Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome)

Neuromyotonia is a rare disorder of unknown cause in which hyperexcitability of peripheral motor nerves leads to incapacitating muscle twitching, cramps, and weakness. We investigated an antibody-mediated mechanism for neuromyotonia in a 24-year-old man with a 7-year history of severe disease unresponsive to pharmacological treatment. Two periods of plasma exchange each produced almost complete disappearance of symptoms for 2-3 weeks, and a highly significant decrease in recorded neuromyotonic discharges. Injection of the patient's plasma or purified IgG into mice significantly enhanced in-vitro resistance to d-tubocurarine at the neuromuscular junction of phrenic nerve-diaphragm preparations. This finding suggests that an increase in neurotransmitter release might result from an antibody-mediated reduction in the number of functional potassium channels that normally regulate nerve excitability. The demonstration of pathogenic IgG autoantibodies in acquired neuromyotonia suggests that immunosuppressive treatment may be helpful in severe cases.