Individual- and community-level social determinants of health are associated with cognition in older adults with focal epilepsy.

OBJECTIVE: Epilepsy is associated with significant health disparities, including access to specialized care and adverse outcomes that have been associated with several social determinants of health (SDOH). We sought to examine the relationship between individual- and community-level SDOH and cognitive outcomes in older adults with epilepsy. MATERIALS AND METHODS: We collected clinical, SDOH, and neuropsychological data in 57 older adults with epilepsy. Individual-level SDOH included patient factors (quality of education, income, insurance, marital status) and early-life environmental factors (parental education and occupation, childhood employment). Neighborhood deprivation was measured with the Area Deprivation Index (ADI). Stepwise regressions were conducted to examine the independent contribution of individual-level SDOH to cognitive performance, and Spearman rho correlations were conducted to examine the relationship between ADI and cognitive performance. The SDOH profiles of patients who met the criteria for cognitive impairment were examined. RESULTS: After controlling for clinical variables, patient factors (public health insurance, poorer quality of education) and early-life environmental factors (lower mother's education, lower father's and mother's occupational complexity, history of childhood employment) were significant predictors of lower performance on measures of global cognition, verbal learning and memory, processing speed, and executive function. Higher ADI values (greater disadvantage) were associated with lower scores on global cognitive measures, verbal learning and memory, and executive function. Patients who met criteria for cognitive impairment had, on average, a greater number of adverse SDOH, including lower household incomes and father's education, and higher ADI values compared to those who were cognitively intact. CONCLUSION: We provide new evidence of the role of individual- and community-level SDOH on cognitive outcomes in older adults with epilepsy. This emerging literature highlights the need to examine SDOH beyond epilepsy-related clinical factors. These data could inform the development of interventions focused on increasing access to epilepsy care, education, and resources and promoting brain and cognitive health within the most at-risk communities.

Validity of the MoCA as a cognitive screening tool in epilepsy: Are there implications for global care and research?

OBJECTIVE: This study evaluated the diagnostic performance of a widely available cognitive screener, the Montreal cognitive assessment (MoCA), to detect cognitive impairment in older patients (age ≥ 55) with epilepsy residing in the US, using the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) as the gold standard. METHODS: Fifty older adults with focal epilepsy completed the MoCA and neuropsychological measures of memory, language, executive function, and processing speed/attention. The IC-CoDE taxonomy divided participants into IC-CoDE Impaired and Intact groups. Sensitivity and specificity across several MoCA cutoffs were examined. Spearman correlations examined relationships between the MoCA total score and clinical and demographic variables and MoCA domain scores and individual neuropsychological tests. RESULTS: IC-CoDE impaired patients demonstrated significantly lower scores on the MoCA total, visuospatial/executive, naming, language, delayed recall, and orientation domain scores (Cohen's d range: 0.336-2.77). The recommended MoCA cutoff score < 26 had an overall accuracy of 72%, 88.2% sensitivity, and 63.6% specificity. A MoCA cutoff score < 24 yielded optimal sensitivity (70.6%) and specificity (78.8%), with overall accuracy of 76%. Higher MoCA total scores were associated with greater years of education (p = 0.016) and fewer antiseizure medications (p = 0.049). The MoCA memory domain was associated with several standardized measures of memory, MoCA language domain with category fluency, and MoCA abstraction domain with letter fluency. SIGNIFICANCE: This study provides initial validation of the MoCA as a useful screening tool for older adults with epilepsy that can be used to identify patients who may benefit from comprehensive neuropsychological testing. Further, we demonstrate that a lower cutoff (i.e., <24) better captures cognitive impairment in older adults with epilepsy than the generally recommended cutoff and provides evidence for construct overlap between MoCA domains and standard neuropsychological tests. Critically, similar efforts in other regions of the world are needed. PLAIN LANGUAGE SUMMARY: The Montreal cognitive assessment (MoCA) can be a helpful tool to screen for cognitive impairment in older adults with epilepsy. We recommend that adults 55 or older with epilepsy who score less than 24 on the MoCA are referred to a neuropsychologist for a comprehensive evaluation to assess any changes in cognitive abilities and mood.

Vitamin B6 and vitamin D deficiency co-occurrence in geriatric memory patients.

INTRODUCTION: Vitamin B6 and D levels are not assessed routinely in geriatric memory patients. This study examined vitamin levels to determine the potential effects on cognition. METHODS: A chart review was conducted of 203 consecutive patients over a 12-month period. Levels of vitamins B1, B6, B12, and D were obtained on the day of clinic to identify deficiencies. A mental status exam (Mini Mental State Examination [MMSE]) was also performed. RESULTS: One hundred sixty-seven patients had one or more vitamin levels obtained on the day of clinical evaluation. Vitamin B6 deficiency was the most common (37.5%), followed by vitamin D deficiency (36.8%). A chi-square test revealed significant co-occurrence of deficiency of vitamins B6 and D (p < 0.001). Vitamin B6 and D deficiencies were associated with lower MMSE scores (p < 0.05). DISCUSSION: Vitamin B6 and D deficiencies are common in geriatric patients. The coexistence of these vitamin deficiencies has a significant association with cognitive performance, indicating the clinical importance of monitoring and supplementation.

Neighborhood disadvantage and intellectual development in youth with epilepsy.

RATIONALE: Recent cross-sectional investigations have demonstrated an adverse impact of socioeconomic disadvantage on cognition and behavior in youth and adults with epilepsy. The goal of this study is to investigate the impact of disadvantage on prospective intellectual development in youth with epilepsy. METHOD: Participants were youth, aged 8-18 years, with recent onset epilepsy (n = 182) and healthy first-degree cousin controls (n = 106). The Wechsler Abbreviated Scale of Intelligence (WASI) was administered at baseline and 2 years later. The Neighborhood Atlas identified each family's Area Deprivation Index via state deciles and national percentiles. WASI data were analyzed by mixed group by time ANOVAs followed by regression analysis to identify other baseline predictors of time 2 outcomes. RESULTS: Youth with epilepsy demonstrated significant interactions between group and time for both verbal (F = 4.02, df = 1,215, p =.05) and nonverbal (F = 4.57, df = 1,215, p =.04) reasoning, demonstrating that disadvantage was associated with slower cognitive development compared to advantaged youth with epilepsy. Similar interactions were not observed for controls. CONCLUSIONS: In youth with new and recent onset epilepsies, neighborhood-level disadvantage is associated with a negative impact on the development of verbal and nonverbal reasoning skills.

Disadvantage and neurocognitive comorbidities in childhood idiopathic epilepsies.

OBJECTIVE: This study was undertaken to characterize the relationship between neighborhood disadvantage and cognitive function as well as clinical, sociodemographic, and family factors in children with new onset idiopathic epilepsy and healthy controls. METHODS: Research participants were 288 children aged 8-18 years with recent onset epilepsy (CWE; n = 182; mean age = 12.2 ± 3.2 years), healthy first-degree cousin controls (HC; n = 106; mean age = 12.5 ± 3.0), and one biological or adopted parent per child (n = 279). All participants were administered a comprehensive neuropsychological battery (reasoning, language, memory, executive function, motor function, and academic achievement). Family residential addresses were entered into the Neighborhood Atlas to determine each family's Area Deprivation Index (ADI), a metric used to quantify income, education, employment, and housing quality. A combination of parametric and nonparametric (χ2 ) tests examined the effect of ADI by group (epilepsy and controls) across cognitive, academic, clinical, and family factors. RESULTS: Disadvantage (ADI) was equally distributed between groups (p = .63). For CWE, high disadvantage was associated with lower overall intellectual quotient (IQ; p = .04), visual naming/expressive language (p = .03), phonemic (letter) fluency (p < .01), passive inattention (omission errors; p = .03), delayed verbal recall (p = .04), and dominant fine motor dexterity and speed (p < .01). Cognitive status of the HC group did not differ by level of disadvantage (p = .40). CWE exhibited greater academic difficulties in comparison to HC (p < .001), which were exacerbated by disadvantage in CWE (p = .02) but not HC (p < .05). High disadvantage was associated with a threefold risk for academic challenges prior to epilepsy onset (odds ratio = 3.31, p = .024). SIGNIFICANCE: Socioeconomic hardship (increased neighborhood disadvantage) exerts a significant adverse impact on the cognitive and academic status of youth with new and recent onset epilepsies, an impact that needs to be incorporated into etiological models of the neurobehavioral comorbidities of epilepsy.

Treatment of Comorbid Anxiety and Epilepsy.

Objective: Anxiety is among the most common psychiatric illnesses, and it commonly co-occurs with epilepsy. This review of the existing literature on anxiety comorbid with epilepsy aims to generate new insights into strategies for assessment and treatment. Methods: The authors conducted a narrative literature review to select key publications that help clarify the phenomenology and management of comorbid anxiety and epilepsy. Results: Anxiety symptoms may be relevant even if the criteria for a diagnosis of an anxiety disorder are not met. Associating specific seizure types or seizure localization with anxiety symptoms remains difficult; however, the amygdala is a brain region commonly associated with seizure foci and panic or fear sensations. The hypothalamic-pituitary-adrenal axis may also be relevant for anxiety symptoms, particularly for the selection of treatments. Nonpharmacological treatment is appropriate for anxiety comorbid with epilepsy, particularly because relaxation techniques may reduce hypersympathetic states, which improve symptoms. Medication options include antidepressants and anticonvulsants that may have efficacy for anxiety symptoms. Benzodiazepines are a good choice to address this comorbid condition, although side effects may limit utility. Conclusions: Ultimately, there are numerous treatment options, and although there is a limited evidence base, quality of life may be improved with appropriate treatment for individuals experiencing comorbid anxiety and epilepsy.

Behavioral phenotypes of temporal lobe epilepsy.

OBJECTIVE: To identity phenotypes of self-reported symptoms of psychopathology and their correlates in patients with temporal lobe epilepsy (TLE). METHOD: 96 patients with TLE and 82 controls were administered the Symptom Checklist 90-Revised (SCL-90-R) to characterize emotional-behavioral status. The nine symptom scales of the SCL-90-R were analyzed by unsupervised machine learning techniques to identify latent TLE groups. Identified clusters were contrasted to controls to characterize their association with sociodemographic, clinical epilepsy, neuropsychological, psychiatric, and neuroimaging factors. RESULTS: TLE patients as a group exhibited significantly higher (abnormal) scores across all SCL-90-R scales compared to controls. However, cluster analysis identified three latent groups: (1) unimpaired with no scale elevations compared to controls (Cluster 1, 42% of TLE patients), (2) mild-to-moderate symptomatology characterized by significant elevations across several SCL-90-R scales compared to controls (Cluster 2, 35% of TLE patients), and (3) marked symptomatology with significant elevations across all scales compared to controls and the other TLE phenotype groups (Cluster 3, 23% of TLE patients). There were significant associations between cluster membership and demographic (education), clinical epilepsy (perceived seizure severity, bitemporal lobe seizure onset), and neuropsychological status (intelligence, memory, executive function), but with minimal structural neuroimaging correlates. Concurrent validity of the behavioral phenotype grouping was demonstrated through association with psychiatric (current and lifetime-to-date DSM IV Axis 1 disorders and current treatment) and quality-of-life variables. SIGNIFICANCE: Symptoms of psychopathology in patients with TLE are characterized by a series of discrete phenotypes with accompanying sociodemographic, cognitive, and clinical correlates. Similar to cognition in TLE, machine learning approaches suggest a developing taxonomy of the comorbidities of epilepsy.

Behavioral phenotypes of childhood idiopathic epilepsies.

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.

Cognitive phenotypes in temporal lobe epilepsy utilizing data- and clinically driven approaches: Moving toward a new taxonomy.

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.

Psychosocial and functional outcomes in young adults with childhood-onset epilepsy: a 10-year follow-up.

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<0.05). These difficulties were due to baseline comorbid ADHD and academic problems. Remission status was not related to measured cognition and overall disability. INTERPRETATION: Psychosocial outcomes of young adults with COE were similar to controls. In contrast, functional outcomes were worse in epilepsy across cognition and overall disability. Baseline comorbid ADHD and academic problems were identified as risk factors at 10-year follow-up suggesting that these early recognized comorbidities at or near diagnosis have long-term impacts. WHAT THIS PAPER ADDS: Young adults with childhood-onset epilepsy (COE) and controls have similar psychosocial outcomes 10 years after diagnosis. Young adults with COE report greater limitations in cognition and overall disability than controls. Baseline presence of attention-deficit/hyperactivity disorder and academic problems significantly affect cognitive and overall disability scores.

Epilepsy Benchmarks Area IV: Limit or Prevent Adverse Consequence of Seizures and Their Treatment Across the Life Span.

Epilepsy represents a complex spectrum disorder, with patients sharing seizures as a common symptom and manifesting a broad array of additional clinical phenotypes. To understand this disorder and treat individuals who live with epilepsy, it is important not only to identify pathogenic mechanisms underlying epilepsy but also to understand their relationships with other health-related factors. Benchmarks Area IV focuses on the impact of seizures and their treatment on quality of life, development, cognitive function, and other aspects and comorbidities that often affect individuals with epilepsy. Included in this review is a discussion on sudden unexpected death in epilepsy and other causes of mortality, a major area of research focus with still many unanswered questions. We also draw attention to special populations, such as individuals with nonepileptic seizures and pregnant women and their offspring. In this study, we review the progress made in these areas since the 2016 review of the Benchmarks Area IV and discuss challenges and opportunities for future study.

The Impact of Risk and Resistance Factors on Quality of Life in Caregivers of Individuals with Dementia.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL IMPLICATIONS: 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.

Network analysis of prospective brain development in youth with benign epilepsy with centrotemporal spikes and its relationship to cognition.

OBJECTIVE: Benign 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. METHODS: GT 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 2 years 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. RESULTS: Groups 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. SIGNIFICANCE: Children 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 2 years 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.

The Timing, Nature, and Range of Neurobehavioral Comorbidities in Juvenile Myoclonic Epilepsy.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Neurobiological substrates of processing speed in childhood epilepsy.

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.

Progressive dissociation of cortical and subcortical network development in children with new-onset juvenile myoclonic epilepsy.

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.

Contribution of Family Relatedness to Neurobehavioral Comorbidities in Idiopathic Childhood Epilepsies.

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 (p<.001). For ADHD, academic problems, and executive dysfunction, children with epilepsy exhibited significantly more problems than unaffected siblings and controls; siblings and controls did not differ statistically significantly from each other. For social competence, children with epilepsy and their unaffected siblings displayed more abnormality compared with controls, with no statistically significant difference between children with epilepsy and unaffected siblings. For behavioral problems, children with epilepsy had more abnormality than siblings and controls, but unaffected siblings also exhibited more abnormalities than controls. CONCLUSIONS: 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, 653-661).