Neuromyotonia occurs due to several causes such as hereditary, immune-mediated and degenerative
neurological disorders.
Isaacs' syndrome (immune-mediated
neuromyotonia) is an antibody-mediated
potassium channel disorder (
channelopathy). Clinical symptoms of
Isaacs' syndrome are characterized by
muscle cramp, slow relaxation following muscle contraction (
pseudomyotonia), and
hyperhidrosis; these symptoms are due to hyperexcitability of the peripheral nerve, including autonomic nerve. These symptoms are relieved by the administration of Na channel blocker and
immunotherapy. Recent studies show that this disease is not infrequently associated with
neoplasm, especially
thymoma. The target channel
proteins of the
antigens are
voltage-gated potassium channels (VGKCs), specifically
dendrotoxin-sensitive fast
potassium channels. The suppression of voltage-gated outward K+ current by
antibodies induces the hyper- excitability of the peripheral nerve. The findings of patch clamp studies show that
antibodies may not directly block the kinetics of VGKCs, but may decrease channel density. From the electrophysiologic, pharmacologic and immunologic view points, the site of origin of spontaneous discharges is located principally in the distal portion of the motor nerve and/or within the terminal arborization. Anti-VGKC
antibodies were also found to be positive in patients with Morvan's syndrome,
limbic encephalitis and temporal
epilepsy. Thus, an increasing number of immune-mediated
neurological disorders with anti-VGKC
antibodies are being identified. However, except in Morvan's syndrome, it is rare to find symptoms pertaining to involvement of both the peripheral and central nervous system in the same patient with anti-VGKC
antibodies. The differences in the pathomechanism of
Isaacs' syndrome and
limbic encephalitis are still unclear.