Craig M. McDonald, MD, Guest Editor

Nanette C. Joyce, DO, Guest Editor

NMDs, a classification category that describes hereditary and acquired diseases of the peripheral neuromuscular system, include those that affect anterior horn cells, peripheral nerves, neuromuscular junctions, and muscle. Combined with all forms of acquired NMDs, the prevalence exceeds 4 million, which is an impressive figure when compared for example to the prevalence of spinal cord injury. There is tremendous diversity of etiologies for both acquired and hereditary neuromuscular diseases. Some NMDs are acquired with diverse causes distinct from genetic etiologies, such as autoimmune, infectious, metabolic, toxic, or paraneoplastic (eg, amyotrophic lateral sclerosis [ALS], myasthenia gravis, Lambert-Eaton syndrome, botulism, Guillain-Barre syndrome, or diabetic peripheral neuropathy). There are over 500 distinct NMDs identified to date, which have specific genes that have been linked causally to these conditions. Virtually every physiatrist or neurologist who treats patients with significant impairments or who performs electrodiagnostic studies will encounter patients with either hereditary or acquired diseases of the peripheral neuromuscular system.

The comprehensive management of all of the varied clinical problems associated with NMDs is a complex task. For this reason, the multidisciplinary approach is critical. It takes advantage of the expertise of many clinicians rather than place the burden on one. This interdisciplinary approach to caring for patients with NMD and participation by committed providers that have NMD disease-specific expertise are key ingredients to the provision of optimal care. No factor has contributed more to the improved survival of persons with neuromuscular diseases than the provision of state-of-the-art multidisciplinary care by subspecialists experienced in the prevention and management of complications related to neuromuscular weakness, cardiac abnormalities, obesity, muscle wasting and cachexia, impaired bone health, progressive spine deformity, restrictive lung disease causing airway clearance problems and ventilatory insufficiency, mobility impairment, and pain. But, while it is recognized that these diseases may remain incurable, NMDs are not untreatable. The last two decades have seen tremendous improvement in patient outcomes as a result of coordinated multidisciplinary care directed by the neuromuscular specialist.

Optimal nutritional management of children and adults with neuromuscular diseases is a foundation of multidisciplinary care. Both rapidly progressive Duchenne muscular dystrophy (DMD) and the more slowly progressive spinal muscular atrophy (SMA) are prototypical pediatric NMDs associated with loss of skeletal muscle, gain of excess body fat, and changes in energy metabolism and physical activity over time. Poor nutrition in NMD is of two spectrums, hypoalimentation and hyperalimentation. These issues occur to different degrees depending on the severity disease and at different disease stages. In ALS, nutrition management is challenging and directly linked to survival. In the first article of this issue, Dr Marlia Braun and colleagues address the complexities of nutrition management in ALS patients with innovative and aggressive approaches to optimizing nutrition and quality of life.

Most neuromuscular diseases are associated with some decrease in bone mineral content and bone mineral density due to musculoskeletal weakness and decreased load on skeletal structures due to sedentary activity and lack of weight-bearing. Dr Joyce and colleagues provide one of the most comprehensive reviews on the topic related to NMD to date. The available evidence is discussed focusing on abnormal calcium metabolism, increased fracture risk, and the prevalence of both scoliosis and hypovitaminosis D in DMD, ALS, and SMA. The problem of osteomalacia often complicates disease-related baseline osteoporosis and may reduce fracture risk if treated. Future directions are discussed, including the urgent need for studies to both determine the nature and extent of poor bone health and evaluate the therapeutic effect of available osteoporosis treatments in patients with NMD.

Major advances in the understanding of the molecular basis of many NMDs have greatly enhanced diagnostic accuracy and provide the basis for novel therapeutic interventions. There have been major pharmacologic advances in the treatment of some NMDs, particularly ALS and DMD. The physiatrist may become involved in the prescription of disease-altering medications for the various NMDs, and therefore, should familiarize him/herself with the appropriate pharmacologic agents available. In the article by Dr Andrew Skalsky and colleagues, the current treatments for ALS, neuromuscular junction disorders, inflammatory myopathies, and myotonia are reviewed. Additionally, investigational treatments for ALS, DMD, and SMA are discussed. If not directly involved in research, the neuromuscular specialist and physiatrist should nonetheless encourage enrollment in experimental protocols, which not only furthers science but provides some hope for the patient.

Despite well-documented efficacy in many chronic inflammatory conditions, chronic use of glucocorticoids also results in an extensive list of side effects, including stunting of growth, weight gain, adrenal suppression, mood changes, decreased bone density, muscle wasting and weakness, and many others. Treatment of DMD with daily prednisone was found to improve muscle strength and delay disease progression with confirmatory placebo-controlled double-blinded clinical trials occurring in the 1980s. Professor Eric Hoffman, from the Center for Genetic Medicine Research, Children’s National Medical Center, Washington, DC, and colleagues review the current efforts to optimize both the specific type of glucocorticoid (eg, prednisone vs deflazacort, or others) and the dosing regimen (daily, every other day, weekend) in DMD. Dr Hoffman’s group and others have made progress in the area of “dissociative steroids”—drugs that are able to separate efficacy and side effects, providing a broader therapeutic window. One such dissociative steroid, a Δ-9,11 drug, is being developed for DMD, and preclinical data suggest better optimization of the balance of efficacy and side effects.

Restrictive lung disease occurs commonly in pediatric and adult patients with neuromuscular disease. Common pediatric diseases with impaired ventilation and airway clearance include DMD and SMA types I and II. In adults, ALS is the most common NMD associated with severe pulmonary complications from neuromuscular weakness producing restrictive lung disease and clearance of airway secretions. The earliest sign of respiratory compromise in the patient with NMD is nocturnal hypoventilation, which progresses over time to include daytime hypoventilation and eventually the need for full-time mechanical ventilation. Dr Lisa Wolfe, a pulmonologist from Northwestern University in Chicago, and colleagues from both adult and pediatric pulmonary medicine and physiatry review the management of pulmonary complications in NMD with a description of many new technologies to provide noninvasive ventilation and improved pulmonary toilet. Appropriate and timely initiation of noninvasive ventilation can improve quality of life and prolong survival in patients with NMDs.

The article by Dr Hugh Allen, a pediatric cardiologist from Texas Children’s Hospital and Baylor College of Medicine, and colleagues from Nationwide Children’s Hospital in Columbus, Ohio addresses the cardiac manifestations, pathophysiology, and treatment of the more common forms of muscular dystrophy, especially those seen in the pediatric and young adult populations. The emphasis of this article is on the ventricular dysfunction seen in dystrophinopathies in that their treatment options are templates for those used in various other forms of dystrophy. Most cardiomyopathy patients are treated with afterload reducers such as angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers, with the addition of other agents such as diuretics or β-blockers as the disease progresses. Emerging is the concept of destination therapies such as left ventricular assist devices and transplantation. Some of the dystrophies, such as Emery-Dreifuss or myotonic dystrophy, can have significant conduction abnormalities requiring pacemaker treatment. Others with ventricular tachydysrhythmias may necessitate internal cardiac defibrillator placement.

Dr Sukanta Maitra and colleagues from the UC Davis Health System next address the management of spinal deformity, which may adversely affect quality of life in several progressive NMDs. Severe spinal deformity in NMDs leads to poor sitting balance, pelvic obliquity, and greater likelihood of pressure sores, functional impairment, poor cosmesis, and reduced quality of life. The surgical management of spinal deformity in NMDs often requires a multidisciplinary approach beginning in the preoperative surgical planning period and continuing to the perioperative and postoperative periods, owing to concomitant restrictive lung disease and cardiomyopathy in selected NMD conditions. Such a multidisciplinary approach leads to optimal planning, prevention of complications, support of patients and families, and improved outcomes.

Dr Wendy Lin from Rady Children’s Hospital and the University of California, San Diego School of Medicine, along with her colleagues, provides an informative review of the role of mobility-assistive technologies in patients with progressive NMD. Lack of appropriate access to mobility-assistive technology in children can have adverse developmental consequences. Children as young as 24 months can learn to safely operate a power wheelchair. The NMD multidisciplinary team needs to consider the patient abilities and the specific neuromuscular disease, plan for future disease progression, and provide proper and modifiable seating and positioning to maximize function and optimize the use of mobility-assistive technologies. The reduced cost of novel electronic control systems to integrate with environmental control systems and computer access makes these devices more available to a wider range of NMD patients.

Physiatrists often participate with the multidisciplinary team in the management of chronic pain syndromes in NMDs. The available data suggest that pain extent and intensity at specific sites are associated with pain interference and negatively impact physical and psychological functioning. The article by Dr Greg Carter and colleagues discusses the importance of assessing the pain site in addition to global pain intensity in patients with chronic, slowly progressive NMDs. The importance of addressing pain at multiple sites will have a major impact on future studies assessing interventions to treat pain in these patient populations. Today, there is wide recognition that the principles of palliative care should be applied as early as possible in the course of any chronic, ultimately fatal illness. This change in thinking emerged from a new understanding that problems at the end of life have their origins at an earlier time in the trajectory of disease. According to the World Health Organization definition of palliative care , it is an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and accurate assessment and treatment of pain and other problems, including physical, psychosocial, and spiritual domains. The new concept of palliative care emphasizes living as well as possible with a disease. This emphasis is engendered in Dr Carter’s final article, which discusses the role of palliative care in the treatment pathway of patients with progressive NMD, including ALS and DMD. People with severe NMDs like DMD and ALS are now living much longer. Strategies are discussed for identifying the most effective modalities to alleviate suffering and improve quality of life in NMD patients receiving palliative services. Best practice standards in pain and symptom management for these patient populations are discussed.

Much of our research in neuromuscular diseases over the years at UC Davis has been funded by the National Institute on Disability and Rehabilitation Research (NIDRR), the largest federal funding source for medical rehabilitation research and training. We recently received a NIDRR Advanced Rehabilitation Research Training Grant focused on training rehabilitation scientists in Neuromuscular and Neurodevelopmental Disorders. NIDRR is to be commended for their long commitment to medical rehabilitation research and research training for persons with neuromuscular diseases.

It has been encouraging to see an increase in the National Institutes of Health, Centers for Disease Control , and Department of Defense portfolios devoted to neuromuscular diseases. The situation in muscular dystrophy is a case in point. In 2001, as a result of effective lobbying efforts by a number of consumer advocacy groups such as the Muscular Dystrophy Association (MDA), Parent Project Muscular Dystrophy, FacioScapuloHumeral Muscular Dystrophy Society, Myotonic Dystrophy Foundation, and others, landmark muscular dystrophy legislation was introduced in Congress. At the time the bill, the Muscular Dystrophy Community Assistance, Research, and Education Amendments (MD-CARE Act), was unveiled in 2001, few bright spots existed for patients and families battling muscular dystrophy. Federal research for varied forms of muscular dystrophy and progressive neuromuscular diseases was minimal; surveillance and data collection were nonexistent, and the federal government lacked a comprehensive muscular dystrophy research and care agenda. The MD-CARE Act forever changed this landscape. Similar advocacy efforts by the Muscular Distrophy Association, the ALS Association, Families of SMA, Charcot-Marie-Tooth Disease Association, and many other advocacy groups are producing great awareness, improved care standards, and increased nonprofit and federal funding for a variety of other NMDs.

As mentioned in the preface in Part I of this issue, the number of MDA-sponsored neuromuscular disease clinics that have active participation by a Physical Medicine and Rehabilitation (PM&R) specialist remains a substantial minority. While over 20 Accreditation Council for Graduate Medical Education–approved Neuromuscular Medicine Fellowships have been developed in US Neurology Departments, there remains just one such training program housed in a Department of Physical Medicine and Rehabilitation (at UC Davis). Our hope is that these two issues will perhaps demonstrate the value of physiatry to current practicing Neuromuscular Medicine specialists, increase participation of PM&R specialists in NMD clinics, spur physiatry residents to consider subspecialty training in Neuromuscular Medicine, motivate the young faculty in PM&R who have graduated from our program and other Neurology-based fellowship programs to develop their own fellowship training programs in Neuromuscular Medicine, and ultimately expand the rehabilitation expertise among all Neuromuscular Medicine specialists. The ultimate goal of these two issues, focusing on diagnostic issues, therapy by allied health providers, specialty care, and disease-altering therapeutic management, is to improve the quality of life for people with neuromuscular diseases and their families.

It should be mentioned that the prior issue was dedicated to William M. Fowler Jr, MD, a pioneer in the rehabilitation management of persons with neuromuscular diseases (see Dedication in Part I). Bill Fowler continues to be a mentor to both Dr Gregory Carter, the Consulting Editor of the PM&R Clinics , and Dr Craig McDonald, the senior Guest Editor of these two issues. No physiatrist in history has been as instrumental as Dr Bill Fowler in advancing the scientific basis of the rehabilitation management of neuromuscular diseases.

Finally, we wish to personally thank all of the contributing authors for all the time and hard work they invested in the articles in Parts I and II, which will provide a tremendous wealth of clinical expertise that can be directly applied to your practice.