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Immunosuppressive or Surgical Treatment for Ocular Myasthenia Gravis

Immunosuppressive or Surgical Treatment for Ocular Myasthenia Gravis Is there any other autoimmune disease treated by surgical removal of a gland? Does the evidence of autoimmunity in myasthenia gravis (MG) support medical treatment of significant ocular involvement? The basis for answering these questions must rest on an understanding of disease progression, the success of treatment, and the risk-benefit ratio for the patient. Although there is a high frequency of autoimmune disease in MG, there are no studies of any other autoimmune disease being treated by surgical removal of a gland or thymectomy. The surgical treatment of MG by thymectomy dates to the series of 20 patients with and without thymoma reported by Blalock1 in 1944; this treatment was innovative and was effective then and still is now, even in the immunomodulatory era. There is little doubt that the thymus is responsible for T-cell development and maintains the autoimmune response, but thymectomy for nonthymomatous MG may not offer any benefit over medical treatment alone. Myasthenia gravis respects the criteria for autoimmunity, and the suspected autoimmune pathogenesis was confirmed by anti–acetylcholine receptor (AChR) antibody identification.2 However, the natural history and degree of disease disability vs the adverse effects of medical therapy must be considered. In generalized MG (GMG), there is no debate as to the efficacy and importance of treatment. Progression of ocular mg to gmg The literature suggests that 85% to 90% of individuals with ocular MG (OMG) eventually progress to GMG, but approximately 15% of patients have persistent ocular signs for 2 years and continue to have ocular findings only.3,4 In greater than 95% of patients, findings from single-fiber electromyography (SF-EMG) are positive if multiple muscles are tested (especially the orbicularis oculi or the superior rectus–levator complex); however, this may not be predictive of generalization of disease.5,6 Conversely, negative SF-EMG findings of the extensor digitorum communis muscle in OMG may carry a lower risk of progression to GMG.6 Most patients with OMG who progress to systemic disease do so in the first 2 to 3 years, suggesting a relatively short period for intense observation and perhaps for treatment.4 Although antibody titers may be lower in OMG than in GMG, high titers can be found in ocular disease. Absolute antibody titers do not mirror disease severity, but their positivity from OMG (40%-70%) to GMG (98%-99%) does increase with disease duration. Blocking antibodies to AChR significantly correlate with generalized weakness.4,7-9 Medical treatment of omg Ocular MG has a lower risk of thymoma, and thymomas are uncommon in younger age groups. Juvenile OMG can, in general, be evaluated as an autoimmune disease, and children with autoimmune OMG parallel adult expression of the disease. Although permanent ocular disability or damage is uncommon, 5 of 14 individuals who initially had OMG eventually progressed to GMG that required thymectomy and medical immunosuppression; 2 of these patients with OMG were treated with prednisone and another by thymectomy. This treatment was provided readily on disease progression; thus, disability may have been minimized in 8 of the 14 patients, and the adverse effects of therapy were not elaborated.10 Preventing severe ocular disease or progression to systemic mg The tendency to be immediately proactive in treating children with progressive OMG may give the misperception that children do well. One of 14 children with ocular involvement progressed so rapidly that aspiration and death occurred before treatment for systemic involvement could be initiated.10 An adult OMG series reported that 17% of 297 patients progressed to bulbar/respiratory symptoms.11 Effectiveness of medical treatment Oral prednisone treatment may be effective in OMG at lower total doses; it is tempting to associate this efficacy with lower antibody levels, but this is not well established in the literature. Antibody positivity does increase with disease duration. Moreover, several studies2,12,13 suggest that prednisone or other immunomodulatory therapy in the first year of OMG is associated with a lower rate of progression to systemic disease than is delayed treatment (ie, 9%-13% of corticosteroid-treated patients compared with 34%-70% of nonimmunomodulated patients). In most studies, this response occurred whether the patient was seropositive or seronegative for MG. Corticosteroid therapy can lead to increased muscle weakness; considering this risk, low-dose, alternate-day corticosteroid use may be the initial regimen of choice. Dosages can begin at 10 to 25 mg every other day. In other studies, prednisone dosages ranged from 10 to 60 mg daily. Treatment has varied from 2 weeks to 32 months, and 0% to 42% of individuals develop adverse effects. Improvement occurs in 80% of patients within a month and persists with tapering in half by 3 months.12,13 Kupersmith and colleagues13 noted that 2 years of even low-dose prednisone therapy reduced the risk of progression to GMG from 33% to 7%; this low dose minimized many dose-related adverse effects of prednisone. Osteopenia, which can occur even with low-dose, long-term use of prednisone, can also be anticipated and minimized. Permanent remissions occur in only 10% of patients.3 Several courses of intravenous methylprednisolone induced clinical improvement in 3 patients with OMG and short disease duration; they remained stable for 7 to 24 months after treatment, and 1 patient had a gradual decline in anti–AChR antibody concentration.14 If clinical relapses occur during prednisone tapering or if therapy is prolonged, it may be advantageous to switch to azathioprine. Azathioprine combined with prednisone showed 91% efficacy for OMG in a small sample of 23 patients who also experienced a reduction in AChR antibodies; however, the duration of preexisting disease before treatment was unclear.15 The induction phase for azathioprine alone can be 3 to 12 months; therefore, it is often paired with prednisone.10 Approximately 50% of patients with GMG treated with azathioprine have a relapse within a year.3 Another small GMG azathioprine sample was less successful; the duration of pretreatment disease averaged 1 to 6 years.16 Azathioprine screening for safety can always be performed because it is corticosteroid sparing.3 Medical therapy with mycophenolate mofetil, cyclosporine, intravenous immunoglobulin, and cyclophosphamide has been largely relegated to GMG, with isolated cases of OMG. Improvement with intravenous immunoglobulin occurs in the first week and lasts 4 to 6 weeks, so it is usually combined with prednisone. This may be especially apparent in OMG and advantageous in juvenile MG. Thymectomy for omg Clinical outcome after thymectomy is also better when it is performed early after onset of the disease. A clinical trial directly comparing thymectomy and prednisone in individuals with OMG has not been performed, but a study2 of 54 patients suggested that thymectomy was no better than medical treatment alone. However, 38% of 286 patients treated with extended thymectomy and high-dose, alternate-day prednisone were more likely to relapse if they had had a delay in onset of therapy beyond 6 months; these patients showed a recrudescence of ocular symptoms when prednisone was discontinued, and all had a hyperplastic thymus.17 In the absence of a thymoma, thymectomy is not commonly recommended for OMG. Nevertheless, some patients with progressive and disabling ocular involvement or an inadequate response to medical treatment have undergone surgery.10,18,19 Clinical improvement was associated with a 40% decline in anti-AChR antibodies in 6 of 9 patients with OMG; it occurred in the first 6 months after thymectomy, and no patient progressed to GMG. However, 1 patient with thymic hyperplasia and prolonged follow-up before thymectomy required additional immunosuppression with prednisone and azathioprine.19 Roberts and colleagues20 noted a 51% cure rate and 20% improvement in OMG symptoms; 20% of these patients had thymoma, and the incidence of early systemic involvement was unclear. In a study8 with a longer disease duration and an unknown incidence of thymoma, the results of thymectomy were less clear for OMG. More recently, muscle-specific kinase antibodies have been associated with OMG, and there is currently no evidence of thymectomy efficacy in this group. Adverse effects of thymectomy and comparison with other regimens Recent thymectomy series describe few complications from surgery and almost no mortality. Respiratory insufficiency sometimes occurs after surgery, but patients with OMG did especially well.20 Juvenile GMG showed 80% remission with either thorascopic or open thymectomy; only 1 patient worsened.21 However, the thymus may be important into adulthood, with long-term abnormal T-cell function after thymectomy in children and young adults.22 Because the myasthenic treatment outcomes with thymectomy are favorable and because surgical risks are low, whether to have early medical or early surgical treatment may be an individual choice. Conclusions Individuals with progressive AChR antibody–positive OMG, particularly those with abnormal SF-EMG findings in a limb muscle, have a high rate of progression to GMG; the literature suggests that medical or surgical therapy is most effective when started early and should be encouraged for nonthymomatous MG.1-7,9,21 Ocular MG can be disabling, and therapy can be offered for extensive (or disabling) OMG that persists for several months and has not shown early remission.10 Although the role of thymectomy in the management of OMG remains controversial, it has a role in some individuals with OMG, perhaps especially patients who fail medical therapy. Thymectomy may be more advantageous in the younger but immunocompetent patient facing a long course of immunosuppressive agents.19-21 These patients should have disease confirmation by antibody and electrodiagnostic testing. Although the OMG treatment path can be debated, it seems clear that early treatment tends to minimize progression.2,12-14,16,17 Perhaps the tendency to “watch and wait” should be replaced with earlier intervention. Would any neurologist with OMG wish to wait for full-blown immunologic disease expression or accept earlier intervention? Initial medical treatment should be followed by thymectomy if there is continued disease expression. Back to top Article Information Correspondence: Pamela S. Chavis, MD, Department of Ophthalmology, Medical University of South Carolina, 167 Ashley Ave, Charleston, SC 29425 (chavisps@musc.edu). Accepted for Publication: April 11, 2007. Author Contributions:Study concept and design: Chavis, Stickler, and Walker. Acquisition of data: Chavis and Stickler. Analysis and interpretation of data: Chavis. Drafting of the manuscript: Chavis and Stickler. Critical revision of the manuscript for important intellectual content: Chavis, Stickler, and Walker. Administrative, technical, and material support: Chavis and Stickler. Study supervision: Chavis. Financial Disclosure: None reported. References 1. Blalock A Thymectomy in the treatment of myasthenia gravis: report of 20 cases. J Thorac Surg 1944;13316- 339Google Scholar 2. Sommer NSigg BMelms A et al. Ocular myasthenia gravis: response to long-term immunosuppressive treatment. J Neurol Neurosurg Psychiatry 1997;62 (2) 156- 162PubMedGoogle ScholarCrossref 3. Tackenberg BHemmer BOertel WHSommer N Immunosuppressive treatment of ocular myasthenia gravis. BioDrugs 2001;15 (6) 369- 378PubMedGoogle ScholarCrossref 4. Grob DArsura ELBrunner NGNamba T The course of myasthenia gravis and therapies affecting the outcome. Ann N Y Acad Sci 1987;505472- 499PubMedGoogle ScholarCrossref 5. Padua LStalberg ELoMonaco MEvoli ABatocchi ATonali P SFEMG in ocular myasthenia gravis diagnosis. Clin Neurophysiol 2000;111 (7) 1203- 1207PubMedGoogle ScholarCrossref 6. Weinberg DHRizzo JF IIIHayes MTKneeland MDKelly JJ Jr Ocular myasthenia gravis: predictive values of single-fiber electromyography. Muscle Nerve 1999;22 (9) 1222- 1227PubMedGoogle ScholarCrossref 7. Mantegazza RBeghi EPareyson D et al. A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy. J Neurol 1990;237 (6) 339- 344PubMedGoogle ScholarCrossref 8. Evoli ATonali PBartoccioni ELoMonaco M Ocular myasthenia: diagnostic and therapeutic problems. Acta Neurol Scand 1988;77 (1) 31- 35PubMedGoogle ScholarCrossref 9. Howard FM JrLennon VAFinley JMatsumoto JElveback LR Clinical correlations of antibodies that bind, block, and modulate human acetylcholine receptors in myasthenia gravis. Ann N Y Acad Sci 1987;505526- 538PubMedGoogle ScholarCrossref 10. Mullaney PVajsar JSmith RBuncic JR The natural history and ophthalmic involvement in childhood myasthenia gravis at The Hospital for Sick Children. Ophthalmology 2000;107 (3) 504- 510PubMedGoogle ScholarCrossref 11. Mantegazza RBaggi FAntozzi L et al. Myasthenia gravis (MG): epidemiological data and prognostic factors. Ann N Y Acad Sci 2003;998413- 423PubMedGoogle ScholarCrossref 12. Monsul NTPatwa HSKnorr AMLesser RLGoldstein JM The effect of prednisone on the progression from ocular to generalized myasthenia gravis. J Neurol Sci 2004;217 (2) 131- 133PubMedGoogle ScholarCrossref 13. Kupersmith MJLatkany RHomel P Development of generalized disease at 2 years in patients with ocular myasthenia gravis. Arch Neurol 2003;60 (2) 243- 248PubMedGoogle ScholarCrossref 14. Komiyama AArai HKijama MHirayama K Extraocular muscle responses to high dose intravenous ethylprednisolone in myasthenia gravis. J Neurol Neurosurg Psychiatry 2000;68 (2) 214- 217PubMedGoogle ScholarCrossref 15. Mantegazza RAntozzi CPeluchetti DSghirlanzoni ACornelio F Azathioprine as a single drug or in combination with steroids in the treatment of myasthenia gravis. J Neurol 1988;235 (8) 449- 453PubMedGoogle ScholarCrossref 16. Bromberg MBWald JJForshew DAFeldman ELAlbers JW Randomized trial of azathioprine or prednisone for initial immunosuppressive treatment of myasthenia gravis. J Neurol Sci 1997;150 (1) 59- 62PubMedGoogle ScholarCrossref 17. Wakata NIguchi HSugimoto HNomoto NKurihara T Relapse of ocular symptoms after remission of myasthenia gravis: a comparison of relapsed and complete remission cases. Clin Neurol Neurosurg 2003;105 (2) 75- 77PubMedGoogle ScholarCrossref 18. Huang C-SHsu H-SHuang B-S et al. Factors influencing the outcome of transsternal thymectomy for myasthenia gravis. Acta Neurol Scand 2005;112 (2) 108- 114PubMedGoogle ScholarCrossref 19. Schumm FWiethölter HFateh-Moghadam ADichgans J Thymectomy in myasthenia with pure ocular symptoms. J Neurol Neurosurg Psychiatry 1985;48 (4) 332- 337PubMedGoogle ScholarCrossref 20. Roberts PFVenuta FRendina E et al. Thymectomy in the treatment of ocular myasthenia gravis. J Thorac Cardiovasc Surg 2001;122 (3) 562- 568PubMedGoogle ScholarCrossref 21. Wagner AJCortes RAStrober J et al. Long-term follow-up after thymectomy for myasthenia gravis: thorascopic vs open. J Pediatr Surg 2006;41 (1) 50- 54PubMedGoogle ScholarCrossref 22. Halnon NJJamieson BPlunkett MKitchen CMPham TKrogstad P Thymic function and impaired maintenance of peripheral T cell populations in children with congenital heart disease and surgical thymectomy. Pediatr Res 2005;57 (1) 42- 48PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Immunosuppressive or Surgical Treatment for Ocular Myasthenia Gravis

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References (22)

Publisher
American Medical Association
Copyright
Copyright © 2007 American Medical Association. All Rights Reserved.
ISSN
0003-9942
DOI
10.1001/archneur.64.12.1792
pmid
18071048
Publisher site
See Article on Publisher Site

Abstract

Is there any other autoimmune disease treated by surgical removal of a gland? Does the evidence of autoimmunity in myasthenia gravis (MG) support medical treatment of significant ocular involvement? The basis for answering these questions must rest on an understanding of disease progression, the success of treatment, and the risk-benefit ratio for the patient. Although there is a high frequency of autoimmune disease in MG, there are no studies of any other autoimmune disease being treated by surgical removal of a gland or thymectomy. The surgical treatment of MG by thymectomy dates to the series of 20 patients with and without thymoma reported by Blalock1 in 1944; this treatment was innovative and was effective then and still is now, even in the immunomodulatory era. There is little doubt that the thymus is responsible for T-cell development and maintains the autoimmune response, but thymectomy for nonthymomatous MG may not offer any benefit over medical treatment alone. Myasthenia gravis respects the criteria for autoimmunity, and the suspected autoimmune pathogenesis was confirmed by anti–acetylcholine receptor (AChR) antibody identification.2 However, the natural history and degree of disease disability vs the adverse effects of medical therapy must be considered. In generalized MG (GMG), there is no debate as to the efficacy and importance of treatment. Progression of ocular mg to gmg The literature suggests that 85% to 90% of individuals with ocular MG (OMG) eventually progress to GMG, but approximately 15% of patients have persistent ocular signs for 2 years and continue to have ocular findings only.3,4 In greater than 95% of patients, findings from single-fiber electromyography (SF-EMG) are positive if multiple muscles are tested (especially the orbicularis oculi or the superior rectus–levator complex); however, this may not be predictive of generalization of disease.5,6 Conversely, negative SF-EMG findings of the extensor digitorum communis muscle in OMG may carry a lower risk of progression to GMG.6 Most patients with OMG who progress to systemic disease do so in the first 2 to 3 years, suggesting a relatively short period for intense observation and perhaps for treatment.4 Although antibody titers may be lower in OMG than in GMG, high titers can be found in ocular disease. Absolute antibody titers do not mirror disease severity, but their positivity from OMG (40%-70%) to GMG (98%-99%) does increase with disease duration. Blocking antibodies to AChR significantly correlate with generalized weakness.4,7-9 Medical treatment of omg Ocular MG has a lower risk of thymoma, and thymomas are uncommon in younger age groups. Juvenile OMG can, in general, be evaluated as an autoimmune disease, and children with autoimmune OMG parallel adult expression of the disease. Although permanent ocular disability or damage is uncommon, 5 of 14 individuals who initially had OMG eventually progressed to GMG that required thymectomy and medical immunosuppression; 2 of these patients with OMG were treated with prednisone and another by thymectomy. This treatment was provided readily on disease progression; thus, disability may have been minimized in 8 of the 14 patients, and the adverse effects of therapy were not elaborated.10 Preventing severe ocular disease or progression to systemic mg The tendency to be immediately proactive in treating children with progressive OMG may give the misperception that children do well. One of 14 children with ocular involvement progressed so rapidly that aspiration and death occurred before treatment for systemic involvement could be initiated.10 An adult OMG series reported that 17% of 297 patients progressed to bulbar/respiratory symptoms.11 Effectiveness of medical treatment Oral prednisone treatment may be effective in OMG at lower total doses; it is tempting to associate this efficacy with lower antibody levels, but this is not well established in the literature. Antibody positivity does increase with disease duration. Moreover, several studies2,12,13 suggest that prednisone or other immunomodulatory therapy in the first year of OMG is associated with a lower rate of progression to systemic disease than is delayed treatment (ie, 9%-13% of corticosteroid-treated patients compared with 34%-70% of nonimmunomodulated patients). In most studies, this response occurred whether the patient was seropositive or seronegative for MG. Corticosteroid therapy can lead to increased muscle weakness; considering this risk, low-dose, alternate-day corticosteroid use may be the initial regimen of choice. Dosages can begin at 10 to 25 mg every other day. In other studies, prednisone dosages ranged from 10 to 60 mg daily. Treatment has varied from 2 weeks to 32 months, and 0% to 42% of individuals develop adverse effects. Improvement occurs in 80% of patients within a month and persists with tapering in half by 3 months.12,13 Kupersmith and colleagues13 noted that 2 years of even low-dose prednisone therapy reduced the risk of progression to GMG from 33% to 7%; this low dose minimized many dose-related adverse effects of prednisone. Osteopenia, which can occur even with low-dose, long-term use of prednisone, can also be anticipated and minimized. Permanent remissions occur in only 10% of patients.3 Several courses of intravenous methylprednisolone induced clinical improvement in 3 patients with OMG and short disease duration; they remained stable for 7 to 24 months after treatment, and 1 patient had a gradual decline in anti–AChR antibody concentration.14 If clinical relapses occur during prednisone tapering or if therapy is prolonged, it may be advantageous to switch to azathioprine. Azathioprine combined with prednisone showed 91% efficacy for OMG in a small sample of 23 patients who also experienced a reduction in AChR antibodies; however, the duration of preexisting disease before treatment was unclear.15 The induction phase for azathioprine alone can be 3 to 12 months; therefore, it is often paired with prednisone.10 Approximately 50% of patients with GMG treated with azathioprine have a relapse within a year.3 Another small GMG azathioprine sample was less successful; the duration of pretreatment disease averaged 1 to 6 years.16 Azathioprine screening for safety can always be performed because it is corticosteroid sparing.3 Medical therapy with mycophenolate mofetil, cyclosporine, intravenous immunoglobulin, and cyclophosphamide has been largely relegated to GMG, with isolated cases of OMG. Improvement with intravenous immunoglobulin occurs in the first week and lasts 4 to 6 weeks, so it is usually combined with prednisone. This may be especially apparent in OMG and advantageous in juvenile MG. Thymectomy for omg Clinical outcome after thymectomy is also better when it is performed early after onset of the disease. A clinical trial directly comparing thymectomy and prednisone in individuals with OMG has not been performed, but a study2 of 54 patients suggested that thymectomy was no better than medical treatment alone. However, 38% of 286 patients treated with extended thymectomy and high-dose, alternate-day prednisone were more likely to relapse if they had had a delay in onset of therapy beyond 6 months; these patients showed a recrudescence of ocular symptoms when prednisone was discontinued, and all had a hyperplastic thymus.17 In the absence of a thymoma, thymectomy is not commonly recommended for OMG. Nevertheless, some patients with progressive and disabling ocular involvement or an inadequate response to medical treatment have undergone surgery.10,18,19 Clinical improvement was associated with a 40% decline in anti-AChR antibodies in 6 of 9 patients with OMG; it occurred in the first 6 months after thymectomy, and no patient progressed to GMG. However, 1 patient with thymic hyperplasia and prolonged follow-up before thymectomy required additional immunosuppression with prednisone and azathioprine.19 Roberts and colleagues20 noted a 51% cure rate and 20% improvement in OMG symptoms; 20% of these patients had thymoma, and the incidence of early systemic involvement was unclear. In a study8 with a longer disease duration and an unknown incidence of thymoma, the results of thymectomy were less clear for OMG. More recently, muscle-specific kinase antibodies have been associated with OMG, and there is currently no evidence of thymectomy efficacy in this group. Adverse effects of thymectomy and comparison with other regimens Recent thymectomy series describe few complications from surgery and almost no mortality. Respiratory insufficiency sometimes occurs after surgery, but patients with OMG did especially well.20 Juvenile GMG showed 80% remission with either thorascopic or open thymectomy; only 1 patient worsened.21 However, the thymus may be important into adulthood, with long-term abnormal T-cell function after thymectomy in children and young adults.22 Because the myasthenic treatment outcomes with thymectomy are favorable and because surgical risks are low, whether to have early medical or early surgical treatment may be an individual choice. Conclusions Individuals with progressive AChR antibody–positive OMG, particularly those with abnormal SF-EMG findings in a limb muscle, have a high rate of progression to GMG; the literature suggests that medical or surgical therapy is most effective when started early and should be encouraged for nonthymomatous MG.1-7,9,21 Ocular MG can be disabling, and therapy can be offered for extensive (or disabling) OMG that persists for several months and has not shown early remission.10 Although the role of thymectomy in the management of OMG remains controversial, it has a role in some individuals with OMG, perhaps especially patients who fail medical therapy. Thymectomy may be more advantageous in the younger but immunocompetent patient facing a long course of immunosuppressive agents.19-21 These patients should have disease confirmation by antibody and electrodiagnostic testing. Although the OMG treatment path can be debated, it seems clear that early treatment tends to minimize progression.2,12-14,16,17 Perhaps the tendency to “watch and wait” should be replaced with earlier intervention. Would any neurologist with OMG wish to wait for full-blown immunologic disease expression or accept earlier intervention? Initial medical treatment should be followed by thymectomy if there is continued disease expression. Back to top Article Information Correspondence: Pamela S. Chavis, MD, Department of Ophthalmology, Medical University of South Carolina, 167 Ashley Ave, Charleston, SC 29425 (chavisps@musc.edu). Accepted for Publication: April 11, 2007. Author Contributions:Study concept and design: Chavis, Stickler, and Walker. Acquisition of data: Chavis and Stickler. Analysis and interpretation of data: Chavis. Drafting of the manuscript: Chavis and Stickler. Critical revision of the manuscript for important intellectual content: Chavis, Stickler, and Walker. Administrative, technical, and material support: Chavis and Stickler. Study supervision: Chavis. Financial Disclosure: None reported. References 1. Blalock A Thymectomy in the treatment of myasthenia gravis: report of 20 cases. J Thorac Surg 1944;13316- 339Google Scholar 2. Sommer NSigg BMelms A et al. Ocular myasthenia gravis: response to long-term immunosuppressive treatment. J Neurol Neurosurg Psychiatry 1997;62 (2) 156- 162PubMedGoogle ScholarCrossref 3. Tackenberg BHemmer BOertel WHSommer N Immunosuppressive treatment of ocular myasthenia gravis. BioDrugs 2001;15 (6) 369- 378PubMedGoogle ScholarCrossref 4. Grob DArsura ELBrunner NGNamba T The course of myasthenia gravis and therapies affecting the outcome. Ann N Y Acad Sci 1987;505472- 499PubMedGoogle ScholarCrossref 5. Padua LStalberg ELoMonaco MEvoli ABatocchi ATonali P SFEMG in ocular myasthenia gravis diagnosis. Clin Neurophysiol 2000;111 (7) 1203- 1207PubMedGoogle ScholarCrossref 6. Weinberg DHRizzo JF IIIHayes MTKneeland MDKelly JJ Jr Ocular myasthenia gravis: predictive values of single-fiber electromyography. Muscle Nerve 1999;22 (9) 1222- 1227PubMedGoogle ScholarCrossref 7. Mantegazza RBeghi EPareyson D et al. A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy. J Neurol 1990;237 (6) 339- 344PubMedGoogle ScholarCrossref 8. Evoli ATonali PBartoccioni ELoMonaco M Ocular myasthenia: diagnostic and therapeutic problems. Acta Neurol Scand 1988;77 (1) 31- 35PubMedGoogle ScholarCrossref 9. Howard FM JrLennon VAFinley JMatsumoto JElveback LR Clinical correlations of antibodies that bind, block, and modulate human acetylcholine receptors in myasthenia gravis. Ann N Y Acad Sci 1987;505526- 538PubMedGoogle ScholarCrossref 10. Mullaney PVajsar JSmith RBuncic JR The natural history and ophthalmic involvement in childhood myasthenia gravis at The Hospital for Sick Children. Ophthalmology 2000;107 (3) 504- 510PubMedGoogle ScholarCrossref 11. Mantegazza RBaggi FAntozzi L et al. Myasthenia gravis (MG): epidemiological data and prognostic factors. Ann N Y Acad Sci 2003;998413- 423PubMedGoogle ScholarCrossref 12. Monsul NTPatwa HSKnorr AMLesser RLGoldstein JM The effect of prednisone on the progression from ocular to generalized myasthenia gravis. J Neurol Sci 2004;217 (2) 131- 133PubMedGoogle ScholarCrossref 13. Kupersmith MJLatkany RHomel P Development of generalized disease at 2 years in patients with ocular myasthenia gravis. Arch Neurol 2003;60 (2) 243- 248PubMedGoogle ScholarCrossref 14. Komiyama AArai HKijama MHirayama K Extraocular muscle responses to high dose intravenous ethylprednisolone in myasthenia gravis. J Neurol Neurosurg Psychiatry 2000;68 (2) 214- 217PubMedGoogle ScholarCrossref 15. Mantegazza RAntozzi CPeluchetti DSghirlanzoni ACornelio F Azathioprine as a single drug or in combination with steroids in the treatment of myasthenia gravis. J Neurol 1988;235 (8) 449- 453PubMedGoogle ScholarCrossref 16. Bromberg MBWald JJForshew DAFeldman ELAlbers JW Randomized trial of azathioprine or prednisone for initial immunosuppressive treatment of myasthenia gravis. J Neurol Sci 1997;150 (1) 59- 62PubMedGoogle ScholarCrossref 17. Wakata NIguchi HSugimoto HNomoto NKurihara T Relapse of ocular symptoms after remission of myasthenia gravis: a comparison of relapsed and complete remission cases. Clin Neurol Neurosurg 2003;105 (2) 75- 77PubMedGoogle ScholarCrossref 18. Huang C-SHsu H-SHuang B-S et al. Factors influencing the outcome of transsternal thymectomy for myasthenia gravis. Acta Neurol Scand 2005;112 (2) 108- 114PubMedGoogle ScholarCrossref 19. Schumm FWiethölter HFateh-Moghadam ADichgans J Thymectomy in myasthenia with pure ocular symptoms. J Neurol Neurosurg Psychiatry 1985;48 (4) 332- 337PubMedGoogle ScholarCrossref 20. Roberts PFVenuta FRendina E et al. Thymectomy in the treatment of ocular myasthenia gravis. J Thorac Cardiovasc Surg 2001;122 (3) 562- 568PubMedGoogle ScholarCrossref 21. Wagner AJCortes RAStrober J et al. Long-term follow-up after thymectomy for myasthenia gravis: thorascopic vs open. J Pediatr Surg 2006;41 (1) 50- 54PubMedGoogle ScholarCrossref 22. Halnon NJJamieson BPlunkett MKitchen CMPham TKrogstad P Thymic function and impaired maintenance of peripheral T cell populations in children with congenital heart disease and surgical thymectomy. Pediatr Res 2005;57 (1) 42- 48PubMedGoogle ScholarCrossref

Journal

Archives of NeurologyAmerican Medical Association

Published: Dec 1, 2007

There are no references for this article.