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1、Parkinson sDisease ZhangluM D Ph D DepartmentofNeurology Outline PartA SummaryofParkinson sdiseasePartB MolecularbiologyofParkinson sdisease PARTA SummaryofParkinson sdisease1 History2 Epidemiology3 Riskfactors4 Clinicalfeatures5 Neuropathology6 Functionalneuroanatomy7 Neurochemistry8 Therapy9 Diagn
2、osis10 Summary HistoryofParkinson sdisease PD Firstdescribedin1817byanEnglishphysician JamesParkinson in AnEssayontheShakingPalsy ThefamousFrenchneurologist Charcot furtherdescribedthesyndromeinthelate1800s History JamesParkinson 1755 1824 whilebestrememberedforthediseasestatenamedafterhimbyCharcot
3、wasamanofmanytalentsandinterests Publishingonchemistry paleontologyandotherdiversetopics hewas earlyinhiscareer asocialactivistchampioningtherightsofthedisenfranchisedandpoor HiseffortsinthisareawereenoughtoresultinhisarrestandappearancebeforeThePrivyCouncilinLondononatleastoneoccasion Incollaborati
4、onwithhisson whowasasurgeon healsoofferedthefirstdescription intheEnglishlanguage ofarupturedappendix ANESSAYONTHESHAKINGPALSYCHAPTERIDEFINITION HISTORY ILLUSTRATIVECASESSHAKINGPALSY ParalysisAgitans MonographbyJamesParkinson1817 JamesParkinson HistoryofParkinson sDisease Hissmallbutfamouspublicatio
5、n EssayontheShakingPalsy appearedin1817 7yearsbeforehisdeathin1824 Theclinicaldescriptionof6patientswasaremarkablemasterpiecetestifyingtohisprodigiouspowersofobservationformostofthe6wereneveractuallyexaminedbyParkinsonhimself rather theyweresimplyobservedwalkingonthestreetsofLondon EpidemiologyofPDT
6、hemostcommonmovementdisorderaffecting1 2 ofthegeneralpopulationovertheageof65years ThesecondmostcommonneurodegenerativedisorderafterAlzheimer sdisease AD IncidenceofPD Age Incidence 100000 PrevalenceofPD Age Prevalence 100000 EpidemiologyofPD MaybelessprevalentinChinaandotherAsiancountries andinAfri
7、can Americans Prevalenceratesinmenareslightlyhigherthaninwomen reasonunknown thougharoleforestrogenhasbeendebated RiskfactorsofPDAge themostimportantriskfactorPositivefamilyhistoryMalegenderEnvironmentalexposure Herbicideandpesticideexposure metals manganese iron wellwater farming ruralresidence woo
8、dpulpmills andsteelalloyindustriesRaceLifeexperiences trauma emotionalstress personalitytraitssuchasshynessanddepressiveness Aninversecorrelationbetweencigarettesmokingandcaffeineintakeincase controlstudies EtiologyofParkinson sDisease Degenerationofthesubstantianigra withLewybodies Parkinson sdisea
9、se PARK 1 a Synuclein PARK 2 Parkin mitochondrialdysfuction oxidativestress geneticsusceptibiliesDebrisoquinhydroxylase PARK 5 UbiquitinCterminalhydrolaseL1 Toxins MPTP Rotenone Neuroinflammation Infection PARK 4 3xa Synuclein PARK 7 DJ1 Parkinson sDisease Thebasalganglia throughtheactionofdopamine
10、areresponsibleforplanningandcontrollingautomaticmovementsofthebody suchaspointingwithafinger pullingonasock writingorwalking Ifthebasalgangliaarenotworkingproperly asinParkinson sdiseasepatients allaspectsofmovementareimpaired resultinginthecharacteristicfeaturesofthedisease slownessofmovement stiff
11、nessandeffortrequiredtomovealimband often tremor ClinicalfeaturesofPD Threecardinalsymptoms restingtremor bradykinesia generalizedslownessofmovements musclerigidity ClinicalfeaturesofPDRestingtremor Mostcommonfirstsymptom usuallyasymmetricandmostevidentinonehandwiththearmatrest Bradykinesia Difficul
12、tywithdailyactivitiessuchaswriting shaving usingaknifeandfork andopeningbuttons decreasedblinking maskedfacies slowedchewingandswallowing Rigidity Muscletoneincreasedinbothflexorandextensormusclesprovidingaconstantresistancetopassivemovementsofthejoints stoopedposture anteroflexedhead andflexedknees
13、andelbows AdditionalclinicalfeaturesofPDPosturalinstability Duetolossofposturalreflexes Dysfunctionoftheautonomicnervoussystem Impairedgastrointestinalmotility bladderdysfunction sialorrhea excessiveheadandnecksweating andorthostatichypotension Depression Mildtomoderatedepressionin50 ofpatients Cogn
14、itiveimpairment Mildcognitivedeclineincludingimpairedvisual spatialperceptionandattention slownessinexecutionofmotortasks andimpairedconcentrationinmostpatients atleast1 3becomedementedduringthecourseofthedisease ClinicalStage Parkinson sDisease NeuropathologyofPDEosinophilic roundintracytoplasmicin
15、clusionscalledlewybodiesandLewyneurites Firstdescribedin1912byaGermanneuropathologist FriedrichLewy Inclusionsparticularlynumerousinthesubstantianigraparscompacta Lewybodies NeuropathologyofPD Whatfeaturehaveyouobserved Asymmetriclesions NeuropathologyofPD LewybodiesNotlimitedtosubstantianigraonly a
16、lsofoundinthelocuscoeruleus motornucleusofthevagusnerve thehypothalamus thenucleusbasalisofMeynert thecerebralcortex theolfactorybulbandtheautonomicnervoussystem Confinedlargelytoneurons glialcellsonlyrarelyaffected Lewybodies FunctionalneuroanatomyofPDSubstantianigra Themajororiginofthedopaminergicinnervationofthestriatum Partofextrapyramidalsystemwhichprocessesinformationcomingfromthecortextothestriatum returningitbacktothecortexthroughthethalamus Onemajorfunctionofthestriatumistheregulationof
