No abstract

The aim of this study was to establish the time scale of developmental changes in innervation of skeletal muscle fibers in man. Specimens of thigh and intercostal muscle from 19 embryos and 18 infants were examined with histological methods which enabled the discrimination between fetal (gamma) and adult (epsilon) types of acetylcholine receptors (AChRs). At 8 weeks of development, AChRs were distributed diffusely in the myotube membranes. Following onset of innervation in approximately the ninth week the length of the AChR positive area diminished and reached its shortest size at the sixteenth developmental week. At the sixteenth and eighteenth week some nerve terminals opposed the muscle membrane outside the AChR positive area. Decrease in the number of nerve terminals, strongly suggesting elimination of polyneuronal innervation, started in the sixteenth week and was completed in the twenty-fifth week. This fetal (gamma) type of AChR could no longer be demonstrated after the thirty-first week. The length of the end-plates as determined by the presence of AChRs increased again in the last week before birth and reached a plateau size by the end of the first year after birth. It is concluded that in man the transition from poly- to mononeuronal innervation takes place between the sixteenth and twenty-fifth weeks of development. The evidence available suggests that the retraction of nerve terminals is preceded by loss of AChRs from the muscle membrane facing the terminals. There is no relationship between retraction of nerve terminals and the switch from fetal to adult type of AChR. The size of the presynaptic apparatus changes little after the first year of life.

It is not known whether or not satellite cell nuclei are more common in the vicinity of motor endplates than in extrasynaptic regions of human muscle, as in animals. If so, perisynaptic satellite cells may have a role in preserving neuromuscular function. We compared the frequencies of satellite cell nuclei and of myonuclei in perisynaptic and extrasynaptic regions of human external intercostal muscle, and found an absolute as well as a relative increase of perisynaptic satellite cells. The mean frequency of satellite cell nuclei per sarcomere was 0.016 in perisynaptic and 0.00003 in extrasynaptic regions. The mean frequency of myonuclei per sarcomere was 0.098 in perisynaptic and 0.014 in extrasynaptic regions. We could not demonstrate any influence of aging on satellite cell distribution. Perisynaptic satellite cells had many processes, and some features suggested a more active state. These cells might add to the pool of junctional myonuclei for synthesis of acetylcholine-receptor molecules or help in the repair of the postsynaptic membrane. Alternatively, they may synthesize basal lamina substances that are specific for the endplate.

The growth associated protein B-50 (GAP-43) is demonstrated in human intramuscular nerves and neuromuscular junctions by light microscopy and electron microscopy. Nearly all fetal endplates are shown to be immunoreactive for B-50. The percentage of B-50 positive endplates decreases significantly during the peri- and neonatal period, but in children and adults a low percentage of B-50 positive endplates remains present. These data indicate that also in the human peripheral nervous system the expression of B-50 is developmentally regulated.

SUMMARYWe describe pathological alterations at the light microscopical and ultrastructural level of motor end plates and muscle fibres in 2 critically ill patients with generalized muscular atrophy and weakness. Axonal degeneration of intramuscular nerve fibres was not conspicuous. The sural nerve in one patient showed only minor abnormalities. There was a marked atrophy of type 1 and especially type 2 muscle fibres. Nodal and ultraterminal nerve sprouts were seen in both biopsies. Motor end plates showed features of regeneration. They were enlarged in one patient. This patient was treated for a prolonged period with vecuronium bromide. Pharmacological denervation may explain the presence of fibrillation potentials, and, partially, of the histological abnormalities. Another factor which must be considered is inhibition of neuromuscular transmission by antibiotics. In addition to disuse atrophy and a minor degree of axonal neuropathy, the production of muscle proteolytic factors may be involved in the rapidly occurring massive loss of muscle fibre size in critically ill patients.