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Current approach to seronegative myasthenia

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The group of patients with weakness or fatigue who have electrophysiological evidence of neuromuscular transmission defects, but no antibodies against either acetyl choline receptor or muscle specific kinase, need special evaluation and therapeutic consideration. Such seronegative patients may have low affinity antibodies but may also be late onset of a congenital myasthenic syndrome. This review discuss the practical approach toward the condition of seronegative myasthenia.

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  1. Evoli A, Tonali P, Padua L et al (2003) Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain 126:2304–2311

    Article  PubMed  Google Scholar 

  2. Vincent A, Leite MI (2005) Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis. Curr Opin Neurol 18:519–525

    Article  CAS  PubMed  Google Scholar 

  3. Vincent A, McConville J, Farrugia ME, Newsome-Davis J (2004) Seronegative myasthenia gravis. Sem Neurol 24:125–133

    Article  Google Scholar 

  4. Zhou L, McConville J, Chaudhry V et al (2004) Clinical comparison of muscle-specific tyrosine kinase (MuSK) antibody-positive and–negative myasthenic patients. Muscle Nerve 30:55–60

    Article  CAS  PubMed  Google Scholar 

  5. Lavrnic D, Losen M, Vujic A et al (2005) The features of myasthenia gravis with antibodies to MuSK. J Neurol Neurosurg Psychiat 76:1099–1102

    Article  CAS  PubMed  Google Scholar 

  6. Nemoto Y, Kuwabara S, Misawa S et al (2005) Pattern and severity of neuromuscular transmission failure in seronegative myasthenia gravis. J Neurol Neurosurg Psychiat 76:714–718

    Article  CAS  PubMed  Google Scholar 

  7. Romi F, Aarli JA, Gilhus NE (2005) Seronegative myasthenia gravis: disease severity and prognosis. Eur J Neurol 12:413–418

    Article  CAS  PubMed  Google Scholar 

  8. Padua L, Tonali P, Aprile I et al (2006) Seronegative myasthenia gravis: comparison of neurophysiological picture in MuSK+ and MUSK− patients. Eur J Neurol 13:273–276

    Article  CAS  PubMed  Google Scholar 

  9. Leite MI, Jacob S, Viegas S et al (2008) IgGI antibodies to acetylcholine receptors in ‘seronegative’ myasthenia gravis. Brain 131:1940–1952

    Article  PubMed  Google Scholar 

  10. Sanders DB, Stalberg EV (1996) AAEM minimonograph #25: single fiber electromyography. Muscle Nerve 19:1069–1083

    Article  CAS  PubMed  Google Scholar 

  11. Denys EH, Norris FH (1979) Amyotrophic lateral sclerosis. Impairment of neuromuscular transmission. Arch Neurol 36:202–205

    CAS  PubMed  Google Scholar 

  12. Stalberg E, Schwartz MS, Trontelj JV (1975) Single fiber electromyography in various processes affecting the anterior horn cell. J Neurol Sci 24:403–415

    Article  CAS  PubMed  Google Scholar 

  13. Vasilescu C, Bucur G, Petrovici A, Florescu A (1978) Myasthenia in patients with dermatomyositis: clinical, electrophysiological and ultrastructural studies. J Neurol Sci 38:129–144

    Article  CAS  PubMed  Google Scholar 

  14. Krendel DA, Sanders DB, Massey JM (1987) Single fiber electromyography in chronic progressive external ophthalmoplegia. Muscle Nerve 10:299–302

    Article  CAS  PubMed  Google Scholar 

  15. Cruz-Martinez A, Arpa J, Santiago S et al (2004) Single fiber electromyography (SFEMG) in mitochondrial diseases (MD). Electromyogr Clin Neurophysiol 44:35–38

    CAS  PubMed  Google Scholar 

  16. Johnson W, Karpati G, Carpenter S et al (1995) Late-onset mitochondrial myopathy. Ann Neurol 37:16–23

    Article  Google Scholar 

  17. Biran I, Cohen O, Diment J et al (1999) Focal, steroid responsive myositis causing dropped head syndrome. Muscle Nerve 22:769–771

    Article  CAS  PubMed  Google Scholar 

  18. Schara U, Lochmuller H (2008) Therapeutic strategies in congenital myasthenic syndromes. Neurotherapeutics 5:542–547

    Article  CAS  PubMed  Google Scholar 

  19. Palace J, Lashley D, Newsom-Davis J et al (2007) Clinical features of the DOK7 neuromuscular junction synaptopathy. Brain 130:1507–1515

    Article  PubMed  Google Scholar 

  20. Muller JS, Herczegfalvi A, Vilchez JJ et al (2007) Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes. Brain 130:1497–1506

    Article  PubMed  Google Scholar 

  21. Muller JS, Petrova S, Kiefer R et al (2004) Synaptic congenital myasthenic syndrome in three patients due to a novel missense mutation (Taa1A) of the COLQ gene. Neuropedatrics 35:183–189

    Article  CAS  Google Scholar 

  22. Burke G, Cossins J, Maxwell S et al (2003) Rapsyn mutations in hereditary myasthenia:distinct early- and late-onset phenotypes. Neurology 61:826–828

    CAS  PubMed  Google Scholar 

  23. Abicht A, Stucka R, Karcagi V et al (1999) A common mutation (epsilon 1267delG) in congenital myasthenic patients of Gypsy ethnic origin. Neurology 53:1564–1569

    CAS  PubMed  Google Scholar 

  24. Chauplannaz G, Bady B (1994) Hereditary myasthenic syndromes with late onset. Value of electrophysiological tests. Rev Neurol 150:142–148

    CAS  PubMed  Google Scholar 

  25. Leite MI, Strobel P, Jones M et al (2005) Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol 57:448–448

    Article  Google Scholar 

  26. Lindstrom J (2008) ‘Seronegative’ myasthenia gravis is no longer seronegative. Brain 131:1684–1685

    Article  PubMed  Google Scholar 

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Correspondence to Zohar Argov.

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Argov, Z. Current approach to seronegative myasthenia. J Neurol 258, 14–18 (2011).

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