Risk of Adverse Pregnancy Outcomes Associated With Antiseizure Medications and Their Indications: A Systematic Review and Meta-Analysis.

Background And Objectives: Aside from congenital malformations and impaired postnatal neurodevelopment, risks associated with antiseizure medication (ASM) use during pregnancy have been sparsely investigated, particularly outside of epilepsy. We aimed to assess these risks through a systematic literature review and meta-analysis, including ASM exposure for indication.

Methods: We searched MEDLINE, EMBASE, and Cochrane for studies including pregnant women on ASMs for any indication and untreated pregnant women, investigating obstetric complications and fetal/neonatal complications other than congenital malformations and impaired neurodevelopment.

Paternal exposure to antiseizure medications and offspring outcomes: a systematic review.

Background: Concerns have recently been raised about risks to the fetus resulting from paternal exposure to antiseizure medications (ASMs). To address these concerns, we conducted a systematic review of the literature to assess neurodevelopmental and anatomical outcomes in offspring born to fathers taking ASMs at the time of conception.

Methods: Electronic searches of MEDLINE, PsycINFO, and Embase were conducted to identify human studies published in English that reported on outcomes, comprising neurodevelopmental disorders, major congenital malformations, small-for-gestational age or low birth weight, in offspring of fathers taking ASMs at conception.

Cognitive outcomes after fetal exposure to carbamazepine, lamotrigine, valproate or levetiracetam monotherapy: Data from the EURAP neurocognitive extension protocol.

Purpose: Prenatal exposure to antiseizure medications (ASMs) has been associated with an increased risk of major malformations and neurodevelopmental disorders, with the latter being mainly associated with valproate (VPA). Our aim was to compare neurocognitive outcome at age 6-7 years in children exposed prenatally to lamotrigine (LTG), carbamazepine (CBZ), valproate (VPA) or levetiracetam (LEV) monotherapy.

Methods: Eligible mother-child pairs were identified from the observational prospective multinational EURAP cohort study.

Safe delivery, perinatal outcomes and breastfeeding in women with epilepsy.

Safe delivery and optimal peripartum and postpartum care in women with epilepsy (WWE) is a major concern which has received limited attention in recent years. A diagnosis of epilepsy per se is not an indication for a planned cesarean section or induction of labor, even though epidemiological studies indicate that cesarean delivery is more common among WWE compared to the general population. Pregnancy in WWE is associated with an increased risk of obstetrical complications and increased perinatal morbidity and mortality, and these risks may be greater among WWE taking ASMs.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Infants, Children, and Adolescents with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes.

Risk of Major Congenital Malformations and Exposure to Antiseizure Medication Monotherapy.

Importance: Women with epilepsy (WWE) require treatment with antiseizure medications (ASMs) during pregnancy, which may be associated with an increased risk of major congenital malformations (MCMs) in their offspring.

Objective: To investigate the prevalence of MCMs after prenatal exposure to 8 commonly used ASM monotherapies and changes in MCM prevalence over time.

Design, Setting, And Participants: This was a prospective, observational, longitudinal cohort study conducted from June 1999 to October 2022.

Stereoselective Analysis of the Antiseizure Activity of Fenfluramine and Norfenfluramine in Mice: Is -Norfenfluramine a Better Follow-Up Compound to Racemic-Fenfluramine?

The aim of this study was to investigate the comparative antiseizure activity of the -enantiomers of ,-fenfluramine and ,-norfenfluramine and to evaluate the relationship between their concentration in plasma and brain and anticonvulsant activity. ,-Fenfluramine, ,-norfenfluramine and their individual enantiomers were evaluated in the mouse maximal electroshock seizure (MES) test. ,-Fenfluramine, ,-norfenfluramine and their individual -enantiomers were also assessed in the DBA/2 mouse audiogenic seizure model.

Which terms should be used to describe medications used in the treatment of seizure disorders? An ILAE position paper.

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English-language terminology applicable to pharmacological agents currently approved for treating seizure disorders.

Call for the use of the ILAE terminology for seizures and epilepsies by health care professionals and regulatory agencies to benefit patients and caregivers.

The International League Against Epilepsy (ILAE) introduced a classification for seizure types in 2017 and updated the classification for epilepsy syndromes in 2022. These classifications aim to improve communication among healthcare professionals and help patients better describe their condition. So far, regulatory agencies have used different terminology.

Pharmacokinetics of d- and l-norfenfluramine following their administration as individual enantiomers in rats.

The effect of fenfluramine and norfenfluramine enantiomers in rodent seizure models and their correlation with the pharmacokinetics of d- and l-fenfluramine in rats have been reported recently. To complement these findings, we investigated the pharmacokinetics of d- and l- norfenfluramine in rat plasma and brain. Sprague-Dawley rats were injected intraperitoneally with 20 mg/kg and 1 mg/kg l- norfenfluramine.

Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults With Focal Epilepsy: A Phase 2b Randomized Clinical Trial.

Importance: Many patients with focal epilepsy experience seizures despite treatment with currently available antiseizure medications (ASMs) and may benefit from novel therapeutics.

Objective: To evaluate the efficacy and safety of XEN1101, a novel small-molecule selective Kv7.2/Kv7.

New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: I. Role of GABA as a Modulator of Seizure Activity and Recently Approved Medications Acting on the GABA System.

γ-Aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter in the mammalian brain and has been found to play an important role in the pathogenesis or the expression of many neurological diseases, including epilepsy. Although GABA can act on different receptor subtypes, the component of the GABA system that is most critical to modulation of seizure activity is the GABA-receptor-chloride (Cl) channel complex, which controls the movement of Cl ions across the neuronal membrane. In the mature brain, binding of GABA to GABA receptors evokes a hyperpolarising (anticonvulsant) response, which is mediated by influx of Cl into the cell driven by its concentration gradient between extracellular and intracellular fluid.

New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development.

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the modulation of neuronal excitability, and a disruption of GABAergic transmission contributes to the pathogenesis of some seizure disorders. Although many currently available antiseizure medications do act at least in part by potentiating GABAergic transmission, there is an opportunity for further research aimed at developing more innovative GABA-targeting therapies. The present article summarises available evidence on a number of such treatments in clinical development.

Drug resistance in epilepsy.

Drug resistance is estimated to affect about a third of individuals with epilepsy, but its prevalence differs in relation to the epilepsy syndrome, the cause of epilepsy, and other factors such as age of seizure onset and presence of associated neurological deficits. Although drug-resistant epilepsy is not synonymous with unresponsiveness to any drug treatment, the probability of achieving seizure freedom on a newly tried medication decreases with increasing number of previously failed treatments. After two appropriately used antiseizure medications have failed to control seizures, individuals should be referred whenever possible to a comprehensive epilepsy centre for diagnostic re-evaluation and targeted management.

Comparative activity of the enantiomers of fenfluramine and norfenfluramine in rodent seizure models, and relationship with their concentrations in plasma and brain.

Objectives: To investigate the comparative antiseizure activity of the individual enantiomers of fenfluramine and its major active primary metabolite norfenfluramine in rodent seizure models, and its relationship with the pharmacokinetics of these compounds in plasma and brain.

Methods: The antiseizure potency of d,l-fenfluramine (racemic fenfluramine) was compared with the respective potencies of its individual enantiomers and the individual enantiomers of norfenfluramine using the maximal electroshock (MES) test in rats and mice, and the 6-Hz 44 mA test in mice. Minimal motor impairment was assessed simultaneously.