Lamotrigine induced Brugada-pattern in a patient with genetic epilepsy associated with a novel variant in SCN9A.
- 作者列表："Banfi P","Coll M","Oliva A","Alcalde M","Striano P","Mauri M","Princiotta L","Campuzano O","Versino M","Brugada R
BACKGROUND:A 30-year-old man presented with intellectual disability associated with epilepsy. The epilepsy was initially treated with sodium valproate and since he was 28 years-old with lamotrigine. With the addition of lamotrigine, a pattern of Brugada syndrome appeared on the electrocardiogram. The family history was positive for epilepsy from the motheŕs side, who had never been treated with lamotrigine. OBJECTIVE:Determine the genetic cause of the intellectual disability, epilepsy and Brugada syndrome of the patient and try to establish a possible correlation between the genetic background and the Brugada syndrome pattern under lamotrigine treatment. METHODS:A standard karyotype, array comparative genomic hybridization and two different NGS panels have done to the index case to identify the genetic causes of the intellectual disability, epilepsy and Brugada syndrome pattern. RESULTS:Genetic analyses in the family identified a de novo duplication of 1.3 Mb in 8p21.3 as well as two novel heterozygous rare variants in SCN9A and AKAP9 genes, both inherited from the mother. CONCLUSION:We hypothesize that in this family the SCN9A variant was responsible for the epileptic syndrome. In addition, given that SCN9A is lightly expressed in the heart tissue, we postulate that this SCN9A variant, alone or in combination with AKAP9 variant, might be responsible for the Brugada pattern when challenged by lamotrigine.
背景: 一名30岁男性患者出现与癫痫相关的智力障碍。癫痫最初用丙戊酸钠治疗，自28岁开始用拉莫三嗪治疗。随着拉莫三嗪的加入，心电图上出现了Brugada综合征的模式。家族史为癫痫阳性，患者从未接受过拉莫三嗪治疗。 目的: 确定患者智力障碍、癫痫和Brugada综合征的遗传原因，并尝试在拉莫三嗪治疗下建立遗传背景与Brugada综合征模式之间可能的相关性。 方法: 标准核型、阵列比较基因组杂交和两个不同的NGS面板已经对索引病例进行了鉴定智力障碍、癫痫和Brugada综合征模式的遗传原因。 结果: 该家系的遗传分析发现8p21.3中有1.3 Mb的从头重复，SCN9A和AKAP9基因中有两个新的杂合罕见变异，都来自母亲。 结论: 我们假设在这个家族中SCN9A变异是导致癫痫综合征的原因。此外，鉴于SCN9A在心脏组织中轻度表达，我们假设这种SCN9A变体，单独或与AKAP9变体组合，在受到拉莫三嗪挑战时可能是Brugada模式的原因.
METHODS:BACKGROUND AND PURPOSE:The current left atrial appendage (LAA) classification system (cLAA-CS) categorizes it into 4 morphologies: chicken wing (CW), windsock, cactus, and cauliflower, though there is limited data on either reliability or associations between different morphologies and stroke risk. We aimed to develop a simplified LAA classification system and to determine its relationship to embolic stroke subtypes. METHODS:Consecutive patients with ischemic stroke from a prospective stroke registry who previously underwent a clinically-indicated chest CT were included. Stroke subtype was determined and LAA morphology was classified using the traditional system (in which CW = low risk) and a new system (LAA-H/L, in which low risk morphology (LAA-L) was defined as an acute angle bend or fold from the proximal/middle portion of the LAA and high risk morphology (LAA-H) was defined as all others). As a proof of concept study, we determined reliability for the two classification systems, and we assessed the associations between both classification systems with stroke subtypes in our cohort and previous studies. RESULTS:We identified 329 ischemic stroke patients with a qualifying chest CT (126 cardioembolic subtype, 116 embolic stroke of undetermined source (ESUS), and 87 non-cardioembolic subtypes). Intra- and inter-rater agreements improved using the LAA-H/L (0.95 and 0.85, respectively) vs. cLAA-CS (0.50 and 0.40). The LAA-H/L led to classifying 69 LAA morphologies that met criteria for CW as LAA-H. In fully adjusted models, LAA-H was associated with cardioembolic stroke (OR 5.4, 95%CI 2.1-13.7) and ESUS (OR 2.8 95% CI 1.2-6.4). Non-CW morphology was also associated with embolic stroke subtypes, but the effect size was much less pronounced. Studies using the cLAA-CS yielded mixed results for inter- and intra-rater agreements but most showed an association between a non-CW morphology and stroke with no difference among the three non-CW subtypes. CONCLUSION:The LAA-H/L classification system is simple, has excellent intra and inter-rater agreements, and may help risk identify patients with cardioembolic stroke subtypes. Larger studies are needed to validate these findings.
METHODS:PURPOSE:Low-molecular-weight heparins are currently the recommended antithrombotic therapy for treatment and prevention of malignancy-related venous thromboembolism. Currently, the evidence evaluating direct oral anticoagulants versus low-molecular-weight heparins or a vitamin K antagonist in cancer patients with hematologic malignancies is limited. We evaluated the safety and efficacy of direct oral anticoagulants for venous thromboembolism treatment or stroke prevention for non-valvular atrial fibrillation in patients with hematologic malignancies. METHODS:This was a retrospective evaluation of adult patients with hematologic malignancies who received at least one dose of the Food and Drug Administration-approved direct oral anticoagulant for venous thromboembolism treatment or stroke prevention. We determined the frequency of major bleeding events, non-major bleeding events, stroke, systemic embolism, appropriateness of initial direct oral anticoagulant doses, holding practices prior to procedures, and the rate of all-cause mortality. An analysis was also performed to compare the incidence of bleeding between patients with a history of hematopoietic stem cell transplant to non-transplant patients. RESULTS:A total of 103 patients were identified, with the majority of patients receiving rivaroxaban for venous thromboembolism treatment. Major bleeding events occurred in four patients and no fatal bleeding events occurred. Non-major bleeding occurred in 29 patients, most commonly epistaxis and bruising. Two patients experienced a systemic embolism while on direct oral anticoagulant therapy. CONCLUSION:Direct oral anticoagulants may be a safe and effective alternative for anticoagulation therapy in patients with hematologic malignancies. However, larger prospective studies comparing direct oral anticoagulants to low-molecular-weight heparins or vitamin K antagonists are warranted to compare efficacy and safety outcomes in this patient population.
METHODS::It has been over two decades since the very first robotic cardiac surgery was performed. Over the years, there has been an increase in the demand for less invasive cardiac surgical techniques. Developments in technology and engineering have provided an opportunity for robotic surgery to be applied to a variety of cardiac procedures, including coronary revascularisation, mitral valve surgery, atrial fibrillation ablation, and others. In coronary revascularisation, it is becoming more widely used in single vessel, as well as hybrid coronary artery approaches. Currently, several international centres are specialising in a totally endoscopic coronary artery bypass surgery involving multiple vessels. Mitral valve and other intracardiac pathologies such as atrial septal defect and intracardiac tumour are also increasingly being addressed robotically. Even though some studies have shown good results with robot-assisted cardiac surgery, there are still concerns about safety, cost and clinical efficacy. There are also limitations and additional challenges with the management of cardiopulmonary bypass and myocardial protection during robotic surgery. Implementing novel strategies to manage these challenges, together with careful patient selection can go a long way to producing satisfactory results. This review examines the current evidence behind robotic surgery in various aspects of cardiac surgery.