Kathi Kinnett

Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management

Duchenne muscular dystrophy (DMD) is a severe, progressive disease that affects 1 in 3600-6000 live male births. Although guidelines are available for various aspects of DMD, comprehensive clinical care recommendations do not exist. The US Centers for Disease Control and Prevention selected 84 clinicians to develop care recommendations using the RAND Corporation-University of California Los Angeles Appropriateness Method. The DMD Care Considerations Working Group evaluated assessments and interventions used in the management of diagnostics, gastroenterology and nutrition, rehabilitation, and neuromuscular, psychosocial, cardiovascular, respiratory, orthopaedic, and surgical aspects of DMD. These recommendations, presented in two parts, are intended for the wide range of practitioners who care for individuals with DMD. They provide a framework for recognising the multisystem primary manifestations and secondary complications of DMD and for providing coordinated multidisciplinary care. In part 1 of this Review, we describe the methods used to generate the recommendations, and the overall perspective on care, pharmacological treatment, and psychosocial management.

Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care

Optimum management of Duchenne muscular dystrophy (DMD) requires a multidisciplinary approach that focuses on anticipatory and preventive measures as well as active interventions to address the primary and secondary aspects of the disorder. Implementing comprehensive management strategies can favourably alter the natural history of the disease and improve function, quality of life, and longevity. Standardised care can also facilitate planning for multicentre trials and help with the identification of areas in which care can be improved. Here, we present a comprehensive set of DMD care recommendations for management of rehabilitation, orthopaedic, respiratory, cardiovascular, gastroenterology/nutrition, and pain issues, as well as general surgical and emergency-room precautions. Together with part 1 of this Review, which focuses on diagnosis, pharmacological treatment, and psychosocial care, these recommendations allow diagnosis and management to occur in a coordinated multidisciplinary fashion.

Corticosteroid treatment retards development of ventricular dysfunction in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is characterized by a predictable decline in cardiac function with age that contributes to early death. Although corticosteroids are a clinically effective pharmacologic therapy for skeletal muscle function, there is limited published work documenting the impact on cardiac function. The primary objective of this work is to determine benefit from steroid treatment on the development of ventricular dysfunction in DMD. We performed a historical cohort study of DMD cases undergoing serial cardiac evaluations from 1998-2006. In addition to the history of steroid use, basic medical characteristics and serial echocardiographic measures were obtained for each identified case meeting inclusion criteria. Data from initial (7.5+/-0.8 years) and follow-up (12+/-0.7 years) evaluation was collected from untreated (n=23) and steroid treated (n=14) DMD cases. Kaplan-Meier freedom from ventricular dysfunction was 93% for steroid treated cases versus 53% for untreated cases at 1500 days. Treatment with steroids was protective against ventricular dysfunction (Hazard ratio 0.16 95% CI 0.04, 0.70). We demonstrate here that steroid treatment, begun prior to ventricular dysfunction retards the anticipated development of ventricular dysfunction.

Contemporary Cardiac Issues in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder diagnosed in childhood. It affects ≈1 in every 5000 live male births (≈20 000 new cases worldwide each year).1,2 This results in a US prevalence of 1.3 to 1.8 per 10 000 males 5 to 24 years of age. DMD is caused by mutations in the gene encoding the dystrophin protein. The loss of dystrophin results in a cascade of events leading to progressive loss of muscle function. Without supportive care, young men with DMD typically die in their late teens and early 20s. Historically, the most common cause of death has been respiratory failure. However, with improved respiratory support, an increasingly important source of morbidity and mortality is cardiomyopathy leading to heart failure and arrhythmias.3,4 There are important differences in DMD cardiomyopathy compared with other types of pediatric dilated cardiomyopathy.5 DMD cardiomyopathy is similar to the cardiomyopathy seen in some forms of limb girdle muscular dystrophy and congenital muscular dystrophy. In particular, a shared cardiomyopathic process is seen in those disorders in which the primary mutation alters components that directly or indirectly interact with dystrophin. There is less left ventricular (LV) enlargement at diagnosis in DMD. Only 30% of boys with DMD have cardiac symptoms at diagnosis (far fewer than other dilated cardiomyopathy). DMD cardiomyopathy is less often treated at the time of diagnosis. However, treatment rates have increased over time. Finally, there is a higher mortality for DMD cardiomyopathy than for other dilated cardiomyopathies. The DMD Care Considerations published in 2010 addressed cardiac care recommendations based on minimal surveillance standards with echocardiography.6,7 However, echocardiography has known limitations in DMD patients.8 Since the 2010 publication of the DMD Care Considerations,6,7 there have been significant advances in the understanding …

Effects of steroids and angiotensin converting enzyme inhibition on circumferential strain in boys with duchenne muscular dystrophy: a cross-sectional and longitudinal study utilizing cardiac magnetic resonance imaging

BackgroundSteroid use has prolonged ambulation in Duchenne muscular dystrophy (DMD) and combined with advances in respiratory care overall management has improved such that cardiac manifestations have become the major cause of death. Unfortunately, there is no consensus for DMD-associated cardiac disease management. Our purpose was to assess effects of steroid use alone or in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) on cardiovascular magnetic resonance (CMR) derived circumferential strain (εcc).MethodsWe used CMR to assess effects of corticosteroids alone (Group A) or in combination with ACEI or ARB (Group B) on heart rate (HR), left ventricular ejection fraction (LVEF), mass (LVM), end diastolic volume (LVEDV) and circumferential strain (εcc) in a cohort of 171 DMD patients >5 years of age. Treatment decisions were made independently by physicians at both our institution and referral centers and not based on CMR results.ResultsPatients in Group A (114 studies) were younger than those in Group B (92 studies)(10 ± 2.4 vs. 12.4 ± 3.2 years, p < 0.0001), but HR, LVEF, LVEDV and LVM were not different. Although εcc magnitude was lower in Group B than Group A (-13.8 ± 1.9 vs. -12.8 ± 2.0, p = 0.0004), age correction using covariance analysis eliminated this effect. In a subset of patients who underwent serial CMR exams with an inter-study time of ~15 months, εcc worsened regardless of treatment group.ConclusionsThese results support the need for prospective clinical trials to identify more effective treatment regimens for DMD associated cardiac disease.

Facilitating family adjustment to a diagnosis of Duchenne muscular dystrophy: April 24–25, 2008, Miami, Florida

Fifteen participants representing clinicians and parents from Canada, the Netherlands, the UK, and the USA met in Miami on April 24–25, 2008 to attend a workshop that focused on facilitating family adjustment to a diagnosis of Duchenne muscular dystrophy (DMD). The workshop, sponsored by Parent Project Muscular Dystrophy (PPMD), was organized in response to parent and clinician concerns that many families do not receive adequate psychosocial support following diagnosis. DMD is a complex multi-systemic medical condition with characteristics of both chronic and terminal disease [1,2]. This can present significant challenges to a family’s ability to adjust to a diagnosis of DMD, and a greater understanding of strategies that can be implemented to maximize positive outcome is necessary. Although not exhaustive, the topics covered in this workshop were judged to be of particular importance to those with DMD, and amenable to the development of specific interventions that could be implemented at the clinic level. The aims of the workshop were to (1) examine important factors that can have an impact on family adjustment and function following a diagnosis of DMD and (2) identify potential interventions and important windows of opportunity for affecting positive adjustment. It is our hope that these initial results will serve as a foundation for future exploration in this area.

Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan

Improvements in the function, quality of life, and longevity of patients with Duchenne muscular dystrophy (DMD) have been achieved through a multidisciplinary approach to management across a range of health-care specialties. In part 3 of this update of the DMD care considerations, we focus on primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Many primary care and emergency medicine clinicians are inexperienced at managing the complications of DMD. We provide a guide to the acute and chronic medical conditions that these first-line providers are likely to encounter. With prolonged survival, individuals with DMD face a unique set of challenges related to psychosocial issues and transitions of care. We discuss assessments and interventions that are designed to improve mental health and independence, functionality, and quality of life in critical domains of living, including health care, education, employment, interpersonal relationships, and intimacy.

Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary

Abstract Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Standard Operating Procedures (SOPs) for Evaluating the Heart in Preclinical Studies of Duchenne Muscular Dystrophy

A recent working group meeting focused on contemporary cardiac issues in Duchenne muscular dystrophy (DMD) was hosted by the National Heart, Lung, and Blood Institute in collaboration with the Parent Project Muscular Dystrophy. An outcome of this meeting was to provide freely available detailed protocols for preclinical animal studies. The goal of these protocols is to improve the quality and reproducibility of cardiac preclinical studies aimed at developing new therapeutics for the prevention and treatment of DMD cardiomyopathy.

The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and Adrenal Suppression

Duchenne muscular dystrophy (DMD or Duchenne) is a progressive, life-limiting muscle-wasting disease that requires comprehensive, multidisciplinary care. This care, at minimum, should include neuromuscular, respiratory, cardiac, orthopedic, endocrine and rehabilitative interventions that address both the primary and secondary manifestations of the disease. The care needs of patients evolve over the cdourse of the disease and as they transition from childhood into young adulthood. In the past two decades, life expectancy has increased significantly by the use of corticosteroids and enhanced clinical management. Nevertheless, each year, patients with Duchenne muscular dystrophy are admitted to emergency departments and intensive care units where medical expertise thrives, but where expertise in rare diseases, such as Duchenne, may not. Emergency care for patients with Duchenne can be as complex as the disease process itself. While any illness or injury may occur in a person with Duchenne, some acute scenarios are much more common in the context of the disease. Making decisions about the clinical care of a person with Duchenne who presents with an acute illness can be quite difficult — in part, because of the extensive use of corticosteroids, which can lead to adrenal suppression. The life of a person with Duchenne needing emergency care may therefore depend upon the ability of the clinician on duty in the emergency department to recognize and mitigate adrenal suppression resulting from corticosteroid dependence. With this in mind, and drawing from expertise and experience with other steroid-dependent diseases, the ‘PJ Nicholoff Steroid Protocol’ was developed. The purpose of this protocol is to provide clinicians information regarding the safe management of corticosteroid during emergency situations in patients who may have accompanying adrenal suppression. The protocol explains how to recognize the signs and symptoms of acute adrenal crisis, how to prevent it with supplemental stress doses of corticosteroids, and how to taper doses after emergency care in order to prevent corticosteroid withdrawal.