《肌肉疾病》(2)ppt课件

1、肌肉疾病华山医院神经内科卢家红概述骨骼肌组成肌纤维类型I型纤维慢收缩纤维II型纤维快收缩纤维ATPase pH 9.4 stain “Checkerboard pattern oftype I Lightand II Darkfibers 神经肌肉接头NMJ运动单位肌肉疾病分类肌肉本身通道病肌营养不良炎症性肌病代谢性肌病先天性肌病神经肌肉接头突触前膜病变LES突触间隙病变有机磷中毒突触后膜病变MG肌肉疾病特点临床特点无力：近端、对称无力萎缩觉得：正常腱反射：明显无力区域反射减退肌肉疾病特点肌电图波幅低、多相短棘波纤颤波、正尖波活动其他实验室检查血清CPKCK高肌肉活检fiber、connect

2、ive tissue肌营养不良muscular dystrophyMuscular dystrophy refers to a group of genetic diseases characterized by progressive weakness and degeneration of the skeletal muscles which control movement. The major forms of MD include Duchenne, Becker, limb-girdle, facioscapulohumeral, oculopharyngeal, distal a

3、nd Emery-Dreifuss. Duchenne is the most common form of MD affecting children. MD can affect people of all ages. Although some forms first become apparent in infancy or childhood, others may not appear until middle age or later. 病因FSHD?病理坏死、再生、大小不均、核内移等NADH、HEnormalDMDDystrophin免疫染色BMD临床表现-分型 DMD/BMD

4、假肥大型肌营养不良性联 FSHD面肩肱型肌营养不良常显 DM强直性肌营养不良常显 LGMD肢带型肌营养不良常显、常隐 CMD先天性肌营养不良常隐 OPMD眼咽型肌营养不良常显 EDMD艾德肌营养不良性联 DD远端肌营养不良-远端肌病常显、常隐特征性病症和体征假肥大型鸭步Gowers景象翼状肩假肥大足跟着地困难肢带型面肩肱型蝠翼、衣架CPK、LDH、ALT、AST升高DMD、BMD肌电图示肌源性损害实验室检查基因检测Chamberlian多重PCR，9对引物分别只能检测基因缺失2/3，另1/3点突变多为研讨检测 1 2 3 4 51 myositis2 LGMD3 normal4 DMD5 DM

5、Ddystrophin诊断和鉴别诊断 年龄、性别 病程 无力分布 肌酶和肌电图 基因、病理组织病理、免疫组化 肢带型肌营养不良 运动神经元病SMA 多发性肌炎运动神经元病SMA多肌炎治疗 以支持治疗为主 治疗进展和展望 强的松DMD临床研讨小组1.5mg/kg/d、Brooke 0.75mg/kg/d、Dubowitz用10天休10或20天假日疗法 成肌细胞移植Dys缺陷鼠 基因治疗基因大 氨基糖甙类药物治疗影响终止密码子 干细胞治疗 上调Utrophin同源蛋白重症肌无力myasthenia gravisMyasthenia gravis is a chronic autoimmune di

6、sease characterized by weakness of the skeletal muscles. The hallmark of myasthenia gravis is muscle weakness that increases during periods of activity and improves after periods of rest. Muscles that control eye and eyelid movements, facial expression, chewing, talking, and swallowing are often, bu

7、t not always, involved. The muscles that control breathing and neck and limb movements may also be affected. Myasthenia gravis is caused by a defect in the transmission of nerve impulses to muscles. In myasthenia gravis, antibodies produced by the bodys own immune system block, alter, or destroy the

8、 receptors for acetylcholine. blockdestroy病因与发病机制本身免疫性疾病anti-AChR antibody is found in approximately 80-90% of patients with MG presence of associated autoimmune disorders in patients suffering from MG infants born to myasthenic mothers can develop a transient myasthenia-like syndrome. Patients with

9、 MG will have a therapeutic response to various immunomodulating therapies active transfer experiments passive transfer experiments MG can be considered a B cell mediated disease, as antibodies (a B cell product) against AChR are responsible for the disease. However, the importance of T cells in pat

10、hogenesis of MG is becoming increasingly apparent. The thymus is the central organ in T cell mediated immunity, and thymic abnormalities such as thymic hyperplasia or thymoma are well recognized in myasthenic patients (90%)病理临床表现 发病年龄女20-30岁、男40-50岁、儿童 动摇晨轻暮重、疲劳加重、休憩缓解 累及骨骼肌颅神经支配肌、脊神经支配肌 首发眼外肌临床分型单纯

11、眼肌型延髓肌型全身肌无力型脊髓肌无力型对称、近端肌萎缩型儿童重症肌无力、新生儿重症肌无力 改良Osserman分型 、a、b、见表 美国重症肌无力基金会MGFA分型 、a、b、a、b、a、b、 国内常用分型 单纯眼肌、延髓肌型、脊髓肌型、全身型、肌萎缩型IOcular myastheniaIIaMild generalized myasthenia with slow progression, no crises, drug-responsiveIIbModerately severe generalized myasthenia, severe skeletal and bulbar inv

12、olvement but no crises, drug response less than satisfactoryIIIAcute fulminant myasthenia, rapid progression of severe symptoms with respiratory crises and poor drug response, high incidence of thymoma, high mortalityIVLate severe myasthenia, symptoms same as III, but resulting from steady progression over 2 years from class I to class II危象呼吸肌无力、麻木不能维持正常通气功能的危急情况肌无力危象疾病开展、感染、药物运用不当胆碱能危象目前以免疫治疗为主，少见反拗性危象实验室检查70%-80%病人AChR抗体阳性，眼肌型阳性率低 部分SNMG中可测到MuSK抗体合并甲亢者可有T3、T4增高胸腺CT示胸腺增生60%-75%或胸腺瘤(10%-15% )RNS低频反复电刺激3Hz