A treatment protocol for autoimmune myasthenia gravis (MG), patients sero-positive for AChR antibodies, is proposed from the University of California, Davis, CA. The greatest advances in outcome have resulted from therapies that reduce the autoimmune attack or modify its effect on the nicotinic acetylcholine receptor (AChR) and prevent damage to the structure of the endplate. More effective symptomatic treatment, including critical care and the use of cholinesterase inhibitors, has contributed to an improved prognosis. The initial therapy is determined on an individual cost/benefit ratio. Cholinesterase inhibitor drugs, first introduced in 1934 [1], and especially pyridostigmine, are usually effective early in the disease course or in mild cases. Tolerance develops and eventually the effect lessens even at maximal, frequently toxic, doses. The more effective treatments directly target the autoimmune response, reducing the likelihood of endplate damage. Immuno-directed treatment should begin when an early spontaneous remission is not obtained with pyridostigmine. High-dose daily prednisone is started, and short-term IV Ig or plasmapheresis is added if symptoms worsen in the first 2 weeks, or given concomitantly. Tapering of the prednisone is begun slowly when remission is established. Later, a steroid-sparing agent (eg azathioprine) and a bisphosphonate to prevent osteoporosis are added to the low-dose prednisone. The minimum amount of prednisone to maintain a remission is the goal in management. Thymectomy also acts as a steroid-sparing treatment and facilitates remission. Uncontrolled studies show that the earlier the operation, the better the result, and newer surgical techniques may carry less risk. The goal for optimal therapy is an increased specificity of immune-directed agents that reduce the antibodies or T-cell responses to the AChR, leaving other immune responses intact. [2]

COMMENT. The incidence of sero-positive acetylcholine receptor (AChR) binding antibodies is lower in juvenile-onset myasthenia gravis compared to adult-onset case-studies; 63% (Afifi and Bell 1993) v 85% (Richman and Agius 2003), respectively. In a series of 30 juvenile MG cases studied in Turkey (Anlar et al, 1996) AchR antibodies were positive in 34%, and response to treatment was not significantly different in seropositive cf seronegative cases. None of the antibody-positive cases was in remission. Myasthenic crises occurred in 33%. In a current report from Mexico [3] the response to thymectomy was evaluated in 71 patients with MG of all ages (14 [20%] seronegative, and 57 [80%) seropositive). The response was similar in the two groups, with no differences in prognosis between the seronegative and seropositive patients.

In the Afifi and Bell, 1993 University of Iowa series of 27 juvenile MG cases, ocular myasthenics responded to pyridostigmine alone, while generalized myasthenics required corticosteroids and/or thymectomy. Those with normal thymus had a higher rate of remission than patients with thymic hyperplasia. Thymectomized patients had a 35% remission rate. In a series of 35 juvenile myasthenics (Millichap and Dodge 1960), 43% had respiratory difficulties, 40% of these requiring tracheostomy. Twenty-one underwent thymectomy and of these 18 (86%) showed complete or partial remission. Complete remission without the need for drug therapy was obtained in 29% of thymectomized compared to 14% of patients treated only with cholinergic drugs. Rodriquez et al, in 1983, found a cumulative 15-year remission rate of 55% following thymectomy, compared to a spontaneous remission rate of 30% in myasthenic children. The remission rate was higher following thymectomy performed within 12 months of the onset of symptoms. The reported high incidence of myasthenic crises and respiratory difficulties, and the satisfactory results of early thymectomy emphasize the importance of prompt introduction of immune-directed management when spontaneous remission is delayed.