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Drug-resistant epilepsy (DRE) occurs in 20%-30% of children with epilepsy with significant impact on their quality of life. Management of this group of children has greatly improved in the recent years with streamlining of epilepsy surgery services and associated quaternary multimodal evaluation. This article provides a review of DRE in children and management based on recent evidence and published opinion. We have also presented an algorithmic approach to the child with possible DRE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Epileptic seizures complicate the management of childhood brain tumours. There are no published standards for clinical practice concerning risk factors, treatment selection or strategies to withdraw treatment with antiepileptic drugs (AED)., Method: we undertook a case note review of 120 patients with newly diagnosed brain tumours, referred to a regional paediatric cancer service., Results: data was available on 117/120 (98%) children <18 years: median age at tumour presentation was 8.1 years (IQR 25°-75° : 3.6-12.7), median follow up was 33 months (IQR 25°-75°: 24-56), and 35/117 (29%) experienced seizures. A cortical tumour location was associated with the highest risk of seizures (OR: 7.1; CI 95% 2.9-17.3). At a median follow up of 24 months (IQR 25°-75° : 15-48), 22/35 (63%) with seizures, had a single seizure episode, 15/35 (43%) were seizure free (SF) on AEDs, 13/35 (37%) were SF off AEDs, and 7/35 (20%) experienced continuing epileptic seizures. Overall 34/35 (97%) were treated with AEDs after a seizure, of whom 12/35 (35%) withdrew from AED medication, and although 4/35 (12%) had seizure relapse, all were after further acute events. The median duration of AED before withdrawal was 11 months (IQR 25°-75° 5-14 months), and the median follow up after withdrawal was 15 months (IQR 25°-75° 5-34 months)., Conclusions: Seizures affect about 1/3rd of children and young people presenting with and being treated for brain tumours particularly when the tumour is in the cerebral cortex. The low risk of recurrent seizures after AED treatment justifies consideration of early withdrawal of AED after seizure control., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study aims to describe the incidence of adverse drug reactions (ADRs) in children receiving antiepileptic drugs (AEDs) and compare ADRs to the individual drugs when given as monotherapy., Method: Paediatric patients (≤18 years old) were enrolled for this prospective observational study over a 6-month period, between September 2015 and March 2016. Adverse reactions to antiepileptic drugs (AEDs) were elicited at the time of enrolment and after 3 months using the Paediatric Epilepsy Side Effects Questionnaire., Results: A total of 1139 suspected ADRs were reported in 124 participants. Eighteen different AEDs were prescribed. Sixty-six children (53%) were receiving AED monotherapy at the time of recruitment; 34/66 (52%) of whom received new generation AEDs. Levetiracetam was the most frequently prescribed AED (62/124, 50%). When only children receiving AED monotherapy were considered, fatigue, drowsiness, weight gain, dizziness were less likely with levetiracetam (p < .01). Slow thinking and decreased concentration were less likely with levetiracetam or carbamazepine than valproic acid (p < .05). Five patients (four on polytherapy) discontinued AED treatment due to ADRs and 2 had a dose reduction., Conclusions: Levetiracetam and carbamazepine were better tolerated than sodium valproate., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug-resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation., Method: Female cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained., Results: Ten cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases., Significance: Truncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

There has been considerable evolution in epilepsy healthcare for children over the last decade in the United Kingdom. There has been no single explanation for this. The development of national clinical guidelines, locally delivered but nationally designed educational programmes, nation-wide clinical audit, clinical networks and development of designated services have all had complimentary roles in enabling the implementation of national recommendations for the development of epilepsy care. These models may be applicable to other healthcare settings outside the UK., (Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: In response to continuing concerns regarding the quality and equality of care for children and young people, the British Paediatric Neurology Association (BPNA) has supported the development of practical and meaningful audit to support quality improvement., Method: In 2006, the Children's Epilepsy Workstream in Trent (CEWT) coordinated a retrospective multi-service audit of paediatric epilepsy care against NICE and SIGN guidelines. This aimed to both facilitate quality improvements for participating services and act as a pilot for future potential national audits., Results: The audit was achieved in 4 hospital services using prospective and retrospective ascertainment methods. 12 performance indicators were applied to each cohort. Overall 54% (12/22) of children with epilepsy had input from a paediatrician with "expertise" and 23% (5/22) had input from an epilepsy specialist nurse., Conclusion: Audit can be developed for epilepsies that delivers standardised quality metrics against national recommendations. As well as supporting local quality improvement initiatives, comparative and aggregate data can be produced to potentially give regional and national perspectives. The results and experience describe the journey towards the 2009-2012 Epilepsy 12 UK multicentre epilepsy audit., (Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess the quality of clinical care at first clinic attendance in children with suspected epilepsy from a defined geographical population., Method: All hospital- and community-based consultant paediatricians in Nottingham City region, UK, were asked to collaborate with a retrospective clinical audit identifying children seen between January 2001 and March 2002. The British Paediatric Neurology Association (BPNA) audit tool (Appleton R, Besag F, Kennedy C, et al. An audit of children referred with suspected epilepsy. Seizure 1998;7(6):489-95) was used to analyse the initial outpatient assessment., Results: All consultants agreed to participate. A total of 147 children were identified as meeting the inclusion criteria. The sequence of events during the episodes was well recorded (91%). Other aspects of the history were less well recorded. Twelve percent were given a diagnosis of epilepsy, 26% non-epileptic and 62% uncertain. Documentation of early development and school performance was low (41%). Twenty-four percent of the children had no written documentation confirming physical and neurological examination. Documentation describing referral to an epilepsy nurse or support group was seen in 11%. Drug treatment and doses and follow-up plans were recorded in nearly all cases where applicable., Discussion: A managed clinical network for children with epilepsy in Nottingham and the surrounding Trent region is currently being discussed which will consider alternative models of care for children with epilepsy. A revision of the BPNA audit tool has been produced with the BPNA Audit group and is available for other centres via the BPNA website's 'clinical toolbox' (http://www.bpna.org.uk/audit).

Background: Multiple sclerosis (MS), epilepsy, and depression are chronic central nervous system conditions in which remote measurement technology (RMT) may offer benefits compared with usual assessment. We previously worked with clinicians, patients, and researchers to develop 13 use cases for RMT: 5 in epilepsy (seizure alert, seizure counting, risk scoring, triage support, and trend analysis), 3 in MS (detecting silent progression, detecting depression in MS, and donating data to a biobank), and 5 in depression (detecting trends, reviewing treatment, self-management, comorbid monitoring, and carer alert). Objective: In this study, we aimed to evaluate the use cases and related implementation issues with an expert panel of clinicians external to our project consortium. Methods: We used a Delphi exercise to validate the use cases and suggest a prioritization among them and to ascertain the importance of a variety of implementation issues related to RMT. The expert panel included clinicians from across Europe who were external to the project consortium. The study had 2 survey rounds (n=23 and n=17) and a follow-up interview round (n=9). Data were analyzed for consensus between participants and for stability between survey rounds. The interviews explored the reasons for answers given in the survey. Results: The findings showed high stability between rounds on questions related to specific use cases but lower stability on questions relating to wider issues around the implementation of RMT. Overall, questions on wider issues also had less consensus. All 5 use cases for epilepsy (seizure alert, seizure counting, risk scoring, triage support, and trend analysis) were considered beneficial, with consensus among participants above the a priori threshold for most questions, although use case 3 (risk scoring) was considered less likely to facilitate or catalyze care. There was very little consensus on the benefits of the use cases in MS, although this may have resulted from a higher dropout rate of MS clinicians (50%). Participants agreed that there would be benefits for all 5 of the depression use cases, although fewer questions on use case 4 (triage support) reached consensus agreement than for depression use cases 1 (detecting trends), 2 (reviewing treatment), 3 (self-management), and 5 (carer alert). The qualitative analysis revealed further insights into each use case and generated 8 themes on practical issues related to implementation. Conclusions: Overall, these findings inform the prioritization of use cases for RMT that could be developed in future work, which may include clinical trials, cost-effectiveness studies, and the commercial development of RMT products and services. Priorities for further development include the use of RMT to provide more accurate records of symptoms and treatment response than is currently possible and to provide data that could help inform patient triage and generate timely alerts for patients and carers. [ABSTRACT FROM AUTHOR]

Background: Rectal diazepam and buccal midazolam are used for emergency treatment of acute febrile and afebrile (epileptic) seizures in children. We aimed to compare the safety and efficacy of these drugs. Methods: A multicentre, randomised controlled trial was undertaken to compare buccal midazolam with rectal diazepam for emergency-room treatment of children aged 6 months and older presenting to hospital with active seizures and without intravenous access. The dose varied according to age from 2 to 10 mg. The primary endpoint was therapeutic success: cessation of seizures within 10 min and for at least 1 hour, without respiratory depression requiring intervention. Analysis was per protocol. Findings: Consent was obtained for 219 separate episodes involving 177 patients, who had a median age of 3 years (IQR 1-5) at initial episode. Therapeutic success was 56% (61 of 109) for buccal midazolam and 27% (30 of 110) for rectal diazepam (percentage difference 29%, 95% CI 16-41). Analysing only initial episodes revealed a similar result. The rate of respiratory depression did not differ between groups. When centre, age, known diagnosis of epilepsy, use of antiepileptic drugs, prior treatment, and length of seizure before treatment were adjusted for with logistic regression, buccal midazolam was more effective than rectal diazepam. Interpretation Buccal midazolam was more effective than rectal diazepam for children presenting to hospital with acute seizures and was not associated with an increased incidence of respiratory depression. [ABSTRACT FROM AUTHOR]

A previous study of 34 nuclear pedigrees segregating juvenile myoclonic epilepsy (JME) gave significant evidence of linkage with heterogeneity to marker loci on chromosome 15q13–14 close to the candidate gene CHRNA7 (Hum. Mol. Genet. 6 (1997) 1329). The aim of this work was to further evaluate the putative aetiological role of CHRNA7 in JME within the 34 families originally described, and to assess the contribution of this locus to a broader phenotype of idiopathic generalised epilepsy (IGE). Multipoint linkage analysis and intrafamilial association studies were performed with microsatellite markers that encompass both CHRNA7 and its partial duplication (CHRFAM7A). A maximum HLOD of 3.45 [α=0.58; (Zall=2.88, P=0.0008)] was observed 8 cM distal to D15S1360, a CHRNA7 intragenic marker. Significant exclusion lod scores were obtained across the region in 12 mixed phenotype JME/IGE families. Mutation screening of the CHRNA7 gene (and consequently exons 5–10 of CHRFAM7A) and its putative promoter sequence identified a total of 13 sequence variants across 23 of 34 JME-affected families. Two variants (c.1354G>A and c.1466C>T) are predicted to result in amino acid changes and one (IVS9+5G>A) is predicted to result in aberrant transcript splicing. However, none of the variants alone appeared either necessary or sufficient to cause JME in the families in which they occurred. In conclusion, linkage analyses continue to support the existence of a locus on chromosome 15q13–14 that confers susceptibility to JME but not to a broader IGE phenotype. Causal sequence variants in the positional candidate CHRNA7 have not been identified but the presence of multiple segmental duplications in this region raises the possibility of undetected disease-causing genomic rearrangements. [Copyright &y& Elsevier]