CHAPTER THIRTEEN
MYOPATHOLOGY

DENERVATION ATROPHY

Denervation atrophy

Diseases that affect the lower motor neuron at any point cause myofiber atrophy. The motor neuron exerts a trophic influence on muscle. This influence is mediated by impulses and by chemical substances (trophic factors) which, acting through the synapse, influence protein synthesis in muscle. Myofibers that lose their innervation become angular and shrink. They lose 80% to 90% of their mass within a few months. At an extreme stage of atrophy, virtually all sarcoplasm is lost and the myofiber is reduced to a cluster of nuclei. In the process of denervation, there is loss and disarray of myofilaments but no myonecrosis occurs. Myofiber atrophy can be best appreciated in cross sections.

Fiber type grouping	Group atrophy	Target fibers

At an early stage, denervation causes atrophy of isolated myofibers, which are scattered in a random fashion. In chronic denervating processes such as chronic neuropathy and motor neuron disease, remaining healthy axons sprout and synapse with denervated fibers (collateral reinnervation). As a result of the combined denervation and reinnervation, motor units enlarge, and their fibers, instead of being scattered, come to lie adjacent to one another. In histochemical stains, such motor units appear as groups of myofibers of the same histochemical type (fiber type grouping). When ultimately these motor units lose their innervation and there are no healthy axons left to connect with them, all their fibers shrink together (group atrophy).

Reinnervation often causes a change in myofibers, the target fiber, characterized by absence of oxidative enzyme activity in the center, surrounded by a rim of more intense than normal activity. Target fibers may be confused with central cores, which occur in a congenital myopathy-central core myopathy.

In the EMG, large motor units appear as polyphasic or giant motor unit potentials. Denervated muscle is overexcitable. Spontaneous discharges from individual myofibers are picked up by the EMG as fibrillations. Spontaneous firing of an entire motor unit causes cotraction of a small group of myofibers that appears as a ripple on the surface of the muscle (fasciculation). Fasciculations of the tongue are an important sign of motor neuron disease. Since denervation does not cause myonecrosis, there is no elevation of CK.

Arthrogryposis	Spinal cord in arthrogryposis

Denervation atrophy is caused by peripheral neuropathies and motor neuron diseases. The most common motor neuron disease in adults is amyotrophic lateral sclerosis. In children, it is the autosomal recessive spinal muscular atrophy and its variants (see Chapter 9-Neurodegeneration). Lower motor neuron damage may also be caused by enteroviruses which include the poliomyelitis virus and some arthropod borne viruses, especially West Nile Virus. Arthrogryposis multiplex congenita is characterized by severe wasting or absence of muscles and contractures present at birth. There are several clinical and genetic forms of arthrogryposis. Some cases are due to loss of motor neurons (see figure above) from unknown causes. This presumably occurs early in gestation and is not progressive. Other cases are caused by a variety of congenital CNS abnormalities or primary muscle diseases. Milder forms of arthrogryposis may also result from primary muscle disease which begins in utero or from restriction of fetal movement due to oligohydramnios.

Type 2 atrophy

Immobilization or disuse of muscle causes atrophy of type 2 fibers. Type 2 fiber atrophy is also seen with prolonged use of corticosteroids (steroid myopathy) and in polymyalgia rheumatica.