Chapter 599 Evaluation and Investigation
The term neuromuscular disease defines disorders of the motor unit and excludes influences on muscular function from the brain, such as spasticity. The motor unit has 4 components: a motor neuron in the brainstem or ventral horn of the spinal cord; its axon, which, together with other axons, forms the peripheral nerve; the neuromuscular junction; and all muscle fibers innervated by a single motor neuron. The size of the motor unit varies among different muscles and with the precision of muscular function required. In large muscles, such as the glutei and quadriceps femoris, hundreds of muscle fibers are innervated by a single motor neuron; in small, finely tuned muscles, such as the stapedius or the extraocular muscles, a 1 : 1 ratio can prevail. The motor unit is influenced by suprasegmental or upper motor neuron control that alters properties of muscle tone, precision of movement, reciprocal inhibition of antagonistic muscles during movement, and sequencing of muscle contractions to achieve smooth, coordinated movements. Suprasegmental impulses also augment or inhibit the monosynaptic stretch reflex; the corticospinal tract is inhibitory upon this reflex.
Diseases of the motor unit are common in children. These neuromuscular diseases may be genetically determined, congenital or acquired, acute or chronic, and progressive or static. Because specific therapy is available for many diseases and because of genetic and prognostic implications, precise diagnosis is important; laboratory confirmation is required for most diseases because of overlapping clinical manifestations.
Many chromosomal loci have been identified with specific neuromuscular diseases as a result of genetic linkage studies and the isolation and cloning of a few specific genes. In some cases, such as Duchenne muscular dystrophy, the genetic defect has been shown to be a deletion of nucleotide sequences and is associated with a defective protein product, dystrophin; in other cases, such as myotonic muscular dystrophy, the genetic defect is an expansion or repetition, rather than a deletion, in a codon (a set of three consecutive nucleotide repeats that encodes for a single amino acid), with many copies of a particular codon, in this example also associated with abnormal mRNA. Some diseases manifest as autosomal dominant and autosomal recessive traits in different pedigrees; these distinct mendelian genotypes can result from different genetic mutations on different chromosomes (nemaline rod myopathy) or may be small differences in the same gene at the same chromosomal locus (myotonia congenita), despite many common phenotypic features and shared histopathologic findings in a muscle biopsy specimen. Among the several clinically defined mitochondrial myopathies, specific mtDNA deletions and tRNA point mutations are recognized. The inheritance patterns and chromosomal and mitochondrial loci of common neuromuscular diseases affecting infants and children are summarized in Table 600-1.
Examination of the neuromuscular system includes an assessment of muscle bulk, tone, and strength. Tone and strength should not be confused: Passive tone is range of motion around a joint; active tone is physiologic resistance to movement. Head lag when an infant is pulled to a sitting position from supine is a sign of weakness, not of low tone. Hypotonia may be associated with normal strength or with weakness; enlarged muscles may be weak or strong; thin, wasted muscles may be weak or have unexpectedly normal strength. The distribution of these components is of diagnostic importance. In general, myopathies follow a proximal distribution of weakness and muscle wasting (with the notable exception of myotonic muscular dystrophy); neuropathies are generally distal in distribution (with the notable exception of juvenile spinal muscular atrophy; Table 599-1). Involvement of the face, tongue, palate, and extraocular muscles provides an important distinction in the differential diagnosis. Tendon stretch reflexes are generally lost in neuropathies and in motor neuron diseases and are diminished but preserved in myopathies (see Table 599-1). A few specific clinical features are important in the diagnosis of some neuromuscular diseases. Fasciculations of muscle, which are often best seen in the tongue, are a sign of denervation. Sensory abnormalities indicate neuropathy. Fatigable weakness is characteristic of neuromuscular junctional disorders. Myotonia is specific for a few myopathies.
Some features do not distinguish myopathy from neuropathy. Muscle pain or myalgias are associated with acute disease of either myopathic or neurogenic origin. Acute dermatomyositis and acute polyneuropathy (Guillain-Barré syndrome) are characterized by myalgias. Muscular dystrophies and spinal muscular atrophies are not associated with muscle pain. Myalgias also occur in several metabolic diseases of muscle and in ischemic myopathy, including vascular diseases such as dermatomyositis. Myalgias denote the acuity, rather than the nature, of the process, so that progressive but chronic diseases, such as muscular dystrophy and spinal muscular atrophy, are not painful, but acute stages of inflammatory myopathies and acute denervation of muscle often do present muscular pain and tenderness to palpation. Contractures of muscles, whether present at birth or developing later in the course of an illness, occur in both myopathic and neurogenic diseases.
Infant boys who are weak in late fetal life and in the neonatal period often have undescended testes. The testes are actively pulled into the scrotum from the anterior abdominal wall by a pair of cords that consist of smooth and striated muscle called the gubernaculum. The gubernaculum is weakened in many congenital neuromuscular diseases, including spinal muscular atrophy, myotonic muscular dystrophy, and many congenital myopathies.
The thorax of infants with congenital neuromuscular disease often has a funnel shape, and the ribs are thin and radiolucent as a result of intercostal muscle weakness during intrauterine growth. This phenomenon is characteristically found in infantile spinal muscular atrophy but also occurs in myotubular myopathy, neonatal myotonic dystrophy, and other disorders (Fig. 599-1). Because of the small muscle mass, birth weight may be low for gestational age.
Figure 599-1 Type 1 spinal muscular atrophy (Werdnig-Hoffmann disease). Characteristic postures in 6 wk old (A) and 1 yr old (B) infants with severe weakness and hypotonia from birth. Note the frog-leg posture of the lower limbs and internal rotation (“jug handle”) (A) or external rotation (B) at the shoulders. Note also intercostal recession, especially evident in B, and normal facial expressions.
(From Volpe J: Neurology of the newborn, ed 4, Philadelphia, 2001, WB Saunders, p 645.)
Generalized hypotonia and motor developmental delay are the most common presenting manifestations of neuromuscular disease in infants and young children (Table 599-2). These features can also be expressions of neurologic disease, endocrine and systemic metabolic diseases, and Down syndrome, or they may be nonspecific neuromuscular expressions of malnutrition or chronic systemic illness (Table 599-3). A prenatal history of decreased fetal movements and intrauterine growth retardation is often found in patients who are symptomatic at birth. Developmental disorders tend to be of slow onset and are progressive. Acute flaccid paralysis in older infants and children has a different differential diagnosis (Table 599-4).
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