCPIe-IaQ Stem Cells 2017;35:1065-1079.

Long-Term School Outcomes of Children and Adolescents With Traumatic Brain Injury.

OBJECTIVE: To better understand the impact of age at injury, severity of injury, and time since injury on long-term school outcomes of children with traumatic brain injury (TBI). PARTICIPANTS: Four groups of children: complicated mild/moderate TBI (n = 23), severe TBI (n = 56), orthopedic injury (n = 35), and healthy controls (n = 42). Children with TBI were either 2 years postinjury or 6 years postinjury. DESIGN: Cross-sectional design. MEASURES: School records as well as parental ratings of functional academic skills and school competency. RESULTS: Children with severe TBI had consistently high usage of school services and low school competency ratings than children with orthopedic injuries and healthy controls. In contrast, children with complicated-mild/moderate TBI were significantly more likely to receive school support services and have lower competence ratings at 6 years than at 2 years postinjury. Students injured at younger ages had lower functional academic skill ratings than those injured at older ages. CONCLUSIONS: These findings highlight the increasing academic challenges faced over time by students with complicated-mild/moderate TBI and the vulnerability of younger children to poorer development of functional academic skills.

Longitudinal diffusion tensor imaging after pediatric traumatic brain injury: Impact of age at injury and time since injury on pathway integrity.

Following pediatric traumatic brain injury (TBI), longitudinal diffusion tensor imaging may characterize alterations in initial recovery and subsequent trajectory of white matter development. Our primary aim examined effects of age at injury and time since injury on pathway microstructure in children ages 6-15 scanned 3 and 24 months after TBI. Microstructural values generated using tract-based spatial statistics extracted from core association, limbic, and projection pathways were analyzed using general linear mixed models. Relative to children with orthopedic injury, the TBI group had lower fractional anisotropy (FA) bilaterally in all seven pathways. In left-hemisphere association pathways, school-aged children with TBI had the lowest initial pathway integrity and showed the greatest increase in FA over time suggesting continued development despite incomplete recovery. Adolescents showed limited change in FA and radial diffusivity and had the greatest residual deficit suggesting relatively arrested development. Radial diffusivity was persistently elevated in the TBI group, implicating dysmyelination as a core contributor to chronic post-traumatic neurodegenerative changes. The secondary aim compared FA values over time in the total sample, including participants contributing either one or two scans to the analysis, to the longitudinal cases contributing two scans. For each pathway, FA values and effect sizes were very similar and indicated extremely small differences in measurement of change over time in the total and longitudinal samples. Statistical approaches incorporating missing data may reliably estimate the effects of TBI and provide increased power to identify whether pathways show neurodegeneration, arrested development, or continued growth following pediatric TBI. Hum Brain Mapp 37:3929-3945, 2016. © 2016 Wiley Periodicals, Inc.

Personality Change Due to Traumatic Brain Injury in Children and Adolescents: Neurocognitive Correlates.

Personality change due to traumatic brain injury (PC) in children is an important psychiatric complication of injury and is a form of severe affective dysregulation. This study aimed to examine neurocognitive correlates of PC. The sample included 177 children 5-14 years old with traumatic brain injury who were enrolled from consecutive admissions to five trauma centers. Patients were followed up prospectively at baseline and at 6 months, and they were assessed with semistructured psychiatric interviews. Injury severity, socioeconomic status, and neurocognitive function (measures of attention, processing speed, verbal memory, IQ, verbal working memory, executive function, naming/reading, expressive language, motor speed, and motor inhibition) were assessed with standardized instruments. Unremitted PC was present in 26 (18%) of 141 participants assessed at 6 months postinjury. Attention, processing speed, verbal memory, IQ, and executive function were significantly associated with PC even after socioeconomic status, injury severity, and preinjury attention deficit hyperactivity disorder were controlled. These findings are a first step in characterizing concomitant cognitive impairments associated with PC. The results have implications beyond brain injury to potentially elucidate the neurocognitive symptom complex associated with mood instability regardless of etiology.

Psychiatric disorders in children and adolescents 24 months after mild traumatic brain injury.

This study aimed to better understand the occurrence of novel psychiatric disorders (NPDs) in children with mild traumatic brain injury (mTBI) in relation to preinjury variables, injury-related variables, and concurrent neurocognitive outcome. Eighty-seven children aged 5-14 years who had experienced mTBI were studied from consecutive hospital admissions with semistructured psychiatric interviews soon after injury (baseline). Fifty-four children were reassessed 24 months postinjury. Standardized instruments were used to evaluate injury severity, lesion characteristics, preinjury variables (lifetime psychiatric disorder, family psychiatric history, family function, socioeconomic status, psychosocial adversity, adaptive function, and academic function), and finally, postinjury neurocognitive and adaptive function. At 24 months postinjury, NPDs had occurred in 17 of 54 (31%) participants. NPD at 24 months was related to frontal white matter lesions and was associated with estimated preinjury reading, preinjury adaptive function, and concurrent deficits in reading, processing speed, and adaptive function. These findings extend earlier reports that the psychiatric morbidity after mTBI in children is more common than previously thought, and moreover, it is linked to preinjury individual variables and injury characteristics and is associated with postinjury adaptive and neurocognitive functioning.

Neuropsychological performance of youth with secondary attention-deficit/hyperactivity disorder 6- and 12-months after traumatic brain injury.

The present study compared executive dysfunction among children with attention-deficit/hyperactivity disorder (ADHD) after traumatic brain injury (TBI), also called secondary ADHD (S-ADHD), pre-injury ADHD and children with TBI only (i.e., no ADHD). Youth aged 6-16 years admitted for TBI to five trauma centers were enrolled (n=177) and evaluated with a semi-structured psychiatric interview scheduled on three occasions (within 2 weeks of TBI, i.e., baseline assessment for pre-injury status; 6-months and 12-months post-TBI). This permitted the determination of 6- and 12-month post-injury classifications of membership in three mutually exclusive groups (S-ADHD; pre-injury ADHD; TBI-only). Several executive control measures were administered. Unremitted S-ADHD was present in 17/141 (12%) children at the 6-month assessment, and in 14/125 (11%) children at 12-months post-injury. The study found that children with S-ADHD exhibited deficient working memory, attention, and psychomotor speed as compared to children with pre-injury ADHD. Furthermore, the children with S-ADHD and the children with TBI-only were impaired compared to the children with pre-injury ADHD with regard to planning. No group differences related to response inhibition emerged. Age, but not injury severity, gender, or adaptive functioning was related to executive function outcome. Neuropsychological sequelae distinguish among children who develop S-ADHD following TBI and those with TBI only. Moreover, there appears to be a different pattern of executive control performance in those who develop S-ADHD than in children with pre-injury ADHD suggesting that differences exist in the underlying neural mechanisms that define each disorder, underscoring the need to identify targeted treatment interventions.

Assessing recovery and disability after physical trauma: the Pediatric Injury Functional Outcome Scale.

OBJECTIVE: To establish reliability and validity of the Pediatric Injury Functional Outcome Scale (PIFOS), a brief injury-specific rating scale covering motor, self-care, communication, social-emotional, cognition, physical, and academic areas. METHODS: In a prospective longitudinal study, the PIFOS structured interview was administered to parents of children 3-15 years of age at 3 and 12 months after hospitalization for traumatic brain injury (TBI) or orthopedic injury (OI). RESULTS: The total score had good internal consistency (α = .90-.93) and inter-rater reliability (α = .90) and correlated significantly with injury severity and neurodevelopmental outcomes. Generalized linear modeling showed the PIFOS was sensitive to the type and severity of injury, showed specific initial and persisting difficulties following TBI and OI, and was responsive to change during the first year after injury. Both groups had residual difficulties with coordination, emotionality, social participation, and discomfort. CONCLUSION: The PIFOS is useful in examining recovery in natural history and intervention studies.

Social interaction in young children with inflicted and accidental traumatic brain injury: relations with family resources and social outcomes.

Core social interaction behaviors were examined in young children 0-36 months of age who were hospitalized for accidental (n = 61) or inflicted (n = 64) traumatic brain injury (TBI) in comparison to typically developing children (n = 60). Responding to and initiating gaze and joint attention (JA) were evaluated during a semi-structured sequence of social interactions between the child and an examiner at 2 and 12 months after injury. The accidental TBI group established gaze less often and had an initial deficit initiating JA that resolved by the follow-up. Contrary to expectation, children with inflicted TBI did not have lower rates of social engagement than other groups. Responding to JA was more strongly related than initiating JA to measures of injury severity and to later cognitive and social outcomes. Compared to complicated-mild/moderate TBI, severe TBI in young children was associated with less responsiveness in social interactions and less favorable caregiver ratings of communication and social behavior. JA response, family resources, and group interacted to predict outcomes. Children with inflicted TBI who were less socially responsive and had lower levels of family resources had the least favorable outcomes. Low social responsiveness after TBI may be an early marker for later cognitive and adaptive behavior difficulties.