What's in the serum of seronegative MG and LEMS?: MuSK et al.

Abstract

Myasthenia gravis (MG) is a postsynaptic and the Lambert-Eaton myasthenic syndrome (LEMS) a presynaptic neuromuscular transmission defect (NMTD). Autoantibodies are important in the pathogenesis of both disorders, and the studies by Plested et al. and Nakao et al. in this issue of Neurology add support to this concept.1,2⇓ The detection of antibodies to the acetylcholine receptor (AChR) in MG justifies immunosuppressive treatment3 and generally excludes inherited defects of neuromuscular transmission, the congenital myasthenic syndromes (CMS). The newly discovered autoantibodies to muscle-specific kinase (MuSK) in previously seronegative MG will now help to stratify the diagnosis and optimize differential therapy.4 Similar developments may be anticipated for LEMS. The clinical diagnosis of MG is straightforward if there is the typical combination of signs: fatigable or at least variable weakness of voluntary muscles, ptosis, ophthalmoparesis, and facial and bulbar weakness. However, oligosymptomatic patients may present with isolated limb weakness, ocular symptoms, and bulbar or respiratory muscle weakness. Correct diagnosis is often difficult in young infants in whom NMTD may present as a floppy infant …