Plasma exchange and intravenous immune globulin For severe myasthenia that is refractory to treatment with anticholinesterase drugs and prednisone, or during an acute period of worsening, one must resort to other measures. Striking temporary remissions (2 to 8 weeks) may be obtained by the use of plasma exchange. This form of treatment may be lifesaving during a myasthenic crisis. It also finds use before and after thymectomy and at the start of immunosuppressive drug therapy. Plasma exchange is also helpful in limiting the aforementioned weakness that is often induced by the institution of high-dose corticosteroids. The number and volume of exchanges required in these circumstances is somewhat arbitrary but they tend to be less than those required for GBS; several exchanges of 2 to 3.5 L each (totaling approximately 125 mL/kg) performed over a week usually suffice. The removed plasma is replaced with albumin and saline. It has been estimated that a 2-L exchange will remove 80 percent of circulating antibodies and that this will be reflected in reduced ACh antibody levels in 3 to 5 days. There is only an approximate correlation between a reduction in the titer of anti-AChR antibody and the degree of clinical improvement. In a crisis requiring plasma exchanges and mechanical ventilation, it has been our practice to discontinue or curtail the use of anticholinesterase drugs and resume them as the patient is being weaned from the ventilator. Also, it may be that sensitivity to these drugs may be enhanced in the hours after an exchange so that their dosages must be adjusted accordingly.
A small number of patients respond so well to plasma exchange and find the side effects of steroids so intolerable that they choose to be maintained with 2 to 3 exchanges every several weeks or months. Immuno–adsorption, a technique similar to plasma exchange that removes antibodies and immune complexes by passing blood over a tryptophan column, is less cumbersome than conventional plasma exchange and has been effective, but experience with this procedure is limited.
Intravenous immune globulin is similarly useful in the short-term control of acutely worsening myasthenia. The usual dose is 2 g/kg given in divided doses over 3 to 5 days. Several small series suggest that the effect is equivalent to a series of plasma exchanges. However, plasma exchange and immune globulin have been subjected to only limited systematic study or comparison and, while these treatments are invaluable in deteriorated patients or those in crisis, they offer only short-term benefit. In two separate small studies, Gajdos and colleagues and Barth et al found no difference between intravenous immune globulin (IVIg) and plasma exchange (1997) and no difference between IVIg 1 g/kg/d given for 1 or 2 days (2005) in myasthenic exacerbations, most cases of which were less severe than typical crisis.
Thymectomy This operation, first introduced by Blalock, despite the absence of proof in trials, is considered an appropriate procedure for many patients with generalized myasthenia gravis between puberty and 55 years of age. The surgery is performed electively and not during an acute deterioration of myasthenia. The remission rate after thymectomy is approximately 35 percent provided that the procedure is done in the first year or 2 after onset of the disease, and another 50 percent will improve to some extent (Buckingham et al). The remission rate is progressively lower, but not negligible, if the operation is postponed beyond this time. In patients with myasthenia restricted to the ocular muscles for a year or longer, the prognosis is so good that thymectomy is unnecessary. The response to thymectomy is not evident for several months and is usually maximal by approximately 3 years. In favorably responding cases, levels of circulating receptor antibody are reduced or disappear entirely. If possible, thymectomy should be postponed until puberty because of the importance of the gland in the development of the immune system, but juvenile myasthenia is also quite responsive. The results are not as predictable in patients who harbor a thymoma.