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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., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

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., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against 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 ( β  = 0.23, 95% confidence interval [0.05, 0.42]) and peer support ( β  = -0.15, 95% CI [-0.28, -0.03]) on mental health. There were no mediating effects of parental support ( β  = -0.07, 95% CI [-0.14, 0.00]) or cognitive comorbidity ( β  = -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., (© 2021 International League Against Epilepsy.)

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., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated with KCNT1, we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT1 mutations in 12 previously unreported patients with focal epilepsy, multifocal epilepsy, cardiac arrhythmia, and in a family with sudden unexpected death in epilepsy (SUDEP), in addition to patients with NFLE and MMFSI. In contrast to the 100% penetrance so far reported for KCNT1 mutations, we observed incomplete penetrance. It is notable that we report that the one KCNT1 mutation, p.Arg398Gln, can lead to either of the two distinct phenotypes, ADNFLE or MMFSI, even within the same family. This indicates that genotype-phenotype relationships for KCNT1 mutations are not straightforward. We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than ADNFLE and MMFSI. KCNT1 mutations are now associated with Ohtahara syndrome, MMFSI, and nocturnal focal epilepsy. They may also be associated with multifocal epilepsy and cardiac disturbances., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Objective: Infantile spasms (IS) are a severe form of childhood epilepsy associated with autism spectrum disorders (ASD) in up to 35% of cases. The objective of this post hoc analysis of our randomized control trial was to determine whether rapid diagnosis and treatment of IS could limit the incidence of ASD while identifying risk factors related to ASD outcome., Methods: Patients with IS were randomized in a standardized diagnostic and treatment protocol. Clinical and electroencephalogram (EEG) evaluations were completed at all eight visits over 5 years, while cognitive evaluations were administered at 0, 6, 24 and 60 months, respectively. Autism was initially screened by means of the Checklist for Autism in Toddlers (CHAT) at 24 months, and formally assessed at the 30-and 60-month follow-ups using the Autism Diagnostic Observation Schedule-Generic (ADOS-G)., Results: Of the 69 patients included in the study, 25 could not be assessed due to severe delay or death. Eleven of the 42 patients screened with CHAT, were found to be at risk of an ASD outcome. ADOS was performed in 44 and 10 were diagnosed with ASD. The CHAT proved to correlate highly with the ADOS (80% ppv). Only patients with symptomatic IS developed ASD (p = 0.003). Earlier diagnosis or successful treatment did not correlate with a reduced rate of ASD. Other risk factors were identified such as having chronic epileptic discharges in the frontotemporal areas after disappearance of hypsarrhythmia (p = 0.005 and p = 0.007) and being of nonwhite origin (p = 0.009)., Significance: ASD was only observed in children with sympyomatic IS. Other clinical risk factors include chronic frontotemporal epileptic activity and being of non-white origin. Early diagnosis and treatment did not prevent ASD as an outcome of IS. However, patients at risk for ASD could be identified early on and should in the future benefit from early intervention to potentially improve their long-term outcome., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Objective: Patient-reported outcome (PRO) measures that assess the effect of epilepsy on children's lives include the concepts of health, health-related quality of life (HRQOL), and quality of life (QOL). They also contain varied health and health-related content. Our objectives were to identify what generic and epilepsy-specific PRO instruments are used in childhood epilepsy research and to make explicit their conceptual approach and biopsychosocial content., Methods: MEDLINE, EMBASE, and PsycINFO were searched from 2001 to 2011 for PRO measures used in pediatric epilepsy. Measures were analyzed on an item-by-item basis according to World Health Organization (WHO) definitions of QOL and the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY) biopsychosocial health framework to distinguish the conceptual approach within each measure. The health content analysis coded each item according to specific ICF-CY components of body function, activity and participation, environment, or personal factors to determine the health content for each measure., Results: Three generic and 13 epilepsy-specific PRO measures were identified; 10 of 16 measures utilized a biopsychosocial health approach rather than an HRQOL or QOL approach. Content analysis showed that in 11 of 16 measures, >25% of the items represented participation and activity components of the ICF-CY, whereas a high proportion of environment items were found in only one epilepsy-specific measure., Significance: This comprehensive review provides information aiding clinicians and researchers in the selection of the appropriate PRO instruments for children with epilepsy on the basis of content. Most epilepsy-specific and generic PROs use a biopsychosocial health approach as opposed to a subjective HRQOL/QOL approach to measurement. Clinicians and researchers must be aware of these concepts and content when intending to measure outcomes validly., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Rolandic epilepsy (RE) and its atypical variants (atypical rolandic epilepsy, ARE) along the spectrum of epilepsy-aphasia disorders are characterized by a strong but largely unknown genetic basis. Two genes with a putative (ELP4) or a proven (SRPX2) function in neuronal migration were postulated to confer susceptibility to parts of the disease spectrum: the ELP4 gene to centrotemporal spikes and SRPX2 to ARE. To reexamine these findings, we investigated a cohort of 280 patients of European ancestry with RE/ARE for the etiological contribution of these genes and their close interaction partners. We performed next-generation sequencing and single-nucleotide polymorphism (SNP)-array based genotyping to screen for sequence and structural variants. In comparison to European controls we could not detect an enrichment of rare deleterious variants of ELP4, SRPX2, or their interaction partners in affected individuals. The previously described functional p.N327S variant in the X chromosomal SRPX2 gene was detected in two affected individuals (0.81%) and also in controls (0.26%), with some preponderance of male patients. We did not detect an association of SNPs in the ELP4 gene with centrotemporal spikes as previously reported. In conclusion our data do not support a major role of ELP4 and SRPX2 in the etiology of RE/ARE., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Purpose: Cognitive impairment is observed commonly in children with a history of infantile spasms (IS). The goal of this study was to prospectively examine the effect on cognitive outcome of a neuroprotective agent used as adjunctive therapy during treatment of the spasms., Methods: In a randomized controlled trial, patients received a standardized therapy plus flunarizine or placebo. The standardized treatment consisted of vigabatrin as first-line therapy. Nonresponders were switched to intramuscular synthetic adrenocorticotropic hormone (sACTH depot) after 2 weeks and, if necessary, to topiramate after two additional weeks. The Vineland Adaptive Behavior Scale (VABS) and Bayley Scales of Infant Development (BSID) were used as outcome measures 24 months after the intervention., Key Findings: Sixty-eight of 101 children diagnosed over 3 years in seven centers in Canada received either adjunctive flunarizine or placebo. Sixty-five of the 68 children (96%) became spasm-free within 8 weeks and no late relapse occurred. Bayley and Vineland results were available at baseline and at 24 months in 45 children. There was no significant difference in the BSID developmental quotient between the flunarizine- and placebo-treated children at baseline (44.3 ± 35.5 vs. 30.9 ± 29.8; p = 0.18) or 24 months later (56.9 ± 33.3 vs. 46 ± 34.2; p = 0.29). However, the 10 flunarizine-treated children with no identified etiology had a better outcome than the eight controls at 24 months on both the Vineland Scale (84.1 ± 11.3 vs. 72.3 ± 9.8; p = 0.03) and the Bayley Scale (87.6 ± 14.7 vs. 69.9 ± 25.3; p = 0.07)., Significance: Our study failed to demonstrate a protective effect of flunarizine on cognitive outcome in a cohort of children with IS. An analysis of subgroups suggested that flunarizine may further improve cognitive outcome in children with no identified etiology., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Purpose: To answer a need to include and measure accurately the impact and burden of epilepsy as outcomes of interventions with affected children, we developed and validated self-report and parent-proxy respondent health-related quality of life (HRQL) instruments for preadolescent children with epilepsy., Methods: We combined qualitative and quantitative research methods. Items were extracted from focus group discussions involving children with epilepsy and their parents. We created scales formatted with alternative paired options of forced responses and used factor analysis to generate relevant subscales and reduce the number of items. We checked internal consistency, assessed test-retest reliability 10-14 days apart, and documented construct validity., Results: A sample of 381 children with epilepsy, age 6-15 years, and their parents independently completed a 67-item questionnaire, from which we chose five items for each subscale. The measures share four subscales, but each measure has an additional distinct subscale. The children and parents could discern differences and report differentially between the various aspects of the HRQL. Internal consistency measured with Cronbach's alpha was acceptable for all subscales; construct validity has been demonstrated from the testing of several hypotheses. Test-retest reliability examined with the intraclass correlation coefficient was satisfactory for the parents and for children age 8 years and older. The correlations between the mothers' and children's responses was poor to moderate., Conclusions: The data demonstrate sound psychometric properties for both related measures, which are easy to administer for children with epilepsy who are 8 years and older and their parents. The subscales encompass HRQL dimensions judged most important by children with epilepsy for the self-report measure and by parents for the proxy response measure. The parent-proxy measure should be useful as a complement to the child self-report measure in evaluating the validity of parental assessment of the child's health status; in longitudinal outcome research; and in HRQL assessment of children who are unable to respond independently.

Purpose: To determine whether long-term treatment with valproate (VPA) and/or lamotrigine (LTG) in children with epilepsy is associated with altered growth and/or bone metabolism., Methods: Twenty-seven boys and 26 girls, aged 3 to 17 years (9.2 +/- 3.9, mean +/- SD), with epilepsy treated with VPA and/or LTG for > or =2 years were evaluated for growth, nutrient intakes, physical activity, bone mineral density (BMD), and blood biochemical indices of mineral and bone metabolism., Results: Twenty-three (43.4%) of the children had a body height below the 10th percentile. Z-scores for BMD below -1.5 occurred in 24.4% of the children. When patients were divided into two groups according to daily activity score, a significantly lower Z-score for total body BMD (p = 0.007), percentile for body height (p = 0.05), and plasma parathyroid hormone (PTH; p = 0.04), osteocalcin (p = 0.04) and 25-hydroxyvitamin D (25OHD) (p = 0.01) were found in the inactive compared with the active group. Z-score for total body BMD was correlated with daily activity score (r = 0.43, p = 0.008). Plasma intact osteocalcin and intact PTH values correlated significantly (r = 0.36, p = 0.02). Plasma 1,25-dihydroxyvitamin D was within normal range for all subjects. When patients were divided into LTG-alone, VPA-alone, and LTG-plus-VPA treatment groups, significantly lower (p < 0.05) plasma osteocalcin and percentile for body height were found in the VPA-plus-LTG treatment group., Conclusions: Long-term VPA and LTG therapy, particularly when combined, is associated with short stature, low BMD, and reduced bone formation. These alterations may be mediated primarily through reduced physical activity rather than through a direct link to the VPA and/or LTG therapy.

The EEG in childhood epilepsy with occipital paroxysms (CEOP) was termed "distinctive" by Gastaut (1985) and Talwar et al. (1992) and "characteristic" by Herranz Tanarro et al. (1984), which suggests that the EEG is specific and diagnostic for CEOP. However, this hypothesis has been challenged (Newton and Aicardi, 1983; Beaumanoir and Grandjean, 1987). To test this, we reviewed 5,291 EEG reports made in 5 1/2 years in the only tertiary pediatric center in Newfoundland and Labrador. We identified 31 children who had one or more EEGs with occipital spike/sharp waves showing suppression of discharges with eye opening and normal background activity. Six had CEOP, 17 had benign nocturnal childhood occipital epilepsy, 5 had symptomatic epilepsy, 3 had unusual complex partial seizures (CPS), 4 had only provoked seizures, and 2 had no definite seizures. Overlap between seizure types was common. The EEG criteria for CEOP are not very specific.