Epilepsia. Official Journal of the International League Against Epilepsy

Abstract

Objective

Brain somatic variants in SLC35A2 were recently identified as a genetic marker for mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). The role of SLC35A2 in cortical development and the contributions of abnormal neurons and oligodendrocytes to seizure activity in MOGHE remain largely unexplored.

Methods

Here, we generated a novel Slc35a2 floxed allele, which we used to develop two Slc35a2 conditional knockout mouse lines targeting (1) the Emx1 dorsal telencephalic lineage (excitatory neurons and glia) and (2) the Olig2 ...

This open-label extension trial assessed the long-term safety, tolerability, and efficacy of lacosamide as adjunctive therapy for generalized-onset tonic-clonic seizures in patients aged ≥4 years with idiopathic generalized epilepsy.

Abstract

Objective

This study was undertaken to assess long-term safety, tolerability, and efficacy of lacosamide (LCM) as adjunctive therapy for generalized onset tonic–clonic seizures (GTCS) in patients aged ≥4 years with idiopathic generalized epilepsy (IGE).

Methods

EP0012 ...

Abstract

We studied the distribution of germline and somatic variants in epilepsy surgery patients with (suspected) malformations of cortical development (MCD) who underwent surgery between 2015 and 2020 at University Medical Center Utrecht (the Netherlands) and pooled our data with four previously published cohort studies. Tissue analysis yielded a pathogenic variant in 203 of 663 (31%) combined cases. In 126 of 379 (33%) focal cortical dysplasia (FCD) type II cases and 23 of 37 (62%) hemimegalencephaly cases, a pathogenic variant was ...

Abstract

Objective

Determining the pathogenicity of missense variants in clinical genetic tests for individuals with epilepsy is crucial for guiding personalized treatment. However, achieving a definitive pathogenic classification remains challenging, with most missense variants still classified as variants of uncertain significance (VUS) and with the availability of many computational tools which may provide conflicting predictions. Here, we aim to evaluate the performance of state-of-the-art computational tools in pathogenicity prediction of missense variants in epilepsy-associated genes. This will assist in selecting the most ...

Abstract

Objective

Recently, we developed a first artificial intelligence (AI)-based digital pathology classifier for focal cortical dysplasia (FCD) as defined by the ILAE classification. Herein, we tested the usefulness of the classifier in a retrospective histopathology workup scenario.

Methods

Eighty-six new cases with histopathologically confirmed FCD ILAE type Ia (FCDIa), FCDIIa, FCDIIb, mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), or mild malformations of cortical development were selected, 20 of which had confirmed gene mosaicism.

Results

The classifier always recognized the correct histopathology ...

Abstract

Objective

Deep brain stimulation, particularly low-frequency stimulation (LFS) targeting fiber tracts, has emerged as a potential therapy for drug-resistant epilepsy (DRE) and for generalized epilepsy, both of which pose significant treatment challenges. LFS diffusely suppresses seizures in the cortex when applied to fiber tracts like the corpus callosum (CC). Nevertheless, the specific processes responsible for suppressing epileptic activity in the cortex induced by LFS remain unclear. This study investigates the mechanisms underlying the antiepileptic effect in the cortex of LFS of ...

Abstract

Time is critical in executing acute seizure treatment, and efforts to minimize operational delays with medication preparation confer potential logistical and practical advantages. Multiple studies have demonstrated the safety and tolerability of intravenous (IV) undiluted levetiracetam (LEV) in adults; however, published pediatric data are limited. This study aims to evaluate the safety and tolerability of IV undiluted LEV in pediatrics. This was a retrospective, dual-center, observational cohort study evaluating concentration-related adverse drug events with IV undiluted (100 mg/mL) LEV in pediatrics ...

Abstract

Here we critique recent arguments proposing to distinguish ictal from non-ictal generalized periodic discharges (GPDs) based on etiology and stimulation response, arguing that these are unreliable. We advocate for an empirical approach to GPDs: describe objectively, interpret through medication trials, and base further treatment on response. We call for evidence-based approaches considering meaningful clinical outcomes.

Abstract

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy. However, there is a lack of reliable predictors of VNS response in clinical use. The identification of factors predictive of VNS response is important for patient selection and stratification as well as tailored stimulation programming. We conducted a narrative review of the existing literature on prognostic markers for VNS response using clinical, demographic, biochemical, and modality-specific information such as from electroencephalography (EEG), magnetoencephalography, and magnetic resonance imaging (MRI). No ...