Abstract
Myasthenia gravis (MG) is caused by autoantibodies against proteins at the neuromuscular junction. This autoimmune process leads to abnormal fatiguability and weakness of striated muscle. Ptosis and diplopia are among the most common manifestations of MG. The term ‘ocular MG’ (OMG) as opposed to ‘generalised MG’ (GMG) is used to define the clinical subtype of MG with isolated eye muscle weakness. Although OMG may appear to cause only moderate disability, it can significantly impair the patient’s activities of daily living and progress to generalised myasthenia. Therefore, a clear management plan should be installed early in these patients. Since prospective treatment trials have not been performed, basic management strategies for OMG have to be deduced from retrospective studies, trials in GMG, and generally accepted clinical experience. Cholinesterase inhibitors are used in all types of MG, but are often less helpful in OMG. In the absence of thymoma, thymectomy is usually not considered in OMG, although a few studies have described histological abnormalities in thymuses from patients with OMG. Corticosteroids are of great short term benefit in most patients with OMG but potential adverse effects limit their long term use. Azathioprine is needed to reduce long term corticosteroid adverse effects, but this agent requires about 6 months to be effective. In summary, OMG has a good prognosis in most patients, with corticosteroids and azathioprine being the major treatment options. The challenges for the clinician are to recognise the condition despite the large number of differential diagnoses, to minimise the patient’s symptoms using the therapies available and to carefully limit potentially hazardous therapeutic efforts, especially in mild or even uncertain cases.
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References
Somnier FE, Keiding N, Paulson OB. Epidemiology of myasthenia gravis in Denmark: a longitudinal and comprehensive population survey. Arch Neurol 1991; 48; 733–9
Tola MR, Granieri E, Paolino E, et al. Epidemiological study of myasthenia gravis in the province of Ferrara, Italy. J Neurol 1989; 236; 388–90
Storm-Mathisen A. Epidemiology of myasthenia gravis in Norway. Acta Neurol Scand 1984; 70; 274–84
Yu YL, Hawkins BR, Ip MSM, et al. Myasthenia gravis in Hong Kong Chinese, 1: epidemiology and adult disease. Acta Neurol Scand 1992; 86: 113–9
Robertson NP, Deans J, Compston DAS. Myasthenia gravis: a population based epidemiological study in Cambridgeshire, England. J Neurol Neurosurg Psychiatry 1998; 65: 492–6
Thomas CE, Mayer SA, Gungor BS, et al. Myasthenic crisis: Clinical features, mortality, complications, and risk factors for prolonged intubation. Neurology 1997; 48: 1253–60
Beekman R, Kuks JBM, Oosterhuis HJGH. Myasthenia gravis: diagnosis and follow-up of 100 consecutive patients. JNeurol 1997; 244: 112–8
Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty years experience in over 1200 patients. Mt Sinai JMed 1971; 38: 497–537
Sommer N, Sigg B, Melms A, et al. Ocular myasthenia gravis: response to long term immunosuppressive treatment. J Neurol Neurosurg Psychiatry 1997; 62: 156–62
Evoli A, Tonali P, Bartoccioni E, et al. Ocular myasthenia: diagnostic and therapeutic problems. Acta Neurol Scand 1988; 77: 31–5
Oosterhuis HJGH. The natural course of myasthenia gravis: a long term follow up study. J Neurol Neurosurg Psychiatry 1989; 52: 1121–7
Vincent A, Newsom-Davis J. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry 1985; 48: 1246–52
Limburg PC, The TH, Hummerl-Tappel E, et al. Anti-acetyl-choline receptor antibodies in myasthenia gravis, part 1: relation to clinical parameters in 250 patients. J Neurol Sci 1983; 58: 357–70
Toyka KV, Heininger K. Acetylcholine-receptor antibodies in the diagnosis of myasthenia gravis. Dtsch Med Wochenschr 1986; 111: 1435–9
Schumm F, Wiethölter H, Fateh-Moghadam A, et al. Thymectomy in myasthenia gravis with pure motor ocular symptoms. J Neurol Neurosurg Psychiatry 1985; 48: 332–7
Evoli A, Tonali P, Bartocchioni E, et al. Ocular myasthenia: diagnostic and therapeutic problems. Acta Neurol Scand 1988; 77: 31–5
Kelly Jr JJ, Daube JR, Lennon VA, et al. The laboratory diagnosis of mild myasthenia gravis. Ann Neurol 1982; 12: 238–42
Francis IC, Nicholson GA, Kappagoda MB. An evaluation of signs in ocular myasthenia gravis and correlation with acetylcholine receptor antibodies. Aust N Z J Ophthalmol 1985; 13: 395–9
Sommer N, Melms A, Weiler M, et al. Ocular myasthenia gravis: a critical review of clinical and pathophysiological aspects. Doc Ophthalmol 1993; 84: 309–33
Moorthy G, Behrens MM, Drachman DB, et al. Ocular pseudomyasthenia or ocular myasthenia ‘plus’: a warning to clinicians. Neurology 1989; 39: 1150–4
Newsom-Davis J. Edrophonium responsiveness not necessarily diagnostic of myasthenia gravis. Muscle Nerve 1990; 13: 1186
Seybold ME. The office Tensilon test for ocular myasthenia gravis. Arch Neurol 1986; 43: 842–3
Daroff RB. The office Tensilon test for ocular myasthenia gravis. Arch Neurol 1986; 43: 843–4
Sanders DB, Howard JF. Single-fiber electromyography in myasthenia gravis. Muscle Nerve 1986; 9: 809–19
Newsom-Davis J. Autoimmunity in neuromuscular disease. Ann NY Acad Sci 1988; 540: 25–38
Newsom-Davis J. Diseases of the neuromuscular junction. In: Asbury AK, McKhann GM, McDonald WI, editors. Diseases of the nervous system. London: Heinemann, 1992: 197–212
Willcox N, Schluep M, Ritter MA, et al. The thymus in seronegative myasthenia gravis patients. J Neurol 1991; 238: 256–61
Willcox N, Schluep M, Ritter MA, et al. Myasthenie and non-myasthenic thymoma: an expansion of a minor cortical epithelial subset? Am J Pathol 1987; 127: 447–60
Sommer N, Willcox N, Harcourt GC, et al. Myasthenie thymus and thymoma are selectively enriched in acetylcholine receptor-reactive T cells. Ann Neurol 1990; 28: 312–9
Gunji K, Skolnick C, Bednarczuk T, et al. Eye muscle antibodies in patients with ocular myasthenia gravis: possible mechanism for eye muscle inflammation in acetylcholine-receptor antibody-negative patients. Clin Immunol Immunopathol 1998; 87: 276–81
Hoch W, McConville J, Helms S, et al. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 2001; 7: 365–8
Bartoccioni E, Sauderi F, Evoli A, et al. Ocular myasthenia gravis: two different diseases. Lancet 1986; 1: 1038–9
Vincent A, Newsom-Davis J. Acetylcholine receptor antibody characteristics in myasthenia gravis. I. Patients with generalized myasthenia or disease restricted to ocular muscles. Clin Exp Immunol 1982; 49: 257–65
Vincent A, Newsom-Davis J. Acetylcholine receptor antibody characteristics in myasthenia gravis. III. Patients with low anti-AChR antibody levels. Clin Exp Immunol 1985; 60: 631–6
Wang ZY, Diethelm-Okita B, Okita DK, et al. T cell recognition of muscle acetylcholine receptor in ocular myasthenia gravis. J Neuroimmunol 2000; 108: 29–39
Monden Y, Fujii Y, Masaoka A. Clinical characteristics of myasthenia gravis with other autoimmune diseases. Ann NY Acad Sci 1987; 505: 876–8
Christensen PB, Jensen TS, Tsiropoulos I, et al. Associated autoimmune diseases in myasthenia gravis: a population-based study. Acta Neurol Scand 1995; 91: 192–5
Bergoffen J, Zmijewski CM, Fischbeck KH. Familial autoimmune myasthenia gravis. Neurology 1994; 44: 551–4
Kupersmith MJ, Moster M, Bhuiyan S, et al. Beneficial effects of corticosteroids on ocular myasthenia gravis. Arch Neurol 1996; 53: 802–4
Grob D, Arsura E, Brunner N, et al. The course of myasthenia gravis and therapies affecting outcome. Ann NY Acad Sci 1987; 505: 472–99
Bever CT, Aquino AV, Penn AS, et al. Prognosis of ocular myasthenia. Ann Neurol 1983; 14: 516–9
Oosterhuis HJGH. The ocular signs and symptoms of myasthenia gravis. Doc Ophthalmol 1982; 52: 363–78
Kaminski HJ, Maas E, Spiegel P, et al. Why are eye muscles frequently involved in myasthenia gravis? Neurology 1990; 40: 1663–9
Kaminski H. Treatment of ocular myasthenia. Arch Neurol 2000; 57: 752–3
Evoli A, Batocchi AP, Palmisani MT, et al. Long-term results of corticosteroid therapy in patients with myasthenia gravis. Eur Neurol 1992; 32: 37–43
Agius MA. Treatment of ocular myasthenia with corticosteroids. Arch Neurol 2000; 57: 750–1
Pestronk A, Drachman DB, Self SG. Measurement of junctional acetylcholine receptors in myasthenia gravis: clinical correlates. Muscle Nerve 1985; 8: 245–51
Sanders DB, Howard Jr JF. Disorders of neuromuscular transmission. In: Bradley WG, Daroff RB, Fenichel GM, et al., editors. Neurology in clinical practice. Boston (MA): Butterworth-Heinemann, 2000: 2167–86
Johns TR. Long-term corticosteroid treatment of myasthenia gravis: Ann NY Acad Sci 1987; 505: 568–86
Saag K, Koehnke R, Caldwell JR, et al. Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 1994; 96: 115–23
Caldwell JR, Furst DE. The efficacy and safety of low-dose corticosteroids for rheumatoid arthritis. Semin Arthritis Rheum 1991; 21: 1–11
Hatz HJ, Helmke K. Polymyalgia rheumatica and giant cell arteritis: diagnosis and side effects of low-dose long-term glucocorticoid therapy. Z Rheumatol 1992; 51: 213–21
Lloyd ME, Spector TD, Howard R. Osteoporosis in neurological disorders [editorial]. J Neurol Neurosurg Psychiatry 2000; 68: 543–9
Helfer EL, Rose LI. Corticosteroids and adrenal suppression: characterising and avoiding the problem. Drugs 1989; 38: 838–45
Cornelio F, Antozzi C, Mantegazza R, et al. Immunosuppressive treatments: their efficacy on myasthenia gravis patients’ outcome and on the natural course of the disease. Ann NY Acad Sci 1993; 681: 594–603
Miano MA, Bosley TM, Heiman-Patterson TD, et al. Factors influencing outcome of prednisone dose reduction in myasthenia gravis. Neurology 1991; 41: 919–21
Palace J, Newsom-Davis J, Leckey B. A randomized double-blind trial of prednisolone alone with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group. Neurology 1998; 50: 1778–83
Kokontis L, Gutmann L. Current treatment of neuromuscular diseases. Arch Neurol 2000; 57: 939–43
Witte AS, Cornblath DR, Parry GJ, et al. Azathioprine in the treatment of myasthenia gravis. Ann Neurol 1984; 15: 602–5
Hohlfeld R, Michels M, Heininger K, et al. Azathioprine toxicity during long-term immunosuppression of generalized myasthenia gravis. Neurology 1988; 38: 258–61
Kissel JT, Levy RJ, Mendell JR, et al. Azathioprine toxicity in neuromuscular disease. Neurology 1986; 36: 35–9
Mantegazza R, Antozzi C, Peluchetti D, et al. Azathioprine as a single drug or in combination with steroids in the treatment of myasthenia gravis. J Neurol 1988; 235: 449–53
Lewis JD, Schwartz JS, Lichtenstein GR. Azathioprine for maintenance of remission in Crohn’s disease: benefits outweigh the risk of lymphoma. Gastroenterology 2000; 118: 1018–24
Connell WR, Kamm MA, Dickson M, et al. Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease. Lancet 1994; 343: 1249–52
Asten P, Barrett J, Symmons D. Risk of developing certain malignancies is related to duration of immunosuppressive drug exposure in patients with rheumatic diseases. J Rheumatol 1999; 26: 1705–14
Kuks JB, Djojoatmodjo S, Oosterhuis HJ. Azathioprine in myasthenia gravis: observations in 41 patients and a review of literature. Neuromuscul Disord 1991; 1: 423–31
Hohlfeld R, Toyka KV, Besinger UA, et al. Myasthenia gravis: reactivation of clinical disease and of autoimmune factors after discontinuation of long-term azathioprine. Ann Neurol 1985; 17: 238–42
Buckingham JM, Howard FM, Bernatz PE, et al. The value of thymectomy in myasthenia gravis: a computer assisted matched study. Ann Surg 1976; 184: 453–7
Lanska DJ. Indications for thymectomy in myasthenia gravis. Neurology 1990; 40: 1828–9
Lindner A, Schalke B, Toyka KV. Outcome in juvenile-onset myasthenia gravis: a retrospective study with long-term follow-up of 79 patients. J Neurol 1997; 244: 515–20
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The Clinical Neuroimmunology Group is supported by the Gemeinnützige Hertie-Stiftung and the Deutsche Forschungsgemeinschaft (SFB 297). There is no conflict of interest that is directly relevant to the contents of this manuscript.
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Tackenberg, B., Hemmer, B., Oertel, W.H. et al. Immunosuppressive Treatment of Ocular Myasthenia Gravis. BioDrugs 15, 369–378 (2001). https://doi.org/10.2165/00063030-200115060-00003
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DOI: https://doi.org/10.2165/00063030-200115060-00003