ABSTRACT
I. INTRODUCTION Myasthenia gravis (MG) is a rare neurological disorder characterized by severe, sometimes life-threatening muscle weakness. MG is a prototypical model for antibody-mediated autoimmune diseases, since the effector pathway (i.e., autoantibodies binding to a known target antigen) has been confirmed by many clinical and experimental settings. The target antigen in MG, the acetylcholine receptor (AChR), and the effects of autoantibody binding have been well characterized. A point that merits particular consideration is the observation that MG is almost invariably associated with pathological alterations of the thymus. There is now very good evidence that MG is not a single disease, but rather a common symptom shared by a variety of pathogenetically different diseases. Recent scientific work has helped to characterize a new subgroup of patients with ‘‘seronegative’’MG (autoantibodies against a muscle-specific receptor tyrosine kinase, MuSK) as opposed to classical ‘‘seropositive’’ MG (autoantibodies against the AChR). MG occurs in two age groups with significant clinical and epidemiological differences. In up to 70% of patients, MG presents between the age of 10 and 40 years (early-onset MG) and is usually associated with significant lymphofollicular hyperplasia of the thymus (thymitis). In elderly patients (lateonset MG), MG may be associated with either thymic epithelial tumors (thymomas) or thymic atrophy. This review will focus on current pathogenetic concepts in the different MG-associated entities. For a review of the Lambert-Eaton myasthenic syndrome, which will not be covered here, see Refs. 1-4.
