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Juvenile and Neonatal Myasthenia Gravis

Background Juvenile myasthenia gravis is a major category of neuromuscular junction disorders that shares many pathophysiologic and clinical features with adult autoimmune myasthenia gravis, yet displays distinct demographic patterns, clinical features, and therapeutic challenges. These considerations underscore the need to discuss this disease separately from its adult counterpart. Juvenile myasthenia gravis affects a broad range of ages within the pediatric population and has a worldwide geographic…

Congenital Myasthenic Syndromes

Introduction Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. These syndromes are neither new nor uncommon. They were recognized by Rothbart, who in 1937 described four brothers with myasthenia younger than 2 years of age in one family, and by Sarah Bundey, who in 1972 collected 97 familial cases with onset…

Acquired Presynaptic Neuromuscular Junction Disorders: Infant Botulism and Lambert-Eaton Myasthenic Syndrome

Infant Botulism Botulism is derived from the Latin botulus , for sausage. Van Ermengem in 1897 isolated the spore-forming anaerobe Bacillus botulinum from the spleen of a victim and the contaminated ham involved. This toxigenic form of botulism is the best known, and before the advent of modern food processing, was the most common form of botulism in the developed world. There are three other forms…

Hansen’s Disease (Leprosy) : Leprous Neuropathy

Introduction Leprosy is a chronic infectious disease caused by Mycobacterium leprae ( M. leprae ), an acid-fast, Gram-positive, rod-shaped, obligate intracellular parasite which has the unique propriety of systematic invasion and multiplication inside peripheral nerves. Although mostly known due to the resulting skin manifestations, most of the feared consequences of leprosy result from nerve damage. Although known from time immemorial, it is still a poorly understood…

Toxic Neuropathies

Introduction In a sense, all peripheral nervous system (PNS) disorders caused by toxic molecules are toxic neuropathies. Even normal PNS proteins can have deleterious effects if overexpressed. For example, Charcot-Marie-Tooth syndrome type 1A (hereditary motor and sensory neuropathy type 1A) results from excess synthesis by Schwann cells of the myelin protein PMP22, caused by inheritance of a duplicated chromosomal segment within which PMP22 is encoded. Excessive…

Neuropathies Secondary to Systemic Disorders

Introduction There is a clear distinction between a peripheral neuropathy that is clinically significant and which is a presenting feature of the underlying condition (e.g. those associated with diabetes mellitus, lymphoma, and uremia) and a peripheral neuropathy that is asymptomatic and detected only by careful neurologic examination and electrophysiologic studies. Peripheral polyneuropathy is frequently asymptomatic in children with systemic disorders. This chapter reviews some of the…

Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Epidemiology Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) comprises a small but important subset of chronic childhood polyneuropathies. One series identified childhood CIDP in 11/125 (9%) of all children with a chronic polyneuropathy confirmed by sural nerve biopsy. A second series reported CIDP in 35/249 (14%) of all children diagnosed with a sensorimotor polyneuropathy. CIDP can present from infancy to late adulthood. The mean age of childhood CIDP…

Acute Polyneuropathies

Introduction The acute polyneuropathies are a group of acquired, generally immune-mediated or infectious disorders causing dysfunction and sometimes degeneration of peripheral nerves, spinal sensory and motor nerve roots, and occasionally the cranial nerves. The most common of these conditions are the Guillain-Barré syndrome and its variants. This chapter will also cover the presentation and treatment of tick paralysis. Guillain-Barré Syndrome Guillain-Barré syndrome (GBS) is an acute…

Peripheral Neuropathy in Inherited Metabolic Disease

Introduction Peripheral neuropathy is associated with numerous inherited metabolic diseases, such as Fabry disease (trihexosylceramide lipidosis) where it may be the presenting complaint, or adrenomyeloneuropathy, in which it may play a relatively minor role in contrast to the more prominent and progressive spastic paraparesis. In the mucopolysaccharidoses, neuropathy may represent a complication of the underlying storage disease, such as an entrapment neuropathy. This chapter describes the…

Hereditary Sensory and Autonomic Neuropathies

Introduction The hereditary sensory and autonomic neuropathies (HSANs) are a group of rare disorders caused by different genetic mutations, each affecting specific aspects of development, function, or survival of small myelinated and unmyelinated neurons resulting in variable phenotypic expression. Affected patients have impaired pain and temperature perception of different severity and varying autonomic abnormalities. These sensory deficits frequently lead to unnoticed acral ulcerations that can become…

Hereditary Neuropathies in Late Childhood and Adolescence

Definition and Nomenclature This chapter will focus on those hereditary neuropathies that can present in late childhood and adolescence. Inherited neuropathies are often referred to collectively as Charcot-Marie-Tooth (CMT) disease, an eponym used in recognition of the three men who initially described the disorder. CMT is, however, an umbrella term that encompasses a wide variety of inherited sensory and/or motor neuropathies. These inherited neuropathies also include…

Congenital and Early Infantile Neuropathies

Introduction The congenital and infantile neuropathies are an uncommon and complex group of conditions with broad phenotypic and genetic diversity. The overwhelming majority have a genetic basis, and will be the main focus of this chapter. Rarely, acquired inflammatory causes may occur. Although significant progress has been made in the genetic diagnosis of infantile neuropathies in the past two decades, more than half of children presenting…

Mononeuropathies

Introduction Mononeuropathies are rare in children, accounting for fewer than 10% of pediatric referrals for electromyographic (EMG) testing. This is in contrast to adults, in whom as many as 30% of EMG referrals are for investigation and characterization of discrete peripheral nerve lesions. Another major difference between pediatric and adult mononeuropathies is the distribution of nerve involvement ( Figure 14.1 ). In children, neuropathies almost equally…

Congenital and Acquired Facial Palsies

Introduction Facial palsy is one of the most frequent mononeuropathies in the pediatric age group. The diagnosis of idiopathic benign Bell’s palsy is based on exclusion of other acquired central or peripheral nervous system conditions, some of which have more ominous implications. Facial paralysis in a newborn may be due to prenatal or obstetric stress to the nerve. Congenital facial weakness or asymmetry may also reveal…

The Stiff-man Syndrome in Children and Adolescents

Introduction The stiff-man syndrome (SMS, also known as stiff-person syndrome) is a rare central nervous system autoimmune disease, but is likely underrecognized. This disorder has only been rarely reported in children. Most of the available literature is in case report form, and a recent series from the Mayo Clinic reported 8 cases identified over a 25-year period. These patients were frequently diagnosed initially with other disorders,…

Infectious or Acquired Motor Neuron Diseases

Infantile Poliomyelitis Historical Background To many physicians in the developed world, poliomyelitis serves as a dramatic example of how basic virologic methods can lead to vaccine development and almost complete eradication of a human viral infection and crippling neuromuscular disease. Today, with a few geographic exceptions, the formidable anxiety and fear that polio once evoked, especially during the late 19th and early 20th centuries, have been…

Juvenile Amyotrophic Lateral Sclerosis

Introduction The motor neuron diseases (MNDs) constitute a debilitating range of disorders that cause variable disability and affect all ages from neonates to the elderly. The best known, most aggressive, and most common MND in adults is amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). In rare cases it can affect children and young (<25 years) adults, in which case it may be designated juvenile ALS…

Spinal Muscular Atrophies

Introduction Spinal muscular atrophies (SMAs) are genetic disorders that are clinically characterized by progressive muscle weakness and atrophy, associated with degeneration of spinal and, in the most severely affected patients, lower bulbar motor neurons. Classic proximal SMA is the most common form of SMA and the leading cause of infant mortality; it seems to be found in practically all populations but is diagnosed more frequently in…