Acquired neuromyotonia: Evidence for autoantibodies directed against K⁺channels of peripheral nerves

TLDR

Acquired neuromyotonia presents with hyperexcitability of motor nerves causing muscle twitching, cramps, and weakness, and its symptoms can improve with plasma exchange or IgG therapy that enhances neuromuscular transmission resistance. The study examined mice injected with plasma or purified IgG from six neuromyotonia patients or controls, and cultured dorsal root ganglion cells treated with patient IgG, to assess effects on nerve and muscle function. Antibodies to voltage‑gated K⁺ channels were found in three patients, and IgG from these patients increased acetylcholine release, prolonged peripheral nerve action potentials, and induced repetitive firing in cultured dorsal root ganglion cells, mirroring the effects of aminopyridines, indicating a pathogenic role of K⁺ channel antibodies in acquired neuromyotonia.

Abstract

Abstract Acquired neuromyotonia is characterized by hyperexcitability of motor nerves leading to muscle twitching, cramps, and weakness. The symptoms may improve following plasma exchange, and injection of immunoglobulin G (IgG) from 1 neuromyotonia patient into mice increased the resistance of neuromuscular transmission to d ‐tubocurarine. Here we examine nerves and muscle in vitro from mice injected with plasma or purified IgG from 6 neuromyotonia patients or pooled control subjects, and cultured dorsal root ganglion cells after treatment with IgG. Three of the patients had antibodies against human voltage‐gated potassium channels labeled with 125 I‐α‐dendrotoxin. The quantal release of acetylcholine (quantal content) at end‐plates in diaphragms from mice treated with neuromyotonia IgG preparations was increased by 21% relative to control values ( p = 0.0053). With one IgG preparation, the duration of the superficial peroneal nerve compound action currents was increased by 93%. The dorsal root ganglion cells treated with this IgG showed a Marchked increase in repetitive firing of action potentials. All effects were similar to those obtained with aminopyridines. We conclude that at least some patients with acquired neuromyotonia have antibodies directed against aminopyridine‐ or α‐dendrotoxin‐sensitive K + channels in motor and sensory neurons, and they are likely to be implicated in the disease process.