Epilepsia. Official Journal of the International League Against Epilepsy

Abstract

Objective

A large proportion of pediatric epilepsies have an underlying genetic etiology. Limited studies have explored the efficacy of whole genome sequencing (WGS) in a clinical setting. Our academic–clinical center implemented clinical whole exome sequencing (WES) in 2014, then transitioned to WGS from 2015. We report the diagnostic yield, genetic and phenotypic findings, and prognostic factors following WGS/WES in pediatric epilepsy.

Methods

The cohort included 733 families with pediatric epilepsy who received clinical WGS/WES between 2014 and 2022. WGS/WES was performed at the ...

Abstract

Objective

Deep brain stimulation of the centromedian nucleus of the thalamus (CM-DBS) is an investigational, off-label treatment for drug-resistant epilepsy (DRE) in children. Although emerging evidence supports its safety and efficacy for select indications, the effect of CM-DBS on quality of life and functional outcomes such as school attendance has not been studied. Here, we analyzed data from the prospective CHILD-DBS (Child & Youth Comprehensive Longitudinal Database for Deep Brain Stimulation) to examine the impact of CM-DBS on patient- and caregiver-reported ...

Abstract

Objective

Individuals with epilepsy are at a higher risk of dying suddenly and without explanation, known as sudden unexpected death in epilepsy (SUDEP). Seizures are a risk factor for SUDEP, and nonadherence to antiseizure medication (ASM) increases this risk. We aimed to assess adherence to ASMs at the time of death among young SUDEP cases by comparing prescription claims with postmortem toxicology at an individual level.

Methods

We identified all forensically autopsied SUDEP cases by assessing autopsy reports, toxicology reports, and Danish health ...

Abstract

Objective

Generalized tonic–clonic seizures (GTCS) are considered to be among the most devastating seizures due to increased health risks. Use of device-based therapies, such as vagus nerve stimulation (VNS), is common for those resistant to antiseizure medications and important for those in whom resective surgery is not feasible. Our objective is to investigate whether adjunctive VNS can reduce the frequency of GTCS.

Methods

Participants were enrolled in an international, multicenter, prospective observational study (CORE-VNS) on seizure and nonseizure outcomes following the implantation of ...

Abstract

Objective

The primary purpose was to assess the diagnostic performance of investigations in children with myoclonic epilepsy. The secondary objectives were to examine the definitive syndromic diagnoses and report the outcomes of pediatric myoclonic epilepsies.

Methods

We conducted a retrospective monocentric study from a pediatric center for rare epilepsies. We included pediatric patients investigated for myoclonic epilepsy at our center from 2009 to 2022. Data were collected from their medical records.

Results

Forty-one children were included; 32 (78%) underwent untargeted etiological investigations, including brain magnetic ...

Abstract

Objective

Brain infection with Theiler’s murine encephalomyelitis virus (TMEV) in C57BL/6J mice produces an etiologically relevant model of acquired seizures. Dietary changes can modify seizure presentation following TMEV brain infection and influence intestinal microbiome diversity and composition. Intestinal dysbiosis may thus similarly affect seizure burden and antiseizure medicine (ASM) activity in this model, independent of pharmacokinetic effects. We thus sought to define the influence of antibiotic (ABX)-induced gut dysbiosis on acute seizure presentation, anticonvulsant activity of carbamazepine (CBZ), and CBZ pharmacokinetics ...

Abstract

Objective

Air pollution has been associated with certain neurological disorders, but its association with epilepsy has been insufficiently explored. The study’s objective was to estimate the association of long-term exposure to fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), and ozone (O₃) with the risk of new-onset epilepsy among adults in Ontario, Canada.

Methods

We used a nested case–control study design and linked health and environmental databases, including Ontario residents ages 18 to 80 as of January 1, 2010, without prior diagnoses of seizures ...

Abstract

Objective

This study aimed to identify the determinants of intellectual and developmental outcomes following pediatric hemispherotomy in a large, contemporary multicenter cohort.

Methods

We retrospectively analyzed the intellectual and developmental outcomes of 296 children and adolescents who underwent hemispherotomy between 2000 and 2016 and received a standardized postsurgical evaluation of intelligence or developmental quotient (IQ/DQ). Outcomes at the last follow-up were classified into four categories: normal (IQ/DQ > 85), mildly impaired (IQ/DQ = 70–84), moderately impaired (IQ/DQ = 55–69), or severely impaired (IQ/DQ < 55). Determinants of these outcomes were identified ...

Abstract

Valproic acid (VPA) is a first-line antiseizure medication (ASM) that is highly efficacious for treating generalized and focal epilepsy disorders. Unfortunately, due to its strong association with teratogenic effects culminating in fetal valproate spectrum disorder (FVSD), which may include neurocognitive and neurobehavioral deficits, the drug has become highly regulated/restricted for women of childbearing potential. This includes those who have been shown to respond well to the drug and respond poorly to alternative ASMs. Concurrently, VPA’s neurotoxic, teratogenic mechanisms have been ...