Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (>10 min) febrile seizures; febrile or afebrile status epilepticus (>30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children’s hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9–57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26–14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93–12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24–9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07–7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy.

The majority of previous studies investigating the impact of epilepsy on the QOL of adolescents have used proxy opinions from clinicians and/or parents. This study highlights the need for research to investigate QOL from the direct perspective of adolescents and consider issues in the context of a developmental perspective. A focus group technique was used. Twenty-two adolescents aged between 12 years 4 months and 18 years 0 months (6 males and 16 females) were stratified by age (12-13, 14-15 and 16+ years) into six focus groups. Data were transcribed and QSR NUD*IST 4.0 was used to help generate central themes. Several procedures were undertaken to increase validity and reliability of findings. Analysis identified two main themes comprising (a) issues related to adolescent development (identity formation) and (b) epilepsy related variables, with five and four main sub-themes, respectively ('peer acceptance', 'development of autonomy', 'school related issues', 'epilepsy as part of me' and 'future', and 'medication issues', 'seizures', 'knowledge of epilepsy' and 'sense of uncertainty'). The main issues related to peer acceptance and development of autonomy. In contrast to previous studies, academic difficulties were not highlighted as an issue. No significant age-related differences in issues were identified. A conceptual model representing these findings is presented and clinical implications and suggestions for future research are reported.

A telephone survey was carried out to evaluate the effectiveness and convenience of nasal/buccal midazolam in terminating prolonged seizures in the community. A total of 33/40 (83%) families who had used it found it effective and easy to use; 20/24 (83%) preferred using midazolam to rectal diazepam. S tatus epilepticus is a life threatening condition associated with long term morbidity that occurs mainly in childhood and becomes more refractory with duration.

We conducted an exploratory RCT to examine feasibility and preliminary efficacy for a manual-based psychosocial group intervention aimed at improving epilepsy knowledge, self-management skills, and quality of life in young people with epilepsy. Method: Eighty-three participants (33:50 m/f; age range 12-17 years) were randomized to either the treatment or control group in seven tertiary paediatric neuroscience centres in the UK, using a wait-list control design. Participants were excluded if they reported suicidal ideation and/or scored above the cut off on mental health screening measures, or if they had a learning disability or other neurological disorder. The intervention consisted of six weekly 2-hour sessions using guided discussion, group exercises and role-plays facilitated by an epilepsy nurse and a clinical psychologist. Results: At three month follow up the treatment group (n = 40) was compared with a wait-list control group (n = 43) on a range of standardized measures. There was a significant increase in epilepsy knowledge in the treatment group (p = 0.02). Participants receiving the intervention were also significantly more confident in speaking to others about their epilepsy (p = 0.04). Quality of life measures did not show significant change. Participants reported the greatest value of attending the group was: Learning about their epilepsy (46%); Learning to cope with difficult feelings (29%); and Meeting others with epilepsy (22%). Caregiver and facilitator feedback was positive, and 92% of participants would recommend the group to others. Conclusion: This brief psychosocial group intervention was effective in increasing participants' knowledge of epilepsy and improved confidence in discussing their epilepsy with others. We discuss the qualitative feedback, feasibility, strengths and limitations of the PIE trial.

Objective:To report the prevalence of anti-neuronal antibodies in a prospectively whole nation cohort of children presenting with seizures before their third birthday.Methods:This was a prospective population-based national cohort study involving all children presenting with new onset epilepsy or complex febrile seizures before their 3rd birthday over a three-year period. Patients with previously identified structural, metabolic or infectious cause for seizures were excluded. Serum samples were obtained at first presentation and tested for seven neuronal antibodies using live cell-based assays. Clinical data were collected using structured proformas at recruitment, and 24 months after presentation. In addition, patients with seizures and clinically suspected autoimmune encephalitis were independently identified by reviewing the case records of all children < 3 years in Scotland who had undergone electroencephalography (EEG).Results:298 patients were identified, recruited and underwent autoantibody testing. Antibody positivity was identified in 18/298 (6.0%). The antibodies identified were: GABABR (n = 8, 2.7%), CASPR2 (n = 4, 1.3%), GlyR (n = 3, 1.0%), LGI1 (n = 2, 0.7%), NMDAR (n = 1, 0.3%), and GABAAR (n = 1, 0.3%). None of these patients had a clinical picture of autoimmune encephalitis. Seizure classification and clinical phenotype did not correlate with antibody positivity.Conclusions:Autoimmune encephalitis is very rare in early childhood. However serum neuronal antibodies are identified in 6.4% of children presenting with seizures < 3 years. Antibody testing should not be a routine clinical test in early childhood-onset epilepsy as in the absence of other features of autoimmune encephalitis antibody-positivity is of doubtful clinical significance. Antibody testing should be reserved for patients with additional features of encephalitis.