Epilepsia. Official Journal of the International League Against Epilepsy

Abstract

Objective

The thalamus participates in seizure propagation and is a target for neuromodulation in epilepsy. Although thalamic connectivity changes have been reported in adults with temporal lobe epilepsy (TLE), pediatric TLE is distinct, characterized by greater etiological diversity and impact on brain maturation. This study applied a novel gradient mapping technique to investigate whole-brain thalamic connectivity patterns in children with TLE.

Methods

Sixty-two children with TLE (ages 5–18) and 61 controls (ages 6–20) underwent a covert verb generation task functional magnetic resonance imaging ...

Abstract

Objective

Developmental and epileptic encephalopathy type 1 (DEE1) is a rare drug-resistant pediatric epilepsy caused by trinucleotide repeat expansions in the X-linked ARX gene, leading to elongation of the first polyalanine tract. It presents with early onset tonic seizures or spasms, developmental and cognition delay, and high risk of premature mortality. We evaluated the therapeutic potential of highly purified cannabidiol (CBD) in Arx
^(GCG)7/Y mice, a genetic DEE1 model that replicates key features of the human condition.

Methods

Arx
^(GCG)7/Y mice received daily ...

Abstract

Objective

Closed-loop neurostimulation is a promising treatment for drug-resistant focal epilepsy. A major challenge is fast and reliable seizure detection via electroencephalography (EEG). Although many approaches have been published, they often lack statistical power and practical utility. The use of various EEG preprocessing parameters and performance metrics hampers comparability. Additionally, the critical issue of energy consumption for an application in medical devices is rarely considered. Addressing these points, we present a systematic analysis of the impact of EEG preprocessing parameters on ...

Abstract

Objective

Patients with drug-resistant epilepsy, including Dravet syndrome, are frequently prescribed multiple antiseizure medications. Nevertheless, people with Dravet syndrome often have inadequate seizure control, and there is an ongoing unmet clinical need to identify novel therapeutics. As a proof-of-principle study to further validate and characterize the Scn1a
^A1783V/WT
mouse model and identify a drug-testing paradigm with face, construct, and predictive validity, we assessed the efficacy of subchronic administration of stiripentol add-on to clobazam and valproic acid at clinically relevant doses ...

Abstract

Objective

Changes in extracellular matrix (ECM) and highly condensed ECM structures called perineuronal nets (PNNs) have been reported in human patients with epilepsy as well as some animal models of epilepsy. We studied potential ECM changes in a mouse model of pilocarpine-induced status epilepticus (PISE) and their potential contributions to seizures.

Methods

We used a reduced intensity pilocarpine model to induce status epilepticus (SE) in mice. Wisteria floribunda agglutinin (WFA) staining was used to identify PNNs. Immunohistochemistry, patch-clamp electrophysiology, drug studies, and transcriptomic ...

Abstract

Objective

This study investigates excitatory/inhibitory (E/I) imbalances in GNAO1-related disorders (GNAO1-RD), linking neuronal dysfunction to clinical severity using E/I-sensitive electroencephalography (EEG) analyses.

Methods

We conducted an observational study involving 12 children with GNAO1-RD caused by pathogenic variants and 36 age-matched, typically developing children (TDC). EEG was recorded during eyes-closed rest. Clinical evaluations included scales for epilepsy, movement disorders, motor and language development, and an overall clinical severity score. Molecular assessments of GNAO1 variants used bioluminescence resonance energy transfer (BRET) assays. Quantitative EEG measures ...

Abstract

Objective

Pathogenic ANKH variants are a known cause of chondrocalcinosis (Online Mendelian Inheritance in Man [OMIM] #118600) and craniometaphyseal dysplasia (OMIM #123000). Here, we describe the phenotype and genotype of autosomal dominant infantile epilepsy caused by a c.-11C>T change upstream of the gene’s normal ATG initiation codon of ANKH in a family of southern Italian descent; we correlate the phenotype with known epilepsy syndromes and provide the first evidence of recurrence of this particular ANKH variant.

Methods

Phenotyping and genotyping (short-read exome/genome sequencing) ...

Abstract

Objective

In patients with focal drug-resistant epilepsy (DRE), resective epilepsy surgery correlates with high rates of remission. However, in cases where the epileptic region is deemed surgically inaccessible, or when it involves a complex network, stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) might be an alternative therapeutic strategy. However, most of the available evidence is limited to small observational studies. An updated meta-analysis is warranted to provide a comprehensive assessment of SEEG-RFTC in patients with DRE.

Methods

Databases were searched until September 9, 2023 to identify ...

Abstract

Objectives

Responsiveness to vagus nerve stimulation (VNS) in children with drug-resistant epilepsy (DRE) is often defined based on reduction in seizure frequency, typically at the 50% threshold, with limited consideration to the effects of therapy on seizure severity and health-related quality of life (HRQoL). In the current report, we sought to better characterize the effects of VNS beyond seizure frequency in children with DRE.

Methods

Sixty-seven children from the Connectomic profiling and Vagus nerve stimulation Outcomes Study (CONNECTiVOS) database, a multicenter study including children ...

Abstract

Objective

Current weight-based dosing fails to account for pharmacokinetic variability in refractory and superrefractory status epilepticus (RSE, SRSE). However, understanding pharmacokinetics in critically ill patients with varying degrees of organ dysfunction can improve both safety and efficacy. Hence, this study aims to quantify key pharmacokinetic variabilities to enable individualized dosing in RSE and SRSE.

Methods

Patients with RSE and SRSE admitted to a neurointensive care unit of a tertiary academic center were retrospectively screened for therapeutic drug monitoring (TDM) samples of phenobarbital. Demographics, ...