Lacosamide effects on placental carriers for essential compounds in comparison with valproate: studies in perfused human placentas

Abstract

Objective

Lacosamide is being increasingly prescribed to pregnant women, although its effects on the developing fetus have not yet been fully clarified. Previously, we have shown that several antiseizure medications, particularly valproate, can affect the expression of carriers for essential compounds in placental cells. Here, our aim was to assess the effect of short ex vivo exposure of human placentas to lacosamide on the expression of carriers for essential nutrients required by the human fetus.

Methods

Placentas were obtained from cesarean deliveries of ...

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Significant improvements in SEIzure interVAL (time between seizure clusters) across time in patients treated with diazepam nasal spray as intermittent rescue therapy for seizure clusters

Abstract

Objective

Intermittent rescue therapy may be used for seizure clusters, which are clinical emergencies that may persist ≥24 h and increase risk of status epilepticus, emergency room visits, and reduced quality of life for patients with epilepsy. Beyond effectiveness for aborting seizure clusters, no data exist on how intermittent rescue therapy may impact the long-term natural course of seizure clusters. This novel analysis explores SEIzure interVAL (SEIVAL; time between seizure clusters) in patients from a long-term safety study of diazepam nasal spray ...

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Elevated photic response is followed by a rapid decay and depressed state in ictogenic networks

Abstract

Objective

The switch between nonseizure and seizure states involves profound alterations in network excitability and synchrony. In this study, we aimed to identify and compare features of neural excitability and dynamics across multiple zebrafish seizure and epilepsy models.

Methods

Inspired by video-electroencephalographic recordings in patients, we developed a framework to study spontaneous and photically evoked neural and locomotor activity in zebrafish larvae, by combining high-throughput behavioral tracking and whole-brain in vivo two-photon calcium imaging.

Results

Our setup allowed us to dissect behavioral and physiological features ...

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Considerations for determining the efficacy of new antiseizure medications in children age 1 month to younger than 2 years

Abstract

Objectives

Drug treatment for children with epilepsy should, ideally, be governed by evidence from adequate and well-controlled clinical studies. However, these studies are difficult to conduct, and so direct evidence supporting the informed use of specific drugs is often lacking. The Research Roundtable for Epilepsy (RRE) met in 2020 to align on an approach to therapy development for focal seizures in children age 1 month <2 years of age.

Methods

The RRE reviewed the regulatory landscape, epidemiology, seizure semiology, antiseizure medicine pharmacology, and safety issues ...

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Molecular and clinical descriptions of patients with GABAA receptor gene variants (GABRA1, GABRB2, GABRB3, GABRG2): A cohort study, review of literature, and genotype–phenotype correlation

Abstract

Objective

γ-Aminobutyric acid (GABA)A-receptor subunit variants have recently been associated with neurodevelopmental disorders and/or epilepsy. The phenotype linked with each gene is becoming better known. Because of the common molecular structure and physiological role of these phenotypes, it seemed interesting to describe a putative phenotype associated with GABAA-receptor–related disorders as a whole and seek possible genotype–phenotype correlations.

Methods

We collected clinical, electrophysiological, therapeutic, and molecular data from patients with GABAA-receptor subunit variants (GABRA1, GABRB2, GABRB3, and GABRG2) through a national French collaboration using ...

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Genetic interaction between Scn8a and potassium channel genes Kcna1 and Kcnq2

Abstract

Voltage-gated sodium and potassium channels regulate the initiation and termination of neuronal action potentials. Gain-of-function mutations of sodium channel Scn8a and loss-of-function mutations of potassium channels Kcna1 and Kcnq2 increase neuronal activity and lead to seizure disorders. We tested the hypothesis that reducing the expression of Scn8a would compensate for loss-of-function mutations of Kcna1 or Kcnq2. Scn8a expression was reduced by the administration of an antisense oligonucleotide (ASO). This treatment lengthened the survival of the Kcn1a and Kcnq2 mutants, and ...

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International consensus recommendations for management of New Onset Refractory Status Epilepticus (NORSE) including Febrile Infection‐Related Epilepsy Syndrome (FIRES): Summary and Clinical Tools

Abstract

Objective

To develop consensus-based recommendations for the management of adult and pediatric patients with NORSE/FIRES based on best available evidence and expert opinion.

Methods

The Delphi methodology was followed. A facilitator group of 9 experts was established, who defined the scope, users and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment and research directions were generated which were then voted on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 ...

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Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): II. Drugs in more advanced clinical development

Abstract

The Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI) was held in Madrid, Spain on May 22–25, 2022 and was attended by 157 delegates from 26 countries representing basic and clinical science, regulatory agencies, and pharmaceutical industries. One day of the conference was dedicated to sessions presenting and discussing investigational compounds under development for the treatment of seizures and epilepsy. The current progress report summarizes recent findings and current knowledge for seven of these compounds in more ...

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