神經(jīng)病學(xué)英文課件：07 MULTIPLE SCLEROSIS

MULTIPLESCLEROSISMULTIPLESCLEROSISDEFINITIONOFMSItisdefinedclinicallybytheinvolvementofdifferentpartsoftheCNSatdifferenttimes-providedthatotherdisorderscausingmultifocalcentraldysfunctionhavebeenexcludedDEFINITIONOFMSItisdefinedEPIDEMIOLOGYInitialsymptomsgenerallycommencebeforetheageof55yearsoldwithapeakincidencebetweenages20and40.WomenareaffectednearlytwiceasoftenasmenEPIDEMIOLOGYInitialsymptomsgEPIDEMIOLOGYANDGENETICSIncidencerateinUnitedStates::30-60/100,000lessthan5/100,000inAsiaGeographicGradientsandincidenceratesEquator:lowLatitude40oNand40oSEPIDEMIOLOGYANDGENETICSIncidGENETICFACTORSINMSGeneticpredispositionissuggestedbytwinstudiesTwins:monozygotic30%dizygotic4%TheoccasionalfamilialincidenceandstrongassociationbetweenthediseaseandspecificHLAalleles(HLA-DRB*15:1,HLA-DB1*15:03)AllelsofIL2RAandIL7RAGENETICFACTORSINMSGeneticpPathologyDemyelinativelesionsarecommonlyincerebralhemisphere,opticnerve,spinalcord,brainstem,cerebellum.Periventricular–scatteredareasofdemyelinationfollowedbyareactivegliosis,theremaybeaxonaldamageaswellTheselesionoccurinthewhitematterofthebrainandcordandinoptic(II)nervePathologyDemyelinativelesionsPathophysiologyThecauseofMSisunknown,buttissuedamageandneurologicalsymptomsarethroughttobetriggeredbyanimmunemechanismdirectedagainstmyelinantigensViralinfectionorotherincitingfactorsmaypromotetheentryofTcellsandantibodiesintotheCNSbydisruptingtheblood–brainbarrierPathophysiologyThecauseofMSInitialorPresentingSymptoms&Signs:Commoninitialcomplaintsarefocalweakness,numbness,tingling,orunsteadinessinalimb,LhermittesignSuddenlossorblurringofvisioninoneeye(opticneuritis)Diplopia,internuclearophthalmoplegia,nystagmusDisequilibriumBladder-functiondisturbance(urinaryurgencyorhesitancy)suchsymptomsareoftentransient,disappearing

afterafewdaysorweekswithresidualdeficitCLINCALFEATURESOFMSInitialorPresentingSymptoms神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSISOtherpatientspresentwithanacuteorgraduallyprogressivespasticparapresisandsensorydeficitSubsequentCourse:IntervalofmonthsoryearsaftertheinitialepisodebeforefurtherneurologicsymptomsappearNewsymptomsmaythendevelop,ororiginalonesmayrecurandprogress.Relapsesmaybetriggeredbyinfectionand,inwomen,aremorelikelyinthe3monthsorsofollowingchildbirthCLINCALFEATURESOFMSOtherpatientspresent神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSISAriseinbodytemperaturecancausetransientdeteriorationinpatientwithafixedandstabledeficitWithtime-andafteranumberofrelapsesandusuallyincompleteremissions-thepatientmaybecomeincreasingdisabledbyweakness,stiffness,sensorydisturbances,unsteadinessofthelimbs,impairedvision,andurinaryincontinenceBasedonitscourse,thediseaseisdividedinto4majortypesCLINCALFEATURESOFMSAriseinbodytemperaturecanCLINICALSUBTYPESOFMS

Relapsingremitting(RR)ProgressiondoesnotoccurbetweenattacksPrimaryprogressive(PP)ThereisgradualprogressionofdisabilityfromclinicalonsetSecondaryprogressive(SP)AprogressivecourseafteraninitialRRpatternProgressiverelapsing(PR)CLINICALSUBTYPESOFMSRelapsMRIFINDINGSSUPPORTIVEOFMSDIAGNOSIS1GD-DTPAcontrastenhancelesionOR9noncontrastenhancehighsignallesionsonMRT2sequenceAtleast1periventricularlesionAtleast1infratentorial(Brainstemorcerebellar)lesionAtleast1juxtacorticallesionOvoidlesionsperpendicularOpenringonGadT1-weightedSpinalMRItor/ocongenitaloracquiredsurgicaltreatablelesionMRIFINDINGSSUPPORTIVEOFMS神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSIS神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSISCEREBROSPINALFLUIDINMSMildlymphocytosisNormalglucoseNormalormodestincreaseinproteinAbsentredbloodcellsIncreasedIgGIndex/SynthesisOligoclonalbands~90%CEREBROSPINALFLUIDINMSMild神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSISLABTESTSMonocularvisualstimulationwithacheckerboardpattern(visualevokedpotentials,VEPs)Monauralstimulationwithrepetitiveclicks(brainstemauditoryevokedpotentials,BAEPs)Electricalstimulationofaperiphralnerve(somatosensoryevokedpotentials,SEPs)oneormoreabnorminMSLABTESTSMonocularvisualstim神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSISSCHUMACHERCRITERIAFORMSOnsetatappropriateageCNSwhitematterdisease

DisseminatedintimeandspaceObjectiveabnormalitiesAttackslastingover24hoursonemonthapartGradualorstepwiseprogressionNoalternativediagnosisSCHUMACHERCRITERIAFORMSOnseDiagnosisCriteriaforMS

Poser(1983)

ClinicaldefiniteMS,CDMSLaboratory-supporteddefiniteMS,LSDMSClinicalprobableMS,CPMSLaboratory-supportedprobableMS,LSPMSDiagnosisCriteriaforMS

Pose2005Rev.McDonaldCriteria2005Rev.McDonaldCriteriaEDSSforMS

theExpandedDisabilityStatusScale

neurologicaltestingoffunctionalsystem1.Pyramidalfunction(abilitytowalk)2.Cerebellarfunction(coordination)3.BrainStem(speech&swallowing)4.Sensory(touch&pain)EDSSforMS

theExpandedDisabEDSSforMS

neurologicaltestingoffunctionalsystem5.Bowel&bladder6.Visual7.Mental8.OtherEDSSforMS

neurologicaltestiEDSSforMS

theExpandedDisabilityStatusScaleFrom0.0normalneurologicalexamto10.0-deathe.g.6.0intermittentorunilateralconstantassistance(cane,crutchorbrace)requiredtowalk100meterswithorwithoutrestinge.g.8.0essentiallyrestrictedtobed,chairorwheelchair,butmaybeoutofbedmuchofday;retainsselfcarefunctions,generallyeffectiveuseofarmsEDSSforMS

theExpandedDisabDIFFERENTIALDIAGNOSISOFMS-NeuromyelitisOptica(NMO)Neuromyelitisoptica:isarelapsingdisorder(formerlyknownasDevicdiseaseandonceconsideredavariantofMS)isassociatedwuthaspecificantibodymarker,NMO-IgG,thattargetsthewaterchannelaquaporin-4.ThefullyestablisheddisorderischararcterizedbyopticneuritisandacutemyelitisandassocitedwithMRIchangesthatextendoveratleast3segmentsofthespinalDIFFERENTIALDIAGNOSISOFMS-NDIFFERENTIALDIAGNOSISOFMS-NeuromyelitisOptica(NMO)Usuallynobrainstem,cerebellar,orcerebraldemyelinativelesionandnormalityonMRIofwhitematter,absenceofOBbandandIgGinCSF,moreinAsiacountriesAcuteattacktreatedwithMPpusal,IVIG,PEwithlongtermimmnosuppressivetheraphyDIFFERENTIALDIAGNOSISOFMS-NDIFFERENTIALOFMS-AcuteDisseminatedEncephalomyelitis(ADEM)Occursasasingleepisodeofneurologicalsymptomssandsignsdevelopedinfewdaysassociatedwithnonspecificviralinfectionorafterimmunization.CSFisnlorProteinincreased,GlucosenlMRIishelpfulinwhitematterlesionevenwithgraymatter.DIFFERENTIALOFMS-AcuteDisseIMMUNOPROPHYLACTIC

AGENTSFORRRMSINTERFERONINTERFERONbeta-1b(Betaseron)Subcutaneous,everyotherdayrecombinantprotein–Ecol,250μgINTERFERONbeta-1a(AVONEX)IM,weekly,recombinantprotein,30μgINTERFERONbeta1-a(REBIF)SQ3X/WEEK22OR44μgMayuseformorethan2yearsGlatirameracetate(Copaxone)Syntheticpolypeptide,subcut20mgdailyIMMUNOPROPHYLACTIC

AGENTSFORIMMUNOPROPHYLACTIC

AGENTSFORRRMSNatalizumab,analpha4integrinantibody,reducestherelapsingrate,butinrareunstancesisassociatedwithprogressivemultifocalleukoencephalopathyMethyl-predinisolone(1gdaily)3-5days,followedbyanoralprednisonetaper(80mg/dforaweek,withrapidreductionovertheensuing1-2weeks)Intravenousimmunoglobulin(IVIG)0.4g/kgfor5daysORPlasmapheresis(PE)IMMUNOPROPHYLACTIC

AGENTSFORTREATMENTOFFEREDFORSPANDPPMSCyclophosphamideAzathiopprine/methotrexateCladribine/cyclosporineMitoxantroneSteroidpulsewithhigh-doseIVMP1.0gonceamonthIFN-beta-1beffectiveTREATMENTOFFEREDFORSPANDTREATMENTOFACUTEEXACERBATIONSOFMSGlucocorticosteroidsHigh-dosei.v.methylprednisolone0.5to1.0g/dayvariablecombinationsPlasmaExchange

TREATMENTOFACUTEEXACERBATIOPROGNOSISAtleastpartialrecoveryfromanacuteepisodecanbeanticipated,butitisimpossibletopredictwhenthenextrelapsewilloccure.Morefavorableprognosis:female,onsetbefore40,andpresentationwithvisualorsomatosensory,ratherthanpyramidalorcellellardysfunction.About50%ofallpatientsareonlymildlyormoderatelydisabled10yearsaftertheonsetofsymptomsPROGNOSISAtleastpartialrecTHANKS!THANKS!MULTIPLESCLEROSISMULTIPLESCLEROSISDEFINITIONOFMSItisdefinedclinicallybytheinvolvementofdifferentpartsoftheCNSatdifferenttimes-providedthatotherdisorderscausingmultifocalcentraldysfunctionhavebeenexcludedDEFINITIONOFMSItisdefinedEPIDEMIOLOGYInitialsymptomsgenerallycommencebeforetheageof55yearsoldwithapeakincidencebetweenages20and40.WomenareaffectednearlytwiceasoftenasmenEPIDEMIOLOGYInitialsymptomsgEPIDEMIOLOGYANDGENETICSIncidencerateinUnitedStates::30-60/100,000lessthan5/100,000inAsiaGeographicGradientsandincidenceratesEquator:lowLatitude40oNand40oSEPIDEMIOLOGYANDGENETICSIncidGENETICFACTORSINMSGeneticpredispositionissuggestedbytwinstudiesTwins:monozygotic30%dizygotic4%TheoccasionalfamilialincidenceandstrongassociationbetweenthediseaseandspecificHLAalleles(HLA-DRB*15:1,HLA-DB1*15:03)AllelsofIL2RAandIL7RAGENETICFACTORSINMSGeneticpPathologyDemyelinativelesionsarecommonlyincerebralhemisphere,opticnerve,spinalcord,brainstem,cerebellum.Periventricular–scatteredareasofdemyelinationfollowedbyareactivegliosis,theremaybeaxonaldamageaswellTheselesionoccurinthewhitematterofthebrainandcordandinoptic(II)nervePathologyDemyelinativelesionsPathophysiologyThecauseofMSisunknown,buttissuedamageandneurologicalsymptomsarethroughttobetriggeredbyanimmunemechanismdirectedagainstmyelinantigensViralinfectionorotherincitingfactorsmaypromotetheentryofTcellsandantibodiesintotheCNSbydisruptingtheblood–brainbarrierPathophysiologyThecauseofMSInitialorPresentingSymptoms&Signs:Commoninitialcomplaintsarefocalweakness,numbness,tingling,orunsteadinessinalimb,LhermittesignSuddenlossorblurringofvisioninoneeye(opticneuritis)Diplopia,internuclearophthalmoplegia,nystagmusDisequilibriumBladder-functiondisturbance(urinaryurgencyorhesitancy)suchsymptomsareoftentransient,disappearing

afterafewdaysorweekswithresidualdeficitCLINCALFEATURESOFMSInitialorPresentingSymptoms神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSISOtherpatientspresentwithanacuteorgraduallyprogressivespasticparapresisandsensorydeficitSubsequentCourse:IntervalofmonthsoryearsaftertheinitialepisodebeforefurtherneurologicsymptomsappearNewsymptomsmaythendevelop,ororiginalonesmayrecurandprogress.Relapsesmaybetriggeredbyinfectionand,inwomen,aremorelikelyinthe3monthsorsofollowingchildbirthCLINCALFEATURESOFMSOtherpatientspresent神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSISAriseinbodytemperaturecancausetransientdeteriorationinpatientwithafixedandstabledeficitWithtime-andafteranumberofrelapsesandusuallyincompleteremissions-thepatientmaybecomeincreasingdisabledbyweakness,stiffness,sensorydisturbances,unsteadinessofthelimbs,impairedvision,andurinaryincontinenceBasedonitscourse,thediseaseisdividedinto4majortypesCLINCALFEATURESOFMSAriseinbodytemperaturecanCLINICALSUBTYPESOFMS

Relapsingremitting(RR)ProgressiondoesnotoccurbetweenattacksPrimaryprogressive(PP)ThereisgradualprogressionofdisabilityfromclinicalonsetSecondaryprogressive(SP)AprogressivecourseafteraninitialRRpatternProgressiverelapsing(PR)CLINICALSUBTYPESOFMSRelapsMRIFINDINGSSUPPORTIVEOFMSDIAGNOSIS1GD-DTPAcontrastenhancelesionOR9noncontrastenhancehighsignallesionsonMRT2sequenceAtleast1periventricularlesionAtleast1infratentorial(Brainstemorcerebellar)lesionAtleast1juxtacorticallesionOvoidlesionsperpendicularOpenringonGadT1-weightedSpinalMRItor/ocongenitaloracquiredsurgicaltreatablelesionMRIFINDINGSSUPPORTIVEOFMS神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSIS神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSISCEREBROSPINALFLUIDINMSMildlymphocytosisNormalglucoseNormalormodestincreaseinproteinAbsentredbloodcellsIncreasedIgGIndex/SynthesisOligoclonalbands~90%CEREBROSPINALFLUIDINMSMild神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSISLABTESTSMonocularvisualstimulationwithacheckerboardpattern(visualevokedpotentials,VEPs)Monauralstimulationwithrepetitiveclicks(brainstemauditoryevokedpotentials,BAEPs)Electricalstimulationofaperiphralnerve(somatosensoryevokedpotentials,SEPs)oneormoreabnorminMSLABTESTSMonocularvisualstim神經(jīng)病學(xué)英文課件：07MULTIPLESCLEROSISSCHUMACHERCRITERIAFORMSOnsetatappropriateageCNSwhitematterdisease

DisseminatedintimeandspaceObjectiveabnormalitiesAttackslastingover24hoursonemonthapartGradualorstepwiseprogressionNoalternativediagnosisSCHUMACHERCRITERIAFORMSOnseDiagnosisCriteriaforMS

Poser(1983)

ClinicaldefiniteMS,CDMSLaboratory-supporteddefiniteMS,LSDMSClinicalprobableMS,CPMSLaboratory-supportedprobableMS,LSPMSDiagnosisCriteriaforMS

Pose2005Rev.McDonaldCriteria2005Rev.McDonaldCriteriaEDSSforMS

theExpandedDisabilityStatusScale

neurologicaltestingoffunctionalsystem1.Pyramidalfunction(abilitytowalk)2.Cerebellarfunction(coordination)3.BrainStem(speech&swallowing)4.Sensory(touch&pain)EDSSforMS

theExpandedDisabEDSSforMS

neurologicaltestingoffunctionalsystem5.Bowel&bladder6.Visual7.Mental8.OtherEDSSforMS

neurologicaltestiEDSSforMS

theExpandedDisabilityStatusScaleFrom0.0normalneurologicalexamto10.0-deathe.g.6.0intermittentorunilateralconstantassistance(cane,crutchorbrace)requiredtowalk100meterswithorwithoutrestinge.g.8.0essentiallyrestrictedtobed,chairorwheelchair,butmaybeoutofbedmuchofday;retainsselfcarefunctions,generallyeffectiveuseofarmsEDSSforMS

theExpandedDisabDIFFERENTIALDIAGNOSISOFMS-NeuromyelitisOptica(NMO)Neuromyelitisoptica:isarelapsingdisorder(formerlyknownasDevicdiseaseandonceconsideredavariantofMS)isassociatedwuthaspecificantibodymarker,NMO-IgG,thattargetsthewaterchannelaquaporin-4.ThefullyestablisheddisorderischararcterizedbyopticneuritisandacutemyelitisandassocitedwithMRIchangesthatextendoveratleast3segmentsofthespinalDIFFERENTIALDIAGNOSISOFMS-NDIFFERENTIALDIAGNOSISOFMS-NeuromyelitisOptica(NMO)Usuallynobrainstem,cerebellar,orcerebraldemyelinativelesionandnormalityonMRIofwhitematter,absenceofOBbandandIgGinCSF,moreinAsiacountriesAcuteattacktreatedwithMPpusal,IVIG,PEwithlongtermimmnosuppressivetheraphyDIFFERENTIALDIAGNOSISOFMS-NDIFFERENTIALOFMS-AcuteDisseminatedEncephalomyelitis(ADEM)Occursasasingleepisodeofneurologicalsymptomssandsignsdevelopedinfewdaysassociatedwithnonspecificviralinfectionorafterimmunization.CSFisnlorProteinincreased,GlucosenlMRIishelpfulinwhitematterlesionevenwithgraymatter.DIFFERENTIALOF