Abstract
Purpose
To clarify the clinical features of patients with Double seronegative (DS) ocular myasthenia gravis (OMG).
Methods
Sixty-one patients diagnosed with DS OMG at the Department of Ophthalmology, Hyogo Medical University Hospital over a 5-year period from 2017 were included. Patients were classified into three groups based on the initial examination findings: group P (ptosis alone), group M (ocular motility disorder alone), and group PM (combination of both). We retrospectively reviewed the patients and clarified their clinical features.
Results
There were 32 males and 29 females, with a mean age of 49.8 ± 20.9:1–82 years. Twenty-one patients (34.4%) were in group P, 23 (37.7%) in group M, and 17 (27.8%) in group PM. The proportion of males (73.9%) was significantly higher in group M compared with the other two groups. The diagnosis was proven by detection of neuromuscular junction (NMJ) disorder in 73.8%, oral pyridostigmine trial test in 13.1%, and eight patients (13.1%) in group M were diagnosed after surgical treatment. The clinical symptoms were resolved by oral pyridostigmine treatment in 54.1% of cases.
Conclusion
About 30% of patients with DS OMG had no obvious NMJ disorder, and an oral pyridostigmine trial test was necessary to diagnose these patients. Although DS OMG is often considered as the mildest form of MG, its prognosis is not optimistic and it requires aggressive therapeutic intervention.
Trial registration
Trial registration number: 202104–750, “2016/4/18,” retrospectively registered.
Similar content being viewed by others
References
Murai H, Yamashita N, Watanabe M, Nomura Y, Motomura M, Yoshikawa H, Nakamura Y, Kawaguchi N, Onodera H, Araga S, Isobe N, Nagai M, Kira J (2011) Characteristics of myasthenia gravis according to onset-age: Japanese nationwide survey. J Neurol Sci 305:97–102. https://doi.org/10.1016/j.jns.2011.03.004
Behbehani R, Ali A, Al-Moosa A (2022) Ocular myasthenia: clinical course and the diagnostic utility of assaying acetylcholine receptor antibodies. Neuroophthalmology 46:220–226. https://doi.org/10.1080/01658107.2022.2037662
Rodríguez Cruz PM, Al-Hajjar M, Huda S, Jacobson L, Woodhall M, Jayawant S, Buckley C, Hilton-Jones D, Beeson D, Vincent A, Leite MI, Palace J (2015) Clinical features and diagnostic usefulness of antibodies to clustered acetylcholine receptors in the diagnosis of seronegative myasthenia gravis. JAMA Neurol 72:642–649. https://doi.org/10.1001/jamaneurol.2015.0203
Gilhus NE, Verschuuren JJ (2015) Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 14:1023–1036. https://doi.org/10.1016/S1474-4422(15)00145-3
Japanese Society of Neurology (2022) Myasthenia gravis/Lambert-Eaton myasthenia syndrome clinical practice guideline 2022. https://www.neurology-jp.org/guidelinem/mg_2022.html. Accessed 7 Sept 2023
Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458. https://doi.org/10.1038/bmt.2012.244
Blum S, Lee D, Gillis D, McEniery DF, Reddel S, McCombe, (2015) P. Clinical features and impact of myasthenia gravis disease in Australian patients. J Clin Neurosci 22:1164–1169. https://doi.org/10.1016/j.jocn.2015.01.022
Nagane Y, Murai H, Imai T, Yamamoto D, Tsuda E, Minami N, Suzuki Y, Kanai T, Uzawa A, Kawaguchi N, Masuda M, Konno S, Suzuki H, Aoki M, Utsugisawa K (2017) Social disadvantages associated with myasthenia gravis and its treatment: a multicentre cross-sectional study. BMJ Open 7:e013278. https://doi.org/10.1136/bmjopen-2016-013278
Pasnoor M, He J, Herbelin L, Burns TM, Nations S, Bril V, Wang AK, Elsheikh BH, Kissel JT, Saperstein D, Shaibani JA (2016) Methotrexate in MG Investigators of the Muscle Study Group (2016) A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis. Neurology 87:57–64. https://doi.org/10.1212/WNL.0000000000002795
Bever CT Jr, Aquino AV, Penn AS, Lovelace RE, Rowland LP (1983) Prognosis of ocular myasthenia. Ann Neurol 14:516–519. https://doi.org/10.1002/ana.410140504
Hendricks TM, Bhatti MT, Hodge DO, Chen JJ (2019) Incidence, epidemiology, and transformation of ocular myasthenia gravis: a population-based study. Am J Ophthalmol 205:99–105. https://doi.org/10.1016/j.ajo.2019.04.017
Drachman DB (1994) Myasthenia gravis. N Engl J Med 330:1797–1810. https://doi.org/10.1056/NEJM199406233302507
Watanabe G, Suzuki Y, Takai Y et al (2012) Clinical features of autoimmune thyroid disease complication in myasthenia gravis. The 24th Annual Meeting of the Japanese Society for Neuroimmunology (Abstract).
Roper J, Fleming ME, Long B, Koyfman A (2017) Myasthenia gravis and crisis: evaluation and management in the emergency department. J Emerg Med 53:843–853. https://doi.org/10.1016/j.jemermed.2017.06.009
Godoy DA, de Mello LJV, Masotti L, Di Napoli M (2013) The myasthenic patient in crisis: an update of the management in neurointensive care unit. Arq Neuropsiquiatr 71:627–639. https://doi.org/10.1590/0004-282X20130108
Kee HJ, Yang HK, Hwang JM, Park KS (2019) Evaluation and validation of sustained upgaze combined with the ice-pack test for ocular myasthenia gravis in Asians. Neuromuscul Disord 29:296–301. https://doi.org/10.1016/j.nmd.2018.12.011
Mittal MK, Barohn RJ, Pasnoor M, McVey A, Herbelin L, Whittaker T, Dimachkie M (2011) Ocular myasthenia gravis in an academic neuro-ophthalmology clinic: clinical features and therapeutic response. J Clin Neuromuscul Dis 13:46–52. https://doi.org/10.1097/CND.0b013e31821c5634
Motomura M (2011) Standard treatment for late-onset myasthenia gravis in Japan. Clin Neurol 51:576–582. https://doi.org/10.5692/clinicalneurol.51.576
Sanders DB (2002) Clinical impact of single-fiber electromyography. Muscle Nerve 25:S15-20. https://doi.org/10.1002/mus.10141
Japanese SFEMG Study Group (2012) Reference values for voluntary and stimulated single-fibre EMG using concentric needle electrodes: a multicentre prospective study. Clin Neurophysiol 123:613–620. https://doi.org/10.1016/j.clinph.2011.07.044
Utsugisawa K, Nagane Y, Akaishi T, Suzuki Y, Imai T, Tsuda E, Minami N, Uzawa A, Kawaguchi N, Masuda M, Konno S, Suzuki H, Murai H, Aoki M (2017) Early fast-acting treatment strategy against generalized myasthenia gravis. Muscle Nerve 55:794–801. https://doi.org/10.1002/mus.25397
Zhang B, Tzartos JS, Belimezi M, Ragheb S, Bealmear B, Lewis RA, Xiong WC, Lisak RP, Tzartos SJ, Mei L (2012) Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol 69:445–451. https://doi.org/10.1001/archneurol.2011.2393
Funding
No funding was received for this research.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Hyogo Medical University Hospital, Hyogo, Japan (No. 202104–750), and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Consent to participate
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Goto, T., Kimura, A., Masuda, A. et al. Clinical features of double seronegative ocular myasthenia gravis. Graefes Arch Clin Exp Ophthalmol (2024). https://doi.org/10.1007/s00417-024-06425-w
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00417-024-06425-w