David W. Dunn

Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders

Objective: To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid tic disorders. Methods: Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders–IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks. Results: Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (–5.5 ± 6.9 vs –3.0 ± 8.7, p = 0.063) and Tic Symptom Self-Report total score (–4.7 ± 6.5 vs –2.9 ± 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (–0.7 ± 1.2 vs –0.1 ± 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (–10.9 ± 10.9 vs –4.9 ± 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (–0.8 ± 1.1 vs –0.3 ± 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures. Conclusions: Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.

Adolescents with active or inactive epilepsy or asthma : A comparison of quality of life

Summary: Purpose: We compared quality of life (QOL) in youth with inactive or active epilepsy with that of a similar sample of youth with asthma. We explored 19 different dimensions in three domains (psychological, social, and school) and also determined differences related to illness severity and gender.

Depression and epilepsy: Epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence☆

Depression is the most frequent psychiatric comorbidity in people with epilepsy (PWE) with lifetime prevalence rates ranging between 30 and 35%. Multifactorial variables play a pathogenic role in the high comorbid occurrence of these two disorders. These variables were critically examined during an international symposium held in Chicago in September 2010, the results of which are presented in two companion manuscripts. The first manuscript summarizes new epidemiologic data highlighting the bidirectional relation between depression and epilepsy and related methodological issues in studying this relationship. An examination of the neurobiologic aspects of primary mood disorders, mood disorders in PWE and pathogenic mechanisms of epilepsy derived from studies in animal models and humans is allowing a better understanding of the complex relation between the two conditions. In the first manuscript, we review data from animal models of epilepsy in which equivalent symptoms of depression and anxiety disorders develop and, conversely, animal models of depression in which the kindling process is facilitated. Data from structural and functional neuroimaging studies in humans provide a further understanding of potential common pathogenic mechanisms operant in depression and epilepsy that may explain their high comorbidity. The negative impact of depression on the control of seizure disorders has been documented in various studies. In this manuscript, these data are reviewed and potential mechanisms explaining this phenomenon are proposed.

Neuropsychological status at seizure onset in children Risk factors for early cognitive deficits

Objective: This large, prospective, community-based study characterized neuropsychological functioning and academic achievement at the time of the first recognized seizure and identified risk factors for cognitive deficits. Methods: We compared 282 children (ages 6–14 years, IQ ≥70) with a first recognized seizure to 147 healthy siblings on a battery of well-standardized and widely used neuropsychological and academic achievement tests and examined relationships with demographic and clinical variables. Results: In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychological deficits at or near onset. Risk factors associated with neuropsychological deficits included multiple seizures (i.e., second unprovoked seizure; odds ratio [OR] = 1.96), use of antiepileptic drugs (OR = 2.27), symptomatic/cryptogenic etiology (OR = 2.15), and epileptiform activity on the initial EEG (OR = 1.90); a child with all 4 risks is 3.00 times more likely than healthy siblings to experience neuropsychological deficits by the first clinic visit. Absence epilepsy carried increased odds for neuropsychological impairment (OR = 2.00). Conclusions: A subgroup of intellectually normal children with seizures showed neuropsychological deficits at onset. Academic achievement was unaffected, suggesting that there is a window early in the disorder for intervention to ameliorate the impact on school performance. Therefore, the risk factors identified here (especially if multiple risks are present) warrant swift referral for neuropsychological evaluation early in the course of the condition.

Consensus statement: the evaluation and treatment of people with epilepsy and affective disorders.

Affective disorders in people with epilepsy (PWE) have become increasingly recognized as a primary factor in the morbidity and mortality of epilepsy. To improve the recognition and treatment of affective disorders in PWE, an expert panel comprising members from the Epilepsy Foundations Mood Disorders Initiative have composed a Consensus Statement. This document focuses on depressive disorders in particular and reviews the appearance and treatment of the disorder in children, adolescents, and adults. Idiosyncratic aspects of the appearance of depression in this population, along with physiological and cognitive issues and barriers to treatment, are reviewed. Finally, a suggested approach to the diagnosis of affective disorders in PWE is presented in detail. This includes the use of psychometric tools for diagnosis and a stepwise algorithmic approach to treatment. Recommendations are based on the general depression literature as well as epilepsy-specific studies. It is hoped that this document will improve the overall detection and subsequent treatment of affective illnesses in PWE.

Recurrent Seizures and Behavior Problems in Children with First Recognized Seizures: A Prospective Study

Summary:  Purpose: Children with epilepsy have high rates of behavior problems. The purpose was to describe prospectively the association of seizures and behavior problems in children with new‐onset seizures.

Neuropsychological Predictors of Academic Underachievement in Pediatric Epilepsy: Moderating Roles of Demographic, Seizure, and Psychosocial Variables

Summary:  Purpose: Academic underachievement is common in pediatric epilepsy. Attempts to identify seizure and psychosocial risk factors for underachievement have yielded inconsistent findings, raising the possibility that seizure and psychosocial variables play a complex role in combination with other variables such as neuropsychological functioning. This study cross‐validated a neuropsychological measurement model for childhood epilepsy, examined the relation between neuropsychological functioning and academic achievement, and tested the degree to which demographic, seizure, and psychosocial variables moderate that relation.

Academic Underachievement Among Children With Epilepsy: Proportion Exceeding Psychometric Criteria for Learning Disability and Associated Risk Factors

This study assessed rates of learning disabilities (LD) by several psychometric definitions in children with epilepsy and identified risk factors. Participants (N = 173, ages 8—15 years) completed IQ screening, academic achievement testing, and structured interviews. Children with significant head injury, chronic physical conditions, or mental retardation were excluded. Using an IQ—achievement discrepancy definition, 48% exceeded the cutoff for LD in at least one academic area; using low-achievement definitions, 41% to 62% exceeded cutoffs in at least one academic area. Younger children with generalized nonabsence seizures were at increased risk for math LD using the IQ—achievement discrepancy definition; age of seizure onset and attention-deficit/hyperactivity disorder (ADHD) were risk factors for reading and math LD using low-achievement definitions. Writing was the most common domain affected, but neither ADHD nor seizure variables reliably identified children at risk for writing LD. Although children with earlier seizure onset, generalized nonabsence seizures, and comorbid ADHD appear to be at increased risk for some types of LD by some definitions, these findings largely suggest that all children with epilepsy should be considered vulnerable to LD. A diagnosis of epilepsy (even with controlled seizures and less severe seizure types) should provide sufficient cause to screen school-age children for LD and comorbid ADHD.

Measuring stigma in children with epilepsy and their parents: instrument development and testing

PURPOSE The goal of this work is to describe psychometric properties of two scales measuring perceived stigma in children with epilepsy and their parents. METHODS Data were collected for the parent scale in two samples: parents of 173 children with epilepsy and of 224 children with new-onset seizures. The child scale was tested in the chronic sample. Content validity, internal consistency reliability, and construct validity were tested. RESULTS Both scales had strong internal consistency reliability and construct validity. Higher scores were associated with greater seizure severity scores. In the parent scale, lower scores were associated with more positive mood, less worry, and more family leisure activities. In the child scale, higher scores were correlated with more negative attitude, greater worry, poorer self-concept, and more depression symptoms. CONCLUSIONS Both scales were found to have strong psychometric properties. They are short, and items are easy to understand. These scales have potential for use in research and in the clinical setting to measure stigma.

Behavioral issues involving children and adolescents with epilepsy and the impact of their families: recent research data

OBJECTIVE Using data from a larger study on new-onset seizures, we reported preliminary findings concerning relationships between family factors and child behavioral problems at baseline and 24 months. We also explored which baseline and changes in family factors were associated with changes in child behavioral problems over the 24-month period. METHODS Subjects were 224 children and their primary caregivers. Data were collected using structured telephone interviews and analyzed using multiple regression. RESULTS Deficient family mastery and parent confidence in managing their childs discipline were associated with behavior problems at baseline and at 24 months; they also predicted child behavior problems over time. Decreasing parent confidence in disciplining their child was associated with increasing child behavior problems. Decreases in parent emotional support of the child were associated with increases in child internalizing problems. CONCLUSION Child behavior problems, family environment, and parenting behaviors should be assessed when children present to the clinical setting with new-onset seizures.