Disorders of the peripheral nervous system can generally be divided
into 3 major categories, based on anatomic localization:
1. Neurogenic disorders, including motor neuron diseases
2. Disorders of the neuromuscular junction
3. Myopathies, including muscular dystrophies
History and physical examination remain critical in focusing
the differential diagnosis of neuromuscular diseases (see also Chapter 569). Polyneuropathies typically present
with distal weakness and atrophy, loss of deep tendon reflexes,
and sensory deficits. Children with chronic polyneuropathies, especially Charcot-Marie-Tooth
disease, may be unaware of sensory loss. Footdrop may develop in
advanced cases. Motor neuron disease such as spinal muscular atrophy
will cause proximal or generalized weakness. Disorders of the neuromuscular
junction are 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.
During the last 20 years, the field of neuromuscular disease
has changed drastically, with advancements in the molecular pathogenesis
of myopathies and other neuromuscular disorders.1 These
breakthroughs have allowed improved and new diagnostic tests that
can confirm clinical diagnoses very accurately and less invasively.
In this chapter, we will describe the diagnostic tests currently
used in clinical practice.
Measurements of serum muscle enzyme levels may be quite 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 (up
to 150 or 175 U/L in many diagnostic laboratories) but
may be released in large quantities when muscle membrane breakdown
occurs in muscular dystrophy and other myopathies.2,3 Mild
elevations in CK levels up to 300 U/L are nonspecific and
may be a normal finding, but values up to 500 U/L are sometimes
found in neuromuscular diseases such as spinal muscular atrophy
or congenital myopathies. Moderate (501 to 1000 U/L) to
severe (above 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 are generally not useful in the evaluation of possible
neuropathies and disorders of the neuromuscular junction.
Other enzymes are also released by injured muscle tissue and
can be measured in serum. Among these, aldolase may also be elevated
in muscle disease.4 Normal aldolase levels typically range
up to 12 U/L. Three liver enzymes are also found in muscle
tissue and may be mildly increased in muscle disease: alanine aminotransferase,
aspartate aminotransferase, and lactate dehydrogenase. Patients
who have unexplained mild elevations of liver enzymes should have
CK and aldolase levels checked before undergoing invasive testing
such as liver ...