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1、1,Myasthenia Gravis重症肌无力,2,Outline,BackgroundAnatomyPathophysiologyEpidemiologyClinical PresentationDiagnosis of MGTherapy For MGDiagnosis of MG CrisisRehabilitation,3,Background,First clinical description in 1672 by Thomas WillisAcquired autoimmune disorderabnormal communication between nerves and
2、muscles.Name from Latin and Greek wordClinically characterized by:Weakness of skeletal muscles Fatigability on exertion.,4,Anatomy-Neuromuscular Junction (NMJ),Neuromuscular Junction (NMJ)Components:Presynaptic membranePostsynaptic membrane Synaptic cleft,The Acetylcholine receptor (AChR) is a sodiu
3、m channel that opens when bound by AChThere is a partial depolarization of the postsynaptic membrane and this causes an excitatory postsynaptic potential (EPSP)If enough sodium channels open and a threshold potential is reached, a muscle action potential is generated in the postsynaptic membrane,5,A
4、natomy-thymus gland,the thymus gland may give incorrect instructions to developing immune cells, ultimately resulting in autoimmunity and the production of the acetylcholine receptor antibodies, thereby setting the stage for the attack on neuromuscular transmission.,6,Pathology thymus,15% of MG pati
5、ents have thymoma of the lymphoepithelial type 70% have lymphoid hyperplasia of the thymus：numerous germinal centers,7,Pathology,muscles contain lymphorrhages,thymoma with MG,loss of synaptic folds and widened clefts,8,Pathophysiology,In MG, antibodies are directed toward the acetylcholine receptor
6、at the neuromuscular junction of skeletal musclesResults in:Decreased number of nicotinic acetylcholine receptors at the motor end-plateReduced postsynaptic membrane foldsWidened synaptic cleft,9,Epidemiology,FrequencyAnnual incidence in US- 2/1,000,000 (E)Worldwide prevalence 1/10,000 (D)Mortality/
7、morbidityRecent decrease in mortality rate due to advances in treatment3-4% (as high as 30-40%)Risk factors Age 40Short history of diseaseThymomaSexF-M (6:4) Mean age of onset (M-42, F-28)Incidence peaks- M- 6-7th decade F- 3rd decade,10,Clinical presentation,Ocular and generalized MG Modified osser
8、man classification Burnt-out stage : after 15-20 years, untreated weakness becomes fixed, and atrophic,11,Ocular,Ptosis(dropping eyelid) asymmetric, fatigues with upgazeDiplopia(double vision) most common involved MR(medial rectus ),12,Bulbar,Dysarthria Dysphagia Dysphonia Masticatory weakness jaw c
9、losure jaw open,Limbs,Commonly proximal, symmetric Arms more affected than legs,Respiratory muscles,Exertional dyspnea TachypneaRespiratory failure (Myasthenic crisis),Axial muscles,Neck flexionNeck extension,13,Clinical presentation,muscle weakness is:painlessfluctuates and progressively worsens ov
10、er course of dayworsens with prolonged use of affected muscles (i.e. fatiguable)variable distribution and severity, occasionally very asymmetricdistal weakness less common and leg weakness often later (rule out steroid myopathy in treated patient).most commonly affected muscle groups: jaw closure, n
11、eck flexors, deltoids, tricepsmay involve respiratory musclesbowel and bladder function preserved,14,Neurologic Examination,muscle weakness depending on distributionno muscle shrinking (atrophy) :muscular wasting is found in about 10% of patients the reflexes are preserved, even in muscles that are
12、weak Fasciculations do not occur, sensation is normal,15,Osserman Classification of MG,Based on the severity of the disease 1.Ocular myasthenia, where disease is confined to ocular muscles.(focal disease)2.Generalized myasthenia gravis of mild (a) or moderate (b) intensity.3.Severe generalized disea
13、se 4.Acute severe generalized disease with respiratory failure.5. Myasthenic crisis with respiratory failure(progression within 2 year).,16,Other types of MG,1.Neonatal MG：12% of infants born to myasthenic mothers begin in the first 48 hours and may last several days or weeks 2. Congenital MG：rarely
14、 3. Drug Induced MG: Penicillamine Gentamicin disappear when drug is discontinued,17,Laboratory test,Repetitive nerve stimulationSingle fiber electromyography,18,Laboratory test,1.Antibodies to AChR generalized MG :80%iocular MG:50%MG and thymoma:98-100%The titer does not match the severity of sympt
15、oms 2. Anti-muscle specific receptor tyrosine kinase (MuSK) antibodies Used if MG suspected, patient seronegativePresent in 4050% of seronegative patients with generalized MG; absent in ocular MG,19,Other test,Radiographs of the chest provide evidence of thymoma in about 15% of patients, especially
16、in those older than 40 years. CT of the mediastinum demonstrates all but microscopic thymomas.,thymoma,hyperplasia of the thymus,20,DIAGNOSIS OF MG,1.History and physical examination：Jolly test2.Diagnostic test of neostigmine orTensilon 3.Laboratory test,BreathingSeeingSwallowingChewingWalkingUsing
17、your arms or handsHolding up your head,21,Tensilon test: Edrophonium hydrochloride, a short-acting anticholinesterase given intravenously (1 mg)temporarily reverses weakness over a period of several minutes. Neostigmine test: 1.5 to 2.0 mg of the drug and atropine sulfate, 0.4 mg, are given intramus
18、cularly. Objective improvement in muscular power is recorded at 20-minute intervals up to 2 hours.,22,Tensilon test & Neostigmine test,A: Severe ptosis of the lids. B: Same patient 1 minute after intravenous injection of edrophonium (10 mg). (From Rowland LP, Hoefer PFR, Aranow H Jr. Myasthenic synd
19、romes. Res Publ Assoc Res Nerv Ment Dis 1961;38; with permission.),23,Differential diagnosis,diseases accompanied by weakness of muscle muscular dystrophies, amyotrophic lateral sclerosis other disorders of neuromuscular transmission botulinum intoxication Lambert-Eaton syndrome Denervating disorder
20、s motor neuron disease or peripheral neuropathy,24,Therapy For MG,symptomatic treatments Anticholinesterase drug(Mestinon) inhibit acetylcholinesterase and increase availability of the acetylcholine to act on the AChRs. Plasmapheresis remove Ach-R antibodies of serum Intravenous immunoglobulin inter
21、fere the function of Ach-R antibodies,Indicationpreparation for thymectomy exacerbation situations,25,altering course treatmentsthymectomy steroids:prednison If a patient is still seriously disabled after thymectomy, Intravenous immunoglobulin NOT AVAILABLEother immunosuppressive drugs(CTX, MTX,azat
22、hioprine) assists in lowering the dose of prednisone and improve the effect,Therapy For MG,26,Myasthenic Gravis crisis,defined as the need for assisted ventilation arises in about 10% of myasthenic patients more likely to occur in patients with dysarthria, dysphagia, and documented respiratory muscle weakness may also occur in other patients after respiratory infection or major surgery,27,Diagnosis of MG Crisis,Myasthenic crisis acetylcholine insufficiency Cholinergic crisis acetylcholine overmuchBrittle crisis non susceptivity to acetylcholine,28,29,Thanks！,
