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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.

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.

To investigate the relationships among age at injury, neuroanatomic lesion location, and measures of executive function (EF) following paediatric traumatic brain injury (TBI).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.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.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.

OBJECTIVES The utility of a depth of lesion classification using an SPGR MRI sequence in children with moderate to severe traumatic brain injury (TBI) was examined. Clinical and depth of lesion classification measures of TBI severity were used to predict neurological and functional outcome after TBI. METHODS One hundred and six children, aged 4 to 19, with moderate to severe TBI admitted to a rehabilitation unit had an SPGR MRI sequence obtained 3 months afterTBI. Acquired images were analyzed for location, number, and size of lesions. The Glasgow coma scale (GCS) was the clinical indicator of severity. The deepest lesion present was used for depth of lesion classification. Speed of injury was inferred from the type of injury. The disability rating scale at the time of discharge from the rehabilitation unit (DRS1) and at 1 year follow up (DRS2) were functional outcome measures. RESULTS The depth of lesion classification was significantly correlated with GCS severity, number of lesions, and both functional measures, DRS1 and DRS2. This result was more robust for time 1, probably due to the greater number of psychosocial factors impacting on functioning at time 2. Lesion volume was not correlated with the depth of lesion model. In multivariate models, depth of lesion was most predictive of DRS1, whereas GCS was most predictive of DRS2. CONCLUSIONS A depth of lesion classification of TBI severity may have clinical utility in predicting functional outcome in children and adolescents with moderate to severe TBI.

Journal of the American Academy of Child & Adolescent Psychiatry - Vol. 53 - N° 2 - p. 138-140

Objective To determine premorbid prevalence of attention-deficit hyperactivity disorder (ADHD) in children with moderate and severe closed head injury (CHI), to determine incidence of ADHD 1 year after injury, and to characterize children who develop ADHD by demographic, neuropsychiatric, and outcome variables. Method Ninety-nine children who had severe and moderate CHI were followed up for 1 year. Premorbid and 1-year postinjury psychiatric status were ascertained by parent and child structured interviews and questionnaires measuring affective lability, aggression, apathy, and social judgment. Result Premorbid prevalence of ADHD was 0.20, significantly higher than in a reference population (0.045). Fifteen of the remaining 80 children (0.19) developed full ADHD criteria (except for age of onset) by the end of the first year. Children who developed secondary ADHD (S-ADHD) had significantly greater premorbid psychosocial adversity, posttraumatic affective lability and aggression, posttraumatic psychiatric comorbidity, and overall disability than children who did not develop S-ADHD. Conclusion There is an excess prevalence of premorbid ADHD among children who present with moderate and severe CHI. Children with high psychosocial adversity are more likely to develop S-ADHD after CHI. S-ADHD has criteria in common with personality change due to CHI, a deficit in behavioral inhibition being the major overlapping feature.

A 16-item Children's Motivation Scale (CMS) was developed to evaluate level of motivation in children and adolescents. The study population consisted of a normative sample of 290 school children and a clinical sample of 165 child and adolescent psychiatric patients. Test-retest, internal consistency, and interrater reliability were fair to good for both samples. Validity of the CMS was demonstrated by its ability to differentiate clinical from normative samples according to the level of motivation, by a significant correlation of the CMS with an independent measure of withdrawal, and by its lack of correlation with an independent measure of depression. Principal components analysis identified a three-component structure. These findings support the conclusion that the CMS accesses a clinically important but often overlooked psychiatric construct.

A composition researcher and psychiatrist report findings from their 3-year study of the revision of the most important book in the mental health profession: the Diagnostic and Statistical Manual o...

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.

MICHAEL V. JOHNSTON, MD, and JOAN P. GERRING, MD

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.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.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.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.

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.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 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.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.

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. Language: en

This practice parameter describes the assessment and treatment of children and adolescents with attention-deficit/ hyperactivity disorder (ADHD) based on the current scientific evidence and clinical consensus of experts in the field. This parameter discusses the clinical evaluation for ADHD, comorbid conditions associated with ADHD, research on the etiology of the disorder, and psychopharmacological and psychosocial interventions for ADHD. J. Am. Acad. Child Adolesc. Psychiatry, 2007;46(7):894Y921. Key Words: attention-deficit/hyperactivity disorder, evaluation, treatment, practice parameter.

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. (JINS, 2005, 11, 686–696.)

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. (JINS, 2005, 11, 645–653.)

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.

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.

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. Copyright RSNA, 2002.

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.

To characterize children who develop Secondary Attention Deficit Hyperactivity Disorder (S-ADHD) after severe and moderate closed head injury (CHI) according to neuroimaging variables.Ninety-nine children from 4-19 years who suffered severe and moderate CHI were prospectively followed for a year after injury. Premorbid psychiatric status was determined by administration to the parent of a structured psychiatric interview. This interview was readministered 1 year after injury to determine the presence of post-closed head injury S-ADHD. An MRI was performed 3 months after injury to define lesion locations and volumes.A set of multiple logistic regression models determined that the odds of developing S-ADHD were 3.64 times higher among children with thalamus injury, and 3.15 times higher among children with basal ganglia injury. There was no significant difference in lesion volumes in any of the locations of interest between the group who developed S-ADHD and the group who did not develop S-ADHD.The data support an association between S-ADHD and injury in either or both the thalamus and basal ganglia, but they do not definitively demonstrate whether injury in either structure has an effect on S-ADHD in the absence of injury in the other.

PURPOSE: To determine whether there is an association between the spatial distribution of lesions detected at magnetic resonance (MR) imaging of the brain in children after closed-head injury and the development of secondary attention-deficit/hyperactivity disorder (ADHD). MATERIALS AND METHODS: Data obtained from 76 children without prior history of ADHD were analyzed. MR images were obtained 3 months after closed-head injury. After manual delineation of lesions, images were registered to the Talairach coordinate system. For each subject, registered images and secondary ADHD status were integrated into a brain-image database, which contains depiction (visualization) and statistical analysis software. Using this database, we assessed visually the spatial distributions of lesions and performed statistical analysis of image and clinical variables. RESULTS: Of the 76 children, 15 developed secondary ADHD. Depiction of the data suggested that children who developed secondary ADHD had more lesions in the right putamen than children who did not develop secondary ADHD; this impression was confirmed statistically. After Bonferroni correction, we could not demonstrate significant differences between secondary ADHD status and lesion burdens for the right caudate nucleus or the right globus pallidus. CONCLUSION: Closed-head injury-induced lesions in the right putamen in children are associated with subsequent development of secondary ADHD. Depiction software is useful in guiding statistical analysis of image data.

The Children's Affective Lability Scale (CALS) is a 20-item parent report measure developed to assess affect regulation in children aged 6-16. It was normed with school children in regular education classrooms and with children hospitalized in a psychiatric facility. Internal-consistency reliability, split-half reliability, and two-week test-retest reliability were excellent. Staff interrater reliability in the psychiatric sample was acceptable. Higher CALS scores were observed in an in-patient psychiatric sample than in either an out-patient or a normative sample. A principal components factor analysis yielded two components for the normative sample.

Severe closed head injury often results in physical, neuropsychologic, and psychiatric sequelae in the patient and in psychosocial disruption within the family. Because of the resulting deficits, the normal movement of the injured child toward increased independence is thwarted, and he or she often moves back to a state of increased dependency. The spectrum of sequelae may be mild to severe and includes almost the full range of child and adolescent psychopathology, perhaps because one of the most common and striking sequela is enhancement of previously existing disturbances. A syndrome of behavioral disinhibition is a disorder unique to this population. The psychiatric sequelae often appear as the physical and cognitive status improves in the year following injury, and they may eventually dominate the clinical picture. Duration of coma and of posttraumtic amnesia are measures of global brain dysfunction and are the best indicators of overall prognosis. Many child and adolescent patients with sequelae of severe closed head injuries have had histories of psychiatric on behavioral disorders or drug or alcohol abuse prior to their injury. Posttraumatic psychiatric sequelae consist of the same behavioral and psychiatric disorders that affect children or adolescents who have not had head injuries. Standard treatment methods for similar on other diagnostic entities are being tailored to the needs of children and adolescents with severe closed head injury. Medications are currently being used to control symptoms of aggression, agitation, and impairment of memory. Because of the integral involvement of the family in the recovery process, psychosocial intervention must be an important component of any treatment program.