Skip to main content

Advertisement

SpringerLink
Log in

Antibody profile may predict outcome in ocular myasthenia gravis

  • Original Article
  • Published:
Acta Neurologica Belgica Aims and scope Submit manuscript

Abstract

An unsolved issue remains whether there are clinical and immunological features to predict in a single patient the risk of conversion from ocular Myasthenia Gravis (OMG) to generalized disease (GMG) as 50–60% of patients may progress within 1–2 years since onset. Anti-acetylcholine receptor antibodies (AChR Abs) are found in up to 50% of OMG patients; muscle-specific tyrosine kinase antibodies (MuSK-Abs) are present in about 70% of the whole seronegative (SN), who usually develop a severe disease with bulbar involvement. We surveyed a cohort of 175 OMG patients with purely ocular symptoms and we compare the outcome of patients with antibodies to AChR or to MuSK with those seronegative for both Abs (DSN). All patients had purely ocular signs for at least 24 months. Gender, age at onset, time to generalization or to worsening in quantitative ocular QMG scores, electrophysiological results were analyzed. Males were 58.9%, females 41.1%. Patients with late onset of symptoms after 50 years (LOMG) were 78.3%. We assayed anti-MuSK-Abs in 4.7%, anti-AChR Abs in 38.5%; 57.3% were defined DSN. Thirty-seven patients (21.1%) progressed to GMG during the observational time: 23 were females, 62% of the whole group of the generalized subjects, 75% of MuSK-positive OMG converted to GMG versus the 26.2% of AChR positive and 13.7% of DSN. Statistical analysis showed that gender and presence of antibodies either to AChR or to MuSK were independent predictors of worse outcome; the DSN subjects had lower risk of conversion to GMG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Vincent A, Palace J, Hilton-Jones D (2001) Myasthenia gravis. Lancet 357:2122–2128. https://doi.org/10.1016/S0140-6736(00)05186-2

    Article  PubMed  CAS  Google Scholar 

  2. Meriggioli MN, Sanders DB (2009) Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 8:475–490. https://doi.org/10.1016/S1474-4422(09)70063-8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Berrih-Aknin S, Frenkian-Cuvelier M, Eymard B (2014) Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimmun 48–49:143–148. https://doi.org/10.1016/j.jaut.2014.01.00352 139–145

    Article  PubMed  Google Scholar 

  4. Vaphiades MS, Bhatti MT, Lesser RL (2012) Ocular myasthenia gravis. Curr Opin Ophthalmol 23(6):537–542. https://doi.org/10.1097/ICU.0b013e328358b94a

    Article  PubMed  Google Scholar 

  5. Benatar M (2006) A systematic review of diagnostic studies in myasthenia gravis. Neuromuscul Disord 16:459–467. https://doi.org/10.1016/j.nmd.2006.05.006

    Article  PubMed  Google Scholar 

  6. Kupersmith MJ, Latkany R, Homel P (2003) Development of generalized disease at 2 years in patients with ocular myasthenia gravis. Arch Neurol 60:243–248. https://doi.org/10.1001/archneur.60.2.243

    Article  PubMed  Google Scholar 

  7. Ariatti A, Stefani M, Miceli P, Benuzzi F, Galassi G (2014) Prognostic factors and health-related quality of life in ocular myasthenia gravis (OMG). Int J Neurosci 124:427–435. https://doi.org/10.3109/00207454.2013.853664

    Article  PubMed  Google Scholar 

  8. Katzberg HD, Barnett C, Bril V (2012) Predictors of response to immunomodulation in patients with myasthenia gravis. Muscle Nerve 45:648–652. https://doi.org/10.1002/mus.23236

    Article  PubMed  Google Scholar 

  9. Grob D, Brunner N, Namba T, Pagala M (2008) Lifetime course of myasthenia gravis. Muscle Nerve 37(2):141–149. https://doi.org/10.1002/mus.20950

    Article  PubMed  Google Scholar 

  10. Peeler CE, De Lott LB, Nagia L, Lemos J, Eggenberger ER, Cornblath WT (2015) Clinical utility of acetylcholine receptor antibody testing in ocular myasthenia gravis. JAMA Neurol 72:1170–1174. https://doi.org/10.1001/jamaneurol.2015.1444

    Article  PubMed  PubMed Central  Google Scholar 

  11. Skeie GO, Apostolski S, Evoli A, Gilhus NE, Illa I, Harms L, Hilton-Jones D, Melms A, Verschuuren J, Horge HW, European Federation of Neurological Societies (2010) Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol 17:893–902. https://doi.org/10.1111/j.1468-1331.2010.03019.x

    Article  PubMed  CAS  Google Scholar 

  12. Bhanushali MJ, Wuu J, Benatar M (2008) Treatment of ocular symptoms in myasthenia gravis. Neurology 71:1335–1341. https://doi.org/10.1212/01.wnl.0000327669.75695.38

    Article  PubMed  CAS  Google Scholar 

  13. Argov Z (2011) Current approach to seronegative myasthenia. J Neurol 258:14–18. https://doi.org/10.1007/s00415-010-5746-6

    Article  PubMed  Google Scholar 

  14. Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD (1998) Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 51:933–933

    PubMed  Google Scholar 

  15. Verschuuren JJ, Huijbers MG, Plomp JJ, Niks EH, Molenaar PC, Martinez-Martinez P, Gomez AM, De Baets MH, Losen M (2013) Pathophysiology of myasthenia gravis with antibodies to the acetylcholine receptor, muscle-specific kinase, and low-density lipoprotein receptor-related protein 4. Autoimmune Rev 12:918–923. https://doi.org/10.1016/j.autrev.2013.03.001

    Article  CAS  Google Scholar 

  16. Benatar M, Mcdermott MP, Sanders DB, Wolfe GI, Barohn RJ, Nowak RJ, Hehir M, Juel V, Katzberg H, Tawil R, Muscle Study Group (MSG) (2016) Efficacy of prednisone for the treatment of ocular myasthenia (EPITOME): a randomized, controlled trial. Muscle Nerve 53:363–369. https://doi.org/10.1002/mus.24769

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Wong SH, Plant GT, Cornblath W (2016) Does treatment of ocular myasthenia gravis with early immunosuppressive therapy prevent secondarily generalization and should it be offered to all such patients? J Neuroophthalmol 36:98–102. https://doi.org/10.1097/WNO.0000000000000270

    Article  PubMed  Google Scholar 

  18. Wong SH, Huda S, Vincent A, Plant GT (2014) Ocular myasthenia gravis: controversies and updates. Curr Neurol Neurosci Rep 14:421. https://doi.org/10.1007/s11910-013-0421-9

    Article  PubMed  CAS  Google Scholar 

  19. Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A (2001) Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 7:365–368. https://doi.org/10.1038/85520

    Article  PubMed  CAS  Google Scholar 

  20. Allen JA, Scala S, Jones HR (2010) Ocular myasthenia gravis in a senior population: diagnosis, therapy, and prognosis. Muscle Nerve 41(3):379–384. https://doi.org/10.1002/mus.21555

    Article  PubMed  Google Scholar 

  21. Romi F, Hong Y, Gilhus NE (2017) Pathophysiology and immunological profile of myasthenia gravis and its subgroups. Curr Opin Immunol 49:9–13. https://doi.org/10.1016/j.coi.2017.07.006

    Article  PubMed  CAS  Google Scholar 

  22. Gilhus NE, Skeie GO, Romi F, Lazaridis K, Zisimopoulou P, Tzartos S (2016) Myasthenia gravis—autoantibody characteristics and their implications for therapy. Nat Rev Neurol 12:259–268. https://doi.org/10.1038/nrneurol.2016.44

    Article  PubMed  CAS  Google Scholar 

  23. Wong SH, Petrie A, Plant GT (2016) Ocular myasthenia gravis: toward a risk of generalization score and sample size calculation for a randomized controlled trial of disease modification. J Neuroophthalmol 36:252–258. https://doi.org/10.1097/WNO.0000000000000350

    Article  PubMed  Google Scholar 

  24. Lee JY, Sung JJ, Cho JY, Oh DH, Kim HJ, Park JH, Lee KW, Choi YC, Vincent A (2006) MuSK antibody-positive, seronegative myasthenia gravis in Korea. J Clin Neurosci 13:353–355. https://doi.org/10.1016/j.jocn.2005.04.028

    Article  PubMed  Google Scholar 

  25. Evoli A, Alboini PE, Iorio R, Damato V, Bartoccioni E (2017) Pattern of ocular involvement in myasthenia gravis with MuSK antibodies. J Neurol Neurosurg Psychiatry 88:761–763. https://doi.org/10.1136/jnnp-2017-315782

    Article  PubMed  Google Scholar 

  26. Guptill JT, Sanders DB, Evoli A (2011) Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve 44:36–40. https://doi.org/10.1002/mus.22006

    Article  PubMed  Google Scholar 

  27. Tsonis AI, Zisimopoulou P, Lazaridis K, Tzartos J, Matsigkou E, Zouvelou V, Mantegazza R, Antozzi C, Andreetta F, Evoli A, Deymeer F, Saruhan-Direskeneli G, Durmus H, Brenner T, Vaknin A, Berrih-Aknin S, Behin A, Sharshar T, De Baets M, Losen M, Martinez-Martinez P, Kleopa KA, Zamba- Papanicolaou E, Kyriakides T, Kostera-Pruszczyk A, Szczudlik P, Szyluk B, Lavrnic D, Basta I, Peric S, Tallaksen C, Maniaol A, Casasnovas Pons C, Pitha J, Jakubı´kova M, Hanisch F, Tzartos SJ (2015) MuSK autoantibodies in myasthenia gravis detected by cell-based assay: a multinational study. J Neuroimmunol 284:10–17. https://doi.org/10.1016/j.jneuroim.2015.04.015

    Article  PubMed  CAS  Google Scholar 

  28. Kerty E, Elsais A, Argov Z, Evoli A, Gilhus NE (2014) EFNS/ENS Guidelines for the treatment of ocular myasthenia. Eur J Neurol 21:687–693. https://doi.org/10.1111/ene.12359

    Article  PubMed  CAS  Google Scholar 

  29. Jaretzki 3rd A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB (2000) Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 55(1):16–23

    Article  PubMed  Google Scholar 

  30. Mazzoli M, Ariatti A, Valzania F, Kaleci S, Tondelli M, Nichelli PF, Galassi G (2018) Factors affecting outcome in ocular myasthenia gravis. Int J Neurosci 128:15–24. https://doi.org/10.1080/00207454.2017.1344237

    Article  PubMed  CAS  Google Scholar 

  31. Zach H, Cetin H, Hilger E, Paul A, Wuschitz B, Jung R, Auff E, Zimprich F (2013) The effect of early prednisolone treatment on the generalization rate in ocular myasthenia gravis. Eur J Neurol 20:708–713. https://doi.org/10.1111/ene.12057

    Article  PubMed  CAS  Google Scholar 

  32. Katzberg HD, Bril V (2005) A comparison of electrodiagnostic tests in ocular myasthenia gravis. J Clin Neuromuscul Dis 6:109–113. https://doi.org/10.1097/01.cnd.0000155026.66153.f0

    Article  PubMed  Google Scholar 

  33. Weinberg DH, Rizzo 3rd JF, Hayes MT, Kneeland MD, Kelly Jr JJ (1999) Ocular myasthenia gravis: predictive value of single-fiber electromyography. Muscle Nerve 22:1222–1227

    Article  PubMed  CAS  Google Scholar 

  34. Mercelis R, Merckaert V (2011) Diagnostic utility of stimulated single-fiber electromyography of the orbicularis oculi muscle in patients with suspected ocular myasthenia. Muscle Nerve 43:168–170. https://doi.org/10.1002/mus.21853

    Article  PubMed  Google Scholar 

  35. Baruca M, Leonardis L, Podnar S, Hojis-Fabian T, Grad A, Jerin SA, Blagus R, Sega-Jazbec S (2016) Single fiber EMG as prognostic tool in myasthenia gravis. Muscle Nerve 54:1034–1040. https://doi.org/10.1002/mus.25174

    Article  PubMed  CAS  Google Scholar 

  36. Bartoccioni E, Scuderi F, Minicuci GM, Marino M, Ciaraffa F, Evoli A (2006) Anti-MuSK antibodies: correlation with myasthenia gravis severity. Neurology 67:505–507. https://doi.org/10.1212/01.wnl.0000228225.23349.5d

    Article  PubMed  CAS  Google Scholar 

  37. Deymeer F, Gungor-Tuncer O, Yilmaz V, Parman Y, Serdaroglu P, Ozdemir C, Vincent A, Saruhan-Direskeneli G (2007) Clinical comparison of anti-MuSK vs anti-AChR-positive and seronegative myasthenia gravis. Neurology 68:609–611. https://doi.org/10.1212/01.wnl.0000254620.45529.97

    Article  PubMed  CAS  Google Scholar 

  38. Chan JW, Orrison WW (2007) Ocular myasthenia: a rare presentation with MuSK antibody and bilateral extraocular muscle atrophy. Br J Ophthalmol 91:842–843. https://doi.org/10.1136/bjo.2006.108498

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hanisch F, Eger K, Zierz S (2006) MuSK-antibody positive pure ocular myasthenia gravis. J Neurol 253:659–660. https://doi.org/10.1007/s00415-005-0032-8

    Article  PubMed  Google Scholar 

  40. Caress JB, Hunt CH, Batish SD (2005) Anti-MuSK myasthenia gravis presenting with purely ocular findings. Arch Neurol 62:1002–1003. https://doi.org/10.1001/archneur.62.6.1002

    Article  PubMed  Google Scholar 

  41. Zouvelou V, Stamboulis E, Skriapa L, Tzartos SJ (2013) MuSK-Ab positive myasthenia: not always grave. J Neurol Sci 331:150–151. https://doi.org/10.1016/j.jns.2013.05.001

    Article  PubMed  CAS  Google Scholar 

  42. Zambelis T, Pappas V, Kokotis P, Zouvelou V, Karandreas N (2015) Patients with ocular symptoms referred for electrodiagnosis: how many of them suffer from myasthenia gravis? Acta Neurol Belg 115:671–674. https://doi.org/10.1007/s13760-015-0460-x

    Article  PubMed  Google Scholar 

  43. Higuchi O, Hamuro J, Motomura M, Yamanashi Y (2011) Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis. Ann Neurol 69:418–422. https://doi.org/10.1002/ana.22312

    Article  PubMed  CAS  Google Scholar 

  44. Hong Y, Zisimopoulou P, Trakas N, Karagiorgou K, Stergiou C, Skeie GO, Hao HL, Gao X, Owe JF, Zhang X, Yue YX, Romi F, Wang Q, Li HF, Gilhus NE, Tzartos SJ (2017) Multiple antibody detection in “seronegative” myasthenia gravis patients. Eur J Neurol 24:844–850. https://doi.org/10.1111/ene.13300

    Article  PubMed  CAS  Google Scholar 

  45. Illa I, Cortés-Vicente E, Martínez M, Gallardo E (2018) Diagnostic utility of cortactin antibodies in myasthenia gravis. Ann N Y Acad Sci 1412:90–94. https://doi.org/10.1111/nyas.13502

    Article  PubMed  CAS  Google Scholar 

  46. Huijbers MG, Vink AF, Niks EH, Westhuis RH, van Zwet EW, de Meel RH, Rojas-García R, Díaz-Manera J, Kuks JB, Klooster R, Straasheijm K, Evoli A, Illa I, van der Maarel SM, Verschuuren JJ (2016) Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity. J Neuroimmunol 291:82–88. https://doi.org/10.1016/j.jneuroim.2015.12.016

    Article  PubMed  CAS  Google Scholar 

  47. Hellmann MA, Mosberg-Galili R, Steiner I (2013) Myasthenia gravis in the elderly. J Neurol Sci 325:1–5. https://doi.org/10.1016/j.jns.2012.10.028

    Article  PubMed  Google Scholar 

  48. Alkhawajah NM, Oger J (2013) Late-onset myasthenia gravis: a review when incidence in older adults keeps increasing. Muscle Nerve 48:705–710. https://doi.org/10.1002/mus.23964

    Article  PubMed  Google Scholar 

  49. Aguirre F, Villa AM (2018) Prognosis of ocular myasthenia gravis in an Argentinian population. Eur Neurol 79:113–117. https://doi.org/10.1159/000487132

    Article  PubMed  Google Scholar 

  50. Andersen JB, Gilhus NE, Sanders DB (2016) Factors affecting outcome in myasthenia gravis. Muscle Nerve 54:1041–1049. https://doi.org/10.1002/mus.25205

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

There was no funding for this study.

Author information

Authors and Affiliations

  1. Department of Biomedical, Metabolic and Neural Sciences, University Hospital, Modena, Italy

    Giuliana Galassi, Marco Mazzoli, Alessandra Ariatti & Paolo F. Nichelli

  2. Department of Neurology, Arcispedale S. Maria Nuova, Reggio Emilia, Italy

    Franco Valzania

  3. Department of Diagnostic Clinical Medicine and Public Health, University of Modena, Modena, Italy

    Shaniko Kaleci

Authors
  1. Giuliana Galassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marco Mazzoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandra Ariatti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shaniko Kaleci
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Franco Valzania
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paolo F. Nichelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuliana Galassi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors. All the procedures were accordance with the ethical standard of yhe Instutional/ and/or national research committee and with the 1964 Helsinki declaration and its later amendements or comparable ethical standards. The original study on Myasthenia gravis was approved by Institutional University Hospital Ethic Board.

Informed consent

For this type of study formal informed consent is not required

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Galassi, G., Mazzoli, M., Ariatti, A. et al. Antibody profile may predict outcome in ocular myasthenia gravis. Acta Neurol Belg 118, 435–443 (2018). https://doi.org/10.1007/s13760-018-0943-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13760-018-0943-7

Keywords

Search

Navigation