Ketogenic dietary therapy utilization in Kenya: A qualitative exploration of dietitian's perceptions.

This study utilized a qualitative design to explore dietitians' perceptions regarding Ketogenic Diet Therapy (KDT) for patients with drug-resistant epilepsy in Kenya. Dietitians from Kenya were selected and consented. Audio-recorded interviews were conducted, followed by thematic analysis of verbatim transcripts to identify recurring patterns. The study enrolled 18 dietitians, fourteen of whom correctly described their understanding of KDT for managing drug-resistant epilepsy. There was a lack of confidence in their capacity to initiate the KDT with all expressing the need for further training and facilitation. Only one dietitian reported having initiated and maintained KDT. There was an overall positive view regarding KDT and willingness to implement KDT for patients with drug-resistant epilepsy. Dietitians expressed concerns regarding the availability of national policies, inadequate staffing to support families who require KDT, and the cost of implementing this intervention. Dietitians expressed interest in virtual training to enhance their understanding of KDT. Dietitians in Kenya are mostly aware of KDT utilization for the management of drug-resistant epilepsy. However, they cited poor capability and various barriers to implementation. There is a need for policies to facilitate KDT as a treatment option for the benefit of patients with drug-resistant epilepsy.

Clinician views regarding early surgery for paediatric epilepsy.

OBJECTIVE: Many children with lesional epilepsies progress to drug resistance, a criterion required for surgical referral. Expedited surgery may reduce exposure of the developing brain to uncontrolled seizures, improving cognitive outcomes. Designing a trial comparing early surgery with standard care necessitates input from specialist clinicians regarding feasibility and measurable outcomes, which this study investigated. METHODS: Online surveys were disseminated from June-July 2022 via regional paediatric epilepsy networks and professional societies. 51 UK clinicians responded, mostly paediatricians, paediatric neurologists and epilepsy specialist nurses. Candidacy for epilepsy surgery, outcome measures and support for the proposed study were surveyed. Clinician views were compared by speciality, using Pearson's chi-squared tests to explore differences. RESULTS: 76-98 % of clinicians would refer children for presurgical evaluation at/before drug resistance development across four subgroups (those younger/older than two years, and those with/without a detectable lesion). Earlier referral, at/before epilepsy diagnosis, was considered mostly in those with visible lesions (53 %) and those under two years (31 %). 73 % would consider early surgery before drug resistance is established. Top outcomes to measure were seizure freedom (39 %) and quality of life (22 %). Views of paediatric neurologists and paediatricians did not differ (p > .05). SIGNIFICANCE: Clinician opinions generally aligned with published guidance regarding epilepsy surgery referral. Some remain cautious to refer young children with lesions prior to trialling more than one antiseizure medication. Most support early surgery in appropriate patients, with seizure and quality of life outcomes rated highly. Incorporating these perspectives will aid future trial design, recruitment and clinical utility.

Perceived impact of epilepsy on sleep: Views of children with epilepsy, parents and school staff.

OBJECTIVE: To gain an understanding of the views of school-aged children with epilepsy, their parents, and school staff regarding the impact of epilepsy on sleep. METHODS: As part of the What I Need in School (WINS) study, school-aged children (n = 18) with 'active epilepsy' (taking Anti-Seizure Medications, ASMs, for epilepsy), their parents (n = 68) and school staff (n = 56) were interviewed or completed bespoke questionnaires. Questions focussed on the potential impact of epilepsy on the child's sleep or tiredness in school and the potential impact of sleep/tiredness on learning and behavior. RESULTS: Fifty-six percent of children believed that epilepsy affects their sleep while 65% of parents believed that their child had more difficulties with sleep than other children of their age. Seventy-eight percent of parents believed that their child's difficulties were due to epilepsy and 95% believed that their child's difficulties impacted their learning and behavior. Fifty-four percent of school staff believed that the child with epilepsy they supported was more tired/fatigued than their peers, and 86% of school staff believed that the child's increased tiredness affected their learning/behavior. Parents of children with intellectual disabilitiy were significantly more likely to indicate that they felt that their child had more sleep difficulties than other children (p = 0.016). Regarding the impact on their sleep, participating children felt that epilepsy contributed to difficulties in falling and staying asleep and daytime tiredness. Their parents reported a range of potential sleep difficulties and potential impacts on the child's learning and behavior. Parental reported difficulties included daytime tiredness, difficulty falling and staying asleep, and the impact of nocturnal seizures. In terms of impact, parents felt that sleep difficulties impacted negatively cognition and emotional-behavioral functioning. Additionally, parents reported that ASMs and medication for ADHD can contribute to sleep difficulties. School staff felt that many of the children appeared tired/fatigued during the day and this could lead to less engagement with classroom activities, impact attention and processing speed negatively, and contribute to behavioral and emotional difficulties. CONCLUSION: The majority of children and parents who responded believed that epilepsy affects the child's sleep. Most parents and school staff also believed that the child's sleep difficulties/excess tiredness were due to the child's epilepsy and that the difficulties significantly impacted the child's learning and behavior. There is a need to better understand the role epilepsy plays in sleep difficulties and associated learning and behavioral impairments. There is also a need to develop interventions to reduce the subsequent impact on child learning and behavior.

Fenfluramine treatment is associated with improvement in everyday executive function in preschool-aged children (<5 years) with Dravet syndrome: A critical period for early neurodevelopment.

OBJECTIVE: To evaluate whether fenfluramine (FFA) is associated with improvement in everyday executive function (EF)-self-regulation-in preschool-aged children with Dravet syndrome (DS). METHODS: Children with DS received placebo or FFA in one of two phase III studies (first study: placebo, FFA 0.2 mg/kg/day, or FFA 0.7 mg/kg/day added to stiripentol-free standard-of-care regimens; second study: placebo or FFA 0.4 mg/kg/day added to stiripentol-inclusive regimens). Everyday EF was evaluated at baseline and Week 14-15 for children aged 2-4 years with parent ratings on the Behavior Rating Inventory of Executive Function®-Preschool (BRIEF®-P); raw scores were transformed to T-scores and summarized in Inhibitory Self-Control Index (ISCI), Flexibility Index (FI), Emergent Metacognition Index (EMI), and Global Executive Composite (GEC). Clinically meaningful improvement and worsening were defined using RCI ≥ 90% and RCI ≥ 80% certainty, respectively. The associations between placebo vs FFA combined (0.2, 0.4, and 0.7 mg/kg/day) or individual treatment groups and the likelihood of clinically meaningful change in BRIEF®-P indexes/composite T-scores were evaluated using Somers'd; pairwise comparisons were calculated by 2-sided Fisher's Exact tests (p ≤ 0.05) and Cramér's V. RESULTS: Data were analyzed for 61 evaluable children of median age 3 years (placebo, n = 22; FFA 0.2 mg/kg/day, n = 15; 0.4 mg/kg/day [with stiripentol], n = 10; 0.7 mg/kg/day, n = 14 [total FFA, n = 39]). Elevated or problematic T-scores (T ≥ 65) were reported in 55% to 86% of patients at baseline for ISCI, EMI, and GEC, and in ∼33% for FI. Seventeen of the 61 children (28%) showed reliable, clinically meaningful improvement (RCI ≥ 90% certainty) in at least one BRIEF®-P index/composite, including a majority of the children in the FFA 0.7 mg/kg/day group (9/14, 64%). Only 53% of these children (9/17) also experienced clinically meaningful reduction (≥50%) in monthly convulsive seizure frequency, including 6/14 patients in the FFA 0.7 mg/kg/day group. Overall, there were positive associations between the four individual treatment groups and the likelihood of reliable, clinically meaningful improvement in all BRIEF®-P indexes/composite (ISCI, p = 0.001; FI, p = 0.005; EMI, p = 0.040; GEC, p = 0.002). The FFA 0.7 mg/kg/day group showed a greater likelihood of reliable, clinically meaningful improvement than placebo in ISCI (50% vs 5%; p = 0.003), FI (36% vs 0%; p = 0.005), and GEC (36% vs 0%; p = 0.005). For EMI, the FFA 0.7 mg/kg/day group showed a greater likelihood of reliable, clinically meaningful improvement than the FFA 0.2 mg/kg/day group (29% vs 0%; p = 0.040), but did not meet the significance threshold compared with placebo (29% vs 5%; p = 0.064). There were no significant associations between treatment and the likelihood of reliable, clinically meaningful worsening (p > 0.05). SIGNIFICANCE: In this preschool-aged DS population with high baseline everyday EF impairment, FFA treatment for 14-15 weeks was associated with dose-dependent, clinically meaningful improvements in regulating behavior, emotion, cognition, and overall everyday EF. These clinically meaningful improvements in everyday EF were not entirely due to seizure frequency reduction, suggesting that FFA may have direct effects on everyday EF during the early formative years of neurodevelopment.

Expedited epilepsy surgery prior to drug resistance in children: a frontier worth crossing?

Epilepsy surgery is an established safe and effective treatment for selected candidates with drug-resistant epilepsy. In this opinion piece, we outline the clinical and experimental evidence for selectively considering epilepsy surgery prior to drug resistance. Our rationale for expedited surgery is based on the observations that (i) a high proportion of patients with lesional epilepsies (e.g. focal cortical dysplasia, epilepsy-associated tumours) will progress to drug resistance; (ii) surgical treatment of these lesions, especially in non-eloquent areas of brain, is safe; and (iii) earlier surgery may be associated with better seizure outcomes. Potential benefits beyond seizure reduction or elimination include less exposure to antiseizure medications, which may lead to improved developmental trajectories in children and optimize long-term neurocognitive outcomes and quality of life. Further, there exists emerging experimental evidence that brain network dysfunction exists at the onset of epilepsy, where continuing dysfunctional activity could exacerbate network perturbations. This in turn could lead to expanded seizure foci and contribution to the comorbidities associated with epilepsy. Taken together, we rationalize that epilepsy surgery, in carefully selected cases, may be considered prior to drug resistance. Last, we outline the path forward, including the challenges associated with developing the evidence base and implementing this paradigm into clinical care.

Proportion of resected seizure onset zone contacts in pediatric stereo-EEG-guided resective surgery does not correlate with outcome.

OBJECTIVE: We aimed to determine whether the proportion of putative seizure onset zone (SOZ) contacts resected associates with seizure outcome in a cohort of children undergoing stereoelectroencephalography (SEEG)-guided resective epilepsy surgery. METHODS: Patients who underwent SEEG-guided resective surgery over a six-year period were included. The proportion of SOZ contacts resected was determined by co-registration of pre- and post-operative imaging. Outcome was classified as seizure free (SF, Engel class I) or not seizure-free (NSF, Engel class II-IV) at last clinical follow-up. RESULTS: Twenty-nine patients underwent resection of whom 22 had sufficient imaging data for analysis (median age at surgery of 10 years, range 5-18). Fifteen (68.2%) were SF at median follow-up of 19.5 months (range 12-46). On univariate analysis, histopathology, was the only significant factor associated with SF (p < 0.05). The percentage of defined SOZ contacts resected ranged from 25-100% and was not associated with SF (p = 0.89). In a binary logistic regression model, it was highly likely that histology was the only independent predictor of outcome. CONCLUSIONS: The percentage of SOZ contacts resected was not associated with SF in children undergoing SEEG-guided resective epilepsy surgery. SIGNIFICANCE: Factors such as spatial organisation of the epileptogenic zone, neurophysiological biomarkers and the prospective identification of pathological tissue may therefore play an important role.

Impact of the COVID-19 pandemic on people with epilepsy: Findings from the Brazilian arm of the COV-E study.

The COVID-19 pandemic has had an unprecedented impact on people and healthcare services. The disruption to chronic illnesses, such as epilepsy, may relate to several factors ranging from direct infection to secondary effects from healthcare reorganization and social distancing measures. OBJECTIVES: As part of the COVID-19 and Epilepsy (COV-E) global study, we ascertained the effects of COVID-19 on people with epilepsy in Brazil, based on their perspectives and those of their caregivers. We also evaluated the impact of COVID-19 on the care delivered to people with epilepsy by healthcare workers. METHODS: We designed separate online surveys for people with epilepsy and their caregivers. A further survey for healthcare workers contained additional assessments of changes to working patterns, productivity, and concerns for those with epilepsy under their care. The Brazilian arm of COV-E initially collected data from May to November 2020 during the country's first wave. We also examined national data to identify the Brazilian states with the highest COVID-19 incidence and related mortality. Lastly, we applied this geographic grouping to our data to explore whether local disease burden played a direct role in difficulties faced by people with epilepsy. RESULTS: Two hundred and forty-one people returned the survey, 20% were individuals with epilepsy (n = 48); 22% were caregivers (n = 53), and 58% were healthcare workers (n = 140). Just under half (43%) of people with epilepsy reported health changes during the pandemic, including worsening seizure control, with specific issues related to stress and impaired mental health. Of respondents prescribed antiseizure medication, 11% reported difficulty taking medication on time due to problems acquiring prescriptions and delayed or canceled medical appointments. Only a small proportion of respondents reported discussing significant epilepsy-related risks in the previous 12 months. Analysis of national COVID-19 data showed a higher disease burden in the states of Sao Paulo and Rio de Janeiro compared to Brazil as a whole. There were, however, no geographic differences observed in survey responses despite variability in the incidence of COVID-19. CONCLUSION: Our findings suggest that Brazilians with epilepsy have been adversely affected by COVID-19 by factors beyond infection or mortality. Mental health issues and the importance of optimal communication are critical during these difficult times. Healthcare services need to find nuanced approaches and learn from shared international experiences to provide optimal care for people with epilepsy as the direct burden of COVID-19 improves in some countries. In contrast, others face resurgent waves of the pandemic.

Importance of access to epilepsy monitoring units during the COVID-19 pandemic: Consensus statement of the International League against epilepsy and the International Federation of Clinical Neurophysiology.

Restructuring of healthcare services during the COVID-19 pandemic has led to lockdown of Epilepsy Monitoring Units (EMUs) in many hospitals. The ad-hoc taskforce of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) highlights the detrimental effect of postponing video-EEG monitoring of patients with epilepsy and other paroxysmal events. The taskforce calls for action to continue functioning of Epilepsy Monitoring Units during emergency situations, such as the COVID-19 pandemic. Long-term video-EEG monitoring is an essential diagnostic service. Access to video-EEG monitoring of the patients in the EMUs must be given high priority. Patients should be screened for COVID-19, before admission, according to the local regulations. Local policies for COVID-19 infection control should be adhered to during the video-EEG monitoring. In cases of differential diagnosis where reduction of antiseizure medication is not required, consider home video-EEG monitoring as an alternative in selected patients.

Evaluating risk to people with epilepsy during the COVID-19 pandemic: Preliminary findings from the COV-E study.

The COVID-19 pandemic has caused global anguish unparalleled in recent times. As cases rise, increased pressure on health services, combined with severe disruption to people's everyday lives, can adversely affect individuals living with chronic illnesses, including people with epilepsy. Stressors related to disruption to healthcare, finances, mental well-being, relationships, schooling, physical activity, and increased isolation could increase seizures and impair epilepsy self-management. We aim to understand the impact that COVID-19 has had on the health and well-being of people with epilepsy focusing on exposure to increased risk of seizures, associated comorbidity, and mortality. We designed two online surveys with one addressing people with epilepsy directly and the second for caregivers to report on behalf of a person with epilepsy. The survey is ongoing and has yielded 463 UK-based responses by the end of September 2020. Forty percent of respondents reported health changes during the pandemic (n = 185). Respondents cited a change in seizures (19%, n = 88), mental health difficulties (34%, n = 161), and sleep disruption (26%, n = 121) as the main reasons. Thirteen percent found it difficult to take medication on time. A third had difficulty accessing medical services (n = 154), with 8% having had an appointment canceled (n = 39). Only a small proportion reported having had discussions about epilepsy-related risks, such as safety precautions (16%, n = 74); mental health (29%, n = 134); sleep (30%, n = 140); and Sudden Unexpected Death in Epilepsy (SUDEP; 15%, n = 69) in the previous 12 months. These findings suggest that people with epilepsy are currently experiencing health changes, coupled with inadequate access to services. Also, there seems to be a history of poor risk communication in the months preceding the pandemic. As the UK witnesses a second COVID-19 wave, those involved in healthcare delivery must ensure optimal care is provided for people with chronic conditions, such as epilepsy, to ensure that avoidable morbidity and mortality is prevented during the pandemic, and beyond.

Clinical outcomes of COVID-19 in long-term care facilities for people with epilepsy.

In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance. During 25-week observation period (16 March-6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate. We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth's (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive. Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes.

Diagnostic algorithm for children presenting with epilepsia partialis continua.

OBJECTIVE: To characterize a cohort of children with epilepsia partialis continua (EPC) and develop a diagnostic algorithm incorporating key differential diagnoses. METHODS: Children presenting with EPC to a tertiary pediatric neurology center between 2002 and 2019 were characterized. RESULTS: Fifty-four children fulfilled EPC criteria. Median age at onset was 7 years (range 0.6-15), with median follow-up of 4.3 years (range 0.2-16). The diagnosis was Rasmussen encephalitis (RE) in 30 of 54 (56%), a mitochondrial disorder in 12 of 54 (22.2%), and magnetic resonance imaging (MRI) lesion-positive focal epilepsy in 6 of 54 (11.1%). No diagnosis was made in 5 of 54 (9%). Children with mitochondrial disorders developed EPC earlier; each additional year at presentation reduced the odds of a mitochondrial diagnosis by 26% (P = .02). Preceding developmental concerns (odds ratio [OR] 22, P < .001), no seizures prior to EPC (OR 22, P < .001), bilateral slowing on electroencephalogram (EEG) (OR 26, P < .001), and increased cerebrospinal fluid (CSF) protein level (OR 16) predicted a mitochondrial disorder. Asymmetry or hemiatrophy was evident on MRI at presentation with EPC in 18 of 30 (60%) children with RE, and in the remainder at a median of 6 months (range 3-15) after EPC onset. The first diagnostic test is brain MRI. Hemiatrophy may permit a diagnosis of RE with unilateral clinical and EEG findings. For children in whom a diagnosis of RE cannot be made on first scan but the clinical and radiological presentation resembles RE, repeat imaging every 6 months is recommended to detect progressive unicortical hemiatrophy, and brain biopsy should be considered. Evidence of intrathecal inflammation (oligoclonal bands and raised neopterin) can be supportive. In children with bihemispheric EPC, rapid polymerase gamma testing is recommended and if negative, sequencing mtDNA and whole-exome sequencing on blood-derived DNA should be performed. SIGNIFICANCE: Children presenting with EPC due to a mitochondrial disorder show clinical features distinguishing them from RE and structural epilepsies. A diagnostic algorithm for children with EPC will allow targeted investigation and timely diagnosis.

Physical activity in people with epilepsy: A systematic review.

This study aimed to systematically review studies focusing on levels of physical activity (PA) in people with epilepsy (PWE) compared with non-epilepsy controls, and identify factors associated with PA in PWE. Intervention studies were also reviewed to consider the effects of psychological interventions on levels of PA, and the effects of PA-based interventions on seizure activity, psychiatric comorbidity, and health-related quality of life (HRQoL). PRISMA guidelines were followed. Searches were conducted using PubMed, Cochrane Controlled Register of Trials, PsycINFO, and Embase. Forty-six studies met inclusion criteria, including case-control, cross-sectional, and intervention studies. Assessment measures included questionnaires, activity trackers, and measures of physiological fitness. Twelve of 22 (54.5%) case-control studies utilizing self-report questionnaire measures reported that PWE were performing lower levels of PA, less likely to be engaging in PA, or less likely to meet PA guidelines than controls. The remaining studies did not find a difference between PWE and controls. Eight of 12 (67%) case-control studies utilizing exercise/fitness tests reported that PWE performed significantly poorer than controls, whereas in two studies PWE performed better than controls. One of three studies investigating the relationship between PA and seizure frequency found that increased self-reported PA was associated with having fewer seizures, whereas two did not find a significant relationship. All seven cross-sectional studies that included measures of HRQoL and depression/anxiety found a positive relationship between levels of PA and HRQoL/reduced levels of depression and anxiety. All four studies that used PA-based interventions demonstrated improvements in levels of PA and increased HRQoL. Study quality was almost universally low. In conclusion, there is some evidence that PWE engage in less PA than peers, and that interventions can improve PA levels and HRQoL. However, there is a need for more robust study designs to better understand PA in individuals with epilepsy.

Autism, ADHD and parent-reported behavioural difficulties in young children with epilepsy.

PURPOSE: To provide data on the prevalence of Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD), and parent reported behaviour difficulties in young children with epilepsy, and to compare results with children with neurodisability (neurodevelopmental/neurological difficulties) without epilepsy. METHOD: Children with epilepsy (1-7 years, n = 48) and children with neurodisability (1-7 years, n = 48) matched for gender, chronological and developmental age underwent psychological assessment. Parents completed measures of behaviour including the Strengths and Difficulties Questionnaire (SDQ). DSM-5 diagnoses of ASD and ADHD were made at consensus case conferences. Factors associated with child behaviour were analysed using linear regression. RESULTS: Of the children with epilepsy, 18% met ASD criteria and 40% met ADHD criteria (corresponding figures in the non-epilepsy group were 41% and 27%). A large proportion (76%-78%) in both groups scored in the at-risk range on the SDQ and frequently had difficulties across multiple behavioural domains. Children with epilepsy had more concerns expressed regarding attention and mood. None of the epilepsy factors were significantly associated with scores on the behavioural measures. SIGNIFICANCE: Young children with epilepsy had a very high level of parent reported behavioural difficulties and a high risk for ADHD and ASD highlighting the need for comprehensive multidisciplinary assessment. Behavioural concerns were not greater than for other children with non-epilepsy related neurodisability with the exception of attention and mood. Epilepsy related factors were not associated with child behaviour, suggesting that seizures per se do not confer a unique risk for behavioural difficulties.

Do behavior and emotions improve after pediatric epilepsy surgery? A systematic review.

OBJECTIVE: The objective was to systematically review studies that have focused on behavioral and emotional functioning before (baseline) and after (follow-up) pediatric epilepsy surgery. METHODS: The systematic review was carried out according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and EMBASE were searched from inception. Findings are described with respect to (1) changes in behavior and emotions between baseline and follow-up, (2) factors associated with changes in behavior and emotions, and (3) impact of study quality on findings. RESULTS: Fifteen studies met inclusion criteria. The majority of studies employed parent report screening checklists. In these studies, scores were reported to have significantly improved at follow-up on at least one domain in seven studies and not to have changed significantly in two studies. In no studies was a deterioration in behavior noted. In studies that used Diagnostic and Statistical Manual of Mental Disorders (DSM) clinical diagnoses, no significant change was noted in the numbers of children diagnosed at baseline and at follow-up. In total, 21 children lost diagnoses, whereas 16 children developed new diagnoses. A better seizure outcome was associated with improvements in behavioral-emotional functioning at follow-up in three of the four studies where it was considered. In terms of study quality, none of the studies was rated as strong (ie, had no weak ratings on a quality assessment tool). SIGNIFICANCE: There is some evidence of improvement in emotional and behavioral functioning after epilepsy surgery. However, this is confined to scores on parent-reported screening measures of emotional and behavioral symptoms and not clinical diagnoses. Future research should focus on including responses from multiple respondents (child, parent, teacher) when using screening instruments, but also diagnostic interviews. There is a need for long-term follow-up (beyond 2 years) with sufficiently large sample sizes including data from nonsurgery controls to understand factors associated with changes in functioning postsurgery.

Diagnostic implications of genetic copy number variation in epilepsy plus.

OBJECTIVE: Copy number variations (CNVs) represent a significant genetic risk for several neurodevelopmental disorders including epilepsy. As knowledge increases, reanalysis of existing data is essential. Reliable estimates of the contribution of CNVs to epilepsies from sizeable populations are not available. METHODS: We assembled a cohort of 1255 patients with preexisting array comparative genomic hybridization or single nucleotide polymorphism array based CNV data. All patients had "epilepsy plus," defined as epilepsy with comorbid features, including intellectual disability, psychiatric symptoms, and other neurological and nonneurological features. CNV classification was conducted using a systematic filtering workflow adapted to epilepsy. RESULTS: Of 1097 patients remaining after genetic data quality control, 120 individuals (10.9%) carried at least one autosomal CNV classified as pathogenic; 19 individuals (1.7%) carried at least one autosomal CNV classified as possibly pathogenic. Eleven patients (1%) carried more than one (possibly) pathogenic CNV. We identified CNVs covering recently reported (HNRNPU) or emerging (RORB) epilepsy genes, and further delineated the phenotype associated with mutations of these genes. Additional novel epilepsy candidate genes emerge from our study. Comparing phenotypic features of pathogenic CNV carriers to those of noncarriers of pathogenic CNVs, we show that patients with nonneurological comorbidities, especially dysmorphism, were more likely to carry pathogenic CNVs (odds ratio = 4.09, confidence interval = 2.51-6.68; P = 2.34 × 10-9 ). Meta-analysis including data from published control groups showed that the presence or absence of epilepsy did not affect the detected frequency of CNVs. SIGNIFICANCE: The use of a specifically adapted workflow enabled identification of pathogenic autosomal CNVs in 10.9% of patients with epilepsy plus, which rose to 12.7% when we also considered possibly pathogenic CNVs. Our data indicate that epilepsy with comorbid features should be considered an indication for patients to be selected for a diagnostic algorithm including CNV detection. Collaborative large-scale CNV reanalysis leads to novel declaration of pathogenicity in unexplained cases and can promote discovery of promising candidate epilepsy genes.

Cognitive outcomes following epilepsy in infancy: A longitudinal community-based study.

OBJECTIVE: Onset of epilepsy before 2 years of age is associated with poor cognitive outcome; however, the natural course of the range of epilepsies that occur at this age is unknown. The aim of this prospective community-based study was to investigate the neuropsychological development of infants with newly diagnosed epilepsy longitudinally and to identify the clinical factors that predict long-term impairment. METHODS: Sixty-six infants <24 months of age were enrolled in the baseline phase of this study; 40 were seen again at 1-year follow-up and 40 at 3-year follow-up. Children underwent a neurological and neuropsychological assessment at each time point. RESULTS: More than 55% of children demonstrated impaired cognitive functioning at each assessment, with a similar percentage showing impaired memory and attention at 3-year follow-up. Cognitive scores obtained at each time point were correlated. More than 20 seizures/seizure clusters prior to assessment and an abnormal neurologic examination predicted poor cognitive functioning at baseline, whereas continuing seizures and baseline cognitive score predicted 3-year intelligence quotient (IQ)/cognitive score. SIGNIFICANCE: These findings demonstrate the following: (1) infants who are performing poorly at baseline continue to display impaired development at follow-up, (2) these children are delayed across a range of neuropsychological functions, and (3) a high number of seizures close to initial diagnosis and continuing seizures at follow-up independently predict cognitive impairment. These findings help to identify those infants with new-onset epilepsy who are most at risk for poor developmental outcome and suggest that multimodal interventions should be instituted early in the course of the disorder to improve outcomes.

Why the TimeToStop trial failed to recruit: a survey on antiepileptic drug withdrawal after paediatric epilepsy surgery.

Following the results of the multicentre European retrospective "TimeToStop" cohort study, we initiated a randomised trial to determine cognitive benefits of early postoperative antiepileptic drug withdrawal. Unfortunately, the trial failed to recruit and was terminated, as almost all parents preferred early drug withdrawal. The objectives of the current survey were to obtain insight into current practices regarding drug withdrawal after paediatric epilepsy surgery among epileptologists, and better understand the reasons for difficulties in recruitment. A survey was sent to three international epilepsy surgery networks, questioning drug withdrawal policies. Forty-seven (19%) surveys were returned. For polytherapy, withdrawal was started at a median of three and six months by the TimeToStop collaborators and other paediatric epileptologists, respectively. Withdrawal was completed at a median of 12 and 20 months, respectively. For monotherapy, tapering was initiated at five and 11 months in these two groups, and ended at a median of seven and 12 months, respectively. Most TimeToStop collaborators believed that it was not justified to wait 12 months after surgery before reducing AEDs, regardless of the number of AEDs taken. Current AED policies in Europe have changed as a consequence of the retrospective TimeToStop results, and this accounts for why recruitment in a randomised trial was not feasible.

Knowledge of and attitudes towards epilepsy among teachers: A systematic review.

The objective of this study was to systematically review research that has focused on knowledge of and attitudes towards epilepsy among teachers. Embase, PubMed, PsycINFO, Google Scholar, and Cochrane library databases from 2000 to 2017 were searched. Cross-sectional and interventional studies were included and analyzed for quality. Thematic analysis was used to identify common themes in the results. Fifty-four eligible studies (17,256 total participants in 27 different countries) were identified in the search period including seven studies that focused on assessing attitudes and knowledge before and after an educational intervention. It was not possible to systematically analyze levels of knowledge and nature of attitudes because of the wide variety of mostly bespoke study specific instruments used. Few studies employed valid and reliable instruments. Thematic analysis revealed three main themes in the results: 1.) deficits in knowledge and negative attitudes were pervasive across all studies; 2.) teachers often had a negative attitude towards participation of children with epilepsy in physical activities/sport; and 3.) teachers often expressed limited knowledge of seizure management/emergency procedures. There was a lower level of knowledge and more negative attitudes among teachers towards epilepsy compared with other conditions. All studies focusing on interventions showed that at least some aspects of knowledge and attitudes improved as a result of teacher participation in an educational intervention, but study quality was universally rated as low. A higher level of education and experience of teaching a child with epilepsy was significantly associated with greater knowledge in a number of studies. Additionally, having experience of teaching a child with epilepsy and greater assessed knowledge of epilepsy were associated with more positive attitudes. The wide range of methods used makes it difficult to generalize regarding level of attitudes and knowledge among teachers towards epilepsy. Nevertheless, all studies indicate that there are some deficits in knowledge of and negative attitudes towards epilepsy among teachers. It would appear that knowledge and attitudes can be improved by educational interventions. Future research should focus on developing psychometrically sound assessment instruments that can be used globally and on identifying the most effective ways of delivering efficacious educational initiatives employing robust study designs.

Advocacy for children with epilepsy: Leveraging the WHA resolution. Advocacy Task Force, Commission of Pediatrics, International League Against Epilepsy.

In May 2015 the World Health Assembly (WHA) approved the Resolution on the Global Burden of Epilepsy. This report addresses how the Resolution can be leveraged to improve the care of children with epilepsy worldwide. Children with epilepsy have unique needs and face unique challenges from stigma at all levels of society. Children lack a voice to lobby for their own needs, including their right to have access to education. Effective leadership and governance should be enhanced through the support of stakeholders empowered to counsel, advise, and lobby for appropriate care. National health care plans should integrate primary and specialist care, and they need to be adapted to local specificities. Antiepileptic medicines should be widely accessible in appropriate, sustained, and affordable ways. Public awareness initiatives are needed to improve the inclusion of affected children in society and to reduce stigma. Cost-effective interventions are also needed to address preventable causes of epilepsy. Without greater investment in research, evidence-based interventions cannot be implemented. Through all of this, civil society must be engaged to ensure that the multivariate dimensions from the clinic to the community are addressed to fulfil the needs of children with epilepsy.