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reviews Indications for thymectomy in myasthenia gravis Douglas J. Lanska, MD, MS
Article abstract-Fifty-six board-certified neurologists with interest and expertise in myasthenia completed a survey of indications for thymectomy in myasthenia gravis. Thymectomy was advocated for virtually all patients with thymoma, for a variable subset of patients with generalized myasthenia without thymoma, and occasionally for selectedpatients with disabling ocular myasthenia. NEUROLOGY 1990;40:1828-1829 In 1939, Alfred Blalock’ reported remission of generalized myasthenia gravis in a 21-year-oldwoman following removal of the cystic remains of a necrotic thymic tumor. Subsequently, case series and retrospective studies from several centers in Europe and the United States have suggested that thymectomy improves the outcome of patients with myasthenia gravis. In spite of this, the procedure remains contro~ersial.~-~ We evaluated current indications for thymectomy among neurologists with interest and expertise in myasthenia gravis. Methods. At present, the Medical Advisory Board of the Myasthenia Gravis Foundation includes 59 neurologists certified by the American Board of Psychiatry and Neurology. A brief survey of indications for thymectomy was sent to all members of the Board in November 1989, with nonrespondents contacted by telephone. Responses were obtained from 56 certified neurologists; the other 3 had retired or were no longer seeing myasthenic patients.
Results. Forty-nine of the 56 neurologists provided some information on the number of myasthenic patients they followed and the proportion that have had a thymectomy. Only 4 advocated the procedure in less than ‘/3 of their patients; 28 advocated it for 113 to 213 of their patients; and 17 advocated it for more than 2/3 of their patients. There was no apparent relationship between the number of myasthenia gravis patients followed by a neurologist and the proportion of these who have undergone thymectomy. Eleven neurologists expressed severe reservations about the efficacy of the procedure. Nevertheless, these individuals advocated surgery for selected patients because of the low morbidity, potential benefit, and widespread acceptance (“by consensus”) of the procedure among physicians caring for myasthenic patients.
Among this group of neurologists, the procedure was generally reserved for patients with severe disease or after other modalities had failed. All 56 individuals advocated thymectomy for most or all patients with suspected thymoma based on radiologic studies, since such tumors are potentially invasive and since removal is sometimes accompanied by improvement in myasthenic ~ymptorns.~.~ Six offered relative contraindications to thymectomy in individuals with suspected thymoma: poor surgical risk, elderly or limited life expectancy, preoperative evidence of local spread, and pregnancy. Most neurologists felt that ocular myasthenia was not an indication for thymectomy, since ocular myasthenia was considered unlikely to be sufficiently disabling to warrant an invasive procedure. In addition, some neurologists felt that ocular myasthenia was likely to spontaneously remit and respond well to medication alone. Seven neurologists advocated thymectomy in selected patients with ocular myasthenia, particularly if it was disabling and unresponsive to anticholinesterase medication. As indicated by these respondents, “disability” could be a result of either cosmetic factors or visual dysfunction from diplopia or ptosis. Generalized myasthenia gravis in the absence of radiologic evidence of thymoma was the most controversial category. Only 3 individuals advocated thymectomy without reservation in this group. The remaining neurologists reserved the procedure for selected patients, depending on the age of the patient, severity of disease, response to medication, and duration of disease. Thirty-two neurologists did not advocate the procedure for older individuals; the age cutoff varied from 50 to 70 years (median, 60 years). Justification for an upper age limit was variable and included (1) a presumption that older individuals had greater morbidity from the pro-
From the Departments of Neurology, Preventive Medicine and Environmental Health, and the Sanders Brown Center on Aging, University of Kentucky Medical Center, Lexington, KY. Received May 14,1990. Accepted for publication in final form May 14,1990. Addreas correspondence and reprint requests to Dr. Douglas J. Lanska, Department of Neurology,Albert B. Chandler Medical Center, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0084. 1838 NEUROLOGY 40 December 1990
cedure; (2) clinical experience suggesting that older individuals were more responsive to medical therapy than younger individuals; (3) concern that the positive effect of therapy might not be manifest within the limited remaining life span of older individuals; and (4) absence of empiric support for the procedure in older individuals. Although recognized as controversial, 6 individuals advocated a lower age limit for thymectomy, varying from 1year to puberty (median, 7.5 years). The rationale for a lower age limit was based on evidence of altered T-cell function in thymectomized infants.l0 Other restrictions were as follows: 21 individuals reserved the procedure for those with disabling myasthenia; 14 reserved t h e procedure for those unresponsive to anticholinesterase medication alone (n = 10) or those unresponsive to anticholinesterase medication and immunosuppressants (n = 4); and 12 reserved the procedure for individuals with myasthenia gravis of recent onset (ie, within 2 to 5 years of onset).
Discussion. A t present, neurologists with interest and expertise in myasthenia gravis use a variety of therapeutic strategies. Most neurologists advocate thymectomy for selected patients with generalized myasthenia without thymoma. Specific restrictions vary as a function of age, disease severity and duration, and response to medication. Thymectomy is occasionally advocated for patients with disabling ocular myasthenia. With few exceptions, thymectomy is recommended for virtually all patients with thymoma. There has been no prospectively controlled trial in which patients with myasthenia gravis are allocated randomly either to surgery or to medical therapy alone. There were attempts to organize such a controlled trial of thymectomy in 1963 and in 1980, but both attempts
foundered under a variety of controversies. In the absence of a controlled trial, therapeutic benefit will remain unproven, and specific indications and contraindications will be based upon the preference of individual neurologists,
Acknowledgment The author thanks Michael P. McQuillen for helpful discussions and for critically reviewing the manuscript.
References 1. Blalwk A, Mason MF, Morgan HJ, Riven SS. Myasthenia gravis and tumors of the thymic region; report of a case in which the tumor was removed. Ann Surg 1939;110:544-559. 2. Buckingham JM. Howard FM, Bernatz PE, et al. The value of thymectomy in myasthenia gravis: a computer-assisted matched study. Ann Surg 1976;184:453-458. 3. Keesey J. Indications for thymectomy in myasthenia gravis. In: Dau PC, ed. Plasmapheresis and the immunobiology of myasthenia gravis. Boston: Houghton Mifflin, 1979:124-136. 4. Keynes G. Surgery of the thymus gland second (and third) thoughts. Lancet 1954;l:1197-1202. 5. Keynes G. The history of myasthenia gravis. Med Hist 1961;5:313-326. 6. Perlo VP. Symposium on therapeutic controversies: myasthenia gravis-thymectomy: pro. T r a n s Am Neurol Assoc 1978;103:282-283. 7. McQuillen MP. Symposium on therapeutic controversies: myasthenia gravis-thymectomy: con. Trans Am Neurol Assoc 1978;103:283-286. 8. McQuillen MP, Leone MG. A treatment carol: thymectomy revisited. Neurology 1977;12:1103-1106. 9. Rowland LP. Controversies about the treatment of myasthenia gravis. J Neurol Neurosurg Psychiatry 1980;43644-659. 10. Brearley S, Gentle TA, Baynham MI, Roberta KD, Abrams LD, Thompson RA. Immunodeficiency following neonatal thymectomy in man. Clin Exp Immunol1987;70322-327.
December 1990 NEUROLOGY 40 1839
Indications for thymectomy in myasthenia gravis Douglas J. Lanska Neurology 1990;40;1828 DOI 10.1212/WNL.40.12.1828 This information is current as of December 1, 1990 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/40/12/1828.full.html
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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1990 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
reviews Indications for thymectomy in myasthenia gravis Douglas J. Lanska, MD, MS
Article abstract-Fifty-six board-certified neurologists with interest and expertise in myasthenia completed a survey of indications for thymectomy in myasthenia gravis. Thymectomy was advocated for virtually all patients with thymoma, for a variable subset of patients with generalized myasthenia without thymoma, and occasionally for selectedpatients with disabling ocular myasthenia. NEUROLOGY 1990;40:1828-1829 In 1939, Alfred Blalock’ reported remission of generalized myasthenia gravis in a 21-year-oldwoman following removal of the cystic remains of a necrotic thymic tumor. Subsequently, case series and retrospective studies from several centers in Europe and the United States have suggested that thymectomy improves the outcome of patients with myasthenia gravis. In spite of this, the procedure remains contro~ersial.~-~ We evaluated current indications for thymectomy among neurologists with interest and expertise in myasthenia gravis. Methods. At present, the Medical Advisory Board of the Myasthenia Gravis Foundation includes 59 neurologists certified by the American Board of Psychiatry and Neurology. A brief survey of indications for thymectomy was sent to all members of the Board in November 1989, with nonrespondents contacted by telephone. Responses were obtained from 56 certified neurologists; the other 3 had retired or were no longer seeing myasthenic patients.
Results. Forty-nine of the 56 neurologists provided some information on the number of myasthenic patients they followed and the proportion that have had a thymectomy. Only 4 advocated the procedure in less than ‘/3 of their patients; 28 advocated it for 113 to 213 of their patients; and 17 advocated it for more than 2/3 of their patients. There was no apparent relationship between the number of myasthenia gravis patients followed by a neurologist and the proportion of these who have undergone thymectomy. Eleven neurologists expressed severe reservations about the efficacy of the procedure. Nevertheless, these individuals advocated surgery for selected patients because of the low morbidity, potential benefit, and widespread acceptance (“by consensus”) of the procedure among physicians caring for myasthenic patients.
Among this group of neurologists, the procedure was generally reserved for patients with severe disease or after other modalities had failed. All 56 individuals advocated thymectomy for most or all patients with suspected thymoma based on radiologic studies, since such tumors are potentially invasive and since removal is sometimes accompanied by improvement in myasthenic ~ymptorns.~.~ Six offered relative contraindications to thymectomy in individuals with suspected thymoma: poor surgical risk, elderly or limited life expectancy, preoperative evidence of local spread, and pregnancy. Most neurologists felt that ocular myasthenia was not an indication for thymectomy, since ocular myasthenia was considered unlikely to be sufficiently disabling to warrant an invasive procedure. In addition, some neurologists felt that ocular myasthenia was likely to spontaneously remit and respond well to medication alone. Seven neurologists advocated thymectomy in selected patients with ocular myasthenia, particularly if it was disabling and unresponsive to anticholinesterase medication. As indicated by these respondents, “disability” could be a result of either cosmetic factors or visual dysfunction from diplopia or ptosis. Generalized myasthenia gravis in the absence of radiologic evidence of thymoma was the most controversial category. Only 3 individuals advocated thymectomy without reservation in this group. The remaining neurologists reserved the procedure for selected patients, depending on the age of the patient, severity of disease, response to medication, and duration of disease. Thirty-two neurologists did not advocate the procedure for older individuals; the age cutoff varied from 50 to 70 years (median, 60 years). Justification for an upper age limit was variable and included (1) a presumption that older individuals had greater morbidity from the pro-
From the Departments of Neurology, Preventive Medicine and Environmental Health, and the Sanders Brown Center on Aging, University of Kentucky Medical Center, Lexington, KY. Received May 14,1990. Accepted for publication in final form May 14,1990. Addreas correspondence and reprint requests to Dr. Douglas J. Lanska, Department of Neurology,Albert B. Chandler Medical Center, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0084. 1838 NEUROLOGY 40 December 1990
cedure; (2) clinical experience suggesting that older individuals were more responsive to medical therapy than younger individuals; (3) concern that the positive effect of therapy might not be manifest within the limited remaining life span of older individuals; and (4) absence of empiric support for the procedure in older individuals. Although recognized as controversial, 6 individuals advocated a lower age limit for thymectomy, varying from 1year to puberty (median, 7.5 years). The rationale for a lower age limit was based on evidence of altered T-cell function in thymectomized infants.l0 Other restrictions were as follows: 21 individuals reserved the procedure for those with disabling myasthenia; 14 reserved t h e procedure for those unresponsive to anticholinesterase medication alone (n = 10) or those unresponsive to anticholinesterase medication and immunosuppressants (n = 4); and 12 reserved the procedure for individuals with myasthenia gravis of recent onset (ie, within 2 to 5 years of onset).
Discussion. A t present, neurologists with interest and expertise in myasthenia gravis use a variety of therapeutic strategies. Most neurologists advocate thymectomy for selected patients with generalized myasthenia without thymoma. Specific restrictions vary as a function of age, disease severity and duration, and response to medication. Thymectomy is occasionally advocated for patients with disabling ocular myasthenia. With few exceptions, thymectomy is recommended for virtually all patients with thymoma. There has been no prospectively controlled trial in which patients with myasthenia gravis are allocated randomly either to surgery or to medical therapy alone. There were attempts to organize such a controlled trial of thymectomy in 1963 and in 1980, but both attempts
foundered under a variety of controversies. In the absence of a controlled trial, therapeutic benefit will remain unproven, and specific indications and contraindications will be based upon the preference of individual neurologists,
Acknowledgment The author thanks Michael P. McQuillen for helpful discussions and for critically reviewing the manuscript.
References 1. Blalwk A, Mason MF, Morgan HJ, Riven SS. Myasthenia gravis and tumors of the thymic region; report of a case in which the tumor was removed. Ann Surg 1939;110:544-559. 2. Buckingham JM. Howard FM, Bernatz PE, et al. The value of thymectomy in myasthenia gravis: a computer-assisted matched study. Ann Surg 1976;184:453-458. 3. Keesey J. Indications for thymectomy in myasthenia gravis. In: Dau PC, ed. Plasmapheresis and the immunobiology of myasthenia gravis. Boston: Houghton Mifflin, 1979:124-136. 4. Keynes G. Surgery of the thymus gland second (and third) thoughts. Lancet 1954;l:1197-1202. 5. Keynes G. The history of myasthenia gravis. Med Hist 1961;5:313-326. 6. Perlo VP. Symposium on therapeutic controversies: myasthenia gravis-thymectomy: pro. T r a n s Am Neurol Assoc 1978;103:282-283. 7. McQuillen MP. Symposium on therapeutic controversies: myasthenia gravis-thymectomy: con. Trans Am Neurol Assoc 1978;103:283-286. 8. McQuillen MP, Leone MG. A treatment carol: thymectomy revisited. Neurology 1977;12:1103-1106. 9. Rowland LP. Controversies about the treatment of myasthenia gravis. J Neurol Neurosurg Psychiatry 1980;43644-659. 10. Brearley S, Gentle TA, Baynham MI, Roberta KD, Abrams LD, Thompson RA. Immunodeficiency following neonatal thymectomy in man. Clin Exp Immunol1987;70322-327.
December 1990 NEUROLOGY 40 1839
Indications for thymectomy in myasthenia gravis Douglas J. Lanska Neurology 1990;40;1828 DOI 10.1212/WNL.40.12.1828 This information is current as of December 1, 1990 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/40/12/1828.full.html
Citations
This article has been cited by 4 HighWire-hosted articles: http://www.neurology.org/content/40/12/1828.full.html##otherarticles
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1990 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
