Cenobamate as add-on treatment for SCN8A developmental and epileptic encephalopathy.

Objectives: Developmental and epileptic encephalopathies (DEEs) caused by pathogenic variants in SCN8A are associated with difficult-to-treat and early-onset seizures, developmental delay/intellectual disability, impaired quality of life, and increased risk of early mortality. High doses of sodium channel blockers are typically used to treat SCN8A-DEE caused by gain-of-function (GoF) variants. However, seizures are often drug resistant, and only a few patients achieve seizure freedom.

Fenfluramine treatment in pediatric patients with Dravet syndrome reduces seizure burden and overall healthcare costs: A retrospective and observational real-world study.

Objectives: Dravet syndrome is a developmental and epileptic encephalopathy characterized by early onset epilepsy with multiple seizure types often intractable to treatment. Randomized clinical trials have demonstrated how treatment with fenfluramine significantly reduces seizure frequency in patients with Dravet syndrome. The study aims to (1) describe the efficacy and tolerability of fenfluramine in a Danish cohort of patients with Dravet syndrome; and (2) evaluate whether treatment with fenfluramine reduces epilepsy-related hospital contacts administrated by pediatricians or epilepsy-trained nurses.

Pharmacokinetic Variability of Rufinamide and Stiripentol in Children With Refractory Epilepsy: A Retrospective Study of Therapeutic Drug Monitoring From the National Epilepsy Centers in Denmark and Norway.

Background: Rufinamide and stiripentol, orphan drugs used in Lennox-Gastaut and Dravet syndromes, respectively, are antiseizure medications (ASMs), often administered to children; however, pharmacokinetic studies are lacking. The authors compared the pharmacokinetic variability of these drugs with respect to the dose, serum concentrations, comedication, age, and duration of treatment.

Methods: Children and adolescents (<18 years) whose serum concentrations were measured were retrospectively identified from the therapeutic drug monitoring (TDM) databases at 2 national epilepsy centers in Norway and Denmark (2012-2021).

Pharmacokinetic Variability of Sulthiame: The Impact of Age, Drug-Drug Interactions, and Biochemical Markers of Toxicity in Patients with Epilepsy.

Purpose: Sulthiame is an antiseizure medication increasingly used for epilepsy. The aim of this study was to investigate the pharmacokinetic variability of sulthiame in children and adults with epilepsy with respect to age, comedication, dose, serum concentration, and biochemical markers of toxicity in a clinical setting.

Method: Retrospective quantitative data from the therapeutic drug monitoring (TDM) database at the Section for Clinical Pharmacology, the National Center for Epilepsy, Norway (2015-2021), were used.

Effectiveness and safety of everolimus treatment in patients with tuberous sclerosis complex in real-world clinical practice.

Background: The randomised double-blinded placebo-controlled EXIST-1-3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms in patients with tuberous sclerosis complex (TSC), although evidence of outcomes in clinical practice remains limited. This study aimed to investigate, in clinical practice, the effectiveness and safety of everolimus for epilepsy, renal angiomyolipoma (rAML), and subependymal giant cell astrocytoma (SEGA) in patients with TSC.

Results: The study included 64 patients with TSC (median age: 19, range 0.

Therapeutic Salivary Monitoring of Perampanel in Patients with Epilepsy Using a Volumetric Absorptive Microsampling Technique.

The objective of this study was to validate a novel assay using the volumetric absorptive microsampling (VAMS) technique combined with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the determination of the antiseizure medication perampanel in saliva and its clinical applicability in patients with epilepsy. VAMS tips were loaded with 30 μL of saliva and dried for 60 min. Analytes were extracted with methanol.

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.

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.

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.

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.

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.

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.

Feasibility of transcutaneous auricular vagus nerve stimulation in treatment of drug resistant epilepsy: A multicenter prospective study.

Background: Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a new non-invasive technique developed as treatment option for drug resistant epilepsy. A few studies have been carried out showing that the efficacy and tolerability of ta-VNS is comparable with traditional implanted VNS but the feasibility of the therapy has been poorly described. This study aimed to explore potential clinical benefits of ta-VNS and to evaluate adaptation, compliance, as well as the usability of the device from a service design perspective.

Childhood seizures after prenatal exposure to maternal influenza infection: a population-based cohort study from Norway, Australia and Canada.

Objective: To assess whether clinical and/or laboratory-confirmed diagnosis of maternal influenza during pregnancy increases the risk of seizures in early childhood.

Design: Analysis of prospectively collected registry data for children born between 2009 and 2013 in three high-income countries. We used Cox regression to estimate country-level adjusted HRs (aHRs); fixed-effects meta-analyses were used to pool adjusted estimates.

Effect and tolerability of perampanel in patients with drug-resistant epilepsy.

Objective: Perampanel is one of the most recently approved antiseizure medications. The aim of the present study was to assess clinical efficacy and tolerability, in combination with pharmacokinetic variability, of perampanel treatment in patients at a tertiary referral center for epilepsy.

Methods: We performed a retrospective observational study of patients given perampanel as adjunctive treatment in the period January 2013 - February 2019 at the National Center for Epilepsy at Oslo University Hospital, Norway.

Pharmacokinetic data on brivaracetam, lacosamide and perampanel during pregnancy and lactation.

We present pharmacokinetic data during pregnancy and lactation for brivaracetam, lacosamide and perampanel based on two case studies. Patient 1 used brivaracetam as monotherapy and gave birth to twins. Patient 2 used a combination of brivaracetam, lacosamide and perampanel.

Antiseizure medication in patients with Glioblastoma- a collaborative cohort study.

Purpose: We investigated, whether epileptic seizures (ES) as presenting symptom in adult patients with GBM are associated with better Overall Survival (OS) compared to ES presenting later during the course of GBM, and efficacy and safety of different antiseizure medications (ASMs).

Methods: Retrospective consecutive cohort study of adults with GBM: 50 from Norway and 50 from Italy. We compared the time to changing ASM treatments.

A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies.

Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies.

A retrospective review of changes and challenges in the use of antiseizure medicines in Dravet syndrome in Norway.

Objective: Dravet syndrome is a developmental and epileptic encephalopathy characterized by severe and drug-resistant seizures in early childhood, followed by developmental delay. The purpose of this study was to investigate aspects of pharmacological treatment of Norwegian patients with Dravet syndrome, focusing on the use of antiseizure medicines (ASMs) and identifying treatment challenges.

Methods: Patients were identified through medical registries at the National Center for Epilepsy in Norway and National Center for Rare Epilepsy Related Disorders during 2008-2018.

Pharmacokinetic Variability During Long-Term Therapeutic Drug Monitoring of Valproate, Clobazam, and Levetiracetam in Patients With Dravet Syndrome.

Background: The use of therapeutic drug monitoring (TDM) for antiseizure medications (ASMs) may contribute to treatment optimization in individual patients. This study included patients with Dravet syndrome as they often require close monitoring because of polypharmacy with various ASMs. The aim was to use long-term TDM to investigate pharmacokinetic variability of ASMs in these patients.

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7.

Purpose: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts.

Methods: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers.

Epilepsy and cannabidiol: a guide to treatment.

The growing interest in cannabidiol (CBD), specifically a pure form of CBD, as a treatment for epilepsy, among other conditions, is reflected in recent changes in legislation in some countries. Although there has been much speculation about the therapeutic value of cannabis-based products as an anti-seizure treatment for some time, it is only within the last two years that Class I evidence has been available for a pure form of CBD, based on placebo-controlled RCTs for patients with Lennox-Gastaut syndrome and Dravet syndrome. However, just as we are beginning to understand the significance of CBD as a treatment for epilepsy, in recent years, a broad spectrum of products advertised to contain CBD has emerged on the market.

Therapeutic drug monitoring of antiepileptic drugs: current status and future prospects.

: Antiepileptic drugs (AEDs) are the cornerstone of treatment of patients with epilepsy, and there are presently 27 licensed AEDs making AEDs among the most common medications for which therapeutic drug monitoring (TDM) is performed. The aim of this review is to provide an overview of the current evidence of the use and implementation of AED TDM in patients with epilepsy and other non-epilepsy conditions.: The pharmacokinetic variability of AEDs is extensive, resulting in pronounced variability in serum concentrations between patients.