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ExtrapyramidalDisorderIntroductionExtrapyramidaldisorderimpairstheregulationofvoluntarymotoractivitywithoutdirectlyaffectingstrength,sensationorcerebellarfunction.Manifestationsinclude:--hyperkineticdisordersassociatedwithabnormal,involuntarymovements--hypokineticdisorders.Tremor:asteadyrhythmicoscillatorymovementofthemusclesChorea:rapid,irregular,jerkymovementsDystonia:co-contractionofagonistsandantagonistmusclesinoneregiononattemptedvoluntarymovement.Myoclonus:Involuntaryshock-likecontractions,irregularinrhythmandamplitude,followedbyrelaxation.SuddenrapidtwitchlikemusclecontractionAbnormalmovementExtrapyramidalSystemTheextrapyramidalsystemconsistsofthosepartsofthecentralnervoussystemotherthanmotorcortexandcorticospinaltracts,whichareconcernedwithmovementsandposture.Theyinclude:
Basalganglia;Subthalamicnuclei;Substantianigra;Rednuclei.Parkinsonism
MajorcharactersTremorHypokinesiaRigidityAbnormalgaitandpostureOccursinallethnicgroups,intheUSAandWesternEuropeitsprevalenceis1-2/1000population,withanapproximatelyequalsexdistribution.Thedisorderbecomesincreasinglycommonwithadvancingage.Etiology
A.IdiopathicAverycommonvarietyofParkinsonismoccurswithoutobviouscause.ThisidiopathicformiscalledParkinson’sdiseaseB.EncephalitislethargicaInthefirsthalfofthetwentiethcentury,ParkinsonismoftendevelopedinpatientswithahistoryofVonEconomo’sencephalitis.Thistypeofinfectionisnotnowencountered,casesofpostencephaliticParkinsonismarebecomingincreasinglyrare.C.Drugortoxin-inducedParkinsonism1.Therapeuticdrugs—phenothiazines,butyrophenones,metoclopramide,reserpine,tetrabenazine,etccancauseareversibleParkinsoniansyndrome.2.Toxicsubstances—EnvironmentaltoxinssuchasmanganesedustcanleadtoParkinsonism.PesticideexposureisalsoassociatedwiththedevelopmentofParkinsonism.Pathogenesis
Dopamineandacetylcholinearepresentinthecorpusstriatum,wheretheyactasneurotransmitters.Inidiopathicparkinsonism,itisgenerallybelievedthatthenormalbalancebetweenthesetwoantagonisticneurotransmittersisdisturbedbecauseofdopaminedepletioninthedopaminergicneuron.ChangesinNeurotransmittersDopaminedecrease70-95%inputamenCholinergicactivityrelativelyincreasedReducedactivityofcholineacetyltransferaseinthenucleusbasalisandinthecortexClinicalFindingsCommonFeaturesOnsetisusuallyinmiddletolatelifeInsidiousonsetandprogressiveOnsetfromonesideProgresslikeas“N”ClinicalfindingsTremor4~6HztremorofParkinsonismischaracteristicallymostconspicuousatrest,itincreasesattimesofemotionalstressandoftenimprovesduringvoluntaryactivity.Itcommonlybeginsinthehandorfoot,whereittakestheformofrhythmic.Thefaceintheareaofthemouthmaybeinvolvedaswell.Itmayultimatelybepresentinallofthelimbs.Rigidity
RigidityisacharacteristicclinicalfeatureofParkinsonism.Thereisstiffnessofthelimbswhichcanbefeltthroughouttherangeofmovementandequallyintheflexorsandextesors.Thisistermed“l(fā)ead-pip”rigidity.Whencombinedwithtremor,thereisajerkyelement,whichistermed“cog-wheel”rigidity.C.Hypokinesia
hypokinesia--aslownessofvoluntarymovementandareductioninautomaticmovement,suchasswingingthearmswhilewalking.Thepatient’sfaceisrelativelymasklikefacies.Thevoiceisoflowvolumeandtendstobepoorlymodulated.rapidlyalternatingmovementsareimpaired,butpowerisnotdiminished.Thehandwritingissmalltremulous,andhardtoread.D.Abnormalgaitandposture
Thepatientgenerallyfindsitdifficulttogetupfrombedandtendstoadoptaflexedpostureonstanding.It’softendifficulttostartwalking.Thegaititselfischaracterizedbysmall,shufflingsteps.Generallysomeunsteadinessonturning,andmaybedifficultyinstopping.Inadvancedcases,thepatienttendstowalkwithincreasingspeedtopreventafallbecauseofthealteredcenterofgravitythatresultsfromtheabnormalposture.TreatmentTheindicatedtreatmentisdirectedtowardrestoringthedopaminergic:cholinergicbalanceinthestriatum.BlockingtheeffectofacetylcholinewithanticholinergicdrugsorenhancingdopaminergictransmissionA.Anticholinergicdrugs
trihexyphenidyl(antan)commonsideeffects:drynessofthemouth,constipation,urinaryretention,confusion.startedwithasmalldose,thengraduallyincreaseduntilbenefitoccursorsideeffectslimitfurtherincrements.B.Amantadine
CanbegivenformildParkinsonismeitheraloneorincombinationwithananticholinergicagent.standarddose:100mgoraltwicedaily.ItcanimproveallclinicalfeaturesofParkinsonism,butmanypatientsfailtorespondforitsbenefitisshort-livedC.Levodopa
Levodopaisconvertedinthebodytodopamine,helpallthemajorclinicalfeaturesofParkinsonism,andisoftenparticularlyhelpfulagainsthypokinesia.
On-offphenomenon:whichabruptbuttransientfluctuationintheseverityofParkinsonismoccuratfrequentintervalsduringthedayapparentlywithoutanyrelationshiptothelastdoseoflevodopa.D.DopamineAgonists
BromocriptinestimulatesdopamineD2receptors,usuallyfolloweddopaminergictherapy,startingdose1.25mg/dfor1weekincrementsevery2weeks,dependingontheresponseanddevelopmentofsideeffects.E.Catechol-O-methyltransferaseinhibitorsTheseinhibitorsmaybeusedtoreducethedoserequirementsofandanyresponsefluctuationstoLevodopa.Tolcapone:100~200mgthreetimesdailyEnta
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