Elsevier

The Lancet Neurology

Volume 17, Issue 4, April 2018, Pages 347-361
The Lancet Neurology

Review
Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management

https://doi.org/10.1016/S1474-4422(18)30025-5Get rights and content

Summary

A coordinated, multidisciplinary approach to care is essential for optimum management of the primary manifestations and secondary complications of Duchenne muscular dystrophy (DMD). Contemporary care has been shaped by the availability of more sensitive diagnostic techniques and the earlier use of therapeutic interventions, which have the potential to improve patients' duration and quality of life. In part 2 of this update of the DMD care considerations, we present the latest recommendations for respiratory, cardiac, bone health and osteoporosis, and orthopaedic and surgical management for boys and men with DMD. Additionally, we provide guidance on cardiac management for female carriers of a disease-causing mutation. The new care considerations acknowledge the effects of long-term glucocorticoid use on the natural history of DMD, and the need for care guidance across the lifespan as patients live longer. The management of DMD looks set to change substantially as new genetic and molecular therapies become available.

Introduction

The 2010 care considerations for Duchenne muscular dystrophy (DMD)1, 2 advocated a multidisciplinary approach to the management of this severe, progressive neuromuscular disease. This three-part update was necessitated by a number of themes that characterise contemporary DMD care: the increasing complexity of subspecialty care and the need for a multidisciplinary clinical team; the use of more sensitive diagnostic techniques and earlier therapeutic interventions; the expectation of prolonged survival, prompting the need for care guidance across the lifespan; and the recognition that the natural history of DMD has been altered by the long-term use of glucocorticoids.3 The new care considerations have also been shaped by the expectation that emerging genetic and molecular therapies will substantially change the nature of DMD management in the near future.

In 2014, the DMD Care Considerations Working Group steering committee, comprising experts from a wide range of disciplines, identified 11 topics to be included in this update. Part 2 contains the latest care considerations for respiratory, cardiac, bone health and osteoporosis, and orthopaedic and surgical management. Large-scale, randomised controlled trials (RCTs) are rare in this field, so guidance was developed using a method that queries a group of experts on the appropriateness and necessity of specific assessments and interventions, using clinical scenarios. This methodology was designed to produce an essential toolkit for DMD care; only assessments and interventions that have been deemed both appropriate and necessary are recommended. A complete description of the methods is provided in part 1 and the appendix.

Figure 1 in part 1 of this Review provides a brief overview of assessments and interventions across all topics, organised by stage of disease. It is intended to serve as a pocket guide to overall disease management.

Section snippets

Respiratory management

Respiratory complications are a major cause of morbidity and mortality in people with DMD. Complications include respiratory muscle fatigue, mucus plugging, atelectasis, pneumonia, and respiratory failure. If left untreated, patients are at risk of severe dyspnoea, lengthy hospital admissions due to atelectasis or pneumonia, and death due to respiratory arrest or respiratory-induced cardiac arrhythmias.4, 5, 6

An anticipatory approach to management includes monitoring of respiratory muscle

Cardiac management

Cardiovascular complications are a leading cause of disease-related morbidity and mortality among individuals with DMD.48 Dystrophin deficiency in the heart manifests as a cardiomyopathy. As the disease progresses, the myocardium fails to meet physiological demands and clinical heart failure develops. The failing myocardium is also at risk of life-threatening rhythm abnormalities.49

Historically, individuals with DMD have not been referred to a cardiac specialist until late in the disease,

Bone health and osteoporosis management

Boys with glucocorticoid-treated DMD frequently develop osteoporosis, which manifests as low-trauma vertebral or long-bone fractures.66 This outcome is not surprising given the potent osteotoxicity of glucocorticoid therapy combined with progressive myopathy, both of which are key risk factors for reduced bone strength. 20–60% of boys with DMD have low-trauma extremity fractures (usually the distal femur, tibia, or fibula), while up to 30% develop symptomatic vertebral fractures.66, 67, 68

Orthopaedic and surgical management

The overall aim of musculoskeletal care is to maintain motor function for as long as possible, minimise joint contractures, maintain a straight spine, and promote bone health. The assessment and treatment of musculoskeletal complications should involve an interdisciplinary team that might include a physical and occupational therapist, rehabilitation physician, neurologist, orthopaedic surgeon, and social worker. When a surgical intervention is recommended, it is crucial to involve the

Conclusions and future directions

Improved approaches to respiratory, cardiac, bone health and osteoporosis, and orthopaedic and surgical management can now be offered to children and adults with DMD. However, despite advances in our knowledge and understanding of best approaches to management, progress is needed across these subspecialties to meet the needs of patients.

For respiratory management, diagnostic tools and measures that might have clinical relevance but need further study include assisted cough peak flow, maximum

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