Neuromyotonia (Isaacs syndrome) is a rare and heterogenous syndrome of cont
inuous motor unit activity of peripheral nerve origin that manifests as var
ious combinations of muscle stiffness, cramps, twitching, weakness, and del
ayed muscle relaxation. Although neuromyotonia may accompany an assortment
of inherited diseases, most cases are acquired. The observation that the ac
quired form is often associated with an autoimmune disorder, and the demons
tration that some cases improve after plasma exchange, has led to a search
for an immune-mediated etiology. This review summarizes the recent immunolo
gical and electrophysiological evidence that autoantibodies to voltage-gate
d potassium channels produce the peripheral motor nerve hyperexcitability t
hat characterizes neuromyotonia and thus establishes acquired neuromyotonia
as an autoantibody-mediated disorder. In the nervous system, ion channels
and neurotransmitter receptors that function as ligand-gated ion channels s
eem to be favored targets for autoantibody attack, and neuromyotonia can no
w be added to the growing list of autoimmune channelopathies.