Elsevier

The Lancet Neurology

Volume 17, Issue 3, March 2018, Pages 251-267
The Lancet Neurology

Review
Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management

https://doi.org/10.1016/S1474-4422(18)30024-3Get rights and content

Summary

Since the publication of the Duchenne muscular dystrophy (DMD) care considerations in 2010, multidisciplinary care of this severe, progressive neuromuscular disease has evolved. In conjunction with improved patient survival, a shift to more anticipatory diagnostic and therapeutic strategies has occurred, with a renewed focus on patient quality of life. In 2014, a steering committee of experts from a wide range of disciplines was established to update the 2010 DMD care considerations, with the goal of improving patient care. The new care considerations aim to address the needs of patients with prolonged survival, to provide guidance on advances in assessments and interventions, and to consider the implications of emerging genetic and molecular therapies for DMD. The committee identified 11 topics to be included in the update, eight of which were addressed in the original care considerations. The three new topics are primary care and emergency management, endocrine management, and transitions of care across the lifespan. In part 1 of this three-part update, we present care considerations for diagnosis of DMD and neuromuscular, rehabilitation, endocrine (growth, puberty, and adrenal insufficiency), and gastrointestinal (including nutrition and dysphagia) management.

Introduction

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive neuromuscular disorder caused by mutations in the dystrophin gene that result in absent or insufficient functional dystrophin, a cytoskeletal protein that enables the strength, stability, and functionality of myofibres. Prevalence of DMD has been reported as 15·9 cases per 100 000 live male births in the USA and 19·5 cases per 100 000 live male births in the UK.1, 2, 3 Progressive muscular damage and degeneration occurs in people with DMD, resulting in muscular weakness, associated motor delays, loss of ambulation, respiratory impairment, and cardiomyopathy. Although the clinical course of skeletal muscle and cardiac involvement can be variable, death usually occurs as a result of cardiac or respiratory compromise.4, 5 This is part 1 of a three-part update of the 2010 DMD care considerations,6, 7, 8 which has been supported by the US Centers for Disease Control and Prevention (CDC) with involvement of the TREAT-NMD network for neuromuscular diseases, the Muscular Dystrophy Association, and Parent Project Muscular Dystrophy.

The decision to update the care considerations was driven by several important developments. First, with multidisciplinary care, the survival of patients with DMD has improved, and the diagnostic and therapeutic approach of the relevant subspecialties is evolving.9, 10, 11, 12 With more widespread realisation of prolonged survival, multiple subspecialties have shifted to more anticipatory diagnostic and therapeutic strategies, to achieve prevention, early identification, and treatment of predictable and potentially modifiable disease complications. Second, accompanying the expectation of longer survival is an increasing emphasis on quality of life and psychosocial management. Moreover, an urgent need now exists to coordinate and improve patient transitions from childhood to adulthood. Third, this update was necessitated by the growing experience with existing therapies and the anticipation of emerging genetic and molecular therapies for DMD.13 Specifically, new information is available on the efficacy, side-effects, and limitations of glucocorticoids,14, 15 and clinically meaningful and reliable biomarkers and outcome measures need to be identified to assess emerging therapies.

In part 1 of this Review, we cover the following topics: diagnosis, neuromuscular management, rehabilitation management, endocrine management (including growth, puberty, and adrenal insufficiency), and gastrointestinal management (including nutrition and dysphagia). Parts 2 and 3 of this Review describe the care considerations for other topic areas, including an expanded section on psychosocial management and new sections on primary care, emergency management, and transitions of care across the lifespan. Figure 1 provides an overview of assessments and interventions across all topics, organised by stage of disease.

Section snippets

Methods

In 2014, based on their clinical perspectives and expertise, the DMD Care Considerations Working Group (CCWG) steering committee identified 11 topics to be included in this update of the 2010 DMD care considerations.6 Eight of the topics were addressed in the original care considerations: (1) diagnosis, (2) neuromuscular management, (3) rehabilitation management, (4) gastrointestinal and nutritional management, (5) respiratory management, (6) cardiac management, (7) orthopaedic and surgical

Diagnosis

Achieving a timely and accurate diagnosis of DMD is a crucial aspect of care. The method for diagnosing DMD has not changed significantly since 2010 (figure 2).6 The diagnostic process typically begins in early childhood after suggestive signs and symptoms are noticed, such as weakness, clumsiness, a Gowers' sign, difficulty with stair climbing, or toe walking. Prompt referral to a neuromuscular specialist, with input from a geneticist or genetic counsellor, can avoid diagnostic delay.18 Less

Neuromuscular management

After diagnosis, the neuromuscular specialist will serve as the lead clinician, taking overall responsibility for care of the person with DMD and performing multiple roles and responsibilities across the individual's lifetime (panel 1). The neuromuscular specialist is uniquely qualified to guide patients and their families through the increasingly complex and technological diagnostic and therapeutic landscape of contemporary DMD care.

Rehabilitation management

DMD is characterised by well known patterns of progressive muscle degeneration and weakness, postural compensations, risk of progressive contracture and deformity, and functional losses resulting from dystrophin deficiency.6, 7 Improved DMD management has resulted in prolongation of ambulation,47 decreased prevalence of severe contracture and deformity, including scoliosis,37 and prolonged function and participation in all areas of life.47, 48 Rehabilitation personnel include physicians,

Endocrine management

The endocrine complications of DMD and its treatment include impaired growth, delayed puberty, and adrenal insufficiency. The goals of endocrine care are to monitor growth and development, identify and diagnose hormone deficiencies, provide endocrine hormone replacement therapy when indicated, and prevent a life-threatening adrenal crisis. A few relevant expert-opinion papers and reviews have been published,94, 95, 96 but data are scarce on the safety and efficacy of growth hormone and

Gastrointestinal and nutritional management

Individuals with DMD often have gastrointestinal or nutritional complications, including weight gain or loss, dietary or nutrient imbalance, fluid imbalance, low bone density, swallowing dysfunction, and mandibular contracture.106 Contributing factors include glucocorticoid treatment, decreased energy expenditure, and immobility.107 These nutritional imbalances can negatively affect the respiratory, skeletal muscle, and cardiac systems.

The aim of nutritional care is to prevent overweight or

Conclusions and future directions

In part 1 of this three-part update of the DMD care considerations, we have presented guidance on diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal management. Highlights of the new care considerations include guidance on the care of female carriers of DMD; an overview of new molecular and genetic therapies; advances in rehabilitation assessments and the emergence of more advanced, technologically enabled rehabilitation therapies; new guidance on endocrine problems,

Search strategy and selection criteria

We searched Medline, Embase, Web of Science, and the Cochrane Library databases for peer-reviewed English-language articles published from Jan 1, 2006, to Sept 30, 2013, for the eight original topics and from Jan 1, 1990, to Sept 30, 2013, for the three new topics. The literature was searched using the key search terms “Duchenne” or “muscular dystrophy,” or both, paired with one of 626 search terms (appendix). The literature search identified 1215 articles after duplicates were removed.

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