P. Shillito et al., ACQUIRED NEUROMYOTONIA - EVIDENCE FOR AUTOANTIBODIES DIRECTED AGAINSTK-NERVES( CHANNELS OF PERIPHERAL), Annals of neurology, 38(5), 1995, pp. 714-722
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 immunoglobuli
n G (IgG) from 1 neuromyotonia patient into mice increased the resista
nce of neuromuscular transmission to d-tubocurarine. Here we examine n
erves and muscle in vitro from mice injected with plasma or purified I
gG from G neuromyotonia patients or pooled control subjects, and cultu
red dorsal root ganglion cells after treatment with IgG. Three of the
patients had antibodies against human voltage-gated potassium channels
labeled with I-125-alpha-dendrotoxin. The quantal release of acetylch
oline (quantal content) at end-plates in diaphragms from mice treated
with neuromyotonia IgG preparations was increased by 21% relative to c
ontrol 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 m
arked increase in repetitive firing of action potentials. All effects
were similar to those obtained with aminopyridines. We conclude that a
t least some patients with acquired neuromyotonia have antibodies dire
cted against aminopyridine- or alpha-dendrotoxin-sensitive K+ channels
in motor and sensory neurons, and they are likely to be implicated in
the disease process.