Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Oromotor Dysfunction in Neuromuscular Disorders: Evaluation and Treatment

Introduction Sucking, chewing, and swallowing are vital functions that are dependent upon the coordinated interaction of a set of neural structures designated by several authors as the “oromotor system” (OMS). Also dependent on this system are other not-so-vital but important functions such as language motor articulation and gestural communication by means of facial expression. Direct control of the OMS is located in the brainstem. Sensory inputs…

Disorders of the Ocular Motor Cranial Nerves and Extraocular Muscles

General Principles The extraocular muscles (EOMs) have many anatomic, physiologic, and molecular characteristics distinct from those of other striated muscles. These unique characteristics, which likely developed in response to the specialized demands placed on EOMs, including tonic position, maintaining contractures, conjugate smooth pursuit and saccades, and dysconjugate vergence movements, may account for the often predictable involvement or sparing of extraocular muscle in specific pediatric neuromuscular disorders.…

Malignant Hyperthermia : An Inherited Disorder of Muscle Calcium Metabolism

Malignant Hyperthermia—Deaths in General Anesthesia The name malignant hyperthermia (MH) is derived from the clinical observations of Denborough and Lovell, who analyzed the unexplained deaths of previously asymptomatic patients undergoing general anesthesia in 1960. These patients exhibited symptoms of muscle rigidity and rapidly rising, irrepressible core body temperature; hence the term MH. Within 2 years, Denborough and colleagues realized that young age and blood relationship is…

Intensive Care Management, Including Cardiorespiratory Care

Historical Background Patients with neuromuscular diseases may present with cardiac dysfunction, arrhythmia, or respiratory failure. Information in the literature regarding intensive care for these patients continues to evolve and single institution results have been published. Standards of care have been established for neuromuscular diseases. Close interaction among the specialties of cardiology, critical care, neurology, and pulmonary medicine are necessary for optimal outcomes. This chapter will provide…

Neuromuscular Problems of the Critically Ill Neonate and Child

Introduction Acute neuromuscular disorders occasionally confront the pediatric intensivist and/or the pediatric neurologist. Many of these are primary disorders of the motor unit that present acutely and may require urgent admission to a neurologic critical care unit. We have chosen to discuss these various processes apropos to two respective age groups, infants and children, because some illnesses are unique to infants and toddlers and because similar…

Juvenile Dermatomyositis and Other Inflammatory Myopathies in Children

Introduction Patients with idiopathic inflammatory myopathies (IIM) manifest a diverse group of syndromes that have in common the loss of muscle function as a disease symptom. The symptoms of inflammatory muscle disease in children can be characterized as either acute (reviewed in Chapter 36, [Case Example 36.3], Chapter 1 ) or chronic in nature. Throughout the world, acute muscle complaints are usually associated with bacterial or…

Mitochondrial Encephalomyopathies

Introduction Historical Background The history of mitochondria can be traced back at least to 1850 when Kolliker described a regular array of subcellular particles in muscle sarcomeres. Fifty-two years were to pass before Luft and colleagues implicated mitochondria as the cause of a human disease. A 39-year-old woman had florid symptoms of hypermetabolism thought initially to be due to thyroid disease. However, antithyroid medication and partial…

Lipid Storage Myopathies Due to Fatty Acid Oxidation Defects

Historical Background Defects in fatty acid oxidation (FAO) are an important group of disorders because they are potentially rapidly fatal and a source of major morbidity. They encompass a spectrum of clinical disorders including progressive lipid storage myopathy, recurrent myoglobinuria, neuropathy, progressive cardiomyopathy, recurrent hypoglycemic hypoketotic encephalopathy or Reye-like syndrome, seizures, and mental retardation. All of the known conditions are inherited as autosomal recessive diseases, and…

Glycogen Storage Diseases of Muscle

Introduction and Background Metabolic myopathies are clinical disorders in which defects of adenosine triphosphate (ATP) production cause muscle dysfunction. A review of muscle metabolism is beyond the scope of this chapter and readers are referred to other reviews for further details. Nevertheless, a brief description of the biochemical pathways supporting the energy requirement of skeletal muscle is necessary to understand the symptoms of patients with metabolic…

Muscle Channelopathies : Myotonias and Periodic Paralyses

Introduction Defective ion channels may play a causal role in disease pathogenesis. This implication was first concluded from the observation of an abnormal ion conductance in muscle fibers biopsied from myotonic goats. In humans, a similar conclusion was reached for patients with paramyotonia congenita (PC) and with periodic paralyses. The term “ion channelopathies” was then coined in the 1990s, and defined for disorders that are caused…

Myotonic Dystrophy

Clinical Presentation and Phenotypes Brief Overview of History and Epidemiology In 1909, Hans Steinert (Leipzig, Germany) described the typical pattern of muscle weakness and myotonia in adult-onset myotonic dystrophy type 1 (DM1). Over subsequent years, clinical studies demonstrated dominant inheritance and a wide spectrum of variable multisystem manifestations (skeletal and smooth muscle, heart, brain, eyes, respiratory, gastrointestinal, immune, and endocrine systems). In 1992, researchers discovered that…

Myopathies of Systemic Disease

Introduction When evaluating a child with myopathy, the clinician must not only determine the pattern and extent of muscle weakness but also the cause. In addition to the many primary disorders of muscle, there are many systemic diseases that produce myopathies. These generalized disorders include endocrine abnormalities, renal disorders, infections, medication-related effects, connective tissue diseases, and eosinophilic syndromes. In this chapter, we detail the disorders that…

Emery-Dreifuss Muscular Dystrophy: Nuclear Envelopathies

Introduction Emery-Dreifuss muscular dystrophy (EDMD) is a rare inherited disorder presenting in childhood or adolescence with relatively benign neuromuscular features and potentially fatal cardiac involvement. It is characterized by the triad of (1) early contractures of the Achilles tendons, elbows, and posterior cervical muscles; (2) slowly progressive muscle weakness and wasting, with humeroperoneal distribution in the early stages; and (3) cardiomyopathy with conduction defects. The disease…

Limb-girdle Muscular Dystrophies

Introduction Historical Background and Definition The limb-girdle muscular dystrophies (LGMDs) are a diverse and heterogeneous group of disorders within the broader field of genetic muscle disease. The term LGMD was first formally introduced in the 1950s to include the category of a larger group of patients with muscle weakness that could not be recognized under the major muscular dystrophy groups identified at the time, such as…

Distal Myopathies

Early Onset Distal Myopathies Laing Distal Myopathy (LDM, MPD1) Clinical Phenotype Symptoms of ankle stiffness are usually observed in infancy before the child starts to walk. However, ankle dorsiflexion weakness may be very mild and remain unnoticed until later. Weakness is marked in ankle dorsiflexor, toe extensor, and neck flexor muscles. Later in the disease course finger extensors and proximal limb muscles are also affected, but…

Facioscapulohumeral Dystrophy

Introduction Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy after dystrophinopathies and myotonic muscular dystrophy. It affects 1 in 15,000 to 20,000 individuals with an estimated prevalence of 4 to 7 per 100,000. FSHD was first described by Landouzy and Dejerine in 1884. A study in 1952 looking at six generations of a single family from Utah further described the clinical manifestations of…

Clinical Management of Dystrophinopathies: A Systematic Approach

Introduction This chapter reviews the current management recommendations for the skeletal muscle predominant disorders caused by mutations in the dystrophin gene: Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and manifesting carriers of dystrophinopathy. Duchenne muscular dystrophy is the most common form of dystrophinopathy, affecting around 1 in 5000 male births. The incidence of Becker muscular dystrophy is around 1 in 14,000. Figures for manifesting carrier…

Dystrophinopathies

Introduction Dystrophinopathies are X-linked recessive diseases related to dystrophin deficiency; the major ones are Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, and Becker muscular dystrophy (BMD). BMD has a presentation similar to that of DMD but a relatively milder clinical course. In addition to DMD and BMD, there is an intermediate group of muscular dystrophy patients with either mild DMD or severe…

Congenital Muscular Dystrophies

Introduction The identification of several new genes responsible for different forms of congenital muscular dystrophies (CMD) has dramatically expanded our knowledge of the spectrum of these conditions and their pathogenesis, allowing a better characterization of the individual forms and of the specific pathomechanisms underlying them. Definition of CMD Classically, the term congenital muscular dystrophy includes a group of genetically, clinically, and biochemically distinct entities sharing clinical…

Congenital and Other Structural Myopathies

The congenital myopathies are a heterogeneous group of neuromuscular conditions defined by distinctive morphologic abnormalities in skeletal muscle ( Figure 28.1 ). These disorders typically present in infancy or early childhood with hypotonia and muscle weakness, and are usually nonprogressive, or only slowly progressive with age. There is wide variation in clinical severity within each group and marked clinical overlap with other neuromuscular disorders, including the…