Prevalence and predictors of affective lability after paediatric traumatic brain injury.

OBJECTIVE: Paediatric severe traumatic brain injury (TBI) is associated with significant post-injury affective and behavioural problems. Few studies have examined the prevalence and characteristics of affective lability after paediatric TBI. METHODS: Ninety-seven children with severe TBI were evaluated 1 year post-injury for the presence of affective lability using the Children's Affective Lability Scale (CALS). Demographic, clinical and brain lesion characteristics were also assessed. RESULTS: Affective lability significantly increased after injury. Eighty-six children had a pre-injury CALS score of 1 SD or less from the group pre-injury mean (M = 8.11, SD = 9.31), of which 35 and 15 children had a 1 SD and 2 SD increase in their CALS score from pre- to post-injury, respectively. A variety of affective shifts manifested post-injury including anxiety, silliness, dysphoria and irritability. The most severe symptoms were irritability and unpredictable temper outbursts. Risk factors for affective lability included elevated pre-injury affective lability and psychosocial adversity as well as greater damage to the orbitofrontal cortex. Post-injury affective lability was most frequently associated with a post-injury diagnosis of attention-deficit hyperactivity disorder. CONCLUSIONS: Affective lability is common after paediatric TBI and frequently manifests as irritability and unpredictable outbursts. Early intervention is needed to improve psychiatric outcomes.

The iron status of children and youth in a community mental health clinic is lower than that of a national sample.

OBJECTIVE: Iron plays a key role in brain function, and a deficiency of iron has been implicated in various cognitive, motor, and psychiatric disorders. Because of recent evidence that iron deficiency may be related to attention-deficit/hyperactivity disorder (ADHD) and other psychiatric disorders, the goal of this study was to compare the iron status of children and youth seen in a community mental health clinic with a national sample of same-aged subjects. METHODS: In this study, a consecutive series of 108 patients (79 males) referred to a community mental health clinic was compared with a National Health and Nutrition Examination Survey (NHANES) sample on measures of iron status. Wilcoxon sign rank and median tests were used to compare distributions of ferritin. Quantile regression was performed to compare the ferritin level in the two samples while adjusting for demographic differences. Chi squared (χ2) was used to compare rates of low hemoglobin in the two samples. RESULTS: The iron status of the clinic sample, as measured by ferritin levels (median=23 µg/L), was significantly lower than that of the national sample (median=43 µg/L). After adjustment for age, gender, and race, the clinic sample was found to have 19.2 µg/L lower ferritin than the national sample (95% CI from 7.6 to 30.9, p value=0.001). There were also significantly more subjects in the clinic sample with low hemoglobin than in the national sample. There were no differences in ferritin levels between those patients in the clinic sample with and without an ADHD or other specific psychiatric diagnosis. CONCLUSIONS: The ferritin levels of children and youth in a mental health clinic sample were significantly lower than those of the same-aged subjects in a national sample. Therefore, compromised iron status may be an additional biological risk factor for cognitive, behavioral, and psychiatric problems in pediatric populations served by the community mental health clinic.

The essential role of psychosocial risk and protective factors in pediatric traumatic brain injury research.

This article builds upon Traumatic Brain Injury Common Data Elements (TBI CDE) version 1.0 and the pediatric CDE Initiative by emphasizing the essential role of psychosocial risk and protective factors in pediatric TBI research. The goals are to provide a compelling rationale for including psychosocial risk and protective factors in addition to socioeconomic status (SES), age, and sex in the study design and analyses of pediatric TBI research and to describe recommendations for core common data elements in this domain. Risk and protective factor research is based on the ecological theory of child development in which children develop through a series of interactions with their immediate and more distant environments. Home, school, religious, and social influences are conceptualized as risk and/or protective factors. Child development and TBI researchers have interpreted risk and protective variables as main effects or as interactions and have used cumulative risk indices and moderation models to describe the relationship among these variables and outcomes that have to do with development and with recovery from TBI. It is likely that the number, type, and interaction among risk and protective factors each contribute unique variance to study outcomes. Longitudinal designs in TBI research will be essential to understanding the reciprocal relationships between risk/protective factors and the recovery/outcome made by the child. The search for effective interventions to hasten TBI recovery mandates the need to target modifiable risks and to promote protective factors in the child's environment.

Recommendations for the use of common outcome measures in pediatric traumatic brain injury research.

This article addresses the need for age-relevant outcome measures for traumatic brain injury (TBI) research and summarizes the recommendations by the inter-agency Pediatric TBI Outcomes Workgroup. The Pediatric Workgroup's recommendations address primary clinical research objectives including characterizing course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements (CDE) Workgroups, the Pediatric TBI Outcomes Workgroup adopted the standard three-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in pediatric TBI from each identified domain including academics, adaptive and daily living skills, family and environment, global outcome, health-related quality of life, infant and toddler measures, language and communication, neuropsychological impairment, physical functioning, psychiatric and psychological functioning, recovery of consciousness, social role participation and social competence, social cognition, and TBI-related symptoms. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.

Disruptive behaviour disorders and disruptive symptoms after severe paediatric traumatic brain injury.

OBJECTIVE: To determine pre-injury prevalence and post-injury incidence of DSM-III-R oppositional defiant disorder (ODD) and conduct disorder (CD), increase in disruptive symptoms after severe paediatric traumatic brain injury (TBI) and risk factors associated with development of these disturbances. METHODS: Ninety-four children were followed 1 one year after severe TBI. Assessments of pre-injury and 1-year psychiatric status were ascertained by parent report. The 1-year incidence of disruptive behaviour disorders/symptoms was the main outcome measure. RESULTS: The pre-injury prevalence of ODD and CD in the TBI sample was 6% and 8%, respectively, the prevalence of pre-injury CD being significantly higher than in a reference population. The incidence of new-onset ODD and CD 1-year post-injury was 9% and 8%, respectively, the incidence of new-onset CD being significantly higher than in a reference population. ODD symptoms and total number of disruptive symptoms increased significantly over the first post-injury year. Significant risk factors for disruptive disorders/symptoms included higher pre-injury psychosocial adversity, delinquency ratings and affective lability. CONCLUSIONS: Pre-injury conduct disorder is a significant risk factor for post-injury disruptive behaviours. New-onset CD and disruptive symptoms are consequences of TBI at 1-year post-injury. Risk factors for these post-injury disturbances are similar to risk factors in non-TBI populations.

Prevalence of aggressive behaviour after severe paediatric traumatic brain injury.

OBJECTIVE: The goals of this study were to explore the prevalence of aggressive behaviours after severe paediatric traumatic brain injury (TBI) and identify predictors of aggressive behaviours 1 year post-injury. METHODS: A cohort of 97 children aged 4-19 years at time of severe TBI (GCS 3-8) were prospectively followed for 1 year. Pre-injury psychiatric status was obtained retrospectively at enrolment and post-injury behavioural and functional concerns were assessed at 1 year. Aggression was measured with a modified version of the Overt Aggression Scale (OAS). RESULTS: Results revealed aggressive behaviour increased from pre-injury to post-injury. Pre-injury factors including aggression, attention problems and anxiety were associated with increased post-injury aggressive behaviour. Children with greater disability after injury were also at increased risk for aggressive behaviours. CONCLUSIONS: Aggression is a prevalent symptom after paediatric TBI and can significantly impede rehabilitation. Awareness of these predictors can aid in early identification of children at risk in order to help appropriately design rehabilitation programmes.

Intensive care unit variables and outcome after pediatric traumatic brain injury: a retrospective study of survivors.

OBJECTIVE: Traumatic brain injury is a leading cause of death and disability in children. Hypotension has been associated with poor survival and outcome in children after traumatic brain injury, but the effect of acute hypertension is less certain. The objective was to obtain acute physiologic variables during the early hospitalization period in a cohort of children prospectively enrolled in another study. DESIGN: Retrospective chart reviews. SETTING: University-affiliated pediatric rehabilitation center. PATIENTS: Fifty-seven survivors, 5-17 yrs of age, admitted for rehabilitation between 1992 and 1995 after sustaining a traumatic brain injury. INTERVENTIONS: Standard of care. MEASUREMENTS AND MAIN RESULTS: Outcomes were assessed at 1 yr postinjury through cognitive testing of the child and parent interview of the child's global functional skills. Cognitive outcome was measured using the Performance IQ from the Wechsler Intelligence Scale for Children, Third Edition. Overall functional outcome was assessed using the Disability Rating Scale. CONCLUSIONS: This study suggests that early markers of secondary injury after moderate to severe traumatic brain injury in children may be predictive of long-term outcome. This study reinforces the need for longer term, systematic, and more precise measurements of outcomes in children with traumatic brain injury and prospective studies to examine the predictive value of acute management variables on multiple types of outcomes after traumatic brain injury in children.

Neuroanatomic correlates of CVLT-C performance following pediatric traumatic brain injury.

Traumatic brain injury (TBI) frequently results in memory problems, and the degree of memory impairment is related to injury severity and is commonly associated with lesions in frontal and temporal brain areas. This study examined the relationship among injury severity, brain lesions, and memory in children with moderate to severe TBI using Donders' (1999) 5-factor model of performance on the California Verbal Learning Test-Children's Version (CVLT-C). Seventy-six children underwent magnetic resonance imaging (MRI) scans 3 months post-TBI and testing 1 year post-TBI. Results showed injury severity (Glasgow Coma Scale) was not predictive of performance on 4 of the 5 factors. Volume of frontal and/or temporal brain lesions was significantly predictive of performance on 3 of the 5 factors. Unexpectedly, lesion volume outside these areas (extra-frontotemporal) was predictive of performance on all 5 factors. In contrast, Verbal IQ at 1 year was most strongly associated with preinjury factors (socioeconomic status and special education involvement), although extra-frontotemporal lesions also contributed to the variability in this measure. Results suggest that in children with moderate to severe TBI, extra-frontal/temporal lesions are predictive of memory outcome 1 year postinjury above and beyond initial severity or frontal/temporal contusions. This finding may relate to widespread diffuse axonal injury, which potentially disconnects brain circuits mediating memory following moderate to severe TBI.

Differences in attention, executive functioning, and memory in children with and without ADHD after severe traumatic brain injury.

Although the development of Attention Deficit Hyperactivity Disorder (ADHD) after traumatic brain injury (TBI) has been described, it is unknown whether children with TBI and ADHD have greater neuropsychological impairments than children with TBI alone. This study examines attention, executive functioning, and memory in children with TBI-only and TBI + ADHD. Caregivers of 82 children with severe TBI completed structured psychiatric interviews at enrollment to diagnose premorbid ADHD and one-year after injury to diagnose post-injury ADHD. Children underwent neuropsychological testing one year after injury. One memory measure significantly differentiated children with TBI-only from children with newly developed ADHD [secondary ADHD (S-ADHD)] and those with premorbid ADHD that persisted after injury [persisting ADHD (P-ADHD)]. Compared with the TBI-only group, children with TBI + ADHD had worse performance on measures of attention, executive functioning, and memory. Results reveal that in children with severe TBI, the behavioral diagnosis of ADHD is associated with more difficulty in attention, executive functioning, and memory. Additionally, results suggest greater deficits in memory skills in the S-ADHD group compared with the P-ADHD group. Although findings provide preliminary support for distinguishing P-ADHD from S-ADHD, further research is needed to investigate neuropsychological differences between these subgroups of children with severe TBI.

Longitudinal evolution of unidentified bright objects in children with neurofibromatosis-1.

Neurofibromatosis type-1 (NF-1) is the most common autosomal dominant disorder affecting the central nervous system. Magnetic resonance imaging (MRI) has revealed distinctive T2-weighted hyperintense foci (termed unidentified bright objects, UBOs) which appear to represent spongiform changes in the white matter. Cross-sectional and longitudinal analyses suggest that UBOs disappear over time; however, none of these studies have examined comprehensively these foci. We conducted a quantitative MRI longitudinal study of number of affected regions, number of UBOs per region, and UBO volume per region, in a sample of 12 children with NF-1. We applied semi-automatic morphometric methods and comprehensive statistical approaches, within a detailed anatomical parcellation framework. Our data demonstrate that, despite a similar UBO regional distribution (e.g., prevalent globus pallidus/internal capsule (GP/IC) location), UBO evolution was more complex than previously reported. In some subjects, the total number of UBO-occupied locations demonstrated a decrease between approximately ages 7 and 12 years, followed by a progressive increase during adolescence. This pattern was also found for UBO number and/or volume for all regions, with the exception of the cerebellar hemispheres. This REGIONAL distinction may reflect differences in white matter structure between affected long tract fiber bundles and that of cerebral and cerebellar myelinated fibers. The findings are also discussed in the context of previous MR and behavioral studies. We conclude that studies like the present one, in association with other MR modalities, are necessary to characterize more completely the nature and evolution of UBOs and their role in the cognitive phenotype of NF-1.

Neuroimaging correlates of anxiety after pediatric traumatic brain injury.

BACKGROUND: Anxiety disorders are common after traumatic brain injury (TBI). Data on the neural correlates of these conditions are lacking. This study examines the relationship between brain damage, particularly to the orbitofrontal cortex (OFC) and temporal lobe, and anxiety symptoms and disorders. METHODS: Ninety-five children and adolescents were followed for one year postinjury. Preinjury and one-year postinjury anxiety status were obtained from the parent. Magnetic resonance imaging was performed to evaluate brain lesions. The primary analysis used regression models to determine relationships between brain lesions and anxiety outcomes. As a secondary analysis, previously reported posttraumatic stress disorder (PTSD) data were reanalyzed using similar methods for purposes of comparison. RESULTS: The primary analysis showed that greater volume and number of OFC lesions correlated with decreased risk for anxiety, whereas lesions in other brain areas did not correlate with anxiety. Consistent with prior data, the secondary analysis showed an inverse correlation between OFC damage and PTSD; temporal lobe damage was positively correlated with PTSD. CONCLUSIONS: After pediatric TBI, greater damage to the OFC is associated with decreased risk for anxiety outcomes. Similar to adult data, these findings implicate OFC dysfunction in childhood anxiety. Temporal lobe damage did not correlate with anxiety, in contrast to the findings for PTSD.

Application of a data-mining method based on Bayesian networks to lesion-deficit analysis.

Although lesion-deficit analysis (LDA) has provided extensive information about structure-function associations in the human brain, LDA has suffered from the difficulties inherent to the analysis of spatial data, i.e., there are many more variables than subjects, and data may be difficult to model using standard distributions, such as the normal distribution. We herein describe a Bayesian method for LDA; this method is based on data-mining techniques that employ Bayesian networks to represent structure-function associations. These methods are computationally tractable, and can represent complex, nonlinear structure-function associations. When applied to the evaluation of data obtained from a study of the psychiatric sequelae of traumatic brain injury in children, this method generates a Bayesian network that demonstrates complex, nonlinear associations among lesions in the left caudate, right globus pallidus, right side of the corpus callosum, right caudate, and left thalamus, and subsequent development of attention-deficit hyperactivity disorder, confirming and extending our previous statistical analysis of these data. Furthermore, analysis of simulated data indicates that methods based on Bayesian networks may be more sensitive and specific for detecting associations among categorical variables than methods based on chi-square and Fisher exact statistics.

Performance on measures of executive function following pediatric traumatic brain injury.

OBJECTIVE: To investigate the relationships among age at injury, neuroanatomic lesion location, and measures of executive function (EF) following paediatric traumatic brain injury (TBI). METHODS: EF was assessed in 68 children (aged 7-15) with moderate-to-severe TBI 1 year post-injury. EF tests included: (1) Tower of Hanoi (TOH), a measure of problem solving ability, (2) Wisconsin Card Sorting Test (WCST), a measure of categorization and ability to shift cognitive strategies, (3) Letter Fluency (LF), a measure of novel lexical search and rule-governed word generation. EF variables included number of moves needed to achieve a 3-ring solution on the TOH, number of perseverative and non-perseverative errors on the WCST, and number of words generated on LF. Intellectual functioning was also assessed using the Verbal Intellectual Quotient (VIQ) from the Wechsler Intelligence Scale from Children-3rd edn (WISC-III). Data from standardized MRIs, performed at 3-months post-injury, were available for all subjects and were used to determine lesion location, lesion volumes, and total number of lesions. The relationships among EF, lesion variables (frontal lesion volume, extrafrontal lesion volume, total number of lesions) and age at injury were examined. Pre-injury special education services and attention deficit hyperactivity disorder (ADHD) were controlled for. RESULTS: Younger age at injury was associated with more perseverative errors on the WCST and worse performance on LF. Frontal lesion volume was not predictive of performance on any measures of EF. Greater extrafrontal lesion volume and total number of lesions were predictive of worse performance on LF. When controlling for pre-injury special education placement and pre-injury ADHD, there was little change in the results. CONCLUSIONS: Younger age at injury places children at greater risk of impairment on measures of EF. Performance on measures of EF depends on brain variables other than frontal lobes including extrafrontal cortical brain areas and total number of lesions. The relationship between extrafrontal brain regions and EF suggests that domain-specific cognitive content (i.e. language or visuospatial analysis), mediated by the parietal or temporal lobes, may disrupt underlying cognitive processes necessary for successful performance on measures of EF. In addition, the association between total number of lesions and EF may be related to disconnections and disruption of frontal/subcortical systems.

Is the spatial distribution of brain lesions associated with closed-head injury in children predictive of subsequent development of posttraumatic stress disorder?

PURPOSE: To determine whether there is an association between the spatial distributions of lesions detected at magnetic resonance (MR) imaging of the brain in children, adolescents, and young adults after closed-head injury (CHI) and development of the reexperiencing symptoms of posttraumatic stress disorder (PTSD). MATERIALS AND METHODS: Data obtained in 94 subjects without a history of PTSD as determined by parental interview were analyzed. MR images were obtained 3 months after CHI. Lesions were manually delineated and registered to the Talairach coordinate system. Mann-Whitney analysis of lesion distribution and PTSD status at 1 year (again, as determined by parental interview) was performed, consisting of an analysis of lesion distribution versus the major symptoms of PTSD: reexperiencing, hyperarousal, and avoidance. RESULTS: Of the 94 subjects, 41 met the PTSD reexperiencing criterion and nine met all three PTSD criteria. Subjects who met the reexperiencing criterion had fewer lesions in limbic system structures (eg, the cingulum) on the right than did subjects who did not meet this criterion (Mann-Whitney, P =.003). CONCLUSION: Lesions induced by CHI in the limbic system on the right may inhibit subsequent manifestation of PTSD reexperiencing symptoms in children, adolescents, and young adults.

Anxiety after severe pediatric closed head injury.

OBJECTIVE: To assess the frequency of anxiety symptoms and disorders 1 year after severe pediatric closed head injury (CHI) and to determine the risk factors associated with these postinjury outcomes. METHOD: Ninety-seven subjects were prospectively followed for 1 year after severe CHI (Glasgow Coma Scale Score = 3-8). Assessments of preinjury and 1-year postinjury psychiatric status and psychosocial adversity were conducted. Frequency of anxiety symptoms and disorders 1 year after injury were the outcome measures. Data collection occurred between 1992 and 1996. RESULTS: There was a significant increase in the total number of anxiety symptoms after injury compared with before injury. The most frequent symptoms were overanxious symptoms, followed by obsessive-compulsive symptoms, separation anxiety symptoms, and simple phobia symptoms. There was a trend toward an increase in the frequency of overanxious disorder after injury. Preinjury anxiety symptoms correlated positively with postinjury anxiety symptoms and disorders. Younger age at injury correlated positively with postinjury anxiety symptoms. CONCLUSIONS: One year after severe CHI, children are at risk for a variety of anxiety symptoms and, possibly, overanxious disorder. Preinjury anxiety and younger age at injury are risk factors for these disturbances.

Clinical predictors of posttraumatic stress disorder after closed head injury in children.

OBJECTIVE: To describe injury, demographic, and neuropsychiatric characteristics of children who develop posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS) after closed head injury (CHI). METHOD: Ninety-five children with severe CHI and amnesia for the event were prospectively followed for 1 year. Structured interviews were administered twice to the parents: shortly after injury to cover the child's premorbid status, and 1 year after injury. The child was also interviewed twice: shortly after injury to cover current status, and 1 year after injury. Outcome measures were diagnostic status (PTSD by parent or child) and symptom severity (PTSS by parent or child). RESULTS: Twelve children developed PTSD by 1 year after injury, 5 according to parent report, 5 according to child report, and 2 according to both parent and child report. Predictors of PTSD at 1 year post-CHI included female gender and early post-CHI anxiety symptoms. Predictors of PTSS at 1 year post-CHI were (1) premorbid psychosocial adversity, premorbid anxiety symptoms, and injury severity; and (2) early post-CHI depression symptoms and nonanxiety psychiatric diagnoses. CONCLUSIONS: PTSD developed in 13% of children with severe CHI accompanied by traumatic amnesia. Predictors of PTSD and PTSS after CHI, according to parent and child report, are consistent with predictors of PTSD and PTSS that develop after non-head injury trauma.