运动障碍病-运动障碍性疾病课件

运动障碍病

MovementDisorders

哈尔滨医科大学附属二院神经科

Concept随意运动调节功能障碍，肌力、感觉及小脑功能不受影响PATHOLOGYBasalganglia：caudatenucleus,lentiformnucleusClaustrum(屏状核)Amygdala(杏仁核)rednucleus(红核)substantianigra(SN)SubthalamicNucleus(STN)Baidu图片Baidu图片

皮质-皮质环路:corticalstriatal(caudate/putamen)medialglobuspallidusthalamiccorticalloop

黑质纹状体环路substantianigra-striatumpathway:SN-caudatanucleusandputamen

纹状体苍白球环路striatal-lobuspallidusloopcaudate/putamen

lateralglobuspallidus

STN

medialglobuspallidus基底节神经联系环路图11-1基底节的基本神经元环路Baidu图片CLINICSYMPTOMSHypokineticdisorders：paleostriatumParkinson’sdiseaseStriaonigraldegenerationProgressivesupranuclearpalsy(PSP)Hyperkineticdisorders：neostriatumchoreaHuntingtondisease,HD

Parkinson’sdiseasefirstdescribedinEnglandin1817byDr.JamesParkinsonANESSAYONTHESHAKINGPALSYCHAPTERIDEFINITION-HISTORY-ILLUSTRATIVECASESSHAKINGPALSY.(ParalysisAgitans.)MonographbyJamesParkinson1817

Baidu图片EPIDOMIOLOGY

Age:1~3%afterage60

Gender：Men>WomanOccupation：teachers,peasantsRuralstyleSmoking:protectivefactorsRace:White；

Hispanic-andAfrican-American；

Asian-Americans(Nelsonetal,1997)??DistributionofindividualswithParkinson’sdisease

Neurology2007,66:384-6ETIOLOGY:

ThecausesofidiopathicParkinson'sdiseaseareunclearETIOLOGY:1.Age

Baidu图片ETIOLOGY:2.GeneticFactors

Familialstudies:：α-synuclein(PARK1)Parkin(PARK2),UbiquitinC-terminal(PARK5)PINK(PARK6)DJ-1(PARK7)

LRRK2(PARK8)

SingleGeneAssociations:

MAO-B,UCH-L1,PON1,DAT,NR4A2,CYP2D6,MTHFRC677T,Synphilin-1Structureofa-synuclein

chromosome4q21-23a-synucleinaggregationandneurodegenerativediseaseETIOLOGY:3.Environmentalfactors

：MPTP,theintravenousinjectionofMPTPbynarcoticsaddicts(Langstonetal,1983)

pesticide(rotenone,paraquart)RurallivingstyleEducationProtectingfactors

PATHOLOGY:

Lossofpigmentationandcells(Dopaminergiccells)inthesubstantianigraandotherbrainstemcenters,蓝斑,脑干中缝核,迷走神经背核

Lewybody:thepresenceofesinophilicintraneuralinclusiongranulesinthebasalganglia(substantianigra)PATHOLOGY:PATHOLOGY:PATHOLOGY:Lewybody:a-synucleinbrainstem,spinalcord,andsympatheticganglia,coeruleus,PATHOLOGY:a.substantianigraatrophyb.control

Parkinson’diseasea.Lewybody，H&Eb.Bielschowskysilverstain病因&发病机制

黑质DA能神经元死亡

PD发病可能与多种因素有关,多种发病机制参与遗传因素环境因素临床症状

生理老化自由基线粒体功能衰竭钙超载兴奋氨基酸

细胞凋亡PATHOLOGY:Baidu图片PATHOGENESIS:

Dopaminedepletioninthedopaminergicnigrostriatalsystem(80%~99%)Baidu图片PATHOGENESIS:CLINICALFINDINGSMainfeaturesStatictremor(60%~70%)Rigidity(10%)Bradykinesia(10%)Postureandgaitdisorders(12%)others

CLINICALFINDINGS–

statictremorOccuratrest,mayoccuratanytime(4-to6-Hztremor)Finger-thumbrubbing(pill-rollingtremor)maybepresent1.statictremorDifferentialwithposturaltremor:Intentiontremor:Asterixis:CLINICALFINDINGS–

rigidity"lead-pipe"/stiffness"cogwheel"/jerkinessandCLINICALFINDINGS–

rigiditySpasticityRigidity:TheresistanceuniformthroughouttherangeofmovementataparticularjointandaffectagonistandantagonistmusclealikeCLINICALFINDINGS--bradykinesiaMaskedfaceCLINICALFINDINGS--

bradykinesiaAslownessofvoluntarymovementandareductioninautomaticmovement.Uncontrolled,slowmovement

CLINICALFINDINGS--

bradykinesiaMicrographicDifficultywriting,maybesmallandillegibleCLINICALFINDINGS–

AbnormalGaitandPosture:

DifficultygettingupfromachairUnstable,stooped,postureLossofbalanceGaitchanges:Difficultybeginningtowalk,Shufflingwalk,absenceofthearmswingthataccompanieslocomotion;

unsteadinessonturning,difficultinstopping,Inadvancedcasesthepatientstendtowalkwithincreasingspeedtopreventafall

(festinatinggait)Freezingofmovementwhenthemovementisstopped,inabilitytoresumemovementCLINICALFINDINGS–

AbnormalGaitandPosture:stoopedstanceunsteadinessBaidu图片CLINICALFINDINGS–

AbnormalGaitandPosture:small,shufflingstepsabsenceofthearmswingthataccompanieslocomotion;unsteadinessonturning,difficultinstopping,festinatinggaitCLINICALFINDINGS–OthersNonmotorSymptoms

DiminishedsenseofsmellLowvoicevolumePainfulfootcrampsSleepdisturbanceCLINICALFINDINGS–OthersDepressionConstipationDrooling,oilyfaceIncreasedsweatingUrinaryfrequency/urgencyMaleerectiledysfunctionINESTIGATIONSBaidu图片PET显示PD脑内DAT功能显著降低Baidu图片DIAGNOSIS英国帕金森病协会脑库(theUKParkinson’sDiseaseSocietyBrainBankClinicalDiagnosticCriteria)制定的原发性帕金森病临床诊断标准DIAGNOSIS2009年根据UK标准制定的中国原发性PD诊断标准1.运动减少：启动随意运动的速度缓慢。重复性动作的运动速度及幅度均降低2.至少存在下列1项特征：

(1)肌肉僵直；

(2)静止性震颤4一6Hz；

(3)姿势不稳(非原发性视觉、前庭、小脑及本体感受功能障碍造成)。

EvaluationofPD—修正Hoen＆Yahr分期(4)变性(遗传性)帕金森综合征(5)帕金森叠加综合征鉴别诊断(1)特发性震颤Essentialtremor(2)抑郁症Depression(3)(继发性)帕金森综合征

弥散性路易体病(DLBD)

肝豆状核变性(WD)

亨廷顿舞蹈病(HD)

多系统萎缩(MSA)

进行性核上性麻痹(PSP)

皮质基底节变性(CBGD)肝豆状核变性HepatolenticularDegeneration,HLDConcept

遗传性铜代谢障碍→脑基底节变性&肝功能损害

也称Wilson病(WD),Wilson(1912)首先描述患病率0.5~3/10万,我国较多见

临床特征:

神经系统表现:锥体外系症状、精神症状角膜:K-F色素环肝硬化\肾功能损害病理病变累及肝\脑\肾&角膜等本病特征性体征角膜色素(Kayser-Fleischerring,KF)环临床表现

liversymptom:

cirrhosis辅助检查3.Iconography

MRI:T1WI低信号,T2WI高信号X线平片:骨质疏松\骨关节炎

&骨软化(96%)DIFFERENTIALDIAGNOSIS

帕金森叠加征群

Multiplesystematrophy

Shy-DragersyndromeStriaonigraldegenerationOPCA2.手术治疗3.康复治疗1.药物治疗促进DA释放(金刚烷胺)L-Dopa替代(L-Dopa)DA受体激动(溴隐亭)抗ACh(安坦)拟DA对症治疗,恢复DA-ACh平衡L-Dopa增效剂(恩托可朋)治疗治疗EarlyparkinsonismrequiresnodrugtreatmentPhysicaltherapyandaidsfordailylivingNeuronprotectionBaidu图片MANAGEMENT–

Medicines用药原则小剂量开始，缓慢递增

A:掌握好用药的时机

B：坚持“细水度流，不求全效”

C：“low”和“slow”D:用药治疗个体化MANAGEMENT–2.MedicinesAnticholinergicDrugsAmantadine:benefitisshortlivedLevodopaandCarbidopaDopamineAgonisis:catechol-O-methyltransferaseinhibitorMonoamineoxidasetypeBinhibitorMANAGEMENT–

Medicines

⑴AnticholinergicDrugs:

helptoalleviatingtremorandrigidity

Benztropine(Cogentin)Trihexyphenidyl(Artane)MANAGEMENT–

Medicines⑵Amantadine:

benefitisshortlived

hassymptomaticbenefitasmonotherapy“likelyefficaciousandclinicallyuseful”1Sideeffectsinsomnia,livedoreticularis,confusion,legoedema,blurredvision?neuroprotectiveDADADADOPAC+H2O2.OHMAOpost-synapticreceptorL-DOPATyrosineCOMT3-MTHVA+H2O2MAOquinone+H2O2+.OHhydroquinoneDDC-多巴脱羧酶TH-酪氨酸羟化酶NQO1reuptakepre-synapticreceptorTyrosine左旋多巴VMT司吉宁SODReserpineTasmarPargylineDeprenylAmphetamineCocaineGTPBH4多巴胺受体激动剂多巴胺合成&代谢途径药物治疗治疗2)复方L-Dopa(L-Dopa+多巴脱羧酶抑制剂)控释剂(作用时间长)

Madopar

HBS息宁(SinemetCR)标准型美多芭(Madopar)--L-Dopa+苄丝肼帕金宁(Sinemet)--L-Dopa+卡比多巴水溶剂(起效快)弥散型美多芭(Madopardispersible)(3)DA替代药物

治疗MANAGEMENT–

Medicines

dopaminereplacementSideeffects：

Nausea,vomitingHypotension、cardiacarrhythmiasAnxiety,halluciation,confusion

effectsideeffectsDuration

5-10yearswearingoffOn-offDyskinesiafreezingDAcontents2.01.37dementia1.47MANAGEMENT–Medicines

dopaminereplacementSideeffects--

MotorFluctuations

Wearing–off

On-offphenomenon:inwhichabruptbuttransientfluctuationsintheseverityofparkinsonismoccuratfrequentintervalsduringtheday,apparentlywithoutanyrelationshiptothelastdoseoflevodopa

FreezingMANAGEMENT–Medicines

dopaminereplacementtime

Advancedstagetime

dopaminecontentsEarlystage

dopaminecontentstimeIncreasingtimesMANAGEMENT–Medicines

dopaminereplacementSideeffects--DyskinesiaEarly-morningdystoniaPeak-dosedyskinesiaOnsetandend-of-dosedyskinesiaMANAGEMENT–Medicines

dopaminereplacementSideeffects--Dyskinesia

onoff左旋多巴Off-perioddystoniaOnset-of-dosedyskinesiaEnd-of-dosedyskinesiaPeak-dosedyskinesiaSideeffects--Dyskinesia

表现多样:

生动的梦境抑郁\焦虑\欣快\轻躁狂错觉\幻觉\精神错乱意识模糊

治疗:调整药物&剂量,无效可用奥氮平(olanzepi