Generation of eight hiPSCs lines from two pathogenic variants in CACNA1A using the CRISPR-Cas9 gene editing technology.

Developmental and epileptic encephalopathies (DEEs) are rare severe neurodevelopmental disorders with a cumulative incidence of 1:6.000 live births. Many epileptic conditions arise from single nucleotide variants in CACNA1A (calcium voltage-gated channel subunit alpha1 A), encoding the CaV2.

GABA receptors in epilepsy: Elucidating phenotypic divergence through functional analysis of genetic variants.

Normal brain function requires a tightly regulated balance between excitatory and inhibitory neurotransmissions. γ-Aminobutyric acid type A (GABA) receptors represent the major class of inhibitory ion channels in the mammalian brain. Dysregulation of these receptors and/or their associated pathways is strongly implicated in the pathophysiology of epilepsy.

Reading epilepsy today: A scoping review and meta-analysis of reports of the last three decades.

Background And Aim: Reading-induced seizures are presumed to be rare phenomena attributed to an epilepsy syndrome not clearly belonging to either focal or generalized epilepsies. The aim of the article was to summarize knowledge and recent developments in the field of reading-induced seizures by reviewing all cases for which data were reported within the last three decades.

Methods: A scoping systematic review of demographic, clinical, electroencephalography (EEG) and imaging data of cases with reading-induced seizures reported in PubMed and Web of Science between 1991-01-01 and 2022-08-21 and a meta-analysis of the findings.

Longer-term verbal and visual memory patterns in patients with temporal lobe and genetic generalized epilepsies.

Objective: To compare forgetting patterns between patients with temporal lobe (TLE) and generalized (GGE) epilepsies and to assess whether recall is associated with epileptic activity.

Methods: Thirty-three patients with TLE (13 left, 17 right, and 3 nonlateralized TLE), 42 patients with GGE, and 57 healthy controls (HCs) were asked to recall words, verbal story material, and the Rey-Osterrieth complex figure at two delays. Accelerated long-term forgetting (ALF) was defined by group performance comparable to HCs at 30 min and worse recall than HCs after 4 weeks.

Variation in prognosis and treatment outcome in juvenile myoclonic epilepsy: a Biology of Juvenile Myoclonic Epilepsy Consortium proposal for a practical definition and stratified medicine classifications.

Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes.

An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal.

O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. Here, we report an OGTC921Y variant that co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity.

Spike count and morphology in the classification of epileptiform discharges.

Purpose: The purpose of this study is to investigate the impact of Bergen Epileptiform Morphology Score (BEMS) and interictal epileptiform discharge (IED) candidate count in EEG classification.

Methods: We included 400 consecutive patients from a clinical SCORE EEG database during 2013-2017 who had focal sharp discharges in their EEG, but no previous diagnosis of epilepsy. Three blinded EEG readers marked all IED candidates.

A new neurodevelopmental disorder linked to heterozygous variants in UNC79.

Purpose: The "NALCN channelosome" is an ion channel complex that consists of multiple proteins, including NALCN, UNC79, UNC80, and FAM155A. Only a small number of individuals with a neurodevelopmental syndrome have been reported with disease causing variants in NALCN and UNC80. However, no pathogenic UNC79 variants have been reported, and in vivo function of UNC79 in humans is largely unknown.

PRRT2 benign familial infantile seizures (BFIS) with atypical evolution to encephalopathy related to status epilepticus during sleep (ESES).

Purpose: Heterozygous variants in PRRT2 are mostly associated with benign phenotypes, being the major genetic cause of benign familial infantile seizures (BFIS), as well as in paroxysmal disorders. We report two children from unrelated families with BFIS that evolved to encephalopathy related to status epilepticus during sleep (ESES).

Methods And Results: Two probands presented with focal motor seizures at 3 months of age, with a limited course.

Automated Interlaboratory Comparison of Therapeutic Drug Monitoring Data and Its Use for Evaluation of Published Therapeutic Reference Ranges.

Therapeutic drug monitoring is a tool for optimising the pharmacological treatment of diseases where the therapeutic effect is difficult to measure or monitor. Therapeutic reference ranges and dose-effect relation are the main requirements for this drug titration tool. Defining and updating therapeutic reference ranges are difficult, and there is no standardised method for the calculation and clinical qualification of these.

Encephalopathy related to status epilepticus during slow sleep (ESES). Pathophysiological insights and nosological considerations.

Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is a childhood epilepsy syndrome characterized by the appearance of cognitive, behavioral, and motor disturbances in conjunction with a striking activation of EEG epileptic abnormalities during non-REM sleep. After more than 50 years since the first description, the pathophysiological mechanisms underlying the appearance of encephalopathy in association with a sleep-related enhancement of epileptic discharges are incompletely elucidated. Recent experimental data support the hypothesis that the development of the ESES encephalopathic picture depends on a spike-induced impairment of the synaptic homeostasis processes occurring during normal sleep and that is particularly pronounced during the developmental age.

Perampanel as precision therapy in rare genetic epilepsies.

Objective: Perampanel, an antiseizure drug with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist properties, may have a targeted effect in genetic epilepsies with overwhelming glutamate receptor activation. Epilepsies with loss of γ-aminobutyric acid inhibition (e.g.

Duration of epileptic seizure types: A data-driven approach.

Objective: To determine the duration of epileptic seizure types in patients who did not undergo withdrawal of antiseizure medication.

Methods: From a large, structured database of 11 919 consecutive, routine video-electroencephalograpy (EEG) recordings, labeled using the SCORE (Standardized Computer-Based Organized Reporting of EEG) system, we extracted and analyzed 2742 seizures. For each seizure type we determined median duration and range after removal of outliers (2.

Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment.

Generation and characterization of induced pluripotent stem (iPS) cell line (SDUCTi001-A) using fibroblasts derived from male-healthy donor.

Induced pluripotent stem (iPS) cell lines have wide valuable applications in experimental research, including developmental, pathological, and drug screening studies. Using integration-free episomal plasmids, we have generated a new iPS cell line from a 26-year-old healthy male donor. Characterization of the established cell line confirmed the expression of pluripotency markers, differentiation into the three germ layers, and absence of chromosomal abnormalities.

Has stigma changed? The image of epilepsy in literature. An essay.

Stigma is perhaps the most important sociopsychological burden for people with epilepsy (PWE), and literature both reflects and influences societal attitudes including stigma. To study how representations of stigma have changed over time could provide interesting insights. Traditionally, often repeated stigmatizing aspects include possession, insanity and crime, the weak, dependent and miserable epileptic, unfitness for marriage and reproduction, unreliability, but also special gifts.

Expanding the pre- and postnatal phenotype of WASHC5 and CCDC22 -related Ritscher-Schinzel syndromes.

Ritscher-Schinzel syndrome (RTSCS) is a rare genetic condition characterized by peculiar craniofacial features and cerebellar and cardiovascular malformations. To date, four genes are implicated in this condition. The first two genes described were the autosomal recessive inherited gene WASHC5 associated with Ritscher-Schinzel syndrome 1 (RTSCS1), and CCDC22, an X-linked recessive gene causing Ritscher-Schinzel syndrome 2 (RTSCS2).

Detecting temporal lobe seizures in ultra long-term subcutaneous EEG using algorithm-based data reduction.

Objective: Ultra long-term monitoring with subcutaneous EEG (sqEEG) offers objective outpatient recording of electrographic seizures as an alternative to self-reported epileptic seizure diaries. This methodology requires an algorithm-based automatic seizure detection to indicate periods of potential seizure activity to reduce the time spent on visual review. The objective of this study was to evaluate the performance of a sqEEG-based automatic seizure detection algorithm.

The importance of an outdoor playground for children with epilepsy and their family during and after hospitalization: A qualitative study of parents' experiences.

Objectives: To explore parents' experiences of using an outdoor playground during hospitalization with their child with epilepsy.

Method: The study is based on a qualitative exploratory design. Semi-structured individual interviews were conducted with 10 parents with a child with epilepsy (6-11 years).

A structured, blended learning program towards proficiency in epileptology: the launch of the ILAE Academy Level 2 Program.

The ILAE Academy is the online learning platform of the International League Against Epilepsy (ILAE) and offers a structured educational program addressing the competency-based ILAE curriculum in epileptology. The platform was launched in July 2020 with a self-paced course portfolio of interactive e-learning modules addressing ILAE Level 1 learning objectives, defined as the entry level in epileptology. Using feedback questionnaires from completed Level 1 courses as well as sociodemographic and learning-related data obtained from 47 participants, we show that over 50% of learners have an entry level in epileptology and do not have access to on-site training and over 40%do not have access to on-site training.

Impact of Genetic Testing on Therapeutic Decision-Making in Childhood-Onset Epilepsies-a Study in a Tertiary Epilepsy Center.

We assessed the frequency of pediatric monogenic epilepsies and precision therapies at a tertiary epilepsy center. We analyzed medical records of children, born in 2006-2011 and followed at the Danish Epilepsy Center from January to December 2015; 357 patients were identified, of whom 27 without epilepsy and 35 with acquired brain damage were excluded. Of the remaining 295 children, 188 were consented for study inclusion and genetic testing.