Objectives: People with neurodevelopmental disorders frequently experience sleep disturbances, negatively impairing their quality of life. We aimed to determine the prevalence and nature of sleep disturbances in patients with SCN8A‐related disorders.Methods: Through a collaborative network of caregivers and clinicians, we collected data about epilepsy, cognitive/motor abilities, medications, and relevant comorbidities of patients harboring a pathogenic SCN8A variant. The Sleep Disturbance Scale for Children (SDSC), the Children's Sleep Habits Questionnaire (CSHQ‐22‐items), and the Pediatric Daytime Sleepiness Scale (PDSS) were distributed and evaluated by factor scores and Composite Sleep Index. Video‐EEG‐polysomnographic recordings were performed.Results: We enrolled 47 patients (age range: 2–39 years), whose phenotypes ranged from SCN8A‐DEE to intellectual disability without epilepsy. In the majority of them (82%), sleep disturbances were reported and/or observed at the SDSC. The most frequent were difficulty in initiating and maintaining sleep (64%), followed by sleep breathing disorder (43%), sleep–wake transition disorder (34%), and daytime sleepiness (34%). Sleep disturbances were more frequent in patients with severe DEE (96%) and ongoing seizures (93%) and were more severe in patients with sleep‐related seizures. The CSHQ and PDSS confirmed difficulty in initiating and maintaining sleep. Polysomnographic recordings (9 patients/20 nights) showed an altered sleep structure in 95%, with frequent arousals, mainly not seizure related.Significance: More than 80% of patients with SCN8A‐related disorders presented with sleep disturbances, primarily consisting of sleep instability with difficulty of initiating and maintaining sleep. Animal studies showed sleep disturbances in SCN8A‐ and SCN1A‐Dravet Syndrome mice models, suggesting a role for voltage‐gated sodium channels in the regulation of sleep. Understanding the effects of SCN8A dysfunction on sleep stability may guide future therapeutic efforts to alleviate this often distressing symptom also in seizure‐free SCN8A patients.Plain Language Summary: In this study, we analyzed sleep disturbances in patients with disorders related to a genetic mutation in the gene SCN8A. We found that the majority of the patients experienced sleep disturbances, mainly consisting in difficulty of initiating and maintaining sleep. Sleep disturbances were more frequent in patients with severe cognitive impairment and active epilepsy and more severe in patients with seizures during sleep.

Objective: EEG patterns and quantitative EEG (qEEG) features have been poorly explored in monogenic epilepsies. Herein, we investigate regional differences in EEG frequency composition in patients with STXBP1 developmental and epileptic encephalopathy (STXBP1‐DEE).Methods: We conducted a retrospective study collecting electroclinical data of patients with STXBP1‐DEE and two control groups of patients with DEEs of different etiologies and typically developing individuals matched for age and sex. We performed a (1) visual EEG assessment, (b) qEEG analysis, and (c) electrical source imaging (ESI). We quantified the relative power (RP) of four frequency bands (α β, θ, δ), in two electrode groups (anterior/posterior), and compared their averages and dynamics (standard deviation [SD] over time). The ESI was performed by applying the standard Distributed Source Modeling algorithm.Results: We analyzed 42 EEG studies in 19 patients with STXBP1‐DEE (10 female), with a median age at recordings of 9.6 years (range 9 months to 29 years). The δRP was higher in recordings of STXBP1‐DEE (p < .001) compared to both control groups, suggesting the pathogenicity and STXBP1‐specificity of these findings. In STXBP1‐DEE, the δRP was significantly higher in the anterior electrode group compared to the posterior one (p = .003). There was no correlation between the anterior δRP and the epilepsy focus, age at recordings, and concomitant medications The ESI modeling of this activity showed a widespread involvement of the dorsomesial frontal cortex, suggesting a large corticosubcortical pathologic network. Finally, we identified two groups of recordings: cluster.1 with higher anterior δRP and low dynamics and cluster.2 with lower δRP and higher dynamics. Patients in cluster.1 had a more severe epilepsy and neurological phenotype compared to patients in cluster 2.Significance: The qEEG analysis showed a predominant frontal slow activity as a specific STXBP1 feature that correlates with the severity of the phenotype and may represent a biomarker for prospective longitudinal studies of STXBP1‐DEE.

Variants of KCNQ2 are associated with a wide spectrum of disorders, ranging from Self-limiting Neonatal Epilepsy (SelNE) to Early Onset Developmental and Epileptic Encephalopathy (KCNQ2-DEE). Comorbidities associated with this end of the spectrum have been seldomly described and their impact on the life of patients and their families is yet to be investigated. Collaborating with caregivers from different European family associations, we have developed a questionnaire aimed at investigating the onset and frequency of epileptic seizures, anti-seizure medications (ASM), hospitalizations, stages of development, and comorbidities. Responses from 80 patients, 40 males, from 14 countries have been collected. Median age 7.6 years (4 months - 43.6 years). Of 76 epileptic patients (93.6%), 55.3% were seizure-free with a mean age at last seizure of 26.7 months. Among patients with active epilepsy, those older have a lower frequency of seizures (p > 0.05). We were able to identify three different clusters of varying severity (Mild, Severe, Profound), based on neurodevelopmental features and symptoms, excluding epilepsy. Patients in a higher severity cluster had a higher mean number of comorbidities, which had a higher impact on families. Notably, patients in different clusters presented different epilepsy onset and courses. This study constitutes the most extensive data collection of patients with KCNQ2-DEE, with a focus on comorbidities in a wide age group. The participation of caregivers helps to define the impact of the disease on the lives of patients and families and can help identify new primary and secondary outcomes beyond seizures in future studies.

Intrapartum-related neonatal encephalopathy (NE) is a leading cause of childhood mortality and morbidity. Continuous electroencephalography (EEG) is gold standard for neonatal brain monitoring; however, low-income country data is lacking. We examined EEG in a Ugandan cohort with NE to describe feasibility, background activity, seizure prevalence and burden, and associations with clinical presentation and outcome. Neonates with NE were recruited from a single hospital referral centre in Kampala, Uganda (Oct 2019–Oct 2020) and underwent EEG monitoring. Feasibility was assessed as to whether EEG monitoring of diagnostic quality could be achieved from days 1–5. Evolution of clinical presentation was assessed by Sarnat classification and daily Thompson score was performed. EEG background severity was graded at 12, 24, 48 and 72 h after birth, and at time of Thompson score. Seizures were annotated remotely by experts and assessed for frequency, duration, burden, and status epilepticus. Early childhood outcome was assessed at follow up, and adverse outcome defined as death or neurodevelopmental impairment (NDI) at 18–24 months of age. In this prospective feasibility cohort study, diagnostic quality EEGs were recorded for 50 of 51 recruited neonates (median duration 71.4 h, IQR 52.4–72.2), indicating feasibility. Of 39 participants followed to 18–24 months, 13 died and 7 had NDI. Daily Thompson score and EEG background grade were strongly correlated across all timepoints (days 1–5). Thompson score of ≥7 was most predictive of moderate-severe EEG background abnormality (AUC 0.83). Prognostic accuracy of moderate-severe EEG background grade to predict NDI was high (AUC 0.74). Electrographic seizures were seen in 52% (26); median seizure burden was high at 264 min (IQR 27.8–523.7, range 1.3–1374.1); half (13) had status epilepticus. EEG monitoring was feasible as a research tool in this sub-Saharan Africa setting. EEG background activity correlated strongly with scored neurological assessment and predicted adverse early childhood outcome. Seizure prevalence and burden, including status epilepticus, were high in this uncooled cohort with important potential longer-term implications for survivors. 10.13039/100000865 Bill & Melinda Gates Foundation grant number OPP1210890; 10.13039/100010269 Wellcome Trust Innovator award (209325/Z/17/Z).