Diagnosis of myasthenia gravis
- Shawn J Bird, MD
Shawn J Bird, MD
- Professor of Neurology
- University of Pennsylvania School of Medicine
- Section Editors
- Jeremy M Shefner, MD, PhD
Jeremy M Shefner, MD, PhD
- Section Editor — Neuromuscular Disease
- Professor and Chair of Neurology, Barrow Neurological Institute
- Professor of Neurology, University of Arizona, Phoenix
- Clinical Professor of Neurology, Creighton University
- Ira N Targoff, MD
Ira N Targoff, MD
- Section Editor — Muscle Disease
- Professor of Medicine, Section of Rheumatology
- University of Oklahoma Health Sciences Center
Myasthenia gravis is the most common disorder of neuromuscular transmission. It is now one of the best characterized and understood autoimmune disorders. The hallmark of the disorder is a fluctuating degree and variable combination of weakness in ocular, bulbar, limb, and respiratory muscles. Weakness is the result of an antibody-mediated, T-cell dependent immunologic attack directed at proteins in the postsynaptic membrane of the neuromuscular junction (acetylcholine receptors or receptor-associated proteins). The diagnosis of myasthenia gravis can be established by clinical and serologic testing [1,2].
This topic will discuss the diagnosis of myasthenia gravis. Other aspects of this disorder are discussed separately. (See "Pathogenesis of myasthenia gravis" and "Clinical manifestations of myasthenia gravis" and "Differential diagnosis of myasthenia gravis" and "Treatment of myasthenia gravis".)
The diagnostic approach to myasthenia is focused on confirming the clinical diagnosis established by the history and typical examination findings. (See "Clinical manifestations of myasthenia gravis".)
Bedside tests (the edrophonium test and the ice pack test) are easy to perform and are sensitive, but they have major limitations due to concerns about excess false-positive results. Confirmation by these tests alone is unwise.
More reliable laboratory methods that aid in the confirmation are serologic tests for autoantibodies and electrophysiologic studies (repetitive nerve stimulation studies and single-fiber electromyography [EMG]). It should be kept in mind that the diagnostic sensitivity of these studies also varies considerably depending on whether the patient has ocular or generalized disease.
- Mahadeva B, Phillips LH 2nd, Juel VC. Autoimmune disorders of neuromuscular transmission. Semin Neurol 2008; 28:212.
- Nicolle MW. Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome. Continuum (Minneap Minn) 2016; 22:1978.
- Benatar M. A systematic review of diagnostic studies in myasthenia gravis. Neuromuscul Disord 2006; 16:459.
- Golnik KC, Pena R, Lee AG, Eggenberger ER. An ice test for the diagnosis of myasthenia gravis. Ophthalmology 1999; 106:1282.
- Larner AJ. The place of the ice pack test in the diagnosis of myasthenia gravis. Int J Clin Pract 2004; 58:887.
- Pascuzzi RM. The edrophonium test. Semin Neurol 2003; 23:83.
- Ing EB, Ing SY, Ing T, Ramocki JA. The complication rate of edrophonium testing for suspected myasthenia gravis. Can J Ophthalmol 2000; 35:141.
- Vernino S, Lennon VA. Autoantibody profiles and neurological correlations of thymoma. Clin Cancer Res 2004; 10:7270.
- Choi Decroos E, Hobson-Webb LD, Juel VC, et al. Do acetylcholine receptor and striated muscle antibodies predict the presence of thymoma in patients with myasthenia gravis? Muscle Nerve 2014; 49:30.
- Lennon VA. Serologic profile of myasthenia gravis and distinction from the Lambert-Eaton myasthenic syndrome. Neurology 1997; 48:S23.
- Vincent A, McConville J, Farrugia ME, et al. Antibodies in myasthenia gravis and related disorders. Ann N Y Acad Sci 2003; 998:324.
- Chan KH, Lachance DH, Harper CM, Lennon VA. Frequency of seronegativity in adult-acquired generalized myasthenia gravis. Muscle Nerve 2007; 36:651.
- Lindstrom JM, Seybold ME, Lennon VA, et al. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 1976; 26:1054.
- 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.
- Howard FM Jr, Lennon VA, Finley J, et al. Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis. Ann N Y Acad Sci 1987; 505:526.
- Mittag TW, Caroscio J. False-positive immunoassay for acetylcholine-receptor antibody in amyotrophic lateral sclerosis. N Engl J Med 1980; 302:868.
- Sundewall AC, Lefvert AK, Olsson R. Anti-acetylcholine receptor antibodies in primary biliary cirrhosis. Acta Med Scand 1985; 217:519.
- Pascuzzi RM, Phillips LH 2nd, Johns TR, Lennon VA. The prevalence of electrophysiological and immunological abnormalities in asymptomatic relatives of patients with myasthenia gravis. Ann N Y Acad Sci 1987; 505:407.
- Sanders DB, Andrews PI, Howard Jr JF, Massey JM. Seronegative myasthenia gravis. Neurology 1997; 48:S40.
- McConville J, Farrugia ME, Beeson D, et al. Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann Neurol 2004; 55:580.
- Sanders DB, El-Salem K, Massey JM, et al. Clinical aspects of MuSK antibody positive seronegative MG. Neurology 2003; 60:1978.
- Vincent A, McConville J, Farrugia ME, Newsom-Davis J. Seronegative myasthenia gravis. Semin Neurol 2004; 24:125.
- Nemoto Y, Kuwabara S, Misawa S, et al. Patterns and severity of neuromuscular transmission failure in seronegative myasthenia gravis. J Neurol Neurosurg Psychiatry 2005; 76:714.
- Lavrnic D, Losen M, Vujic A, et al. The features of myasthenia gravis with autoantibodies to MuSK. J Neurol Neurosurg Psychiatry 2005; 76:1099.
- Zhou L, McConville J, Chaudhry V, et al. Clinical comparison of muscle-specific tyrosine kinase (MuSK) antibody-positive and -negative myasthenic patients. Muscle Nerve 2004; 30:55.
- Deymeer F, Gungor-Tuncer O, Yilmaz V, et al. Clinical comparison of anti-MuSK- vs anti-AChR-positive and seronegative myasthenia gravis. Neurology 2007; 68:609.
- Lindstrom J. Is "seronegative" MG explained by autoantibodies to MuSK? Neurology 2004; 62:1920.
- Caress JB, Hunt CH, Batish SD. Anti-MuSK myasthenia gravis presenting with purely ocular findings. Arch Neurol 2005; 62:1002.
- Hanisch F, Eger K, Zierz S. MuSK-antibody positive pure ocular myasthenia gravis. J Neurol 2006; 253:659.
- Ohta K, Shigemoto K, Kubo S, et al. MuSK antibodies in AChR Ab-seropositive MG vs AChR Ab-seronegative MG. Neurology 2004; 62:2132.
- Yeh JH, Chen WH, Chiu HC, Vincent A. Low frequency of MuSK antibody in generalized seronegative myasthenia gravis among Chinese. Neurology 2004; 62:2131.
- Romi F, Aarli JA, Gilhus NE. Seronegative myasthenia gravis: disease severity and prognosis. Eur J Neurol 2005; 12:413.
- Willcox N, Schluep M, Ritter MA, Newsom-Davis J. The thymus in seronegative myasthenia gravis patients. J Neurol 1991; 238:256.
- Verma PK, Oger JJ. Seronegative generalized myasthenia gravis: low frequency of thymic pathology. Neurology 1992; 42:586.
- Lauriola L, Ranelletti F, Maggiano N, et al. Thymus changes in anti-MuSK-positive and -negative myasthenia gravis. Neurology 2005; 64:536.
- Leite MI, Ströbel P, Jones M, et al. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol 2005; 57:444.
- Scuderi F, Marino M, Colonna L, et al. Anti-p110 autoantibodies identify a subtype of "seronegative" myasthenia gravis with prominent oculobulbar involvement. Lab Invest 2002; 82:1139.
- Evoli A, Tonali PA, Padua L, et al. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain 2003; 126:2304.
- Vincent A, Bowen J, Newsom-Davis J, McConville J. Seronegative generalised myasthenia gravis: clinical features, antibodies, and their targets. Lancet Neurol 2003; 2:99.
- Pasnoor M, Wolfe GI, Nations S, et al. Clinical findings in MuSK-antibody positive myasthenia gravis: a U.S. experience. Muscle Nerve 2010; 41:370.
- Evoli A, Alboini PE, Iorio R, et al. Pattern of ocular involvement in myasthenia gravis with MuSK antibodies. J Neurol Neurosurg Psychiatry 2017; 88:761.
- Sanders DB, Massey JM. The diagnostic utility of anti-striational antibodies in myasthenia gravis. Neurology 2002; 58:A229.
- Voltz RD, Albrich WC, Nägele A, et al. Paraneoplastic myasthenia gravis: detection of anti-MGT30 (titin) antibodies predicts thymic epithelial tumor. Neurology 1997; 49:1454.
- Gautel M, Lakey A, Barlow DP, et al. Titin antibodies in myasthenia gravis: identification of a major immunogenic region of titin. Neurology 1993; 43:1581.
- Romi F, Skeie GO, Gilhus NE, Aarli JA. Striational antibodies in myasthenia gravis: reactivity and possible clinical significance. Arch Neurol 2005; 62:442.
- Chen XJ, Qiao J, Xiao BG, Lu CZ. The significance of titin antibodies in myasthenia gravis--correlation with thymoma and severity of myasthenia gravis. J Neurol 2004; 251:1006.
- Skeie GO, Romi F. Paraneoplastic myasthenia gravis: immunological and clinical aspects. Eur J Neurol 2008; 15:1029.
- Oh SJ, Kim DE, Kuruoglu R, et al. Diagnostic sensitivity of the laboratory tests in myasthenia gravis. Muscle Nerve 1992; 15:720.
- AAEM Quality Assurance Committee. American Association of Electrodiagnostic Medicine. Literature review of the usefulness of repetitive nerve stimulation and single fiber EMG in the electrodiagnostic evaluation of patients with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome. Muscle Nerve 2001; 24:1239.
- Padua L, Caliandro P, Di Iasi G, et al. Reliability of SFEMG in diagnosing myasthenia gravis: sensitivity and specificity calculated on 100 prospective cases. Clin Neurophysiol 2014; 125:1270.
- Morren JA, Levin KH, Shields RW. Diagnostic Accuracy of Single Fiber Electromyography for Myasthenia Gravis in Patients Followed Longitudinally. J Clin Neurophysiol 2016; 33:469.
- Krendel DA, Sanders DB, Massey JM. Single fiber electromyography in chronic progressive external ophthalmoplegia. Muscle Nerve 1987; 10:299.
- Milone M, Monaco ML, Evoli A, et al. Ocular myasthenia: diagnostic value of single fibre EMG in the orbicularis oculi muscle. J Neurol Neurosurg Psychiatry 1993; 56:720.
- Sanders DB, Massey EW, Buckley EG. Botulinum toxin for blepharospasm: single-fiber EMG studies. Neurology 1986; 36:545.
- Castleman B. The pathology of the thymus gland in myasthenia gravis. Ann N Y Acad Sci 1966; 135:496.
- Fujita J, Yamadori I, Yamaji Y, et al. Myasthenia gravis associated with small-cell carcinoma of the lung. Chest 1994; 105:624.
- Levin N, Abramsky O, Lossos A, et al. Extrathymic malignancies in patients with myasthenia gravis. J Neurol Sci 2005; 237:39.
- Abrey LE. Association of myasthenia gravis with extrathymic Hodgkin's lymphoma: complete resolution of myasthenic symptoms following antineoplastic therapy. Neurology 1995; 45:1019.
- DIAGNOSTIC APPROACH
- BEDSIDE TESTS
- Ice pack test
- Edrophonium test
- SEROLOGIC TESTING
- Acetylcholine receptor antibodies
- MuSK antibodies
- - Clinical features
- Seronegative myasthenia
- Other antibodies
- ELECTROPHYSIOLOGIC CONFIRMATION
- Repetitive nerve stimulation
- Single-fiber electromyography
- ASSOCIATED CONDITIONS
- Thymic tumors and other malignancies
- Autoimmune disorders
- DIFFERENTIAL DIAGNOSIS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS