Epilepsia. Official Journal of the International League Against Epilepsy

Abstract

Objectives

The loop diuretic bumetanide has been proposed previously as an adjunct treatment for neonatal seizures because bumetanide is thought to potentiate the action of γ‐aminobutyric acid (GABA)ergic drugs such as phenobarbital by preventing abnormal intracellular accumulation of chloride and the subsequent “GABA shift.” However, a clinical trial in neonates failed to demonstrate such a synergistic effect of bumetanide, most likely because this drug only poorly penetrates into the brain. This prompted us to develop lipophilic prodrugs of bumetanide, such as ...

Abstract

Objective

Adult drug‐resistant epilepsy (DRE) is associated with significant morbidity. Infiltration of immune cells is observed in DRE epileptic foci; however, the relation between DRE and the peripheral immune cell compartment remains only partially understood. We aimed to investigate differences in immune cell populations, cytokines, and neurodegenerative biomarkers in the peripheral blood of subjects with epilepsy versus healthy controls, and in DRE compared to well‐controlled epilepsy (WCE).

Methods

Peripheral blood mononuclear cells and serum from >120 age‐ and sex‐matched adults suffering from focal ...

Abstract

Objective

SCN8A encephalopathy is a developmental epileptic encephalopathy typically caused by de novo gain‐of‐function mutations in Na_v1.6. Severely affected individuals exhibit refractory seizures, developmental delay, cognitive disabilities, movement disorders, and elevated risk of sudden death. Patients with the identical SCN8A variant can differ in clinical course, suggesting a role for modifier genes in determining disease severity. The identification of genetic modifiers contributes to understanding disease pathogenesis and suggesting therapeutic interventions.

Methods

We generated F1 and F2 crosses between inbred mouse strains and mice ...

Abstract

Objective

We report data from the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) to see if there are significant differences in relation to the courses and outcomes of the twin pregnancies contained in the register, as compared with the singleton ones.

Methods

The APR has been under the oversight of Melbourne institutional Human Ethics Research Committees; all women enrolled in the APR have provided written informed consent. Data from the APR were transferred to a spreadsheet and then analyzed using ...

Abstract

Objective

Midazolam nasal spray (MDZ‐NS) is indicated for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern, in patients 12 years of age and older with epilepsy. This trial evaluated safety and efficacy of MDZ‐NS in patients with epilepsy who were admitted to the epilepsy monitoring unit for seizure characterization/presurgical evaluation.

Methods

In this randomized, double‐blind, placebo‐controlled phase 3 trial (P261‐301; NCT01999777), eligible patients with ≥2 seizures in ...

Abstract

One‐third of epilepsy patients have drug‐resistant epilepsy (DRE), which is often complicated by polydrug toxicity and psychiatric and cognitive comorbidities. Advances in understanding the microbiome and gut‐brain‐axis are likely to shed light on epilepsy pathogenesis, anti‐seizure medication (ASM) resistance, and potential therapeutic targets. Gut dysbiosis is associated with inflammation, blood‐brain barrier disruption, and altered neuromodulators. High‐throughput and metagenomic sequencing has advanced the characterization of microbial species and functional pathways. DRE patients show altered gut microbiome composition compared to drug‐sensitive patients ...

Abstract

Objective

The posterior cingulate cortex (PCC)/precuneus is a key hub of the default mode network, whose function is known to be altered in epilepsy. Glutamate and γ‐aminobutyric acid (GABA) are the main excitatory and inhibitory neurotransmitters in the central nervous system, respectively. Glutathione (GSH) is the most important free radical scavenging compound in the brain. Quantification of these molecules by magnetic resonance spectroscopy (MRS) up to 4 T is limited by overlapping resonances from other molecules. In this study, we used ...

Abstract

Objective

Leucine‐rich glioma‐inactivated 1 (LGI1) is a secreted transsynaptic protein that interacts presynaptically with Kv1.1 potassium channels and a disintegrin and metalloprotease (ADAM) protein 23, and postsynaptically influences α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptors through a direct link with the ADAM22 cell adhesion protein. Haploinsufficiency of LGI1 or autoantibodies directed against LGI1 are associated with human epilepsy, generating the hypothesis that a subacute reduction of LGI1 is sufficient to increase network excitability.

Methods

We tested this hypothesis in ex vivo hippocampal slices and in neuronal cultures, by ...

Abstract

Objective

The role of α_2A adrenergic receptors (α_2AARs) in absence epilepsy is not well characterized. Therefore, we investigated the outcomes of the specific antagonism of α_2AARs on the spike‐and‐wave discharges (SWDs) in genetic absence epilepsy rats from Strasbourg (GAERSs), together with its influence on the behavior and second messenger systems, which may point to the mechanisms to which a possible SWD modulation can be related.

Methods

Atipamezole, an α_2AAR antagonist, was administered intracerebroventricularly to the adult GAERSs, and electroencephalography (EEG) was conducted. The ...