CLASSIFICATION AND CLINICAL EVALUATION
Disorders of the peripheral nervous system generally can be divided into 3 major anatomic categories: (1) neurogenic disorders, including motor neuron diseases; (2) disorders of the neuromuscular junction; and (3) myopathies, including muscular dystrophies. History and physical examination remain critical in focusing the differential diagnosis of neuromuscular diseases. Polyneuropathies typically present with distal weakness and atrophy (manifesting as foot drop), loss of deep tendon reflexes, and sensory deficits. Children with chronic polyneuropathies, especially Charcot-Marie-Tooth disease, may be unaware of sensory loss. Motor neuron disease such as spinal muscular atrophy will cause proximal or generalized weakness. Disorders of the neuromuscular junction are sometimes difficult to diagnose in children. Infant botulism typically begins with constipation, followed by a descending pattern of weakness. Juvenile myasthenia gravis may present with a variety of symptoms, including fatigue, but this disorder is almost always accompanied by ocular or bulbar deficits. Myopathies tend to cause proximal or generalized weakness. Neither neuromuscular junction disorders nor myopathies are accompanied by sensory loss, although myalgias may be present in the latter.
During the last quarter century, the field of neuromuscular disease has changed dramatically, with advances in the molecular pathogenesis of all types of inherited neuromuscular disorders (see also Chapter 562). These breakthroughs have allowed improved and new diagnostic tests that can confirm clinical diagnoses very accurately and less invasively. In this section, we will describe the diagnostic tests currently used in clinical practice.
Measurements of serum muscle enzyme levels can be useful in the initial evaluation of children with suspected neuromuscular disease. The most well-known serum marker of neuromuscular disease is creatine kinase (CK), also known as creatine phosphokinase (CPK). This muscle enzyme is normally found in small amounts in serum (150 and 175 U/L are common upper limits of the normal range in many diagnostic laboratories) but may be released in large quantities when muscle membrane breakdown occurs in muscular dystrophy and other myopathies. Mild elevations in CK levels in the 300 to 500 U/L range are of unclear significance and may signify a normal variant in many cases, but such values are sometimes found in neuromuscular diseases such as spinal muscular atrophy or congenital myopathies. Moderate (501–1000 U/L) to severe (> 1000 U/L) elevations in CK levels are usually associated with primary muscle disease, which can be inherited, as in muscular dystrophy, or acquired, as in acute rhabdomyolysis. CK levels usually are normal in the presence of neuropathies and disorders of the neuromuscular junction.
Other enzymes are also released by injured muscle tissue and can be measured in serum. Among them, aldolase may also be elevated in muscle disease. Normal aldolase levels typically range up to 12 U/L. Three transaminases that are commonly thought of as “liver enzymes” are also found in muscle tissue and may be mildly increased in muscle disease: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and ...