Predictive factors for successful vagus nerve stimulation in patients with refractory epilepsy: real-life insights from a multicenter study.

Introduction: Vagus nerve stimulation (VNS) therapy is an established treatment for patients with drug-resistant epilepsy that reduces seizure frequency by at least 50% in approximately half of patients; however, the characteristics of the patients with the best response have not yet been identified. Thus, it is important to identify the profile of patients who would have the best response to guide early indications and better patient selection. Methods: This retrospective study evaluated vagus nerve stimulation (VNS) as an adjuvant therapy for patients with drug-resistant epilepsy from six epilepsy centers in Brazil. Data from 192 patients aged 2-66 years were analyzed, and all patients received at least 6 months of therapy to be included. Results: Included patients were aged 2-66 years (25.6 ± 14.3), 105 (54.7%) males and 87 (45.8%) females. Median follow-up interval was 5 years (range, 2005-2018). Overall, the response rate (≥50% seizure reduction) after VNS implantation was 65.6% (126/192 patients). Most patients had 50-90% seizure reduction (60.9%) and nine patients became seizure-free. There were no serious complications associated with VNS implantation. The rate of a ≥ 50% seizure reduction response was significantly higher in patients with no history of neurosurgery. The presence of focal without generalized seizures and focal discharges on interictal EEG was associated with better response. Overall, etiological predictors of a better VNS response profile were tumors while a worse response to VNS was related to the presence of vascular malformations and Lennox-Gastaut Syndrome. Discussion: We observed an association between a better response to VNS therapy no history of neurosurgery, focal interictal epileptiform activity, and focal seizure pattern. Additionally, it is important to highlight that age was not a determinant factor of the response, as children and adults had similar response rates. Thus, VNS therapy should be considered in both adults and children with DRE.

Use of lacosamide in children: experience of a tertiary medical care center in Brazil.

BACKGROUND: Lacosamide (LCM) is a third-generation anti-seizure drug approved in Europe and the United States, either as a monotherapy or adjunctive therapy, to treat partial-onset seizures in adults, adolescents, and children. In Brazil, LCM is licensed for treatment only in patients older than 16 years of age. OBJECTIVE: To evaluate a cohort of children presenting with refractory epilepsy who received LCM as an add-on therapy and observe the response and tolerability to the LCM treatment. METHODS: A retrospective cohort study conducted in a tertiary health care facility, which included 26 children, aged up to 16 years, who presented with refractory epilepsy and received LCM as an add-on treatment. The follow-up visits were scheduled every 3 months until 9 months of treatment with LCM. RESULTS: After 3 months of LCM administration, in 73.1% of the children, there was a reduction of > 50% in the frequency of seizures, and this clinical improvement was maintained in most patients (73.9%) for the following 9 months. Mild (such as, somnolence and behavioral changes) or severe (seizure worsening) adverse effects were observed in two and three children respectively. Among responders to LCM, there was a higher prevalence of males, fewer concomitant anti-seizure drugs, and lower percentage of patients using sodium channel blockers. CONCLUSIONS: Lacosamide should be considered as an early treatment option in pediatric patients with refractory epilepsy, mainly focal seizures.

ANTECEDENTES: Lacosamida (LCM) é um fármaco anticrise de terceira geração aprovado na Europa e nos Estados Unidos, utilizado como monoterapia ou terapia adjuvante para tratar crises epilépticas focais em adultos, adolescentes e crianças. No Brasil, a LCM só é aprovada para tratamento em pacientes com mais de 16 anos de idade. OBJETIVO: Avaliar uma coorte de crianças com epilepsia refratária que receberam LCM como terapia adjuvante e observar a resposta e tolerabilidade ao tratamento. MéTODOS: Um estudo de coorte retrospectivo conduzido em uma unidade terciária de saúde, que incluiu 26 crianças de até 16 anos de idade que apresentavam epilepsia refratária e receberam um tratamento complementar com LCM. As visitas de acompanhamento foram agendadas a cada 3 meses, até 9 meses de tratamento com LCM. RESULTADOS: Após 3 meses de administração de LCM, em 73,1% das crianças, a frequência das crises teve uma redução maior do que 50%, e essa melhora clínica foi mantida na maioria dos pacientes (73,9%) pelos 9 meses seguintes. Efeitos adversos leves (como, sonolência e alterações comportamentais) ou graves (agravamento das crises) foram observados em duas e três crianças, respectivamente. Entre as crianças que responderam ao tratamento com LCM, houve uma maior prevalência do sexo masculino, o uso de um menor número de medicações anticrise associadas e o uso de bloqueadores dos canais de sódio. CONCLUSõES: A LCM deve ser considerada uma opção de tratamento precoce em pacientes pediátricos com epilepsia refratária, principalmente aqueles que apresentam crises focais.

Use of lacosamide in children: experience of a tertiary medical care center in Brazil / Utilização da lacosamida em crianças: experiência de um centro terciário no Brasil

Abstract Background Lacosamide (LCM) is a third-generation anti-seizure drug approved in Europe and the United States, either as a monotherapy or adjunctive therapy, to treat partial-onset seizures in adults, adolescents, and children. In Brazil, LCM is licensed for treatment only in patients older than 16 years of age. Objective To evaluate a cohort of children presenting with refractory epilepsy who received LCM as an add-on therapy and observe the response and tolerability to the LCM treatment. Methods A retrospective cohort study conducted in a tertiary health care facility, which included 26 children, aged up to 16 years, who presented with refractory epilepsy and received LCM as an add-on treatment. The follow-up visits were scheduled every 3 months until 9 months of treatment with LCM. Results After 3 months of LCM administration, in 73.1% of the children, there was a reduction of > 50% in the frequency of seizures, and this clinical improvement was maintained in most patients (73.9%) for the following 9 months. Mild (such as, somnolence and behavioral changes) or severe (seizure worsening) adverse effects were observed in two and three children respectively. Among responders to LCM, there was a higher prevalence of males, fewer concomitant anti-seizure drugs, and lower percentage of patients using sodium channel blockers. Conclusions Lacosamide should be considered as an early treatment option in pediatric patients with refractory epilepsy, mainly focal seizures.

Resumo Antecedentes Lacosamida (LCM) é um fármaco anticrise de terceira geração aprovado na Europa e nos Estados Unidos, utilizado como monoterapia ou terapia adjuvante para tratar crises epilépticas focais em adultos, adolescentes e crianças. No Brasil, a LCM só é aprovada para tratamento em pacientes com mais de 16 anos de idade. Objetivo Avaliar uma coorte de crianças com epilepsia refratária que receberam LCM como terapia adjuvante e observar a resposta e tolerabilidade ao tratamento. Métodos Um estudo de coorte retrospectivo conduzido em uma unidade terciária de saúde, que incluiu 26 crianças de até 16 anos de idade que apresentavam epilepsia refratária e receberam um tratamento complementar com LCM. As visitas de acompanhamento foram agendadas a cada 3 meses, até 9 meses de tratamento com LCM. Resultados Após 3 meses de administração de LCM, em 73,1% das crianças, a frequência das crises teve uma redução maior do que 50%, e essa melhora clínica foi mantida na maioria dos pacientes (73,9%) pelos 9 meses seguintes. Efeitos adversos leves (como, sonolência e alterações comportamentais) ou graves (agravamento das crises) foram observados em duas e três crianças, respectivamente. Entre as crianças que responderam ao tratamento com LCM, houve uma maior prevalência do sexo masculino, o uso de um menor número de medicações anticrise associadas e o uso de bloqueadores dos canais de sódio. Conclusões A LCM deve ser considerada uma opção de tratamento precoce em pacientes pediátricos com epilepsia refratária, principalmente aqueles que apresentam crises focais.

Epilepsy and acute respiratory syndrome ­ related coronavirus 2 (SARS-CoV-2): are people with epilepsy at risk? / Epilepsia e síndrome respiratória aguda relacionada ao coronavírus 2 (SARS-CoV-2): as pessoas com epilepsia estão em risco?

In February 2020, the pandemic disease designated COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has shown to be able to cause severe illness in some patients. Recent studies have hypothesized that the SARS-CoV-2 exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells and so reach the central nervous system1. Amid this context, we have about 50 million people with epilepsy taking antiseizure drugs (ASDs) and or other medications (eg.: steroids, Cannabidiol, etc.) that are at risk to be infected by SARS-CoV-2 virus. So, we did an extensive review in the literature searching for recent studies that had explored the effects of the role of SARS-CoV-2 infection and epilepsy. We did not find evidence of poor outcomes between epilepsy and COVID-19. Regarding ASDs, we have found that enzyme inducers and inhibitors can have significant interactions with drugs that have been used to treat COVID-19 such as antiretrovirals, antibiotics, and antimalarial drugs. In contrast, others have fewer or no interactions with them as such as benzodiazepines, Lamotrigine, Levetiracetam, Topiramate, Perampanel, and so on. Besides that, the management of seizures in epileptic patients and status epilepticus should not be different from the usual protocol. However, the acknowledgment of these potential drug interactions could help in the right choice of ASDs, and also be aware of potential risk drug combinations and the importance in some cases of close monitoring of serum levels and adverse events.

Desde de Fevereiro de 2020, a doença pandêmica conhecida como COVID-19, causada pelo Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) tem se mostrado capaz de acometer gravemente alguns pacientes. Estudos recentes levantaram hipóteses de que o SARSCoV-2 explora o receptor da enzima conversora de angiotensina 2 (ACE2) para entrar no interior das células e atingir o sistema nervoso central1 . Nesse contexto, temos cerca de 50 milhões de pessoas com epilepsia em uso de medicações antiepilépticas (DAEs) e ou outras medicações (como corticoesteroides, Canabidiol, etc.). Por isso, fizemos uma extensa revisão na literatura, buscando estudos recentes que exploraram os efeitos do papel da infecção por SARS-CoV-2 e da epilepsia. Até o momento, não há evidências de que pessoas com epilepsia apresentam prognóstico ruim no que se refere ao COVID-19. No que se refere aos antiepilépticos, foi encontrado que indutores e inibidores enzimáticos são os que apresentam mais interação medicamentosa com drogas utilizadas no tratamento do COVID-19, tais como antirretrovirais, antibióticos, e drogas antimaláricas, enquanto outras apresentam pouca ou nenhuma interação com esses. Além disso, o manejo de crises epilépticas e estado de mal epiléptico não deve diferente do protocolo usual. No entanto, o reconhecimento das potenciais interações medicamentosas nesse contexto pode auxiliar na escolha correta do antiepiléptico, e alertar sobre os potenciais riscos de combinação entre drogas e a importância de em alguns casos monitorizar de perto os níveis séricos e eventos adversos.

Ketogenic Diet and Epilepsy: What We Know So Far.

The Ketogenic Diet (KD) is a modality of treatment used since the 1920s as a treatment for intractable epilepsy. It has been proposed as a dietary treatment that would produce similar benefits to fasting, which is already recorded in the Hippocratic collection. The KD has a high fat content (90%) and low protein and carbohydrate. Evidence shows that KD and its variants are a good alternative for non-surgical pharmacoresistant patients with epilepsy of any age, taking into account that the type of diet should be designed individually and that less-restrictive and more-palatable diets are usually better options for adults and adolescents. This review discusses the KD, including the possible mechanisms of action, applicability, side effects, and evidence for its efficacy, and for the more-palatable diets such as the Modified Atkins Diet (MAD) and the Low Glycemic Index Diet (LGID) in children and adults.