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Objective To characterize the presence and nature of discrete behavioral phenotypes and their correlates in a cohort of youth with new and recent onset focal and generalized epilepsies. Methods The parents of 290 youth (age = 8-18 years) with epilepsy (n = 183) and typically developing participants (n = 107) completed the Child Behavior Checklist for children aged 6-18 from the Achenbach System of Empirically Based Assessment. The eight behavior problem scales were subjected to hierarchical clustering analytics to identify behavioral subgroups. To characterize the external validity and co-occurring comorbidities of the identified subgroups, we examined demographic features (age, gender, handedness), cognition (language, perception, attention, executive function, speed), academic problems (present/absent), clinical epilepsy characteristics (epilepsy syndrome, medications), familial factors (parental intelligence quotient, education, employment), neuroimaging features (cortical thickness), parent-observed day-to-day executive function, and number of lifetime-to-date Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses. Results Hierarchical clustering identified three behavioral phenotypes, which included no behavioral complications (Cluster 1, 67% of epilepsy cohort [n = 122]), nonexternalizing problems (Cluster 2, 11% of cohort [n = 21]), and combined internalizing and externalizing problems (Cluster 3, 22% of cohort [n = 40]). These behavioral phenotypes were characterized by orderly differences in personal characteristics, neuropsychological status, history of academic problems, parental status, cortical thickness, daily executive function, and number of lifetime-to-date DSM-IV diagnoses. Cluster 1 was most similar to controls across most metrics, whereas Cluster 3 was the most abnormal compared to controls. Epilepsy syndrome was not a predictor of cluster membership. Significance Youth with new and recent onset epilepsy fall into three distinct behavioral phenotypes associated with a variety of co-occurring features and comorbidities. This approach identifies important phenotypes of behavior problem presentations and their accompanying factors that serve to advance clinical and theoretical understanding of the behavioral complications of children with epilepsy and the complex conditions with which they co-occur.

Objective To identify cognitive phenotypes in temporal lobe epilepsy (TLE) and test their reproducibility in a large, multi-site cohort of patients using both data-driven and clinically driven approaches. Method Four-hundred seven patients with TLE who underwent a comprehensive neuropsychological evaluation at one of four epilepsy centers were included. Scores on tests of verbal memory, naming, fluency, executive function, and psychomotor speed were converted into z-scores based on 151 healthy controls (HCs). For the data-driven method, cluster analysis (k-means) was used to determine the optimal number of clusters. For the clinically driven method, impairment was defined as >1.5 standard deviations below the mean of the HC, and patients were classified into groups based on the pattern of impairment. Results Cluster analysis revealed a three-cluster solution characterized by (a) generalized impairment (29%), (b) language and memory impairment (28%), and (c) no impairment (43%). Based on the clinical criteria, the same broad categories were identified, but with a different distribution: (a) generalized impairment (37%), (b) language and memory impairment (30%), and (c) no impairment (33%). There was a 82.6% concordance rate with good agreement (κ = .716) between the methods. Forty-eight patients classified as having a normal profile based on cluster analysis were classified as having generalized impairment (n = 16) or an isolated language/memory impairment (n = 32) based on the clinical criteria. Patients with generalized impairment had a longer disease duration and patients with no impairment had more years of education. However, patients demonstrating the classic TLE profile (ie, language and memory impairment) were not more likely to have an earlier age at onset or mesial temporal sclerosis. Significance We validate previous findings from single-site studies that have identified three unique cognitive phenotypes in TLE and offer a means of translating the patterns into a clinical diagnostic criteria, representing a novel taxonomy of neuropsychological status in TLE.

AIM To compare long-term psychosocial and functional outcomes of young adults with uncomplicated childhood-onset epilepsy (COE) to population norm controls utilizing a controlled prospective cohort study. METHOD Psychosocial and functional outcomes were assessed at 10-year follow-up. Fifty-three young adults (27 males, 26 females) with COE (n=21 remission; 18y 1mo-30y 9mo; mean age 23y 4mo [SD 3y 4mo]; mean age of epilepsy onset 12y [SD 3y 2mo]) were compared to 55 (23 males, 32 females) first-degree cousin controls (18y 5mo-29y 8mo; mean age 23y 6mo [SD 3y]). Seizure remission status and baseline comorbidities (attention-deficit/hyperactivity disorder [ADHD], depressive disorders, anxiety disorders, and academic problems) were examined as possible risk factors for significant differences in functional outcomes. RESULTS Poorer functional outcomes, indicated by patient rated cognition and overall disability, were evident among young adults with epilepsy compared to controls (all p

Purpose To characterize the impact of slowed processing speed on the efficiency of broader cognitive function in temporal lobe epilepsy (TLE). Methods Participants included 100 patients with TLE and 89 healthy controls (mean ages 36.8 and 33.6, respectively) administered a neuropsychological battery consisting of 15 cognitive metrics. Confirmatory factor analysis using structural equation modeling (SEM) latent variable modeling demonstrated a cognitive structure representing the domains of verbal intelligence, immediate memory, delayed memory, executive function, working memory, and processing speed. Furthermore, the latent variable measurement model determined the direct and indirect relationships of verbal intelligence and processing speed with immediate memory, delayed memory, executive function, and working memory. Results Following SEM of hypothesized structural models, the results demonstrated that, among controls, intelligence had a direct and unmediated (by processing speed) relationship with all identified cognitive domains. In contrast, among participants with TLE, processing speed mediated the relationship between verbal intelligence and performance across all cognitive domains. Conclusion Slowing of cognitive/psychomotor processing speed appears to play a critical mediating role in the broader cognitive status of participants with TLE and may serve as a target through which to attempt to exert a broad positive impact on neuropsychological status.

The present study investigates the effect of caregiver and care recipient risk and resistance factors on caregiver quality of life (QOL). Risk factors are those characteristics that contribute to psychosocial maladjustment of the caregiver and reduce QOL, while resistance factors promote caregiver adjustment and improve QOL.One-hundred and three caregiver/care recipient dyads were recruited from a memory assessment clinic in Midwestern United States. Caregivers completed questionnaires estimating perceived social support, spirituality, social problem-solving, and care recipient functional dependence. Care recipients' results from the Mini-Mental State Examination and Animal Naming task were also collected.In the final model, caregiver age, relationship type, social problem-solving, perceived social support, and care recipient functional dependence each accounted for a significant portion of variance in caregiver QOL. The final model accounted for 46.1% of the variance in caregiver QOL.Caregiver age, relationship type, social problem-solving, perceived social support, and care recipient functional dependence are important contributors to caregiver QOL. Further research is needed to specify which caregiver and care recipient characteristics are most important to caregiver QOL.Health professionals should assess caregiver problem-solving skills, social support, and care recipient functional dependence, as these may provide important information about caregiver QOL. Study results also suggest that caregiving has more of a negative impact on caregiver QOL for midlife adult caregivers compared to older adult caregivers, and appears to have a greater negative effect on spouses than on children.

This study investigated the association between processing speed and cortical morphometry in children with idiopathic epilepsies (n = 81) versus healthy controls (n = 57), age 8-18. Participants underwent 1.5 T MRI scanning and cognitive testing including assessment of psychomotor speed (Digit Symbol) at or near the time of epilepsy diagnosis. Vertex analyses of cortical volume, thickness, surface area, and local gyrification index (LGI), as well as volume-based analyses of subcortical structures and cerebellum, were used to determine the morphometric correlates of Digit Symbol performance. Group comparisons revealed that the epilepsy and control groups exhibited different patterns of morphometric association with Digit Symbol performance - controls exhibited several areas of correlation between LGI and psychomotor speed, whereas participants with focal epilepsies exhibited different areas of correlation in different directions, and participants with generalized epilepsy exhibited no correlations. The other cortical morphometric measures showed no regions of significant correlation with Digit Symbol performance. In addition, cerebellum and brain stem volumes correlated with Digit Symbol performance in the control group, but not in epilepsy patients. These results suggest that LGI analysis is able to capture nuanced relationships between features of cortical and subcortical morphology with psychomotor speed, these relationships disrupted in different ways in children with epilepsy.

Purpose Psychomotor slowing is a common but understudied cognitive impairment in epilepsy. Here we test the hypothesis that psychomotor slowing is associated with alterations in brain status reflected through network analysis of large scale structural networks. We test the hypothesis that children with epilepsy with cognitive slowing at diagnosis will exhibit a cross-sectional and prospective pattern of altered brain development. Methods A total of 78 children (age 8–18) with new/recent idiopathic epilepsies underwent 1.5 T MRI with network analysis of cortical, subcortical and cerebellar volumes. Children with epilepsy were divided into slow and fast psychomotor speed groups (adjusted for age, intelligence and epilepsy syndrome). Results At baseline, slow-speed performers (SSP) presented lower modularity, lower global efficiency, higher transitivity, and lower number of hubs than fast-speed performers (FSP). Community structure in SSP exhibited poor association between cortical regions and both subcortical structures and the cerebellum while FSP presented well-defined communities. Prospectively, SSP displayed lower modularity but higher global efficiency and transitivity compared to FSP. Modules in FSP showed higher integration between and within themselves compared to SSP. SSP showed hubs mainly from frontal and temporal regions while in FSP were spread among frontal, temporal, parietal, subcortical areas and the left cerebellum. Implications Results suggest the presence of widespread alterations in large scale networks between fast- and slow-speed children with recent onset epilepsies both at baseline and 2 years later. Slower processing speed appears to be a marker of abnormal brain development antecedent to epilepsy onset as well as brain development over the 2 years following diagnosis., Highlights • Baseline: slow-speed performers (SSP) showed lower modularity and global efficiency • They also showed higher transitivity but fewer hubs than fast-speed performers (FSP) • Prospective: SSP showed lower modularity, harmonic mean and higher transitivity • Regional volume changes seem to be occurring as one in SSP, but more modular in FSP • SSP showed hubs mainly from frontal and temporal while FSP showed them widespread

ObjectiveBenign epilepsy with centrotemporal spikes (BECTS) is the most common childhood idiopathic localization-related epilepsy syndrome. BECTS presents normal routine magnetic resonance imaging (MRI); however, quantitative analytic techniques have captured subtle cortical and subcortical magnetic resonance anomalies. Network science, including graph theory (GT) analyses, facilitates understanding of brain covariance patterns, potentially informing in important ways how this common self-limiting epilepsy syndrome may impact normal patterns of brain and cognitive development.MethodsGT analyses examined the developmental covariance among cortical and subcortical regions in children with new/recent onset BECTS (n=19) and typically developing healthy controls (n=22) who underwent high-resolution MRI and cognitive assessment at baseline and 2years later. Global (transitivity, global efficiency, and modularity index [Q]) and regional measures (local efficiency and hubs) were investigated to characterize network development in each group. Associations between baseline-based GT measures and cognition at both time points addressed the implications of GT analyses for cognition and prospective cognitive development. Furthermore, an individual contribution measure was investigated, reflecting how important for cognition it is for BECTS to resemble the correlation matrices of controls.ResultsGroups exhibited similar Q and overall network configuration, with BECTS presenting significantly higher transitivity and both global and local efficiency. Furthermore, both groups presented a similar number of hubs, with BECTS showing a higher number in temporal lobe regions compared to controls. The investigated measures were negatively associated with 2-year cognitive outcomes in BECTS.SignificanceChildren with BECTS present a higher-than-normal global developmental configuration compared to controls, along with divergence from normality in terms of regional configuration. Baseline GT measures demonstrate potential as a cognitive biomarker to predict cognitive outcome in BECTS 2years after diagnosis. Similarities and differences in developmental network configurations and their implications for cognition and behavior across common epilepsy syndromes are of theoretical interest and clinical relevance.

AIM: To determine whether the first degree cousins of children with idiopathic focal and genetic generalized epilepsies (cases) show any association across measures of cognition, behavior and brain structure. The presence/absence of associations addresses the question of whether and to what degree first degree cousins may serve as unbiased controls in research addressing the cognitive, psychiatric, and neuroimaging features of pediatric epilepsies. METHODS: Participants were children (age 8 – 18) with epilepsy who had at least one first-degree cousin control enrolled in the study (n=37) and all enrolled cousin controls (n=100). Participants underwent neuropsychological assessment, brain imaging (cortical, subcortical and cerebellar volumes) and parents completed the Child Behavior Checklist (CBCL). Data (42 outcome measures) from cousin controls were regressed on the corresponding epilepsy cognitive, behavioral and imaging measures in a linear mixed model and case – control correlations were examined. RESULTS: Of the 42 uncorrected correlations involving cognitive, behavioral and neuroimaging measures, only 2 were significant (p 0.25). Similar results held for the cognition/behavior and brain imaging measures separately. CONCLUSIONS: Given the lack of association between cases and first degree cousin performances on measures of cognition, behavior and neuroimaging, the results suggest a non-significant genetic influence on control group performance. First -degree cousins appear to be unbiased controls for cognitive, behavioral, and neuroimaging research in pediatric epilepsy.

Objective The objective of this study was to identify cognitive phenotypes in children with new-onset focal and generalized idiopathic epilepsies and determine their relationship with epilepsy syndrome, brain structure, neurodevelopmental history, and family characteristics. Methods One hundred thirty-eight children with new-onset epilepsy and 95 controls (age: 8–18) underwent neuropsychological, clinical, and quantitative MR evaluations. Control participants' neuropsychological data were subjected to confirmatory factor analysis and then resultant factor scores were applied to participants with epilepsy and subjected to latent class analysis. Identified cognitive phenotypes were examined in relation to epilepsy syndrome, quantitative neuroimaging, and familial and neurodevelopmental variables. Results Confirmatory factor analysis identified five cognitive factors (verbal, perceptual, speed, attention, executive), and latent class analysis identified three clusters of participants with epilepsy: 1) average and similar to controls, 2) mild impairment across multiple cognitive domains, and 3) impairment across all domains with severe attentional impairment, representing 44%, 44%, and 12% of the epilepsy sample, respectively. Cognitive phenotype membership was not associated with epilepsy syndrome but was associated with increasing abnormalities in brain structure, parental IQ, and features of early developmental history. Significance Cognitive phenotypes are present in idiopathic childhood epilepsies that are unassociated with traditional epilepsy syndromes but are associated with measures of brain structure, family history, and neurodevelopmental features.

Accumulating evidence suggests that considerable cognitive and psychiatric comorbidity is associated with juvenile myoclonic epilepsy, for which the etiology remains controversial. Our goal was to comprehensively characterize the status of multiple neurobehavioral comorbidities in youth with new- or recent-onset juvenile myoclonic epilepsy, before effects of chronic seizures and medications.A total of 111 children aged eight to 18 years (41 new- or recent-onset juvenile myoclonic epilepsy and 70 first-degree cousin controls) underwent neuropsychological assessment (attention, executive, verbal, perceptual, speed), structured review of need for supportive academic services, parent reports of behavior and executive function (Child Behavior Checklist and Behavior Rating Inventory of Executive Function), and formal structured psychiatric interview and diagnosis (Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version).Children with juvenile myoclonic epilepsy performed worse than controls across all tested cognitive domains (F(1,105) = 3.85, P 0.01), utilized more academic services (47% versus 19%, P = 0.002), had more parent-reported behavioral problems and dysexecutive function with lower competence (P 0.001), and had a higher prevalence of current Axis I diagnoses (attention-deficit/hyperactivity disorder, depression, and anxiety; 54% versus 23%, P = 0.001). Academic and psychiatric problems occurred antecedent to epilepsy onset compared with comparable timeline in controls.Comprehensive assessment of cognitive, academic, behavioral, and psychiatric comorbidities in youth with new- or recent-onset juvenile myoclonic epilepsy reveals a pattern of significantly increased neurobehavioral comorbidities across a broad spectrum of areas. These early evident comorbidities are of clear clinical importance with worrisome implications for future cognitive, behavioral, and social function. It is important for health care providers to avoid delays in intervention by assessing potential comorbidities early in the course of the disorder to optimize their patients' social, academic and behavioral progress.

Objective Structural and functional magnetic resonance imaging (MRI) studies have consistently documented cortical and subcortical abnormalities in patients with juvenile myoclonic epilepsy (JME). However, little is known about how these structural abnormalities emerge from the time of epilepsy onset and how network interactions between and within cortical and subcortical regions may diverge in youth with JME compared to typically developing children. Methods We examined prospective covariations of volumetric differences derived from high-resolution structural MRI during the first 2 years of epilepsy diagnosis in a group of youth with JME (n = 21) compared to healthy controls (n = 22). We indexed developmental brain changes using graph theory by computing network metrics based on the correlation of the cortical and subcortical structural covariance near the time of epilepsy and 2 years later. Results Over 2 years, normally developing children showed modular cortical development and network integration between cortical and subcortical regions. In contrast, children with JME developed a highly correlated and less modular cortical network, which was atypically dissociated from subcortical structures. Furthermore, the JME group also presented higher clustering and lower modularity indices than controls, indicating weaker modules or communities. The local efficiency in JME was higher than controls across the majority of cortical nodes. Regarding network hubs, controls presented a higher number than youth with JME that were spread across the brain with ample representation from the different modules. In contrast, children with JME showed a lower number of hubs that were mainly from one module and comprised mostly subcortical structures. Significance Youth with JME prospectively developed a network of highly correlated cortical regions dissociated from subcortical structures during the first 2 years after epilepsy onset. The cortical-subcortical network dissociation provides converging insights into the disparate literature of cortical and subcortical abnormalities found in previous studies.

Objectives:Rates of cognitive, academic and behavioral comorbidities are elevated in children with epilepsy. The contribution of environmental and genetic influences to comorbidity risk is not fully understood. This study investigated children with epilepsy, their unaffected siblings, and controls to determine the presence and extent of risk associated with family relatedness across a range of epilepsy comorbidities.Methods:Participants were 346 children (8–18 years),n=180 with recent-onset epilepsy, their unaffected siblings (n=67), and healthy first-degree cousin controls (n=99). Assessments included: (1) Child Behavior Checklist/6-18 (CBCL), (2) Behavior Rating Inventory of Executive Function (BRIEF), (3) history of education and academic services, and (4) lifetime attention deficit hyperactivity disorder (ADHD) diagnosis. Analyses consisted of linear mixed effect models for continuous variables, and logistic mixed models for binary variables.Results:Differences were detected between the three groups of children across all measures (pConclusions:The contribution of epilepsy and family relatedness varies across specific neurobehavioral comorbidities. Family relatedness was not significantly associated with rates of ADHD, academic problems and executive dysfunction, but was associated with competence and behavioral problems. (JINS, 2018,24, 1–9)

Epilepsy is one of the most common neurological disorders, with approximately 50 million people worldwide diagnosed with epilepsy. Suicide is a potentially preventable cause of death in epilepsy, yet it accounts for a large proportion of mortality in epilepsy with rates reported to be three to five times higher compared to healthy controls in population-based studies. In this chapter, we reviewed a number of the complexities involved in suicide among people with epilepsy, including the following: (a) prevalence of suicide compared to the general population in adults and children, (b) risk factors for suicidal behavior, (c) the bidirectional relationship between epilepsy and suicide, (d) the role of antiepileptic drugs (AEDs) in suicide risk, and (e) assessment of suicidal behavior as well as a review of clinical interventions aimed at treatment and prevention of suicidal behavior and its risk factors in epilepsy.

Using a hypothesis-driven approach, subcortical and cortical regions implicated in anxiety disorders in the general population were examined in children with recent-onset epilepsy with versus without anxiety compared to controls. This study reports frequency of anxiety disorders while examining familial, clinical, and demographic variables associated with anxiety in children with epilepsy.Participants included 88 children with epilepsy aged 8-18 years: 25 with a current anxiety disorder and 63 children with epilepsy and no current anxiety disorder. Forty-nine controls without anxiety disorders were included. T1 volumetric magnetic resonance imaging (MRI) scans were collected; subcortical volumes and cortical thickness were computed using the FreeSurfer image analysis suite. Analyses focused on adjusted measures of subcortical volumes and cortical thickness.Relative to controls, larger left amygdala volumes were found in the Epilepsy with Anxiety group compared to the Epilepsy without Anxiety group (p = 0.027). In the hippocampus, there were no significant differences between groups. Examination of cortical thickness demonstrated that the Epilepsy with Anxiety group showed thinning in left medial orbitofrontal (p = 0.001), right lateral orbitofrontal (p = 0.017), and right frontal pole (p = 0.009). There were no differences between groups in age, sex, IQ, age of onset, medications, or duration of epilepsy. There were more family members with a history of anxiety disorders in the Epilepsy with Anxiety group compared to the Epilepsy without Anxiety group (p = 0.005).Anxiety is a common psychiatric comorbidity in children with recent-onset epilepsy with volumetric enlargement of the amygdala and thinner cortex in orbital and other regions of prefrontal cortex, suggesting structural abnormalities in brain regions that are part of the dysfunctional networks reported in individuals with anxiety disorders in the general population. These findings are evident early in the course of epilepsy, are not related to chronicity of seizures, and may be linked to a family history of anxiety and depressive disorders.

Attentional vigilance, the ability to maintain focus over time, is frequently impaired in childhood epilepsy. Typically, indices of Omissions (failure to detect a target) and Commissions (responding to a nontarget) are considered primary indices of attentional vigilance. Recently, the concept of intraindividual variability (IIV) has been identified as an important measure of attentional vigilance in several pediatric and adult clinical populations, but has not yet been systematically examined in childhood epilepsy. Here, we examined IIV on the Connors Continuous Performance Task-II (CCPT-II) for 144 newly diagnosed children with epilepsy (age 8-18years) and a matched age group of healthy children (n=82). Intraindividual variability showed a large effect size difference (d=0.68) between groups. In addition, IIV significantly predicted both intellectual functioning and academic achievement. These findings support the utility of examining IIV in the assessment of attentional ability in childhood epilepsy.

BACKGROUND High definition transcranial direct current stimulation (HD-tDCS) has been administered over single brain regions for small numbers of sessions. Safety, feasibility and tolerability of HD-tDCS over multiple brain regions, multiple daily stimulations and long periods are not established. OBJECTIVE We studied safety, feasibility and tolerability of daily HD-tDCS over 2-4 brain regions for 20 sessions in healthy adults. METHODS Five healthy adults underwent physical and neurological examination, electrocardiogram (EKG), electroencephalogram (EEG) and cognitive screening (ImpACT) before, during and after HD-tDCS. Four networks (left/right temporoparietal and frontal) were stimulated in sequence (20 min each) using HD-tDCS in 20 daily sessions. Sessions 1-10 included sequential stimulation of both temporoparietal networks, sessions 11-15 stimulations of 4 networks and sessions 16-20 two daily stimulation cycles of 4 networks/cycle (1.5 mA/network). Side effects, ImpACT scores and EEG power spectrum were compared before and after HD-tDCS. RESULTS All subjects completed the trial. Adverse events were tingling, transient redness at the stimulation site, perception of continuing stimulation after end of session and one self-resolving headache. EEG power spectrum showed decreased delta power in frontal areas several days after HD-tDCS. While at the group level ImpACT scores did not differ before and after stimulations, we found a trend for correlation between decreased EEG delta power and individual improvements in ImpACT scores after HD-tDCS. CONCLUSION Prolonged, repeat daily stimulation of multiple brain regions using HD-tDCS is feasible and safe in healthy adults. Preliminary EEG results suggest that HD-tDCS may induce long lasting changes in excitability in the brain.

PurposeThe purpose of this study was to assess the impact of a cognitive behavioral therapy (CBT) anxiety intervention on social phobia, social skill development, and self-concept.MethodFifteen children with epilepsy and a primary anxiety disorder participated in a CBT intervention for 12 weeks plus a 3-month follow-up visit. Children were assessed at baseline, week 7, week 12, and 3 months post treatment to measure changes in social phobia using the Screen for Child Anxiety Related Emotional Disorders (SCARED). Self-concept was also assessed by using the Piers-Harris Children's Self-Concept Scale II (Piers-Harris 2).ResultsThere was a significant reduction in symptoms of social phobia and improved self-concept at the end of the 12-week intervention and at the 3 month follow-up. Repeated measures ANOVA's of child ratings revealed significant change over time on the SCARED-Social Phobia/Social Anxiety subscale score (p=0.024). In terms of self-concept, significant change over time was detected on the Piers-Harris 2-Total score (p=0.015) and several subscale scores of Piers-Harris 2, including: Physical Appearance and Attributes (p=0.016), Freedom from Anxiety (p=0.005), and Popularity (p=0.003).ConclusionThis pilot investigation utilized an evidenced based CBT intervention to reduce symptoms of social phobia, which in turn provided a vehicle to address specific social skills improving self-concept in children with epilepsy.

Children with epilepsy are at significant risk of psychiatric disorders, which can in turn negatively impact social skills development, academic achievement, and quality of life. The most commonly reported psychiatric comorbidities in pediatric epilepsy are ADHD, depression, and anxiety. The prevalence rates of anxiety disorders in pediatric epilepsy range from 5 to 49%, and in the general population, anxiety disorders are the most common psychiatric disorder in childhood. For the purposes of this review, anxiety disorders will be examined in order to 1) examine rates of anxiety disorders in children and adolescents with epilepsy, 2) review treatment options for anxiety disorders in children with epilepsy, and 3) identify future avenues for the development of evidence-based practices for the treatment of anxiety disorders in youth with epilepsy.

This study aimed to examine the association between vocational rehabilitation (VR) services and employment outcomes of people with epilepsy (PWE), after controlling for demographic covariates. Data was retrieved from the Rehabilitation Services Administration Case Service Report (RSA-911) database for fiscal year (FY) 2011. Multivariate logistic regression was used to predict employment outcomes of PWE. Of the 2030 previously unemployed PWE who received services, 884 (43.5%) achieved successful competitive employment. Results indicate that higher education level and cost of VR services consumed were positively related to successful employment. In contrast, having co-occurring anxiety/depression, receiving cash benefits, or increasing time spent in the VR system was negatively associated with employment. Eight specific VR services (e.g., education, vocational training, and job search and placement assistance) were also found to be significant predictors of employment. Services provided by state VR agencies were proven to be beneficial in improving employment outcomes. PWE should be encouraged to pursue VR services to increase the chances of attaining employment. Health care providers should also become familiar with the array of VR services.

OBJECTIVE Adults with juvenile myoclonic epilepsy (JME) have subtle brain structural abnormalities in the frontothalamocortical network, poorer cognitive function, and worse long-term social outcomes, even when their seizures are controlled and/or remitted. The natural history of JME and development of abnormalities in brain structure and cognition from epilepsy onset has not been studied. METHODS The maturational trajectories of cognitive and brain development were prospectively compared between 19 children with new-onset JME in the first 2 years after diagnosis and 57 healthy controls. RESULTS Cognitive abilities of children with JME were similar to or worse than healthy controls at baseline but failed to reach the competence level of healthy controls at follow-up across most of the tested cognitive abilities. Abnormal patterns of brain development, as assessed by magnetic resonance imaging studies, were evident in children with JME and included attenuation of age-related decline in cortical volume, thickness, and surface area compared to typically developing children. The altered brain developmental trajectory in the JME group was evident in higher-association frontoparietotemporal brain regions (p < 0.05, corrected for multiple comparisons). INTERPRETATION Children with JME have abnormal structural brain development and impaired cognitive development early in the course of their epilepsy.

Purpose In order to develop a theoretical framework for person-centered care models for children with epilepsy and their parents, we conducted a qualitative study to explore and understand parents' needs, values, and preferences to ultimately reduce barriers that may be impeding parents from accessing and obtaining help for their children's co-occurring problems. Methods A qualitative grounded theory study design was utilized to understand parents' perspectives. The participants were 22 parents of children with epilepsy whose age ranged from 31 to 53 years. Interviews were conducted using open-ended semistructured questions to facilitate conversation. Transcripts were analyzed using grounded theory guidelines. Results In order to understand the different perspectives parents had about their child, we devised a theory composed of three zones (Zones 1, 2, and 3) that can be used to conceptualize parents' viewpoints. Zone location was based on a parent's perspectives on their child's comorbidities in the context of epilepsy. These zones were developed to help identify distinctions between parents' perspectives and to provide a framework within which to understand parents' readiness to access and implement interventions to address the child's struggles. These zones of understanding describe a parent's perspectives on their children's struggles at a particular point in time. This is the perspective from which parents address their child's needs. This theoretical perspective provides a structure in which to discuss a parent's perspectives on conceptualizing or comprehending the child's struggles in the context of epilepsy. The zones are based on how the parents describe (a) their concerns about the child's struggles and (b) their understanding of the struggles and (c) the parent's view of the child's future. Conclusions Clinicians working with individuals and families with epilepsy are aware that epilepsy is a complex and unpredictable disorder. The zones help clinicians conceptualize and build a framework within which to understand how parents view their child's struggles, which influences the parents' ability to understand and act on clinician feedback and recommendations. Zones allow for increased understanding of the parent at a particular time and provide a structure within which a clinician can provide guidance and feedback to meet parents' needs, values, and preferences. This theory allows clinicians to meet the parents where they are and address their needs in a way that benefits the parents, family, and child.

Summary Objective Birth weight is an important indicator of prenatal environment, and subtle variations of birth weight within the normal range have been associated with differential risk for cognitive and behavioral problems. Therefore, we aimed to determine if there are differences in birth weight between full-term children with uncomplicated new/recent-onset epilepsies and typically developing healthy controls. We further examined the relationships between birth weight and childhood/adolescent cognition, behavior, and academic achievement. Methods One hundred eight children with new-onset/recent-onset epilepsy and 70 healthy controls underwent neuropsychological assessment. All participants were born full-term (>37 weeks) without birth complications. Parents were interviewed regarding their child's gestation, birth, and neurodevelopmental history. Results Birth weight of children with epilepsy was significantly lower than healthy controls (p = 0.023). Whereas birth weight (covaried with age, sex, handedness, and mother's education) was significantly associated with cognition in controls in multiple domains (intelligence, language, aspects of academic achievement), this relationship was absent in children with epilepsy. Birth weight was not associated with clinical epilepsy variables (age of onset, epilepsy syndrome) and was not predictive of a variety of other academic or psychiatric comorbidities of epilepsy. Significance Although the origin of lower birth weight in children with epilepsy is unknown, these findings raise the possibility that abnormal prenatal environment may affect childhood-onset epilepsy. Furthermore, the positive relationship between birth weight and cognition evident in healthy controls was disrupted in children with epilepsy. However, birth weight was not related to academic and psychiatric comorbidities of childhood epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Summary Introduction Diffusion tensor imaging (DTI) studies have reported white matter abnormalities in childhood-onset epilepsy, but the mechanisms and timing underlying these abnormalities, and their resolution, are not well understood. This study examined white matter integrity in children with active versus remitted epilepsy. Methods Tract-based spatial statistics (TBSS) was used to examine whole-brain DTI indices of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in 20 children with epilepsy 5–6 years after diagnosis, compared to 29 healthy controls. To determine the status of white matter following cessation of seizures, participants with epilepsy were classified as active versus remitted and comparisons included: (1) controls versus all children with epilepsy, (2) controls versus children with remitted seizures, (3) controls versus children with active seizures, and (4) children with active versus remitted epilepsy. Results In the active compared to remitted epilepsy group, significantly higher FA and lower MD, AD and RD values were dispersed in the internal capsule, cingulum, body of the corpus callosum, superior corona radiata and superior fronto-occipital fasciculus. Similar differences were found between the active epilepsy and the control group. There were no significant differences between the remitted epilepsy and control groups. Conclusion Children with active epilepsy differed in white matter integrity compared to children with remitted epilepsy and healthy controls. It remains to be determined whether these findings represent the outcomes of seizure remission versus an initial biomarker for those children who will ultimately have intractable epilepsy.

The purpose of this investigation was to characterize the neuroanatomical correlates (cortical thickness) of variations in parent-reported Child Behavior Checklist (CBCL) scores. Ninety children with epilepsy (aged 8-18) underwent brain MRI, and their parents completed the CBCL. FreeSurfer-derived measures of cortical thickness were examined in relation to the CBCL broad and narrow band competence and behavioral problem scales, as well as the newer DSM-oriented scales. Parent reports of higher (better) social competence skills were associated with increased cortical thickness, especially in frontal regions. Parent reports of behavioral problems were associated with patterns of decreased cortical thickness that varied as a function of the specific behavioral issue under investigation. Congruence of patterns of cortical thinning between the DSM-oriented scales and conceptually related specific problem scales (e.g., ADHD Problems and Attention Problems) was generally weak. The parent-report version of the CBCL is associated with variations in cortical thickness among children with epilepsy. Anatomic abnormalities specific to selected competence and behavioral problem scales can be identified, with more reliable and robust patterns of thinning across scales assessing externalizing behaviors, with generally less prominent findings on scales assessing internalizing behaviors.

BACKGROUND: At 3 time points, this study examined long-term psychosocial life outcomes of individuals who underwent anterior temporal lobectomy in comparison with individuals with temporal lobe epilepsy who were medically managed. OBJECTIVE: To examine seizure frequency, employment, driving, independent living, financial independence, mental health, and quality of life at each follow-up assessment, as well as predictors of outcomes. METHODS: All participants were diagnosed with medically intractable complex partial seizures of temporal lobe origin with or without secondary generalization. A structured clinical interview was used at all 3 time points. Information was obtained regarding seizure frequency, antiepilepsy medications, employment, driving status, financial assistance, and independent living. Additionally, questions regarding quality of life, satisfaction with surgery, and the presence of depression or anxiety were included. Participants were, on average, 17 years postsurgery. RESULTS: Surgery resulted in significantly improved and sustained seizure outcomes. At the first, second, and third follow-ups, 67%, 72%, and 67% of participants in the surgery group remained seizure-free in the year before the follow-up interview. At each follow-up, 97%, 84%, and 84% reported that they would undergo surgery again. Seizure freedom predicted driving outcomes at all 3 time points, but was not a significant predictor for employment, independent living, or financial independence. Psychosocial life outcomes in the surgical group were improved and maintained over time in comparison with the medically managed group. CONCLUSION: This systematic long-term investigation provides strong support for the positive impact of anterior temporal lobectomy on psychosocial life outcomes including driving, employment, independent living, and financial independence.

Anxiety disorders are prevalent in children with epilepsy. The purpose of this study was to evaluate the efficacy, adaptability, and feasibility of a manual-based, computer-assisted cognitive behavioral therapy (CBT) intervention for anxiety disorders in children with epilepsy. Fifteen anxious youth (aged 8-13 years) with epilepsy completed 12 weeks of manualized computer-assisted CBT. The children and parents completed a semi-structured interview at baseline, and questionnaires assessing symptoms of anxiety, depression, and behavior problems were completed prior to treatment, at treatment midpoint, after treatment completion, and at three months posttreatment. There were significant reductions in the symptoms of anxiety and depression reported by the children at completion of the intervention and at the three-month follow-up. Similarly, the parents reported fewer symptoms of anxiety and a reduction in behavior problems. No adverse events were reported. This CBT intervention for children with epilepsy and anxiety disorders appears to be safe, effective, and feasible and should be incorporated into future intervention studies.

To help their child problem-solve, it is essential for parents to recognize and accept that the child has stressors. This can be challenging because the parents often are not psychologically minded, might be unaware of the child’s struggles, and/or do not know how to help the child problem-solve. They might misinterpret the child’s avoidance of problem solving as being lazy and think that the child’s request for help is a way to get attention or be manipulative. Your role in this process is to help the parents recognize and understand the difficulties and stressors the child faces, as well as to give the parents a framework for how to respond using the approaches presented in this chapter.

Adaptive problem-solving is clearly a challenge for children with PNES. This goal focuses on how the parents can help the child problem-solve adaptively. To do this, it includes the methods described for the child in Chap. 9 and how the parents can help the child operationalize them.

This guide devotes a whole section to the diagnosis of pediatric PNES because this process is challenging. In fact, the diagnosis is often missed, and the average time it takes for the diagnosis to be confirmed is 6 months to 3.5 years. The longer it takes to reach a diagnosis and begin treatment, the worse the outcome is. In this section, we describe the underlying psychopathology, risk factors, and triggers of pediatric PNES; the gold standard diagnosis; why it is difficult to make the diagnosis in children; red flags, suggesting a possible PNES diagnosis; and the techniques to overcome the challenges of diagnosing this disorder.

The ultimate therapy goal for a child with PNES is that the child acquires adaptive problem-solving skills. To do this, the child needs to be able to tune into negative emotions (anxiety, fear, anger, sadness) (Goal 1), identify the stressors and difficulties that trigger these feelings (Goal 2), and be aware of physical sensations that accompany stress (Goal 3) without using avoidance and channeling the negative emotions and stressors through the body (Goal 4). Although problem-solving is the ultimate goal, your work with the child on adaptive problem-solving starts from early in therapy.

Children with PNES have difficulty identifying stressors other than the physical symptoms that they experience. Early in treatment, these often are the only stressors that they and/or their parents acknowledge. Management of the child’s physical symptoms builds the rapport and trust in the therapist that is needed to help the child and parents explore the child’s other stressors. Identification of stressors should be part of each therapy session using the techniques described in this chapter.

Goals 1 and 2 provide techniques to help the child recognize negative emotions the child experiences and identify stressors, respectively. Goal 3 now focuses on how to assist the child to tune into and verbalize the negative affect associated with stressors.

The main objective of this goal is to improve the relationships between the parents and child. Communication within the family involves a dynamic interplay between the parents and child. This chapter guides you on how best to identify and understand communication breakdowns that occur between the parents and the child, their triggers, how they evolve, as well as what can be done to prevent and/or fix them.

Anxiety disorders and depression are common in youth with PNES. These disorders are frequently under-recognized and under-treated. They can appear before NES symptom onset and remain after PNES is diagnosed. Cognitive behavioral therapy (CBT) is an evidenced-based treatment for anxiety disorders and depression, disorders that are common in childhood and adolescence. This chapter describes the indications for CBT in the anxiety disorder and depression found in youth with PNES. It also includes an overview of the essential elements of CBT that have been demonstrated to have the strongest evidence for efficacy.

During the course of treatment, it often becomes apparent that the child’s NES and other physical symptoms are emotionally based. But the child is unaware of the link between the child’s negatively charged emotions or thoughts and these symptoms. As a result of therapy, the child begins to understand that stressful situations evoke negative emotions in most people and in the child. Once this is achieved, it is important to examine how stress and negative emotions are associated with the child’s NES episodes and other physical sensations.