1、 神经肌接头病 (Disorders of neuromuscular transmission)重症肌无力Lambert-Eaton 综合征Dep. of NeurologyThe 2nd Hospital Harbin Medical UniversityNeuromuscular Disorders DefinitionThe diseases of neuromuscular junction (NMJ) describes a sets of disease caused by circulating factors such as neurotoxins or autoantibo
2、dies which bind with high affinity to specific proteins at the NMJ and disturb the neuromuscular transmission. Neuromusuclar Junction (NMJ)Physiology the nerve AP reaches the nerve terminal which inflated and without myelin and leads to the opening of calcium channel and release of ACh into the syna
3、ptic cleft by exocytosis. Neuromusuclar Junction (NMJ)Physiology 1/3 of the ACh diffuses rapidly to the postsynaptic membrane and binds to the AChRs, leading to opening of the AChR-associated cation channel and depolarization called the end-plate potential (EPP). If the EPP exceeds certain threshold
4、, voltage gated sodium channel at the postsynaptic membrane are opened. This generates the muscle action potential (CMAP) that propagates along the muscle fiber and activates contraction. Neuromusuclar Junction (NMJ)Physiology Another 1/3 of the ACh is hydrolyzed by cholinesterase (ChE). The remaini
5、ng 1/3 of the ACh is recaptured by the presynaptic membrane. 重症肌无力 (Myasthenia Gravis, MG)概念病因及发病机制病理临床表现诊断及鉴别诊断治疗Myasthenia gravis (MG)Definition MG was originated from Latin, meaning very severe weakness. acquired MG is an antibody and complement-mediated, T cell-dependent autoimmune disease leadi
6、ng to a defect in neuromuscular transmission.Myasthenia gravis ( MG)Epidemiology It is the prototypic neuromuscular disorders with an incidence of 80-200 per million and prevalence about 500 per million. In China, it is estimated that 0.6 million people were diagnosed as MG and most of them lives in
7、 the South of China. It had been a life-threatening disease before 1970s, though nowadays the incidence of death has been greatly reduced to about 0.2%. Myasthenia Gravis (MG)Etiology The autoimmune origin of MG is proposed long before it was established in 1973 by the direct evidence provided by Pa
8、trick and Lindstrom, who have immunized rabbit with affinity-purified Torpedo AChR with CFA and reproduced the animal models representing human MG (EAMG). The AChR is the autoantigen.Myasthenia Gravis (MG)Etiology The presence of anti-AChR Abs can be demonstrated in 80%-90% of MG patients. There is a 3:1 female-male ratio for patients who develop MG in early adult life. Overall, the above makes MG fulfills the criteria for autoimmune diseases.
