Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications.

Resistance to anti-seizure medications (ASMs) presents a significant hurdle in the treatment of people with epilepsy. Genetic markers for resistance to individual ASMs could support clinicians to make better-informed choices for their patients. In this study, we aimed to elucidate whether the response to individual ASMs was associated with common genetic variation.

Predictors of seizure freedom, response and retention after 12 months of treatment with eslicarbazepine acetate: A post-hoc analysis of the Euro-Esli study.

Eslicarbazepine acetate (ESL) is a once-daily antiseizure medication (ASM) that is approved in Europe and the USA for the treatment of focal-onset seizures. The Euro-Esli study, which included over 2000 patients, investigated the real-world effectiveness, safety and tolerability of ESL when used in everyday clinical practice in Europe. This post-hoc analysis of Euro-Esli employed univariate and multivariate binary logistic regression analyses to investigate the relationship between demographic and baseline characteristics (including epilepsy- and treatment-related factors) and the likelihood of seizure freedom, response and retention in adult patients with focal seizures after 12 months of ESL treatment in the real-world setting.

Reversible male infertility with valproate use: A review of the literature.

Sodium valproate is a broad spectrum anti-seizure medication useful in the treatment of both generalized and focal epilepsies. The association between valproate and female reproductive disorders is well understood and delineated. Male infertility however is an under-recognised adverse effect of Valproate therapy.

Multiple Disruptions of Glial-Neuronal Networks in Epileptogenesis That Follows Prolonged Febrile Seizures.

Bi-directional neuronal-glial communication is a critical mediator of normal brain function and is disrupted in the epileptic brain. The potential role of aberrant microglia and astrocyte function during epileptogenesis is important because the mediators involved provide tangible targets for intervention and prevention of epilepsy. Glial activation is intrinsically involved in the generation of childhood febrile seizures (FS), and prolonged FS (febrile status epilepticus, FSE) antecede a proportion of adult temporal lobe epilepsy (TLE).

Derivation of four iPSC lines from a male ASD patient carrying a deletion in the middle coding region of NRXN1α gene (NUIGi039-A and NUIGi039-B) and a male sibling control (NUIGi040-A and NUIGi040-B).

NRXN1 deletions are commonly found in autism spectrum disorder (ASD) and other neurodevelopmental/neuropsychiatric disorders. Derivation of induced pluripotent stem cells (iPSCs) from different diseases involving different deletion regions are essential, as NRXN1 may produce thousands of splicing variants. We report here the derivation of iPSCs from a sibling control and an ASD proband carrying de novo heterozygous deletions in the middle region of NRXN1, using a non-integrating Sendai viral kit.

Derivation of iPSC lines from two patients with autism spectrum disorder carrying NRXN1α deletion (NUIGi041-A, NUIG041-B; NUIGi045-A) and one sibling control (NUIGi042-A, NUIGi042-B).

NRXN1 encodes thousands of splicing variants categorized into long NRXN1α, short NRXN1β and extremely short NRXN1γ, which exert differential roles in neuronal excitation/inhibition. NRXN1α deletions are common in autism spectrum disorder (ASD) and other neurodevelopmental/neuropsychiatric disorders. We derived induced pluripotent stem cells (iPSCs) from one sibling control and two ASD probands carrying NRXN1α, using non-integrating Sendai viral method.

Climate change and epilepsy: Insights from clinical and basic science studies.

Climate change is with us. As professionals who place value on evidence-based practice, climate change is something we cannot ignore. The current pandemic of the novel coronavirus, SARS-CoV-2, has demonstrated how global crises can arise suddenly and have a significant impact on public health.

Aluminum-Induced Alterations in Purinergic System Parameters of BV-2 Brain Microglial Cells.

Aluminum (Al) is ubiquitously present in the environment and known to be a neurotoxin for humans. The trivalent free Al anion (Al) can cross the blood-brain barrier (BBB), accumulate in the brain, and elicit harmful effects to the central nervous system (CNS) cells. Thus, evidence has suggested that Al increases the risk of developing neurodegenerative diseases, particularly Alzheimer's disease (AD).

Derivation of iPSC lines from three young healthy donors of Caucasian origin (NUIGi035-A; NUIGi036-A; NUIGi037-A).

The induced pluripotent stem cell (iPSC) technology has offered an unprecedented opportunity for disease modelling and drug discovery. Here we used non-integrating Sendai viral method and derived iPSCs from three young healthy Caucasian donors. All iPSCs expressed pluripotency markers highly and could be differentiated into three germ lineages.

Evaluating risk to people with epilepsy during the COVID-19 pandemic: Preliminary findings from the COV-E study.

The COVID-19 pandemic has caused global anguish unparalleled in recent times. As cases rise, increased pressure on health services, combined with severe disruption to people's everyday lives, can adversely affect individuals living with chronic illnesses, including people with epilepsy. Stressors related to disruption to healthcare, finances, mental well-being, relationships, schooling, physical activity, and increased isolation could increase seizures and impair epilepsy self-management.

Coupling of autism genes to tissue-wide expression and dysfunction of synapse, calcium signalling and transcriptional regulation.

Autism Spectrum Disorder (ASD) is a heterogeneous disorder that is often accompanied with many co-morbidities. Recent genetic studies have identified various pathways from hundreds of candidate risk genes with varying levels of association to ASD. However, it is unknown which pathways are specific to the core symptoms or which are shared by the co-morbidities.

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.

Temporally Altered miRNA Expression in a Piglet Model of Hypoxic Ischemic Brain Injury.

Hypoxic ischemic encephalopathy (HIE) is the most frequent cause of acquired infant brain injury. Early, clinically relevant biomarkers are required to allow timely application of therapeutic interventions. We previously reported early alterations in several microRNAs (miRNA) in umbilical cord blood at birth in infants with HIE.

Generation of three induced pluripotent stem cell (iPSC) lines from a patient with developmental epileptic encephalopathy due to the pathogenic KCNA2 variant c.869T>G; p.Leu290Arg (NUIGi052-A, NUIGi052-B, NUIGi052-C).

De novo pathogenic variants in KCNA2 are implicated in causing a spectrum of human neurological disorders, in particular developmental and epileptic encephalopathies. KCNA2 encodes the voltage-gated delayed rectifier potassium channel K1.2, which is vital in regulating neuronal membrane potential and repolarization.

Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study.

Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). We conducted a genome-wide association study (GWAS) of 3.

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years.

Testing association of rare genetic variants with resistance to three common antiseizure medications.

Objective: Drug resistance is a major concern in the treatment of individuals with epilepsy. No genetic markers for resistance to individual antiseizure medication (ASM) have yet been identified. We aimed to identify the role of rare genetic variants in drug resistance for three common ASMs: levetiracetam (LEV), lamotrigine (LTG), and valproic acid (VPA).

Derivation of two iPSC lines from a sporadic ASD patient (NUIGi033-A) and a paternal control (NUIGi034-A).

Hundreds of rare risk factors have been identified for ASD, however, the underlying causes for ~70% of sporadic cases are unknown. Sporadic ASD models are thus essential for validating phenotypic commonality and drug suitability to the majority of patients. Here, we derived induced pluripotent stem cells (iPSCs) from one sporadic ASD child and one paternal control, using non-integrating Sendai viral methods.

Plasma microRNA levels in male and female children with cystic fibrosis.

A gender gap exists in cystic fibrosis (CF). Here we investigate whether plasma microRNA expression profiles differ between the sexes in CF children. MicroRNA expression was quantified in paediatric CF plasma (n = 12; six females; Age range:1-6; Median Age: 3; 9 p.

Epilepsy Benchmarks Area III: Improved Treatment Options for Controlling Seizures and Epilepsy-Related Conditions Without Side Effects.

The goals of Epilepsy Benchmark Area III involve identifying areas that are ripe for progress in terms of controlling seizures and patient symptoms in light of the most recent advances in both basic and clinical research. These goals were developed with an emphasis on potential new therapeutic strategies that will reduce seizure burden and improve quality of life for patients with epilepsy. In particular, we continue to support the proposition that a better understanding of how seizures are initiated, propagated, and terminated in different forms of epilepsy is central to enabling new approaches to treatment, including pharmacological as well as surgical and device-oriented approaches.

Derivation of familial iPSC lines from three patients with retinitis pigmentosa carrying an autosomal dominant RPE65 mutation (NUIGi027-A, NUIGi028-A, NUIGi029-A).

Retinitis Pigmentosa (RP) is an inherited disorder of retinal degeneration with progressive loss of rod and cone photoreceptors. RPE65 is a gene encoding the trans-cis isomerase which is essential for the classical visual cycle. While most RPE65 mutations associated with RP have been reported as autosome, an Irish c.

Re-annotation of 191 developmental and epileptic encephalopathy-associated genes unmasks de novo variants in .

The developmental and epileptic encephalopathies (DEE) are a group of rare, severe neurodevelopmental disorders, where even the most thorough sequencing studies leave 60-65% of patients without a molecular diagnosis. Here, we explore the incompleteness of transcript models used for exome and genome analysis as one potential explanation for a lack of current diagnoses. Therefore, we have updated the GENCODE gene annotation for 191 epilepsy-associated genes, using human brain-derived transcriptomic libraries and other data to build 3,550 putative transcript models.

Are patients ready for integrated person-centered care? A qualitative study of people with epilepsy in Ireland.

The National Clinical Programme for Epilepsy (NCPE) in Ireland aims to deliver a holistic model of integrated person-centered care (PCC) that addresses the full spectrum of biomedical and psychosocial needs of people with epilepsy (PwE). However, like all strategic plans, the model encompasses an inherent set of assumptions about the readiness of the environment to implement and sustain the actions required to realize its goals. In this study, through the lens of PwE, the Irish epilepsy care setting was explored to understand its capacity to adopt a new paradigm of integrated PCC.