E2730, an uncompetitive γ‐aminobutyric acid transporter‐1 inhibitor, suppresses epileptic seizures in a rat model of chronic mesial temporal lobe epilepsy

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 ...

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Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings

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 ...

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Identification of drug resistance in a validated cohort of incident epilepsy patients in the Danish National Patient Register

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, ...

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Patient‐derived SLC6A1 variant S295L results in an epileptic phenotype similar to haploinsufficient mice

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 ...

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Wrist‐worn smartwatch and predictive models for seizures

Abstract

Objective

This study was undertaken to describe extracerebral biosignal characteristics of overall and various seizure types as compared with baseline physical activities using multimodal devices (Empatica E4); develop predictive models for overall and each seizure type; and assess diagnostic performance of each model.

Methods

We prospectively recruited patients with focal epilepsy who were admitted to the epilepsy monitoring unit for presurgical evaluation during January to December 2020. All study participants were simultaneously applied gold standard long-term video-electroencephalographic (EEG) monitoring and an index test, ...

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