Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

Background: Prenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment.

Objectives: To examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy.

Methods: We included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, Father, and Child Cohort Study.

Prenatal Exposure to Antiseizure Medication and Incidence of Childhood- and Adolescence-Onset Psychiatric Disorders.

Importance: Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points have not been studied.

Objective: To examine the association between prenatal exposure to ASM with a spectrum of psychiatric disorders in childhood and adolescence in children of mothers with epilepsy.

Design, Setting, And Participants: This prospective, population-based register study assessed 4 546 605 singleton children born alive in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017.

Health-related quality of life in adults with drug-resistant focal epilepsy treated with modified Atkins diet in a randomized clinical trial.

Ketogenic diet, a high-fat, low-carbohydrate diet, is an established treatment for patients with severe epilepsy. We have previously reported a moderate reduction in seizure frequency after treatment with a modified Atkins diet. This study aimed to see whether dietary therapy impacts patients' health-related quality of life (HRQOL).

Identification of novel genomic risk loci shared between common epilepsies and psychiatric disorders.

Psychiatric disorders and common epilepsies are heritable disorders with a high comorbidity and overlapping symptoms. However, the causative mechanisms underlying this relationship are poorly understood. Here we aimed to identify overlapping genetic loci between epilepsy and psychiatric disorders to gain a better understanding of their comorbidity and shared clinical features.

Development and validation of a new non-disease-specific survey tool to assess self-reported adherence to medication.

Patients' non-adherence to medication affects both patients themselves and healthcare systems. Consequences include higher mortality, worsening of disease, patient injuries, and increased healthcare costs. Many existing survey tools for assessing adherence are linked to specific diseases and assessing medication-taking behavior or identifying barriers or beliefs.

Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations.

Objective: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype.

Methods: We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose.

Bidirectionality of antiseizure and antipsychotic treatment: A population-based study.

Purpose: To study the prevalence and directionality of comorbid epilepsy and psychosis in Norway.

Methods: The Norwegian Prescription Database (NorPD) provided individual-based information on all antiseizure medications (ASMs) and antipsychotic drugs (APDs) dispensed during 2004-2017. Subjects were ≥18 years of age at the end of the study period.

Germline homozygous missense DEPDC5 variants cause severe refractory early-onset epilepsy, macrocephaly and bilateral polymicrogyria.

DEPDC5 (DEP Domain-Containing Protein 5) encodes an inhibitory component of the mammalian target of rapamycin (mTOR) pathway and is commonly implicated in sporadic and familial focal epilepsies, both non-lesional and in association with focal cortical dysplasia. Germline pathogenic variants are typically heterozygous and inactivating. We describe a novel phenotype caused by germline biallelic missense variants in DEPDC5.

Monogenic developmental and epileptic encephalopathies of infancy and childhood, a population cohort from Norway.

Introduction: Developmental and epileptic encephalopathies (DEE) is a group of epilepsies where the epileptic activity, seizures and the underlying neurobiology contributes to cognitive and behavioral impairments. Uncovering the causes of DEE is important in order to develop guidelines for treatment and follow-up. The aim of the present study was to describe the clinical picture and to identify genetic causes in a patient cohort with DEE without known etiology, from a Norwegian regional hospital.

Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): II. Drugs in more advanced clinical development.

The Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI) was held in Madrid, Spain on May 22-25, 2022 and was attended by 157 delegates from 26 countries representing basic and clinical science, regulatory agencies, and pharmaceutical industries. One day of the conference was dedicated to sessions presenting and discussing investigational compounds under development for the treatment of seizures and epilepsy. The current progress report summarizes recent findings and current knowledge for seven of these compounds in more advanced clinical development for which either novel preclinical or patient data are available.

Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): I. Drugs in preclinical and early clinical development.

The Eilat Conferences have provided a forum for discussion of novel treatments of epilepsy among basic and clinical scientists, clinicians, and representatives from regulatory agencies as well as from the pharmaceutical industry for 3 decades. Initially with a focus on pharmacological treatments, the Eilat Conferences now also include sessions dedicated to devices for treatment and monitoring. The Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI) was held in Madrid, Spain, on May 22-25, 2022 and was attended by 157 delegates from 26 countries.

Genome-wide decrease in DNA methylation in adults with epilepsy treated with modified ketogenic diet: A prospective study.

Objective: The aim of this study was to investigate the impact of the modified ketogenic diet on DNA methylation in adults with epilepsy.

Methods: In this prospective study, we investigated the genome-wide DNA methylation in whole blood in 58 adults with epilepsy treated with the modified ketogenic for 12 weeks. Patients were recruited from the National Center for Epilepsy, Norway, from March 1, 2011 to February 28, 2017.

ANT-DBS in epilepsy shows no effect on selected neuropsychiatric tests.

Objectives: Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) is an established option in treatment-resistant epilepsy and obtained FDA approval in 2018. Increased psychiatric comorbidity is well known in epilepsy. The main objective of this study was to investigate possible neuropsychiatric treatment-related changes in patients receiving ANT-DBS.

Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability.

Importance: Women with epilepsy frequently need antiseizure medication (ASM) to prevent seizures in pregnancy. Risk of neurodevelopmental disorders after prenatal exposure to AMSs is uncertain.

Objective: To determine whether children exposed prenatally to ASMs in monotherapy and duotherapy have increased risk of neurodevelopmental disorders.

Efficacy, tolerability and pharmacokinetic variability of brivaracetam in adults with difficult-to-treat epilepsy.

Purpose: Brivaracetam (BRV) is one of our latest antiseizure medications (ASMs). It is an analogue of levetiracetam with limited real-life experience. The purpose of this study was to evaluate clinical experience with BRV with focus on efficacy, tolerability and pharmacokinetic variability among adult patients with difficult-to-treat epilepsy.

Folic Acid and Risk of Preterm Birth, Preeclampsia, and Fetal Growth Restriction Among Women With Epilepsy: A Prospective Cohort Study.

Background And Objectives: Women with epilepsy treated with antiseizure medication (ASM) have increased risk of pregnancy complications including preterm birth, fetal growth restriction, and preeclampsia. We aimed to investigate whether folic acid supplementation is associated with these pregnancy complications in women with epilepsy using ASM.

Methods: Singleton pregnancies in the prospective Norwegian Mother and Child Cohort Study (MoBa) (1999-2008) were included.

Reappraisal of the Medical Research Council Antiepileptic Drug Withdrawal Study: Contamination-adjusted and dose-response re-analysis.

Objective: The 1991 Medical Research Council (MRC) Study compared seizure relapse for seizure-free patients randomized to withdraw vs continue of antiseizure medications (ASMs). We re-analyzed this trial to account for crossover between arms using contamination-adjusted intention to treat (CA ITT) methods, to explore dose-response curves, and to validate predictions against external data. ITT assesses the effect of being randomized to withdraw, as-treated analysis assesses the confounded effect of withdrawing, but CA ITT assesses the unconfounded effect of actually withdrawing.

Changes in the use of antiseizure medications in children and adolescents in Norway, 2009-2018.

Background: The use of antiseizure medications (ASMs) in the pediatric population is poorly studied. The purpose of this study was to investigate changes in the use of ASMs in children and adolescents compared to adults, and to elucidate safety considerations of certain drugs.

Method: In this population-based pharmacoepidemiological study we used the Norwegian Prescription Database (NorPD), 2009-2018.

Substantial early changes in bone and calcium metabolism among adult pharmacoresistant epilepsy patients on a modified Atkins diet.

Objective: The aim of this study was to investigate whether the modified Atkins diet (MAD), a variant of the ketogenic diet, has an impact on bone- and calcium (Ca) metabolism.

Methods: Two groups of adult patients with pharmacoresistant epilepsy were investigated. One, the diet group (n = 53), was treated with MAD for 12 weeks, whereas the other, the reference group (n = 28), stayed on their habitual diet in the same period.

Norwegian population-based study of long-term effects, safety, and predictors of response of vagus nerve stimulation treatment in drug-resistant epilepsy: The NORPulse study.

Objective: This study was undertaken to evaluate the efficacy of vagus nerve stimulation (VNS) over time, and to determine which patient groups derive the most benefit.

Methods: Long-term outcomes are reported in 436 epilepsy patients from a VNS quality registry (52.8% adults, 47.

Association Between Antiseizure Drug Monotherapy and Mortality for Patients With Poststroke Epilepsy.

Importance: There is little evidence to guide the choice of antiseizure medication (ASM) for patients with poststroke epilepsy. Theoretical concerns about detrimental effects of ASMs on survival exist. Enzyme-inducing drugs could interfere with secondary stroke prevention.

Lamotrigine effects on immune gene expression in larval zebrafish.

Purpose: Despite growing evidence that neuroinflammation and pro-inflammatory cytokines are involved in the pathogenesis of seizures and epilepsy, this knowledge has not been incorporated in the proposed mechanism of action of any of the current antiseizure medications (ASMs). Here, we tested the hypothesis by assessing inflammation markers in larval zebrafish (Danio rerio) exposed to lamotrigine (LTG).

Methods: In order to establish the most appropriate LTG concentrations for the transcriptome analysis (RNAseq), we initially assessed for teratogenic (spinal cord deformation, heart oedema, failed inflation of the swim bladder) and behavioural effects (distance moved, time spent active, and average swimming speed during a light/dark test) in zebrafish larvae exposed to 0, 50, 100, 300, 500, 750, and 1000 μM LTG continuously between 5 and 120 h post fertilisation.

International Recommendations for the Management of Adults Treated With Ketogenic Diet Therapies.

Objective: To evaluate current clinical practices and evidence-based literature to establish preliminary recommendations for the management of adults using ketogenic diet therapies (KDTs).

Methods: A 12-topic survey was distributed to international experts on KDTs in adults consisting of neurologists and dietitians at medical institutions providing KDTs to adults with epilepsy and other neurologic disorders. Panel survey responses were tabulated by the authors to determine the common and disparate practices between institutions and to compare these practices in adults with KDT recommendations in children and the medical literature.

Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients.

Purpose: To report the clinical outcome of nicotine exposure in patients with autosomal dominant sleep-related hypermotor epilepsy (ADSHE), along with serum concentrations of the major nicotine metabolite cotinine.

Methods: We recruited 17 ADSHE patients with CHRNA4 mutations (12 with p.S280F and 5 with p.

Cognitive change after DBS in refractory epilepsy: A randomized-controlled trial.

Objectives: Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) reduces seizure frequency in patients with refractory epilepsy. There are, however, few studies on treatment-related changes in cognitive functions. The main objective of this study was to investigate cognitive changes in patients receiving ANT-DBS.