Rare Genetic Variation and Outcome of Surgery for Mesial Temporal Lobe Epilepsy.

Objective: Genetic factors have long been debated as a cause of failure of surgery for mesial temporal lobe epilepsy (MTLE). We investigated whether rare genetic variation influences seizure outcomes of MTLE surgery.

Methods: We performed an international, multicenter, whole exome sequencing study of patients who underwent surgery for drug-resistant, unilateral MTLE with normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis and ≥2-year postsurgical follow-up.

Germline mosaicism in a family with haploinsufficiency.

Haploinsufficiency of the methyl-CpG-binding domain protein 5 () gene causes a neurodevelopmental disorder that includes intellectual disability, developmental delay, speech impairment, seizures, sleep disturbances, and behavioral difficulties. Microdeletion of 2q23.1 is the most common cause of haploinsufficiency, although haploinsufficiency may also cause this genetic disorder.

Tuberous Sclerosis: A Rare Disease with an Orphan Complex.

Introduction In the Republic of Ireland, there are no tuberous sclerosis complex (TSC) specialist clinics. Methods A clinical audit was carried out to assess the care received by patients attending two specialist adult epilepsy specialist centres, measuring their care against the UK guidelines. Results Although many baseline investigations are carried out, only one-third of patients had diagnostic genetic testing results available.

Modeling native and seeded Synuclein aggregation and related cellular dysfunctions in dopaminergic neurons derived by a new set of isogenic iPSC lines with SNCA multiplications.

Triplication of the SNCA gene, encoding the protein alpha-Synuclein (αSyn), is a rare cause of aggressive and early-onset parkinsonism. Herein, we generated iPSCs from two siblings with a recently described compact SNCA gene triplication and suffering from severe motor impairments, psychiatric symptoms, and cognitive deterioration. Using CRISPR/Cas9 gene editing, each SNCA copy was inactivated by targeted indel mutations generating a panel of isogenic iPSCs with a decremental number from 4 down to none of functional SNCA gene alleles.

A companion to the preclinical common data elements for proteomics, lipidomics, and metabolomics data in rodent epilepsy models. A report of the TASK3-WG4 omics working group of the ILAE/AES joint translational TASK force.

The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force established the TASK3 working groups to create common data elements (CDEs) for various preclinical epilepsy research disciplines. This is the second in a two-part series of omics papers, with the other including genomics, transcriptomics, and epigenomics. The aim of the CDEs was to improve the standardization of experimental designs across a range of epilepsy research-related methods.

Transdiagnostic inflammatory subgroups among psychiatric disorders and their relevance to role functioning: a nested case-control study of the ALSPAC cohort.

Individuals with psychotic disorders and depressive disorder exhibit altered concentrations of peripheral inflammatory markers. It has been suggested that clinical trials of anti-inflammatory therapies for psychiatric disorders should stratify patients by their inflammatory profile. Hence, we investigated whether different subgroups of individuals exist across psychiatric disorders, based on their inflammatory biomarker signatures.

BOK controls ER proteostasis and physiological ER stress responses in neurons.

The Bcl-2 family proteins BAK and BAX control the crucial step of pore formation in the mitochondrial outer membrane during intrinsic apoptosis. Bcl-2-related ovarian killer (BOK) is a Bcl-2 family protein with a high sequence similarity to BAK and BAX. However, intrinsic apoptosis can proceed in the absence of BOK.

A companion to the preclinical common data elements for genomics, transcriptomics, and epigenomics data in rodent epilepsy models. A report of the TASK3-WG4 omics working group of the ILAE/AES joint translational TASK force.

The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force established the TASK3 working groups to create common data elements (CDEs) for various preclinical epilepsy research disciplines. The aim of the CDEs is to improve the standardization of experimental designs across a range of epilepsy research-related methods. Here, we have generated CDE tables with key parameters and case report forms (CRFs) containing the essential contents of the study protocols for genomics, transcriptomics, and epigenomics in rodent models of epilepsy, with a specific focus on adult rats and mice.

The role of common genetic variation in presumed monogenic epilepsies.

Background: The developmental and epileptic encephalopathies (DEEs) are the most severe group of epilepsies which co-present with developmental delay and intellectual disability (ID). DEEs usually occur in people without a family history of epilepsy and have emerged as primarily monogenic, with damaging rare mutations found in 50% of patients. Little is known about the genetic architecture of patients with DEEs in whom no pathogenic variant is identified.

Mechanisms and mathematical modeling of ROS production by the mitochondrial electron transport chain.

Reactive oxygen species (ROS) are recognized both as damaging molecules and intracellular signaling entities. In addition to its role in ATP generation, the mitochondrial electron transport chain (ETC) constitutes a relevant source of mitochondrial ROS, in particular during pathological conditions. Mitochondrial ROS homeostasis depends on species- and site-dependent ROS production, their bioreactivity, diffusion, and scavenging.

A pharmacogenomic assessment of psychiatric adverse drug reactions to levetiracetam.

Objective: Levetiracetam (LEV) is an effective antiseizure medicine, but 10%-20% of people treated with LEV report psychiatric side-effects, and up to 1% may have psychotic episodes. Pharmacogenomic predictors of these adverse drug reactions (ADRs) have yet to be identified. We sought to determine the contribution of both common and rare genetic variation to psychiatric and behavioral ADRs associated with LEV.

Evaluation of policies and practices to support safe and appropriate analgesic and sedative prescribing: The CDRx (controlled drug prescribing) protocol.

Medications provide many therapeutic benefits; however, these must be balanced against the potential for patient harm. Two high-risk medications are benzodiazepine receptor agonists or BZRAs (including benzodiazepines and Z-drugs hypnotics) and opioid analgesics, which carry a risk of dependence, misuse, and abuse. Use of these medications has been growing internationally, along with associated morbidity and mortality.

Expert Perspective: Who May Benefit Most From the New Ultra Long-Term Subcutaneous EEG Monitoring?

Today's modalities for short-term monitoring of EEG are primarily meant for supporting clinical diagnosis of epilepsy or classifying seizures and interictal epileptiform discharges while long-term EEG adds the value of differential diagnosis investigation or pre-surgical evaluation. However, longitudinal epilepsy care relies on patient diaries, which is known to be unreliable for most patients and especially those with focal impaired awareness or nocturnal seizures. The subcutaneous ultra long-term EEG (ULT-EEG) systems alleviate those issue by enabling objective, continuous EEG monitoring for days, weeks, months, or years.

Concordance between PCR-based extraction-free saliva and nasopharyngeal swabs for SARS-CoV-2 testing.

: Saliva represents a less invasive alternative to nasopharyngeal swab (NPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. SalivaDirect is a nucleic acid extraction-free method for detecting SARS-CoV2 in saliva specimens. Studies evaluating the concordance of gold standard NPS and newly developed SalivaDirect protocols are limited.

NRXN1α is associated with increased excitability in ASD iPSC-derived neurons.

Background: NRXN1 deletions are identified as one of major rare risk factors for autism spectrum disorder (ASD) and other neurodevelopmental disorders. ASD has 30% co-morbidity with epilepsy, and the latter is associated with excessive neuronal firing. NRXN1 encodes hundreds of presynaptic neuro-adhesion proteins categorized as NRXN1α/β/γ.

Impact of the COVID-19 pandemic on people with epilepsy: Findings from the Brazilian arm of the COV-E study.

Unlabelled: The COVID-19 pandemic has had an unprecedented impact on people and healthcare services. The disruption to chronic illnesses, such as epilepsy, may relate to several factors ranging from direct infection to secondary effects from healthcare reorganization and social distancing measures.

Objectives: As part of the COVID-19 and Epilepsy (COV-E) global study, we ascertained the effects of COVID-19 on people with epilepsy in Brazil, based on their perspectives and those of their caregivers.

Exploring the prevalence and profile of epilepsy across Europe using a standard retrospective chart review: Challenges and opportunities.

Objective: This study aimed to determine the prevalence of epilepsy in four European countries (Austria, Denmark, Ireland, and Romania) employing a standard methodology. The study was conducted under the auspices of ESBACE (European Study on the Burden and Care of Epilepsy).

Methods: All hospitals and general practitioners serving a region of at least 50 000 persons in each country were asked to identify patients living in the region who had a diagnosis of epilepsy or experienced a single unprovoked seizure.

Postictal Psychosis in Epilepsy: A Clinicogenetic Study.

Objective: Psychoses affecting people with epilepsy increase disease burden and diminish quality of life. We characterized postictal psychosis, which comprises about one quarter of epilepsy-related psychoses, and has unknown causation.

Methods: We conducted a case-control cohort study including patients diagnosed with postictal psychosis, confirmed by psychiatric assessment, with available data regarding epilepsy, treatment, psychiatric history, psychosis profile, and outcomes.

Zonisamide safety in pregnancy: Data from the UK and Ireland epilepsy and pregnancy register.

Background: Animal data suggest teratogenic effects with zonisamide use and risk of pregnancy losses. Human data following zonisamide exposure are presently limited, but suggest low risk of malformation with elevated risk of low birth weight.

Objective: To calculate the major congenital malformation (MCM) rate of zonisamide in human pregnancy and assess for a signal of any specific malformation pattern and associations with birth weight.

tRNA-derived fragments: A new class of non-coding RNA with key roles in nervous system function and dysfunction.

tRNA-derived small RNAs (tsRNA) are a recently identified family of non-coding RNA that have been associated with a variety of cellular functions including the regulation of protein translation and gene expression. Recent sequencing and bioinformatic studies have identified the broad spectrum of tsRNA in the nervous system and demonstrated that this new class of non-coding RNA is produced from tRNA by specific cleavage events catalysed by ribonucleases such as angiogenin and dicer. Evidence is also accumulating that production of tsRNA is increased during disease processes where they regulate stress responses, proteostasis, and neuronal survival.

Genome-Wide Association Study Identifies Risk Loci for Cluster Headache.

Objective: This study was undertaken to identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways.

Methods: We carried out a genome-wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model for each cohort.