重症肌无力

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
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 the South of China. It had been a life-threatening disease before 1970’s, though nowadays the incidence of death has been greatly reduced to about 0.2%.
Definition
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.
Myasthenia Gravis (MG)
Clinical 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)
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.
Myasthenia Gravis (MG)
Clinical 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.
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
Mቤተ መጻሕፍቲ ባይዱasthenia gravis (MG)
Definition
MG was originated from Latin, meaning very severe weakness. acquired MG is an antibody and complementmediated, T cell-dependent autoimmune disease leading to a defect in neuromuscular transmission.
Myasthenia Gravis (MG)
Pathology
At the NMJ, grossly simplified postsynaptic folds with deposition of immune-complex and the antiAChR 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)
Crisis—classification
Myasthenic crisis: able to react to AChE drugs and being hypersensitive to the curare. Cholinergic crisis: 1. overmedication can lead to increased weakness, which, unlike myasthenic weakness, is unaffected or enhanced by intravenous edrophonium. 2. It may be accompanied by pallor, sweating, nausea, vomiting, salivation, colic, and diarrhea (muscarinic syndrome). Brittie crisis: unresponsive to AChE.
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, 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.
Myasthenia Gravis (MG)
Pathology
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)
Etiology
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)
Crisis—definition
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.
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.
Myasthenia Gravis (MG)