The experience of Colombian boys and young men living with Duchenne muscular dystrophy / A experiência dos meninos e jovens colombianos que vivem com distrofia muscular de Duchenne / L'expérience des garçons et des jeunes hommes colombiens vivant avec dystrophie musculaire de Duchenne / La experiencia de niños y jóvenes colombianos que viven con distrofia muscular de Duchenne

Abstract Duchenne muscular dystrophy (DMD) is a chronic disease that primarily affects males and is characterized by progressive physical impairment and, eventually, death. This qualitative study aimed to explore and understand the experience of diagnosis and disease in young people with DMD living in Bogotá, Colombia. After securing approval from the Research Ethics Committee (CEI-ABN026-000311), nine individuals took part of a semi-structured interview, and their narratives were analyzed using thematic analysis. The main topics developed throughout the narratives were: negative representation of the disease; fear; difficulty expressing emotions; the patient-doctor relationship; the wheelchair; the caregivers and coping strategies. We conclude that young people affected by DMD face several challenging experiences that underscore the need for better, more respectful, and compassionate interactions with healthcare providers. Also, their experiences are indicative of a socio-cultural context that needs to become more responsive and compassionate towards young people and disability.

Resumo A distrofia muscular de Duchenne (DMD) é uma doença crônica que afeta principalmente os homens, caracterizada pelo deterioro físico progressivo e por conduzir à morte. Este estudo qualitativo teve como objetivo a exploração e a compreensão da experiência do diagnóstico e da doença em jovens com DMD residentes em Bogotá, Colômbia. Após a aprovação do Comitê de Ética em Pesquisa (CEI-ABN026-000311), nove participantes participaram numa entrevista semiestruturada e as suas narrativas foram analisadas através da análise temática. Os principais temas abordados foram: a representação negativa da doença; o medo; a dificuldade em expressar emoções; a relação paciente-médico; a cadeira de rodas; os cuidadores e as estratégias de resiliência. Concluímos que os jovens afetados pela DMD enfrentam experiências desafiantes que evidenciam a necessidade de interações melhores, mais respeitosas e compassivas com os profissionais de saúde. Ao mesmo tempo, as suas experiências são indicativas de um contexto sociocultural que precisa de se tornar mais recetivo e compassivo para com os jovens e as deficiências.

Résumé La Dystrophie Musculaire de Duchenne (DMD) est une maladie chronique qui touche principalement les hommes et se caractérise par détérioration physique progressive et, éventuellement, la mort. Cette rechérche qualitative a explorer l'expérience du diagnostic et de la maladie chez les jeunes atteints de DMD à Bogotá, Colombie. Cette rechérche a été évaluée et approuvée par un comité d'éthique de la recherche (CEI-ABN026-000311). Neuf jeunes ont participé à un entretien semi-structuré et leurs récits ont été analysés à l'aide d'une analyse thématique. Les principaux thèmes développés dans les récits étaient: la représentation négative de la maladie; peur; difficulté à exprimer ses émotions; la relation médecin-patient; le fauteuil roulant; soignants et stratégies d'adaptation. Nous concluons que les jeunes touchés par la DMD vivent de multiples expériences difficiles qui mettent en évidence la nécessité d'interactions plus respectueuses et plus compatissantes avec les prestataires de services de santé. En même temps, leurs expériences montrent un contexte socioculturel qui doit être plus sensible et compatissant envers les enfants et les jeunes handicapés.

Resumen La distrofia muscular de Duchenne (DMD) es una enfermedad crónica que afecta principalmente a hombres y se caracteriza por deterioro físico progresivo y, eventualmente, la muerte. Este estudio cualitativo buscó explorar y comprender la experiencia del diagnóstico y la enfermedad en jóvenes con DMD en la ciudad de Bogotá, Colombia. Tras recibir autorización del Comité de Ética en Investigación (CEI-ABN026-000311), nueve participantes colaboraron con una entrevista semiestructurada y sus narrativas fueron analizadas usando análisis temático. Los principales temas desarrollados en las narrativas fueron: representación negativa de la enfermedad; miedo; dificultad expresando emociones; la relación médico-paciente; la silla de ruedas; los cuidadores y las estrategias de afrontamiento. Concluimos que los jóvenes afectados por la DMD enfrentan múltiples experiencias retadoras que hacen evidente la necesidad de interacciones más respetuosas y compasivas con los proveedores de servicios de salud. Al mismo tiempo, sus experiencias muestran un contexto sociocultural que necesita ser más sensible y compasivo con los niños y jóvenes en situación de discapacidad.

Exercise biology of neuromuscular disorders.

Neuromuscular disorders (NMDs) are chronic conditions that affect the neuromuscular system. Many NMDs currently have no cure; however, as more effective therapies become available for NMD patients, these individuals will exhibit improved health and/or prolonged lifespans. As a result, persons with NMDs will likely desire to engage in a more diverse variety of activities of daily living, including increased physical activity or exercise. Therefore, there is a need to increase our knowledge of the effects of acute exercise and chronic training on the neuromuscular system in NMD contexts. Here, we discuss the disease mechanisms and exercise biology of Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), and myotonic dystrophy type 1 (DM1), which are among the most prevalent NMDs in children and adults. Evidence from clinical and preclinical studies are reviewed, with emphasis on the functional outcomes of exercise, as well as on the putative cellular mechanisms that drive exercise-induced remodelling of the neuromuscular system. Continued investigation of the molecular mechanisms of exercise adaptation in DMD, SMA, and DM1 will assist in enhancing our understanding of the biology of these most prevalent NMDs. This information may also be useful for guiding the development of novel therapeutic targets for future pursuit.

Na+-H+ exchanger and proton channel in heart failure associated with Becker and Duchenne muscular dystrophies.

Cardiomyopathy is found in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies, which are linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects are not limited to DMD but are also present in mild BMD. The hereditary cardiomyopathic hamster of the UM-X7.1 strain is a particular experimental model of heart failure (HF) leading to early death in muscular dystrophy (dystrophin deficiency and sarcoglycan mutation) and heart disease (δ-sarcoglycan deficiency and dystrophin mutation) in human DMD. Using this model, our previous work showed a defect in intracellular sodium homeostasis before the appearance of any apparent biochemical and histological defects. This was attributed to the continual presence of the fetal slow sodium channel, which was also found to be active in human DMD. Due to muscular intracellular acidosis, the intracellular sodium overload in DMD and BMD was also due to sodium influx through the sodium-hydrogen exchanger NHE-1. Lifetime treatment with an NHE-1 inhibitor prevented intracellular Na+ overload and early death due to HF. Our previous work also showed that another proton transporter, the voltage-gated proton channel (Hv1), exists in many cell types including heart cells and skeletal muscle fibers. The Hv1 could be indirectly implicated in the beneficial effect of blocking NHE-1.

[Phenotypic heterogeneity and phenotype-genotype correlations in dystrophinopathies: Contribution of genetic and clinical databases]. / Variabilité phénotypique et corrélations génotype-phénotype des dystrophinopathies : contribution des banques de données.

The objective of this work was to study the natural history of dystrophinopathies and the genotype-phenotype correlations made possible by the development of the clinical part of the French DMD database. The collection of 70,000 clinical data for 600 patients with an average longitudinal follow-up of 12years enabled clarification of the natural history of Duchenne and Becker muscular dystrophies and clinical presentations in symptomatic females. We were able to specify the phenotypic heterogeneity of motor, orthopedic and respiratory involvements (severe, standard and intermediary form), of the cardiac disorder (severe, standard or absent cardiomyopathy, absence of correlation between motor and cardiac involvements), and of brain function (mental deficiency in the patients with Becker muscular dystrophy, psychopathological disorders in dystrophinopathies). Phenotypic variability did not correlate with a specific mutational spectrum. We propose a model of phenotypic analysis based on the presence or not of muscular and cardiac involvements (described by age at onset and rate of progression) and brain involvement (described by the type and the severity of the cognitive impairment and of the psychological disorders). The methodology developed for the DMD gene can be generalized and used for other databases dedicated to genetic diseases. Application of this model of phenotypic analysis for each patient and further development of the database should contribute substantially to clinical research providing useful tools for future clinical trials.

Evolution of life expectancy of patients with Duchenne muscular dystrophy at AFM Yolaine de Kepper centre between 1981 and 2011.

OBJECTIVES: Retrospective study over the last 30 years of life expectancy in patients suffering from Duchenne muscular dystrophy (DMD). Analysis of the role of ventilatory assistance and causes of death. PATIENTS AND METHODS: One hundred and nineteen adult DMD patients were hosted during 1981 to 2011 at AFM Yolaine de Kepper centre, Saint-Georges-sur-Loire, France. Patients' life expectancy was calculated using Kaplan-Meier model. RESULTS: Life expectancy without or with ventilatory assistance was 22.16 and 36.23 years, respectively. Similarly, life expectancy of patients born from 1970 (mostly with ventilatory assistance) was 40.95 years old from 1970 and 25.77 years old before 1970. Causes of death changed. Cardiac origins of death have increased from 8% to 44%. CONCLUSION: Ventilator assistance, in this study mostly through tracheotomy prolongs by more than 15 years life expectancy of DMD patients. It allows conservation of a satisfactory quality of life, and should be systematically proposed to patients.