Concomitant synaptic impairment of neuromuscular junction and axonal polyneuropathies

Abstract

Peripheral axonal neuropathy (PAN) is a progressive axonopathy marked by loss of motor, sensory and autonomic fibers with reduced stability of neuromuscular transmission. In a previous work in demyelinating neuropathies, we showed that repetitive nerve stimulation (RNS) induced significant decremental responses in amplitude and area of muscle action potentials (CMAPs). In this work we studied prospectively, 111 diagnosed patients (clinically and electrophysiologically) with PAN, by performing RNS to assess the degree of weakened synaptic transmission at the NMJ and find out whether it is one of the aspects of PAN. Males constituted 61 patients while females are 50 with a mean age of 56 years. Nerve conduction study (NCS) and Electromyogram (EMG) revealed that patients with sensorimotor axonal neuropathy (n75), motor (n28) and the least (n8) were those with pure axonal sensory neuropathy. RNS of both axillary, musculocutaneous and Left Ulnar nerves, showed 87%, 80% and 28% decrements in amplitude and 91%, 84% and 43% in area for axillary, musculocutaneous and Left Ulnar nerves, respectively in 85 patients. This would suggest lower safety factors in neuromuscular transmission. The proximal nerves were significantly more sensitive in revealing the deficit than the distal ulnar nerve. The highly significant decrements of CMAPs in this study, could be attributed to disorders of peripheral nerves at the presynaptic level, induced by axonal loss. This leads to deficient exocytosis of Acetylcholine at the NMJ. Hence, this lack of availability of neurotransmitter would not be secure enough to stimulate the nicotinic postsynaptic receptors.