Lifetime course of myasthenia gravis

Abstract

Between 1940 and 2000 a total of 1976 patients with myasthenia gravis (MG) were studied. Diagnosis was made by improvement in weakness after anticholinesterase medication. The historical developments in diagnosis and treatment of MG are reviewed. We analyzed the clinical course of MG as influenced by age, gender, thymectomy, thymomectomy, and the presence of antibodies to acetylcholine receptors (AChR). The clinical course of MG was significantly influenced by age and gender, and these need special attention in managing patients. The most severe level of weakness and high mortality occurred during the first 1 to 2 years of the disease, after which many patients experienced improvement. For treating MG patients the usefulness of thymectomy remains to be proven, and novel drugs need to be developed to increase the number as well as normal functioning of the AChRs and other components of the neuromuscular system.

Thymoma and autoimmunity

“…The exact role of the thymus and cellular immunity in the pathogenesis of this autoimmune disease is not clear; however, 75% of patients with MG demonstrate some degree of thymus abnormality, including thymic hyperplasia in 85% of those patients and thymoma in 15% of cases. 6 Additionally, in the study by Okumura et al, 9 a strong connection was documented between MG and thymoma in 467 MG patients who underwent thymectomy between 1962 and 2001. The majority of patients were female, and no sex differences were documented between patients with thymoma-associated MG and those with non-thymoma MG. 9 Furthermore, a link was found between MG and certain types of thymomas (B1 and B2) that matched the WHO classifications (Table 1).…”

Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations

“…in 5). As summarized in Table 1, these subgroups consistently show contrasting sex ratios, thymic histology and HLA associations (6,(10)(11)(12)(13). Moreover, several autoantibodies are almost uniquely shared by patients with LOMG or thymomatous MG but not EOMG, which remains unexplained.…”

Precision medicine in myasthenia graves: begin from the data precision

“…Although immunosuppressive treatment may prevent generalization worsening of MG, the maximum severity is seemingly determined by genetic factors, as reflected by the facts that maximum severity is attained after several relapses, regardless of potent immunosuppressive treatment. This is also supported by natural history studies that generalization from ocular MG and worsening to the maximum severity tend to occur during the initial 2 years after onset (44). Therefore, clinical severity measured during the maximum worsening during the long-term follow-up will provide endophenotype information for MG research.…”

“…The early subgrouping systems of MG were based on muscle involvement range and severity, such as in Osserman (32) (21) includes: non-thymoma MG (AChR antibody positive, subdivided into early-onset MG and late-onset MG), thymoma MG, MuSK associated MG, LRP4 associated MG, antibody-negative generalized MG, and ocular MG. In all three systems, the definition of ocular MG required a follow-up of at least 2 years, citing that if the involvement remains limited to the ocular muscles after 2 years, there is 90% likelihood that the disease will not generalize (44). For the generalized subgroups, thymoma-related and antibody-related subgroups, once the data of muscle involvement, thymoma or specific antibodies is satisfied, the subgroup can be defined.…”