Functional and behavioral signatures of Kv7 activator drug subtypes

Abstract

Objective

Voltage‐gated potassium channels of the KCNQ (Kv7) family are targeted by a variety of activator compounds with therapeutic potential for treatment of epilepsy. Exploration of this drug class has revealed a variety of effective compounds with diverse mechanisms. In this study, we aimed to clarify functional criteria for categorization of Kv7 activator compounds, and to compare the effects of prototypical drugs in a zebrafish larvae model.

Methods

In vitro electrophysiological approaches with recombinant ion channels were used to highlight functional properties important ...

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Reduced expression of the glucocorticoid receptor in the hippocampus of patients with drug‐resistant temporal lobe epilepsy and comorbid depression

Abstract

Objective

Depressive disorders are common among about 50% of the patients with drug‐resistant temporal lobe epilepsy (TLE). The underlying etiology remains elusive, but hypothalamus‐pituitary‐adrenal (HPA) axis activation due to changes in glucocorticoid receptor (GR) protein expression could play an important role. Therefore, we set out to investigate expression of the GR in the hippocampus, an important brain region for HPA axis feedback, of patients with drug‐resistant TLE, with and without comorbid depression.

Methods

GR expression was studied using immunohistochemistry on hippocampal sections from ...

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Photoplethysmographic evaluation of generalized tonic‐clonic seizures

Abstract

Objective

Photoplethysmography (PPG) is an optical technique measuring variations of blood perfusion in peripheral tissues. We evaluated alterations in PPG signals in relationship to the occurrence of generalized tonic‐clonic seizures (GTCSs) in patients with epilepsy to evaluate the feasibility of seizure detection.

Methods

During electroencephalographic (EEG) long‐term monitoring, patients wore portable wristband sensor(s) on their wrists or ankles recording PPG signals. We analyzed PPG signals during three time periods, which were defined with respect to seizures detected on EEG: (1) baseline (>30 minutes prior ...

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Defining the phenotype of FHF1 developmental and epileptic encephalopathy

Abstract

Fibroblast growth‐factor homologous factor (FHF1 ) gene variants have recently been associated with developmental and epileptic encephalopathy (DEE). FHF1 encodes a cytosolic protein that modulates neuronal sodium channel gating. We aim to refine the electroclinical phenotypic spectrum of patients with pathogenic FHF1 variants. We retrospectively collected clinical, genetic, neurophysiologic, and neuroimaging data of 17 patients with FHF1‐DEE. Sixteen patients had recurrent heterozygous FHF1 missense variants: 14 had the recurrent p.Arg114His variant and two had a novel likely ...

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Assessment of the long‐term efficacy and safety of adjunctive perampanel in tonic‐clonic seizures: Analysis of four open‐label extension studies

Abstract

Objective

This post hoc analysis evaluated long‐term efficacy and safety in patients with focal to bilateral tonic‐clonic seizures (FBTCS) or generalized tonic‐clonic seizures (GTCS) who entered open‐label extension (OLEx) studies to receive long‐term adjunctive perampanel.

Methods

Patients aged 12 years and older who completed phase II or III randomized, double‐blind, placebo‐controlled studies could enter an OLEx study, each comprising a blinded conversion period followed by an open‐label maintenance period (32‐424 weeks; maximum perampanel dose = 12 mg/d). Exposure, seizure outcomes, and treatment‐emergent adverse events (TEAEs) were ...

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Family resources moderate the relationship between seizure control and health‐related quality of life in children with drug‐resistant epilepsy

Abstract

Objective

Pediatric drug‐resistant epilepsy (DRE) is associated with poor health‐related quality of life (HRQOL). Achieving seizure control, however, does not improve HRQOL in all children. This study sought to evaluate whether (1) baseline caregiver and family factors are associated with child HRQOL at 1‐year follow‐up over and above epilepsy characteristics, treatment, and seizure outcome; and (2) baseline family factors moderate the association between seizure outcome and child HRQOL at 1‐year follow‐up.

Methods

This multicenter longitudinal cohort study recruited 152 children with DRE who ...

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