Abstract
In 1976 antibodies against acetyl-choline receptor were identified on the serum of patients with myasthenia gravis. However, some years later, it became clear that about 20% of patients with generalized MG and an electro physiologic disorder on the neuromuscular junction did not express these antibodies by radioimmunoassay (RIPA). These cases represent seronegative myasthenia gravis (SNMG). The diagnosis of these patients is difficult, given the absence of detectable autoantibodies on serum and the lack of sensitive neurophysiologic tests. Recently, a new method based on cellular assays shows an increase on detection of seropositive MG from cases, which were initially diagnosed as seronegative. This article reviews the physiopathology of seronegative MG and gives an update on the latest advances concerning its diagnosis. It also hopes to approach the current general context of the illness in Colombia.
References
Cruz PMR, Al-Hajjar M, Huda S, Jacobson L, Woodhall M, Jayawant S, et al. Clinical Features and Diagnostic Usefulness of Antibodies to Clustered Acetylcholine Receptors in the Diagnosis of Seronegative Myasthenia Gravis. JAMA Neurol [Internet]. 2015 [cited 2015 Dec 21]; 72(6):642-9. Available from: Available from: http://archneur.jamanetwork.com/data/Journals/NEUR/0/noi150011.pdf?v=635645517095870000
Zisimopoulou P, Brenner T, Trakas N, Tzartos SJ. Serological diagnostics in myasthenia gravis based on novel assays and recently identified antigens. Autoimmun Rev. 2013;12(9):924- 30.
Cortés-Vicente E, Gallardo E, Martínez MÁ, Díaz-Manera J, Querol L, Rojas-García R, et al. Clinical characteristics of patients with double-seronegative myasthenia gravis and antibodies to cortactin. Jama Neurol. 2016;73(9):1099-1104.
Boldingh MI, Maniaol AH, Brunborg C, Dekker L, Heldal AT, Lipka AF, et al. Geographical Distribution of Myasthenia Gravis in Northern Europe - Results from a Population-Based Study from Two Countries. Neuroepidemiology. 2015;44(4):221-31.
Oh SJ, Morgan MB, Lu L, Hatanaka Y, Hemmi S, Young A, et al. Different characteristic phenotypes according to antibody in myasthenia gravis. J Clin Neuromuscul Dis. 2012;14(2):57-65.
Nemoto Y, Kuwabara S, Misawa S, Kawaguchi N, Hattori T, Takamori M, et al. Patterns and severity of neuromuscular transmission failure in seronegative myasthenia gravis. J Neurol Neurosurg Psychiatry. 2005;76(5):714-18.
Mori S, Shigemoto K. Mechanisms associated with the pathogenicity of antibodies against muscle-specific kinase in myasthenia gravis. Autoimmun Rev. 2013;12(9):912-917.
Vincent A, Leite MI, Farrugia ME, Jacob S, Viegas S, Shiraishi H, et al. Myasthenia gravis seronegative for acetylcholine receptor antibodies. Ann N Y Acad Sci. 2008;1132(1):84-92.
McConville J, Farrugia ME, Beeson D, Kishore U, Metcalfe R, Newsom-Davis J, et al. Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann Neurol. 2004;55(4):580-4.
Vincent A, McCONVILLE J, Farrugia ME, Bowen J, Plested P, Tang T, et al. Antibodies in Myasthenia Gravis and Related Disorders. Ann N Y Acad Sci. 2003;998(1):324-35.
Argov Z. Current approach to seronegative myasthenia. J Neurol. 2011;258(1):14-8.
Vernino S. Unraveling the Enigma of Seronegative Myasthenia Gravis. JAMA Neurol. 2015;72(6):630-31.
Blanco-Hernández T, Navarré-Gimeno A, Brocalero-Camacho A, Cervelló-Donderis A, López-Trigo J, Ortiz-Sánchez P, et al. [Methods for diagnosing seronegative myasthenia gravis]. Rev Neurol. 2007;46(6):360-364.
Aubert S, Salort-Campana E, Franques J, Uzenot D, Pouget J. Myasthénie séronégative et myasthénie avec anticorps anti-MuSK : une série rétrospective de 20 cas. Rev Neurol (Paris). 2009;165(11):901-10.
Huang Y-C, Yeh J-H, Chiu H-C, Chen W-H. Clinical Characteristics of MuSK Antibody-positive Myasthenia Gravis in Taiwan. J Formos Med Assoc. 2008;107(7):572-5.
Guptill JT, Sanders DB, Evoli A. Anti-musk antibody myas-thenia gravis: Clinical findings and response to treatment in two large cohorts. Muscle Nerve. 2011;44(1):36-40.
Romi F, Aarli JA, Gilhus NE. Seronegative myasthenia gravis: disease severity and prognosis. Eur J Neurol. 2005;12(6):413-8.
Pasutharnchat N, Wacharapluesadee S, Hemachudha T. Clinical manifestations of acetylcholine receptor antibody positive and negative myasthenia gravis. J Med Assoc Thail Chotmaihet Thangphaet. 2012;95(3):313-319.
Oh SJ. Muscle-Specific Receptor Tyrosine Kinase Antibody Positive Myasthenia Gravis Current Status. J Clin Neurol. 2009;5(2):53.
Lavrnic D. The features of myasthenia gravis with autoantibodies to MuSK. J Neurol Neurosurg Psychiatry. 2005;76(8):1099-102.
Evoli A, Padua L. Diagnosis and therapy of myasthenia gravis with antibodies to muscle-specific kinase. Autoimmun Rev 2013;12(9):931-5.
Witoonpanich R, Dejthevaporn C, Sriphrapradang A, Pulkes T. Electrophysiological and immunological study in myasthenia gravis: Diagnostic sensitivity and correlation. Clin Neurophysiol. 2011;122(9):1873-7.
Muppidi S, Wolfe GI. Muscle-Specific Receptor Tyrosine Kinase Antibody-Positive and Seronegative Myasthenia Gravis. In: Pourmand R, editor. Frontiers of Neurology and Neuroscience [Internet]. Basel: KARGER; 2009 [cited 2015 Dec 21]. p. 109-19. Available from: Available from: http://www.karger.com/doi/10.1159/000212372
Leite MI, Jacob S, Viegas S, Cossins J, Clover L, Morgan BP, et al. IgG1 antibodies to acetylcholine receptors in "seronegative"myasthenia gravis. Brain. 2008;131(7):1940-1952.
Chang T, Leite MI, Senanayake S, Gunaratne PS, Gamage R, Riffsy MTM, et al. Clinical and serological study of myasthenia gravis using both radioimmunoprecipitation and cell-based assays in a South Asian population. J Neurol Sci. 2014;343(1-2):82-7.
Tsonis AI, Zisimopoulou P, Lazaridis K, Tzartos J, Matsigkou E, Zouvelou V, et al. MuSK autoantibodies in myasthenia gravis detected by cell based assay - A multinational study. J Neuroimmunol. 2015;284:10-7.
Devic P, Petiot P, Simonet T, Stojkovic T, Delmont E, Franques J, et al. Antibodies to clustered acetylcholine receptor: expanding the phenotype. Eur J Neurol. 2014;21(1):130-4.
Rodriguez Cruz PM, Huda S, López-Ruiz P, Vincent A. Use of cell-based assays in myasthenia gravis and other antibodymediated diseases. Exp Neurol. 2015;270:66-71.
Evoli A, Bianchi MR, Riso R, Minicuci GM, Batocchi AP, Ser-videi S, et al. Response to Therapy in Myasthenia Gravis with Anti-MuSK Antibodies. Ann N Y Acad Sci. 2008;1132(1):76-83.
Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, et al. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain. 2003;126(10):2304-2311.
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