Seronegative Myasthenia Gravis

Angela Vincent; John McConville; Maria Elena Farrugia; John Newsom-Davis

doi:10.1055/s-2004-829589

Seminars in Neurology, Table of Contents

Semin Neurol 2004; 24(1): 125-133
DOI: 10.1055/s-2004-829589

Seronegative Myasthenia Gravis

Angela Vincent¹ , John McConville¹ , Maria Elena Farrugia¹ , John Newsom-Davis¹

¹Department of Clinical Neurology, University of Oxford, Oxford, United Kingdom

Abstract

Some myasthenia gravis (MG) patients do not have detectable acetylcholine receptor (AChR) antibodies and have been termed “seronegative” (SNMG) in many previous studies. A high proportion of patients with purely ocular symptoms, ocular MG, are seronegative; this may be because the sensitivity of the assay is insufficient to detect low levels of circulating AChR antibodies and because of intrinsic differences in the ocular muscles that make them more susceptible to circulating factors. Seronegative generalized myasthenia is proving to be heterogeneous both clinically and immunologically. Plasma from SNMG patients often contains a factor, probably an immunoglobulin M antibody, that alters AChR function in in vitro assays, but its target is not yet clear. A variable proportion of SNMG patients have antibodies to the muscle-specific tyrosine kinase (MuSK). These antibodies are directed against the extracellular domain of MuSK and inhibit agrin-induced AChR clustering in muscle myotubes. Although the role of these antibodies in causing myasthenic symptoms in vivo has not been elucidated, MuSK antibodies appear to define a group of patients who are often female with bulbar weakness, contrasting with MuSK antibody-negative SNMG patients who are more likely to have generalized weakness. MuSK antibody-positive patients may also differ in the distribution of their electrophysiological abnormalities and their responses to treatments.

KEYWORDS

Myasthenia - seronegative - muscle-specific kinase - MuSK - acetylcholine receptor desensitization

Full Text

References

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Angela VincentM.D.

Neurosciences Group, Department of Clinical Neurology, Weatherall Institute of Molecular Medicine

John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom