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Acetylcholine receptor and titin antibody in Chinese myasthenia gravis patients
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Abstracts / Neuromuscular Disorders 25 (2015) S184–S316
not correlate with disease severity and antibody status. Although serum BAFF levels do not correlate with disease severity, our data suggest that BAFF is likely to play a role in the pathogenesis of MG by promoting the survival and maturation of autoreactive B cells. http://dx.doi.org/10.1016/j.nmd.2015.06.086
G.P.72 Familial MuSK antibody positive myasthenia gravis O. Ekmekci *, A. Yuceyar, H. Karasoy Ege University, Neurology, Izmir, Turkey Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junction. Familial cases of autoimmune MG are very rare. Familial occurrence of MG with anti-acetylcholine receptor antibodies or antimuscle specific kinase antibodies (MuSK ab) has been rarely reported. Presence of different antibodies in the same family members has also been reported. Herein, we report 2 siblings with MuSK ab positive MG. Case 1, the brother, aged 47 years, was admitted to our hospital with a 2 months history of difficulty in swallowing, dysphonia, dyspnea and dropped head. His family history revealed that his sister had undergone thymectomy for MG. On neurologic examination, he had bilateral ptosis and bilateral facial weakness. There were restriction of eye movements and weakness in legs and neck muscles. He had nasal speech. Simpson test was positive. Single fiber EMG revealed abnormal jitter in orbicularis oculi muscles. AChR ab was not detected. The MuSK ab titer was 2.11 nmol/L (normal < 0.05 nmol/L). Thorax CT was normal. Intravenous immunoglobulin was given for his bulbar symptoms and oral prednisolone was added to the treatment regimen. After this treatment, his dysphagia, dyspnea, ptosis, extremity and neck weakness improved. Six months later, he complained of dysphagia again. He did not tolerate pyridostigmine and dysphagia worsened. Azathioprine was added to steroid treatment. On 20 months follow-up, he is still in pharmacological remission. Case 2 was the elder sister of Case 1 who developed ptosis, nasal speech, and difficulty of swallowing and chewing at age 22. She underwent thymectomy for MG at age 30. Pathologic examination showed normal thymus. On neurologic examination at age 52, she had bilateral facial weakness, nasal speech, mild weakness in legs, and atrophy of the tongue. She is in pharmacological remission with low dose corticosteroid. The presence of familial MG cases suggests the influence of genetic factors in disease. http://dx.doi.org/10.1016/j.nmd.2015.06.087
G.P.73 Clinical characteristics of juvenile myasthenia gravis: A tertiary center experience H. Lee *,1, H. Shin 2, H. Kang 3, S. Kim 2, J. Lee 3, H. Kim 3, S. Il Nam 2, Y. Lee 1 1 Gangnam Severance Hospital, Yonsei University College of Medicine, Department of Pediatrics, Seoul, Republic of Korea; 2 Severance Hospital, Yonsei University College of Medicine, Department of Neurology, Seoul, Republic of Korea; 3 Severance Children’s Hospital, Yonsei University College of Medicine, Division of Pediatric Neurology, Department of Pe, Seoul, Republic of Korea This study aims to review and evaluate clinical characteristics, diagnostic testings, treatment and responses of Korean Juvenile Myasthenia Gravis (JMG) patients. We retrospectively reviewed the electronic medical records of myasthenia gravis patients diagnosed and treated at the Division of Pediatric Neurology and Department of Neurology at Severance Hospital from September 2005 to August 2014. A total 87 patients were recruited including 56 (64%) females and 31 (36%) males. Age of onset was from 4 months to 17 years 6 months. Prepubertal onset before age 12 years was in 63 patients (72%) and 24 (28%) were postpubertal onset. Female to male ratio in the prepubertal group was about 1.9:1 and in postpubertal group was 1.7:1. Overall, 86 (99%)
presented with ocular symptoms, while 14 (16%), 3 (3%) and 14 (16%) patients presented with skeletal, respiratory and bulbar weakness, respectively. In terms of treatment, 86 patients (99%) were treated with acetylcholine esterase inhibitor at some point, and 59 (68%) were treated with chronic oral glucocorticoids. 7 (8%) were treated with steroid-sparing agents. Thymectomy was done in a total 13 patients including 0 (prepubertal onset male), 1 (prepubertal onset female), 1 (postpubertal onset male) and 11 (postpubertal onset female), respectively. In the last group, all had positive anti-acetylcholine receptor antibody with high titers (9.66 ± 5.47 nmol/L, reference 0–0.500), and 9 (82%) were pathologically confirmed with thymic follicular hyperplasia. In contrary, the prepubertal onset male group obtained complete remission via acetylcholine esterase inhibitor and/or chronic glucocorticoid treatment. In conclusion, our study results were compatible with previous literature of distinct features of JMG, and further study is warranted for the best treatment decisions, especially for female patients with postpubertal onset with high rate of thymectomy as seen in our study. http://dx.doi.org/10.1016/j.nmd.2015.06.088
G.P.74 Acetylcholine receptor and titin antibody in Chinese myasthenia gravis patients Y. Hong *,1, H. Li 2, G. Skeie 3, N. Gilhus 1 1 University of Bergen, Clinical Medicine Department, Bergen, Norway; 2 Qilu Hospital of Shandong University, Neurology Department, Qingdao, China; 3 Haukelands University Hospital, Neurology Department, Bergen, Norway Myasthenia gravis (MG) is an autoimmune disease caused by antibodymediated destruction at the neuromuscular junction. Autoantibodies against acetylcholine receptor (AChR) and muscle specific kinase (MuSK) have been found to play roles in the pathogenesis of MG. Besides, some MG patients also have autoantibodies against proteins inside the striated muscle cells. The AChR and titin antibody status of Chinese MG patients is still not well elucidated. 522 MG patients followed in the Neurology Department of Qingdao University Affiliated Hospital were included in the study. All patients were of Han Chinese origin. MG subgroups were classified into: 1 Juvenile: onset age <15 years, no thymoma; 2 Early-onset: generalized, ≤15 onset age <50 years, no thymoma; 3 Late-onset: generalized, onset age ≥50 years, no thymoma; 4 Thymoma: thymoma diagnosed by CT and/or pathology; 5 Ocular: Ocular symptoms only, onset age ≥15 years. AChR antibody and titin antibody were tested by ELISA methods. 399 (76%) patients have AChR antibody, 125 (24%) have titin antibody. No significant differences were found between female and male MG patients (P > 0.05). The distribution of AChR and titin antibody showed significant differences among different subgroups (P < 0.05). The positive rates of titin antibodies were higher in thymoma (51%) and late onset MG subgroups (41%) (P < 0.05), and were lowest in the juvenile MG subgroup (1.3%). The positive rates of AChR antibody were highest in thymoma MG (97.6%) and lowest in ocular MG (60.2%). The positive rates of titin antibodies showed an increasing trend as the onset age increases in nonthymomatous MG patients. The titin and AChR antibody positive rates were correlated with maximum Osserman classification. Titin antibody was distributed mainly in elderly and thymoma MG patients; AChR antibody positive rate was higher in thymoma MG subgroups; Titin and AChR antibody were correlated with maximum Osserman classification of MG patients. http://dx.doi.org/10.1016/j.nmd.2015.06.089
G.P.75 Very late-onset myasthenia gravis in Slovakia: Epidemiology and clinical characteristics P. Spalek *,1, M. Fulova 2, I. Martinka 1, M. Spalekova 2, M. Soskova 1, I. Urminska 1 1 University Hospital Bratislava, Centre for Neuromuscular Diseases,
Abstracts / Neuromuscular Disorders 25 (2015) S184–S316
not correlate with disease severity and antibody status. Although serum BAFF levels do not correlate with disease severity, our data suggest that BAFF is likely to play a role in the pathogenesis of MG by promoting the survival and maturation of autoreactive B cells. http://dx.doi.org/10.1016/j.nmd.2015.06.086
G.P.72 Familial MuSK antibody positive myasthenia gravis O. Ekmekci *, A. Yuceyar, H. Karasoy Ege University, Neurology, Izmir, Turkey Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junction. Familial cases of autoimmune MG are very rare. Familial occurrence of MG with anti-acetylcholine receptor antibodies or antimuscle specific kinase antibodies (MuSK ab) has been rarely reported. Presence of different antibodies in the same family members has also been reported. Herein, we report 2 siblings with MuSK ab positive MG. Case 1, the brother, aged 47 years, was admitted to our hospital with a 2 months history of difficulty in swallowing, dysphonia, dyspnea and dropped head. His family history revealed that his sister had undergone thymectomy for MG. On neurologic examination, he had bilateral ptosis and bilateral facial weakness. There were restriction of eye movements and weakness in legs and neck muscles. He had nasal speech. Simpson test was positive. Single fiber EMG revealed abnormal jitter in orbicularis oculi muscles. AChR ab was not detected. The MuSK ab titer was 2.11 nmol/L (normal < 0.05 nmol/L). Thorax CT was normal. Intravenous immunoglobulin was given for his bulbar symptoms and oral prednisolone was added to the treatment regimen. After this treatment, his dysphagia, dyspnea, ptosis, extremity and neck weakness improved. Six months later, he complained of dysphagia again. He did not tolerate pyridostigmine and dysphagia worsened. Azathioprine was added to steroid treatment. On 20 months follow-up, he is still in pharmacological remission. Case 2 was the elder sister of Case 1 who developed ptosis, nasal speech, and difficulty of swallowing and chewing at age 22. She underwent thymectomy for MG at age 30. Pathologic examination showed normal thymus. On neurologic examination at age 52, she had bilateral facial weakness, nasal speech, mild weakness in legs, and atrophy of the tongue. She is in pharmacological remission with low dose corticosteroid. The presence of familial MG cases suggests the influence of genetic factors in disease. http://dx.doi.org/10.1016/j.nmd.2015.06.087
G.P.73 Clinical characteristics of juvenile myasthenia gravis: A tertiary center experience H. Lee *,1, H. Shin 2, H. Kang 3, S. Kim 2, J. Lee 3, H. Kim 3, S. Il Nam 2, Y. Lee 1 1 Gangnam Severance Hospital, Yonsei University College of Medicine, Department of Pediatrics, Seoul, Republic of Korea; 2 Severance Hospital, Yonsei University College of Medicine, Department of Neurology, Seoul, Republic of Korea; 3 Severance Children’s Hospital, Yonsei University College of Medicine, Division of Pediatric Neurology, Department of Pe, Seoul, Republic of Korea This study aims to review and evaluate clinical characteristics, diagnostic testings, treatment and responses of Korean Juvenile Myasthenia Gravis (JMG) patients. We retrospectively reviewed the electronic medical records of myasthenia gravis patients diagnosed and treated at the Division of Pediatric Neurology and Department of Neurology at Severance Hospital from September 2005 to August 2014. A total 87 patients were recruited including 56 (64%) females and 31 (36%) males. Age of onset was from 4 months to 17 years 6 months. Prepubertal onset before age 12 years was in 63 patients (72%) and 24 (28%) were postpubertal onset. Female to male ratio in the prepubertal group was about 1.9:1 and in postpubertal group was 1.7:1. Overall, 86 (99%)
presented with ocular symptoms, while 14 (16%), 3 (3%) and 14 (16%) patients presented with skeletal, respiratory and bulbar weakness, respectively. In terms of treatment, 86 patients (99%) were treated with acetylcholine esterase inhibitor at some point, and 59 (68%) were treated with chronic oral glucocorticoids. 7 (8%) were treated with steroid-sparing agents. Thymectomy was done in a total 13 patients including 0 (prepubertal onset male), 1 (prepubertal onset female), 1 (postpubertal onset male) and 11 (postpubertal onset female), respectively. In the last group, all had positive anti-acetylcholine receptor antibody with high titers (9.66 ± 5.47 nmol/L, reference 0–0.500), and 9 (82%) were pathologically confirmed with thymic follicular hyperplasia. In contrary, the prepubertal onset male group obtained complete remission via acetylcholine esterase inhibitor and/or chronic glucocorticoid treatment. In conclusion, our study results were compatible with previous literature of distinct features of JMG, and further study is warranted for the best treatment decisions, especially for female patients with postpubertal onset with high rate of thymectomy as seen in our study. http://dx.doi.org/10.1016/j.nmd.2015.06.088
G.P.74 Acetylcholine receptor and titin antibody in Chinese myasthenia gravis patients Y. Hong *,1, H. Li 2, G. Skeie 3, N. Gilhus 1 1 University of Bergen, Clinical Medicine Department, Bergen, Norway; 2 Qilu Hospital of Shandong University, Neurology Department, Qingdao, China; 3 Haukelands University Hospital, Neurology Department, Bergen, Norway Myasthenia gravis (MG) is an autoimmune disease caused by antibodymediated destruction at the neuromuscular junction. Autoantibodies against acetylcholine receptor (AChR) and muscle specific kinase (MuSK) have been found to play roles in the pathogenesis of MG. Besides, some MG patients also have autoantibodies against proteins inside the striated muscle cells. The AChR and titin antibody status of Chinese MG patients is still not well elucidated. 522 MG patients followed in the Neurology Department of Qingdao University Affiliated Hospital were included in the study. All patients were of Han Chinese origin. MG subgroups were classified into: 1 Juvenile: onset age <15 years, no thymoma; 2 Early-onset: generalized, ≤15 onset age <50 years, no thymoma; 3 Late-onset: generalized, onset age ≥50 years, no thymoma; 4 Thymoma: thymoma diagnosed by CT and/or pathology; 5 Ocular: Ocular symptoms only, onset age ≥15 years. AChR antibody and titin antibody were tested by ELISA methods. 399 (76%) patients have AChR antibody, 125 (24%) have titin antibody. No significant differences were found between female and male MG patients (P > 0.05). The distribution of AChR and titin antibody showed significant differences among different subgroups (P < 0.05). The positive rates of titin antibodies were higher in thymoma (51%) and late onset MG subgroups (41%) (P < 0.05), and were lowest in the juvenile MG subgroup (1.3%). The positive rates of AChR antibody were highest in thymoma MG (97.6%) and lowest in ocular MG (60.2%). The positive rates of titin antibodies showed an increasing trend as the onset age increases in nonthymomatous MG patients. The titin and AChR antibody positive rates were correlated with maximum Osserman classification. Titin antibody was distributed mainly in elderly and thymoma MG patients; AChR antibody positive rate was higher in thymoma MG subgroups; Titin and AChR antibody were correlated with maximum Osserman classification of MG patients. http://dx.doi.org/10.1016/j.nmd.2015.06.089
G.P.75 Very late-onset myasthenia gravis in Slovakia: Epidemiology and clinical characteristics P. Spalek *,1, M. Fulova 2, I. Martinka 1, M. Spalekova 2, M. Soskova 1, I. Urminska 1 1 University Hospital Bratislava, Centre for Neuromuscular Diseases,