神經(jīng)病學(xué)課件：Movement-Disorders

MovementDisordersMovementDisordersIntroductiontomovementdisorders“movementdisorders”isoftenusedwith“extrapyramidalorbasalganglia(BG)”diseaseLesionsofbasalgangliaorpyramidalsystemarerelatedtosome,butnotall,ofthemovementdisordersIntroductiontomovementdisorPathwaysofextrapyramidalsystem

1.Cortex-cortex

2.Substatianigra-striatum

3.Striatum-globuspallidusPathwaysofextrapyramidalsysMajorneurotransmittersDopamine,acetylcholineGABAglutamatesomeneuropeptidessuchasENKandSubstancePTheyworksynchronouslytomaintainnormalexcitationandinhibitions.MajorneurotransmittersDopamiNormalfunctionofextrapyramidalsystemRegulatesmuscletoneMaintainspostureCo-ordinatesvoluntarymovementNormalfunctionofextrapyramiBasalGangliaDamagetothebasalganglia:Produceseithertoomuchactivation(hyperkinetic)responses=twitches,movementsbursts,jarring,etc.ORProducestoolittleforce(hypokinetic)=rigidityParkinson’sdiseasePink=inhibitionBlue=excitationBasalGangliaDamagetothebasCommonsymptomsofmovementdisordersAkinesia-rigidParkinsonism-brdykinesiaDyskinesiaChoreaDystoniaTremorticsCommonsymptomsofmovementdiChorea

Choreaisarapid,purposeless,irregular,jerkymovementthatseemstoflowrandomlyfromonepartofthebodytoanother.ChoreaChoreaisarapid,puDystoniaandAthetosisDystoniaisasyndromeofsustainedmusclecontractionscausingabnormalposturesortwistingandrepetitivemovements.Athetoticmovementsarecomplex,wormlike,irregular,nonpropositionalandpredominateoverposturalanomaliesandonthedistalpartsoflimbsandface.DystoniaandAthetosisDystoniaticsTwitchesoftheface,limbsorthewholebody.CanbereproducedvoluntarilyPatienthaspartialcontrolDonotinterferewithvoluntaryactivityMaypersistinsleepticsTwitchesoftheface,limbCommonformsofmovementdisordersParkinson’sDiseaseWilson’sDisease(Hepatolenticulardegeneration)EssentialtremorSydenham’sChorea(Rheumaticchorea)Tourette’sSyndromeCommonformsofmovementdisorParkinson’sDisease（PD）IsalsocalledparalysisagitansIscharacterizedbyaneuronalaccumulationof-synucleinandneuronallossinSNPresentswithbradykinesia,tremor,rigidity,shufflinggait,andflexedpostureParkinson’sDisease（PD）IsalsoHistoryofPDFirstdescribedin1817byanEnglishphysician,JamesParkinson,in“AnEssayontheShakingPalsy.”ThefamousFrenchneurologist,Charcot,furtherdescribedthesyndromeinthelate1800s.HistoryofPDEpidemiologyofPD~1%ofthose>55yearsRiskfactors:ageing,positivefamilyhistory,malegender,headinjury,exposuretopesticides,consumptionofwellwater,andruralliving.Factorslinkedtoreducedincidence:coffeedrinking,smoking,nonsteroidalanti-inflammatorydrugs,andestrogen.EpidemiologyofPD~1%ofthoseDopaminepathwaysinhumanbrainDopaminepathwaysinhumanbra

Dopaminesynthesis DopaminesynthesisDAmetabolismDAmetabolismDAdegradationDAdegradationLewybodiesLewybodiesEtiopathogenicmechanismsEtiopathogenicmechanismsMechanisms-summaryCelldeathmaybecausedby-synucleinaggregationproteosomalandlysosomalsystemdysfunction,reducedmitochondrialactivity.Excitotoxicityandinflammationarelikelytoplayarelevantroleinprogressiveneuronaldegeneration.Mechanisms-summaryCelldeathClinicalfeaturesMotorfeaturesBradykinesia,tremor,rigidity,shufflinggait,andflexedpostureNon-motorfeaturesDepressionandanxiety,cognition,sleepdisturbances,sensory,andautonomicdysfunctionsClinicalfeaturesMotorfeatureParkinson’sDisease（PD）Parkinson’sDisease（PD）MotorfeaturesBradykinesia.Slowinmovement.micrographia(hypophonia)-----softspeech“Maskedface”Tremoratrest.4-6Hz.“pillrolling”.Thelips,tongue,andjawmaybeinvolvedbutsparesthehead.Rigidity.“cogwheeling”or“l(fā)ead-pipe”.Gaitdisturbance:shufflingshortsteps.Festinating(hurried)gait.Atlaterstage,freezingofgait(starthesitation).MotorfeaturesBradykinesia.SNon-motorfeaturesDepressionandanxietyaffects~50%ofpatients,intrinsiccognitiveimpairmentsleepdisturbancessensoryabnormalitiesandpain,lossofsmell(anosmia)disturbancesofautonomicfunctionNon-motorfeaturesDepressionaDiagnosis50~55years,developsslowlyAtleasttwoofthefollowing:tremoratrest,rigidity,bradykinesiaorgaitdisturbance.IsresponsibletodopamineExcludeotherparkinsonismssecondaryparkinsonismsParkinson-plussyndromesDiagnosis50~55years,developsDifferentialdiagnosisSecondaryParkinsonismParkinson’s-plussyndromesParkinsonismwithabnormalmetabolismsofTAU(Taupathies)and-synuclein(-synucleinopathies)Wilson’sDisease(Hepatolenticulardegeneration)Essentialtremor(ET)DifferentialdiagnosisSecondarSecondaryParkinsonismVascularparkinsonismSeeninlacunarinfarctionPoorresponsetoL-dopaDrug-inducedparkinsonism(DIP).SecondaryParkinsonismVascularDrug-inducedparkinsonism(DIP)Isduetoneuroleptics,someatypicalantipsychosis,lithiumcarbonate,orantiemeticagents(especiallymetochlopromide).Lesscommon:valproicacid,fluoxetine(antidepressant).Antihypertensiveagentssuchasreserpineandalpha-methyldopa.ExposuretotoxinssuchasCO,disulfide,cyanideandmethanolcanalsoleadtoparkinsonism.DIPmayrespondtoanticholinergicagents,amantadine,andL-dopa.Drug-inducedparkinsonism(DIPDifferentialdiagnosisSecondaryParkinsonismParkinson’s-plussyndromesParkinsonismwithabnormalmetabolismsof-synuclein(-synucleinopathies)andTAU(Taupathies)Wilson’sDisease(Hepatolenticulardegeneration)Essentialtremor(ET)DifferentialdiagnosisSecondarParkinson’s-plussyndromesParkinsonismwithabnormalmetabolismsof-synuclein(-synucleinopathies)Multiplesystematrophy(MSA)Lewybodydisease(dementiawithLewybodies,DLB)ParkinsonismwithabnormalmetabolismsofTAU(Taupathies)Progressivesupranuclearpalsy(PSP)Corticobasaldegeneration(CBD)Parkinson’s-plussyndromesParkParkinsonismwithabnormalmetabolismsof-synuclein(-synucleinopathies)Multiplesystematrophy(MSA)parkinsonismwithsignsofCerebellar,pyramidaltractandautonomicdysfunction.Lewybodydisease(dementiawithLewybodies,DLB),DementiawithvisualhallucinationsextremelysensitivetoL-dopaParkinsonismwithabnormalmeParkinsonismwithabnormalmetabolismsofTAU(Taupathies)Progressivesupranuclearpalsy(PSP)Earlyfalls,supranuclearpalsy(botheyes,reflexicmovementisintact)Corticobasaldegeneration(CBD)alienlimb,apraxiaParkinsonismwithabnormalmeParkinson-plussyndromes

summaryShareparkinsonianfeaturesLackofresponsetoL-dopaSuggestivesignsCorticaldysfunctions:demetia,hallusination,apraxia,alienlimbOcularsignsEarlyautonomicdysfunctionandpyramidaltractsignsParkinson-plussyndromes

summaDifferentialdiagnosisSecondaryParkinsonismParkinson’s-plussyndromesParkinsonismwithabnormalmetabolismsofTAU(Taupathies)and-synuclein(-synucleinopathies)Wilson’sDisease(Hepatolenticulardegeneration)Essentialtremor(ET)DifferentialdiagnosisSecondarWilson’sDisease

(HepatolenticularDegeneration)Defectinthemetabolismofcopper(ceruloplasmin)affectingtheliver(cirrhosis),thelentiformnucleiFeaturestremor,rigidityandchoreiformmovements.CornealKayser-Fleischer(K-F)ring.Lowserumceruloplasmin,elevatedurinaryexcretionofcopper.Treatment:Copper-chelatingagentD-penicillaminWilson’sDisease

(HepatolentiCornealKayser-Fleischer(K-F)ringCornealKayser-Fleischer(K-F)Essentialtremor(ET)a6-to12Hzposturalandkinetictremor,bilateralDiagnosiscanbemadewhenthecourseismorethan3years.TreatmentPropranolol(40to320mg/d)primidone(50to750mg/d).Others:Benzodiazepines,gabapentin,topiramateEssentialtremor(ET)a6-to1HistoryandexaminationfeaturesthatwouldquestionthediagnosisofidiopathicParkinson’sDiseaseSymptoms/signsAlternativediagnosistoconsiderHistoryFallsasthefirstsymptomPSPExposuretoneurolepticsDrug-inducedParkinsonismOnsetpriortoage40IfPD,thinkgeneticcausesAssociatedwithunexplainedliverdiseaseWilson’sDiseaseSuddenonsetofparkinsonismVascularParkinsonismPhysicalexamDementiaasfirstsymptomLewybodydementiaProminentorthostasisMSAEarlydysarthriaMSALackoftremorVariousParkinson’s-plussyndromesHighfrequency(8-10Hz)symmetrictremorEssentialtremorHistoryandexaminationfeaturTreatmentofPD

GeneralconsiderationsSymptomresponsivenessBrdykinesia,rigidity,andabnormalposturerespondwellearlyinthecourseofillness.Incontrast,cognitivesymptoms,andautonomicdysfunctionrespondpoorly.RegularactivityPhysicalandmentalactivities.SlowincrementofdoselowinitiationandaslowincrementofdrugdoseAgedifferenceolderpatients(>70years):dopaminereplacementyoungerpatients:dopaminereceptoragonists.TreatmentofPD

GeneralconsidTreatmentofPDAnticholinergicagentsAntiglutamatergicagentsDopaminergicagents:mosteffectiveNeuroprotectivetherapySurgicaltreatmentanddeepbrainstimulation(DBS)TreatmentofPDAnticholinergicTreatmentofPD

DrugchoicesAnticholinergic:Trihexyphenidyl(苯海索，安坦)1-2mg,tid;Procyclidine（開(kāi)馬君，環(huán)丙啶）2.5mgtidgraduallyincreasedto20~30mg/d.Sideeffectsincludeblurring,retention,constipation.AvoiduseinolderpatientsasinitiationtherapyAntiglutamatergic:Amantadine(金剛烷胺)0.1gtidTreatmentofPD

DrugchoicesAnL-dopaLDdoseEquivalency,mgAvailablestrength,mgInitialdoseOtherconsiderationsMadopa（美多巴）

(Ldopa/benserazide)100100/25200/50200/500.5tabtidTargetdose=3-6100/25tabs/dCarbidopa/levodopaIR25/100(Sinemet,信尼麥)10010/10025/10025/1000.5tabtidTargetdose=3-625/100tabs/dCarbidopa/levodopaCR50/20015025/10050/20050/2001tabbidtotidIncreasedbioavailabilitywithfoodCarbidopa/levodopa/entacopone25/100/20012012.5/50/20025/100/20037.5/150/20025/100/2001tabbidtotidDonotsplittabletCarbidopa/levodopa/phenylalanine10010/100/3.425/100/3.425/250/825/100/3.40.5tabtidDonottakeconcomitantlywithMAOIL-dopaLDdoseAvailablestrengtDopamineagonistsAvailablestrength,mgInitialdosemgTargetdoseAsmonotherapymg/dTargetdoseAsadjuncttoLDmg/dOtherconsiderationsNon-ergotalkoloidsRopinirole(d2+d3)羅匹尼羅0.25,0.5,1,2,3,4,50.25tid12-246-16HepaticmetabolismPramipexole(d3)普拉克索0.125,0.25,1,1.50.125,tid1.5-4.50.375-3RenalmetabolismPiribedil(d2+d3)吡貝地爾5050,qd150-250ErgotalkoloidsPergolide0.05,0.25,1.00.05tid0.5-60.3-3Valvularheartdiseasebromocriptine2.5,5.01.25Bidtotid7.5-153.75-7.5PulmonaryandretroperitonealfibrosisDopamineagonistsAvailablestrLevodopainducedmotorcomplicationsIn90%ofpatientswithPDreceivedL-dopa5to10years.Twoforms:MotorfluctuationDyskinesia:(coreiform,athetotic)Treatment:Chronicreleaseformulation(CR),DAreceptoragonistLevodopainducedmotorcomplicLevodopainducedmotorcomplicationsMotorfluctuationEndofdose(wearingoff)Unpredictedmotorfluctuation(“on-off”)Dosefailuresand“delayed-on”Dyskinesia:(coreiform,athetotic)Peak-dosedyskinesiadi-phasicdyskinesia:dyskinesia-improvement-dyskinesiaEarlyAMdystonia(crampintheleg)LevodopainducedmotorcomplicLevodopacomplications-summaryComplicationsManagement1)MotorfluctuationEndofdose(wearingoff)Increasedrugtakingtime,shifttoCRformulation,addadjunctagents(entacopone,amantadine,etc.)Unpredictedmotorfluctuation(“on-off”)Difficult.CRformulation,adddopamineagonistDosefailuresand“delayed-on”Caffeinemaybebeneficial2)Dyskinesia:(coreiform,athetotic)Peak-dosedyskinesiaReducesingledose,dopamineagonistatlaterstageDi-phasicdyskinesia:dyskinesia-improvement-dyskinesiaDifficult.Increasedosageortime,addDAagonistEarlyAMdystonia(crampintheleg)CRformulationLevodopacomplications-summaryNeuroprotectivetherapyNonsteroidalanti-inflammatoryagentsorestrogen.Selegiline(MAOI,2.5~5mg,qdtobid).LargedoseofCoQ10(1200mg/d).Othersacetyl-levo-carnitine(乙酰左旋肉堿)andcreatinemonohydrate(一水肌酸).NeuroprotectivetherapyNonsterSurgicaltreatmentanddeepbrainstimulation(DBS)SurgicaltreatmentPallidotomy,thalamotomy.Nobetterthanantiparkinsonmedication.Posturalinstabilityandfalling,hypophonia,micrographia,drooling,andautonomicdysfunction,areunlikelytobenefitfromsurgery.Deepbrainstimulation(DBS)offersimpressiveresultsinproperlyselectedpatients.SurgicaltreatmentanddeepbrOthertreatmentchoicesNeurotransplantationisdisappointingDirectinfusionofGDNF(glialcell-derivedgrowthfactor)totheputamenhasbeenencouraging.OthertreatmentchoicesNeurotrSummaryofPDFeaturedbybradykinesia,tremor,rigidity,shufflinggaitandflexedposture.Differentialdiagnosis:SecondaryParkinsonisms,Parkinson’s-plussyndromes,Wilson’sDiseaseandEssentialTremor.Motorcomplications:motorfluctuationanddyskinesiaDopaminereplacementtherapycanalleviatesyndromesbutcannotcureSummaryofPDFeaturedbybradySydenham’sChoreaMostcommoncauseofchoreainchildrenTypicalageis8-9yrswithfemalepreponderance.4-8weeksafterGABHSpharyngitis.20–35%mayhavehemichorea.Hypotonia,emotionallability,ADHD,tics,OCDsymptomsmayaccompanyit.60-80%ptshavecardiacinvolvement.Sydenham’sChoreaMostcommoncSydenham’schoreaSelflimiteddisorderwithremissionwithin6-9months.Recurrenceisreportedin20-50%ofpatientsInv:ASOtitres,throatculture,cardiacexamination.Treatment:Penicillin10~14daysforstreptococcusinfection.Steroidalornon-steroidalanti-inflammationagentsSodiumValproate,Carbamazepine,Pimozide.Rheumaticfeverprophylaxis.Sydenham’schoreaSelflimitedHyperkineticDisorder

Tourette’sSyndromeThreestages:Onlymultipletics(twitchesoftheface,limbsorthewholebody)InarticulatecriesareaddedtomultipleticsEmissionofarticulatewordswithecholalia–repeatingwhatothershavesaidordone–andcoprolalia–utteringofobscenewords–areaddedinthisstageOnsetistypically2-15yearsofageDrugsthatblockdopamine(e.g.,haloperidol)amelioratethedisorderHyperkineticDis