The Physio-Pathology of Neuromuscular Transmission and the Trophic Influence of Motor Innervation

Abstract

The long-neglected field of neurological diseases affecting the peripheral motor sj'stem is now being investigated with growing interest. Improved methods (19) have increased substantially the amount of information that can be extracted from biopsies of the neuromuscular junction in patients. On the otlier hand, biophysical research on vertebrates has recently harvested quite significant results about the elementary processes of nerve conduction (53), of neuromuscular transmission (16) and of muscular contraction (55). AU thèse and other advances undoubtedly call for more critical analyses of disturbed mechanisms in patients with motor impairment. It can be surmised that doser investigations are going to lead to a reconsideration of current neurological entities and to the isolation of new neuromuscular syndromes (e.g., 66). Significant progress along thèse lines will be promoted if the physiopathological and histopathological approaches are intimateh' correlated and if the functional significance of structural anomalies can be established. Indeed it is only by confronting observations coUected by either method on the same material that some of the pending problems can eventually be solved. PHYSI0-P.4TH0L0GY OF MOTOR INNERVATION Mere eommon sensé indicates that interruption of motor nerve fibers at any level will make the attached muscle fibers useless. More interesting for the purpose of the présent discussion arc those clinieal cases in which the anatomical continuity of the lower motor neuron is preserved. Such cases raise the problem of localizing the defective link in the chain of excitatory processes which enable the nerve impulse to elicit the contractile response.

Transient eyelid retraction in myasthenia gravis.

“…To our knowledge, this type has not been reported previously in myasthenia gravis. Transient eyelid retraction may be due to posttetanic facilitation of the levator palpebrae superioris, similar to the mechanism described in small muscles of the hands of myasthenics by Desmedt (1959), and in an in vitro preparation by Elmqvist et al (1964). In our patients the retraction was most likely to appear after either prolonged upgaze or staring straight ahead.…”

The formation of synapses in reinnervated mammalian striated muscle

“…The reappearance of m.e.p.p.s before transmission is re-established has been described in both amphibian (Miledi, 1960) and avian (Bennett et al 1973) muscle, at the same time as there is a retraction of ACh sensitivity to the end-plate region. Histological evidence of nerve endings at the end-plates (Gutmann & Young, 1944), and the regression of denervation changes such as fibrillation and increased chronaxie in the muscle fibres (Desmedt, 1959), also occurs before the onset of functional transmission. Unless some axons transmitted impulses in vivo which did not do so in vitro, these observations suggest that the nerve exerts a neurotrophic control on the muscle which is not necessarily mediated by impulses (cf.…”

The formation of synapses in mammalian sympathetic ganglia reinnervated with preganglionic or somatic nerves

“…Thus, denervated adult striated muscle fibres increase their protein synthesis initially, but after some weeks they atrophy and later may disintegrate (Gutmann, 1962(Gutmann, , 1964. Soon after denervation, the muscle fibres have decreased resting membrane potentials and increased membrane resistances (Albuquerque & McIsaac, 1970); hyperexcitability is observed at later times (Desmedt, 1959). Deafferentation in the central nervous system may lead to retraction of peripheral dendrites (Jones & Thomas, 1962;Matthews & Powell, 1962); this is also seen in somatic motorneurones following hemisection of the cord (Bernstein & Bernstein, 1971.…”