Chapter 14 Peripheral nerve hyperexcitability and the neuromuscular junction

Abstract

Publisher Summary This chapter describes the peripheral nerve hyperexcitability and the neuromuscular junction. Neuromyotonia, myokymia, neuromuscular hyperexcitability, peripheral nerve hyperexcitability (PNH), continuous muscle fiber activity, quantal squander, cramp-fasciculation syndrome, Armadillo syndrome, rippling muscles and the eponyms “Isaacs syndrome” and “Morvan syndrome” describe a heterogeneous group of neuromuscular disorders characterized by spontaneous and continuous muscle activity. A majority of these disorders result from hyperexcitability of the distal motor nerve or motor nerve terminal. The clinical and electromyographic features of PNH are quite varied and reflect a continuous spectrum of manifestations ranging from frequent fasciculations to high-frequency bursts of motor unit discharges (neuromyotonia). PNH can result from genetic causes, especially mutations in voltage-gated potassium channels (VGKC). Toxins can affect the neuromuscular junction (NMJ) or motor nerve terminal. Drugs and toxins increase acetylcholine levels at the NMJ, can also produce motor nerve hyperexcitability. Demyelination or radiation injury of peripheral nerves can produce focal PNH. Inflammation at the site of demyelination may also contribute to nerve hyperexcitability. Many acquired cases of generalized PNH appear to have an autoimmune basis. The chapter discusses the neuromyotonia (Isaacs syndrome), Morvan syndrome, and cramp-fasciculation syndrome. Rippling muscle syndrome, another unusual neuromuscular hyperexcitability disorder, is characterized by waves of rippling or rolling muscle movements following muscle percussion or stretching. Neuromyotonia may occur in association with other autoimmune disorders or with cancer. Encephalopathy, seizures or behavioral changes may co-exist with PNH and may represent the effects of VGKC antibodies on neuronal excitability in the central nervous system (CNS).