BRIVA-ONE study: 12-month outcomes of brivaracetam monotherapy in clinical practice.

OBJECTIVE: This study investigated the effectiveness and tolerability of brivaracetam (BRV) monotherapy in a large series of patients with epilepsy. METHOD: This was a multicenter, retrospective, observational, non-interventional study in 24 hospitals across Spain. Patients aged ≥18 years who started on BRV monotherapy, either as first-line or following conversion, at least 1 year before database closure were included. Patients were evaluated at baseline and at 3, 6 and 12 months after initiation of BRV monotherapy, in accordance with usual clinical practice at these centers. Data were collected retrospectively from patients' individual charts by participating physicians. The primary effectiveness and safety endpoints were the percentage of seizure-free patients 1 year after initiation of BRV monotherapy and the proportion of patients reporting adverse events (AEs) over the complete follow-up period. Retention rates and subpopulation analysis (levetiracetam switchers, elderly and different etiologies) were also investigated. RESULTS: A total of 276 patients were included (48 with BRV as first-line monotherapy and 228 who converted to BRV monotherapy). The overall retention rate in monotherapy at 12 months was 89.9% (87.5% for first-line monotherapy group; 90.4% for conversion-to-monotherapy group). Seizure-freedom rates at 12 months were 77.8% (75% for first-line monotherapy group; 78.4% for conversion-to-monotherapy group). AEs occurred in 39.5% of patients at 12 months (35.4% for first-line monotherapy group; 40.4% for conversion-to-monotherapy group). Most AEs were mild-to-moderate. The most frequent AEs were irritability (12.3%) and dizziness (10.1%). The most frequent AEs leading to BRV withdrawal were dizziness (1.8%) and memory problems (1.4%). Similar outcomes in terms of effectiveness and tolerability of BRV monotherapy were observed in patients switching from levetiracetam, those with different epilepsy etiologies, and elderly patients. SIGNIFICANCE: BRV was effective and well tolerated both as first-line monotherapy and following conversion to monotherapy in a real-world setting of patients with epilepsy. PLAIN LANGUAGE SUMMARY: The goal of the medical treatment of epilepsy is to ensure best possible patient quality of life, by maximizing seizure control and minimizing medication toxicity. Brivaracetam (BRV) is a new-generation epilepsy treatment that is well tolerated by patients. In our study, monotherapy with BRV reduced seizures in patients who had not received other treatments and in patients who switched from a previous treatment to BRV monotherapy. BRV was well tolerated and also effective in sensitive patients (i.e., the elderly and those who had epilepsy caused by a brain tumor or a brain injury).

Case Report: Probable Myocarditis After Covid-19 mRNA Vaccine in a Patient With Arrhythmogenic Left Ventricular Cardiomyopathy.

Arrhythmogenic left ventricular cardiomyopathy (ALVC) is a rare heritable heart-muscle disorder characterized by a progressive loss of left ventricular myocardium and its replacement by fibrofatty tissue. Myocarditis is an inflammatory disease of the heart that may occur secondary to infections, immune system activation or exposure to drugs. Hot phases of ALVC present with chest pain and troponin rise, mimicking acute viral myocarditis and indicate a progression of the disease. Recently, myocarditis has also been described as an infrequent complication of coronavirus disease 2019 (Covid-19) mRNA vaccines. We herein report for the first time a case of probable myocarditis induced by Covid-19 vaccine in a patient with previous medical history of ALVC. We aim to highlight the common characteristics of ALVC and Covid-19 vaccine myocarditis and work through the differential diagnosis of these two entities.

Novel EGR2 variant that associates with Charcot-Marie-Tooth disease when combined with lipopolysaccharide-induced TNF-α factor T49M polymorphism.

OBJECTIVE: To identify novel genetic mechanisms causing Charcot-Marie-Tooth (CMT) disease. METHODS: We performed a next-generation sequencing study of 34 genes associated with CMT in a patient with peripheral neuropathy. RESULTS: We found a non-previously described mutation in EGR2 (p.P397H). P397H mutation is located within the loop that connects zinc fingers 2 and 3, a pivotal domain for the activity of this transcription factor. Using promoter activity luciferase assays, we found that this mutation promotes decreased transcriptional activity of EGR2. In this patient, we also found a previously described nonpathogenic polymorphism in lipopolysaccharide-induced TNF-α factor (LITAF) (p.T49M). We show that the p.T49M mutation decreases the steady-state levels of the LITAF protein in Schwann cells. Loss of function of LITAF has been shown to produce deregulation in the NRG1-erbB signaling, a pivotal pathway for EGR2 expression by Schwann cells. Surprisingly, our segregation study demonstrates that p.P397H mutation in EGR2 is not sufficient to produce CMT disease. Most notably, only those patients expressing simultaneously the LITAF T49M polymorphism develop peripheral neuropathy. CONCLUSIONS: Our data support that the LITAF loss-of-function interferes with the expression of the transcriptional-deficient EGR2 P397H mutant hampering Schwann cell differentiation and suggest that in vivo both genes act in tandem to allow the proper development of myelin.

[Effect of lacosamide on the quality of life of patients with epilepsy]. / Efecto de la lacosamida sobre la calidad de vida del paciente con epilepsia.

INTRODUCTION: Epilepsy causes psychiatric disorders in 20-40% of patients impacting negatively on their quality of life. Lacosamide is a new antiepileptic as adjunctive therapy in partial seizures with or without generalization. AIM: We conducted a study to assess the impact of lacosamide as to the quality of life of epileptic patients. We used the HAD scale for anxiety and depression and QOLIE-10 scale for quality of life. We evaluated the efficacy and tolerability. PATIENTS AND METHODS: We collected prospectively poorly controlled epileptic patients are and added lacosamide treatment. Baseline visit, at 3 and 6 months were performed. The questionnaires are completed and the epilepsy information has been collected. RESULTS: 31 patients, age 45.5 ± 17.2 years, 64.5% males are included. Number of previous monthly crisis 1.6 ± 1.8. HAD anxiety scale shows a significant improvement at 3 and 6 months. HAD scale for depression reflects a significant improvement in quality parameters. QOLIE-10 shows significant improvement for the group with low quality of life after 3 and 6 months. After 6 months 61.3% of patients have a seizure reduction equal or more than 50% and 54.8% are seizure free. Dizziness is the most common side effect (22.8%). 74.2% continued treatment. CONCLUSIONS: Lacosamide may improve anxiety, depression and quality of life of epileptic patients regardless of seizure control. Response to treatment, adherence and side effects are similar to previous studies.

TITLE: Efecto de la lacosamida sobre la calidad de vida del paciente con epilepsia.Introduccion. La epilepsia provoca trastornos psiquiatricos en un 20-40% de los pacientes y repercute de forma negativa en su calidad de vida. La lacosamida es un nuevo antiepileptico que se utiliza como terapia añadida en crisis parciales con o sin generalizacion. Objetivo. Hemos realizado un estudio para valorar el impacto de la lacosamida en cuanto a la calidad de vida del paciente con epilepsia. Se han utilizado la escala hospitalaria de ansiedad y depresion (HADS) y la escala de calidad de vida en la epilepsia (QOLIE-10). Se ha valorado la eficacia y la tolerabilidad. Pacientes y metodos. Se recogen prospectivamente pacientes con epilepsia mal controlada y a los que se añade lacosamida. Se realiza una visita basal, a los tres y a los seis meses. Se cumplimentan los cuestionarios y se recaban los datos sobre la epilepsia. Resultados. Se incluyen 31 pacientes, con una edad media de 45,5 ± 17,2 años, un 64,5% varones. El numero de crisis mensuales previas es de 1,6 ± 1,8. La HADS para ansiedad muestra una mejoria significativa a los tres y seis meses. La HADS para depresion refleja una mejoria significativa en los parametros cualitativos. La QOLIE-10 muestra mejoria significativa para el grupo con baja calidad de vida previa a los tres y seis meses. Tras seis meses, el 61,3% de los pacientes presenta una reduccion de las crisis igual o superior al 50%, y el 54,8% esta libre de crisis. El mareo es el efecto secundario mas frecuente (22,8%). El 74,2% continua con el tratamiento. Conclusiones. La lacosamida podria mejorar la ansiedad, depresion y calidad de vida del paciente epileptico con independencia del control de las crisis. La respuesta al tratamiento, la adhesion y los efectos secundarios son similares a estudios previos.

[Treatment of neuropathic pain with lacosamide]. / Tratamiento del dolor neuropatico con lacosamida.

INTRODUCTION: Lacosamide is a new antiepileptic drug with a novel mechanism of action, as it selectively promotes the slow inactivation of voltage-dependent sodium channels without affecting fast inactivation. There are studies in the literature regarding its effectiveness in controlling neuropathic pain. CASE REPORTS: We describe the use of intravenous lacosamide in the treatment of three patients with neuropathic pain: a woman with neuropathic pain in the first branch of the right trigeminal nerve during the acute phase of herpes zoster, a woman with central pain secondary to Dejerine-Roussy syndrome due to a malignant brain tumour, and a man with facial pain due to infiltration of the trigeminal nerve by a secondary lymphoma of the central nervous system. In the three cases, the administration of intravenous lacosamide has led to a considerable improvement in pain. The lacosamide dose has been 200 mg/day with excellent tolerability. CONCLUSION: Lacosamide can be an effective and well-tolerated alternative in the treatment of neuropathic pain and, moreover, its intravenous use can achieve pain control faster or be suitable when it is not tolerated orally.