Neuraxial block anesthetic technique in a patient with SCN8A encephalopathy: case report

Abstract Mutations in SCN8A gene lead to changes in sodium channels in the brain, which are correlated with severe epileptic syndrome. Due to the rarity, there are few studies that support anesthesia in that population. The present study aims to report alternatives to inhalation anesthesia at epileptic encephalopathy. Case report: Male, 4 years old, with SCN8A encephalopathy with surgical indication of orchidopexy. Neuroaxis block was performed and dexmedetomidine was used as a pre-anesthetic and sedation. The anestheticsurgical act was uneventful. Conclusion: The association of neuraxial block and dexmedetomidine proved to be a viable alternative for surgery in patients with SCN8A encephalopathy.

Lidocaine in oncological surgery: the role of blocking in voltage-gated sodium channels. A narrative review / Lidocaína em cirurgia oncológica: o papel do bloqueio dos canais de sódio dependentes de voltagem. Revisão narrativa

Abstract Background: The current evidence suggests that oncological surgery, which is a therapy used in the treatment of solid tumors, increases the risk of metastasis. In this regard, a wide range of tumor cells express Voltage-Gated Sodium Channels (VGSC), whose biological roles are not related to the generation of action potentials. In epithelial tumor cells, VGSC are part of cellular structures named invadopodia, involved in cell proliferation, migration, and metastasis. Recent studies showed that lidocaine could decrease cancer recurrence through its direct effects on tumor cells and immunomodulatory properties on the stress response. Objective: The aim of this narrative review is to highlight the role of VGSC in tumor cells, and to describe the potential antiproliferative effect of lidocaine during the pathogenesis of metastasis. Contents: A critical review of literature from April 2017 to April 2019 was performed. Articles found on PubMed (2000-2019) were considered. A free text and MeSH-lidocaine; voltage-gated sodium channels; tumor cells; invadopodia; surgical stress; cell proliferation; metastasis; cancer recurrence - for articles in English, Spanish and Portuguese language - was used. A total of 62 were selected. Conclusion: In animal studies, lidocaine acts by blocking VGSC and other receptors, decreasing migration, invasion, and metastasis. These studies need to be replicated in humans in the context of oncological surgery.

Resumo Justificativa: As evidências atuais sugerem que a cirurgia oncológica, usada no tratamento de tumores sólidos, aumenta o risco de metástase. Nesse sentido, uma ampla gama de células tumorais expressa Canais de Sódio Dependentes de Voltagem (CSDV), cujos papéis biológicos não estão relacionados à produção de potencial de ação. Nas células epiteliais tumorais, o CSDV é parte integrante de estruturas celulares denominadas invadópodes, que participam da proliferação, migração e metástase celular. Estudos recentes mostraram que a lidocaína pode diminuir a recorrência do câncer através de efeitos diretos nas células tumorais e de propriedades imunomoduladoras na resposta ao estresse. Objetivo: O objetivo desta revisão narrativa é analisar o papel do CSDV nas células tumorais e descrever o possível efeito antiproliferativo da lidocaína na patogênese das metástases. Conteúdo: Foi realizada uma revisão crítica da literatura de Abril de 2017 a Abril de 2019. Os artigos encontrados no PubMed (2000 − 2019) foram analisados. Pesquisamos textos de linguagem livre e descritores MeSH-lidocaína; canais de sódio dependentes de voltagem; células tumorais; invadópodes; estresse cirúrgico; proliferação celular; metástase; recorrência do câncer − em artigos publicados em inglês, espanhol e português. Foram selecionadas 62 publicações. Conclusão: Em estudos empregando animais, a lidocaína atua bloqueando o CSDV e outros receptores, diminuindo a migração, invasão e metástase. Esses estudos precisam ser replicados em humanos submetidos a cirurgia oncológica.

[Lidocaine in oncological surgery: the role of blocking in voltage-gated sodium channels. A narrative review]. / Lidocaína em cirurgia oncológica: o papel do bloqueio dos canais de sódio dependentes de voltagem. Revisão narrativa.

BACKGROUND: The current evidence suggests that oncological surgery, which is a therapy used in the treatment of solid tumors, increases the risk of metastasis. In this regard, a wide range of tumor cells express Voltage-Gated Sodium Channels (VGSC), whose biological roles are not related to the generation of action potentials. In epithelial tumor cells, VGSC are part of cellular structures named invadopodia, involved in cell proliferation, migration, and metastasis. Recent studies showed that lidocaine could decrease cancer recurrence through its direct effects on tumor cells and immunomodulatory properties on the stress response. OBJECTIVE: The aim of this narrative review is to highlight the role of VGSC in tumor cells, and to describe the potential antiproliferative effect of lidocaine during the pathogenesis of metastasis. CONTENTS: A critical review of literature from April 2017 to April 2019 was performed. Articles found on PubMed (2000-2019) were considered. A free text and MeSH-lidocaine; voltage-gated sodium channels; tumor cells; invadopodia; surgical stress; cell proliferation; metastasis; cancer recurrence-for articles in English, Spanish and Portuguese language-was used. A total of 62 were selected. CONCLUSION: In animal studies, lidocaine acts by blocking VGSC and other receptors, decreasing migration, invasion, and metastasis. These studies need to be replicated in humans in the context of oncological surgery.

Cardiac channelopathies: The role of sodium channel mutations. / Canalopatias cardíacas: o papel das mutações nos canais de sódio.

INTRODUCTION AND OBJECTIVES: The importance of sodium channels for the normal electrical activity of the heart is emphasized by the fact that mutations (inherited or de novo) in genes that encode for these channels or their associated proteins cause arrhythmogenic syndromes such as the Brugada syndrome and the long QT syndrome (LQTS). The aim of this study is to conduct a review of the literature on the mutations in the sodium channel complex responsible for heart disease and the implications of a close relationship between genetics and the clinical aspects of the main cardiac channelopathies, namely at the level of diagnosis, risk stratification, prognosis, screening of family members and treatment. METHODS: The online Pubmed® database was used to search for articles published in this field in indexed journals. The MeSH database was used to define the following query: "Mutation [Mesh] AND Sodium Channels [Mesh] AND Heart Diseases [Mesh]", and articles published in the last 15 years, written in English or Portuguese and referring to research in human beings were included. CONCLUSIONS: In the past few years, significant advances have been made to clarify the genetic and molecular basis of these syndromes. A greater understanding of the underlying pathophysiological mechanisms showed the importance of the relationship between genotype and phenotype and led to progress in the clinical approach to these patients. However, it is still necessary to improve diagnostic capacity, optimize risk stratification, and develop new specific treatments according to the genotype-phenotype binomial.

Behavior of ion channels controlled by electric potential difference and of Toll-type receptors in neuropathic pain pathophysiology / O comportamento dos canais iônicos controlados por diferença de potencial elétrico e dos receptores do tipo Toll na fisiopatologia da dor neuropática

ABSTRACT BACKGROUND AND OBJECTIVES: Neuropathic pain is a severe and refractory medical condition, for which only partially effective treatments are currently available. Recent experimental data on the role of voltage-gated ion channels, particularly sodium and potassium channels, have been described. In this brief review, we aimed at addressing the role of sodium and potassium channels in the pathophysiology of neuropathic pain and recent evidences about their role as a new therapeutic target in painful conditions. CONTENTS: Pharmacological and biophysical studies have shown that voltage-gated sodium channels, particularly Nav1.3, Nav1.7, Nav1.8, and Nav1.9 isoforms are important in the pathophysiology of neuropathic pain. Similarly, the involvement of voltage-gated potassium channels, especially KV1 and KV7 isoforms, has been clearly shown in the establishment of chronic painful conditions. Recent evidences that ion sodium and potassium channels dysfunction is involved in the development of chronic painful conditions corroborate the possibility of pharmacologically modulate them as new therapeutic strategies. CONCLUSION: Recent evidences suggest that selective sodium channel blockers and potassium channels activating of modulating drugs are important and promising targets in the search for new options to treat neuropathic pain.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor neuropática constitui-se em uma condição clínica grave e refratária, para a qual apenas tratamentos com eficácia parcial estão disponíveis. Estudos experimentais recentes sobre o papel relevante de canais iônicos controlados por diferença de potencial elétrico ou voltagem, especialmente canais de sódio e potássio, tem sido descritos. Nesta breve revisão, objetivou-se abordar o papel dos canais de sódio e potássio na fisiopatologia da dor neuropática e as recentes evidências a respeito do seu papel como novo alvo terapêutico em quadros dolorosos. CONTEÚDO: Estudos farmacológicos e biofísicos tem demonstrado que os canais de sódio dependentes de voltagem, particularmente as isoformas Nav1.3, Nav1.7, Nav1.8 e Nav1.9 são relevantes na fisiopatologia da dor neuropática. De forma similar, o envolvimento dos canais de potássio dependentes de voltagem, especialmente as isoformas Kv1 e Kv7, tem sido claramente demonstrado no estabelecimento de quadros dolorosos crônicos. As evidências recentes de que a disfunção de canais iônicos de sódio e potássio está envolvida no desenvolvimento de quadros dolorosos crônicos evidenciam a capacidade de modulá-los farmacologicamente em novas estratégias terapêuticas. CONCLUSÃO: Evidências recentes sugerem que bloqueadores seletivos de canais de sódio e fármacos ativadores ou moduladores dos canais de potássio representam um alvo relevante e promissor na busca por novas opções no tratamento da dor neuropática.

Efeitos secundários potencialmente desejáveis dos anestésicos locais: [revisão] / Potentially desirable secondary effects of local anesthetics: [review]

Apesar do uso dos anestésicos locais (ALs) ter a finalidade principal de produzir bloqueios nervosos pela inibição dos canais de Na+, a literatura tem mostrado que esses agentes podem ter ações farmacológicas adicionais, afetando também, os canais de potássio e de cálcio e agindo em mecanismos intracelulares. Os ALs podem, além de causar anestesia, agir diretamente sobre outros receptores e suas vias de sinalização que estão envolvidos nos processos de inflamação, ativação plaquetária, nocicepção, dor periférica e arritmias, dentre outras, buscando cada vez mais, uma melhor eficácia e segurança clínica, além de novas e potencialmente úteis propriedades para os ALs. Assim, o objetivo deste estudo foi pesquisar em literatura científica e descrever uma revisão da farmacologia e dos efeitos adicionais potencialmente desejáveis dos principais anestésicos locais usados na clínica médica.

Despite the use of local anesthetics (LAs) having the primary purpose of producing nerve blockages by the inhibition of Na+ channels, the literature has shown that these agents may have additional pharmacological actions, also affecting the potassium and calcium channels and acting on intracellular mechanisms. Besides causing anesthesia, the LAs may act directly on other receptors and their signaling pathways which are involved in processes of inflammation, platelet activation, nociception, peripheral pain and arrhythmias, among others, increasingly seeking better clinical efficacy and safety, in addition to new and potentially useful properties for the LAs. Therefore, the aim of this study is to search the scientific literature and review the pharmacology and the additional potentially desirable effects of the LAs used in medical clinic.

O papel dos canais iônicos nas epilepsias e considerações sobre as drogas antiepilépticas: uma breve revisão / Ion channels role in epilepsy and considers of the antiepileptic drugs: a short review

INTRODUÇÃO: A epilepsia é um transtorno neurológico que chega a afetar cerca de 1 por cento da população mundial. Muitas formas de epilepsias não conseguem ser tratadas adequadamente com os fármacos atualmente utilizados na clínica e o desenvolvimento de novas propostas terapêuticas que as tratem, não apenas de forma sintomática, mas em sua gênese, é uma busca constante de novos estudos. OBJETIVO E DISCUSSÃO: Nesse sentido, a presente revisão busca fazer um breve levantamento sobre os aspectos científicos mais consistentes acerca do papel dos canais iônicos no desenvolvimento das epilepsias, bem como correlacionar com o estudo de drogas antiepilépticas (DAEs) e mostrar as principais características farmacológicas das DAEs mais utilizadas na clínica atualmente. O papel dos canais de Na+ e Ca+2 como alvo de novas DAEs e a participação de outros receptores nesse processo são igualmente discutidos. CONCLUSÃO: A compreensão da fisiopatologia das epilepsias e dos possíveis alvos moleculares para novos fármacos é um dos principais focos para o descobrimento de tratamentos mais eficazes e com menos efeitos adversos.

INTRODUCTION: Current epidemiological studies show a prevalence rate for active epilepsy in 0,5-1 percent of the population. Many forms of epilepsy are intractable to current therapies and there is a pressing need to develop agents and strategies to not only suppress seizures, but also cure epilepsy. OBJECTIVE AND DISCUSSION: The aim of this review was to the recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new informations on the genetics of idiopathic epilepsies, and current antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the a-subunits of voltage gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. CONCLUSION: The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies.

Vasculopatia livedóide: relato de caso com possível evidência de etiopatogenia neurovascular / Livedoid vasculopathy: report of a case with evidence for a possible neurovascular etiopathogenesis

A etiopatogênese da vasculopatia livedóide ainda hoje permanece indeterminada e, apesar de algumas etiologias aventadas, com freqüência elas não apresentam associação com a vasculopatia em seu curso. Os tratamentos descritos na literatura não apresentam resultados reproduzíveis. Relata-se caso de paciente de 42 anos, com vasculopatia livedóide e boa resposta ao tratamento pioneiro com a carbamazepina. A droga foi instituída diante das discretas evidências de inflamação, da inconstância dos achados relacionados às teorias sugeridas, da forte sintomatologia dolorosa e dos recentes relatos da participação neural na coagulação, que levaram os autores a considerar a possibilidade de associação vasculoneural na patogênese dessa vasculopatia.

Etiopathogenesis of livedoid vasculopathy remains elusive, and this condition is still frequently designated as idiopathic or secondary to various disorders. While several etiologies have been proposed, neither are they always associated with the disease, nor do they necessarily include livedoid vasculopathy in their course. Moreover, treatments described in the literature do not present reproducible results. We present the case of a 42-year-old man with livedoid vasculopathy who presented a good response to treatment with carbamazepine, a previously unattempted approach. In view of the very scarce evidence for vascular inflammation, discrepancies in the proposed etiologies of this pathological state and the intense pain that is the hallmark symptom; and considering recent reports on the neural participation in coagulation processes, the authors here address the question of a potential association between the vascular and nervous systems in the etiology of this vasculopathy.