Molecular and clinical descriptions of patients with GABA receptor gene variants (GABRA1, GABRB2, GABRB3, GABRG2): A cohort study, review of literature, and genotype-phenotype correlation.

Objective: γ-Aminobutyric acid (GABA) -receptor subunit variants have recently been associated with neurodevelopmental disorders and/or epilepsy. The phenotype linked with each gene is becoming better known. Because of the common molecular structure and physiological role of these phenotypes, it seemed interesting to describe a putative phenotype associated with GABA -receptor-related disorders as a whole and seek possible genotype-phenotype correlations.

Phenotypic and genetic spectrum of ATP6V1A encephalopathy: a disorder of lysosomal homeostasis.

Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease.

Recommendations for whole genome sequencing in diagnostics for rare diseases.

In 2016, guidelines for diagnostic Next Generation Sequencing (NGS) have been published by EuroGentest in order to assist laboratories in the implementation and accreditation of NGS in a diagnostic setting. These guidelines mainly focused on Whole Exome Sequencing (WES) and targeted (gene panels) sequencing detecting small germline variants (Single Nucleotide Variants (SNVs) and insertions/deletions (indels)). Since then, Whole Genome Sequencing (WGS) has been increasingly introduced in the diagnosis of rare diseases as WGS allows the simultaneous detection of SNVs, Structural Variants (SVs) and other types of variants such as repeat expansions.

International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE Task Force on Nosology and Definitions.

The goal of this paper is to provide updated diagnostic criteria for the epilepsy syndromes that have a variable age of onset, based on expert consensus of the International League Against Epilepsy Nosology and Definitions Taskforce (2017-2021). We use language consistent with current accepted epilepsy and seizure classifications and incorporate knowledge from advances in genetics, electroencephalography, and imaging. Our aim in delineating the epilepsy syndromes that present at a variable age is to aid diagnosis and to guide investigations for etiology and treatments for these patients.

ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions.

The International League Against Epilepsy (ILAE) Task Force on Nosology and Definitions proposes a classification and definition of epilepsy syndromes in the neonate and infant with seizure onset up to 2 years of age. The incidence of epilepsy is high in this age group and epilepsy is frequently associated with significant comorbidities and mortality. The licensing of syndrome specific antiseizure medications following randomized controlled trials and the development of precision, gene-related therapies are two of the drivers defining the electroclinical phenotypes of syndromes with onset in infancy.

Efficacy and Safety of Fenfluramine for the Treatment of Seizures Associated With Lennox-Gastaut Syndrome: A Randomized Clinical Trial.

Importance: New treatment options are needed for patients with Lennox-Gastaut syndrome (LGS), a profoundly impairing, treatment-resistant, developmental and epileptic encephalopathy.

Objective: To evaluate the efficacy and safety of fenfluramine in patients with LGS.

Design, Setting, And Participants: This multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted from November 27, 2017, to October 25, 2019, and had a 20-week trial duration.

Adaptive behavior and psychiatric comorbidities in KCNB1 encephalopathy.

Aim: KCNB1 encephalopathy encompasses a broad phenotypic spectrum associating intellectual disability, behavioral disturbances, and epilepsies of various severity. Using standardized parental questionnaires, we aimed to capture the heterogeneity of the adaptive and behavioral features in a series of patients with KCNB1 pathogenic variants.

Methods: We included 25 patients with a KCNB1 encephalopathy, aged from 3.

Historical Patterns of Diagnosis, Treatments, and Outcome of Epilepsy Associated With Tuberous Sclerosis Complex: Results From TOSCA Registry.

Epilepsy is the most common neurological manifestation in individuals with tuberous sclerosis complex (TSC). However, real-world evidence on diagnosis and treatment patterns is limited. Here, we present data from TuberOus Sclerosis registry to increase disease Awareness (TOSCA) on changes in patterns of epilepsy diagnosis, treatments, and outcomes over time, and detailed epilepsy characteristics from the epilepsy substudy.

Pharmacotherapy for Seizures in Tuberous Sclerosis Complex.

Epilepsy is one of the main symptoms affecting the lives of individuals with tuberous sclerosis complex (TSC), causing a high rate of morbidity. Individuals with TSC can present with various types of seizures, epilepsies, and epilepsy syndromes that can coexist or appear in relation to age. Focal epilepsy is the most frequent epilepsy type with two developmental and epileptic encephalopathies: infantile spasms syndrome and Lennox-Gastaut syndrome.

Inflammation in pediatric epilepsies: Update on clinical features and treatment options.

The role of inflammation is increasingly recognized in triggering or sustaining epileptic activity. In the last decades, increasing research has provided definite evidence to support the link between immunity, inflammatory process, and epilepsy. Neuro- and systemic inflammation play a pivotal role in driving epileptogenesis through different pathogenetic mechanisms: the activation of innate immunity in glia, neurons, and microvasculature, the brain mediated by blood-brain barrier (BBB) impairment, and the imbalance of pro- and anti-inflammatory molecules produced by both arms of immunity.

Early epileptiform EEG activity in infants with tuberous sclerosis complex predicts epilepsy and neurodevelopmental outcomes.

Objective: To study the association between timing and characteristics of the first electroencephalography (EEG) with epileptiform discharges (ED-EEG) and epilepsy and neurodevelopment at 24 months in infants with tuberous sclerosis complex (TSC).

Methods: Patients enrolled in the prospective Epileptogenesis in a genetic model of epilepsy - Tuberous sclerosis complex (EPISTOP) trial, had serial EEG monitoring until the age of 24 months. The timing and characteristics of the first ED-EEG were studied in relation to clinical outcome.

A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies.

Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies.

Proposal to optimize evaluation and treatment of Febrile infection-related epilepsy syndrome (FIRES): A Report from FIRES workshop.

Febrile infection-related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES.

Safety considerations selecting antiseizure medications for the treatment of individuals with Dravet syndrome.

: Management of individuals with Dravet Syndrome has evolved significantly over the past 10 years. Progress has been made in understanding the pathophysiology, the long-term outcome and possible consequences of inappropriate therapies, new drugs have been approved by the regulatory authorities and patients and families expressed their needs beyond seizures' control.: The authors aimed at providing an overview of the main antiseizure medications used in Dravet syndrome with a particular focus on safety considerations.

SYNGAP1-DEE: A visual sensitive epilepsy.

Objective: To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants.

Methods: Participants with pathogenic SYNGAP1 variants and available video-electroencephalogram (EEG) recordings were recruited within five European epilepsy reference centers. We obtained molecular and clinical data, analyzed EEG recordings and archived video-EEGs of seizures and detailed characteristics of interictal and ictal EEG patterns for every patient.

Deep phenotyping unstructured data mining in an extensive pediatric database to unravel a common KCNA2 variant in neurodevelopmental syndromes.

Purpose: Electronic health records are gaining popularity to detect and propose interdisciplinary treatments for patients with similar medical histories, diagnoses, and outcomes. These files are compiled by different nonexperts and expert clinicians. Data mining in these unstructured data is a transposable and sustainable methodology to search for patients presenting a high similitude of clinical features.

Prevention of Epilepsy in Infants with Tuberous Sclerosis Complex in the EPISTOP Trial.

Objective: Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants.

Prediction of Neurodevelopment in Infants With Tuberous Sclerosis Complex Using Early EEG Characteristics.

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder with a high risk of early-onset epilepsy and a high prevalence of neurodevelopmental comorbidities, including intellectual disability and autism spectrum disorder (ASD). Therefore, TSC is an interesting disease model to investigate early biomarkers of neurodevelopmental comorbidities when interventions are favourable. We investigated whether early EEG characteristics can be used to predict neurodevelopment in infants with TSC.

Attachment insecurity in infants with infantile spasms: Maternal anxiety and sadness, and infant's temperament outweigh disease severity.

Objective: The aim of this study was to investigate attachment behavior in a population of infants with infantile spasms (ISs) using the Strange Situation Procedure (SSP) and to explore factors associated with the infants' attachment behavior.

Methods: The SSP was assessed in a population of 29 children with ISs during the second year of life. In mothers, we assessed anxiety, depression, maternal emotions, and perception of the temperament of the child, and sociodemographic characteristics.

Impact of predictive, preventive and precision medicine strategies in epilepsy.

Over the last decade, advances in genetics, neuroimaging and EEG have enabled the aetiology of epilepsy to be identified earlier in the disease course than ever before. At the same time, progress in the study of experimental models of epilepsy has provided a better understanding of the mechanisms underlying the condition and has enabled the identification of therapies that target specific aetiologies. We are now witnessing the impact of these advances in our daily clinical practice.

Add-on cannabidiol significantly decreases seizures in 3 patients with SYNGAP1 developmental and epileptic encephalopathy.

Mutations in are associated with developmental delay, epilepsy, and autism spectrum disorder (ASD). Epilepsy is often drug-resistant in this syndrome with frequent drop attacks. In a prospective study of add-on cannabidiol (CBD), we identified three patients with mutations: two boys and one girl.

Slow Titration of Cannabidiol Add-On in Drug-Resistant Epilepsies Can Improve Safety With Maintained Efficacy in an Open-Label Study.

To assess adverse events (AEs) and efficacy of add-on cannabidiol (CBD) with a slower titration protocol in pediatric clinical practice. We conducted a prospective, open-label, multicenter study in seven French reference centers for rare epilepsies. Patients had slow titration to reach a target dose of 10 mg/kg/day within at least 1 month and then gradually increased to a maximum dose of 20 mg/kg/day.

An accelerated shift in the use of remote systems in epilepsy due to the COVID-19 pandemic.

Purpose: The purpose of the study was to describe epileptologists' opinion on the increased use of remote systems implemented during the COVID-19 pandemic across clinics, education, and scientific meetings activities.

Methods: Between April and May 2020, we conducted a cross-sectional, electronic survey on remote systems use before and during the COVID-19 pandemic through the European reference center for rare and complex epilepsies (EpiCARE) network, the International and the French Leagues Against Epilepsy, and the International and the French Child Neurology Associations. After descriptive statistical analysis, we compared the results of France, China, and Italy.