1、Myasthenia Gravis重重 症症 肌肌 无无 力力(see P341346)YAN YONGDep. of Neurology, the 1st Hospital, Chongqing University of Medical Science The myasthenia gravismyasthenia gravis (MG，重症肌无力) is a neuromuscular-transmission disorderseuromuscular-transmission disorders神经肌肉传递障碍, and an acquired immunologicalan acq
2、uired immunological获得性免疫disorderdisorder (probably immune mediated), of unknown cause, in which antibodies are directed against the postsynaptic突触后突触后 acetylcholine 乙酰胆碱receptor (AChR). This results in weakness and fatigability of skeletal muscle groups; the most commonly affected muscles are the pr
3、oximal limbs肢体近端肢体近端 and ocular and bulbar眼和延髓muscles. Myopathic disorders肌病 includesskeletal muscles by gene, Inflammation, Metabolic or toxicity:Muscular dystrophies肌营养不良:Duchenne肌营养不良，BeckersCongenital myopathies先天性肌病:mitochondrial肌病、肌管肌病等Myotonic disorders 肌强直Inflammatory myopathies炎症性肌病AIDSMeta
4、bolic myopathies：Hypo-hyperkalemia,osteomalacia等Endocrine myopathies：Hyper-or hypothyroidism等Alcoholic myopathiesDrug-induced myopathies：corticosteroids, certain -blockers,chloroquine,clofibrate,emetrine,colchicine,and so on.Myoglobinuria 肌红蛋白尿: by muscle injury or ischemia,Neuromuscular junction: M
5、G,lambert-Eaton syndrome A. How do occur the MGHow do occur the MG? In motor nerves, when the stimulus reaches the end of the nerve terminal acetylcholine(Ach) is released from vesicles via voltage-gated calcium channels. The Ach crosses the synaptic cheft and binds AchRs on thepostsynaptic muscle e
6、nd-plate membrane. This results indepolarization and subsequentcontraction of muscle. The Ach is then broken down by acetyl-cholinesterase,which is bound to the basal lamina in the synaptic folds. A. How do occur the MGHow do occur the MG?The MG results from the Ach decreased by acetylcholinesterase
7、 overdose or the sensitive reduced ofthe Ach receptors. B. Clinical manifestation 1.MG can occur at any age. There are two peaks of incidence for MG, split by age and sex: a.Young women(2040 yrs),who tend to have anacute,severely fluctuating,more generalized condition,with increased association with
8、 HLA-B8 and HLA-DR3.and more common in females than males. There is an associated abnormality of the thymus胸腺胸腺 in patients with MG. Thymic hyperplasic增生增生 is found in 80% of patients below the age of 40 years. b.Older men(40-75yrs),who tend to have a more oculobulbar presentation and thymoma, and m
9、ore common in males than females. In 10%20% of all patients with myasthenia gravis, a thymic tumor胸腺肿瘤 (thymoma) is found, the incidence increasing with age. In patients with thymoma, antibodies to striated 横纹肌抗体muscle may also be found. 2. Clinical features The clinical features of MG is characteri
10、zed by fluctuating weakness (mild at morning and severe at evening晨轻暮重 or which relieve after rest and worse after exercise or action) and easy fatigability易疲劳 of voluntary muscles. The easy fatigability cause fluctuating weakness波动性无力. The most commonly affected muscles are the proximal limbs肢体近端肢体
11、近端 and cranial allocating muscles such as ocular and bulbar. MG可累及全身骨骼肌,但最常累及的是四肢近端肌群和脑神经支配的肌肉(如眼外肌和延髓肌肉). Fatigability test 疲劳试验疲劳试验 Fatigability can be demonstrated by exercisingaffected muscles,e.g. let patients look upwards or looking at ceiling for a few seconds the ptosis睑下垂睑下垂will become appa
12、rent. Similar maneuver手法手法 can be carried out for the proximal limb muscles,such as looking at lateral,vertical gaze or reading for 23 mins or moving limbs . 3.Presenting symptoms in MGSymptoms percentage of patientsDiplopia复视复视 41Ptosis眼睑下垂眼睑下垂 25Dysarthria构音困难构音困难 16Lower extremity weakness 13Gene
13、ralized weakness 11Dysphagia吞咽困难吞咽困难 10Upper extremity weakness 7Masticatory weakness咀嚼无力咀嚼无力 7Herrmann CJ. West J Med 1985:142:797 C. Clinic classification(P343).Ocular myasthenia(15%20%) 眼肌型MGA. Mild generalized myasthenia with slow progression; no crisis;drug-responsive(30%)缓慢进展的轻度全身型,无危象B. Moder
14、ately severe generalized myasthenia ;severe skeletal and bulbar involvement but no crisis; drug response less than satisfactory(25%)中重度全身型,严重累及骨骼肌和延髓肌但无危象,药物治疗不满意. Acute fulminating myasthenia; rapid progression of severe symptoms with respiratory crisis and poor drug response; high incidence of thy
15、moma;high mortality (15%)急性爆发性MG,快速进展伴呼吸危象,药物效差,高胸腺瘤死亡率.Late severe myasthenia; symptoms same as , but resulting from steady progression over 2 yr from class to (10%).晚发型重症MG,症状同,但从但从到到稳缓进超2年 D. Diagnosis In patients who present with changeable (fluctuating) diplopia, typical myasthenic facies, uneq
16、ually drooping eyelids, difficulty in speaking or swallowing, or weakness of the limbs -the diagnosis can hardly be overlooked. If those symptoms are at first mild and inconstant, you can do fatigability test for patients . If the diagnosis remains in doubt, the measurement of specific examinations
17、are necessary. Diagnostic test 1.Repeating nerve electric stimulation (RNES 重复电刺激): Impaired neuromuscular transmission can bedetected electrophysiologically by a decremental response of muscle to repetitive supramaximal stimulation(at 2 or 3 Hz) of its motor nerve, but normal findings do not exclud
18、e the diagnosis. 2.Single fiber electromyography(SFEMG单纤维肌电图) shows increased variability in the interval between two muscle fiber action potential from the same motor unit in clinically weak muscles. 3.Acetylcholine receptor antibody: 乙酰胆碱受体抗体乙酰胆碱受体抗体 The highly specific AchR antibody is present in
19、 the serum of up to 80% -90% of patients with generalized MG.4.Thymus胸腺胸腺 imaging: It is always essential to image the chest with X-ray, CT or MRI, for the presence of thymic hyperplasia胸腺增生胸腺增生 or thymoma胸腺肿瘤胸腺肿瘤, as removal of a hyperplasic thymus improves the condition in many patients. 5.Neostig
20、mine新斯的明新斯的明 test: 1.0mg of neostigmine can be given intramuscularly ,with a response that lasts for about 2 hours. 6.Tensilon(edrophonium腾喜龙腾喜龙) test: Tensilon is given iv.in a dose of 10mg(1 ml), of which 2 mg is given initially and the remaining 8 mg about 30 seconds later if the test dose is wel
21、l tolerated. In MG,there is an obvious improvement in the strength of weak muscles that lasts for about 5 minutes. Only mild muscarinic毒覃碱毒覃碱 effects(pallor, nausea, vomiting,bowel, activation, sweating, salivation) Differential diagnosisDifferential diagnosis1.Lambert-Eatom syndrome肌无力综合症肌无力综合症To r
22、epetitive supramaximal stimulation (at 10 Hz) of its motor nerve,with cancer usually2. Ocular dystrophiesdystrophies眼肌型肌营养不良眼肌型肌营养不良 prognostic worse ,no fluctuating weakness, Tensilon and fatigability test(-)3.Polymyositis3.Polymyositis多发性肌炎多发性肌炎 It is often associated with muscle pain, no fluctuat
23、ing weakness.the serum CK is generally elevated. E. Treatment1.Anticholinesterase drugs抗胆碱酯酶药物抗胆碱酯酶药物AChD: Pyridostigmine bromide吡啶斯的明吡啶斯的明 at doses individually determined but usually between 60mg 120mg, tidqid. Small doses of atropine may attenuate side effectssuch as bowel hypermotility or hypers
24、alivation. Mysuran and neostigmine bromide has not be used now.2.Corticosteroids: Corticosteroids provide the mainstay of immuno-suppressive treatment.They succeed in 70% of patients, but must be increased slowly.Methylprednisolone-1000mg,iv.qd.35d;Prednisolone-12mg/kg(6080mg), po.qd/ morning;2weeks
25、, then gradually reduced, sustained over 1 year.Azathioprine硫唑嘌呤硫唑嘌呤:23mg/kg/d.Cyclosporine A环孢素环孢素A: 6mg.kg.d x12mons3.Plasmapheresis: It is sometimes used especially during an acute exacerbation or when there is respiratory involvement.4.Thymectomy: Its beneficial effect 70% for thymoma or hyperpl
26、asic thymus,may not be evident immediately.5.Medications That impair neuromuscular transmission should be avoided such as Quinine,Aminoglycosides氨基糖甙类氨基糖甙类，Phenobarbital苯巴比妥苯巴比妥, Diazepam安定安定,and so on. F. Crisis Crisis危象危象A rapid deterioration of the MGitself, can bring the respiratory failure呼吸衰竭呼
27、吸衰竭 and severe quadriparesis四肢瘫痪四肢瘫痪. 1.Myasthenic crisis肌无力危象肌无力危象: It is a most common type, anticholinesterase drugs (AChD) are not enough. We have to increase the AChD dose if the edrophonium腾喜龙腾喜龙 testis positive .2.Cholinergic crisis胆碱能危象胆碱能危象: It is often excessof the AChD.Overmedication can
28、led to increasedweakness. Stopping AChD immediately,with themechanical ventilation机械通气机械通气,then gradually modifythe doses of AChD when all AChD clear out from the body.3. Brittle crisis反拗性危象反拗性危象: The response to AChD is poor , of unknown cause. Stopping AChD immediately,with the mechanical ventilat
29、ion,thengradually modify the doses of AChD if responsewell to AChD in course of time. G. Prognosis Most patients can be managed successfully with drug treatment. The disease may have a fatal outcome because of respiratory complications such as aspiration pneumonia. A typical case A woman, 32yrs old.
30、 She was admitted in hospital with symmetrically weakness of limbs for a month, the weakness is mild at morning and severe at evening, and the more severe on the proximal limbs. She has had diplopia for 4 d and mild dysphagia 2 days.Its normal sphincter. The examination of NS showed that: wakefulnes
31、s, a litter dysarthria,mild dysphagia.The motor abnormal of bilateral eyeball and diplopia,the palsy of bilateral palata. There are low-grade of muscle tone and decreased tendon reflex on four limbs. The proximal muscular strength of limbs is 4 grade and 5 grade on distal. The pathologic reflexes ar
32、e deficit. There are normal sensory. 对此患者，最可能的诊断是什么？ 提出应该完成那些主要的检查？应主要与哪些疾病鉴别？治疗过程中会出现那些危险？ Key points 1.Classification of sensory2. Sensory pathway(痛温觉、触觉和深感觉传导痛温觉、触觉和深感觉传导3种通路种通路)3. The location of sensory disorders 4. Location and lamination of sensory pathways in the spinal cord5. The comprise o
33、f motor system重点是锥体系统重点是锥体系统6. The feature of lower/upper neuron disorders 7.The location of motor systemic disorders;8. The difference diagnosis between UMN and LMN paralysis.9. Reflex：kinds and clinical significance, reflex arc.10. Where are the common sits of the lesions of MS? CNS or PNS?11. Wha
34、t are the classic features of MS?12. What are the most effective investigations for MS?13. How do treat to MS?14. Albuminocytologic dissociation in CSF蛋白蛋白-细胞细胞分离分离15. the main clinical features of GBS (AIDP) :16. What changes of electrophysiologic in the early stage of GBS (AIDP)?17. How do differe
35、ntial diagnosis with other LMNP?18. What are the main clinical features of MG? fluctuating weakness (mild at morning and severe at evening 晨轻暮重 or which relive after rest and worse after exercise or action) and easy fatigability易疲劳 of voluntary muscles (fatigability test). The most commonly affected muscles are the proximal limbs肢体近端 and cranial allocating muscles such as ocular and bulbar19. How do diagnose the MG(clinical features and diagnostic test)?20. What is the myasthenic crisis?21. What is the cholinergic crisis?22. How do treat the MG?Thank you ! !Thank you ! !
