Epilepsia. Official Journal of the International League Against Epilepsy

Abstract

Objectives

Genetic variants in the SCN8A gene underlie a wide spectrum of neurodevelopmental phenotypes including several distinct seizure types and a host of comorbidities. One of the major challenges facing clinicians and researchers alike is to identify genotype-phenotype (G-P) correlations that may improve prognosis, guide treatment decisions, and lead to precision medicine approaches.

Methods

We investigated genotype-phenotype correlations among 270 participants harboring gain-of-function (GOF) variants enrolled in the International SCN8A Registry, a patient-driven online database. We performed correlation analyses stratifying the cohort by ...

Abstract

Objective

Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism.

Methods

Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels ...

Abstract

Objective

To investigate the clinical feature and potential pathogenesis mechanism of de novo CLPTM1 variants associated with epilepsy.

Methods

Identify de novo genetic variants associated with epilepsy by reanalyzing trio-based whole-exome sequencing data. We analyzed the clinical characteristics of patients with these variants and performed functional in vitro studies in cells expressing mutant cDNA for these variants using whole-cell voltage-clamp current recordings and outside-out patch-clamp recordings from transiently transfected HEK cells.

Results

Two de novo missense variants related to epilepsy were identified in CLPTM1 gene. ...

Abstract

Objective

The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics.

Methods

We investigated 123 participants—23 patients with ...

Abstract

Objective

More than one third of mesial temporal lobe epilepsy (MTLE) patients are resistant to current antiseizure medications (ASMs), and half experience mild-to-moderate adverse effects of ASMs. There is therefore a strong need to develop and test novel ASMs. The objective of this work is to evaluate the pharmacokinetics and neurological toxicity of E2730, a novel uncompetitive inhibitor of γ-aminobutyric acid transporter-1, and to test its seizure suppression effects in a rat model of chronic MTLE.

Methods

We first examined plasma levels and ...

Abstract

Objective

The main purposes of this study were to validate the epilepsy diagnosis in incident epilepsy cases in the Danish National Patient Registry (DNPR), which contains information on nearly 9 000 000 individuals, and to identify persons in the validated cohort who fulfilled the International League Against Epilepsy (ILAE) criteria for drug-resistant epilepsy (DRE).

Methods

We reviewed a random sample of medical records from all individuals registered with a first diagnosis of epilepsy (International Classification of Diseases, 10th Revision [ICD-10]: G40) or seizures (ICD-10: G41, ...

Abstract

The solute carrier family 6 member 1 (SLC6A1) gene encodes GAT-1, a γ-aminobutyric acid transporter expressed on astrocytes and inhibitory neurons. Mutations in SLC6A1 are associated with epilepsy and developmental disorders, including motor and social impairments, but variant-specific animal models are needed to elucidate mechanisms. Here, we report electrocorticographic (ECoG) recordings and clinical data from a patient with a variant in SLC6A1 that encodes GAT-1 with a serine-to-leucine substitution at amino acid 295 (S295L), who was diagnosed with childhood absence ...