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Treatment and Management of Spinal Muscular Atrophy and Congenital Myopathies

Introduction Although spinal muscular atrophy (SMA) and the congenital myopathies (CMs) have different etiologic features, they have similar clinical characteristics, and the decision to address them together is consistent with the similarities in the supportive management of these two groups. Advances in gene-based therapies over the last few years have significantly altered the therapeutic management and natural course of these disorders, in particular SMA. We will…

Treatment and Management of Adult Motor Neuron Diseases

Many diseases specifically affect the motor neurons, ranging from infectious processes such as polio and West Nile viruses to hereditary conditions such as spinal muscular atrophy (SMA) and Kennedy disease ( ). Radiation therapy can cause motor neuron degeneration many years later, mimicking the adult motor neuron disease amyotrophic lateral sclerosis (ALS) ( ). Sometimes, the motor neuron degeneration remains curiously restricted to just the cervical…

Molecular and Genetic Therapies

Genetic testing and development of genetically based therapies for hereditary neuromuscular disorders (NMD) have undergone an explosive growth over the last decade leading to widespread use of genetic testing in clinical practice and availability of novel genetically based therapies for disorders such as Duchenne muscular dystrophy (DMD, discussed in Chapter 20), spinal muscular atrophy (SMA; discussed in Chapter 13), and peripheral neuropathy associated with hereditary transthyretin…

Perioperative Management of Patients With Neuromuscular Disorders

Introduction Patients with neuromuscular disorders (NMDs) are at increased risk for complications during or immediately after surgery; they share a common risk of respiratory failure, atelectasis, and pneumonia and may have longer hospital stays and increased risks of morbidity, as compared with those without neuromuscular diseases ( ; ). Hypoventilation can occur due to respiratory muscle weakness. Increased chest wall compliance in younger patients can contribute…

Orthopedic Surgery in Neuromuscular Disorders

Neuromuscular disorders (NMDs) in children include conditions that affect the spinal cord, peripheral nerves, neuromuscular junction, and muscles. Orthopedic treatment of children with NMD has been aimed at preventing worsening of deformities and providing stability to the skeletal system to improve the quality of life for these children. Patients with severe NMDs have listed their priorities as the ability to communicate with others, the ability to…

Rehabilitation in Neuromuscular Disorders

∗ The first edition of this chapter was coauthored with Lisa Krivickas, MD. This current chapter includes some of Dr. Krivickas’ original work. While there are no cures for so many neuromuscular disorders (NMDs), pharmacologic and other interventions are increasingly available to slow the progression of some NMDs. Rehabilitation is currently a cornerstone of comprehensive NMD management, optimizing quality of life and facilitating function and independence…

Principles and Guidelines of Immunotherapy in Neuromuscular Disorders

Among the variety of diseases seen by neuromuscular specialists, immune-mediated disorders generate tremendous interest. These disorders are relatively common and often respond favorably to treatment. The field has become more exciting but has also become more complicated due to the many treatments available as well due to the side effects that can arise from manipulation of the immune system. However, the timely and accurate diagnosis and…

A Practical Approach to the Treatment of Painful Polyneuropathies

Conflict of Interest Statement Daniel Menkes, MD, has previously served as a consultant for the Eli Lilly Company, manufacturer of duloxetine (Cymbalta). He has received honoraria in the past from this company for providing lectures on the diagnosis and treatment of diabetic peripheral NP and FM. He is no longer a speaker for any pharmaceutical manufacturer. He has also served as a consultant and expert witness…

Autonomic Dysfunction in Neuromuscular Disorders

Overview of the Autonomic Nervous System The autonomic nervous system extends to every organ in the human body, creating a dizzying array of central and peripheral nerves, nuclei, ganglia, and neurotransmitters that often defy conventional attempts at learning through memorization. Although colloquial understanding of the autonomic nervous system is discovered in the medical students’ mantra of “fight or flight,” true comprehension of the system often occurs…

Gastrointestinal Complications of Neuromuscular Disorders

Introduction The gastrointestinal (GI) tract is an extremely dynamic organ with its extensive muscle regulated not only by enteric nervous system but also by the central nervous system, autonomic nervous system, as well as humoral factors. It is therefore not surprising that many neuromuscular diseases affect the GI tract ( ). GI symptoms occur commonly in neurological diseases, usually as transfer/oropharyngeal dysphagia, nausea, early satiety, constipation,…

Cardiac Complications of Neuromuscular Disorders

Cardiac disease has a significant association with neuromuscular diseases ( Table 3.1 ). In all cases, early recognition of the neuromuscular diagnosis can improve timely recognition of forthcoming cardiac disease. The extent and severity of cardiac disease can vary significantly within and between specific neuromuscular disorders. In some cases, cardiac disease is the presenting symptom, long before skeletal muscle symptoms develop. In other cases, where skeletal…

Respiratory Complications in Neuromuscular Disorders

Respiratory management of patients with neuromuscular diseases has changed significantly during the 21st century, aided by the development of lightweight, noninvasive technologies to assist in airway clearance and ventilation. These devices, coupled with a more aggressive approach to diseases that had previously been treated with a nihilistic approach, have resulted in reduced morbidity and greatly extended survival. Management of Neuromuscular Diseases Resulting In Respiratory Insufficiency While…

Introduction: Evaluation of Patients with Neuromuscular Disorders

This book is dedicated to the treatment of neuromuscular disorders (NMDs), which include those that affect the anterior horn cells, nerve roots, plexi, peripheral nerves, neuromuscular junction, and muscles ( Fig. 1.1 ) ( ); some also affect other areas of the nervous system, such as amyotrophic lateral sclerosis (ALS). These disorders may be caused by genetic defects or may be acquired, as the autoimmune diseases,…

Outcome Measures in Neuromuscular Diseases

Introduction: What are Outcome Measures? Good outcome measures are a critical component of any successful therapeutics evaluation program. Although some pediatric neuromuscular diseases are now seeing discoveries translated into early-phase clinical trials, there remains a great need for better therapeutics. Bringing these therapeutics to patients requires clinical trials using outcome measures that ideally are easy to implement, are sensitive to change, and reflect an important aspect…

Rehabilitation of the Child with a Neuromuscular Disorder

Introduction Rehabilitation is that branch of medicine concerned with helping patients gain optimal function within the scope of their physical and cognitive limitations. The development and implementation of a realistic and cost-effective rehabilitation program for the patient necessitates a “correct diagnosis” and an understanding of the natural course of disease. Furthermore, a team of professionals skilled in all areas of rehabilitation best develops a rehabilitation program.…

Orthopedic Management

Introduction Childhood-onset neuromuscular diseases are typically inherited genetic diseases characterized by general neurodevelopmental dysfunction, aberrant muscular function and development, and resulting pediatric deformity. This population often requires early orthopedic intervention to address mobility and motor deficits, and in some cases improve the patient’s comfort, hygiene, and general quality of life. This chapter systematically addresses the various childhood-onset neuromuscular diseases that are most frequently seen and treated…

Principles and Practice of Molecular Therapies

Introduction Treatment for the muscular dystrophy group of disorders continues to gain momentum based on improvements in therapeutic strategies, facilitated by a greater availability of funding for translational research. This review emphasizes the progress made for Duchenne muscular dystrophy (DMD) and related dystrophinopathies as well as the limb girdle muscular dystrophies (LGMDs). Clinical gene therapy trials for DMD, Becker muscular dystrophy (BMD), and LGMDs are underway.…

Dominantly Inherited Spinocerebellar Syndromes

Introduction The dominantly inherited ataxias are a heterogeneous group of neurologic disorders that currently include 30 spinocerebellar ataxias (SCAs), the related disorder dentatorubral-pallidoluysian atrophy (DRPLA), and 7 episodic ataxias (EAs). The number of these disorders will undoubtedly grow as only 60% to 70% of the dominantly inherited ataxias fall into one of the current categories. As a group they are rare: the estimated prevalence of SCA…

Friedreich Ataxia

Introduction In 1863, Nicholaus Friedreich, professor of medicine in Heidelberg, Germany, wrote three articles “about a degenerative atrophy of the posterior columns of the spinal cord” causing progressive ataxia, sensory loss, and muscle weakness. The cause of what was called “Friedreich ataxia” (now abbreviated as FRDA) remained mysterious for more than 130 years thereafter. For many years, even the definition of this entity, as well as…

Complex Regional Pain Syndromes I and II (Reflex Sympathetic Dystrophy, Causalgia)

Introduction The definitions of reflex sympathetic dystrophy (RSD) and causalgia syndromes have been revised recently to avoid implicating the sympathetic nervous system in treatment or mechanism; the syndromes have been renamed with the clinically descriptive terms of complex regional pain syndrome types I and II (CRPS type I and CRPS type II). Given the incomplete understanding of these syndromes, restructuring the diagnostic criteria of RSD to…