NEW AND OLD STRATEGIES IN THE TREATMENT OF MYASTHENIA GRAVIS

Although the term “Myasthenia Gravis Pseudoparalytica”, coined by Jolly in 1895, emphasized the grave prognosis of the disease at that time, the outlook for myasthenic patients has improved dramatically in recent years as a result of important advances in treatment. At present, with optimal treatment, the mortality rate is essentially zero, and nearly all myasthenic patients can be returned to full productive lives. Myasthenia (MG) is now the best understood human autoimmune disease, and is certainly the most treatable neuromuscular disease.

The goal of treatment of MG is defined in terms of clinical benefit: ie- to restore the patient to fully functional status, and maintain the improved condition without recurrence or adverse effects of the treatments. This talk will emphasize a practical treatment plan based on a “Time-linked” strategy, in which the short-term, intermediate term, and long term needs of the myasthenic patient are dealt with.

The steps in the treatment program can be divided into: (1) Preliminaries; (2) Selection of agents for treatment; (3) Avoidance of agents or treatments that pose undue risks; (4) Adjusting the treatment parameters needed for the individual patient throughout the entire disease course, which is commonly lifelong.

Preliminaries involve (1) establishing the diagnosis unequivocally, since it commits the patient and physician to a prolonged course of medical and sometimes surgical treatment, with potential risks; (2) Searching for Associated Conditions (a) that may occur with increased incidence in myasthenic patients; (b) that may coexist, and lead to exacerbation of MG; (c) that may influence the choice of treatment methods for MG.

Selection of agents for treatment: Treatment options for MG fall into 6 categories: (1) Enhancement of cholinergic transmission; (2) Short term immunotherapy: (3) Immunosuppression; (4) Thymectomy; (5) Management of associated conditions; and (6) Treatment of refractory MG. The most important advance in the treatment of MG has been the development and understanding of an array of immunosuppressive agents, which can be used in creative ways for almost all patients. Recently, we have treated the relatively few “refractory” MG patients by “re-booting” the immune system, with high-dose cyclophosphamide, which results in dramatic improvement in most cases. Future immunotherapy will involve specific methods that target the pathogenic autoreactive immune cells without affecting the otherwise normal components of the immune system.