Myasthenia Gravis Associated with Thymoma – a Cohort of Patients in the Slovak Republic (1978–2015)

Czech version

Authors: I. Martinka ¹; M. Fulová ² ; M. Schnorrer ³; F. Cibulčík ¹; P. Špalek ¹
Authors‘ workplace: Centrum pre neuromuskulárne ochorenia, Neurologická klinika SZU a UN Bratislava ¹; Epidemiologický ústav, LF UK, Bratislava ²; III. chirurgická klinika LF UK a UN Milosrdní bratia, Bratislava ³
Published in: Cesk Slov Neurol N 2016; 79/112(5): 552-559
Category: Original Paper

Overview

Introduction:
Thymoma-associated myasthenia gravis (TAMG) differs from other forms of MG mainly by combined presence of intrathymic (thymus, thymoma) and extrathymic autoimmune mechanisms in their immunopathogenesis.

Aims:
We present a retrospective longitudinal study of 123 patients with TAMG registered in the Slovak Centre for Neuromuscular Diseases between 1978 and 2015. The aim of the study was to analyse epidemiological and clinical data, laboratory findings and factors affecting prognosis of TAMG.

Material and methods:
We analysed data from medical records of patients with TAMG. We examined the age at disease onset, gender, presence of autoantibodies against AChRs and MuSK and type of clinical symptomatology. We evaluated therapies used, clinical status at the last examination and prognosis of TAMG patients.

Results:
Out of 2,074 MG patients, we found TAMG in 123 patients (5.9%), 46 men and 77 women. Median age at disease onset was 51 years. All patients, except one, had AChR seropositive MG. In 78 patients (63.4%) remission or significant improvement by immunotherapy and surgical treatment was achieved. The best results were obtained in patients with early TAMG diagnosis. MG has not been the primary cause of death in any patient for the last 20 years. 91 patients had benign and 32 malignant thymoma. Six patients with malignant thymoma died following thymoma dissemination, four of these had MG in remission.

Conclusion:
TAMG was found in 5.9 % of 2,074 patients. TAMG is AChR-seropositive. Both, MG severity and biological characteristics of thymoma, determine TAMG prognosis. Early diagnosis and optimal treatment of TAMG are crucial for favourable prognosis.

Key words:
myasthenia gravis – thymoma – immunopathogenesis – diagnosis – treatment – prognosis

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Sources

1. Špalek P, Schnorrer M, Krajč T. Imunopatogenéza paraneoplastickej myasténie gravis asociovanej s tymómom. Neurológia 2010; 5 (1): 7–11.

2. Evoli A, Minisci C, Di Schino C, et al. Thymoma in patients with MG: characteristics and long-term outcome. Neurology 2002; 59 (12): 1844–50.

3. Marx A, Pfister F, Schalke B, et al. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmunity Reviews 2013; 12 (9): 875–84. doi: 10.1016/j.autrev.2013.03.007.

4. Špalek P. Tymómy a paraneoplastická imunita. Cesk Slov Neur N 2002; 65/98 (3): 367–73.

5. McCombe P, Meenakshi R, Henderson R, et al. A case series of patients with autoimmune myasthenia gravis in association with invasive thymoma. J Clin Neuromusc Dis 2016; 17 (3): 129–34. doi: 10.1097/CND.0000000000000 101.

6. Hohlfeld R, Wekerle H, Marx A. Immunopthogenesis of myasthenia gravis. In: Engel AG. Myasthenia gravis and other myasthenic disorders. Ney York. Oxford University Press 2012: 70–4.

7. Romi F. Thymoma in myasthenia gravis: from diagnosis to treatment. Autoimmune Dis 2011; 2011: 474512. doi: 10.4061/2011/474512.

8. Marx A, Kirchner T, Hoppe F. Proteins with epitopes of the acetylcholine receptor in epithelial cell cultures of thymomas in myasthenia gravis. Am J Pathol 1989; 134 (4): 865–77.

9. Romi F, Bo L, Skeie GO, et al. Titin and ryanodine receptor epitopes are expressed in cortical thymoma along with costimulatory molecules. J Neuroimmunol 2002; 128 (1–2): 82–9.

10. Špalek P. Myasthenia gravis – register a epidemiológia na Slovensku. Diagnostický význam stapediovej reflexometrie. Analýza účinnosti imunologických foriem liečby. Kandidátska dizertačná práca. Bratislava: LF Univerzity Komenského 1983.

11. Masaoka A, Yamakawa Y, Niwa H, et al. Extended thymectomy for myasthenia gravis patients: a 20-year review. Ann Thorac Surg 1996; 62 (3): 853–9.

12. Mao ZF, Mo XA, Qin C, et al. Incidence of thymoma in myasthenia gravis: a systematic review. J Clin Neurol 2012; 8 (3): 161–9. doi: 10.3988/jcn.2012.8.3.161.

13. Papatestas AE, Genkins G, Kornfeld P, et al. Effects of thymectomy in myasthenia gravis. Ann Surg 1987; 206 (1): 79–88.

14. Maggi G, Casadio C, Cavallo A, et al. Thymectomy in myasthenia gravis. Results of 662 cases operated upon in 15 years. Eur J Cardiothorac Surg 1989; 3 (6): 504–9.

15. Oosterhuis HJ. The natural course of myasthenia gravis: a long term follow up study. J Neurol Neurosurg Psychiatry 1989; 52 (10): 1121–7.

16. Budde JM, Morris CD, Gal AA, et al. Predictors of outcome in thymectomy for myasthenia gravis. Ann Thorac Surg 2001; 72 (1): 197–202.

17. de Perrot M, Liu J, Bril V, et al. Prognostic significance of thymomas in patients with myasthenia gravis. Ann Thorac Surg 2002; 74 (5): 1658–62.

18. Yasukawa Y, Yoshikawa H, Iwasa K, et al. Comparative study of pre-operative thymic imaging and pathology in patients with myasthenia gravis. J Clin Neurosci 2004; 11 (6): 610–3.

19. Kim HK, Park MS, Choi YS, et al. Neurologic outcomes of thymectomy in myasthenia gravis: comparative analysis of the effect of thymoma. J Thorac Cardiovasc Surg 2007; 34 (3): 601–7.

20. Tsinzerling N, Lefvert AK, Matell G, et al. Myasthenia gravis: a long term follow-up study of Swedish patients with specific reference to thymic histology. J Neurol Neurosurg Psychiatry 2007; 78 (10): 1109–12.

21. Špalek P, Schnorrer M, Krajč T. Diagnostika a liečba paraneoplastickej myasténie gravis asociovanej s tymómom. Neurológia 2010; 5 (2): 79–85.

22. Murai H, Masuda M, Utsugisawa K, et al. Clinical features and treatment status of adult myasthenia gravis in Japan. Clin Exper Neuroimm 2014; 5: 84–9.

23. Romi F, Gilhus NE, Varhaug JE, et al. Disease severity and outcome in thymoma myasthenia gravis: a long term observation study. Eur J Neurol 2003; 10 (6): 701–6.

24. Kondo Y, Monden Y. Thymoma and myasthenia gravis: a clinical study of 1089 patients from Japan. Ann Thorac Surg 2005; 79 (1): 535–40.

25. Špalek P, Schnorrer M, Cibulčík F. Kombinovaný výskyt akútnej myasténie gravis a akútnej polymyozitídy u troch pacientov, u dvoch v asociácii s tymómom. Rozhl Chir 2000; 79: 468–70.

26. Špalek P. Thymomy, myasthenia gravis a autoimunitní onemocnění – pohled klinika. In: Piťha J, ed. Myasthenia gravis a ostatní poruchy nervosvalového přenosu. Praha, Maxdorf Jesenius 2010: 236–54.

27. Witoonpanich R, Dejthevaporn C, Sriphrapradang A, et al. Electrophysiological and immunological study in myasthenia gravis: diagnostic sensitivity and correlation. Clin Neurophysiol 2011; 122 (9): 1873–7. doi: 10.1016/j.clinph.2011.02.026.

28. Zisimopoulou P, Brenner T, Trakas N, et al. Serological diagnostics in myasthenia gravis based on novel assays and recently identified antigens. Autoimmun Rev 2013; 12 (9): 924–30. doi: 10.1016/j.autrev.2013.03. 002.

29. Priola AM, Priola SM. Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor. Clin Radiol 2014; 69 (5): e230–45. doi: 10.1016/j.crad.2014.01.005.

30. Rigamonti A, Lauria G, Piamarta F, et al. Thymoma- -associated myasthenia gravis without acetylcholine receptor antibodies. J Neurol Sci 2011; 302 (1–2): 112–3. doi: 10.1016/j.jns.2010.12.013.

31. Schnorrer M jr, Spalek P, Belacek J, et al. Thymom und Myasthenia gravis. Viszeralchirurgie 1998; 33: 171–4.

32. Piťha J. Myasthenia gravis. Med Praxi 2015; 12 (3): 121–5.

33. Schnorrer M jr, Hraška V, Špalek P, et al. Stanovenie významu prognostických faktorov pri chirurgickej liečbe myasténie gravis. Rozhl Chir 1999; 78: 223–7.

34. Špalek P. Vznik myasthenie gravis po tymektómii pre tymóm. Rozhl Chir 1995; 74: 100–2.

35. Piťha J, Schutzner J, Šmat V. Manifestace myasthenia gravis po exstirpaci thymomu thotakotomií. Rozhl Chir 1998; 77 (6): 241–4.

36. Lindenmann J, Fink-Neuboeck N, Pichler M, et al. Stage-based treatment for thymoma in due to consideration of thymectomy: a single-center experience and comparison with the literature. World J Surg Oncol 2015; 303 (13): 1186. doi: 10.1186/s12957-015-0718-z.

37. Schutzner J. Surgical therapy of thymomas. Sborn Lék 1999; 100 (1): 27–31.

38. Schutzner J. Tvrdoň J. Chirurgická léčba tymomu. In: Schutzner J, Šmat V, eds. Myasthenia gravis. Komplexní pojetí a chirurgická léčba. Praha: Galén 2005: 63–71.

39. Schnorrer M jr, Špalek P, Hraška V, et al. Parciálna mediálna sternotómia v chirurgickej liečbe myasthenia gravis. Lek Obz 1998; 47 (11–12): 311–3.

40. Krajč T, Špalek P, Lučenič M, et al. Tymómy a ich miniinvazívna chirurgická liečba. Onkológia 2011; 6 (6): 339–43.

41. Zielinski M, Kuzdzal J, Szlubowski A, et al. Transcervical-subxiphoid-videothoracoscopic „maximal“ thymectomy – operative technique and early results. Ann Thorac Surg 2004; 78 (2): 404–9.

42. Krajč T, Špalek P, Janík M, et al. Transcervikálna – subxifoidálna – bilaterálna VATS „maximálna“ tymektómia pre myasténiu alebo tymóm – iniciálne skúsenosti. Neurológia 2011; 6 (1): 24–30.