Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome.

Copy number variations (CNVs) are associated with psychiatric and neurodevelopmental disorders (NDDs), and most, including the recurrent 15q13.3 microdeletion disorder, have unknown disease mechanisms. We used a heterozygous 15q13.3 microdeletion mouse model and patient iPSC-derived neurons to reveal developmental defects in neuronal maturation and network activity. To identify the underlying molecular dysfunction, we developed a neuron-specific proximity-labeling proteomics (BioID2) pipeline, combined with patient mutations, to target the 15q13.3 CNV genetic driver OTUD7A. OTUD7A is an emerging independent NDD risk gene with no known function in the brain, but has putative deubiquitinase function. The OTUD7A protein-protein interaction network included synaptic, axonal, and cytoskeletal proteins and was enriched for ASD and epilepsy risk genes (Ank3, Ank2, SPTAN1, SPTBN1). The interactions between OTUD7A and Ankyrin-G (Ank3) and Ankyrin-B (Ank2) were disrupted by an epilepsy-associated OTUD7A L233F variant. Further investigation of Ankyrin-G in mouse and human 15q13.3 microdeletion and OTUD7AL233F/L233F models revealed protein instability, increased polyubiquitination, and decreased levels in the axon initial segment, while structured illumination microscopy identified reduced Ankyrin-G nanodomains in dendritic spines. Functional analysis of human 15q13.3 microdeletion and OTUD7AL233F/L233F models revealed shared and distinct impairments to axonal growth and intrinsic excitability. Importantly, restoring OTUD7A or Ankyrin-G expression in 15q13.3 microdeletion neurons led to a reversal of abnormalities. These data reveal a critical OTUD7A-Ankyrin pathway in neuronal development, which is impaired in the 15q13.3 microdeletion syndrome, leading to neuronal dysfunction. Furthermore, our study highlights the utility of targeting CNV genes using cell type-specific proteomics to identify shared and unexplored disease mechanisms across NDDs.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Infants, Children, and Adolescents with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy. Consensus methods identified 20 core outcomes. In addition to the outcomes identified for the ICHOM Epilepsy adult standard set, behavioral, motor, and cognitive/language development outcomes were voted as essential for all infants and children with epilepsy. The proposed set of outcomes and measurement methods will facilitate the implementation of the use of patient-centered outcomes in daily practice.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes. Measurement tools were recommended based on their evidence of strong clinical measurement properties, feasibility, and cross-cultural applicability. The essential outcomes included many non-seizure outcomes: anxiety, depression, suicidality, memory and attention, sleep quality, functional status, and the social impact of epilepsy. The proposed set will facilitate the implementation of the use of patient-centered outcomes in daily practice, ensuring holistic care. They also encourage harmonization of outcome measurement, and if widely implemented should reduce the heterogeneity of outcome measurement, accelerate comparative research, and facilitate quality improvement efforts.

Revisiting the meaning and the source of health-related constructs and their applications in neurodisability.

The aim of this review is to revisit the meaning of common concepts and frameworks promoted to capture subjective outcomes of patients, the content of their corresponding measurements, and the preferred sources of the information of interest. This is important because conceptualizations of 'health' and the subject evaluations thereof continue to evolve. Related but distinct concepts like quality of life (QoL), health-related QoL (HRQoL), functional status, health status, and well-being are often used indiscriminately to assess clinical impacts of interventions and to influence decisions about patient care and policymaking. The discussion addresses and illustrates the following issues: (1) the required features of effective and valid health-related concepts; (2) understanding underlying factors that often create confusion about QoL and HRQoL; and (3) how these concepts provide insight into, and promote, health in the context of populations with neurodisability. The hope is to illustrate how a combination of a clear research question, a hypothesis, conceptualization of the required outcomes, and operational definitions of the domains and items of interest, including item mapping, can help to achieve robust methodology and valid findings beyond the required psychometric properties. WHAT THIS PAPER ADDS: The language, content, and the source of perceived health and life issues are clarified. Using the same terms for different constructs, or different terms for the same constructs, creates confusion and hinders outcome research. The challenges of using patient-reported outcomes in neurodisability are addressed.

Patient perspectives in pediatric neurology: a critical shift in the paradigm of outcome measurement.

This review explores children's self-reported outcome measurements in pediatric neurology. We examine the following questions: (1) What is meant by patient-reported health, functioning, and quality of life outcomes? (2) How can patients express whether the interventions they receive do more good than harm? (3) Why and how should pediatric neurology patients help determine the outcomes of interest? (4) What tools and recommendations are available to evaluate the outcomes of interest? Applying patients' perspectives across the processes of evaluation of medical interventions has become an important expectation. These developments, consistent with current healthcare goals, coincide with the evolution of pediatric neurology into a sophisticated diagnostic-interventional field that aims to prolong survival, decrease impairments and symptoms, and improve patients' well-being - the recognized essential endpoints of interest in all medicine.

Self-esteem mediates mental health outcomes in young people with epilepsy.

OBJECTIVE: To evaluate the extent to which self-esteem mediates the impacts of epilepsy-specific and environmental factors on mental health outcomes in young people with epilepsy. METHODS: A prospective cohort of 480 young people with epilepsy and their families participated in five visits over 28 months. We collected data on clinical seizure burden, cognitive comorbidity, peer and parental support, self-esteem, and self-reported mental health symptoms. We used structural equation modeling to specify and test relationships among these constructs simultaneously. Direct, indirect, and total effects were estimated with confidence intervals constructed through bias-corrected bootstrapping. RESULTS: Self-esteem mediated the effects of clinical seizure burden ( ß  = 0.23, 95% confidence interval [0.05, 0.42]) and peer support ( ß  = -0.15, 95% CI [-0.28, -0.03]) on mental health. There were no mediating effects of parental support ( ß  = -0.07, 95% CI [-0.14, 0.00]) or cognitive comorbidity ( ß  = -0.01, 95% CI [-0.02, 0.01]) on mental health. SIGNIFICANCE: We found evidence that self-esteem mediates the impact that both clinical seizure burden and peer support have on mental health outcomes, indicating that assessment of and interventions targeting self-esteem may be appropriate for young people with epilepsy. Supporting self-esteem could mitigate negative influences on mental health, whether from resistant epilepsy or low peer support.

Engaging the Voices of Children: A Scoping Review of How Children and Adolescents Are Involved in the Development of Quality-of-Life-Related Measures.

OBJECTIVES: Patient-reported outcomes are increasingly recommended to guide patient care, develop and evaluate interventions, and modify health systems. However, not enough is known about whether and how children and adolescents, as "experts" in their own health and quality of life (QoL), are being engaged in the development of instruments. Our goals in this review were (1) to identify all QoL-related instruments that have included children and/or adolescents in the development of questionnaire content, including identification of themes and items; and (2) to report how this was done; and (3) to highlight those that used qualitative methods. METHODS: MEDLINE and Embase were searched for child- or adolescent-completed QoL-related instruments, supplemented by hand-searching of relevant reviews until 2020. Original development papers were identified and retrieved when possible, from which instrument characteristics and details of qualitative development methods were extracted. RESULTS: We identified 445 instruments, of which 88 used qualitative methods for content development. Interviews and focus groups were the most common methods. A variety of play techniques were used to engage the child and adolescent participants. The specific criteria for the inclusion of children and adolescents (age, developmental stage, duration, and nonclinical location) varied considerably. CONCLUSIONS: Researchers frequently involve children and adolescents in qualitative methods when developing QoL-related measures; however, there is little information about the methods used. Better reporting of methodology, improved dissemination of methods guidelines, and research into optimal ways of including children and adolescents in the process of instrument development would be useful.

Associations between 24-hour movement guideline adherence and mental health disorders among young people with active and inactive epilepsy.

OBJECTIVE: (1) Examine 24-hour movement guideline adherence among young people with active and inactive epilepsy compared to population norms. (2) Investigate associations between 24-hour movement guideline adherence and mental health disorders among these subpopulations. METHODS: Cross-sectional data from the 2016 to 2019 cycles of the National Survey of Children's Health were used. Parental/caregiver reports of movement behaviors (physical activity, screen time, sleep, and sport participation) were used to determine adherence to the 24-hour movement guidelines and associations with mental health disorders for young people with active (n = 663) and inactive epilepsy (n = 526) as well as population norms (n = 49,067) between 6 and 17 years old. Multivariate logistic regression analyses were conducted. RESULTS: Young people with active epilepsy were less likely to meet the 24-hour movement guidelines than population norms, largely driven by below average levels of physical activity guideline adherence. Sport participation was lower among both young people with active and inactive epilepsy; seizure severity and health-related limitations played an influential role. Beneficial associations were generally observed between 24-hour movement guideline adherence and mental health disorders, although for young people with active and inactive epilepsy, there was considerable variability among these relationships. CONCLUSIONS: Further dissemination of the International League Against Epilepsy's Task Force on Sports and Epilepsy report can help improve promotion of physical activity and sport participation among young people with active and inactive epilepsy. The relationship between 24-hour movement guideline adherence and mental health disorders is complex among young people with epilepsy and longitudinal research is needed to determine causal links.

Quality of life (QOL) narratives of growing up with epilepsy from youth and family perspectives.

PURPOSE: Qualitative research studies deepen our understanding of growing up with epilepsy but are limited to the singular perspective of children or their parents at one point in childhood. A more complete view requires multiple perspectives and narrative accounts that represent development from early childhood to young adulthood. Thematic study of life narratives of 7 young people and at least one person within their families were interviewed separately (15 participants) for two interviews each (30 interviews). The objective was to obtain narratives of the life experiences, the attributions of those experiences, and crucial periods relating to quality of life (QOL) with no apriori assumptions that their lives were shaped by epilepsy. Themes were formed inductively from subthemes and codes were created based on the constant comparative method by two interviewers who iteratively co-coded the data. RESULTS: Themes emerging from the data: "Story of My Health," "Growing by Doing," "To Adapt or Not to Adapt," "Supports and Challenges," "Parent World," and "Looking in and Out, Forward and Back", often included components of seizure and epilepsy experiences but also mirrored life challenges of growing up in general. The only exclusively epilepsy-specific theme: "To Adapt or Not to Adapt", was about the challenges and solutions for dealing with the uncertainty caused by seizures and potential isolation that results from others' reactions. CONCLUSIONS: There were a range of experiences related to QOL described by participants growing up with epilepsy. The 'ingredients' of a good life (e.g., social and self-acceptance) were consistent with QOL research for general populations, although these were often expressed as more difficult to attain when growing up with epilepsy.

Quality of life in adolescents with epilepsy, cerebral palsy, and population norms.

AIM: To compare: (1) self- and proxy-reported quality of life (QoL) in adolescents with epilepsy, cerebral palsy (CP), both epilepsy and CP, and a representative general population sample; and (2) parental stress between parents of adolescents with epilepsy, CP, or both epilepsy and CP. METHOD: This was a cross-sectional observational study with 496 adolescents with epilepsy, 699 with CP, 192 with both CP and epilepsy, and 15 396 from the general population, assessed with the KIDSCREEN-52 and Parenting Stress Index (PSI). RESULTS: All KIDSCREEN-52 domains showed statistically significant differences across groups. The epilepsy population showed clinically better scores for 'school environment' than the general population (Cohen's d=0.62). Parents scored adolescents with CP lower than adolescents with epilepsy or general populations on 'physical health' (d=0.57, d=0.55) and 'social-support and peers' (d=0.82, d=0.91). Parents of adolescents with CP scored them lower than parents of the epilepsy group on 'autonomy' (d=0.62). Parents of adolescents with epilepsy scored them lower on 'mood and emotions' (d=0.52) and 'social acceptance' (d=0.66) than the general population. PSI scores were better for parents of adolescents with CP than for parents of adolescents with epilepsy (d=2.12, d=2.70, d=3.35, d=1.67). INTERPRETATION: Adolescents with epilepsy or CP self-report equal or better QoL than the general adolescent population, which should comfort families and allow clinicians to address parental concerns. WHAT THIS PAPER ADDS: Adolescents with epilepsy, with or without cerebral palsy (CP), self-reported better school environment than adolescents in the general population. Proxy quality of life (QoL) results showed clinically important differences across groups in 6 out of 10 domains of the KIDSCREEN-52. Proxy-reported results showed poorer QoL scores for adolescents with epilepsy or CP than the general population. Parental stress level was lower in parents of children with CP or both CP and epilepsy, than in those with only epilepsy.

Longitudinal trajectories of depression symptoms in children with epilepsy.

AIM: To examine self- and proxy-reported symptoms of depression in children with epilepsy. METHOD: This was a prospective longitudinal cohort study of children with epilepsy. Participants were treated at six Canadian tertiary-care centers and followed over 28 months with repeated assessments of child self-reported symptoms of depression using the Children's Depression Inventory Short-Form (CDI-S). Trajectories of symptoms of depression were estimated using linear mixed effects (LME) modeling. RESULTS: At baseline, 477 children had complete data (mean age [SD] 11y 5mo [2y 1mo], range 7y 7mo-15y 1mo; 234 females, 243 males). Mean CDI-S T score at baseline was 45.7 (SD=7.5) and at 28 months was 44.9 (SD=8.2), both were within the 'average' range. Results from LME modeling revealed mean raw CDI-S score of 1.897, corrected for age 10 years (corresponding to T scores slightly below the normed mean of 50), with no significant change over three measurements (slope=-0.113, p=0.135), indicating that CDI-S scores were stable over 28 months. Children with high initial CDI-S scores had lower subsequent scores, as demonstrated by the correlation of -0.827 between intercept and slope (p<0.001). Parents reported comparable findings. INTERPRETATION: Self- and proxy-reported symptoms of depression were generally low and stable over an extended follow-up period. Normalization of scores was seen upon repeated assessment, even in children with higher scores of symptoms of depression at one point. These findings speak to the value and importance of repeated assessment over time. WHAT THIS PAPER ADDS: In children with epilepsy, self- and proxy-reported symptoms of depression were generally low and stable over 28 months. The trajectory of symptoms of depression was not associated with seizure severity, whether considering the frequency or type of seizures. Parents' reports of symptoms of depression were comparable to the children's self-evaluations.

BRAT1 encephalopathy: a recessive cause of epilepsy of infancy with migrating focal seizures.

Epilepsy of infancy with migrating focal seizures (EIMFS), one of the most severe developmental and epileptic encephalopathy syndromes, is characterized by seizures that migrate from one hemisphere to the other. EIMFS is genetically heterogeneous with 33 genes. We report five patients with EIMFS caused by recessive BRAT1 variants, identified via next generation sequencing. Recessive pathogenic variants in BRAT1 cause the rigidity and multifocal seizure syndrome, lethal neonatal with hypertonia, microcephaly, and intractable multifocal seizures. The epileptology of BRAT1 encephalopathy has not been well described. All five patients were profoundly impaired with seizure onset in the first week of life and focal seizure migration between hemispheres. We show that BRAT1 is an important recessive cause of EIMFS with onset in the first week of life, profound impairment, and early death. Early recognition of this genetic aetiology will inform management and reproductive counselling.

Parent Proxy Discrepancy Groups of Quality of Life in Childhood Epilepsy.

OBJECTIVES: To study the extent to which parents are able to serve as true proxies for their children with epilepsy using a more granular approach than has been found in any study to date. METHODS: Proxy resemblance to the child was based on discrepancy in z-centered child minus parent scores of matching quality-of-life (QOL) domains for 477 dyads. Latent class mixed models (LCMMs) were built, with child's age as the independent variable for epilepsy-specific and generic QOL. Data were obtained from the QUALITÉ Canadian cohort, which recruited children with epilepsy aged 8 to 14 years at baseline and their parents. RESULTS: Both epilepsy-specific and generic LCMMs produced latent classes representing proxies that were overly positive, overly negative, or in agreement relative to their children with posterior probabilities of 79% to 84%. The "agreement" classes had N = 411 and N = 349 in the epilepsy-specific and generic LCMMs, respectively. The epilepsy-specific LCMM had a small unique class of N = 5 with a posterior probability of 88% called "growing discrepancy." CONCLUSIONS: Most parents of children with epilepsy can serve as valid proxies for their children on QOL scales. Poorer parental adaptation is more related to overly negative proxies, whereas low peer support from the child's perspective is more related to overly positive proxies.

Can behavioral strategies increase physical activity and influence depressive symptoms and quality of life among children with epilepsy? Results of a randomized controlled trial.

PURPOSE: This study examined whether increasing physical activity (PA) through 6 months of behavioral counseling positively influenced depressive symptoms and quality of life (QoL) over 12 months among children with epilepsy (CWE). METHODS: A longitudinal multisite randomized controlled trial (RCT) was conducted with 8-14-year-old children with active epilepsy. Participants wore a pedometer to track daily PA and completed 3 measures at 4 time points to examine depressive symptoms and QoL. Stratified by site and activity level, participants were randomized to an intervention or control group. The 6-month intervention included 11 behavioral counseling sessions targeting self-regulation of PA. To assess the associations among PA, depression scores, and QoL, primary analysis involved mixed-effects models. RESULTS: We recruited 122 CWE, of whom 115 were randomized (Mage = 11 ±â€¯2; 50% female) and included in the analysis. The intervention did not increase PA in the treatment compared with the control group. No differences were found between groups over time during the subsequent 6 months, where PA decreased among all participants. Results did not show differences between the groups and over time for measures of depressive symptoms and QoL. SIGNIFICANCE: The intervention did not improve or sustain PA levels over 12 months. Both groups demonstrated declines in PA over one year, but there were no changes in depression scores or QoL. As most participants were already nearly reaching the Canadian average of step counts of children their age, with a baseline daily step count of over 9000, there may be a challenge for further increasing PA over a longer period.

Patterns of daily activity among young people with epilepsy.

AIM: To: (1) explore how young people with epilepsy spend time on physical activity, screen-time, and sleep in a 24-hour period; (2) compare these findings to young people without epilepsy; and (3) evaluate the findings relative to the Canadian 24-hour movement guidelines for children and youth. METHOD: The study is based on Canadian data from the 2013 to 2014 'Health Behaviour in School-aged Children study' (HBSC), a cross-sectional sample of young people aged 10 to 17 years. Three groups participated: 163 young people with epilepsy, 3613 young people with non-neurological conditions, and 18 339 population norms. Self-reported activity data were compared across groups. RESULTS: Demographics were similar across groups. Young people with epilepsy spent 5.8 hours per week on moderate-to-vigorous physical activity versus 5.6 hours per week in population norms; 32% met the recommended 1 hour or more per day. Screen-time was 8.7 hours per day versus 7.4 hours per day in population norms; only 5.4% met the 2 hours or less per day recommendation. Sleep duration was 10.2 hours per day versus 9.8 hours per day in population norms, and 50.7% met the recommendation. Overall, 25.7% of young people with epilepsy did not meet any of the guidelines, 60.5% met one, 13.5% met two, and 0.3% met all three recommendations; whereas 2.8% of population norms and 2% of young people with non-neurological conditions met all three recommendations. INTERPRETATION: These data could inform future interventions and alert policy-makers, health care professionals, parents, educators, and advocacy-groups to the low adherence of young people with epilepsy with Canadian guidelines and their risk for poor health. WHAT THIS PAPER ADDS: Young people with epilepsy adhere poorly to Canadian guidelines for daily sleep duration, physical activity, and sedentary screen time. Young people with epilepsy accumulate more screen-time than those with non-neurological conditions or population norms.

PATRONES DE ACTIVIDAD DIARIA ENTRE JÓVENES CON EPILEPSIA: OBJETIVO: 1) Explorar como los jóvenes con epilepsia invierten su tiempo en actividad física, tiempo de pantalla, y sueño, en un período de 24 horas. 2) Comparar estos hallazgos con jóvenes sin epilepsia. 3) Evaluar estos hallazgos en relación con las guías canadienses de movimiento en 24 horas para niños y jóvenes. METODO: El estudio se basa en datos canadienses de 2013 a 2014. Estudio del comportamiento saludable en niños de edad escolar. Es un estudio transversal con jóvenes de 10 a 17 años. Tres grupos participaron: 163 jóvenes con epilepsia, 3.613 jóvenes con condiciones no neurológicas y 18.339 jóvenes con desarrollo típico. Los auto reportes fueron comparados entre los grupos. RESULTADOS: Los datos demográficos fueron similares entre los grupos. Los jóvenes con epilepsia pasan 5,8 horas por semana con actividad física moderada a vigorosa, versus 5,6 horas por semana en la población normal. En total, 32% cumplía la recomendación de actividad física de 1 hora o más al día. El tiempo de pantalla fue de 8,7 horas al día versus 7,4 horas al día en población típica, solo 5,4% cumple las 2 horas o menos al día recomendadas. La duración del sueño fue de 10,2 horas al día versus 9,8 horas al día en población típica y 50,7% cumple la recomendación. En general 25,7% de los jóvenes con epilepsia no cumple ninguna de las recomendaciones, 60,5% cumple una recomendación, 13,5% cumple 2 y el 0,3% cumple las 3 recomendaciones; mientras que 2,8% de la población sana y 2% de la población con condiciones no neurológicas cumple las 3 recomendaciones. INTERPRETACIÓN: Estos datos pueden ayudar a planear intervenciones futuras y alertar a responsables de crear políticas públicas, profesionales de la salud, padres, educadores y grupos de derechos, sobre la baja adherencia de jóvenes con epilepsia a las guías canadienses y su riesgo para la salud.

PADRÕES DE ATIVIDADE DIÁRIA EM JOVENS COM EPILEPSIA: OBJETIVO: (1) Explorar como jovens com epilepsia passam o tempo com relação a atividade física, tempo de tela e sono em um período de 24 horas; (2) comparar esses achados com jovens sem epilepsia e (3) avaliar os achados relativos as Diretrizes Canadenses de movimentação 24 horas para crianças e jovens. MÉTODOS: O estudo foi baseado nos dados Canadenses de 2013 a 2014 'Estudo do comportamento em saúde em crianças em idade escolar' (ECSCE), uma amostra transversal de jovens de 10 a 17 anos. Participaram três grupos: 163 jovens com epilepsia, 3.613 jovens com condições não neurológicas e 18.339 jovens da população típica. Os dados de atividades autorreferidos foram comparados entre os grupos. RESULTADOS: Os dados demográficos foram semelhantes entre os grupos. Jovens com epilepsia gastaram 5,8 horas por semana realizando atividade física moderada a vigorosa versus 5,6 horas por semana na população típica; 32% cumpriram a recomendação de 1 hora ou mais por dia. O tempo de tela foi de 8,7 horas por dia versus 7,4 horas por dia na população típica; apenas 5,4% cumpriram a recomendação de 2 horas ou menos por dia. A duração do sono foi de 10,2 horas por dia versus 9,8 horas por dia na população típica e 50,7% cumpriram a recomendação. No geral, 25,7% dos jovens com epilepsia não cumpriram nenhuma das orientações, 60,5% cumpriram uma, 13,5% cumpriram duas e 0,3 por cento cumpriram as três recomendações; encontrou-se que 2,8% da população típica e 2% dos jovens com condições não neurológicas cumpriram as três recomendações. INTERPRETAÇÃO: Esses dados podem orientar futuras intervenções e alertar formuladores de políticas, profissionais de saúde, pais, educadores e grupos de defesa da baixa aderência dos jovens com epilepsia segundo às diretrizes Canadenses e seu risco de problemas de saúde.

Youth with epilepsy: Their insight into participating in enhanced physical activity study.

PURPOSE: We aimed to explore (i) the impact that a motivated walking program had on youth with epilepsy and (ii) the facilitators and barriers to implementing and sustaining the program. METHODS: Data were gathered using semi-structured interviews with the intervention group of a randomized controlled trial to study the effect of enhanced physical activity on youth with epilepsy. Participants had active epilepsy and were 8-14 years at recruitment. All wore an activity tracker for a year and received coaching via phone calls during the first six months to encourage reaching a step goal, which they then attempted to maintain independently for the following six months. Nine participants and one parent per child were separately interviewed at six months. Eleven participants including the original nine, and one parent per youth, were interviewed at twelve months. Data collection and analysis used a phenomenological research framework and coded the data according to the International Classification of Functioning, Disability and Health (the ICF). This was done in order to capture all relevant impacts of the intervention. RESULTS: Physical activity was associated with benefits in all components of the ICF. Changes in personal factors such as improved attitude, confidence, and insight into activity were emphasized. Parents also experienced personal benefits as a result of their child engaging in the program. CONCLUSIONS: Physical activity had positive effects in many aspects of the lives of the participants and their parents. The ICF was a relatively useful and effective system for coding qualitative research. These findings should assist in development of future exercise programs.

Patient-reported quality of life and biopsychosocial health outcomes in pediatric epilepsy: An update for healthcare providers.

In the 21st century, clinicians are expected to listen to, and understand their patients' views about, their conditions and the effects that these conditions have on their functioning, values, life goals, and welfare. The goals of this review are as follows: (i) to inform, update, and guide clinicians caring for children with epilepsy about developments in the content and new methods of research on patient-reported outcomes, quality of life, and functioning; and (ii) to discuss the value of using these concepts to explore the impact of diverse interventions that are implemented in daily practice. Drawing on the literature and our program of research over the past two decades, we focus on our current understanding of a variety of health concepts and recently acquired knowledge about their significance for the lives of patients and their families. We discuss the advantages of measuring patient-reported outcomes that tell us what is important to patients. We advise on what characteristics to look for when choosing a patient-reported measure, and the relevance of these considerations. In addition, we address gaps in research knowledge and the causes of confusion that have limited their use in our daily clinical practice.

Child- and parent-reported quality of life trajectories in children with epilepsy: A prospective cohort study.

OBJECTIVE: To describe the developmental trajectories of quality of life (QoL) in a large cohort of children with epilepsy, and to assess the relative contribution of clinical, psychosocial, and sociodemographic variables on QoL trajectories. METHODS: Five assessments during a 28-month prospective cohort study were used to model trajectories of QoL. Participants were recruited with their parents from six Canadian tertiary centers. A convenience sample of 506 children aged 8-14 years with epilepsy and without intellectual disability or autism spectrum disorder were enrolled. A total of 894 children were eligible and 330 refused participation. Participating children were, on average, 11.4 years of age, and 49% were female. Nearly one third (32%) had partial seizures. At baseline, 479 and 503 child- and parent-reported questionnaires were completed. In total, 354 children (74%) and 366 parents (73%) completed the 28-month follow-up. QoL was measured using the child- and parent-reported version of the Childhood Epilepsy QoL scale (CHEQOL-25). RESULTS: Child-reported QoL was fitted best by a six-class model and parent-reported QoL by a five-class model. In both models, trajectories remained either stable or improved over 28 months. Of these children, 62% rated their QoL as high or moderately high, defined as at least one standard deviation above the average CHEQOL-25 score. Greater family, classmate, and peer social support, fewer symptoms of child and parent depression, and higher receptive vocabulary were identified as the most robust predictors of better QoL (all p < 0.001). SIGNIFICANCE: Most children with epilepsy and their parents reported relatively good QoL in this first joint self- and proxy-reported trajectory study. Findings confirm the heterogeneous QoL outcomes for children with epilepsy and the primary importance of psychosocial factors rather than seizure and AED-specific factors in influencing QoL. These predictors that are potentially amenable to change should now be the focus of specific intervention studies.

Reflections on Ethics and Humanity in Pediatric Neurology: the Value of Recognizing Ethical Issues in Common Clinical Practice.

Our goals in this reflection are to (i) identify the ethical dimensions inherent in any clinical encounter and (ii) bring to the forefront of our pediatric neurology practice the myriad of opportunities to explore and learn from these ethical questions. We highlight specifically Beauchamp and Childress's principles of biomedical ethics. We use the terms ethics in common clinical practice and an ethical lens to remind people of the ubiquity of ethical situations and the usefulness of using existing ethical principles to analyze and resolve difficult situations in clinical practice. We start with a few common situations with which many of us tend to struggle. We describe what we understand as ethics and how and why developments in technology, novel potential interventions, policies, and societal perspectives challenge us to think about and debate ethical issues. Individual patients are not a singular population; each patient has their own unique life situations, culture, goals, and expectations that need to be considered with a good dose of humanity and humility. We believe that using an ethical lens-by which we mean making an explicit effort to identify and consider these issues openly-will help us to achieve this goal in practice, education, and research.

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy.

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65,046 European population controls (5/393 cases versus 32/65,046 controls; Fisher's exact test P = 2.83 × 10(-6), odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10(-4)). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE.