Do germline genetic variants influence surgical outcomes in drug-resistant epilepsy?

Objective: We retrospectively explored patients with drug-resistant epilepsy (DRE) who previously underwent presurgical evaluation to identify correlations between surgical outcomes and pathogenic variants in epilepsy genes.

Methods: Through an international collaboration, we evaluated adult DRE patients who were screened for surgical candidacy. Patients with pathogenic (P) or likely pathogenic (LP) germline variants in genes relevant to their epilepsy were included, regardless of whether the genetic diagnosis was made before or after the presurgical evaluation.

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.

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.

Everolimus precision therapy for the GATOR1-related epilepsies: A case series.

Background: Pathogenic variants in the GAP activity towards RAGs 1 (GATOR1) complex genes (DEPDC5, NPRL2, NPRL3) cause focal epilepsy through hyperactivation of the mechanistic target of rapamycin pathway. We report our experience using everolimus in patients with refractory GATOR1-related epilepsy.

Methods: We performed an open-label observational study of everolimus for drug-resistant epilepsy caused by variants in DEPDC5, NPRL2 and NPRL3.

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.

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.

Ictal aphasia in -related autosomal dominant epilepsy with auditory features.

Autosomal dominant epilepsy with auditory features (OMIM 600512) is characterised by focal seizures with distinctive auditory auras and/or ictal aphasia. We describe a 17-year-old girl with recurrent attacks of ictal aphasia and rare nocturnal convulsions. She had a four-generation paternal family history of epilepsy.

Epilepsy in the mTORopathies: opportunities for precision medicine.

The mechanistic target of rapamycin signalling pathway serves as a ubiquitous regulator of cell metabolism, growth, proliferation and survival. The main cellular activity of the mechanistic target of rapamycin cascade funnels through mechanistic target of rapamycin complex 1, which is inhibited by rapamycin, a macrolide compound produced by the bacterium . Pathogenic variants in genes encoding upstream regulators of mechanistic target of rapamycin complex 1 cause epilepsies and neurodevelopmental disorders.

The Diagnostic Yield of Electromyography at Detecting Abnormalities on Muscle Biopsy: A Single Center Experience.

Historically, electromyography (EMG) is utilized early in the diagnostic evaluation of neuromuscular disorders, but its importance may be diminishing with more sophisticated genetic, imaging and immunohistochemistry investigations now available. In the present study, the diagnostic yield of EMG at predicting pathological abnormalities confirmed by muscle biopsy was determined at our neuroscience center. A retrospective study of consecutive cases reviewed at neuromuscular multidisciplinary meetings between 2007 and 2016 identified patients who had EMG and muscle biopsy as part of their diagnostic evaluation.

Unanticipated improvement in seizure control in drug-resistant epilepsy- real world observations.

Objectives: To determine the clinical features and anti-seizure medication (ASM) strategies associated with an unanticipated substantial improvement in seizure control in patients with drug-resistant epilepsy (DRE).

Methods: This retrospective analysis of patients attending a tertiary care epilepsy clinic between 2008 and 2017 identified all patients with active DRE (at least 1 seizure per month for 6 months, despite treatment with 2 different ASMs). All treatment interventions were recorded from when DRE was first identified to the end of the study.

Possible N-methyl-D-aspartate receptor antibody-mediated encephalitis in the setting of HIV cerebrospinal fluid escape.

Discordant elevations of cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) ribonucleic acid (RNA) in chronically treated patients known as 'CSF escape' may present as acute encephalitis. Infectious encephalitis caused by herpes simplex virus (HSV) and other neurotropic viruses have been identified as potential triggers of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Autoantibody-mediated encephalitis has been infrequently reported in HIV infected patients and may mimic HIV encephalitis.