Skip to main content
Top
Published in: Acta Neurologica Belgica 2/2023

14-06-2022 | Myasthenia Gravis | Review article

Cross-syndrome: myasthenia gravis and the demyelinating diseases of the central nervous system combination. Systematic literature review and case reports

Authors: Ekaterina Luzanova, Svetlana Stepanova, Nikita Nadtochiy, Elena Kryukova, Maria Karpova

Published in: Acta Neurologica Belgica | Issue 2/2023

Login to get access

Abstract

Nowadays the problem of comorbidity is still relevant. In this review, we describe clinical cases of the disease of the neuromuscular junction (myasthenia gravis (MG) generalized form) and the demyelinating disease of the central nervous system (DD CNS) (multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), etc.) combinations registered in our practice with precise pathogenetic analysis. Although the number of the described associations is growing every year, the exact development mechanisms of this cross syndrome as well as the nature of the association between the discussed autoimmune diseases remain unknown. At the beginning of both disorders there is a considerable loss of auto tolerance of the immune system and, as a result, an increased response from autoreactive T-lymphocytes to the structures of the nervous system: brain cells and neuromuscular synapses. There are three main theories for comorbidity: initial predisposition, direct case relationship with disease-modifying therapy (DMT) application, and coincidence. It is known that early diagnostics of MG and timely administration of necessary adequate treatment reduce the risk of process generalization and lead to a decline in mortality. Therefore, the offer to examine MS patients with atypical symptoms for possible MG identification seems very rational. Similarly, MG patients having uncharacteristic symptoms that can be indicative of other autoimmune nervous system diseases also demand special diagnostics. Considering the presence of similar pathogenetic links, several authors propose a possibility of a new nosological unit establishment, including described comorbidity.
Literature
1.
go back to reference Park SY, Lee JY, Lim NG, Hong YH (2016) Incidence and prevalence of Myasthenia gravis in Korea: a populationbased study using the national health insurance claims database. J Clin Neurol 12(3):340–344PubMedCentralPubMed Park SY, Lee JY, Lim NG, Hong YH (2016) Incidence and prevalence of Myasthenia gravis in Korea: a populationbased study using the national health insurance claims database. J Clin Neurol 12(3):340–344PubMedCentralPubMed
2.
go back to reference Martinka I, Fulova M, Spalekova M, Spalek P (2018) Epidemiology of Myasthenia gravis in Slovakia in the years 1977–2015. Neuroepidemiology 50(3–4):153–159PubMed Martinka I, Fulova M, Spalekova M, Spalek P (2018) Epidemiology of Myasthenia gravis in Slovakia in the years 1977–2015. Neuroepidemiology 50(3–4):153–159PubMed
3.
go back to reference Mullges W, Stoll G (2019) Myasthenia gravis. Nervenarzt 90(10):1055–1066PubMed Mullges W, Stoll G (2019) Myasthenia gravis. Nervenarzt 90(10):1055–1066PubMed
4.
go back to reference Gilhus NE, Verschuuren JJ (2015) Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 14(10):1023–1036PubMed Gilhus NE, Verschuuren JJ (2015) Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 14(10):1023–1036PubMed
5.
go back to reference Khatke YAZNV, Ivanisova AV, Petropavlovskaya TA, Gerasimenko GA (2018) Epidemiological features of myastenia gravis. Kuban Sci Med Bull. 25(1):195–198 Khatke YAZNV, Ivanisova AV, Petropavlovskaya TA, Gerasimenko GA (2018) Epidemiological features of myastenia gravis. Kuban Sci Med Bull. 25(1):195–198
6.
go back to reference Alekseeva TMKVV, Stuchevskaya TR, Khalmurzina AN (2018) Epidemiologic studies of myasthenia gravis: literature review. Neuromuscular Dis 8(3):12–18 Alekseeva TMKVV, Stuchevskaya TR, Khalmurzina AN (2018) Epidemiologic studies of myasthenia gravis: literature review. Neuromuscular Dis 8(3):12–18
7.
go back to reference Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):177–189PubMedCentralPubMed Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):177–189PubMedCentralPubMed
8.
go back to reference Kimura K, Okada Y, Fujii C, Komatsu K, Takahashi R, Matsumoto S et al (2019) Clinical characteristics of autoimmune disorders in the central nervous system associated with myasthenia gravis. J Neurol 266(11):2743–2751PubMed Kimura K, Okada Y, Fujii C, Komatsu K, Takahashi R, Matsumoto S et al (2019) Clinical characteristics of autoimmune disorders in the central nervous system associated with myasthenia gravis. J Neurol 266(11):2743–2751PubMed
9.
go back to reference Leite MI, Coutinho E, Lana-Peixoto M, Apostolos S, Waters P, Sato D et al (2012) Myasthenia gravis and neuromyelitis optica spectrum disorder: a multicenter study of 16 patients. Neurology 78(20):1601–1607PubMedCentralPubMed Leite MI, Coutinho E, Lana-Peixoto M, Apostolos S, Waters P, Sato D et al (2012) Myasthenia gravis and neuromyelitis optica spectrum disorder: a multicenter study of 16 patients. Neurology 78(20):1601–1607PubMedCentralPubMed
10.
go back to reference Basiri K, Etemadifar M, Maghzi AH, Zarghami N (2009) Frequency of myasthenia gravis in multiple sclerosis: report of five cases from Isfahan. Iran Neurol India 57(5):638–640PubMed Basiri K, Etemadifar M, Maghzi AH, Zarghami N (2009) Frequency of myasthenia gravis in multiple sclerosis: report of five cases from Isfahan. Iran Neurol India 57(5):638–640PubMed
11.
go back to reference Isbister CM, Mackenzie PJ, Anderson D, Wade NK, Oger J (2003) Co-occurrence of multiple sclerosis and myasthenia gravis in British Columbia. Mult Scler 9(6):550–553PubMed Isbister CM, Mackenzie PJ, Anderson D, Wade NK, Oger J (2003) Co-occurrence of multiple sclerosis and myasthenia gravis in British Columbia. Mult Scler 9(6):550–553PubMed
12.
go back to reference Somer H, Muller K, Kinnunen E (1989) Myasthenia gravis associated with multiple sclerosis. Epidemiological survey and immunological findings. J Neurol Sci 89(1):37–48PubMed Somer H, Muller K, Kinnunen E (1989) Myasthenia gravis associated with multiple sclerosis. Epidemiological survey and immunological findings. J Neurol Sci 89(1):37–48PubMed
13.
go back to reference Alanazy MH, Alomar MA, Aljafen BN, Muayqil TA (2018) Multiple sclerosis and myasthenia gravis following severe weight loss. Neurosciences (Riyadh) 23(2):158–161PubMedCentralPubMed Alanazy MH, Alomar MA, Aljafen BN, Muayqil TA (2018) Multiple sclerosis and myasthenia gravis following severe weight loss. Neurosciences (Riyadh) 23(2):158–161PubMedCentralPubMed
14.
go back to reference Luchtman DW, Ellwardt E, Larochelle C, Zipp F (2014) IL-17 and related cytokines involved in the pathology and immunotherapy of multiple sclerosis: current and future developments. Cytokine Growth Factor Rev 25(4):403–413PubMed Luchtman DW, Ellwardt E, Larochelle C, Zipp F (2014) IL-17 and related cytokines involved in the pathology and immunotherapy of multiple sclerosis: current and future developments. Cytokine Growth Factor Rev 25(4):403–413PubMed
15.
go back to reference Buckner JH (2010) Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol 10(12):849–859PubMedCentralPubMed Buckner JH (2010) Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol 10(12):849–859PubMedCentralPubMed
16.
go back to reference Mastorodemos V, Ioannou M, Verginis P (2015) Cell-based modulation of autoimmune responses in multiple sclerosis and experimental autoimmmune encephalomyelitis: therapeutic implications. NeuroImmunoModulation 22(3):181–195PubMed Mastorodemos V, Ioannou M, Verginis P (2015) Cell-based modulation of autoimmune responses in multiple sclerosis and experimental autoimmmune encephalomyelitis: therapeutic implications. NeuroImmunoModulation 22(3):181–195PubMed
17.
go back to reference Berrih-Aknin S (2014) Myasthenia Gravis: paradox versus paradigm in autoimmunity. J Autoimmun 52:1–28PubMed Berrih-Aknin S (2014) Myasthenia Gravis: paradox versus paradigm in autoimmunity. J Autoimmun 52:1–28PubMed
18.
go back to reference Oksenberg JR, Sherritt M, Begovich AB, Erlich HA, Bernard CC, Cavalli-Sforza LL et al (1989) T-cell receptor V alpha and C alpha alleles associated with multiple and myasthenia gravis. Proc Natl Acad Sci USA 86(3):988–992PubMedCentralPubMed Oksenberg JR, Sherritt M, Begovich AB, Erlich HA, Bernard CC, Cavalli-Sforza LL et al (1989) T-cell receptor V alpha and C alpha alleles associated with multiple and myasthenia gravis. Proc Natl Acad Sci USA 86(3):988–992PubMedCentralPubMed
19.
go back to reference Danikowski KM, Jayaraman S, Prabhakar BS (2017) Regulatory T cells in multiple sclerosis and myasthenia gravis. J Neuroinflammation 14(1):117PubMedCentralPubMed Danikowski KM, Jayaraman S, Prabhakar BS (2017) Regulatory T cells in multiple sclerosis and myasthenia gravis. J Neuroinflammation 14(1):117PubMedCentralPubMed
20.
go back to reference Raphael I, Nalawade S, Eagar TN, Forsthuber TG (2015) T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 74(1):5–17PubMed Raphael I, Nalawade S, Eagar TN, Forsthuber TG (2015) T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 74(1):5–17PubMed
21.
go back to reference Yi JS, Guidon A, Sparks S, Osborne R, Juel VC, Massey JM et al (2014) Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis. J Autoimmun 52:130–138PubMed Yi JS, Guidon A, Sparks S, Osborne R, Juel VC, Massey JM et al (2014) Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis. J Autoimmun 52:130–138PubMed
22.
go back to reference Li S, Jin T, Zhang HL, Yu H, Meng F, Concha Quezada H et al (2014) Circulating Th17, Th22, and Th1 cells are elevated in the Guillain-Barre syndrome and downregulated by IVIg treatments. Mediators Inflamm 2014:740947PubMedCentralPubMed Li S, Jin T, Zhang HL, Yu H, Meng F, Concha Quezada H et al (2014) Circulating Th17, Th22, and Th1 cells are elevated in the Guillain-Barre syndrome and downregulated by IVIg treatments. Mediators Inflamm 2014:740947PubMedCentralPubMed
23.
go back to reference Link J (1994) Interferon-gamma, interleukin-4 and transforming growth factor-beta mRNA expression in multiple sclerosis and myasthenia gravis. Acta Neurol Scand Suppl 158:1–58PubMed Link J (1994) Interferon-gamma, interleukin-4 and transforming growth factor-beta mRNA expression in multiple sclerosis and myasthenia gravis. Acta Neurol Scand Suppl 158:1–58PubMed
24.
go back to reference Lu J, Li J, Zhu TQ, Zhang L, Wang Y, Tian FF et al (2013) Modulation of B cell regulatory molecules CD22 and CD72 in myasthenia gravis and multiple sclerosis. Inflammation 36(3):521–528PubMed Lu J, Li J, Zhu TQ, Zhang L, Wang Y, Tian FF et al (2013) Modulation of B cell regulatory molecules CD22 and CD72 in myasthenia gravis and multiple sclerosis. Inflammation 36(3):521–528PubMed
25.
go back to reference Kaegi C, Wuest B, Schreiner J, Steiner UC, Vultaggio A, Matucci A et al (2019) Systematic review of safety and efficacy of rituximab in treating immune-mediated disorders. Front Immunol 10:1990PubMedCentralPubMed Kaegi C, Wuest B, Schreiner J, Steiner UC, Vultaggio A, Matucci A et al (2019) Systematic review of safety and efficacy of rituximab in treating immune-mediated disorders. Front Immunol 10:1990PubMedCentralPubMed
26.
go back to reference Fang F, Sveinsson O, Thormar G, Granqvist M, Askling J, Lundberg IE et al (2015) The autoimmune spectrum of myasthenia gravis: a Swedish population-based study. J Intern Med 277(5):594–604PubMed Fang F, Sveinsson O, Thormar G, Granqvist M, Askling J, Lundberg IE et al (2015) The autoimmune spectrum of myasthenia gravis: a Swedish population-based study. J Intern Med 277(5):594–604PubMed
27.
go back to reference Gotkine M, Fellig Y, Abramsky O (2006) Occurrence of CNS demyelinating disease in patients with myasthenia gravis. Neurology 67(5):881–883PubMed Gotkine M, Fellig Y, Abramsky O (2006) Occurrence of CNS demyelinating disease in patients with myasthenia gravis. Neurology 67(5):881–883PubMed
28.
go back to reference Tola MR, Casetta I, Granieri E, Caniatti LM, Monetti VC, Pascarella R (1996) Systemic lupus erythematosus related recurrent transverse myelitis in a patient with myasthenia gravis and multiple sclerosis. Eur Neurol 36(5):327–328PubMed Tola MR, Casetta I, Granieri E, Caniatti LM, Monetti VC, Pascarella R (1996) Systemic lupus erythematosus related recurrent transverse myelitis in a patient with myasthenia gravis and multiple sclerosis. Eur Neurol 36(5):327–328PubMed
29.
go back to reference Jarius S, Paul F, Franciotta D, de Seze J, Munch C, Salvetti M et al (2012) Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature. Mult Scler 18(8):1135–1143PubMed Jarius S, Paul F, Franciotta D, de Seze J, Munch C, Salvetti M et al (2012) Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature. Mult Scler 18(8):1135–1143PubMed
30.
go back to reference Iyer A, Elsone L, Appleton R, Jacob A (2014) A review of the current literature and a guide to the early diagnosis of autoimmune disorders associated with neuromyelitis optica. Autoimmunity 47(3):154–161PubMed Iyer A, Elsone L, Appleton R, Jacob A (2014) A review of the current literature and a guide to the early diagnosis of autoimmune disorders associated with neuromyelitis optica. Autoimmunity 47(3):154–161PubMed
31.
go back to reference Vaknin-Dembinsky A, Abramsky O, Petrou P, Ben-Hur T, Gotkine M, Brill L et al (2011) Myasthenia gravis- associated neuromyelitis optica-like disease: an immunological link between the central nervous system and muscle? Arch Neurol 68(12):1557–1561PubMed Vaknin-Dembinsky A, Abramsky O, Petrou P, Ben-Hur T, Gotkine M, Brill L et al (2011) Myasthenia gravis- associated neuromyelitis optica-like disease: an immunological link between the central nervous system and muscle? Arch Neurol 68(12):1557–1561PubMed
32.
go back to reference Mizrachi T, Brill L, Rabie M, Nevo Y, Fellig Y, Zur M et al (2018) NMO-IgG and AQP4 peptide can induce aggravation of EAMG and immune-mediated muscle weakness. J Immunol Res 2018:5389282PubMedCentralPubMed Mizrachi T, Brill L, Rabie M, Nevo Y, Fellig Y, Zur M et al (2018) NMO-IgG and AQP4 peptide can induce aggravation of EAMG and immune-mediated muscle weakness. J Immunol Res 2018:5389282PubMedCentralPubMed
33.
go back to reference Sylvester J, Purdie G, Slee M, Gray JX, Burnet S, Koblar S (2013) Muscle-specific kinase antibody positive myaesthenia gravis and multiple sclerosis co-presentation: a case report and literature review. J Neuroimmunol 264(1–2):130–133PubMed Sylvester J, Purdie G, Slee M, Gray JX, Burnet S, Koblar S (2013) Muscle-specific kinase antibody positive myaesthenia gravis and multiple sclerosis co-presentation: a case report and literature review. J Neuroimmunol 264(1–2):130–133PubMed
34.
go back to reference Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K et al (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364(9451):2106–2112PubMed Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K et al (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364(9451):2106–2112PubMed
35.
go back to reference Dehbashi S, Hamouda D, Shanina E (2019) Co-occurrence of multiple sclerosis and myasthenia gravis: a case report and review of immunological theories. Mult Scler Relat Disord 34:135–136PubMed Dehbashi S, Hamouda D, Shanina E (2019) Co-occurrence of multiple sclerosis and myasthenia gravis: a case report and review of immunological theories. Mult Scler Relat Disord 34:135–136PubMed
36.
go back to reference Midaglia L, Gratacos M, Caronna E, Raguer N, Sastre-Garriga J, Montalban X et al (2018) Myasthenia gravis following alemtuzumab therapy for multiple sclerosis. Neurology 91(13):622–624PubMedCentralPubMed Midaglia L, Gratacos M, Caronna E, Raguer N, Sastre-Garriga J, Montalban X et al (2018) Myasthenia gravis following alemtuzumab therapy for multiple sclerosis. Neurology 91(13):622–624PubMedCentralPubMed
37.
go back to reference Dhib-Jalbut S (1997) Mechanisms of interferon beta action in multiple sclerosis. Mult Scler 3(6):397–401PubMed Dhib-Jalbut S (1997) Mechanisms of interferon beta action in multiple sclerosis. Mult Scler 3(6):397–401PubMed
38.
go back to reference Yong VW, Chabot S, Stuve O, Williams G (1998) Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology 51(3):682–689PubMed Yong VW, Chabot S, Stuve O, Williams G (1998) Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology 51(3):682–689PubMed
39.
go back to reference Dionisiotis J, Zoukos Y, Thomaides T (2004) Development of myasthenia gravis in two patients with multiple sclerosis following interferon beta treatment. J Neurol Neurosurg Psychiatry 75(7):1079PubMedCentralPubMed Dionisiotis J, Zoukos Y, Thomaides T (2004) Development of myasthenia gravis in two patients with multiple sclerosis following interferon beta treatment. J Neurol Neurosurg Psychiatry 75(7):1079PubMedCentralPubMed
40.
go back to reference Kluger BM, Krupp LB, Enoka RM (2013) Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology 80(4):409–416PubMedCentralPubMed Kluger BM, Krupp LB, Enoka RM (2013) Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology 80(4):409–416PubMedCentralPubMed
41.
go back to reference Cantor F (2010) Central and peripheral fatigue: exemplified by multiple sclerosis and myasthenia gravis. PM R 2(5):399–405PubMed Cantor F (2010) Central and peripheral fatigue: exemplified by multiple sclerosis and myasthenia gravis. PM R 2(5):399–405PubMed
Metadata
Title
Cross-syndrome: myasthenia gravis and the demyelinating diseases of the central nervous system combination. Systematic literature review and case reports
Authors
Ekaterina Luzanova
Svetlana Stepanova
Nikita Nadtochiy
Elena Kryukova
Maria Karpova
Publication date
14-06-2022
Publisher
Springer International Publishing
Published in
Acta Neurologica Belgica / Issue 2/2023
Print ISSN: 0300-9009
Electronic ISSN: 2240-2993
DOI
https://doi.org/10.1007/s13760-022-01926-z

Other articles of this Issue 2/2023

Acta Neurologica Belgica 2/2023 Go to the issue