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Italian recommendations for the diagnosis and treatment of myasthenia gravis

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Abstract

Myasthenia gravis is a well-treatable disease, in which a prompt diagnosis and an adequate management can achieve satisfactory control of symptoms in the great majority of patients. Improved knowledge of the disease pathogenesis has led to recognition of patient subgroups, according to associated antibodies, age at onset and thymus pathology, and to a more personalized treatment. When myasthenia gravis is suspected on clinical grounds, diagnostic confirmation relies mainly on the detection of specific antibodies. Neurophysiological studies and, to a lesser extent, clinical response to cholinesterase inhibitors support the diagnosis in seronegative patients. In these cases, the differentiation from congenital myasthenia can be challenging. Treatment planning must consider weakness extension and severity, disease subtype, thymus pathology, together with patient characteristics and comorbidities. Since most subjects with myasthenia gravis require long-term immunosuppressive therapy, surveillance of expected and potential adverse events is critical. For patients refractory to conventional immunosuppression, the use of biologic agents is highly promising. These recommendations are addressed to non-experts on neuromuscular transmission disorders. The diagnostic procedures and therapeutic approaches hereafter described are largely accessible in Italy.

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References

  1. Andersen JB, Heldal AT, Engeland A, Gihlus NE (2014) Myasthenia gravis epidemiology in a national cohort; combining multiple disease registries. Acta Neurol Scand Suppl 198:26–31

    Article  CAS  Google Scholar 

  2. Gihlus NE, Verschuuren JJ (2015) Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 14:1023–1036

    Article  CAS  Google Scholar 

  3. Marx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Ströbel P (2013) The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev 12:875–884

    Article  CAS  PubMed  Google Scholar 

  4. Burden SJ, Yumoto N, Zhang W (2013) The role of MuSK in synapse formation and neuromuscular disease. Cold Spring Harb Perspect Biol 5:009167

    Article  CAS  Google Scholar 

  5. Huijbers MG, Zhang W, Klooster R, Niks EH, Friese MB, Straasheijm KR, Thijssen PE, Vrolijk H, Plomp JJ, Vogels P, Losen M, van der Maarel SM, Burden SJ, Verschuuren JJ (2013) MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4. Proc Natl Acad Sci U S A 110:20783–20788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Evoli A, Padua L (2013) Diagnosis and therapy of myasthenia gravis with antibodies to muscle-specific kinase. Autoimmun Rev 12:931–935

    Article  CAS  PubMed  Google Scholar 

  7. Keesey JC (2004) Clinical evaluation and management of myasthenia gravis. Muscle Nerve 29:484–505

    Article  PubMed  Google Scholar 

  8. Wendell LC, Levine JM (2011) Myasthenic crisis. Neurohospitalist 1:16–22

    Article  PubMed  PubMed Central  Google Scholar 

  9. Rabinstein AA (2015) Acute neuromuscular respiratory failure. Continuum (Minneap Minn) 21:1324–1345

    Google Scholar 

  10. Mehrizi M, Fontem RF, Gearhart TR, Pascuzzi RM (2012) Medications and myasthenia gravis (a reference for health care professionals). Myasthenia Gravis Foundation of America. http://www.myasthenia.org/portals/0/draft_medications_and_myasthenia_gravis_for_MGFA_website. Published Summer 2015

  11. Makarious D, Horwood K, Coward JIG (2017) Myasthenia gravis: an emerging toxicity of immune checkpoint inhibitors. Eur J Cancer 82:128–136

    Article  CAS  PubMed  Google Scholar 

  12. Schaller SF, Fink H (2013) Sugammadex as a reversal agent for neuromuscular block: an evidence-based review. Core Evid 8:57–67

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Zisimopoulou P, Evangelakou P, Tzartos J, Lazaridis K, Zouvelou V, Mantegazza R, Antozzi C, Andreetta F, Evoli A, Deymeer F, Saruhan-Direskeneli G, Durmus H, Brenner T, Vaknin A, Berrih-Aknin S, Frenkian Cuvelier M, Stojkovic T, DeBaets 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, Tzartos SJ (2014) A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis. J Autoimmun 52:139–145

    Article  CAS  PubMed  Google Scholar 

  14. Osserman KE, Genkins G (1971) Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med 38:497–537

    CAS  PubMed  Google Scholar 

  15. Jaretzki A 3rd, Barohn RJ, Ernstoff RM et al (2000) Myasthenia gravis: recommendations for clinical research standards. Task force of the medical scientific advisory Board of the Myasthenia Gravis Foundation of America. Neurology 5:16–23

    Article  Google Scholar 

  16. Burns TM (2012) The MG composite: an outcome measure for MG for use in clinical trials and everyday practice. Ann N Y Acad Sci 1274:99–106

    Article  PubMed  Google Scholar 

  17. Sanders DB, Tucker-Lipscomb B, Massey JM (2003) A simple manual muscle test for myasthenia gravis. Validation ad comparison with the QMG score. Ann N Y Acad Sci 998:440–444

    Article  PubMed  Google Scholar 

  18. Antozzi C, Brenna G, Baggi F, Camera G, Maggi L, Rezzani C, Montomoli C, Mantegazza R (2016) Validation of the Besta Neurological Institute rating scale for myasthenia gravis. Muscle Nerve 53:32–37

    Article  PubMed  Google Scholar 

  19. Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ (1999) Myasthenia gravis activities of daily living profile. Neurology 52:1487–1489

    Article  CAS  PubMed  Google Scholar 

  20. Padua L, Evoli A, Aprile I, Caliandro P, D'Amico P, Rabini A, Tonali P (2002) Quality of life in patients with myasthenia gravis. Muscle Nerve 25:466–467

    Article  CAS  PubMed  Google Scholar 

  21. Raggi A, Leonardi M, Ayadi R, Antozzi C, Maggi L, Baggi F, Mantegazza R (2017) Validation of the Italian version of the 15-item myasthenia gravis quality-of-life questionnaire. Muscle Nerve 56:716–720

    Article  PubMed  Google Scholar 

  22. Howard JF Jr (2013) Electrodiagnosis of disorders of neuromuscular transmission. Phys Med Rehabil Clin N Am 24:169–192

    Article  PubMed  Google Scholar 

  23. Shumm F, Stohr M (1984) Accessory nerve stimulation in the assessment of myasthenia gravis. Muscle Nerve 7:147–151

    Article  Google Scholar 

  24. Oh SJ, Hatanaka Y, Hemmi S, Young AM, Scheufele ML, Nations SP, Lu L, Claussen GC, Wolfe GI (2006) Repetitive nerve stimulation of facial muscles in MuSK antibody-positive myasthenia gravis. Muscle Nerve 33:500–504

    Article  PubMed  Google Scholar 

  25. Sanders DB, Stålberg EV (1996) AAEM Minimonograph #25: single-fiber electromyography. Muscle Nerve 19:1069–1083

    Article  CAS  PubMed  Google Scholar 

  26. Benatar M (2006) A systematic revue of diagnostic studies in myasthenia gravis. Neuromuscul Disord 16:459–467

    Article  PubMed  Google Scholar 

  27. Sanders DB (2002) The clinical impact of single-fiber electromyography. Muscle Nerve 11:S15–S20

    Article  PubMed  Google Scholar 

  28. Oh SJ, Cho HK (1990) Edrophonium responsiveness not necessarily diagnostic of myasthenia gravis. Muscle Nerve 13:187–191

    Article  CAS  PubMed  Google Scholar 

  29. Dirr LY, Donofrio PD, Patton JF, Troost BT (1989) A false-positive edrophonium test in a patient with a brainstem glioma. Neurology 39:865–867

    Article  CAS  PubMed  Google Scholar 

  30. Andreetta F, Rinaldi E, Bartoccioni E et al (2017) Diagnostics of myasthenic syndromes: detection of anti-AChR and anti-MuSK antibodies. Neurol Sci 38(Suppl 2):S253–S257

    Article  Google Scholar 

  31. Mehanna R, Patton EL Jr, Phan CL et al (2012) Amyotrophic lateral sclerosis with positive anti-acetylcholine receptor antibodies. Case report and review of the literature. J Clin Neuromuscul Dis 14:82–85

    Article  PubMed  Google Scholar 

  32. Vernino S, Lennon VA (2004) Autoantibody profiles and neurological correlations of thymoma. Clin Cancer Res 10:7270–7275

    Article  CAS  PubMed  Google Scholar 

  33. Meriggioli MN, Sanders DB (2012) Muscle autoantibodies in myasthenia gravis: beyond diagnosis? Expert Rev Clin Immunol 8:427–438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rodríguez Cruz PM, Al-Hajjar M, Huda S et al (2015) Clinical features and diagnostic usefulness of antibodies to clustered acetylcholine receptors in the diagnosis of seronegative myasthenia gravis. JAMA Neurol 72:642–649

    Article  PubMed  PubMed Central  Google Scholar 

  35. Huda S, Waters P, Woodhall M, Leite MI, Jacobson L, de Rosa A, Maestri M, Ricciardi R, Heckmann JM, Maniaol A, Evoli A, Cossins J, Hilton-Jones D, Vincent A (2017) IgG-specific cell-based assay detects potentially pathogenic MuSK-Abs in seronegative MG. Neurol Neuroimmunol Neuroinflamm 4:e357

    Article  PubMed  PubMed Central  Google Scholar 

  36. Fakiri MO, Tavy DL, Hama-Amin AD, Wirtz PW (2013) Accuracy of the ice test in the diagnosis of myasthenia gravis in patients with ptosis. Muscle Nerve 48:902–904

    Article  PubMed  Google Scholar 

  37. Maggi L, Bernasconi P, D'Amico A et al (2018) Italian recommendations for diagnosis and management of congenital myasthenic syndromes. Neurol Sci. https://doi.org/10.1007/s10072-018-3682-x

  38. Tzartos JS, Zisimopoulou P, Rentzos M, Karandreas N, Zouvelou V, Evangelakou P, Tsonis A, Thomaidis T, Lauria G, Andreetta F, Mantegazza R, Tzartos SJ (2014) LRP4 antibodies in serum and CSF from amyotrophic lateral sclerosis patients. Ann Clin Transl Neurol 1:80–87

    Article  CAS  PubMed  Google Scholar 

  39. Lo YL, Chan LL, Pan A et al (2004) Acute ophthalmoparesis in the anti-GQ1b antibody syndrome: electrophysiological evidence of neuromuscular transmission defect in the orbicularis oculi. J Neurol Neurosurg Psychiatry 75:436–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mantegazza R, Bonanno S, Camera G et al (2011) Current and emerging therapies for the treatment of myasthenia gravis. Neuropsychiatr Dis Treat 7:151–160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Sghirlanzoni A, Peluchetti D, Mantegazza R, Fiacchino F, Cornelio F (1984) Myasthenia gravis: prolonged treatment with steroids. Neurology 34:170–174

    Article  CAS  PubMed  Google Scholar 

  42. Sanders DB, Evoli A (2010) Immunosuppressive therapies in myasthenia gravis. Autoimmunity 43:428–435

    Article  CAS  PubMed  Google Scholar 

  43. 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

    Article  CAS  PubMed  Google Scholar 

  44. Palace J, Newsom-Davis J, Lecky B (1998) A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group. Neurology 50:1778–1783

    Article  CAS  PubMed  Google Scholar 

  45. Dean L (2012) Azathioprine therapy and TPMT genotype. In: Pratt V, McLeod H, Dean L, Malheiro A, Rubinstein W (eds) Source medical genetics summaries [Internet]. National Center for Biotechnology Information (US), Bethesda [updated 2016 May 3]

    Google Scholar 

  46. Sanders DB, Siddiqi ZA (2008) Lessons from two trials of mycophenolate mofetil in myasthenia gravis. Ann N Y Acad Sci 1132:249–255

    Article  CAS  PubMed  Google Scholar 

  47. Hehir MK, Burns TM, Alpers J, Conaway MR, Sawa M, Sanders DB (2010) Mycophenolate mofetil in AChR-antibody-positive myasthenia gravis: outcomes in 102 patients. Muscle Nerve 41:593–598

    Article  CAS  PubMed  Google Scholar 

  48. Gotterer L, Li Y (2016) Maintenance immunosuppression in myasthenia gravis. J Neurol Sci 369:294–302

    Article  PubMed  Google Scholar 

  49. Tindall RS, Phillips JT, Rollins JA et al (1993) A clinical therapeutic trial of cyclosporine in myasthenia gravis. Ann N Y Acad Sci 681:539–551

    Article  CAS  PubMed  Google Scholar 

  50. Cruz JL, Wolff ML, Vanderman AJ, Brown JN (2015) The emerging role of tacrolimus in myasthenia gravis. Ther Adv Neurol Disord 8:92–103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Nagane Y, Utsugisawa K, Obara D, Kondoh R, Terayama Y (2005) Efficacy of low-dose FK506 in the treatment of myasthenia gravis-a randomized pilot study. Eur Neurol 53:146–150

    Article  CAS  PubMed  Google Scholar 

  52. Heckmann JM, Rawoot A, Bateman K et al (2015) A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. BMC Neurol 11:97

    Article  CAS  Google Scholar 

  53. Pasnoor M, He J, Herbelin L, Burns TM, Nations S, Bril V, Wang AK, Elsheikh BH, Kissel JT, Saperstein D, Shaibani JA, Jackson C, Swenson A, Howard JF Jr, Goyal N, David W, Wicklund M, Pulley M, Becker M, Mozaffar T, Benatar M, Pazcuzzi R, Simpson E, Rosenfeld J, Dimachkie MM, Statland JM, Barohn RJ, The 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, Kuntz N, Massey JM, Melms A, Murai H, Nicolle M, Palace J, Richman DP, Verschuuren J, Narayanaswami P (2016) International consensus guidance for management of myasthenia gravis: executive summary. Neurology 87:419–425

    Article  PubMed  PubMed Central  Google Scholar 

  55. de Feo LG, Schottlender J, Martelli NA, Molfino NA (2002) Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia gravis. Muscle Nerve 26:31–36

    Article  CAS  PubMed  Google Scholar 

  56. Afanasiev V, Demeret S, Bolgert F, Eymard B, Laforêt P, Benveniste O (2017) Resistant myasthenia gravis and rituximab: a monocentric retrospective study of 28 patients. Neuromuscul Disord 27:251–258

    Article  PubMed  Google Scholar 

  57. Tandan R, Hehir MK 2nd, Waheed W, Howard DB (2017) Rituximab treatment of myasthenia gravis: a systematic review. Muscle Nerve 56:185–196

    Article  CAS  PubMed  Google Scholar 

  58. Kanth KM, Solorzano GE, Goldman MD (2016) PML in a patient with myasthenia gravis treated with multiple immunosuppressing agents. Neurol Clin Pract 6:e17–e19

    Article  PubMed  PubMed Central  Google Scholar 

  59. Hewett K, Sanders DB, Grove RA, Broderick CL, Rudo TJ, Bassiri A, Zvartau-Hind M, Bril V, On behalf of the BEL115123 Study Group (2018) Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis. Neurology 90(16):e1425–e1434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Howard JF Jr, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Muppidi S, Nowak RJ, O'Brien F, Wang JJ, Mantegazza R, Mazia CG, Wilken M, Ortea C, Saba J, Rugiero M, Bettini M, Vidal G, Garcia AD, Lamont P, Leong WK, Boterhoven H, Fyfe B, Roberts L, Jasinarachchi M, Willlems N, Wanschitz J, Löscher W, de Bleecker J, van den Abeele G, de Koning K, de Mey K, Mercelis R, Wagemaekers L, Mahieu D, van Damme P, Smetcoren C, Stevens O, Verjans S, D'Hondt A, Tilkin P, Alves de Siqueira Carvalho A, Hasan R, Dias Brockhausen I, Feder D, Ambrosio D, Melo AP, Rocha R, Rosa B, Veiga T, Augusto da Silva L, Gonçalves Geraldo J, da Penha Morita Ananias M, Nogueira Coelho E, Paiva G, Pozo M, Prando N, Dada Martineli Torres D, Fernanda Butinhao C, Coelho E, Renata Cubas Volpe L, Duran G, Gomes da Silva TC, Otavio Maia Gonçalves L, Pazetto LE, Souza Duca L, Suriane Fialho TA, Gheller Friedrich MA, Guerreiro A, Mohr H, Pereira Martins M, da Cruz Pacheco D, Macagnan AP, de Cassia Santos A, Bulle Oliveira AS, Amaral de Andrade AC, Annes M, Cavalcante Lino V, Pinto W, Miranda C, Carrara F, Souza I, Genge A, Massie R, Campbell N, Bril V, Katzberg H, Soltani M, Ng E, Siddiqi Z, Phan C, Blackmore D, Vohanka S, Bednarik J, Chmelikova M, Cierny M, Toncrova S, Junkerova J, Kurkova B, Reguliova K, Zapletalova O, Pitha J, Novakova I, Tyblova M, Wolfova M, Jurajdova I, Andersen H, Harbo T, Vinge L, Mogensen A, Højgaard J, Witting N, Autzen AM, Pedersen J, Färkkilä M, Atula S, Nyrhinen A, Erälinna JP, Laaksonen M, Oksaranta O, Eriksson J, Harrison T, Desnuelle C, Sacconi S, Soriani MH, Decressac S, Moutarde J, Lahaut P, Solé G, le Masson G, Wielanek-Bachelet AC, Gaboreau M, Moreau C, Wilson A, Vial C, Bouhour F, Gervais-Bernard H, Merle H, Hourquin C, Lacour A, Outteryck O, Vermersch P, Zephir H, Millois E, Deneve M, Deruelle F, Schoser B, Wenninger S, Stangel M, Alvermann S, Gingele S, Skripuletz T, Suehs KW, Trebst C, Fricke K, Papagiannopoulos S, Bostantzopoulou S, Vlaikidis N, Zampaki M, Papadopoulou N, Mitsikostas DD, Kasioti E, Mitropoulou E, Charalambous D, Rozsa C, Horvath M, Lovas G, Matolcsi J, Szabo G, Szabadosne B, Vecsei L, Dezsi L, Varga E, Konyane M, Gross B, Azrilin O, Greenbereg N, Bali Kuperman H, Antonini G, Garibaldi M, Morino S, Troili F, di Pasquale A, Filla A, Costabile T, Marano E, Sacca F, Marsil A, Puorro G, Maestri Tassoni M, de Rosa A, Bonanno S, Antozzi C, Maggi L, Campanella A, Angelini C, Cudia P, Pegoraro V, Pinzan E, Bevilacqua F, Orrico D, Bonifati DM, Evoli A, Alboini PE, D'Amato V, Iorio R, Inghilleri M, Fionda L, Frasca V, Giacomelli E, Gori M, Lopergolo D, Onesti E, Gabriele M, Patti F, Salvatore Caramma A, Messina S, Reggio E, Caserta C, Uzawa A, Kanai T, Mori M, Kaneko Y, Kanzaki A, Kobayashi E, Masaki K, Matsuse D, Matsushita T, Uehara T, Shimpo M, Jingu M, Kikutake K, Nakamura Y, Sano Y, Nagane Y, Kamegamori I, Fujii Y, Futono K, Tsuda T, Saito Y, Suzuki H, Morikawa M, Samukawa M, Kamakura S, Shiraishi H, Mitazaki T, Motomura M, Mukaino A, Yoshimura S, Asada S, Kobashikawa T, Koga M, Maeda Y, Takada K, Takada MT, Yamashita Y, Yoshida S, Suzuki Y, Akiyama T, Narikawa K, Tsukita K, Meguro F, Fukuda Y, Sato M, Matsuo H, Fukudome T, Gondo Y, Maeda Y, Nagaishi A, Nakane S, Okubo Y, Okumura M, Funaka S, Kawamura T, Makamori M, Takahashi M, Hasuike T, Higuchi E, Kobayashi H, Osakada K, Taichi N, Tsuda E, Hayashi T, Hisahara S, Imai T, Kawamata J, Murahara T, Saitoh M, Shimohama S, Suzuki S, Yamamoto D, Konno S, Imamura T, Inoue M, Murata M, Nakazora H, Nakayama R, Ikeda Y, Ogawa M, Shirane M, Kanda T, Kawai M, Koga M, Ogasawara J, Omoto M, Sano Y, Arima H, Fukui S, Shimose S, Shinozaki H, Watanabe M, Yoshikawa C, van der Kooi A, de Visser M, Gibson T, Maessen J, de Baets M, Faber C, Keijzers MJ, Miesen M, Kostera-Pruszczyk A, Kaminska A, Kim BJ, Lee CN, Koo YS, Seok HY, Kang HN, Ra HJ, Kim BJ, Cho EB, Lee HL, Min JH, Seok J, Koh DY, Kwon JY, Lee JE, Park SA, Hong YH, Lim JS, Kim MR, Kim SM, Kim YH, Lee HS, Shin HY, Hwang EB, Shin MJ, Sazonov D, Yarmoschuk A, Babenko L, Malkova N, Melnikova A, Korobko D, Kosykh E, Pokhabov D, Nesterova Y, Abramov V, Balyazin V, Casasnovas Pons C, Alberti Aguilo M, Homedes-Pedret C, Palacios NJ, Lazaro A, Diez Tejedor E, Fernandez-Fournier M, Lopez Ruiz P, Rodriguez de Rivera FJ, Salvado Figueras M, Gamez J, Salvado M, Cortes Vicente E, Diaz-Manera J, Querol Gutierrez L, Rojas Garcia R, Vidal N, Arribas-Ibar E, Piehl F, Hietala A, Bjarbo L, Lindberg C, Jons D, Andersson B, Sengun I, Ozcelik P, Tuga C, Ugur M, Boz C, Altiparmak D, Gazioglu S, Ozen Aydin C, Erdem-Ozdamar S, Bekircan-Kurt CE, Yilmaz E, Acar NP, Caliskan Y, Efendi H, Aydinlik S, Cavus H, Semiz C, Tun O, Terzi M, Dogan B, Onar MK, Sen S, Cavdar TK, Norwood F, Dimitriou A, Gollogly J, Mahdi-Rogers M, Seddigh A, Maier G, Sohail F, Sathasivam S, Arndt H, Davies D, Watling D, Rivner M, Hartmann JE, Quarles B, Smalley N, Amato A, Cochrane T, Salajegheh M, Roe K, Amato K, Toska S, Wolfe G, Silvestri N, Patrick K, Zakalik K, Katz J, Miller R, Engel M, Bravver E, Brooks B, Plevka S, Burdette M, Sanjak M, Kramer M, Nemeth J, Schommer C, Juel V, Guptill J, Hobson-Webb L, Beck K, Carnes D, Loor J, Anderson A, Lange D, Agopian E, Goldstein J, Manning E, Kaplan L, Holzberg S, Kassebaum N, Pascuzzi R, Bodkin C, Kincaid J, Snook R, Guinrich S, Micheels A, Chaudhry V, Corse A, Mosmiller B, Ho D, Srinivasan J, Vytopil M, Ventura N, Scala S, Carter C, Donahue C, Herbert C, Weiner E, McKinnon J, Haar L, McKinnon N, Alcon K, Daniels K, Sattar N, Jeffery D, McKenna K, Guidon A, David W, Dheel C, Levine-Weinberg M, Nigro C, Simpson E, Appel SH, Lai E, Lay L Jr, Pleitez M, Halton S, Faigle C, Thompson L, Sivak M, Shin S, Bratton J, Jacobs D, Brown G, Bandukwala I, Brown M, Kane J, Blount I, Freimer M, Hoyle JC, Agriesti J, Khoury J, Marburger T, Kaur H, Dimitrova D, Mellion M, Sachs G, Crabtree B, Keo R, Perez EK, Taber S, Gilchrist J, Andoin A, Darnell T, Goyal N, Sakamuri S, So YT, Welsh LW, Bhavaraju-Sanka R, Tobon Gonzalez A, Jones F, Saklad A, Nations S, Trivedi J, Hopkins S, Kazamel M, Alsharabati M, Lu L, Mumfrey-Thomas S, Woodall A, Richman D, Butters J, Lindsay M, Mozaffar T, Cash T, Goyal N, Roy G, Mathew V, Maqsood F, Minton B, Jones HJ, Rosenfeld J, Garcia R, Garcia S, Echevarria L, Pulley M, Aranke S, Berger AR, Shah J, Shabbir Y, Smith L, Varghese M, Gutmann L, Gutmann L, Swenson A, Olalde H, Hafer-Macko C, Kwan J, Zilliox L, Callison K, DiSanzo B, Naunton K, Bilsker M, Sharma K, Reyes E, Cooley A, Michon SC, Steele J, Karam CK, Chopra M, Bird S, Kaufman J, Gallatti N, Vu T, Katzin L, McClain T, Harvey B, Hart A, Huynh K, Beydoun S, Chilingaryan A, Droker B, Lin F, Shah A, Tran A, Akhter S, Malekniazi A, Tandan R, Hehir M, Waheed W, Lucy S, Weiss M, Distad J, Downing S, Strom S, Lisak R, Bernitsas E, Khan O, Kumar Sriwastava S, Tselis A, Jia K, Bertorini T, Arnold T, Henderson K, Pillai R, Liu Y, Wheeler L, Hewlett J, Vanderhook M, Dicapua D, Keung B, Kumar A, Patwa H, Robeson K, Nye J, Vu H (2017) Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol 16:976–986

    Article  CAS  PubMed  Google Scholar 

  61. Gajdos P, Chevret S, Clair B, Tranchant C, Chastang C, for the Myasthenia Gravis Clinical Study Group (1997) Clinical trial of plasma exchange and high-dose intravenous immunoglobulins in myasthenia gravis. Ann Neurol 41:789–796

    Article  CAS  PubMed  Google Scholar 

  62. Barth D, Nabavi Nouri M, Ng E, Nwe P, Bril V (2011) Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology 76:2017–2023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Dhawan PS, Goodman BP, Harper CM, Bosch PE, Hoffman-Snyder CR, Wellik KE, Wingerchuk DM, Demaerschalk BM (2015) IVIG versus PLEX in the treatment of worsening myasthenia gravis: what is the evidence? A critically appraised topic. Neurologist 19:145–148

    Article  PubMed  Google Scholar 

  64. Antozzi C (2013) Immunoadsorption in patients with autoimmune ion channel disorders of the peripheral nervous system. Atheroscler Suppl 14:219–222

    Article  CAS  PubMed  Google Scholar 

  65. Bourque PR, Pringle CE, Cameron W, Cowan J, Chardon JW (2016) Subcutaneous immunoglobulin therapy in the chronic management of myasthenia gravis: a retrospective cohort study. PLoS One 11:e0159993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo HC, Marx A, Ströbel P, Mazia C, Oger J, Cea JG, Heckmann JM, Evoli A, Nix W, Ciafaloni E, Antonini G, Witoonpanich R, King JO, Beydoun SR, Chalk CH, Barboi AC, Amato AA, Shaibani AI, Katirji B, Lecky BR, Buckley C, Vincent A, Dias-Tosta E, Yoshikawa H, Waddington-Cruz M, Pulley MT, Rivner MH, Kostera-Pruszczyk A, Pascuzzi RM, Jackson CE, Garcia Ramos GS, Verschuuren JJ, Massey JM, Kissel JT, Werneck LC, Benatar M, Barohn RJ, Tandan R, Mozaffar T, Conwit R, Odenkirchen J, Sonett JR, Jaretzki A 3rd, Newsom-Davis J, Cutter GR, MGTX Study Group (2016) Randomized trial of thymectomy in myasthenia gravis. N Engl J Med 375:511–522

    Article  PubMed  PubMed Central  Google Scholar 

  67. Mantegazza R, Baggi F, Bernasconi P, Antozzi C, Confalonieri P, Novellino L, Spinelli L, Ferrò MT, Beghi E, Cornelio F (2003) Video-assisted thoracoscopic extended thymectomy and extended transsternal thymectomy (T-3b) in non-thymomatous myasthenia gravis patients: remission after 6 years of follow-up. J Neurol Sci 212:31–36

    Article  PubMed  Google Scholar 

  68. Ricciardi R, Melfi F, Maestri M, de Rosa A, Petsa A, Lucchi M, Mussi A (2016) Endoscopic thymectomy: a neurologist's perspective. Ann Cardiothorac Surg 5:38–44

    PubMed  PubMed Central  Google Scholar 

  69. Rea F, Schiavon M, Marulli G (2015) Robotic thymectomy for myasthenia gravis. Ann Cardiothorac Surg 4:558–560

    PubMed  PubMed Central  Google Scholar 

  70. Bandoli G, Palmsten K, Forbess Smith CJ, Chambers CD (2017) A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum Dis Clin N Am 43:489–502

    Article  Google Scholar 

  71. Briggs GG, Freeman RK, Yaffe SJ (2015) Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. Wolters Kluwer/Lippincott Williams & Wilkins Health, Philadelphia

    Google Scholar 

  72. Das G, Damotte V, Gelfand JM, Bevan C, Cree BAC, Do L, Green AJ, Hauser SL, Bove R (2018) Rituximab before and during pregnancy: a systematic review, and a case series in MS and NMOSD. Neurol Neuroimmunol Neuroinflamm 5:e453

    Article  PubMed  PubMed Central  Google Scholar 

  73. Lake AJ, AI Khabbaz A, Keeney R (2017) Severe preeclampsia in the setting of myasthenia gravis. Case Rep Obstet Gynecol 2017:9204930

    PubMed  PubMed Central  Google Scholar 

  74. Ozcan J, Balson IF, Dennis AT (2015) New diagnosis myasthenia gravis and preeclampsia in late pregnancy. BMJ Case Rep 2015:bcr2014208323. https://doi.org/10.1136/bcr-2014-208323

    Article  PubMed  PubMed Central  Google Scholar 

  75. Esposito S, Bruno C, Berardinelli A, Filosto M, Mongini T, Morandi L, Musumeci O, Pegoraro E, Siciliano G, Tonin P, Marrosu G, Minetti C, Servida M, Fiorillo C, Conforti G, Scapolan S, Ansaldi F, Vianello A, Castaldi S, Principi N, Toscano A, Moggio M (2014) Vaccination recommendations for patients with neuromuscular disease. Vaccine 32:5893–5900

    Article  PubMed  Google Scholar 

  76. Seok HY, Shin HY, Kim JK et al (2017) The impacts of influenza infection and vaccination on exacerbation of myasthenia gravis. J Clin Neurol 14:325–330

    Article  Google Scholar 

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Correspondence to Amelia Evoli.

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Conflict of interest

Amelia Evoli served on an advisory board for Alexion and as jury member for research grant award for Grifols.

Giovanni Antonini received conference honoraries from Kedrion, Sanofi-Genzyme and travel grants from Kedrion, Sanofi-Genzyme, Pfizer, Almylan.

Carlo Antozzi has no conflicts of interest to disclose.

Antonio Di Muzio has no conflicts of interest to disclose.

Francesco Habetswallner has no conflicts of interest to disclose.

Cesare Iani has no conflicts of interest to disclose.

Maurizio Inghilleri has no conflicts of interest to disclose.

Rocco Liguori served on advisory boards for Biogen, Sanofi-Genzyme, Argon Healthcare s.r.l., Editree Eventi s.r.l., received Lecture fees from Dynamicom Education, SIMG Service, Adnkronos Salute unipersonale s.r.l., DOC Congress s.r.l., First Class s.r.l., and is a consultant for Alfasigma and Amicus Therapeutics s.r.l.

Renato Mantegazza has received funding for travel or meeting attendance from: Sanofi-Aventis, Teva, Biomarin, Alexion, Argenx, Novartis, Catalyst, Merck, and for advisory boards or SSC from: Biomarin, Alexion, Argenx.

Roberto Massa received Travel grants from Sanofi-Genzyme, CSL-Behring, Pfizer, Almylan.

Elena Pegoraro reports personal fees from PTC Therapeutics, Santhera, Roche and Sanofi-Genzyme.

Roberta Ricciardi has no conflicts of interest to disclose.

Carmelo Rodolico has no conflicts of interest to disclose.

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This document takes into consideration recent advances in the field and international guidelines. It represents an update of diagnostic procedures and therapeutic approaches used in Italian neurological departments with experience in neuromuscular transmission (NMT) disorders.

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Evoli, A., Antonini, G., Antozzi, C. et al. Italian recommendations for the diagnosis and treatment of myasthenia gravis. Neurol Sci 40, 1111–1124 (2019). https://doi.org/10.1007/s10072-019-03746-1

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