神经肌肉接头疾病分型及诊断

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,*,重 症 肌 无 力(myasthenia gravis, MG),教学目的,掌握重症肌无力的临床特点,熟悉MG的临床分型,掌握MG的诊断标准,熟悉MG的治疗措施,Diseases of Neuromuscular Junction,定义：指一组神经-肌肉接头处传递功能障碍疾病。特征表现是波动性无力和肌肉易疲劳。,本组疾病包括：,重症肌无力：体内产生AChR自身抗体使AChR受损或减少,有机磷中毒：胆碱酯酶活力受抑制，使ACh作用过度延长而产生去极化传递障碍,Diseases of Neuromuscular Junction,本组疾病包括：,Lambert-Eaton综合征和氨基甙类药物：使ACh合成和释放减少,肉毒杆菌中毒和高镁血症：阻碍钙离子进入神经末梢,美洲箭毒素与AChR结合，阻断了ACh AChR结合,Diseases of Neuromuscular Junction,Myasthenia Gravis,定义：乙酰胆碱受体抗体介导的、细胞免疫依赖的及补体参与的一种神经-肌肉接头处传递障碍的自身免疫性疾病，主要累及NMJ突触后膜上乙酰胆碱受体,临床特征：部分或全身骨骼肌易于疲劳；症状的波动性,Myasthenia gravis is characterized by fluctuating weakness and easy fatigability of voluntary muscles.,Etiology,实验性自身免疫性重症肌无力(experimental auto-immune myasthenia gravis, EAMG)动物模型的建立，在动物血清中检测到AChR (acetylcholine receptor),胸腺的异常，MG合并胸腺瘤(thymic tumor)及胸腺肥大，发现肌样细胞(myoid cell)，具有横纹并载有AChR,MG患者常合并甲亢(thyrotoxicosis)，SLE (systemic lupus erythematosus)，类风湿性关节炎(rheumatoid arthritis)等自身免疫性疾病,MG患者HLA基因型(B8,DR3,DQB1)频率较高,病理,70%患者胸腺肥大,10%患者有胸腺瘤，好发于年龄较大者,NMJ的病理改变：突触后膜皱褶减少，突触间隙加宽，皱褶中有抗体和免疫复合物存在,Clinical findings,MG can occur at any age , and more common in females than males. MG is insidious and follows a slowly progressive course. Exacerbation may occur in infection, pregnancy or before menses.,There is a predilection for the external ocular muscles and certain other cranial muscles, including the masticatory, facial, pharyngeal, and laryngeal muscles.Respiratory and limb muscles may also be affected.,Clinical findings,Presentation: ptosis, diplopia, difficulty in chewing or swallowing, nasal speech, respiratory difficulties, or weakness of the limbs.,Clinical findings,Myasthenia gravis is characterized by fluctuating weakness and easy fatigability of voluntary muscles.,The symptoms often fluctuate in intensity during the day, and this diurnal variation is superimposed on longer-term spontaneous relapses and remissions that may last for weeks.,Neurological examination,The weakness does not conform to the distribution of any single nerve, root, or level of the central nervous system.,The extraocular muscles are often involved, leading to asymmetric ocular palsies and ptosis. Pupillary responses are not affected.,Neurological examination,Sustained activity of affected muscles leads to temporarily increased weakness.Sustained upgaze for 2 minutes can lead to increased ptosis, with power in the affected muscles improving after a brief rest.,In advanced cases, there may be some mild atrophy of affected muscles.,Sensation is normal, and there are usually no reflex changes.,Myasthenia gravis crisis,危象：急骤发生延髓支配肌肉及呼吸肌无力，以致不能维持换气功能,classification:,肌无力危象(myasthenic crisis)，胆碱能危象(cholinergic crisis)，反拗性危象(brittle crisis),Classification of MG,Osserman classification,型：眼肌型,A型：轻度全身型,B型：中度全身型,型：重症激进型，胸腺瘤高发,型：迟发重症型，由A 及B 转化来,型：伴肌萎缩型,Classification of MG,其他分型,青少年型和成人型,新生儿MG：母亲为MG患者，生后48小时内出现症状,先天性MG：常隐遗传，属于离子通道病。AChR基因突变，婴儿期出现症状,药源性MG：青霉胺,实验室检查(laboratory examination),X-rays and CT scans of the chest: thymoma,electrophysiology: decremental response of muscles to repetitive stimulation(at 2 or 3 Hz) of motor nerve, but normal findings do not exclude the diagnosis.,Serum acetylcholine receptor antibody levels are increased in 8090% of patients with generalized MG.,Diagnosis,病变主要侵犯骨骼肌，症状的波动性,疲劳试验(Jolly test),高滴度的AChR-Ab,重复频率刺激检查,抗胆碱酯酶药物实验：新斯的明实验(neostigmine test)，腾喜龙实验(Tensilon test),Differential diagnosis,伴有口咽、肢体肌无力的疾病，如进行性肌营养不良(progressive muscular dystrophy, PMD)，肌萎缩性侧索硬化(amyotrophic lateral sclerosis, ALS)，神经症(neurosis)等引起的肌无力,Lambert-Eaton Syndrome,肉毒杆菌中毒(Botulism)、有机磷农药中毒(organophosphorous insecticides toxicosis)、蛇咬伤(venomous snake bite)等引起的肌无力,Treatment,抗胆碱酯酶药物(anticholinesterase drugs)：吡啶斯的明(pyridostigmine),病因治疗,肾上腺皮质类固醇类(corticosteroids)：,适应症：抗胆碱酯酶药不足以控制症状的轻症者,所有年龄的中至重度MG病人,胸腺切除术的术前处理,胸腺切除术后的过度期,胸腺切除无效者,疗法有三种，大剂量递减隔日疗法，小剂量递增隔日疗法，大剂量冲击疗法,Treatment,病因治疗,免疫抑制剂(immunodepressive)：激素治疗半年内无效。,环孢霉素A：100300mg/次，23次/周。,血浆置换(plasmapheresis)：用于胸腺切除的术前处理，,或MG危象。,免疫球蛋白(intravenous immunoglobulins)：用于MG危象。0.4g/(kgd)静脉滴注，连用5天。,胸腺切除(thymectomy)：适用于全身型MG。,危象的处理,立即气管切开，人工呼吸器辅助呼吸,鉴别危象的类型，采取相应的措施,甲基强的松龙冲击疗法。也可应用环磷酰胺或血浆置换,防止肺部并发症,保证营养，防止水电解质和酸碱平衡紊乱,危象的处理,肌无力危象：抗胆碱酯酶药量不足引起，注射腾喜龙后症状减轻。,常见于有肺部感染和胸腺切除术后的患者,停用抗胆碱酯酶药，使运动终板得到休息，增加AChR对ACh的敏感性,维持呼吸功能，预防及控制感染,危象的处理,胆碱能危象：抗胆碱酯酶药过量。,表现为肌无力加重，出现肌束震颤和毒蕈碱样反应,腾喜龙试验：症状加重,停用该药，重新调整剂量，或改用其他疗法,危象的处理,反拗危象：,抗胆碱酯酶药不敏感。,腾喜龙试验无反应,停用该药，输液维持，可改用其他疗法,参考文献,神经病学（第四版）,临床神经病学（英文原版）,实用神经病学（史玉泉编）,教学后记,在课堂上列举病例，并结合实验演示，对加深学生的感官认识，提高学习兴趣有重要意义。,