High-resolution multimodal profiling of human epileptic brain activity via explanted depth electrodes.

The availability and integration of electrophysiological and molecular data from the living brain is critical in understanding and diagnosing complex human disease. Intracranial stereo electroencephalography (SEEG) electrodes used for identifying the seizure focus in patients with epilepsy could enable the integration of such multimodal data. Here, we report multimodal profiling of epileptic brain activity via explanted depth electrodes (MoPEDE), a method that recovers extensive protein-coding transcripts, including cell type markers, DNA methylation, and short variant profiles from explanted SEEG electrodes matched with electrophysiological and radiological data allowing for high-resolution reconstructions of brain structure and function.

Oligoepilepsy and lifelong seizure susceptibility in epilepsy with generalized tonic-clonic seizures alone: Experience at an adult tertiary center.

Objective: Epilepsy with generalized tonic-clonic seizures alone (GTCA) is the least studied syndrome within the idiopathic generalized epilepsy (IGE) spectrum. We characterize a large cohort of adult patients with GTCA to understand natural history and drug responsiveness.

Methods: In this retrospective single-center study using our epilepsy electronic record, we evaluated clinical characteristics, seizure outcomes, anti-seizure medication (ASM) response including seizure recurrence after ASM withdrawal, and sex differences in a cohort of GTCA patients aged ≥17 years.

Somatic variants as a cause of drug-resistant epilepsy including mesial temporal lobe epilepsy with hippocampal sclerosis.

Objective: The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology of malformations of cortical development. The aim of this study was to determine the diagnostic yield of somatic variants in genes that have been previously associated with a somatic or germline epilepsy model, ascertained from resected brain tissue from patients with multidrug-resistant focal epilepsy.

Methods: Forty-two patients were recruited across three categories: (1) malformations of cortical development, (2) mesial temporal lobe epilepsy with hippocampal sclerosis, and (3) nonlesional focal epilepsy.

Vagus nerve stimulation in refractory idiopathic generalised epilepsy: An Irish retrospective observational study.

Objective: Refractory idiopathic generalised epilepsy (IGE; also known as genetic generalised epilepsy) is a clinical challenge due to limited available therapeutic options. While vagus nerve stimulation (VNS) is approved as an adjunctive treatment for drug-resistant focal epilepsy, there is limited evidence supporting its efficacy for refractory IGE.

Methods: We conducted a single-centre retrospective analysis of adult IGE patients treated with VNS between January 2003 and January 2022.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Adjunctive cenobamate in highly active and ultra-refractory focal epilepsy: A "real-world" retrospective study.

Objective: Recent clinical trials have shown that cenobamate substantially improves seizure control in focal-onset drug-resistant epilepsy (DRE). However, little is known about cenobamate's performance in highly active (≥20 seizures/month) and ultra-refractory focal epilepsy (≥6 failed epilepsy treatments, including antiseizure medications [ASMs], epilepsy surgery, and vagus nerve stimulation). Here, we studied cenobamate's efficacy and tolerability in a "real-world" severe DRE cohort.

A retrospective study of the correlation between duration of monitoring in the epilepsy monitoring unit and diagnostic yield.

Objective: Long-term video-electroencephalographic (LTVEM) monitoring is a valuable tool in the evaluation of paroxysmal clinical events. However, vEEG itself is costly. Hence, we aimed to establish if longer duration of monitoring (DOM) is associated with higher diagnostic yield.

Genomics in the presurgical epilepsy evaluation.

Epilepsy surgery should be considered in all patients with drug-resistant focal epilepsy. The diagnostic presurgical evaluation aims to delineate the epileptogenic zone and its relationship to eloquent brain regions. Genetic testing is not yet routine in presurgical evaluations, despite many monogenic causes of severe epilepsies, including some focal epilepsies.

A Case of GCH-1 Mutation Dopa-Responsive Dystonia Requiring High Doses of Levodopa for Treatment.

Background: Mutations in the GCH-1 gene are associated with Autosomal Dominant Dopamine Responsive Dystonia (DYT 5). One of the hallmarks of this condition is dramatic and sustained response to low doses of levodopa.

Case Report: We present the case of a 22 year old female patient with genetically confirmed GCH-1 Dopa-Responsive Dystonia who had no response to low dose Levodopa but who achieved symptom control on a total dose of 900 mg/day.

Association of Missense Variants With Genetic Epilepsy With Febrile Seizures Plus.

Objective: To identify the causative gene in a large unsolved family with genetic epilepsy with febrile seizures plus (GEFS+), we sequenced the genomes of family members, and then determined the contribution of the identified gene to the pathogenicity of epilepsies by examining sequencing data from 2,772 additional patients.

Methods: We performed whole genome sequencing of 3 members of a GEFS+ family. Subsequently, whole exome sequencing data from 1,165 patients with epilepsy from the Epi4K dataset and 1,329 Australian patients with epilepsy from the Epi25 dataset were interrogated.

Analysis of the aetiology of epilepsy in 3,216 adult patients attending a tertiary referral center enabled by an electronic patient record.

Purpose: The aim of this study was to review the causes of the epilepsies in our institution, an adult tertiary referral center for neurology and neurosurgery in Dublin, Ireland. Data was obtained from a bespoke epilepsy electronic patient record (EPR).

Methods: Predetermined search parameters of well-established broad categories of epilepsy aetiology were used to identify patients with a diagnosis of epilepsy attending Beaumont Hospital, Dublin.