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Behavioural sleep problems are common in children with autism spectrum disorder (ASD); however, evidence for the efficacy of behavioural sleep interventions is limited. This study examined the efficacy of a brief behavioural sleep intervention in autistic children. It was hypothesised that the intervention would reduce overall child sleep problems (primary outcome), in addition to improvements in children's social, emotional, cognitive, academic functioning, and quality of life, and parent/caregivers' stress, quality of life, and mental health (secondary outcomes).A randomised controlled trial was conducted with participants randomised via a computer-generated sequence to the sleeping sound intervention (n = 123) or treatment as usual (n = 122) group. Participants comprised 245 children with an ASD diagnosis. Inclusion criteria were as follows: confirmation of DSM IV or DSM-5 diagnosis of ASD, participants aged between 5 and 13 years and parent/caregiver report of moderate-severe sleep problems. Exclusion criteria were as follows: parent/caregiver intellectual disability or lacking sufficient English to complete questionnaires; and child participant with co-occurring medical conditions known to impact sleep. The intervention group received the sleeping sound intervention (2 × 50-min face-to-face sessions plus follow-up phone call) by a trained clinician.Change in children's sleep problems was measured by the Children's Sleep Habits Questionnaire (CSHQ) at 3 months post randomisation. Parents/caregivers of children in the intervention group reported a reduction in child sleep problems at 3 months post randomisation (effect size: E.S -0.7). There were also small effects in a number of child (internalising symptoms, emotional behavioural disturbance and quality of life) and parent/caregiver (mental health, parenting stress and quality of life) outcomes; however, these did not remain significant when controlling for multiple comparisons.The sleeping sound ASD intervention is an efficacious and practical way to reduce sleep problems for autistic children. This brief behavioural intervention has the potential to be embedded easily into the Australian healthcare system.

OBJECTIVE: Classification of epilepsy into types and subtypes is important for both clinical care and research into underlying disease mechanisms. A quantitative, data-driven approach may augment traditional electroclinical classification and shed new light on existing classification frameworks. METHODS: We used latent class analysis, a statistical method that assigns subjects into groups called latent classes based on phenotypic elements, to classify individuals with common familial epilepsies from the Epi4K Multiplex Families study. Phenotypic elements included seizure types, seizure symptoms, and other elements of the medical history. We compared class assignments to traditional electroclinical classifications and assessed familial aggregation of latent classes. RESULTS: A total of 1120 subjects with epilepsy were assigned to five latent classes. Classes 1 and 2 contained subjects with generalized epilepsy, largely reflecting the distinction between absence epilepsies and younger onset (class 1) versus myoclonic epilepsies and older onset (class 2). Classes 3 and 4 contained subjects with focal epilepsies, and in contrast to classes 1 and 2, these did not adhere as closely to clinically defined focal epilepsy subtypes. Class 5 contained nearly all subjects with febrile seizures plus or unknown epilepsy type, as well as a few subjects with generalized epilepsy and a few with focal epilepsy. Family concordance of latent classes was similar to or greater than concordance of clinically defined epilepsy types. SIGNIFICANCE: Quantitative classification of epilepsy has the potential to augment traditional electroclinical classification by (1) combining some syndromes into a single class, (2) splitting some syndromes into different classes, (3) helping to classify subjects who could not be classified clinically, and (4) defining the boundaries of clinically defined classifications. This approach can guide future research, including molecular genetic studies, by identifying homogeneous sets of individuals that may share underlying disease mechanisms.

Objective: The cause of mesial temporal lobe epilepsy (MTLE) is often unknown. We ascertained to what extent newly-diagnosed non-lesional MTLE actually represents familial MTLE (FMTLE). Methods: We identified all consecutive patients presenting to the Austin Heath First Seizure Clinic with MTLE and a normal MRI or MRI-evidence of hippocampal sclerosis over a 10-year period. Patients' first-degree relatives and pairwise age- and sex-matched controls underwent a comprehensive epilepsy interview. Each interview transcript was reviewed independently by two epileptologists, blinded to relative or control status. Reviewers classified each subject as follows: epilepsy, specifying if MTLE; manifestations suspicious of epilepsy; or unaffected. Physiological deja vu was noted. Results: Forty-four patients were included. At the Clinic, MTLE had been recognized to be familial in 2 patients only. Among 242 subjects interviewed, MTLE was diagnosed in 9/121 relatives vs 0/121 controls (p=0.008). All affected relatives had seizures with intense deja vu and accompanying features; 6 relatives had not been previously diagnosed. Deja vu experiences which were suspicious, but not diagnostic, of MTLE occurred in 6 additional relatives vs none of the controls (p=0.04). Physiological deja vu was common, and did not differ significantly between relatives and controls. After completing the relatives' interviews, FMTLE was diagnosed in 8 of 44 patients (18.2%). Interpretation: FMTLE accounts for almost one-fifth of newly diagnosed non-lesional MTLE, and it is largely unrecognized without direct questioning of relatives. Relatives of patients with MTLE may experience deja vu phenomena which clinically lie in the ‘borderland' between epileptic seizures and physiological deja vu. This article is protected by copyright. All rights reserved.

OBJECTIVE: We tested 2 hypotheses regarding age at onset within familial epilepsies: (1) family members with epilepsy tend to have similar ages at onset, independent of epilepsy syndrome; and (2) age at onset is younger in successive generations after controlling for sampling bias. METHODS: We analyzed clinical data collected by the Epi4K Consortium (303 multiplex families, 1,120 individuals). To test hypothesis 1, we used both linear mixed models commonly used for heritability analysis and Cox regression models with frailty terms to assess clustering of onset within families after controlling for other predictors. To test hypothesis 2, we used mixed effects models, pairwise analyses, and survival analysis to address sampling-related bias that may mimic anticipation. RESULTS: Regarding hypothesis 1, age at seizure onset was significantly heritable (intraclass correlation coefficient = 0.17, p < 0.001) after adjusting for epilepsy type, sex, site, history of febrile seizure, and age at last observation. This finding remained significant after adjusting for epilepsy syndromes, and was robust across statistical methods in all families and in generalized families. Regarding hypothesis 2, the mean age at onset decreased in successive generations (p < 0.001). After adjusting for age at last observation, this effect was not significant in mixed effects models (p = 0.14), but remained significant in pairwise (p = 0.0003) and survival analyses (p = 0.02). INTERPRETATION: Age at seizure onset is an independent familial trait, and may have genetic determinants distinct from the determinants of particular epilepsy syndromes. Younger onsets in successive generations can be explained in part by sampling bias, but the presence of genetic anticipation cannot be excluded. ANN NEUROL 2019.

Juvenile myoclonic epilepsy (JME) is a common syndrome of genetic generalized epilepsies (GGEs). Linkage and association studies suggest that the gene encoding the bromodomain-containing protein 2 (BRD2) may increase risk of JME. The present methylation and association study followed up a recent report highlighting that the BRD2 promoter CpG island (CpG76) is differentially hypermethylated in lymphoblastoid cells from Caucasian patients with JME compared to patients with other GGE subtypes and unaffected relatives. In contrast, we found a uniform low average percentage of methylation (

Aim To show that atypical multifocal Dravet syndrome is a recognizable, electroclinical syndrome associated with sodium channel gene (SCN1A) mutations that readily escapes diagnosis owing to later cognitive decline and tonic seizures. Method Eight patients underwent electroclinical characterization. SCN1A was sequenced and copy number variations sought by multiplex ligation-dependent probe amplification. Results All patients were female (age range at assessment 5–26y) with median seizure onset at 6.5 months (range 4–19mo). The initial seizure was brief in seven and status epilepticus only occurred in one; three were febrile. Focal seizures occurred in four patients and bilateral convulsion in the other four. All patients developed multiple focal seizure types and bilateral convulsions, with seizure clusters in six. The most common focal seizure semiology (six out of eight) comprised unilateral clonic activity. Five also had focal or asymmetric tonic seizures. Rare or transient myoclonic seizures occurred in six individuals, often triggered by specific antiepileptic drugs. Developmental slowing occurred in all: six between 3 years and 8 years, and two around 1 year 6 months. Cognitive outcome varied from severe to mild intellectual disability. Multifocal epileptiform discharges were seen on electroencephalography. Seven out of eight patients had SCN1A mutations. Interpretation Atypical, multifocal Dravet syndrome with SCN1A mutations may not be recognized because of later cognitive decline and frequent tonic seizures.