Thymectomy for the Elderly Myasthenic
Abstract & Commentary
Source: Tsuchida M, et al. Efficacy and safety of extended thymectomy for elderly patients with myasthenia gravis. Ann Thorac Surg 1999;67:1563-1567.
Among 94 patients who underwent thymecto-my for myasthenia gravis (MG) between 1985 and 1996, comparison between those older (n = 69) and younger (n = 25) than 60 years of age was performed to determine and contrast safety and efficacy of the procedure in these two groups. Diagnosis was based on clinical signs and symptoms, positive edrophonium test, and electromyography, and indications for surgery included generalized and ocular MG under maximum medical therapy. All patients underwent transsternal thymectomy and postoperative management included anticholinesterase agents and corticosteroids as needed. Outcome was evaluated at one year or more postoperatively and scored as remission, improvement with the same or less medication, same symptoms with more medication, or worse. Statistical analysis used the X2 test and P less than 0.05 was considered significant.
Although the two groups differed significantly regarding thymic pathology postoperatively, with hyperplasia more common in the young (45% vs 16%) and thymoma in the old (40% vs 32%), preoperative data, apart from age, did not differ between the groups. Remission was more likely in the young (40% vs 8%; P < 0.05) but improvement, worsening, or death occurred equally in both groups. Thymectomy was of benefit in 97% and 83% overall in the young and old, respectively. Older age is not a contraindication to thymectomy in MG, and improvement requiring continued medication, though not remission, is to be expected.
Commentary
Thymectomy is of demonstrable benefit in the management of MG but a growing literature suggests that it may not be without long-term risks, including the late emergence of autoimmune disorders encompassing systemic lupus erythematosus, Hashimoto’s thyroiditis, ulcerative colitis, polymyositis, and primary antiphospholipid antibody syndrome (N Engl J Med 1964;278: 229-232; Neurology 1979;29:1436-1437; Acta Neurol Scand 1992;85:63-65; Lupus 1997;6:474-476). To explore the pathophysiology of this association, 16 long-term (> 8 years) post-thymectomy MG patients were compared to six recent (< 1 year) post-thymectomy MG patients, 13 nonthymectomized MG patients, and 32 normal controls (Gerli R, et al. J Allergy Clin Immunol 1999;103:865-872). All patients were off immunoactive agents for at least 22 months and only anticholinesterase agents were permitted. Serologic studies were undertaken, encompassing rheumatoid factor, IgG, IgA, and IgM levels, anticardiolipin IgG or IgM antibodies, and thyroid and acetylcholine receptor antibodies. T- and B-cell subtypes were also analyzed, including CD3+, CD4+, and CD8+ T cells, and CD19+, and CD19+/CD5+ B cells, as well as the Vb T-cell receptor repertoire of CD4+ and CD8+ cells comprising Vb2, Vb3, Vb5a, Vb5b, and Vb6a. Follow-up of MG patients was undertaken for three years to ascertain the development of autoimmune disorders, and statistical analysis of the results used one-way ANOVA comparison.
Significantly reduced numbers of T cells, with normal CD4+/CD8+ ratio, and expansion of natural killer CD16+/CD57- cells characterized the long-term post-thymectomy group. Total and CD5+ B cells were normal but IgG, IgM, anticardiolipin, and anti-dsDNA antibodies were increased, and ANA titre of 1:160 or more were only seen in this group. Two long-term patients, but none in the other groups, developed autoimmune disease, one with lupus and one with undifferentiated connective tissue disease. T-cell lymphopenia and hypergammaglobulinemia are seen long-term post-thymectomy and these long-term effects may explain the development of autoimmune disease in MG as a consequence of thymectomy rather than as an association of autoimmune disease with MG ab initio. —mr
Which of the following statements is correct?
a. Older age is not a contraindication to thymectomy in myasthenia.
b. Complete remission following thymectomy in myasthenia is most likely when surgery is performed late in the disease.
c. Stage IV myasthenia patients are more likely than stages I-III to achieve complete remission following thymectomy.
d. T-cell lymphopenia is seen short-term post-thymectomy in myasthenia.
e. Hypergammaglobulinemia is seen long-term in nonthymectomized myasthenic patients.
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