Chapter 14 Peripheral nerve hyperexcitability and the neuromuscular junction

Neuromytonia is a rare, but dramatic, disorder resulting from high frequency spontaneous repetitive discharges arising at or near the motor nerve terminal. This along with myokymia, cramp-fasciculation syndrome and other forms of PNH are characterized by abnormal muscle twitching. PNH can result from genetic causes, especially mutations in voltage-gated potassium channels such as episodic ataxia type 1. Focal nerve injury or toxins that alter nerve excitability can produce PNH. Recent evidence indicates that many cases of acquired generalized PNH have an autoimmune etiology. Antibodies against voltage-gated potassium channels (VGKC, specifically α-dendrotoxin sensitive Kv1 channels found in juxtaparanodal regions of myelinated peripheral nerves) are found in many patients and appear to alter VGKC function directly. Neuromyotonia may occur in association with other autoimmune disorders or with cancer (especially thymoma or small-cell lung carcinoma). Encephalopathy, seizures or behavioral changes may co-exist with PNH and may represent the effects of VGKC antibodies on neuronal excitability in the CNS. Autoimmune neuromyotonia represents one of several antibody-mediated disorders of the neuromuscular junction.