Objective: To study the clinical effect of thymectomy in a well-defined early-onset MG subgroup and to correlate it to MG severity, the presence of circulating muscle autoantibodies, and the need for pharmacological treatment in a long-term setting. Methods: Fifty-two consecutive AChR antibody-positive early-onset MG patients (34 thymectomized and 18 nonthymectomized) were included. Severity was assessed and the pharmacological treatment monitored on a yearly basis, starting from the year of MG onset, for 5, 10, 15, and 20 consecutive years; AChR, titin, and RyR antibodies were assayed. Results: In the four follow-up groups, MG severity was significantly higher in nonthymectomized compared to thymectomized MG patients. The postthymectomy MG improvement was significant and persistent. There were 21/34 remissions in thymectomized patients and only 4/18 in the nonthymectomized group. Patients with initially high or low AChR antibody concentration had a similar thymectomy outcome. Only 6 patients had titin antibodies, and none had RyR antibodies. Conclusion: The present study indicates a benefit of thymectomy in early-onset MG. The muscle autoantibody concentration does not influence the outcome of thymectomy in early-onset MG.

Keywords:
Myasthenia gravis, early-onset, Muscle autoantibodies, Thymectomy
1.
Aarli JA, Stefansson K, Marton LSG, Wollmann RL: Patients with myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin. Clin Exp Immunol 1990;82:284–288.
2.
Mygland Å, Tysnes OB, Aarli JA, Flood PR, Gilhus NE: Myasthenia gravis patients with a thymoma have antibodies against a high molecular weight protein in sarcoplasmatic reticulum. J Neuroimmunol 1992;37:1–7.
3.
Romi F, Gilhus NE, Varhaug JE, Myking A, Skeie GO, Aarli JA: Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis. Eur J Neurol 2002;9:55–61.
4.
Venuta F, Rendina EA, De Giacomo T, Della Rocca G, Antonini G, Ciccone AM, Ricci C, Coloni GF: Thymectomy for myasthenia gravis: A 27-year experience. Eur J Cardiothorac Surg 1999;15:621–625.
5.
Gronseth GS, Barohn RJ: Practice parameter: Thymectomy for autoimmune myasthenia gravis (an evidence-based review). Neurology 2000;55:7–15.
6.
Aarli JA: Late-onset myasthenia gravis. A changing scene. Arch Neurol 1999;56:25–27.
7.
Romi F, Skeie GO, Aarli JA, Gilhus NE: Muscle autoantibodies in subgroups of myasthenia gravis patients. J Neurol 2000;247:369–375.
8.
Oosterhuis HJ, Kuks JB: Myasthenia gravis and myasthenic syndromes. Curr Opin Neurol Neurosurg 1992;5:638–644.
9.
Salabe GB: Pathogenesis of thyroid nodules: Histological classification? Biomed Pharmacother 2001;55:39–53.
10.
Saraux A, Berthelot JM, Chales G, Le Henaff C, Thorel JB, Hoang S, Valls I, Devauchelle V, Martin A, Baron D, Pennec Y, Botton E, Mary JY, Le Goff P, Youinou P: Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later. Arthritis Rheum 2001;44:2485–2491.
11.
Ainiala H, Hietaharju A, Loukkola J, Peltola J, Korpela M, Metsanoja R, Auvinen A: Validity of the new American College of Rheumatology criteria for neuropsychiatric lupus syndromes: A population-based evaluation. Arthritis Rheum 2001;45:419–423.
12.
Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, Nanjo K, Sasaki A, Seino Y, Ito C, Shima K, Nonaka K, Kadowaki T: Report of the Committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract 2002;55:65–85.
13.
Cross SS, Harrison RF: Discriminant histological features in the diagnosis of chronic idiopathic inflammatory bowel disease: Analysis of a large dataset by a novel data visualisation technique. J Clin Pathol 2002;55:51–57.
14.
Stafford L, Youssef PP: Spondyloarthropathies: An overview. Intern Med J 2002;32:40–46.
15.
MacMahon B: Cohort studies; in MacMahon B, Trichopoulos D (eds): Epidemiology Principles and Methods. Boston, Little, Brown and Company, 1996, pp 168–223.
16.
Jaretzki A III, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB: Myasthenia gravis: Recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 2000;55:16–23.
17.
Osserman K, Genkins G: Studies in myasthenia gravis: Review of a twenty-year experience in over 1200 patients. Mount Sinai J Med 1981;38:497–537.
18.
Detterbeck FC, Scott WW, Howard JF, Egan TM, Keagy BA, Starek JK, Mill MR, Willcox BR: One hundred consecutive thymectomies for myasthenia gravis. Ann Thorac Surg 1996;62:242–245.
19.
Scott W, Detterbeck F: Transsternal thymectomy for myasthenia gravis. Semin Thorac Cardiovasc Surg 1999;11:54–58.
20.
Thorlacius S, Mollnes TE, Garred P, Aarli JA, Matre R, Tonder O, Halvorsen K: Plasma exchange in myasthenia gravis: Changes in serum complement and immunoglobulins. Acta Neurol Scand 1988;78:221–227.
21.
Lefvert AK, Bergstrøm K, Matell G, Osterman PO, Pirskanen R: Determination of acetylcholine receptor antibody in myasthenia gravis – Clinical usefulness and pathogenic implications. J Neurol Neurosurg Psychiat 1978;41:394–403.
22.
Skeie GO, Mygland Å, Aarli JA, Gilhus NE: Titin antibodies in patients with late-onset myasthenia gravis: Clinical correlations. Autoimmunity 1995;20:99–104.
23.
Romi F, Skeie GO, Aarli JA, Gilhus NE: The severity of myasthenia gravis correlates with the serum concentration of titin and ryanodine receptor antibodies. Arch Neurol 2000;57:1596–1600.
24.
Skeie GO, Mygland Å, Trevers S, Gilhus NE, Aarli JA, Zorzato F: Ryanodine receptor antibodies in myasthenia gravis: Epitope mapping and effect on calcium release in vitro. Muscle Nerve 2003;27:81–89.
25.
Mygland Å, Tysnes OB, Matre R, Volpe P, Aarli JA, Gilhus NE: Ryanodine receptor autoantibodies in myasthenia gravis patients with thymoma. Ann Neurol 1992;32:589–591.
26.
Keynes G: The results of thymectomy in myasthenia gravis. BMJ 1949;2:611–616.
27.
Simpson JA: An evaluation of thymectomy in myasthenia gravis. Brain 1958;81:112–144.
28.
Perlo VP, Arnason B, Castleman B: The thymus gland in elderly patients with myasthenia gravis. Neurology 1975;25:294–295.
29.
Slater G, Papatestas AE, Genkins G, Kornfeld P, Horowitz SH: Thymectomy in patients more than forty years of age with myasthenia gravis. Surg Gynecol Obstet 1978;146:54–56.
30.
Frist WH, Thirumalai S, Doehring CB, Merrill WH, Stewart JR, Fenichel GM, Bender HW Jr: Thymectomy for the myasthenis gravis patient: Factors influencing outcome. Ann Thorac Surg 1994;57:334–338.
31.
Busch C, Machens A, Pichlmeier U, Emskötter T, Izbicki JR: Long-term outcome and quality of life after thymectomy for myasthenia gravis. Ann Surg 1996;224:225–232.
32.
Romi F, Skeie GO, Vedeler C, Aarli JA, Zorzato F, Gilhus NE: Complement activation by titin and ryanodine receptor autoantibodies in myasthenia gravis. A study of IgG subclasses and clinical correlations. J Neuroimmunol 2000;111:169–176.
33.
Aarli JA, Gilhus NE, Hofstad H: CA-antibody: An immunological marker of thymic neoplasia in myasthenia gravis ? Acta Neurol Scand 1987;63:55–57.
34.
Voltz RD, Albrich WC, Nägele A, Schumm F, Wick M, Freiburg A, Gautel M, Thaler HT, Aarli JA, Kirchner T, Hohlfeld R: Paraneoplastic myasthenia gravis: Detection of anti-MGT30 (titin) antibodies predicts thymic epithelial tumor. Neurology 1997;49:1454–1457.
35.
Mygland Å, Aarli JA, Matre R, Gilhus NE: Ryanodine receptor antibodies related to severity of thymoma associated myasthenia gravis. J Neurol Neurosurg Psychiatry 1994;57:843–846.
36.
Skeie GO, Bartoccioni E, Evoli A, Aarli JA, Gilhus NE: Ryanodine receptor antibodies are associated with severe myasthenia gravis. Eur J Neurol 1996;3:136–140.
37.
Müller-Hermelink HK, Marx A, Kirchner T: The pathological basis of thymoma-associated myasthenia gravis. Ann NY Acad Sci 1993;681:56–65.
38.
Willcox N, Vincent A: Myasthenia gravis as an example of organ specific autoimmune disease; in Bird G, Calvert JE (eds): B Lymphocytes in Human Disease. Oxford, Oxford University Press, 1988, pp 469–506.
39.
Myking AO, Skeie GO, Varhaug JE, Andersen KS, Gilhus NE, Aarli JA: The histomorphology of the thymus in late-onset, non-thymoma myasthenia gravis. Eur J Neurol 1998;5:401–405.
40.
Giraud M, Beaurain G, Yamamoto AM, Eymard B, Tranchant C, Gajdos P, Garchon HJ: Linkage of HLA to myasthenia gravis and genetic heterogeneity depending on anti-titin antibodies. Neurology 2001;57:1555–1560.
41.
Yamamoto AM, Gajdos P, Eymard B, Tranchant C, Warter JM, Gomez L, Bourquin C, Bach JF, Garchon HJ: Anti-titin antibodies in myasthenia gravis: Tight association with thymoma and heterogeneity of nonthymoma patients. Arch Neurol 2001;58:885–890.
42.
Slesak G, Melms A, Gerneth F, Sommer N, Weissert R, Dichgans J: Late-onset myasthenia gravis. Follow-up of 113 patients diagnosed after age 60. Ann NY Acad Sci 1998;841:777–780.
© 2003 S. Karger AG, Basel
2003
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.