Neural recruitment by ephaptic coupling in epilepsy

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 ...

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Astrocyte and glutamate involvement in the pathogenesis of epilepsy in Alzheimer’s disease

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 ...

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The clinical utility of a memory specialization index in epilepsy surgery patients with unilateral hippocampal sclerosis

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 ...

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A combination of phenobarbital and the bumetanide derivative bumepamine prevents neonatal seizures and subsequent hippocampal neurodegeneration in a rat model of birth asphyxia

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 ...

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T cell numbers correlate with neuronal loss rather than with seizure activity in medial temporal lobe epilepsy

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 ...

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Cell death of hippocampal CA1 astrocytes during early epileptogenesis

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 ...

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The molecular and phenotypic spectrum of CLCN4‐related epilepsy

Abstract

Objective

This study was undertaken to expand the phenotypic and genetic spectrum of CLCN4‐related epilepsy and to investigate genotype–phenotype correlations.

Methods

We systematically reviewed the phenotypic and genetic spectrum of newly diagnosed and previously reported patients with CLCN4‐related epilepsy. Three novel variants identified in four patients reported in this study were evaluated through in silico prediction and functional analysis by Western blot, immunofluorescence, and electrophysiological measurements.

Results

Epilepsy was diagnosed in 54.55% (24/44) of individuals with CLCN4‐related disorders and was drug‐resistant in most cases. Of ...

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Increased branched‐chain amino acids at baseline and hours before a spontaneous seizure in the human epileptic brain

Abstract

The objective of this study was to monitor the extracellular brain chemistry dynamics at baseline and in relation to spontaneous seizures in human patients with refractory epilepsy. Thirty patients with drug‐resistant focal epilepsy underwent intracranial electroencephalography and concurrent brain microdialysis for up to 8 continuous days. Extracellular brain glutamate, glutamine, and the branched‐chain amino acids (BCAAs) valine, leucine, and isoleucine were quantified in the dialysis samples by liquid chromatography–tandem mass spectrometry. Extracellular BCAAs and glutamate were chronically elevated at baseline ...

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Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial

Abstract

Objective

Focal cortical dysplasia (FCD) is a major cause of difficult‐to‐treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme.

Methods

Four web‐based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical ...

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Modeling seizures in the Human Phenotype Ontology according to contemporary ILAE concepts makes big phenotypic data tractable

Abstract

Objective

The clinical features of epilepsy determine how it is defined, which in turn guides management. Therefore, consideration of the fundamental clinical entities that comprise an epilepsy is essential in the study of causes, trajectories, and treatment responses. The Human Phenotype Ontology (HPO) is used widely in clinical and research genetics for concise communication and modeling of clinical features, allowing extracted data to be harmonized using logical inference. We sought to redesign the HPO seizure subontology to improve its consistency with ...

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