PROGNOSIS AFTER THYMECTOMY IN OLDER PATIENTS WITH MYASTHENIA GRAVIS

Abstract

To the Editor: The management of older patients (onset after age 60) with myasthenia gravis (MG) is frequently troublesome, and definite guidelines for treatment of these patients have not yet been established. The article by Evoli et al.,1 reporting the clinical characteristics and prognosis of 172 older patients with MG, was of great interest. The number of older patients with MG has been increasing in Japan. We evaluated 135 unrelated Japanese patients with MG who were seen at Keio University Hospital from January 1991 through December 2000, and identified 24 (17.7%) in whom the onset of MG was at or after the age of 60. There were 13 men and 11 women (M/F = 1.18), and age at onset ranged from 60 to 87 years (mean, 69.0). At maximum disease severity, eight patients (33.3%) had the ocular form of MG, whereas 16 (66.6%) had the generalized form. Anti-acetylcholine receptor antibody, measured by conventional assay, was positive in 21 patients (87.5%). The frequency of older patients with MG and the clinical characteristics of in-series were therefore compatible with recent published series describing Caucasians.1–3 In Japan, prednisone was the only approved immunosuppressive agent for MG treatment until September 2000, when tacrolimus (FK-506) received approval as a medication for MG from the Ministry of Welfare. Of 24 patients, only nine (37.5%) required immunosuppressive therapy with prednisone (starting dose of 0.5–1.0 mg/kg/day). This frequency was much lower than that in the report by Evoli et al. (80.5%).1 This is attributable to seven patients (29.1%) with the ocular form in our series whose symptoms could be controlled with anticholine esterase agents alone. Good results, as defined by Evoli et al.,1 were obtained in 17 patients (70.8%). Better outcomes might have been obtained in our series had we chosen the combination treatment with prednisone plus azathioprine, as proposed by Evoli et al.1 In particular, some older patients with bulbar symptoms experienced ongoing deterioration, and it was difficult to control the disease. Side effects of prednisone were observed in four patients (44.4%), although no cancers other than thymoma were found during follow-up. The four side effects were tuberculosis, myopathy, diabetes mellitus, and osteoporosis. This frequency was similar to that in the series by Evoli et al. (46.2%).1 The indications for and benefits of thymectomy in older patients with generalized MG remain controversial. We question whether the prognosis of older patients in whom thymectomy was performed was actually good in the series of Evoli et al.1 We conducted the following comparisons in our series. Statistical analysis was performed by chi-square and Student's t-tests. First, we divided older patients with generalized MG into two groups, a thymectomized group (n = 7) and a nonthymectomized group (n = 9). According to the general consensus,4 transsternal extended thymectomy was generally performed in our hospital when thymoma was detected on computed tomography or magnetic resonance images. Thymectomy could not be performed in one patient because of an old myocardial infarction. Prednisone treatment was required in four patients (57%) in the thymectomized group and in four patients (44%) in the nonthymectomized group (P = .6). Rates of good results were 57% in the thymectomized groups and 66% in the nonthymectomized group (P> 1.0). These data suggest that the prognosis of older patients with MG does not depend on thymectomy. Second, we compared prognosis after thymectomy in older patients to that in younger patients. Thymectomy was performed in 70 patients with onset of MG before the age of 60. To exclude any bias associated with pathological differences, we selected 34 patients (48.5%) with thymoma from this younger group. The clinical characteristics and prognosis of these two groups (the younger group (n = 34) and the older group (n = 7)) are summarized in Table 1. The prognosis tended to be worse in the older than in the younger group. The higher frequency of invasive thymoma in older patients appears to contribute to their poorer prognosis. Although Tsuchida et al. reported that thymectomy was effective for older patients with MG,5 even if no thymoma was detected, most of their patients required prednisone treatment after thymectomy. In fact, they showed the remission rate to be 40% in younger patients, but 8% in older patients.5 Considering these observations together, we emphasize that the prognosis after thymectomy in older patients is not as good as in younger patients, and that their clinical features constitute a particular challenge in treating older patients with MG.