P1:SFK/UKS P2:SFK Color:1C BLBK360-FM BLBK360-Olanow March5,2011 7:39 Trim:276mmX219mm PrinterName:YettoCome Parkinson’s Disease Non-Motor and Non-Dopaminergic Features i P1:SFK/UKS P2:SFK Color:1C BLBK360-FM BLBK360-Olanow March5,2011 7:39 Trim:276mmX219mm PrinterName:YettoCome Parkinson’s Disease Non-Motor and Non-Dopaminergic Features EDITED BY C. WARREN OLANOW MD, FRCPC HenryP.andGeorgetteGoldschmidtProfessor ChairmanEmeritus,DepartmentofNeurology Professor,DepartmentofNeuroscience Director,RobertandJohnM.BendheimParkinson’sDiseaseCenter MountSinaiSchoolofMedicine NewYork,NY,USA FABRIZIO STOCCHI MD, PhD ProfessorofNeurology Director,Parkinson’sDiseaseandMovementDisordersResearchCentre InstituteforResearchandMedicalCare IRCCSSanRaffaelePisana Rome,Italy ANTHONY E. LANG MD, FRCPC Director,DivisionofNeurology,UniversityofToronto JackClarkChairforParkinson’sDiseaseResearch,UniversityofToronto Director,MovementDisorderCentre,TorontoWesternHospital Toronto,ON,Canada A John Wiley & Sons, Ltd., Publication iii P1:SFK/UKS P2:SFK Color:1C BLBK360-FM BLBK360-Olanow March5,2011 7:39 Trim:276mmX219mm PrinterName:YettoCome Thiseditionfirstpublished2011,(cid:2)c 2011byBlackwellPublishingLtd BlackwellPublishingwasacquiredbyJohnWiley&SonsinFebruary2007.Blackwell’s publishingprogramhasbeenmergedwithWiley’sglobalScientific,TechnicalandMedical businesstoformWiley-Blackwell. 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LibraryofCongressCataloging-in-PublicationData Parkinson’sdisease:non-motorandnon-dopaminergicfeatures/editedbyC.Warren Olanow,FabrizioStocchi,AnthonyE.Lang. p.;cm. Includesbibliographicalreferencesandindex. ISBN978-1-4051-9185-2(hardcover:alk.paper) 1.Parkinson’sdisease–Diagnosis. 2.Parkinson’sdisease–Pathophysiology. I.Olanow,C.W.(CharlesWarren),1941- II.Stocchi,F. III.Lang,AnthonyE. [DNLM:1.ParkinsonDisease–complications.2.Dopamine–physiology.3.Parkinson Disease–physiopathology.WL359] RC382.P26572011 616.8(cid:2)33–dc22 2010047397 AcataloguerecordforthisbookisavailablefromtheBritishLibrary. Thisbookispublishedinthefollowingelectronicformats:ePDF9781444397956;WileyOnline Library9781444397970;ePub9781444397963 (cid:3) Setin9.25/12ptPalatinobyAptaraR Inc.,NewDelhi,India 1 2011 iv P1:SFK/UKS P2:SFK Color:1C BLBK360-FM BLBK360-Olanow March5,2011 7:39 Trim:276mmX219mm PrinterName:YettoCome Contents ListofContributors, vii 12 ClinicalFeaturesofDementiaAssociatedwith Parkinson’sDiseaseandDementiawith 1 TheDopaminergicandNon-DopaminergicFeatures LewyBodies,134 ofParkinson’sDisease,1 DavidJ.Burn C.WarrenOlanow,FabrizioStocchi,&AnthonyE.Lang 13 NeuropsychologicFeaturesofParkinson’s 2 NeuropathologicInvolvementoftheDopaminergic Dementias,145 NeuronalSystemsinParkinson’sDisease,7 LeonardoCruzdeSouza,VirginieCzernecki, DanielP.Perl &BrunoDubois 3 Non-DopaminergicPathologyofParkinson’s 14 NeuropathologyofDementiainParkinson’s Disease,15 Disease,153 HeikoBraak&KellyDelTredici DennisW.Dickson&CarolynF.Orr 4 FunctionalAnatomyoftheMotorandNon-Motor 15 TreatmentofDementiaAssociatedwithParkinson’s CircuitryoftheBasalGanglia,32 Disease,163 YolandSmith MuratEmre 5 FunctionalOrganizationoftheBasalGanglia: 16 PsychosisinParkinson’sDisease,170 DopaminergicandNon-DopaminergicFeatures,56 JosephH.Friedman CarlosJuri,MariaC.Rodriguez-Oroz,&JoseA.Obeso 17 DepressioninParkinson’sDisease,183 6 AnatomyandPhysiologyofLimbicSystem TiffiniVoss&IreneHegemanRichard DysfunctioninParkinson’sDisease,70 AnthonyA.Grace 18 AnxietySyndromesandPanicAttacks,193 DanielWeintraub&StaciHoops 7 AnimalModelsofParkinson’sDisease:the Non-MotorandNon-DopaminergicFeatures,79 19 DopamineDysregulationSyndrome,202 KatherineE.Soderstrom,ShilpaRamaswamy,C.Warren SeanS.O’Sullivan&AndrewJ.Lees Olanow,&JeffreyH.Kordower 20 NeurobiologyofImpulseControlDisordersin 8 TheEmergingEntityofPre-MotorParkinson’s Parkinson’sDisease,215 Disease,93 ThomasD.L.Steeves,JanisMiyasaki,AnthonyE.Lang, J.WilliamLangston &AntonioP.Strafella 9 FunctionalImagingStudiesinParkinson’sDisease: 21 SleepDisordersinParkinson’sDisease,233 theNon-DopaminergicSystems,105 FriederikeSixel-Do¨ring&ClaudiaTrenkwalder A.JonStoessl 22 NeuronalMechanismsofREMSleepandTheirRole 10 AssessmentofNon-MotorFeaturesofParkinson’s inREMSleepBehaviorDisorder,240 Disease:ScalesandRatingTools,111 JunLu&CliffordB.Saper ChristopherG.Goetz&CristinaSampaio 23 REMSleepBehaviorDisorderand 11 ClinicalTrialMeasuresoftheNon-MotorFeaturesof NeurodegenerativeDisorders,246 Parkinson’sDisease,126 MarkW.Mahowald,CarlosH.Schenck,&MichelA. KarlKieburtz CramerBornemann v P1:SFK/UKS P2:SFK Color:1C BLBK360-FM BLBK360-Olanow March5,2011 7:39 Trim:276mmX219mm PrinterName:YettoCome vi Contents 24 GastrointestinalandSwallowingDisturbancesin 33 OrthopedicComplicationsofParkinson’sDisease,374 Parkinson’sDisease,257 JosephRudolph&MicheleTagliati RonaldF.Pfeiffer 34 OtherNon-MotorSymptomsofParkinson’s 25 BladderDysfunctioninParkinson’sDiseaseand Disease,387 OtherParkinsonism,274 MarkJ.Edwards&KailashP.Bhatia FabrizioStocchi,MargheritaTorti,GiovanniPalleschi, 35 OverviewoftheMedicalTreatmentoftheNon-Motor &AntonioCarbone andNon-DopaminergicFeaturesofParkinson’s 26 OrthostaticHypotensioninParkinson’sDisease,284 Disease,394 UdayMuthane&ChristopherJ.Mathias MarkStacy&JosephJankovic 27 SexualDysfunction,296 36 SurgeryforNon-DopaminergicandNon-Motor KimberlyPargeon,KarenAnderson,&WilliamJ.Weiner FeaturesofParkinson’sDisease,409 BrianJ.Snyder&AndresM.Lozano 28 OlfactoryDysfunction,304 JohnE.Duda&MatthewB.Stern 37 EffectsofExerciseonBasalGangliaFunctionin Parkinson’sDiseaseandItsAnimalModels,416 29 PainandParesthesiainParkinson’sDisease,315 GiselleM.Petzinger,BethE.Fisher,CharlieK.Meshul, Shen-YangLim&AndrewH.Evans JohnP.Walsh,GarnikAkopian,&MichaelW.Jakowec 30 RestlessLegsSyndromeandAkathisiainParkinson’s 38 Non-DopaminergicApproachestotheTreatmentof Disease,333 Parkinson’sDisease,432 AlexIranzo&CynthiaL.Comella SusanH.Fox&JonathanM.Brotchie 31 SpeechandVoiceDisordersinParkinson’s 39 ProspectsforNeuroprotectiveTherapiesThatCan Disease,346 ModulateNon-DopaminergicFeaturesinParkinson’s LorraineRamig,CynthiaFox,&ShimonSapir Disease,455 32 Gait,PosturalInstability,andFreezing,361 C.WarrenOlanow&AnthonyE.Lang YvetteA.M.Grimbergen,Arle`neD.Speelman,Marjolein Index, 463 A.vanderMarck,YvonneSchoon,&BastiaanR.Bloem Colourplatesectioncanbefoundfacingp.182 P1:SFK/UKS P2:SFK Color:1C BLBK360-FM BLBK360-Olanow March5,2011 7:39 Trim:276mmX219mm PrinterName:YettoCome List of Contributors Garnik Akopian MD Leonardo Cruz de Souza MD AndrusGerontologyCenter,UniversityofSouthernCalifornia, DepartmentofNeurology,Salpeˆtrie`reUniversityHospital,Paris, LosAngeles,CA,USA France Karen Anderson MD Virginie Czernecki PhD DepartmentofNeurology,UniversityofMarylandMedical DepartmentofNeurology,Salpeˆtrie`reUniversityHospital,Paris, Center,Baltimore,MD,USA France Kelly Del Tredici MD,PhD Kailash P. Bhatia MD,FRCP ClinicalNeuroanatomy,DepartmentofNeurology,Centerfor SobellDepartmentofMotorNeuroscienceandMovement ClinicalResearch,UniversityofUlm,Ulm,Germany Disorders,InstituteofNeurology,UniversityCollegeLondon, QueenSquare,London,UK Dennis W. Dickson MD DepartmentofNeuroscience,MayoClinic,Jacksonville,FL,USA Bastiaan R. Bloem MD DepartmentofNeurologyandParkinsonCentreNijmegen, Bruno Dubois MD DondersInstituteforBrainCognitionandBehaviour,Radboud ProfessorofNeurology,DepartmentofNeurology,Salpeˆtrie`re UniversityNijmegenMedicalCentre,Nijmegen,TheNetherlands UniversityHospital,Paris,France Heiko Braak MD John E. Duda MD ClinicalNeuroanatomy,DepartmentofNeurology,Centerfor Parkinson’sDiseaseResearch,EducationandClinicalCenter ClinicalResearch,UniversityofUlm,Ulm,Germany (PADRECC),PhiladelphiaVeteransAffairsMedicalCenterand DepartmentofNeurology,UniversityofPennsylvaniaSchoolof Jonathan M. Brotchie PhD Medicine,Philadelphia,PA,USA TorontoWesternResearchInstitute,TorontoWesternHospital, Toronto,ON,Canada Mark J. Edwards PhD SobellDepartmentofMotorNeuroscienceandMovement David J. Burn FRCP,MD,MA Disorders,InstituteofNeurology,UniversityCollegeLondon, QueenSquare,London,UK ProfessorofMovementDisordersNeurologyandHonorary ConsultantNeurologist,ClinicalAgeingResearchUnit,Campus forAgeingandVitality,NewcastleuponTyne,UK Murat Emre MD ProfessorofNeurology,IstanbulFacultyofMedicine,Department ofNeurology,BehavioralNeurologyandMovementDisorders Antonio Carbone MD Unit,IstanbulUniversity,C¸apaIstanbul,Turkey InstituteofUrology,University“LaSapienza”,Rome,Italy Andrew H. Evans MD,FRACP Cynthia L. Comella MD DepartmentofNeurology,RoyalMelbourneHospital,Parkville, Professor,DepartmentofNeurologicalSciences,RushUniversity Victoria,andDepartmentofMedicine,UniversityofMelbourne, MedicalCenter,Chicago,IL,USA Australia Michel A. Cramer Bornemann MD Beth E. Fisher MD MinnesotaRegionalSleepDisordersCenterandHennepin DivisionofBiokinesiologyandPhysicalTherapy,Departmentof CountyMedicalCenter,UniversityofMinnesotaMedicalSchool, Neurology,KeckSchoolofMedicine,UniversityofSouthern Minneapolis,MN,USA California,LosAngeles,CA,USA vii P1:SFK/UKS P2:SFK Color:1C BLBK360-FM BLBK360-Olanow March5,2011 7:39 Trim:276mmX219mm PrinterName:YettoCome viii ListofContributors Cynthia M. Fox PhD,CCC-SLP Jeffrey H. Kordower PhD ResearchAssociate,DepartmentofSpeech,Languageand DepartmentofNeurologicalSciences,RushUniversityMedical HearingScience,UniversityofColorado–Boulderandthe Center,Chicago,IL,USA NationalCenterforVoiceandSpeech–Denver,CO,USA J. William Langston MD Susan H. Fox BSc,MB,ChB,MRCP(UK),PhD ScientificDirectorandCEO,Parkinson’sInstitute,Sunnyvale,CA, AssistantProfessorofNeurology,MovementDisordersClinic, USA DivisionofNeurology,UniversityofToronto,Toronto,ON, Canada Andrew J. Lees FRCP DirectorofResearch,RetaLilaWestonInstituteofNeurological Jospeh H. Friedman MD Studies,InstituteofNeurology,UniversityCollegeLondon, MovementDisordersProgram,ButlerHospitalandDepartment London,UK ofNeurology,WarrenAlpertMedicalSchoolofBrownUniversity, Providence,RI,USA Shen-Yang Lim MD,FRACP FacultyofMedicine,UniversityofMalaya,KualaLumpur, Christopher G. Goetz MD Malaysia ProfessorofNeurologicalSciencesandProfessorof Pharmacology,RushUniversityMedicalCenter,Chicago,IL,USA Andres W. Lozano MD,PhD,FRCSC,FRS ProfessorandDanFamilyChairmanofNeurosurgery,University Anthony A. Grace PhD ofTorontoandSeniorScientist,TorontoWesternResearch DepartmentsofNeuroscience,Psychiatry,andPsychology, Institute,CanadaResearchChairinNeuroscience,Toronto,ON, UniversityofPittsburgh,Pittsburgh,PA,USA Canada Yvette Grimbergen MD Jun Lu MD,PhD DepartmentofNeurology,PrograminNeuroscienceandDivision DepartmentofNeurology,LeidenUniversityMedicalCentre, ofSleepMedicine,HarvardMedicalSchoolandBethIsrael LeidenandDepartmentofNeurology,SintFranciscusGasthuis, DeaconessMedicalCenter,Boston,MA,USA Rotterdam,TheNetherlands Mark W. Mahowald MD Staci Hoops BA Director,MinnesotaRegionalSleepDisordersCenterand DepartmentofPsychiatry,UniversityofPennsylvania, HennepinCountyMedicalCenter,UniversityofMinnesota Philadelphia,PA,USA MedicalSchool,Minneapolis,MN,USA Alex Iranzo MD Christopher J. Mathias DPhil,DSc,FRCP,FMedSci NeurologyService,HospitalClinicandInstitutd’Investigacio´ AutonomicandNeurovascularMedicineUnit,ImperialCollege Biome`diquesAugustPiiSunyer(IDIBAPS),Barcelona,Spain LondonatStMary’sHospitalandAutonomicUnit,National HospitalforNeurologyandNeurosurgery,QueenSquareand Michael Jakowec MD InstituteofNeurology,UniversityCollegeLondon,London,UK DepartmentofNeurology,KeckSchoolofMedicineandDivision ofBiokinesiologyandPhysicalTherapy,UniversityofSouthern Charlie K. Meshul MD California,LosAngeles,CA,USA DepartmentofBehavioralNeurosciences,OregonHealthSciences University,ResearchServices,PortlandVAMedicalCenter, Joseph Jankovic MD Portland,OR,USA ProfessorofNeurology,Director,Parkinson’sDiseaseCenterand MovementDisordersClinic,BaylorCollegeofMedicine, Janis Miyasaki MD,FRCPC Houston,TX,USA TorontoWesternHospital(MovementDisordersCentre), UniversityHealthNetwork(UHN),UniversityofToronto, Carlos Juri MD Toronto,ON,Canada ClinicaUniversitariaandMedicalSchool,NeuroscienceDivision, CIMAandCentrodeInvestigacionBiomedicaenRedsobre Uday Muthane DM,FNASc EnfermedadesNeurodegenerativas(CIBERNED),Universityof ParkinsonandAgingResearchFoundation,Bangalore,India Navarra,Pamplona,Spain Jose A. Obeso MD,PhD Karl Kieburtz MD,MPH ClinicaUniversitariaandMedicalSchool,NeuroscienceDivision, ProfessorofNeurologyandCommunityandPreventive CIMAandCentrodeInvestigacionBiomedicaenRedsobre Medicine,DepartmentofNeurology,UniversityofRochester EnfermedadesNeurodegenerativas(CIBERNED),Universityof MedicalCenter,Rochester,NY,USA Navarra,Pamplona,Spain P1:SFK/UKS P2:SFK Color:1C BLBK360-FM BLBK360-Olanow March5,2011 7:39 Trim:276mmX219mm PrinterName:YettoCome ListofContributors ix Carolyn F. Orr FRACP,PhD Clifford B. Saper MD,PhD DepartmentofNeurology,MayoClinic,Rochester,NY,USA DepartmentofNeurology,PrograminNeuroscienceandDivision ofSleepMedicine,HarvardMedicalSchoolandBethIsrael Sean S. O’Sullivan MRCPI DeaconessMedicalCenter,Boston,MA,USA ClincialResearchFellow,RetaLilaWestonInstituteofNeurolgical Studies,InstituteofNeurology,UniversityCollegeLondon, Shimon Sapir PhD,CCC-SLP London,UK AssociateProfessor,CommunicationSciencesandDisorders, FacultyofSocialWelfareandHealthSciences,UniversityofHaifa, Giovanni Palleschi MD Haifa,Israel InstituteofUrology,University“LaSapienza”,Rome,Italy Carlos H. Schenck MD MinnesotaRegionalSleepDisordersCenterandHennepin Kimberly Pargeon MD CountyMedicalCenter,UniversityofMinnesotaMedicalSchool, DepartmentofNeurology,UniversityofMarylandMedical Minneapolis,MN,USA Center,Baltimore,MD,USA Yvonne Schoon MD Daniel P. Perl MD DepartmentofGeriatrics,RadboudUniversityNijmegenMedical ProfessorofPathology(Neuropathology),UniformedServices Centre,Nijmegen,TheNetherlands UniversityoftheHealthSciences,Bethesda,MD,USA Friederike Sixel-Do¨ring MD Giselle Petzinger MD Paracelsus-Elena-Klinik,CenterforParkinsonismandMovement DepartmentofNeurology,KeckSchoolofMedicineandDivision Disorders,KasselandPhilippsUniversity,Marburg,Germany ofBiokinesiologyandPhysicalTherapy,UniversityofSouthern California,LosAngeles,CA,USA Yoland Smith PhD ProfessorofNeurology,YerkesNationalPrimateResearchCenter Ronald F. Pfeiffer MD andDepartmentofNeurology,EmoryUniversity,Atlanta,GA, DepartmentofNeurology,UniversityofTennesseeHealthScience USA Center,Memphis,TN,USA Brian J. Snyder MD Shilpa Ramaswamy PhD DivisionofNeurosurgery,TorontoWesternHospital,University DepartmentofNeurologicalSciences,RushUniversityMedical ofToronto,Toronto,ON,Canada Center,Chicago,IL,USA Katherine E. Soderstrom BA Lorraine Ramig PhD,CCC-SLP DepartmentofNeurologicalSciences,RushUniversityMedical Professor,UniversityofColorado–Boulder,SeniorScientist, Center,Chicago,IL,USA NationalCenterforVoiceandSpeech–Denver,CO,andAdjunct Professor,ColumbiaUniversity,NewYork,NY,USA Arle`ne D. Speelman MSc DepartmentofNeurologyandParkinsonCentreNijmegen, Irene Hegeman Richard MD DondersInstituteforBrainCognitionandBehaviour,Radboud DepartmentofNeurology,UniversityofRochesterSchoolof UniversityNijmegenMedicalCentre,Nijmegen, MedicineandDentistry,Rochester,NY,USA TheNetherlands Maria C. Rodriquez-Oroz MD,PhD Mark Stacy MD ClinicaUniversitariaandMedicalSchool,NeuroscienceDivision, DivisionofNeurology,DukeUniversityMedicalSchool,Durham, CIMAandCentrodeInvestigacionBiomedicaenRedsobre NC,USA EnfermedadesNeurodegenerativas(CIBERNED),Universityof Navarra,Pamplona,Spain Thomas D.L. Steeves MD,FRCPC TorontoWesternHospital(MovementDisordersCentre), Jospeh Rudolph MD UniversityHealthNetwork(UHN),UniversityofToronto, DepartmentofNeurology,MountSinaiSchoolofMedicine,New Toronto,ON,Canada York,NY,USA Matthew B. Stern MD Cristina Sampaio MD,PhD Parkinson’sDiseaseResearch,EducationandClinicalCenter ProfessorofClinicalPharmacologyandTherapeutics,Laboratory (PADRECC),PhiladelphiaVeteransAffairsMedicalCenter,and ofClinicalPharmacologyandTherapeutics,InstitutodeMedicina DepartmentofNeurology,UniversityofPennsylvaniaSchoolof Molecular,FaculdadedeMedicinadeLisboa,Lisbon,Portugal Medicine,Philadelphia,PA,USA P1:SFK/UKS P2:SFK Color:1C BLBK360-FM BLBK360-Olanow March5,2011 7:39 Trim:276mmX219mm PrinterName:YettoCome x ListofContributors A. Jon Stoessl CM,MD,FRCPC Marjolein A. van der Marck MSc PacificParkinson’sResearchCentre,UniversityofBritish DepartmentofNeurologyandParkinsonCentreNijmegen, Columbia,Vancouver,BC,Canada DondersInstituteforBrainCognitionandBehaviour,Radboud UniversityNijmegenMedicalCentre,Nijmegen,TheNetherlands Antonio P. Strafella MD,PhD,FRCPC AssociateProfessor,DepartmentofMedicine/Neurology, Tiffini Voss MD MovementDisordersCentre,TorontoWesternHospitaland DepartmentofNeurology,UniversityofRochesterSchoolof SeniorScientist,DivisionofBrain,Imagingand MedicineandDentistry,Rochester,NY,USA Behaviour–SystemsNeuroscience,TorontoWesternResearch InstituteandAssociateScientist,PETImagingCenter,Centerfor John P. Walsh MD AddictionandMentalHealth,UniversityofToronto,Toronto, AndrusGerontologyCenter,UniversityofSouthernCalifornia, ON,Canada LosAngeles,CA,USA Michele Tagliati MD,FAAN ViceChairman,DepartmentofNeurology,Director,Movement William J. Weiner MD Disorders,Cedars-SinaiMedicalCenter,LosAngeles,CA,USA ProfessorandDepartmentChairman,DepartmentofNeurology, UniversityofMarylandMedicalCenter,Baltimore,MD,USA Margherita Torti MD InstituteofNeurology,IRCCSSanRaffaelePisana,Rome,Italy Daniel Weintraub MD AssistantProfessorofPsychiatry,UniversityofPennsylvaniaand Claudia Trenkwalder MD Parkinson’sDiseaseResearch,EducationandClinicalCenter Paracelsus-Elena-Klinik,CenterforParkinsonismandMovement (PADRECC)andMentalIllnessResearch,EducationandClinical Disorders,KasselandUniversityofGo¨ttingen,Go¨ttingen, Center(MIRECC),VeteransAffairsMedicalCenterPhiladelphia, Germany PA,USA P1:SFK/UKS P2:SFK Color:1C BLBK360-CP BLBK360-Olanow February28,2011 10:45 Trim:276mmX219mm PrinterName:YettoCome (a) (b) Plate2.1 SubstantianigraparscompactaneuronswithLewybodies;hematoxylinandeosinstain(a)andα-synucleinimmunostain(b). (a) (b) Plate2.2 Grossappearanceofthemidbrain:transversesectionofanormalcontrol(a)andacaseofParkinson’sdisease(b). 1