Muscle Specific Receptor Thyrosine Kinase (MuSK) Myasthenia Gravis (MG) is a rare auto-immune disorder of the neuromuscular junction. The clinical presentation of MG is dominated by fluctuating weakness of the extra-o...Muscle Specific Receptor Thyrosine Kinase (MuSK) Myasthenia Gravis (MG) is a rare auto-immune disorder of the neuromuscular junction. The clinical presentation of MG is dominated by fluctuating weakness of the extra-ocular, orofacial and limb muscles. The clinical presentation of MuSK MG can vary, which may delay diagnostic procedures. We present a patient who initially presented with severe weight loss and slowly progressive developing neck extensor weakness and diplopia. A single fiber EMG led to the diagnosis MG and antibodies directed towards MuSK were detected. He was treated with prednisone and the steroid sparing agent azathioprine after which he made full recovery.展开更多
Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles.The classical form of this autoimmune disease is characterized by the presence of antibodies against the m...Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles.The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction,the nicotinic acetylcholine receptor.Other variants of the disease involve autoimmune attack of non-receptor scaffolding proteins or enzymes essential for building or maintaining the integrity of this peripheral synapse.This review summarizes the participation of the above proteins in building the neuromuscular junction and the destruction of this cholinergic synapse by autoimmune aggression in myasthenia gravis.The review also covers the application of a powerful biophysical technique,superresolution optical microscopy,to image the nicotinic receptor in live cells and follow its motional dynamics.The hypothesis is entertained that anomalous nanocluster formation by antibody crosslinking may lead to accelerated endocytic internalization and elevated turnover of the receptor,as observed in myasthenia gravis.展开更多
文摘Muscle Specific Receptor Thyrosine Kinase (MuSK) Myasthenia Gravis (MG) is a rare auto-immune disorder of the neuromuscular junction. The clinical presentation of MG is dominated by fluctuating weakness of the extra-ocular, orofacial and limb muscles. The clinical presentation of MuSK MG can vary, which may delay diagnostic procedures. We present a patient who initially presented with severe weight loss and slowly progressive developing neck extensor weakness and diplopia. A single fiber EMG led to the diagnosis MG and antibodies directed towards MuSK were detected. He was treated with prednisone and the steroid sparing agent azathioprine after which he made full recovery.
文摘目的评价利妥昔单抗治疗重症肌无力(MG)的有效性和安全性。方法回顾性收集2018年2月至2019年7月北京医院神经内科收治的MG患者21例,所有患者血清抗乙酰胆碱受体(acetylcholine receptor,AChR)抗体或抗肌肉特异性酪氨酸激酶(muscle specific kinase,MuSK)抗体阳性。给予患者4次500mg利妥昔单抗治疗。分析患者治疗前后许氏评分,血CD19阳性B淋巴细胞、CD20阳性B淋巴细胞百分数以及相关抗体变化情况,同时观察利妥昔单抗的不良反应。结果共20例患者在使用4次500mg利妥昔单抗治疗后复查许氏评分,治疗前基线许氏评分为7~44分,平均(18.5±10.56)分,治疗后许氏评分为0~25分,平均(10.45±7.70)分,经利妥昔单抗治疗后患者许氏评分减低为6.5(3.25,12.75)分〔Md(P25,P75)〕,差异有统计学意义(P<0.01)。共16例患者于第1次、第2次、第3次及第4次利妥昔单抗用药后复查许氏评分,与用药前比较许氏评分降低分别为2(0,7)分〔Md(P25,P75)〕以及(6.12±4.54)、(6.18±5.98)、(8.12±5.80)分,与治疗前相比差异均有统计学意义(均P<0.01)。患者外周血CD19、CD20阳性B淋巴细胞计数于第一次用药后分别下降96%、97%。抗AChR抗体阳性患者共19例,用药后不同时间复查抗体水平14次,共发现2例患者抗体滴度降低。共9例患者出现不良反应,均为良性不良反应。结论4次500mg利妥昔单抗治疗MG显示出良好治疗效果,且安全性高,耐受性好。
文摘Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles.The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction,the nicotinic acetylcholine receptor.Other variants of the disease involve autoimmune attack of non-receptor scaffolding proteins or enzymes essential for building or maintaining the integrity of this peripheral synapse.This review summarizes the participation of the above proteins in building the neuromuscular junction and the destruction of this cholinergic synapse by autoimmune aggression in myasthenia gravis.The review also covers the application of a powerful biophysical technique,superresolution optical microscopy,to image the nicotinic receptor in live cells and follow its motional dynamics.The hypothesis is entertained that anomalous nanocluster formation by antibody crosslinking may lead to accelerated endocytic internalization and elevated turnover of the receptor,as observed in myasthenia gravis.
