神經(jīng)病學課件：重癥肌無力

1MyastheniaGravis

重癥肌無力2Outline BackgroundAnatomyPathophysiologyEpidemiologyClinicalPresentationDiagnosisofMGTherapyForMGDiagnosisofMGCrisisRehabilitation3BackgroundFirstclinicaldescriptionin1672byThomasWillisAcquiredautoimmunedisorderabnormalcommunicationbetweennervesandmuscles.NamefromLatinandGreekwordClinicallycharacterizedby:WeaknessofskeletalmusclesFatigabilityonexertion.4Anatomy---NeuromuscularJunction(NMJ)

NeuromuscularJunction(NMJ)Components:PresynapticmembranePostsynapticmembraneSynapticcleftTheAcetylcholinereceptor(AChR)isasodiumchannelthatopenswhenboundbyAChThereisapartialdepolarizationofthepostsynapticmembraneandthiscausesanexcitatorypostsynapticpotential(EPSP)Ifenoughsodiumchannelsopenandathresholdpotentialisreached,amuscleactionpotentialisgeneratedinthepostsynapticmembrane5Anatomy---thymusglandthethymusglandmaygiveincorrectinstructionstodevelopingimmunecells,ultimatelyresultinginautoimmunityandtheproductionoftheacetylcholinereceptorantibodies,therebysettingthestagefortheattackonneuromusculartransmission.6Pathology

—thymus15%ofMGpatientshavethymomaofthelymphoepithelialtype

70%havelymphoid

hyperplasiaofthethymus：numerous

germinalcenters7PathologymusclescontainlymphorrhagesthymomawithMGlossofsynapticfoldsandwidenedclefts8PathophysiologyInMG,antibodiesaredirectedtowardtheacetylcholinereceptorattheneuromuscularjunctionofskeletalmusclesResultsin:Decreasednumberofnicotinicacetylcholinereceptorsatthemotorend-plateReducedpostsynapticmembranefoldsWidenedsynapticcleft9Epidemiology FrequencyAnnualincidenceinUS-2/1,000,000(E)Worldwideprevalence1/10,000(D)Mortality/morbidityRecentdecreaseinmortalityrateduetoadvancesintreatment3-4%(ashighas30-40%)RiskfactorsAge>40ShorthistoryofdiseaseThymomaSexF-M(6:4)Meanageofonset(M-42,F-28)Incidencepeaks-M-6-7thdecadeF-3rddecade10ClinicalpresentationOcularandgeneralizedMGModifiedossermanclassificationBurnt-outstage:after15-20years,untreatedweaknessbecomesfixed,andatrophic11OcularPtosis(droppingeyelid)–asymmetric,fatigueswithupgazeDiplopia(doublevision)–mostcommoninvolvedMR(medialrectus)12Bulbar

Dysarthria

Dysphagia

Dysphonia

Masticatoryweakness–jawclosure>jawopenLimbs

Commonlyproximal,symmetric

ArmsmoreaffectedthanlegsRespiratorymusclesExertionaldyspneaTachypneaRespiratoryfailure

(Myastheniccrisis)AxialmusclesNeckflexionNeckextension13Clinicalpresentationmuscleweaknessis:painlessfluctuates

andprogressivelyworsensovercourseofdayworsenswithprolongeduseofaffectedmuscles(i.e.

fatiguable)variabledistributionandseverity,occasionallyveryasymmetricdistalweaknesslesscommonandlegweaknessoftenlater(ruleoutsteroidmyopathyintreatedpatient).mostcommonlyaffectedmusclegroups:jawclosure,neckflexors,deltoids,tricepsmayinvolverespiratorymusclesbowelandbladderfunctionpreserved14

NeurologicExamination

muscleweaknessdependingondistributionnomuscleshrinking(atrophy):muscularwastingisfoundinabout10%ofpatients

thereflexesarepreserved,eveninmusclesthatareweakFasciculationsdonotoccur,sensationisnormal

15OssermanClassificationofMGBasedontheseverityofthedisease1.Ocularmyasthenia,wherediseaseisconfinedtoocularmuscles.(focaldisease)2.Generalizedmyastheniagravisofmild(a)ormoderate(b)intensity.3.Severegeneralizeddisease4.Acuteseveregeneralizeddiseasewithrespiratoryfailure.5.Myastheniccrisiswithrespiratoryfailure(progressionwithin2year).16OthertypesofMG

1.NeonatalMG：12%ofinfantsborntomyasthenicmothersbegininthefirst48hoursandmaylastseveraldaysorweeks2.CongenitalMG：rarely3.DrugInducedMG:PenicillamineGentamicindisappearwhendrugisdiscontinued

17LaboratorytestRepetitivenervestimulationSinglefiberelectromyographyNormalSFEMG

Increasedjitter:MGpatient18Laboratorytest1.AntibodiestoAChR

generalizedMG:>80%iocularMG:50%MGandthymoma:98-100%Thetiterdoesnotmatchtheseverityofsymptoms2.Anti-musclespecificreceptortyrosinekinase(MuSK)antibodies

UsedifMGsuspected,patientseronegativePresentin40–50%ofseronegativepatientswithgeneralizedMG;absentinocularMG

19Othertest

Radiographsofthechestprovideevidenceofthymomainabout15%ofpatients,especiallyinthoseolderthan40years.CTofthemediastinumdemonstratesallbutmicroscopicthymomas.thymomahyperplasiaofthethymus20

DIAGNOSISOFMG

1.Historyandphysicalexamination：Jollytest2.DiagnostictestofneostigmineorTensilon3.LaboratorytestBreathingSeeingSwallowingChewingWalkingUsingyourarmsorhandsHoldingupyourhead21Tensilontest:Edrophoniumhydrochloride,ashort-actinganticholinesterasegivenintravenously(<1mg)

temporarilyreversesweaknessoveraperiodofseveralminutes.Neostigminetest:1.5to2.0mgofthedrugandatropinesulfate,0.4mg,aregivenintramuscularly.Objectiveimprovementinmuscularpowerisrecordedat20-minuteintervalsupto2hours.22Tensilontest&NeostigminetestA:Severeptosisofthelids.B:Samepatient1minuteafterintravenousinjectionofedrophonium(10mg).(FromRowlandLP,HoeferPFR,AranowHJr.Myasthenicsyndromes.ResPublAssocResNervMentDis1961;38;withpermission.)23Differentialdiagnosisdiseasesaccompaniedbyweaknessofmusclemusculardystrophies,amyotrophiclateralsclerosisotherdisordersofneuromusculartransmissionbotulinumintoxicationLambert-EatonsyndromeDenervatingdisorders

motorneurondiseaseorperipheralneuropathy24TherapyForMGsymptomatictreatments

Anticholinesterasedrug(Mestinon)

inhibitacetylcholinesteraseandincreaseavailabilityoftheacetylcholinetoactontheAChRs.

PlasmapheresisremoveAch-Rantibodiesofserum

IntravenousimmunoglobulininterferethefunctionofAch-RantibodiesIndicationpreparationforthymectomyexacerbationsituations25alteringcoursetreatmentsthymectomysteroids:prednisonIfapatientisstillseriouslydisabledafterthymectomy,IntravenousimmunoglobulinNOTAVAILABLEotherimmunosuppressivedrugs(CTX,MTX,azathioprine)

assistsinloweringthedoseofprednisoneandimprovetheeffectTherapyForMG26MyasthenicGraviscrisis

definedastheneedforassistedventilationarisesinabout10%ofmyasthenic