《肌肉疾病》(2)ppt課件

1、肌肉疾病華山醫(yī)院神經內科盧家紅概述骨骼肌組成肌纖維類型I型纖維慢收縮纖維II型纖維快收縮纖維ATPase pH 9.4 stain “Checkerboard pattern oftype I Lightand II Darkfibers 神經肌肉接頭NMJ運動單位肌肉疾病分類肌肉本身通道病肌營養(yǎng)不良炎癥性肌病代謝性肌病先天性肌病神經肌肉接頭突觸前膜病變LES突觸間隙病變有機磷中毒突觸后膜病變MG肌肉疾病特點臨床特點無力：近端、對稱無力萎縮覺得：正常腱反射：明顯無力區(qū)域反射減退肌肉疾病特點肌電圖波幅低、多相短棘波纖顫波、正尖波活動其他實驗室檢查血清CPKCK高肌肉活檢fiber、connect

2、ive tissue肌營養(yǎng)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?病理壞死、再生、大小不均、核內移等NADH、HEnormalDMDDystrophin免疫染色BMD臨床表現-分型 DMD/BMD

4、假肥大型肌營養(yǎng)不良性聯(lián) FSHD面肩肱型肌營養(yǎng)不良常顯 DM強直性肌營養(yǎng)不良常顯 LGMD肢帶型肌營養(yǎng)不良常顯、常隱 CMD先天性肌營養(yǎng)不良常隱 OPMD眼咽型肌營養(yǎng)不良常顯 EDMD艾德肌營養(yǎng)不良性聯(lián) DD遠端肌營養(yǎng)不良-遠端肌病常顯、常隱特征性病癥和體征假肥大型鴨步Gowers景象翼狀肩假肥大足跟著地困難肢帶型面肩肱型蝠翼、衣架CPK、LDH、ALT、AST升高DMD、BMD肌電圖示肌源性損害實驗室檢查基因檢測Chamberlian多重PCR，9對引物分別只能檢測基因缺失2/3，另1/3點突變多為研討檢測 1 2 3 4 51 myositis2 LGMD3 normal4 DMD5 DM

5、Ddystrophin診斷和鑒別診斷 年齡、性別 病程 無力分布 肌酶和肌電圖 基因、病理組織病理、免疫組化 肢帶型肌營養(yǎng)不良 運動神經元病SMA 多發(fā)性肌炎運動神經元病SMA多肌炎治療 以支持治療為主 治療進展和展望 強的松DMD臨床研討小組1.5mg/kg/d、Brooke 0.75mg/kg/d、Dubowitz用10天休10或20天假日療法 成肌細胞移植Dys缺陷鼠 基因治療基因大 氨基糖甙類藥物治療影響終止密碼子 干細胞治療 上調Utrophin同源蛋白重癥肌無力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病因與發(fā)病機制本身免疫性疾病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%)病理臨床表現 發(fā)病年齡女20-30歲、男40-50歲、兒童 動搖晨輕暮重、疲勞加重、休憩緩解 累及骨骼肌顱神經支配肌、脊神經支配肌 首發(fā)眼外肌臨床分型單純

11、眼肌型延髓肌型全身肌無力型脊髓肌無力型對稱、近端肌萎縮型兒童重癥肌無力、新生兒重癥肌無力 改良Osserman分型 、a、b、見表 美國重癥肌無力基金會MGFA分型 、a、b、a、b、a、b、 國內常用分型 單純眼肌、延髓肌型、脊髓肌型、全身型、肌萎縮型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危象呼吸肌無力、麻木不能維持正常通氣功能的危急情況肌無力危象疾病開展、感染、藥物運用不當膽堿能危象目前以免疫治療為主，少見反拗性危象實驗室檢查70%-80%病人AChR抗體陽性，眼肌型陽性率低 部分SNMG中可測到MuSK抗體合并甲亢者可有T3、T4增高胸腺CT示胸腺增生60%-75%或胸腺瘤(10%-15% )RNS低頻反復電刺激3Hz