dravet

OBJECTIVE: SCN1A variants are associated with epilepsy syndromes ranging from mild genetic epilepsy with febrile seizures plus (GEFS+) to severe Dravet syndrome (DS). Many variants are de novo, making early phenotype prediction difficult, and genotype-phenotype associations remain poorly understood. METHODS: We assessed data from a retrospective cohort of 1018 individuals with SCN1A-related epilepsies. We explored relationships between variant characteristics (position, in silico prediction scores: Combined Annotation Dependent Depletion (CADD), Rare Exome Variant Ensemble Learner (REVEL), SCN1A genetic score), seizure characteristics, and epilepsy phenotype...

The emergence of gene editing technologies offers a unique opportunity to develop mutation-specific treatments for pediatric neurological disorders. Gene editing systems can potentially alter disease trajectory by correcting dysfunctional mutations or therapeutically altering gene expression. Clustered regularly interspaced short palindromic repeats (CRISPR)-based approaches are attractive gene therapy platforms to personalize treatments because of their specificity, ease of design, versatility, and cost. However, many such approaches remain in the early stages of development, with ongoing efforts to optimize editing efficiency, minimize unintended off-target effects, and mitigate pathologic immune responses...

The purpose of this study was to demonstrate the performance of a fully automated, deep learning-based brain segmentation (DLS) method in healthy controls and in patients with neurodevelopmental disorders, SCN1A mutation, under eleven. The whole, cortical, and subcortical volumes of previously enrolled 21 participants, under 11 years of age, with a SCN1A mutation, and 42 healthy controls, were obtained using a DLS method, and compared to volumes measured by Freesurfer with manual correction. Additionally, the volumes which were calculated with the DLS method between the patients and the control group...

BACKGROUND: Novel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE. METHODS: A case of an adult patient with Lennox-Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search...

BAER-101 (formerly AZD7325) is a selective partial potentiator of α2/3-containing γ-amino-butyric acid A receptors (GABAARs) and produces minimal sedation and dizziness. Antiseizure effects in models of Dravet and Fragile X Syndromes have been published. BAER-101 has been administered to over 700 healthy human volunteers and patients where it was found to be safe and well tolerated. To test the extent of the antiseizure activity of BAER-1010, we tested BAER-101 in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model, a widely used and translationally relevant model...

Dravet Syndrome (DS) is a severe developmental epileptic encephalopathy with frequent intractable seizures accompanied by cognitive impairment, often caused by pathogenic variants in SCN1A encoding sodium channel NaV 1.1. Recent research utilizing in vitro patient-derived neuronal networks and accompanying in silico models uncovered that not just sodium-but also potassium-and synaptic currents were impaired in DS networks. Here, we explore the implications of these findings for three questions that remain elusive in DS: How do sodium channel impairments result in epilepsy? How can identical variants lead to varying phenotypes? What mechanisms underlie the developmental delay in DS patients? We speculate that impaired potassium currents might be a secondary effect to NaV 1...

BACKGROUND: Numerous anti-seizure medications (ASMs) have been developed to treat Dravet syndrome (DS). This network meta-analysis aimed to comprehensively analyse the efficacy of ASMs in DS patients, especially in non-seizure-free patients after treatment. METHODS: PubMed, EMBASE, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched. The treatment efficacy was assessed by the percentage reduction in monthly convulsive seizure frequency (MCSF) from baseline or individuals who achieved at least a 50 % or 75 % reduction from baseline in convulsive seizure frequency (CSF)...

Cannabidiol (CBD 1 ) is a nonpsychotic cannabinoid-based drug approved by the U.S. FDA for treating refractory epilepsy, namely, Lennox-Gastaut and Dravet syndrome. However, its low aqueous solubility and oral bioavailability are compensated by administering high doses, and there is an increased demand for conjugates with improved properties. In this direction, the present work is focused on synthesizing CBD-based prodrugs to address the issue of poor solubility and oral bioavailability. Several CBD-based prodrugs were synthesized and studied in a battery of assays: viz, release kinetic ( ex vivo ), solubility ( in vitro ), chemical stability ( in vitro ), plasma stability ( ex vivo ), pharmacokinetics ( in vivo ), and efficacy studies ( in vivo )...

Vagus nerve stimulation (VNS) is a palliative treatment for drug-resistant epilepsy (DRE) that has been in use for over two decades. VNS suppresses epileptic seizures, prevents emotional disorders, and improves cognitive function and sleep quality, a parallel effect associated with the control of epileptic seizures. The seizure suppression rate with VNS increases monthly to annually, and the incidence of side effects reduces over time. This method is effective in treating DRE in children as well as adults, such as epilepsy associated with tuberous sclerosis, Dravet syndrome, and Lennox-Gastaut syndrome...

No abstract text is available yet for this article.

OBJECTIVE: Evaluate the long-term efficacy of vagus nerve stimulation (VNS) in patients with developmental and epileptic encephalopathies (DEE) compared with epilepsy patients without intellectual disability (ID). METHODS: Long-term outcomes from a Norwegian VNS quality registry are reported in 105 patients with DEEs (Lennox-Gastaut syndrome [LGS] n = 62; Dravet n = 16; Rett n = 9; other syndromes n = 18) were compared with 212 epilepsy patients without ID, with median follow-up of 88 and 72 months, respectively...

Cannabidiol (CBD) is a pharmacologically active metabolite of cannabis that is FDA-approved to treat seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex in children aged one year and older. During clinical trials, CBD caused dose-dependent hepatocellular toxicity at therapeutic doses. The risk for toxicity was increased in patients taking valproate (VPA), another hepatotoxic antiepileptic drug, through an unknown mechanism. With the growing popularity of CBD in the consumer market, an improved understanding of the safety risks associated with CBD is needed to ensure public health...

OBJECTIVE: Heterozygous mutations within the voltage-gated sodium channel α subunit ( SCN1A ) are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of SCN1A are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches...

Dravet syndrome is a severe form of epilepsy characterised by recurrent seizures and cognitive impairment. It is mainly caused by variant in the SCN1A gene in 90% of cases, which codes for the α subunit of the voltage-gated sodium channel. In this study, we present one suspected case of Dravet syndrome in Moroccan child that underwent exome analysis and were confirmed by Sanger sequencing. The variant was identified in the SCN1A gene, and is a new variant that has never been described in the literature...

OBJECTIVE: This study aimed to evaluate the efficacy and safety of six new antiseizure medications (ASMs) for adjunctive treatment in adult patients with focal epilepsy and adolescents with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), or tuberous sclerosis complex (TSC). METHODS: A comprehensive literature search was performed using PubMed, Medline, Embase, and Cochrane library databases from inception to October 13, 2023. We included published studies for a systematic review and a network meta-analysis (NMA)...

Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare developmental and epileptic encephalopathies associated with seizure and nonseizure symptoms. A comprehensive understanding of how many individuals are affected globally, the diagnostic journey they face, and the extent of mortality associated with these conditions is lacking. Here, we summarize and evaluate published data on the epidemiology of DS and LGS in terms of prevalence, incidence, diagnosis, genetic mutations, and mortality and sudden unexpected death in epilepsy (SUDEP) rates...

OBJECTIVE: We aimed to compare the electroclinical correlates of truncating and missense variants of SCN1A variants in children with Dravet syndrome (DS) and to determine phenotypic features in relation to variants identified and seizure outcomes. METHODS: A single center prospective study was carried out on a South Indian cohort. Patients below 18 years of age who met the clinical criteria for DS who had undergone genetic testing and completed a minimum of one year follow up were included...

Dravet syndrome is a severe infantile onset developmental and epileptic encephalopathy associated with mutations in the sodium channel alpha 1 subunit gene SCN1A . Prospective data on long-term developmental and clinical outcomes are limited; this study seeks to evaluate the clinical course of Dravet syndrome over a 10-year period and identify predictors of developmental outcome. SCN1A mutation-positive Dravet syndrome patients were prospectively followed up in the UK from 2010 to 2020. Caregivers completed structured questionnaires on clinical features and disease burden; the Epilepsy & Learning Disability Quality of Life Questionnaire, the Adaptive Behavioural Assessment System-3 and the Sleep Disturbance Scale for Children...

No abstract text is available yet for this article.

RATIONALE: Epilepsy is a complex condition and seizures are only one part of this disease. The move from pediatric to adult healthcare system proves difficult for many adolescents with epilepsy and their families. The challenges increase when patients have epilepsies associated with intellectual and/or developmental disabilities, autism spectrum disorder, and motor disorders. Knowledge and system gaps may exist between the two systems, adding to the challenges. The main goal of this study is to understand the perception of patients with epilepsy and their families who were preparing to move from pediatric to adult healthcare system or had already moved...