神经肌接头病-重症肌无力Lambert-Eaton 综合征

,单击此处编辑母版标题样式,*,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,神经肌接头病(Disorders of neuromuscular transmission),重症肌无力 Lambert-Eaton 综合征,Dep.of Neurology,The 2nd Hospital,Harbin Medical University,Neuromuscular Disorders,D,efinition,The diseases of neuromuscular junction(NMJ)describes a sets of disease caused by circulating factors such as neurotoxins or autoantibodies 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 synaptic cleft by exocytosis.,Neuromusuclar Junction(NMJ)Physiology,1/3 of the ACh diffuses rapidly to the postsynaptic membrane and binds to the,AChR,s,leading to opening of the AChR-associated cation channel and depolarization called the end-plate potential(EPP).,If the EPP exceeds certain threshold,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 remaining 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),D,efinition,MG was originated from Latin,meaning very severe weakness.,acquired MG is an antibody and complement-mediated,T cell-dependent autoimmune disease leading to a defect in neuromuscular transmission.,Myasthenia gravis(MG),E,pidemiology,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 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),E,tiology,The autoimmune origin of MG is proposed long before it was established in 1973 by the direct evidence provided by Patrick 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),E,tiology,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.,Myasthenia Gravis(MG),E,tiology,Most of the patients with MG have abnormalities in the thymus,e.g.thymic hyperplastic or thymoma.,Although the primary antiself event being unclear,thymus appears to be the place where it initiates.,The general opinion is that virus infection or other nonspecific factors invades the thymus in genetically predisposed individuals leading to the development of MG.,Myasthenia Gravis(MG),P,athology,Lymphoid folliculus can be seen in thymus.About 10%of MG patients has thymoma of epithelia type.,Lymphorage,defined by aggregated lymphoid cells around the blood vessels,is sometimes seen in otherwise normal musculature in MG patients.,Myasthenia Gravis(MG),P,athology,At the NMJ,grossly simplified postsynaptic folds with deposition of immune-complex and the anti-AChR Abs is demonstrated by immunochemical studies.There is also considerable debris within the widened synaptic cleft.,Normal NMJ、NMJ in MG patients,示意图,电镜,Myasthenia Gravis(MG),C,linical Manifestations,MG can arise at any age,although young females and old males are more vulnerable to it.,Precipitating factors:concurrent infection,stress,weariness,menses,pregnancy or parturition.,The disease initiates insidious and follows a slowly progressive course.,Myasthenia Gravis(MG),C,linical Manifestations,Clinically,MG features with fluctuated muscular weakness in intensity during the day and easy fatigability.,Typically,the weakness varies in distribution and severity from day to day.,Characterized by abnormal weakness,which being worse at the end of the day or after exertion and tends to improve after rest or AChE treatment.,Myasthenia Gravis(MG),C,linical Manifestations,The weakness often begins with the lateral or bilateral extra-ocular muscles,leading to asymmetric ocular palsies(e.g.diplopia,strabismic)and ptosis.,Pupillary responses are not affected.,Myasthenia Gravis(MG),C,linical Manifestations,The patients may present with less wrinkles,amimia,difficulty in closing the eyes or disclosing tooth;,difficulty in chewing or swallowing,nasal speech;,weakness of the neck or the proximal upper limbs.,Myasthenia Gravis(MG),C,risisdefinition,Crisis describes a rapidly developed weakness in the bulbar muscles and respiratory insufficiency that necessitates assisted ventilation.,It is the leading cause of death in patients with MG.,Myasthenia Gravis(MG),C,risisclassification,Myasthenic crisis:able