神经病学课件：重症肌无力

1、1 Myasthenia Gravis 重症肌无力重症肌无力 2 Outline lBackground lAnatomy lPathophysiology lEpidemiology lClinical Presentation lDiagnosis of MG lTherapy For MG lDiagnosis of MG Crisis lRehabilitation 3 Background lFirst clinical description in 1672 by Thomas Willis lAcquired autoimmune disorder labnormal commu

2、nication between nerves an d muscles. lName from Latin and Greek word lClinically characterized by: lWeakness of skeletal muscles lFatigability on exertion. 4 Anatomy-Neuromuscular Junction (NMJ) Neuromuscular Junction (NMJ) Components: Presynaptic membrane Postsynaptic membrane Synaptic cleft The A

3、cetylcholine receptor (AChR) is a sodium channel that opens when bound by ACh There is a partial depolarization of the postsynaptic membrane and this causes an excit atory postsynaptic potential (EPSP) If enough sodium channels open and a threshold potential is reached, a muscle action potential is

4、generated in the postsynaptic membrane 5 Anatomy-thymus gland the thymus gland may give incorrect instructi ons to developing immune cells, ultimately re sulting in autoimmunity and the production of the acetylcholine receptor antibodies, thereb y setting the stage for the attack on neuromu scular t

5、ransmission. 6 Pathology thymus 15% of MG patients have thymoma of the ly mphoepithelial type 70% have lymphoid hyperplasia of the thym us：numerous germinal centers 7 Pathology muscles contain lymphorrhages thymoma with MG loss of synaptic folds and widened clefts 8 Pathophysiology lIn MG, antibodie

6、s are directe d toward the acetylcholine re ceptor at the neuromuscular j unction of skeletal muscles lResults in: lDecreased number of nicotinic ace tylcholine receptors at the motor e nd-plate lReduced postsynaptic membrane f olds lWidened synaptic cleft 9 lFrequency lAnnual incidence in US- 2/1,0

7、00,000 (E) lWorldwide prevalence 1/10,000 (D) lMortality/morbidity lRecent decrease in mortality rate due to advances in treatment l3-4% (as high as 30-40%) lRisk factors lAge 40 lShort history of disease lThymoma lSex lF-M (6:4) lMean age of onset (M-42, F-28) lIncidence peaks- M- 6-7th decade F- 3

8、rd decade 10 nOcular and generalized MG nModified osserman classification nBurnt-out stage : after 15-20 years, untreat ed weakness becomes fixed, and atrophic 11 nPtosis(dropping eyelid) asymmetric, fatigues with upgaze nDiplopia(double vision) most common involved M R(medial rectus ) 12 n Dysarthr

9、ia n Dysphagia n Dysphonia n Masticatory weakness n jaw closure jaw open n Commonly proximal, symmetric n Arms more affected than legs nExertional dyspnea nTachypnea nRespiratory failure (Myasthenic crisis) nNeck flexion nNeck extension 13 nmuscle weakness is: npainless nfluctuates and progressively

10、 worsens over course of day nworsens with prolonged use of affected muscles (i.e. fatiguabl e) nvariable distribution and severity, occasionally very asymmetr ic ndistal weakness less common and leg weakness often later (r ule out steroid myopathy in treated patient). nmost commonly affected muscle

11、groups: jaw closure, neck fle xors, deltoids, triceps nmay involve respiratory muscles nbowel and bladder function preserved 14 nmuscle weakness depending on distribution nno muscle shrinking (atrophy) :muscular wasting is f ound in about 10% of patients nthe reflexes are preserved, even in muscles

12、that are weak nFasciculations do not occur, sensation is normal 15 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 disease 4.Acute severe

13、generalized disease with respiratory failure. 5. Myasthenic crisis with respiratory failure(progression wit hin 2 year). 16 1.Neonatal MG：12% of infants born to myasth enic mothers begin in the first 48 hours and may last several days or weeks 2. Congenital MG：rarely 3. Drug Induced MG: Penicillamin

14、e Gentamicin disappear when drug is discontinued 17 nRepetitive nerve sti mulation nSingle fiber electro myography Normal SFEMG Increased jitter: MG p atient 18 1.Antibodies to AChR generalized MG :80% iocular MG:50% MG and thymoma:98-100% The titer does not match the severity of symptoms 2. Anti-mu

15、scle specific receptor tyrosine kinase (MuSK) antibodies Used if MG suspected, patient seronegative Present in 4050% of seronegative patients with gen eralized MG; absent in ocular MG 19 nRadiographs of the chest provide evide nce of thymoma in a bout 15% of patients, especially in those o lder than

16、 40 years. nCT of the mediastin um demonstrates all but microscopic thy momas. thymoma hyperplasia of the thymus 20 1.History and physical examination： Jolly test 2.Diagnostic test of neostigmine or Tensilon 3.Laboratory test nBreathing nSeeing nSwallowing nChewing nWalking nUsing your arms or hands

17、 nHolding up your head 21 Tensilon test: Edrophonium hydrochloride, a short-acting anticholinesterase given intraven ously (1 mg) temporarily reverses weakness over a period of several minutes. Neostigmine test: 1.5 to 2.0 mg of the drug an d atropine sulfate, 0.4 mg, are given intramus cularly. Obj

18、ective improvement in muscular p ower is recorded at 20-minute intervals up to 2 hours. 22 nA: Severe ptosis of the lid s. nB: Same patient 1 minute after intravenous injection of edrophonium (10 mg). (From Rowland LP, Hoef er PFR, Aranow H Jr. My asthenic syndromes. Res Publ Assoc Res Nerv Me nt Di

19、s 1961;38; with perm ission.) 23 ndiseases accompanied by weakness of muscle muscular dystrophies, amyotrophic lateral sclerosis nother disorders of neuromuscular transmission b otulinum intoxication Lambert-Eaton syndrome nDenervating disorders motor neuron disease or peripheral neuropathy 24 nsymp

20、tomatic treatments Anticholinesterase drug(Mestinon) inhibit acetylcholinesterase and increase availability of th e acetylcholine to act on the AChRs. Plasmapheresis remove Ach-R antibodies of serum Intravenous immunoglobulin interfere the function of Ach-R antibodies Indication preparation for thym

21、ectomy exacerbation situations 25 altering course treatments thymectomy steroids:prednison If a patient is still seriously disabled after thymectomy, I ntravenous immunoglobulin NOT AVAILABLE other immunosuppressive drugs(CTX, MTX,azathioprine) assists in lowering the dose of prednisone and improve t he effect 26 ndefined as the need for assisted ventilatio n narises in about 10% of myas