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.

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.

Neighborhood disadvantage and health-related quality of life in pediatric epilepsy.

INTRODUCTION: While several demographic and epilepsy-specific characteristics are associated with diminished HRQoL in children and adolescents with epilepsy, prior investigations have failed to incorporate and address the influence of broader social contextual factors on functional outcomes. To address this gap, the purpose of the current study was to investigate the role of neighborhood disadvantage on HRQoL, including the extent to which familial and seizure-specific risk factors are impacted. METHODS: Data included parental ratings on the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 135 children and adolescents with epilepsy, and the Area Deprivation Index (ADI) to measure neighborhood disadvantage. Bivariate correlations were conducted to identify significant associations with neighborhood disadvantage, followed by a three-stage hierarchical multiple regression to predict HRQoL. Follow-up binary logistic regressions were used to determine the risk conferred by neighborhood disadvantage on sociodemographic, seizure-specific, and HRQoL factors. RESULTS: Moderate associations between neighborhood disadvantage and familial factors, including parental psychiatric history and Medicaid insurance, were identified, while disadvantage and greater seizure frequency were marginally associated. Neighborhood disadvantage independently predicted HRQoL, and was the sole significant predictor of HRQoL when familial factors were incorporated. Children with epilepsy living in disadvantaged areas were four times more likely to have diminished HRQoL, five times more likely to live with a parent with a significant psychiatric history, and four times more likely to reside with a family receiving Medicaid insurance. CONCLUSIONS: These results highlight the importance of identifying high-risk groups, as the cumulative burden of social context, familial factors, and seizure-specific characteristics contribute to lower HRQoL in pediatric epilepsy which disproportionately affects patients from lower-resourced backgrounds. Potentially modifiable factors such as parental psychiatric status exist within the child's environment, emphasizing the importance of a whole-child approach to patient care. Further exploration of disadvantage in this population is needed to better understand these relationships over time.

Behavioral phenotypes of pediatric temporal lobe epilepsy.

OBJECTIVE: A broad spectrum of emotional-behavioral problems have been reported in pediatric temporal lobe epilepsy (TLE), but with considerable variability in their presence and nature of expression, which hampers precise identification and treatment. The present study aimed to empirically identify latent patterns or behavioral phenotypes and their correlates. METHODS: Data included parental ratings of emotional-behavioral status on the Behavior Assessment System for Children, 2nd Edition (BASC-2) of 81 children (mean age = 11.79, standard deviation [SD] = 3.93) with TLE. The nine clinical subscales were subjected to unsupervised machine learning to identify behavioral subgroups. To explore concurrent validity and the underlying composition of the identified clusters, we examined demographic factors, seizure characteristics, psychosocial factors, neuropsychological performance, psychiatric status, and health-related quality of life (HRQoL). RESULTS: Three behavioral phenotypes were identified, which included no behavioral concerns (Cluster 1, 43% of sample), externalizing problems (Cluster 2, 41% of sample), and internalizing problems (Cluster 3, 16% of sample). Behavioral phenotypes were characterized by important differences across clinical seizure variables, psychosocial/familial factors, everyday executive functioning, and HRQoL. Cluster 2 was associated with younger child age, lower maternal education, and higher rate of single-parent households. Cluster 3 was associated with older age at epilepsy onset and higher rates of hippocampal sclerosis and parental psychiatric history. Both Cluster 2 and 3 demonstrated elevated family stress. Concurrent validity was demonstrated through the association of psychiatric (i.e., rate of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) disorders and psychotropic medication) and parent-rated HRQoL variables. SIGNIFICANCE: Youth with TLE present with three distinct behavioral phenotypes that correspond with important clinical and sociodemographic markers. The current findings demonstrate the variability of behavioral presentations in youth with TLE and provide a preliminary framework for screening and targeting intervention to enhance support for youth with TLE and their families.

Neuropsychological Phenotypes in Pediatric Temporal Lobe Epilepsy.

OBJECTIVE: Adults with temporal lobe epilepsy (TLE) have been found to have a fairly characteristic pattern of neuropsychological performance, but there is considerably less research and more variability in findings with children. Because the cognitive domains included in most studies with children have been limited, the current study attempted to better characterize the cognitive phenotype of children with TLE using a broader neuropsychological battery. METHODS: The study included 59 children with TLE (59% male) age 7 to 16 (M = 12.67; SD = 3.12) who underwent comprehensive neuropsychological evaluation. Patient results were grouped into cognitive domains (reasoning, language, visuoperceptual, verbal memory, executive function, and motor function) based upon their test performance. These factor scores were subjected to Ward's hierarchical clustering method with squared Euclidean distance. RESULTS: Cluster analysis revealed three distinct cognitive profiles: (1) normal functioning (20% of sample); (2) delayed verbal memory and motor weaknesses (61% of the sample); and (3) global impairment (19% of the sample). Cluster 3 had longer epilepsy duration and a higher incidence of hippocampal sclerosis (HS) compared to Cluster 1 (p < .05). There were no significant differences among the three cluster groups on demographic characteristics or remaining clinical characteristics. CONCLUSIONS: Children with TLE present with distinct cognitive phenotypes ranging from average performance to global impairment. Results partially support previous hypotheses highlighting the cumulative neurobiological burden on the developing brain in the context of chronic epilepsy and provide a preliminary framework for the cognitive domains most vulnerable to the TLE disease process.

Global network alterations of the cognitive phenotypes in pediatric temporal lobe epilepsy.

OBJECTIVE: An emerging literature suggests that the neuropsychological sequelae of pediatric temporal lobe epilepsy (TLE) are characterized by a continuum of cognitive phenotypes that range in type and severity. The goal of the present investigation was to better characterize the neuropsychological networks that underlie these phenotypes. METHODS: The study included 59 patients with TLE who were empirically categorized into three cognitive phenotypes (normal, focal, and generalized impairment). Nine neuropsychological measures representing multiple cognitive domains (i.e., reasoning, language, visouperception, memory, and executive function) were examined by graph theory to characterize the global network properties of the cognitive phenotypes. RESULTS: Across the cognitive phenotype groups (i.e., normal, focal, generalized impaired) the following findings emerged: (1) the adjacency matrices demonstrated different patterns of association between cognitive measures within the neuropsychological network; (2) global measures including global efficiency (GE) and average clustering coefficient (aCC) showed a stepwise increase across the range of impaired pediatric TLE phenotypes; however, modularity (M) demonstrated the opposite pattern. IMPRESSIONS: Cognitive networks in pediatric TLE demonstrate stepwise perturbation in underlying neuropsychological networks. Graph theory offers a novel approach to examine cognitive abnormalities in pediatric TLE that may be applied to other pediatric epilepsies.

Executive function and depressed mood are independently disruptive to health-related quality of life in pediatric temporal lobe epilepsy.

OBJECTIVE: Youth with temporal lobe epilepsy (TLE) are at increased risk of depressive features and diminished health-related quality of life (HRQOL). To assist in the development of future behavioral interventions for youth with TLE, the current study explored potential pathways by which executive functioning (EF) and depressive features impinge upon HRQOL in the context of psychosocial and seizure-specific factors. METHODS: Data included parental ratings on the Behavior Assessment System for Children (BASC-2), Behavior Rating Inventory of Executive Function (BRIEF), and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaires for 82 children (Age = 11.99, SD = 3.80) with TLE. Observed path analysis was used to simultaneously investigate the determinants of HRQOL in pediatric TLE. Indirect effects were evaluated with bootstrap analyses. RESULTS: Both executive dysfunction and depressive features were negatively linked to child HRQOL, and, furthermore, EF and HRQOL were indirectly connected by depressive features. In addition, depressive features were linked to lower EF, current antiepileptic drug (AED) regimen, and the presence of hippocampal sclerosis. Diminished EF was linked to parental psychiatric history and family stress; EF mediated the relationship of parental psychiatric history and family stress on both depressive features and diminished HRQOL. Finally, a more complicated AED regimen and higher HRQOL were indirectly connected by depressive features. CONCLUSION: This study underscores the importance of child depressive features and EF along with environmental and epilepsy-specific factors on HRQOL in pediatric TLE.

Executive Dysfunction and Depression in Pediatric Temporal Lobe Epilepsy: The Contribution of Hippocampal Sclerosis and Psychosocial Factors.

OBJECTIVES: Temporal lobe epilepsy (TLE) has been identified as a risk factor for increased depression features in children and adolescents; however, less is known regarding specific neurocognitive predictors of depression in this population above and beyond seizure-specific and sociodemographic factors. METHODS: The study included 62 patients with TLE (64% male) aged 8 to 16 years (M=12.62; SD=2.26) who underwent comprehensive neuropsychological evaluation. RESULTS: Correlation analyses revealed significant association between patient depression and WCST Total Perseverations, BRIEF Behavioral Regulation Index (BRI) and family stress. Perseverative errors on the WCST and the BRI were found to significantly predict depression features in youth with TLE. Patient performance on WCST was also found to fully mediate the significant relationship between hippocampal sclerosis (HS) and depression in pediatric TLE. Finally, logistic regression indicated HS in the presence of TLE was associated with a four-fold risk of clinically significant depression ratings. CONCLUSIONS: The current findings offer strong support for the relationship between executive function (EF) and depression in pediatric TLE. Also, as HS is not modifiable, these findings suggest EF intervention may be a potential modality for improving health-related quality of life (HRQOL) in youth with TLE. (JINS, 2018, 24, 606-616).

Parental coping and its role in predicting health-related quality of life in pediatric epilepsy.

OBJECTIVE: Psychosocial difficulties are known to greatly impact the health-related quality of life (HRQOL) of a child with epilepsy, and parental coping is a unique aspect that has not been examined in relation to HRQOL in the pediatric population with epilepsy. This study assessed the relationship of parental coping with HRQOL and other clinical and sociodemographic factors. METHODS: Data included parental ratings on the Illness Cognition Questionnaire-Parent (ICQ-P) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 108 children and adolescents with epilepsy (mean 11.34 years of age). The ICQ-P examines parental coping through constructs of illness cognitions while QOLCE determines overall functioning as indicated by parents. Bivariate correlations were conducted to identify significant associations with parental coping, followed by a multiple linear regression to determine the relative contribution of parental coping on HRQOL. Sociodemographic factors on parental coping were explored with an analysis of covariance. RESULTS: Longer duration of epilepsy (r = 0.202) and higher HRQOL (r = 0.208) were significantly associated with parental acceptance on the ICQ-P. Higher parental helplessness was significantly associated with female gender of the child (r = 0.262), diminished HRQOL (r = -0.566), greater seizure frequency (r = 0.255), and higher number of prescribed antiepileptic drugs (AEDs) (r = 0.226). Parent-rated perceived benefits did not have significant association with study variables. Multiple linear regression revealed age of seizure onset (ß = 0.19, p = 0.05), seizure frequency (ß = -0.22, p = 0.01), and degree of parental helplessness (ß = -0.50, p ≤ 0.01) as unique predictors of HRQOL. Two separate ANCOVAs revealed no significant associations between maternal education or insurance type on parental helplessness. SIGNIFICANCE: Parental coping is significantly related to HRQOL in youth with epilepsy, and elevated feelings of helplessness, along with epilepsy severity, predict lower HRQOL. These findings are the first to demonstrate the unique role of parental coping in HRQOL among youth with epilepsy, and they highlight the importance of providing support to the whole family during pediatric epilepsy treatment.

The influence of endophenotypic, disease-specific, and environmental variables on the expression of anxiety in pediatric epilepsy.

Children and adolescents with epilepsy often show higher rates of anxiety, which carries an increased risk for reduced health-related quality of life (HRQOL). The current study assessed the role of parental psychiatric history (i.e., anxiety, depression, and/or bipolar disorder) on the rate of anxiety features in youth seen in a tertiary epilepsy clinic. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 180 children and adolescents (mean age=11.40, SD=3.98). Our results identified clinically elevated anxiety ratings in nearly half the sample (47%) with previous psychiatric history endorsed by 48% of parents. The effect of parental psychiatric history on youth anxiety was found to be significant and associated with a threefold increase in the rate of youth anxiety features. This risk increased to fourfold in refractory epilepsy, and the impact of family psychiatric history is greater in adolescent females and in families that report higher levels of stress. In those families who reported no psychiatric history, anxiety was best predicted by epilepsy-specific factors above and beyond sociodemographic factors. Parental psychiatric history was also identified as a significant risk factor for diminished patient HRQOL, even after accounting for seizure control. These findings highlight the impact of family and epilepsy factors on psychological functioning and offer further support for the strong relationship between parental adjustment and child outcome in pediatric epilepsy.

The relationship of seizure focus with depression, anxiety, and health-related quality of life in children and adolescents with epilepsy.

For youth with epilepsy, comorbid psychiatric conditions, such as depression and anxiety, require further examination as they carry increased risk for reduced health-related quality of life (HRQOL). The current study assessed whether rates of depression, anxiety, and withdrawal behaviors differed based on seizure location. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 132 children and adolescents (mean age=11.34, SD=3.95) with generalized or partial (i.e., frontal [FLE] or temporal lobe epilepsy [TLE]) epilepsy. Our results identified clinically significant internalizing psychopathology in nearly half of our sample (41%). Although rates of internalizing behavior were similar between generalized and partial groups, children and adolescents with TLE demonstrated higher rates of depression compared to youth with FLE. No effects of laterality on internalizing behaviors were identified between TLE and FLE groups. Finally, for youth with TLE, parental depression ratings along with current number of antiepileptic medications (AEDs) were found to be significant barriers to HRQOL above and beyond anxiety, withdrawal, and epilepsy-specific variables. Temporal lobe epilepsy was associated with a two-fold risk of clinically significant depression ratings. These findings highlight the high prevalence of internalizing psychopathology features in pediatric epilepsy and offer further support for the relationship between depression and TLE in children and adolescents with epilepsy.

Executive function and health-related quality of life in pediatric epilepsy.

Children and adolescents with epilepsy often show higher rates of executive functioning deficits and are at an increased risk of diminished health-related quality of life (HRQOL). The purpose of the current study was to determine the extent to which executive dysfunction predicts HRQOL in youth with epilepsy. Data included parental ratings on the Behavior Rating Inventory of Executive Function (BRIEF) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 130 children and adolescents with epilepsy (mean age=11years, 6months; SD=3years, 6months). Our results identified executive dysfunction in nearly half of the sample (49%). Moderate-to-large correlations were identified between the BRIEF and the QOLCE subscales of well-being, cognition, and behavior. The working memory subscale on the BRIEF emerged as the sole significant predictor of HRQOL. These results underscore the significant role of executive function in pediatric epilepsy. Proactive screening for executive dysfunction to identify those at risk of poor HRQOL is merited, and these results bring to question the potential role of behavioral interventions to improve HRQOL in pediatric epilepsy by specifically treating and/or accommodating for executive deficits.

List-learning and verbal memory profiles in childhood epilepsy syndromes.

Findings of material-specific influences on memory performance in pediatric epilepsy are inconsistent and merit further investigation. This study compared 90 children (aged 6years to 16years) with childhood absence epilepsy (CAE), frontal lobe epilepsy (FLE), and temporal lobe epilepsy (TLE) to determine whether they displayed distinct list-learning and verbal memory profiles on the California Verbal Learning Test - Children's Version (CVLT-C). Group comparison identified greater risk of memory impairment in children with TLE and FLE syndromes but not for those with CAE. While children with TLE performed worst overall on Short Delay Free Recall, groups with TLE and FLE performed similarly on Long Delay Free Recall. Contrast indices were then employed to explore these differences. Children with TLE demonstrated a significantly greater retroactive interference (RI) effect compared with groups with FLE and CAE. Conversely, children with FLE demonstrated a significantly worse learning efficiency index (LEI), which compares verbal memory following repetition with initial recall of the same list, than both children with TLE and CAE. These findings indicated shallow encoding related to attentional control for children with FLE and retrieval deficits in children with TLE. Finally, our combined sample showed significantly higher rates of extreme contrast indices (i.e., 1.5 SD difference) compared with the CVLT-C standardization sample. These results underscore the high prevalence of memory dysfunction in pediatric epilepsy and offer support for distinct patterns of verbal memory performance based on childhood epilepsy syndrome.

Chasing elusive expressive writing effects: emotion-acceptance instructions and writer engagement improve outcomes.

Introduction: Pennebaker's expressive writing (EW) paradigm in which participants are encouraged to explore their "deepest thoughts and feelings" about a difficult experience in several short writing sessions has yielded impressive mental health outcomes and holds great promise as a cost-effective intervention. Yet results have been difficult to replicate and it is unclear what conditions are necessary for observing the effect. Our aim was to discover reasons for the variability in EW outcomes. We explored the impact of augmenting writing instructions to encourage acceptance of emotional experience, which we thought would encourage engagement with writing; and we examined essay length, an index of writer engagement, as a possible moderator of writing outcomes. Methods: We compared traditional expressive writing (tEW), conducted according to Pennebaker's paradigm in which participants write about a self-chosen emotional experience for 15 min at a time on each of three closely spaced days, with an acceptance-enhanced version (AEEW), identical except that it supplemented traditional instructions with encouragement of an accepting approach to emotional experience, and with a control condition which asked participants to write about their use of time on particular days. Self-reported depression was the outcome measure. Results: Essay length (a proxy for writer engagement) moderated effects of writing at posttest 2 weeks later: Condition differences were found only for participants who wrote longer essays: For these participants the AEEW condition outperformed both control and tEW; and tEW did not differ significantly from control. Conclusion: Findings suggest that degree of engagement in the writing process may partially explain the puzzle of variable outcomes in the EW literature. Results also provide practical guidance: those who are motivated to engage deeply in the writing process are most likely to benefit; and encouraging writers to accept and to openly explore emotional experience is expected to enhance benefits.

MEG language mapping using a novel automatic ECD algorithm in comparison with MNE, dSPM, and DICS beamformer.

Introduction: The single equivalent current dipole (sECD) is the standard clinical procedure for presurgical language mapping in epilepsy using magnetoencephalography (MEG). However, the sECD approach has not been widely used in clinical assessments, mainly because it requires subjective judgements in selecting several critical parameters. To address this limitation, we developed an automatic sECD algorithm (AsECDa) for language mapping. Methods: The localization accuracy of the AsECDa was evaluated using synthetic MEG data. Subsequently, the reliability and efficiency of AsECDa were compared to three other common source localization methods using MEG data recorded during two sessions of a receptive language task in 21 epilepsy patients. These methods include minimum norm estimation (MNE), dynamic statistical parametric mapping (dSPM), and dynamic imaging of coherent sources (DICS) beamformer. Results: For the synthetic single dipole MEG data with a typical signal-to-noise ratio, the average localization error of AsECDa was less than 2 mm for simulated superficial and deep dipoles. For the patient data, AsECDa showed better test-retest reliability (TRR) of the language laterality index (LI) than MNE, dSPM, and DICS beamformer. Specifically, the LI calculated with AsECDa revealed excellent TRR between the two MEG sessions across all patients (Cor = 0.80), while the LI for MNE, dSPM, DICS-event-related desynchronization (ERD) in the alpha band, and DICS-ERD in the low beta band ranged lower (Cor = 0.71, 0.64, 0.54, and 0.48, respectively). Furthermore, AsECDa identified 38% of patients with atypical language lateralization (i.e., right lateralization or bilateral), compared to 73%, 68%, 55%, and 50% identified by DICS-ERD in the low beta band, DICS-ERD in the alpha band, MNE, and dSPM, respectively. Compared to other methods, AsECDa's results were more consistent with previous studies that reported atypical language lateralization in 20-30% of epilepsy patients. Discussion: Our study suggests that AsECDa is a promising approach for presurgical language mapping, and its fully automated nature makes it easy to implement and reliable for clinical evaluations.

The future is now: pediatric neuropsychological presurgical epilepsy evaluation in the age of COVID-19.

The objective of this brief report is to review an assessment paradigm for conducting virtual neuropsychological pre-surgical evaluations in the context of the COVID-19 pandemic. A multidisciplinary epilepsy team at a Level 4 epilepsy center within a large children's academic medical center convened to discuss the challenges and possible solutions for Phase II evaluations for pediatric patients with pharmacoresistant epilepsy during the COVID-19 pandemic. The neuropsychologists explored evidence-based methods of virtual evaluation and developed a systematic decision-making process for youth requiring a Phase II evaluation. We propose models of assessment which prioritize teleneuropsychology when possible to reduce the risk of infection: (1) evaluation with directly administered tests through a completely virtual format; (2) virtual/in-person hybrid evaluation; and (3) clinical observation/interview in a virtual format supplemented by survey data. These models are illustrated by three cases. Using virtual assessment models, the team was able to meet the urgent patient care needs and collect useful data while minimizing the risk of virus spread. The paradigms presented may be useful examples for other multidisciplinary surgical teams interested in incorporating teleneuropsychology into their practices.