Key words: seronegative myasthenia gravis, muscle atrophy, muscle-specific receptor tyrosine kinase (MuSK) antibody, tongue atrophy Myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disorder with easy fatigability of the muscles based on a neuromuscular transmission defect. Most myasthenic patients have antiacetylcholine receptor antibodies which attach to the acetycholine receptor of the postsynaptic membrane of the skeletal muscles and decrease the amplitude of miniature endplate potentials (mepp) and endplate potentials (epp) causing subthreshold epp, which become too low to produce muscle action potentials after exercise and subsequently muscle contraction power is reduced. Some myasthenic patients do not have Ach receptor antibodies in the serum; these cases are termed seronegative MG (1). In generalized MG 67–93% of patients have serum antibodies, but 10–15 % of patients with generalized MG and 30–50% of ocular MG do not have Ach receptor antibodies even with repeated studies. Recently serum antibody against the muscle-specific receptor tyrosine kinase (MuSK) have been reported and this antibody is present in the serum in 70% of seronegative MG patients (1). How this antibody causes myasthenic symptoms to develop is still controversial. The hypothesis is that MuSK antibody may block agrin, which is a protein released from the nerve endings, to meet MuSK for cluster formation of acetylcholine (Ach) receptor (2). However, the report of Selcen et al (3) does not agree with this hypothesis and MuSK antibody does not cause deficiency of MuSK, nor Ach receptor. Clinical characteristics of seronegative MG (2) can be summarized as 1) female preponderance (M : F= 4 : 23), 2) no thymoma, 3) bulbar palsy and respiratory muscle weakness, and some of the cases have muscle atrophy of the face and the tongue, 4) poor response to pyridostigmine, and some may respond to high-dose prednisolone, cyclosporin, or mycophenolate mofetil. The response to thymectomy among seronegative and seropositive MG patients was studied by Guillermo et al (4) and the results showed no differences between the two groups: 21% of the thymectomized patients had remission and 30–36% of the thymectomized patients had improvement, and no change in 36–44% of the patients. Most effective therapy for seronegative MG is apheresis. Ishii et al (5) reported a 24-year-old Japanese woman, a case of generalized MG with anti-MuSK antibody who had a progressive muscular atrophy and weakness mainly in the bulbar region and the upper extremities.