Brugada syndrome and the story of Dave.

Brugada syndrome (BrS) is a little known genetic condition that causes severe disturbances in cardiac rhythm and may result in sudden unexpected cardiac death in an apparently healthy person. The heart structure is typically normal but there are problems with electrical activity. The syndrome is named after Spanish brothers who are cardiologists, Pedro and Josep Brugada. BrS is the major cause of sudden unexplained death syndrome (SUDS), also known as sudden arrhythmic death syndrome (SADS). Following a description of the syndrome, including its prevalence and incidence, how it is diagnosed and how it can be treated, we consider those who survive a cardiac arrest and what problems they may face. Most publications focus on the medical aspects of BrS but, of course, cardiac arrest can result in hypoxic brain damage. We conclude with the story of Dave, a 25-year-old man diagnosed with BrS following a nose bleed and subsequent cardiac arrest. He was left with a visual impairment, dystonia, hypersensitivity, and language and cognitive dysfunction. We look at Dave's strengths and weaknesses, his response to offered treatment, and his consequent improvement. We stress the contributions from members of the multidisciplinary team and offer suggestions for the rehabilitation of other survivors of BrS.

Convulsive seizures and SUDEP in a mouse model of SCN8A epileptic encephalopathy.

De novo mutations of the voltage-gated sodium channel gene SCN8A have recently been recognized as a cause of epileptic encephalopathy, which is characterized by refractory seizures with developmental delay and cognitive disability. We previously described the heterozygous SCN8A missense mutation p.Asn1768Asp in a child with epileptic encephalopathy that included seizures, ataxia, and sudden unexpected death in epilepsy (SUDEP). The mutation results in increased persistent sodium current and hyperactivity of transfected neurons. We have characterized a knock-in mouse model expressing this dominant gain-of-function mutation to investigate the pathology of the altered channel in vivo. The mutant channel protein is stable in vivo. Heterozygous Scn8a(N1768D/+) mice exhibit seizures and SUDEP, confirming the causality of the de novo mutation in the proband. Using video/EEG analysis, we detect ictal discharges that coincide with convulsive seizures and myoclonic jerks. Prior to seizure onset, heterozygous mutants are not defective in motor learning or fear conditioning, but do exhibit mild impairment of motor coordination and social discrimination. Homozygous mutant mice exhibit earlier seizure onset than heterozygotes and more rapid progression to death. Analysis of the intermediate phenotype of functionally hemizygous Scn8a(N1768D/-) mice indicates that severity is increased by a double dose of mutant protein and reduced by the presence of wild-type protein. Scn8a(N1768D) mutant mice provide a model of epileptic encephalopathy that will be valuable for studying the in vivo effects of hyperactive Nav1.6 and the response to therapeutic interventions.

Disclosing Genetic Information to Family Members About Inherited Cardiac Arrhythmias: An Obligation or a Choice?

Inherited cardiac arrhythmias such as long QT syndrome and Brugada syndrome, present clinical as well as ethical, legal, and social challenges. Many individuals who carry a deleterious mutation are largely asymptomatic and therefore may not be diagnosed until after the occurrence of a personal or family member's cardiac event. The familial nature of inherited genetic information raises numerous ethical, legal, and social issues regarding the sharing of genetic information, particularly when an individual found to carry a deleterious mutation refuses to disclose his or her results to at-risk family members who could benefit from life-saving treatments. This qualitative study sought to understand the experiences with genetic testing for individuals (n = 50) with a personal or family history of cardiac events or sudden death. Unstructured in-person focus groups or interviews were conducted for each participant in the study. The recordings of these interviews were transcribed verbatim and subsequently analyzed and coded. Participants' comments regarding sharing of genetic information centered around four main themes: (1) motivation to disclose; (2) extent of disclosure; (3) effect of disclosure on family dynamics; and (4) reasons for not sharing genetic information. The majority of individuals believed that affected individuals are obligated to disclose genetic information to family members. In the era of personalized medicine, the disclosure of genetic information provides individuals the opportunities to learn about the genetics, disease characteristics, and treatment options in order to reduce morbidity and mortality in themselves and their family members. Further research is necessary to identify and explore the barriers to sharing genetic information with at-risk family members.

[Was that something?]. / War da was?

My defi has now saved my life several times in the past. On the other hand it has also often given me a shock in situations which from a medical point of view were not absolutely necessary. In particular it is the coping with this shock which brings me to contradict the standard phrase"Don't be afraid you are protected by the defibrillator!". But I am afraid because my quality of life is substantially impaired not only by the high number of shocks suffered. Each new defi shock triggers in me a series of recurring reaction patterns. There is a tendency to observe by me that with every new shock the restoration of a rudimentary emotional equilibrium always takes longer. However, I want to be able to appear in public again without being accompanied every step of the way by the notion of collapsing in public or to twitch like an electric eel. I can't get used to the idea of an existence as a ticking time bomb.

The psychological impact of implantable cardioverter defibrillator implantation on Brugada syndrome patients.

AIMS: Brugada syndrome (BrS) is a hereditary arrhythmic disease, responsible for sudden death in patients without known heart disease. An implantable cardioverter defibrillator (ICD) is recommended in patients at high risk of sudden death, but the resulting psychological impact has never been studied. The aim of our study was to assess the impact on quality of life of BrS and ICD implantation. METHODS AND RESULTS: Patients were selected from the reference centre for hereditary arrhythmic disease database in Nantes. This population was divided into three groups: Group 1 (G1), symptomatic implanted patients; Group 2 (G2), asymptomatic implanted patients; and Group 3 (G3), asymptomatic patients without ICD. One hundred and ninety questionnaires [36-item short-form health survey (SF-36) and subsidiary questions] were analysed (60 in G1, 78 in G2, and 52 in G3). We failed to identify any difference in the evaluation of the SF-36 between the three groups and the SF-36 score was similar to the French population score. However, specific questions regarding tolerance of the ICD showed that ICD implantation resulted in significant negative impact, especially for professional careers and purchasing insurance, even though the patient considered ICD implantation as reassuring. CONCLUSION: Whatever the group, BrS patients have a good quality of life with no difference between implanted and non-implanted patients. However, ICD implantation is accompanied by difficulties in their social and professional life. This work emphasizes the need to propose specific recommendations applicable to insurance to reduce the complications experienced by these patients.