Myasthenia gravis with both acetylcholine receptor antibody and muscle-specific tyrosine kinase antibody positivity: clinical analysis of 13 cases_West China Medical Journal

Authors：

LIU Ju , LIAN Zhiyun , CHEN Hongxi , SHI Ziyan , FENG Huiru , MIAO Xiaohui , DU Qin ,  ZHOU Hongyu

Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

ZHOU Hongyu, Email: zhouhy@scu.edu.cn

Keywords：

Myasthenia gravis; Acetylcholine receptor antibody; Muscle-specific tyrosine kinase antibody; Clinical analysis

DOI：

10.7507/1002-0179.201611178

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ObjectiveTo explore the clinical features of myasthenia gravis (MG) harboring both acetylcholine receptor antibody (AChRAb) and muscle-specific tyrosine kinase antibody (MuSKAb) positivity.MethodsWe searched PubMed, Web of Science, Embase and China National Knowledge Infrastructure databases (from inception to November 2016), to collect the case reports of MG with both AChRAb and MuSKAb positivity. Along with one case discovered in Department of Neurology, West China Hospital, the clinical data of the cases were retrospectively analyzed.ResultsA total of 13 double-seropositive MG patients were enrolled in this study, demonstrating a marked female predominance (including 1 male and 12 females) and a younger age at onset [(31.07±24.77) years]. During the disease course, 10 of the included patients presented severe bulbar involvement, dyspnea and neck weakness, with myasthenic crisis in 6 individuals. Among the 11 patients with detailed records, abnormal thymus glands comprised 4 thymus hyperplasia and one thymoma. While the response to oral pyridostigmine was unsatisfactory in 11 double-seropositive MG patients, ranging from mild benefit to overt intolerance; the patients treated with plasma exchange (3/3), rituximab (1/1) or corticosteroid (7/12) improved dramatically, with other immumosuppressants and intravenous immunoglobulin partially responsive. Moreover, 5 patients undergoing thymectomy improved markedly or partially.ConclusionsCompared with MG patients with MuSKAb positivity merely, the condition of the double-seropositive MG patients seem to be more severe and further inclined to myasthenic crisis. The incidence of abnormal thymus, such as thymus hyperplasia, is higher. Thymectomy may be an effective treatment for such patients.

Citation： LIU Ju, LIAN Zhiyun, CHEN Hongxi, SHI Ziyan, FENG Huiru, MIAO Xiaohui, DU Qin, ZHOU Hongyu. Myasthenia gravis with both acetylcholine receptor antibody and muscle-specific tyrosine kinase antibody positivity: clinical analysis of 13 cases. West China Medical Journal, 2018, 33(6): 696-702. doi: 10.7507/1002-0179.201611178 Copy

1.	Ohta K, Shigemoto K, Fujinami A, et al. Clinical and experimental features of MuSK antibody positive MG in Japan. Eur J Neurol, 2007, 14(9): 1029-1034.
2.	Pasnoor M, Wolfe GI, Nations S, et al. Clinical findings in MuSk-antibody positive myasthenia gravis: a U.S. experience. Muscle Nerve, 2010, 41(3): 370-374.
3.	Guptill JT, Sanders DB, Evoli A. Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve, 2011, 44(1): 36-40.
4.	Witoonpanich R, Dejthevaporn C, Pulkes T, et al. Prevalence, clinical features and treatment outcomes of patients with myasthenia gravis positive for antibodies to muscle-specific kinase in Thailand. J Clin Neurosci, 2013, 20(5): 707-709.
5.	Hoch W, McConville J, Helms S, et al. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med, 2001, 7(3): 365-368.
6.	Suhail H, Vivekanandhan S, Singh S, et al. Coexistent of muscle specific tyrosine kinase and acetylcholine receptor antibodies in a myasthenia gravis patient. Neurol India, 2010, 58(4): 668-669.
7.	Poulas K, Koutsouraki E, Kordas G, et al. Anti-MuSK- and anti-AChR-positive myasthenia gravis induced by d-penicillamine. J Neuroimmunol, 2012, 250(1/2): 94-98.
8.	Zouvelou V, Zisimopoulou P, Psimenou E, et al. AChR-myasthenia gravis switching to double-seropositive several years after the onset. J Neuroimmunol, 2014, 267(1-2): 111-112.
9.	Ohta K, Shigemoto K, Kubo S, et al. MuSK Ab described in seropositive MG sera found to be Ab to alkaline phosphatase. Neurology, 2005, 65(12): 1988.
10.	Tsonis AI, Zisimopoulou P, Lazaridis K, et al. MuSK autoantibodies in myasthenia gravis detected by cell based assay: a multinational study. J Neuroimmunol, 2015, 284: 10-17.
11.	Evoli A, Tonali PA, Padua L, et al. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain, 2003, 126(Pt 10): 2304-2311.
12.	Rajakulendran S, Viegas S, Spillane J, et al. Clinically biphasic myasthenia gravis with both AChR and MuSK antibodies. J Neurol, 2012, 259(12): 2736-2739.
13.	Saleh A Al, Cariga P. Myasthenia gravis with AChR and MuSK antibodies positivity: case report. Clin Neurophysiol, 2007, 118(5): e165-e167.
14.	Diaz-Manera J, Rojas-García R, Gallardo E, et al. Antibodies to AChR, MuSK and VGKC in a patient with myasthenia gravis and Morvan’s syndrome. Nat Clin Pract Neurol, 2007, 3(7): 405-410.
15.	Saulat B, Maertens P, Hamilton WJ, et al. Anti-muSK antibody after thymectomy in a previously seropositive myasthenic child. Neurology, 2007, 69(8): 803-804.
16.	Sanders DB, Juel VC. MuSK-antibody positive myasthenia gravis: questions from the clinic. J Neuroimmunol, 2008, 201-202: 85-89.
17.	Kostera-Pruszczyk A, Kwiecinski H. Juvenile seropositive myasthenia gravis with anti-MuSK antibody after thymectomy. J Neurol, 2009, 256(10): 1780-1781.
18.	Zouvelou V, Kyriazi S, Rentzos M, et al. Double-seropositive myasthenia gravis. Muscle Nerve, 2013, 47(3): 465-466.
19.	崔伟. 乙酰胆碱受体抗体及肌肉特异性受体酪氨酸激酶抗体均阳性的重症肌无力 1 例报告. 临床神经病学杂志, 2015, 28(4): 258, 261.
20.	Skjei KL, Lennon VA, Kuntz NL. Muscle specific kinase autoimmune myasthenia gravis in children: a case series. Neuromuscul Disord, 2013, 23(11): 874-882.
21.	Jaretzki A 3rd, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis: recommendations for clinical research standards. Task force of the medical scientific advisory board of the myasthenia gravis foundation of America. Neurology, 2000, 55(1): 16-23.
22.	Lebrun C, Bourg V, Tieulie N, et al. Successful treatment of refractory generalized myasthenia gravis with rituximab. Eur J Neurol, 2009, 16(2): 246-250.

1. Ohta K, Shigemoto K, Fujinami A, et al. Clinical and experimental features of MuSK antibody positive MG in Japan. Eur J Neurol, 2007, 14(9): 1029-1034.
2. Pasnoor M, Wolfe GI, Nations S, et al. Clinical findings in MuSk-antibody positive myasthenia gravis: a U.S. experience. Muscle Nerve, 2010, 41(3): 370-374.
3. Guptill JT, Sanders DB, Evoli A. Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve, 2011, 44(1): 36-40.
4. Witoonpanich R, Dejthevaporn C, Pulkes T, et al. Prevalence, clinical features and treatment outcomes of patients with myasthenia gravis positive for antibodies to muscle-specific kinase in Thailand. J Clin Neurosci, 2013, 20(5): 707-709.
5. Hoch W, McConville J, Helms S, et al. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med, 2001, 7(3): 365-368.
6. Suhail H, Vivekanandhan S, Singh S, et al. Coexistent of muscle specific tyrosine kinase and acetylcholine receptor antibodies in a myasthenia gravis patient. Neurol India, 2010, 58(4): 668-669.
7. Poulas K, Koutsouraki E, Kordas G, et al. Anti-MuSK- and anti-AChR-positive myasthenia gravis induced by d-penicillamine. J Neuroimmunol, 2012, 250(1/2): 94-98.
8. Zouvelou V, Zisimopoulou P, Psimenou E, et al. AChR-myasthenia gravis switching to double-seropositive several years after the onset. J Neuroimmunol, 2014, 267(1-2): 111-112.
9. Ohta K, Shigemoto K, Kubo S, et al. MuSK Ab described in seropositive MG sera found to be Ab to alkaline phosphatase. Neurology, 2005, 65(12): 1988.
10. Tsonis AI, Zisimopoulou P, Lazaridis K, et al. MuSK autoantibodies in myasthenia gravis detected by cell based assay: a multinational study. J Neuroimmunol, 2015, 284: 10-17.
11. Evoli A, Tonali PA, Padua L, et al. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain, 2003, 126(Pt 10): 2304-2311.
12. Rajakulendran S, Viegas S, Spillane J, et al. Clinically biphasic myasthenia gravis with both AChR and MuSK antibodies. J Neurol, 2012, 259(12): 2736-2739.
13. Saleh A Al, Cariga P. Myasthenia gravis with AChR and MuSK antibodies positivity: case report. Clin Neurophysiol, 2007, 118(5): e165-e167.
14. Diaz-Manera J, Rojas-García R, Gallardo E, et al. Antibodies to AChR, MuSK and VGKC in a patient with myasthenia gravis and Morvan’s syndrome. Nat Clin Pract Neurol, 2007, 3(7): 405-410.
15. Saulat B, Maertens P, Hamilton WJ, et al. Anti-muSK antibody after thymectomy in a previously seropositive myasthenic child. Neurology, 2007, 69(8): 803-804.
16. Sanders DB, Juel VC. MuSK-antibody positive myasthenia gravis: questions from the clinic. J Neuroimmunol, 2008, 201-202: 85-89.
17. Kostera-Pruszczyk A, Kwiecinski H. Juvenile seropositive myasthenia gravis with anti-MuSK antibody after thymectomy. J Neurol, 2009, 256(10): 1780-1781.
18. Zouvelou V, Kyriazi S, Rentzos M, et al. Double-seropositive myasthenia gravis. Muscle Nerve, 2013, 47(3): 465-466.
19. 崔伟. 乙酰胆碱受体抗体及肌肉特异性受体酪氨酸激酶抗体均阳性的重症肌无力 1 例报告. 临床神经病学杂志, 2015, 28(4): 258, 261.
20. Skjei KL, Lennon VA, Kuntz NL. Muscle specific kinase autoimmune myasthenia gravis in children: a case series. Neuromuscul Disord, 2013, 23(11): 874-882.
21. Jaretzki A 3rd, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis: recommendations for clinical research standards. Task force of the medical scientific advisory board of the myasthenia gravis foundation of America. Neurology, 2000, 55(1): 16-23.
22. Lebrun C, Bourg V, Tieulie N, et al. Successful treatment of refractory generalized myasthenia gravis with rituximab. Eur J Neurol, 2009, 16(2): 246-250.

West China Medical Journal

Myasthenia gravis with both acetylcholine receptor antibody and muscle-specific tyrosine kinase antibody positivity: clinical analysis of 13 cases

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