Lambert-Eaton myasthenic syndrome: a review.

Abstract

LEMS, often associated with SCLC, is a disorder of neuromuscular transmission characterised by reduced nerve-evoked and resting release of acetylcholine, and by disorganisation and paucity of presynaptic active zone particles. Clinical and electromyographic improvement can follow plasma exchange. Daily injection of LEMS IgG into mice transfers the typical electrophysiological and morphological changes, and by immunostaining can be localised at the nerve terminal membrane. The experimental findings are consistent with an IgG antibody causing a reduction in the number of functional VGCC, perhaps by cross-linking closely adjacent active zone particles. Cultured human SCLC cell lines express functional VGCC, and K+-stimulated 45Ca2+ flux is inhibited by LEMS IgG; this inhibition associates with the severity of the neuromuscular transmission defect. In SCLC-associated LEMS, tumour VGCC may trigger the autoantibody response; the stimulus in the remainder of the cases is unknown.