Epilepsia. Official Journal of the International League Against Epilepsy

Abstract

Objective

Fetal exposure to the anticonvulsant drug valproic acid (VPA), used to treat certain types of epilepsy, increases the risk for birth defects, including neural tube defects, as well as learning difficulties and behavioral problems. Here, we investigated neurotoxic effects of VPA exposure using zebrafish as a model organism. The capacity of folic acid (FA) supplementation to rescue the VPA-induced neuronal and behavioral perturbations was also examined.

Methods

Zebrafish embryos of different transgenic lines with neuronal green fluorescent protein expression were exposed to ...

Summary

Objective

Fibroblast growth factor homologous factors (FHFs) are brain and cardiac sodium channel‐binding proteins that modulate channel density and inactivation gating. A recurrent de novo gain‐of‐function missense mutation in the FHF1(FGF12) gene (p.Arg52His) is associated with early infantile epileptic encephalopathy 47 (EIEE47; Online Mendelian Inheritance in Man database 617166). To determine whether the FHF1 missense mutation is sufficient to cause EIEE and to establish an animal model for EIEE47, we sought to engineer this mutation into mice.

Methods

The Arg52His mutation was introduced ...

Abstract

Objective

This study was undertaken to examine the efficacy of a family‐tailored education and problem‐solving behavioral intervention, Supporting Treatment Adherence Regimens (STAR), in young children (2–12 years old) with new onset epilepsy compared to an attention control (i.e., education only [EO]) intervention. Participants randomized to the STAR intervention were hypothesized to demonstrate significantly improved adherence at postintervention and 3‐, 6‐, and 12‐month follow‐up visits compared to the EO intervention. Seizure and health‐related quality of life (HRQOL) outcomes were also examined.

Methods

Two hundred children ...

Abstract

CDKL5 deficiency disorder (CDD) is an X‐linked pharmacoresistant neurogenetic disorder characterized by global developmental delays and uncontrolled seizures. Fenfluramine (FFA), an antiseizure medication (ASM) indicated for treating convulsive seizures in Dravet syndrome, was assessed in six patients (five female; 83%) with CDD whose seizures had failed 5–12 ASMs or therapies. Median age at enrollment was 6.5 years (range: 2–26 years). Mean FFA treatment duration was 5.3 months (range: 2–9 months) at 0.4 mg/kg/day (n = 2) or 0.7 mg/kg/day (n = 4; maximum: 26 mg/day). One patient had valproate added for ...

Abstract

Objective

One of the challenges in treating patients with drug‐resistant epilepsy is that the mechanisms of seizures are unknown. Most current interventions are based on the assumption that epileptic activity recruits neurons and progresses by synaptic transmission. However, several experimental studies have shown that neural activity in rodent hippocampi can propagate independently of synaptic transmission. Recent studies suggest these waves are self‐propagating by electric field (ephaptic) coupling. In this study, we tested the hypothesis that neural recruitment during seizures can occur ...

Abstract

Alzheimer’s disease (AD) can increase the risk of epilepsy by up to 10‐fold compared to healthy age‐matched controls. However, the pathological mechanisms that underlie this increased risk are poorly understood. Because disruption in brain glutamate homeostasis has been implicated in both AD and epilepsy, this might play a mechanistic role in the pathogenesis of epilepsy in AD. Prior to the formation of amyloid beta (Aβ) plaques, the brain can undergo pathological changes as a result of increased production of amyloid ...

Abstract

Objective

Although group studies provide some support for the material‐specific model of memory function, there are considerable individual variations in memory function in people with temporal lobe epilepsy, even in those with the same underlying pathology. In this proof‐of‐concept study, we examined the sensitivity and specificity of a single measure of an individual’s relative strength for the encoding of verbal or visual learning.

Methods

Six hundred ninety‐two patients with left hemisphere language dominance and unilateral hippocampal sclerosis completed verbal and visual encoding tasks ...

Abstract

Objectives

Bumetanide was suggested as an adjunct to phenobarbital for suppression of neonatal seizures. This suggestion was based on the idea that bumetanide, by reducing intraneuronal chloride accumulation through inhibition of the Na‐K‐2Cl cotransporter NKCC1, may attenuate or abolish depolarizing γ‐aminobutyric acid (GABA) responses caused by birth asphyxia. However, a first proof‐of‐concept clinical trial failed. This could have had several reasons, including bumetanide’s poor brain penetration, the wide cellular NKCC1 expression pattern in the brain, and problems with the general concept ...

Abstract

Objective

Medial temporal lobe epilepsy (MTLE) is a drug‐resistant focal epilepsy that can be caused by a broad spectrum of different inciting events, including tumors, febrile seizures, and viral infections. In human epilepsy surgical resections as well as in animal models, an involvement of the adaptive immune system was observed. We here analyzed the presence of T cells in various subgroups of MTLE. We aimed to answer the question of how much inflammation was present and whether the presence of T ...

Summary

Objective

Growing evidence suggests that dysfunctional astrocytes are crucial players in the development of mesial temporal lobe epilepsy (MTLE). Using a mouse model closely recapitulating key alterations of chronic human MTLE with hippocampal sclerosis, here we asked whether death of astrocytes contributes to the initiation of the disease and investigated potential underlying molecular mechanisms.

Methods

Antibody staining was combined with confocal imaging and semiquantitative real‐time polymerase chain reaction analysis to identify markers of different cellular death mechanisms between 4 h and 3 days after epilepsy ...