神經(jīng)肌接頭病-重癥肌無力Lambert-Eaton-綜合征課件

神經(jīng)肌接頭病-重癥肌無力Lambert-Eaton綜合征神經(jīng)肌接頭病-重癥肌無力Lambert-Eaton綜合征1NeuromuscularDisorders

DefinitionThediseasesofneuromuscularjunction(NMJ)describesasetsofdiseasecausedbycirculatingfactorssuchasneurotoxinsorautoantibodieswhichbindwithhighaffinitytospecificproteinsattheNMJanddisturbtheneuromusculartransmission.NeuromuscularDisorders

2NeuromusuclarJunction(NMJ)

PhysiologythenerveAPreachesthenerveterminalwhichinflatedandwithoutmyelinandleadstotheopeningofcalciumchannelandreleaseofAChintothesynapticcleftbyexocytosis.NeuromusuclarJunction(NMJ)

3NeuromusuclarJunction(NMJ)

Physiology1/3oftheAChdiffusesrapidlytothepostsynapticmembraneandbindstotheAChRs,leadingtoopeningoftheAChR-associatedcationchannelanddepolarizationcalledtheend-platepotential(EPP).IftheEPPexceedscertainthreshold,voltagegatedsodiumchannelatthepostsynapticmembraneareopened.Thisgeneratesthemuscleactionpotential(CMAP)thatpropagatesalongthemusclefiberandactivatescontraction.NeuromusuclarJunction(NMJ)

4NeuromusuclarJunction(NMJ)

PhysiologyAnother1/3oftheAChishydrolyzedbycholinesterase(ChE).Theremaining1/3oftheAChisrecapturedbythepresynapticmembrane.NeuromusuclarJunction(NMJ)

5重癥肌無力(MyastheniaGravis,MG)概念病因及發(fā)病機(jī)制病理臨床表現(xiàn)診斷及鑒別診斷治療重癥肌無力(MyastheniaGravis,MG)概6Myastheniagravis(MG)

DefinitionMGwasoriginatedfromLatin,meaningverysevereweakness.acquiredMGisanantibodyandcomplement-mediated,Tcell-dependentautoimmunediseaseleadingtoadefectinneuromusculartransmission.Myastheniagravis(MG)

Definit7Myastheniagravis(MG)

EpidemiologyItistheprototypicneuromusculardisorderswithanincidenceof80-200permillionandprevalenceabout500permillion.InChina,itisestimatedthat0.6millionpeoplewerediagnosedasMGandmostofthemlivesintheSouthofChina.Ithadbeenalife-threateningdiseasebefore1970’s,thoughnowadaystheincidenceofdeathhasbeengreatlyreducedtoabout0.2%.Myastheniagravis(MG)

Ep8MyastheniaGravis(MG)

EtiologyTheautoimmuneoriginofMGisproposedlongbeforeitwasestablishedin1973bythedirectevidenceprovidedbyPatrickandLindstrom,whohaveimmunizedrabbitwithaffinity-purifiedTorpedoAChRwithCFAandreproducedtheanimalmodelsrepresentinghumanMG(EAMG).TheAChRistheautoantigen.MyastheniaGravis(MG)

Etiolog9MyastheniaGravis(MG)

EtiologyThepresenceofanti-AChRAbscanbedemonstratedin80%-90%ofMGpatients.Thereisa3:1female-maleratioforpatientswhodevelopMGinearlyadultlife.Overall,theabovemakesMGfulfillsthecriteriaforautoimmunediseases.MyastheniaGravis(MG)

Etiolog10MyastheniaGravis(MG)

EtiologyMostofthepatientswithMGhaveabnormalitiesinthethymus,e.g.thymichyperplasticorthymoma.Althoughtheprimaryantiselfeventbeingunclear,thymusappearstobetheplacewhereitinitiates.ThegeneralopinionisthatvirusinfectionorothernonspecificfactorsinvadesthethymusingeneticallypredisposedindividualsleadingtothedevelopmentofMG.MyastheniaGravis(MG)

Etiolog11MyastheniaGravis(MG)

PathologyLymphoidfolliculuscanbeseeninthymus.About10%ofMGpatientshasthymomaofepitheliatype.Lymphorage,definedbyaggregatedlymphoidcellsaroundthebloodvessels,issometimesseeninotherwisenormalmusculatureinMGpatients.MyastheniaGravis(MG)

Patholo12MyastheniaGravis(MG)

PathologyAttheNMJ,grosslysimplifiedpostsynapticfoldswithdepositionofimmune-complexandtheanti-AChRAbsisdemonstratedbyimmunochemicalstudies.Thereisalsoconsiderabledebriswithinthewidenedsynapticcleft.

NormalNMJ、NMJinMGpatients（示意圖）（電鏡）MyastheniaGravis(MG)

Patholo13MyastheniaGravis(MG)

ClinicalManifestationsMGcanariseatanyage,althoughyoungfemalesandoldmalesaremorevulnerabletoit.Precipitatingfactors:concurrentinfection,stress,weariness,menses,pregnancyorparturition.Thediseaseinitiatesinsidiousandfollowsaslowlyprogressivecourse.MyastheniaGravis(MG)

Clinica14MyastheniaGravis(MG)

ClinicalManifestationsClinically,MGfeatureswithfluctuatedmuscularweaknessinintensityduringthedayandeasyfatigability.Typically,theweaknessvariesindistributionandseverityfromdaytoday.Characterizedbyabnormalweakness,whichbeingworseattheendofthedayorafterexertionandtendstoimproveafterrestorAChEtreatment.MyastheniaGravis(MG)

Clinica15MyastheniaGravis(MG)

ClinicalManifestationsTheweaknessoftenbeginswiththelateralorbilateralextra-ocularmuscles,leadingtoasymmetricocularpalsies(e.g.diplopia,strabismic)andptosis.Pupillaryresponsesarenotaffected.MyastheniaGravis(MG)

Clinica16MyastheniaGravis(MG)

ClinicalManifestationsThepatientsmaypresentwithlesswrinkles,amimia,difficultyinclosingtheeyesordisclosingtooth;difficultyinchewingorswallowing,nasalspeech;weaknessoftheneckortheproximalupperlimbs.MyastheniaGravis(MG)

Clinica17MyastheniaGravis(MG)

Crisis—definitionCrisisdescribesarapidlydevelopedweaknessinthebulbarmusclesandrespiratoryinsufficiencythatnecessitatesassistedventilation.ItistheleadingcauseofdeathinpatientswithMG.MyastheniaGravis(MG)

Crisis—18MyastheniaGravis(MG)

Crisis—classificationMyastheniccrisis:abletoreacttoAChEdrugsandbeinghypersensitivetothecurare.Cholinergiccrisis: 1.overmedicationcanleadtoincreased weakness,which,unlikemyasthenicweakness, isunaffectedorenhancedbyintravenous edrophonium. 2.Itmaybeaccompaniedbypallor,sweating, nausea,vomiting,salivation,colic,and diarrhea(muscarinicsyndrome).Brittiecrisis:unresponsivetoAChE.MyastheniaGravis(MG)

Crisis—19MyastheniaGravis(MG)

OssermanClassificationFivesubgroupscanbedefinedamongpatientswithmyasthenia.I.

OcularIIa.MildgeneralizedIIb.ModerategeneralizedIII.ProgressivelysevereIV.latesevereMyastheniaGravis(MG)

Osserma20MyastheniaGravis(MG)

OtherclassificationMGcanalsobesubdividedintoadolescentandadulttype,neonatalMG,congenitalmyasthenia,D-Penicillamineinducedmyasthenia:asimilardisorderinpatientsreceivingpenicillamineforrheumatoidarthritisfrequentlyremitswhenthedrugisdiscontinued.MyastheniaGravis(MG)

Otherc21MyastheniaGravis(MG)

InvestigationRoutineexaminationontheblood,ureaandCSFarenormal.X-raysandCTscansofthechestmayrevealacoexistingthymomainpatientsover40years.MyastheniaGravis(MG)

Investi22MyastheniaGravis(MG)

InvestigationEMG:increaseddecrement(>10%)oftheevokedCMAPuponrepeatedstimuliat3or5Hz.SinglefibermyographyshowsreducedamplitudeofMEPPandincreasedvariability(jitter)ormoreblockadeofimpulses.MyastheniaGravis(MG)

Investi23MyastheniaGravis(MG)

InvestigationTheanti-AChRAbspresentin85-90%ofpatientswithgeneralizedMGandin50%ofpatientswithocularMG,butnotpresentinhealthyindividuals.Whentheanti-AChRAbsareidentified,thediagnosisisestablished.autoantibodiesagainststriatedmuscles.MyastheniaGravis(MG)

Investi24MyastheniaGravis(MG)

Diagnosis疲勞試驗(yàn)（Jolly試驗(yàn)）抗膽堿酯酶藥物試驗(yàn)1.騰喜龍（tensilon）試驗(yàn)2.新斯的明（neostigmine）試驗(yàn)重復(fù)神經(jīng)電刺激AChR抗體滴度測定：特征性意義MyastheniaGravis(MG)

Diagnos25MyastheniaGravis(MG)

Diagnosisedrophoniumin2-3dose(totally10mg)giveni.v.givearapid(within2’)butshort-lived(lessthan5’)improvementinstrengthinmostpatientswithMG.neostigmineof1.5mggiveni.m.improvesmusclestrengthwithin30’andlastsfor2hs.false-positiveandfalse-negativeresultscanoccur.thereisasmallriskofcardiorespiratorycollapse.MyastheniaGravis(MG)

D26MyastheniaGravis(MG)

DiagnosisOncethediagnosishasbeenmade,CTorMRIofthechestshouldbedonetoexcludeanassociatedthymoma.ThyroidfunctionandthyroidAbsshouldbemeasured,becauseoftheincreasedfrequencyofthyroiddisease.MyastheniaGravis(MG)

Di27MyastheniaGravis(MG)

DifferentialdiagnosisThedifferentialdiagnosisofMGiswide.AcquiredMGv.s.congenitalMGand

neurotoxinse.g.botulism,venoms.OcularMG(ofwhomabout50%areAChRAb-negative)v.s.ocularmusculardystrophyandmitochodrialcytopathy.Bulbarmyastheniav.s.brainstemstrokeandmotor-neurondisease(e.g.ALS).MyastheniaGravis(MG)

Diffe28MyastheniaGravis(MG)

DifferentialdiagnosispatientswithgeneralizedweaknessbutarenegativeforAChRAbsv.s.

＊neuropathiesandmyopathies

＊myasthenicsyndromes(otherdisordersoftheNMJwhichneurophysiologicalstudiesmightshowchangessimilartothoseofMG).MyastheniaGravis(MG)

Differe29MyastheniaGravis(MG)

TreatmentAChEdrugsprovidessymptomaticbenefitwithoutinfluencingthecourseoftheunderlyingdisease.pyridostigmine,atdosesindividuallydeterminedbutusuallybetween60and180mgq.q.d.Smalldosesofatropinemayattenuatesideeffectssuchasdiarrhea.MyastheniaGravis(MG)

Trea30MyastheniaGravis(MG)

Treatmentthymectomyshouldbeperformedinpatientsunder60yearsofage.usuallyleadstosymptomaticbenefitorremissionHowever,itsbeneficialeffectmaynotbeevidentimmediately.MyastheniaGravis(MG)

Tre31MyastheniaGravis(MG)

TreatmentcorticosteriodsareindicatedforpatientswhohaverespondedpoorlytoAChEandhavealreadyunderthymectomy.Treatmentsareinitiatedwiththepatientinhospital,sinceweaknessmayinitiallybeexacerbated.Aninitialhighdoseofpredinisone(60-80mg/dorally)cangraduallybetaperedtoarelativelylowmaintenancelevel(10-20mg/d)asimprovementoccurs.MyastheniaGravis(MG)

Trea32MyastheniaGravis(MG)

TreatmentImmunosuppressant,e.g.azathioprine,isusedassteriod-sparingagent.Itcanalsobegiveninplaceofcorticosteroidstopatientswhoshownosustainedbenefitwithlowdoses.Theusualdoseis1-3mg/kg/d,increasedfromalowerinitialdose.MyastheniaGravis(MG)

Tre33MyastheniaGravis(MG)

Treatmentplasmapheresis(PE)maybeusedduringanacuteexacerbation,myastheniccrisis,orundercertainspecialcircumstances,ravenousimmunoglobulins(IVIG)havebeenusedtoprovidetemporarybenefitincircumstancessimilartothoseinwhichPEisused.MyastheniaGravis(MG)

Tre34MyastheniaGravis(MG)

TreatmentCrisis:respiratoryandbulbarcomplicationsrequireappropriatesupportivemeasures,e.g.assistedventilationand/ornasogastricfeeding.PEandIVIGareneeded.MyastheniaGravis(MG)

Tre35Lambert-EatonSyndrome(LEMS)概念病因及發(fā)病機(jī)制臨床表現(xiàn)診斷及鑒別診斷治療Lambert-EatonSyndrome(LEMS)36Lambert-EatonSyndrome(LEMS)

DefinitionIntheparaneoplasticdisorder,Absagainsttumorantigenscross-reactwithvoltage-gatedcalciumchannelsinvolvedinacetylcholinerelease,leadingtoadisturbanceofNMT.Lambert-EatonSyndrome(LEMS)37Lambert-EatonSyndrome(LEMS)

EtiologyIn1957,LambertandEatondescribedamyasthenicsyndromethatwaselectrophysiologicallydistinctfromMG.anarchetypalparaneoplasticneurologicdisorder,frequentlyassociatedwithSCLC.occasionallyassociatedwithperniciousanemia.Lambert-EatonSyndrome(LEMS)

38Lambert-EatonSyndrome(LEMS)

ClinicalManifestationsLEMSismorecommoninmalesthanfemales.Weaknessinvolvespredominantlyproximalmusclesofthelimbsandnearlyalwaysaffectsthelegsfirst.Strengthmayincreaseduringthefirstfewsecondsofavoluntarycontraction.Lambert-EatonSyndrome(LEMS)39Lambert-EatonSyndrome(LEMS)

ClinicalManifestationsOcularsyndromesarefarlesscommonthaninMG.Weaknessandfatigueofhipmuscleswithachingbackandthighmusclesarecommon.Reflexesareabsent.Autonomicdisturbances,suchasdrymouth,constipation,andimpotence,mayalsooccur.Lambert-EatonSyndrome(LEMS)40Lambert-EatonSyndrome(LEMS)

InvestigationCMAPamplitudeisdecreasedatlowratesofrepetitivenervestimulation.theCMAPshowsanincrementfollowinghigh-frequency(>10Hz)stimulationorafewsecondsofvoluntarycontraction.ThefindingscontrastedwiththoseinMG.autoantibodiesagainsttheP/Qsubtypeofvoltage-gatedcalciumchannels(VGCC)ishighlysensitiveandspecific.AChR-Ab(-).Lambert-EatonSyndrome(LEMS)

41Lambert-EatonSyndrome(LEMS)

Diagnosisanddifferentialdiagnosis肌無力、腱反射減低、自主收縮后肌力增加。典型的電生理改變。通過檢測VGCC抗體加以驗(yàn)證(陽性率>90%)。表17-1Lambert-EatonSyndrome(LEMS)42TreatmentTherapybasedontheetiology.PE.IVIG.TreatmentTherapybasedonthe43本課重點(diǎn)MG的臨床表現(xiàn)肌肉病態(tài)疲勞，晨輕暮重MG危象的概念及分型MG的診斷MG和LEMS的鑒別本課重點(diǎn)MG的臨床表現(xiàn)44神經(jīng)肌接頭病-重癥肌無力Lambert-Eaton綜合征神經(jīng)肌接頭病-重癥肌無力Lambert-Eaton綜合征45NeuromuscularDisorders

DefinitionThediseasesofneuromuscularjunction(NMJ)describesasetsofdiseasecausedbycirculatingfactorssuchasneurotoxinsorautoantibodieswhichbindwithhighaffinitytospecificproteinsattheNMJanddisturbtheneuromusculartransmission.NeuromuscularDisorders

46NeuromusuclarJunction(NMJ)

PhysiologythenerveAPreachesthenerveterminalwhichinflatedandwithoutmyelinandleadstotheopeningofcalciumchannelandreleaseofAChintothesynapticcleftbyexocytosis.NeuromusuclarJunction(NMJ)

47NeuromusuclarJunction(NMJ)

Physiology1/3oftheAChdiffusesrapidlytothepostsynapticmembraneandbindstotheAChRs,leadingtoopeningoftheAChR-associatedcationchannelanddepolarizationcalledtheend-platepotential(EPP).IftheEPPexceedscertainthreshold,voltagegatedsodiumchannelatthepostsynapticmembraneareopened.Thisgeneratesthemuscleactionpotential(CMAP)thatpropagatesalongthemusclefiberandactivatescontraction.NeuromusuclarJunction(NMJ)

48NeuromusuclarJunction(NMJ)

PhysiologyAnother1/3oftheAChishydrolyzedbycholinesterase(ChE).Theremaining1/3oftheAChisrecapturedbythepresynapticmembrane.NeuromusuclarJunction(NMJ)

49重癥肌無力(MyastheniaGravis,MG)概念病因及發(fā)病機(jī)制病理臨床表現(xiàn)診斷及鑒別診斷治療重癥肌無力(MyastheniaGravis,MG)概50Myastheniagravis(MG)

DefinitionMGwasoriginatedfromLatin,meaningverysevereweakness.acquiredMGisanantibodyandcomplement-mediated,Tcell-dependentautoimmunediseaseleadingtoadefectinneuromusculartransmission.Myastheniagravis(MG)

Definit51Myastheniagravis(MG)

EpidemiologyItistheprototypicneuromusculardisorderswithanincidenceof80-200permillionandprevalenceabout500permillion.InChina,itisestimatedthat0.6millionpeoplewerediagnosedasMGandmostofthemlivesintheSouthofChina.Ithadbeenalife-threateningdiseasebefore1970’s,thoughnowadaystheincidenceofdeathhasbeengreatlyreducedtoabout0.2%.Myastheniagravis(MG)

Ep52MyastheniaGravis(MG)

EtiologyTheautoimmuneoriginofMGisproposedlongbeforeitwasestablishedin1973bythedirectevidenceprovidedbyPatrickandLindstrom,whohaveimmunizedrabbitwithaffinity-purifiedTorpedoAChRwithCFAandreproducedtheanimalmodelsrepresentinghumanMG(EAMG).TheAChRistheautoantigen.MyastheniaGravis(MG)

Etiolog53MyastheniaGravis(MG)

EtiologyThepresenceofanti-AChRAbscanbedemonstratedin80%-90%ofMGpatients.Thereisa3:1female-maleratioforpatientswhodevelopMGinearlyadultlife.Overall,theabovemakesMGfulfillsthecriteriaforautoimmunediseases.MyastheniaGravis(MG)

Etiolog54MyastheniaGravis(MG)

EtiologyMostofthepatientswithMGhaveabnormalitiesinthethymus,e.g.thymichyperplasticorthymoma.Althoughtheprimaryantiselfeventbeingunclear,thymusappearstobetheplacewhereitinitiates.ThegeneralopinionisthatvirusinfectionorothernonspecificfactorsinvadesthethymusingeneticallypredisposedindividualsleadingtothedevelopmentofMG.MyastheniaGravis(MG)

Etiolog55MyastheniaGravis(MG)

PathologyLymphoidfolliculuscanbeseeninthymus.About10%ofMGpatientshasthymomaofepitheliatype.Lymphorage,definedbyaggregatedlymphoidcellsaroundthebloodvessels,issometimesseeninotherwisenormalmusculatureinMGpatients.MyastheniaGravis(MG)

Patholo56MyastheniaGravis(MG)

PathologyAttheNMJ,grosslysimplifiedpostsynapticfoldswithdepositionofimmune-complexandtheanti-AChRAbsisdemonstratedbyimmunochemicalstudies.Thereisalsoconsiderabledebriswithinthewidenedsynapticcleft.

NormalNMJ、NMJinMGpatients（示意圖）（電鏡）MyastheniaGravis(MG)

Patholo57MyastheniaGravis(MG)

ClinicalManifestationsMGcanariseatanyage,althoughyoungfemalesandoldmalesaremorevulnerabletoit.Precipitatingfactors:concurrentinfection,stress,weariness,menses,pregnancyorparturition.Thediseaseinitiatesinsidiousandfollowsaslowlyprogressivecourse.MyastheniaGravis(MG)

Clinica58MyastheniaGravis(MG)

ClinicalManifestationsClinically,MGfeatureswithfluctuatedmuscularweaknessinintensityduringthedayandeasyfatigability.Typically,theweaknessvariesindistributionandseverityfromdaytoday.Characterizedbyabnormalweakness,whichbeingworseattheendofthedayorafterexertionandtendstoimproveafterrestorAChEtreatment.MyastheniaGravis(MG)

Clinica59MyastheniaGravis(MG)

ClinicalManifestationsTheweaknessoftenbeginswiththelateralorbilateralextra-ocularmuscles,leadingtoasymmetricocularpalsies(e.g.diplopia,strabismic)andptosis.Pupillaryresponsesarenotaffected.MyastheniaGravis(MG)

Clinica60MyastheniaGravis(MG)

ClinicalManifestationsThepatientsmaypresentwithlesswrinkles,amimia,difficultyinclosingtheeyesordisclosingtooth;difficultyinchewingorswallowing,nasalspeech;weaknessoftheneckortheproximalupperlimbs.MyastheniaGravis(MG)

Clinica61MyastheniaGravis(MG)

Crisis—definitionCrisisdescribesarapidlydevelopedweaknessinthebulbarmusclesandrespiratoryinsufficiencythatnecessitatesassistedventilation.ItistheleadingcauseofdeathinpatientswithMG.MyastheniaGravis(MG)

Crisis—62MyastheniaGravis(MG)

Crisis—classificationMyastheniccrisis:abletoreacttoAChEdrugsandbeinghypersensitivetothecurare.Cholinergiccrisis: 1.overmedicationcanleadtoincreased weakness,which,unlikemyasthenicweakness, isunaffectedorenhancedbyintravenous edrophonium. 2.Itmaybeaccompaniedbypallor,sweating, nausea,vomiting,salivation,colic,and diarrhea(muscarinicsyndrome).Brittiecrisis:unresponsivetoAChE.MyastheniaGravis(MG)

Crisis—63MyastheniaGravis(MG)

OssermanClassificationFivesubgroupscanbedefinedamongpatientswithmyasthenia.I.

OcularIIa.MildgeneralizedIIb.ModerategeneralizedIII.ProgressivelysevereIV.latesevereMyastheniaGravis(MG)

Osserma64MyastheniaGravis(MG)

OtherclassificationMGcanalsobesubdividedintoadolescentandadulttype,neonatalMG,congenitalmyasthenia,D-Penicillamineinducedmyasthenia:asimilardisorderinpatientsreceivingpenicillamineforrheumatoidarthritisfrequentlyremitswhenthedrugisdiscontinued.MyastheniaGravis(MG)

Otherc65MyastheniaGravis(MG)

InvestigationRoutineexaminationontheblood,ureaandCSFarenormal.X-raysandCTscansofthechestmayrevealacoexistingthymomainpatientsover40years.MyastheniaGravis(MG)

Investi66MyastheniaGravis(MG)

InvestigationEMG:increaseddecrement(>10%)oftheevokedCMAPuponrepeatedstimuliat3or5Hz.SinglefibermyographyshowsreducedamplitudeofMEPPandincreasedvariability(jitter)ormoreblockadeofimpulses.MyastheniaGravis(MG)

Investi67MyastheniaGravis(MG)

InvestigationTheanti-AChRAbspresentin85-90%ofpatientswithgeneralizedMGandin50%ofpatientswithocularMG,butnotpresentinhealthyindividuals.Whentheanti-AChRAbsareidentified,thediagnosisisestablished.autoantibodiesagainststriatedmuscles.MyastheniaGravis(MG)

Investi68MyastheniaGravis(MG)

Diagnosis疲勞試驗(yàn)（Jolly試驗(yàn)）抗膽堿酯酶藥物試驗(yàn)1.騰喜龍（tensilon）試驗(yàn)2.新斯的明（neostigmine）試驗(yàn)重復(fù)神經(jīng)電刺激AChR抗體滴度測定：特征性意義MyastheniaGravis(MG)

Diagnos69MyastheniaGravis(MG)

Diagnosisedrophoniumin2-3dose(totally10mg)giveni.v.givearapid(within2’)butshort-lived(lessthan5’)improvementinstrengthinmostpatientswithMG.neostigmineof1.5mggiveni.m.improvesmusclestrengthwithin30’andlastsfor2hs.false-positiveandfalse-negativeresultscanoccur.thereisasmallriskofcardiorespiratorycollapse.MyastheniaGravis(MG)

D70MyastheniaGravis(MG)

DiagnosisOncethediagnosishasbeenmade,CTorMRIofthechestshouldbedonetoexcludeanassociatedthymoma.ThyroidfunctionandthyroidAbsshouldbemeasured,becauseoftheincreasedfrequencyofthyroiddisease.MyastheniaGravis(MG)

Di71MyastheniaGravis(MG)

DifferentialdiagnosisThedifferentialdiagnosisofMGiswide.AcquiredMGv.s.congenitalMGand

neurotoxinse.g.botulism,venoms.OcularMG(ofwhomabout50%areAChRAb-negative)v.s.ocularmusculardystrophyandmitochodrialcytopathy.Bulbarmyastheniav.s.brainstemstrokeandmotor-neurondisease(e.g.ALS).MyastheniaGravis(MG)

Diffe72MyastheniaGravis(MG)

DifferentialdiagnosispatientswithgeneralizedweaknessbutarenegativeforAChRAbsv.s.

＊neuropathiesandmyopathies

＊myasthenicsyndromes(otherdisordersoftheNMJwhichneurophysiologicalstudiesmightshowchangessimilartothoseofMG).MyastheniaGravis(MG)

Differe73MyastheniaGravis(MG)

TreatmentAChEdrugsprovidessymptomaticbenefitwithoutinfluencingthecourseoftheunderlyingdisease.pyridostigmine,atdosesindividuallydeterminedbutusuallybetween60and180mgq.q.d.Smalldosesofatropinemayattenuatesideeffectssuchasdiarrhea.MyastheniaGravis(MG)

Trea74MyastheniaGravis(MG)

Treatmentthymectomyshouldbeperformedinpatientsunder60yearsofage.usuallyleadstosymptomaticbenefitorremissionHowever,itsbeneficialeffectmaynotbeevidentimmediately.MyastheniaGravis(MG)

Tre75MyastheniaGravis(MG)

TreatmentcorticosteriodsareindicatedforpatientswhohaverespondedpoorlytoAChEandhavealreadyunderthymectomy.Treatmentsareinitiatedwiththepatientinhospital,sinceweaknessmayinitiallybeexacerbated.Aninitialhighdoseofpredinisone(60-80mg/dorally)cangraduallybetaperedtoarelativelylowmaintenancelevel(10-20mg/d)asimprovementoccurs.MyastheniaGravis(MG)

Trea76MyastheniaGravis(MG)

TreatmentImmunosuppressant,e.g.azathioprine,isusedassteriod-sparingagent.Itcanalsobegiveninplaceofcorticosteroidstopatientswhoshownosustainedbenefitwithlowdoses.Theusualdoseis1-3mg/kg/d,increasedfromalowerinitialdose.MyastheniaGravis(MG)

Tre77MyastheniaGravis(MG)

Treatmentplasmaph