運(yùn)動(dòng)障礙和帕金森病英文版課件

Movementdisorders1運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

Movementdisorders:

Theregulationofvoluntarymotoractivityisimpairedwithoutdirectlyaffectingstrength,sensation,orcerebellarfunction.

2運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

Extrapyramidalsystem:Basalganglia:Corpusstriatum:3運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

pyramidalsystemExtrapyramidalsystem4運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

Extrapyramidalsystem

5運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

Basalganglia:Nouniversallyacceptedanatomicdefinition.Forclinicalpurposesitmaycomprisecaudatenucleus,putamen,globuspallidus,(subthalamicnucleus,andsubstantianigra).6運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

Basalganglia:7運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

Basalganglia:8運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

Corpusstriatum:Neostriatum:CaudatenucleusPutamenPaleostriatum:PallidumLentiformnucleus9運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

Corpusstriatum10運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

BasicneuronalcircuitryofthebasalgangliaBasiccircuitryofthebasalgangliaconsistsofthreeinteractingneuronalloops:CorticocorticalloopNigrostriatalloopStriatopallidalloop11運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersIntroduction:

Classificationofmovementdisorders

*Tremor:

Asteadyrhythmicoscillatorymovementofthemuscles.Tremormaybenormal(physiological)orabnormal(pathological)

12運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisorders*Tremor:

*Posturaltremor

PhysiologictremorEnhancedphysiologictremorFamilialoridiopathictremor(Essentialtremor)

13運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisorders*Tremor:

*Intentiontremor

CerebellardiseaseRednucleartremor

DrugtoxicityWilson’sdisease*Resttremor

Parkinson’sdiseaseWilson’sdiseaseHeavymetalpoisoning14運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisorders*Choreaandathetosis15運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisorders

*Chorea:Rapid,irregular,jerkymovementsaffactingtheface,trunk,andlimbs.

Athetosis:

Slow,writhingmovementswhichaffectallmusclegroups.

Choreoathetosis:Twotypesofmovementdisorderoftenoccurtogether.

16運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisorders*Hemiballismus:Unilateralviolentflingingmovementsoftheproximallimbmuscles.

Alesionofcontralateralsubthalmicnucleus.*Asterixis:Flappingofhandsobservedwitharmsoutstretchedandhandsdorsiflexed.Theflapoccursseveraltimesaminute.

17運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisorders*Tics:Repetitivebriefcontractionofamuscleorgroupofmuscles.GillesdelaTourettesyndrome*Habitspasms:Habitualmovementsthatapersonfeelstheneedtomaketorelievetensionandmaybesuppressedvoluntarily,suchassniffing,blinking.18運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisorders*Ticsandhabitspasms

19運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisorders*Dystonia:

prolongedmuscularcontractiononattemptedvoluntarymovement,whichresultsinabnormalposturing.

20運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisorders*Dystonia:

DystoniamaybeGeneralizedorFocal.

Generalizeddystonia:&dystoniamusculorumdeformans:&Drugs:&Symptomaticdystonia:Wilson’sdisease:&Paroxysmaldystonia:

Focaldystonia:

&Cervicaldystonia(spasmodictorticollis’)

&Blepharospasm:

&Oromandibulardystonia:

&writer’scramp:21運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisorders*Myoclonus:Shock-likeasymmetricalmuscularcontractionsthatoccurirregularly.

GeneralizedorFocal

Physiologicmyoclonus:Nocturnal,HiccupEssentialmyoclonus:Epilepticmyoclonus:Symptomaticmyoclonus:

22運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersClinicalEvaluationofPatients

*Hstory:AgeatonsetModeofonsetCourseMedicalhistory:drugandfamilyhistorygeneralmedicalhistory

*Examination*Investigativestudies:23運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024MovementDisordersThedisorderarisesfromdiseasesofthebasalganglia

Hereditary:

Huntington’sdisease

Staticencephalopathy(cerebralpalsy):Sydenham’schorea:Choreagravidarum:Drugtoxicity:

Miscelaneousmedicaldisorders:CerebrovasculardisordersStructurallesionsofthesubthalamicnucleus24運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024Parkinson’sdisease

帕金森病25運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024帕金森病的歷史回顧Jean-MartinCharcot，1867臨床分類和鑒別診斷提議以帕金森的名字命名該病為“帕金森病”最早的有效治療：顛茄類生物鹼JamesParkinson，1817首次對疾病的臨床表現(xiàn)進(jìn)行了較為系統(tǒng)的分析，並命名為“震顫麻痹”26運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024流行病學(xué)Ruralliving,well-waterconsumption,mining,welding,MPTP：environmentalfactors?Male/femaleprevalence=1.5Recently,geneticlinkageandassociationstudieshavedemonstratedastronggeneticcontributiontoPD.About15%ofPDcasesareinherited,and17PDsusceptibilitychromosomalloci(PARK1-17)andatleast10specificPDsusceptibilitygenesforfamilialPDhavenowbeenidentified.Theremaining85%ofPDcasesare“idiopathic,”(i.e.,ofunknowncause),butPDsusceptibilitygeneshavealsobeenimplicatedinasmallpercentageofsporadiccases.27運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024流行病學(xué)UnitedStatesandWesternEurope:

US:107-329per100,000(~0.5-1millionpersons)Germany:183per100,000Asia:Japan:76–193per100,000China:130per100,000(~1.7millionpersons)Africa:Nigeria:67per100,000Ethiopia:7per100,000(duetolowlife-expectancy?)Specialpopulations:Amish(US):970per100,000!

28運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024著名帕金森病患者OwenChamberlainSalvadoreDaliDengXiaopingYasirArafatMohamedAli29運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024帕金森病的患病率與年齡相關(guān)LancetNeurol2006原發(fā)性帕金森病是一種常見的與年齡相關(guān)的疾病以人群為基礎(chǔ)的帕金森病流行率研究0510152025303540455030405060708090100荷蘭鹿特丹西班牙中部美國Copiah縣法國西西里島西班牙阿拉貢歐洲中國中國臺(tái)灣年齡（歲）患病率（%）30運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024中國65歲以上人群帕金森病患病率高達(dá)1.66%中國PD標(biāo)準(zhǔn)化患病率*(所有性別)如下：≥65歲：1.66％(95％CI1.48-1.86)≥55歲：0.96％(95％CI0.85-1.08)*標(biāo)準(zhǔn)化患病率：從1999年中國人口普查使用直接方法計(jì)算每100人患病率患病率據(jù)統(tǒng)計(jì)，中國目前有200多萬的帕金森病患者Lancet2005據(jù)估計(jì)，到2030年，中國將有近500萬帕金森病患者。中國帕金森病患病率31運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024帕金森病的直接/間接疾病負(fù)擔(dān)構(gòu)成（美國，2005年）Movementdisorder2005間接和醫(yī)療支出是帕金森病主要經(jīng)濟(jì)負(fù)擔(dān)在總的經(jīng)濟(jì)負(fù)擔(dān)中，大部分與間接醫(yī)療服務(wù)費(fèi)用相關(guān)，如勞動(dòng)力的喪失和護(hù)理照顧，處方藥物費(fèi)用僅占4%。帕金森病經(jīng)濟(jì)負(fù)擔(dān)32運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024帕金森病組織病理學(xué)含色素的多巴胺能神經(jīng)元缺失正常黑質(zhì)正常黑質(zhì)多巴胺能細(xì)胞變性帕金森病Lewy小體NeuropatholApplNeurobiol1989圖片由JJHauw博士（法國巴黎Pitié-Salpêtrière醫(yī)院神經(jīng)病理科）提供。圖片由étienneHirsch博士（INSERMU679，法國巴黎Pitié-Salpêtrière醫(yī)院）提供。病理特徵33運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024帕金森病環(huán)境因素:MPTPMPTP=1-methyl-4-phenyl-1,2,3,6-tetrahydropyridineMPP+=1-methyl-4-phenylpyridinium=potentinhibitorofmitochondrialcomplexI(toxic!)Note:MPTPalsoproducesexcessiveactivationofmicroglialcellsleadingtothereleaseoftoxiccytokines34運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024CigarettesmokeCaffeinatedcoffeeNon-steroidalanti-inflammatorydrugs(NSAIDs)帕金森病環(huán)境因素:保護(hù)因素

35運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024遺傳學(xué)線索Lateonset,autosomaldominantinheritancePD:

SNCA(alpha-synuclein)

LRRK2(Leucine-richrepeatkinase2)Earlyonset,autosomalrecessiveinheritancePD*:

PRKN(parkin,PARK2:E3ubiquitinligase)

PINK1

(PARK6;PTEN-inducedputativekinase2)

DJ-1(PARK7;molecularchaperone/anti-oxidant)*PDisobservedinindividualshomozygousforthesamemutationorindividualsharboringdifferentpathogenicmutationsinthesamegene(termedcompoundheterozygotes).36運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024Parkinson’sdiseaseEtiology:Genetics?

遺傳方式定位基因蛋白功能發(fā)病時(shí)間LBPark1AD4q21α-Sunuclein分子伴侶40s+Park2AR6q25ParkinE3泛素蛋白連接酶20s-Park3AD2p13?？60s+Park4AD4q21α-Sunuclein分子伴侶30s+Park5AD4p14UCH-L1泛素蛋白連接酶50s+Park6AR1p36Pink-1線粒體蛋白激酶30s?Park7AR1p36DJ1分子伴侶線粒體蛋白激酶30s?Park8AD12p11LRRK2細(xì)胞凋亡與骨架重排？50s±Park9AR1p36ATP13A2溶酶體5型P族ATP酶-?Park10AR1p32?？-?Park11Park12？Park13？?？？2q36-375q232q22?Synphilin-1NR4A2？？？50s50s50s?？？37運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024與病因相關(guān)的細(xì)胞機(jī)制Cell-autonomous(dopamineneuronsinSNpc)Proteinaggregation(SNCA,DJ1,ATP13A2,MAPT)IncreasedCa2+influxMitochondriadysfunction(parkin,PINK1,DJ-1)Autophagy/Mitophagy(parkin,PINK1)OxidativedamageduetoROSproductionProteosomes(parkin,UCHL1)Lysosomes(LRRK2,GBA,ATP13A2)Non-cell-autonomousExcitotoxicityInflammation,includingproductionofapoptosis-promotingcytokinesbymicroglia(possiblypotentiatedbyLRRK2mutants)andfas-ligandbyinvasiveCD4T-lymphocytesPrion-likespreadofalpha-synucleinaggregation(?)

38運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024Lancet2014新藥研發(fā)39運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024AnnuRevMed2004皮層GPeSTNGPiSNprPPNVL殼核SNpc皮層GPeSTNGPiSNprPPNVL殼核SNpc皮層GPeSTNGPiSNprPPNVL殼核SNpc(a)(b)(c)正常帕金森病左旋多巴誘導(dǎo)的運(yùn)動(dòng)障礙多巴胺多巴胺興奮性的神經(jīng)元放電抑制性的神經(jīng)元放電病理損害機(jī)制40運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024臨床表現(xiàn)又稱“震顫麻痹”，進(jìn)行性、以運(yùn)動(dòng)障礙為主要表現(xiàn)臨床特徵為：靜止性震顫,Tremor肌強(qiáng)直,Rigidity運(yùn)動(dòng)遲緩,Akinesia(Bradykinesia)姿勢步態(tài)異常,Postralabnormality通常為非對稱性發(fā)病，對多巴胺能藥物治療反應(yīng)良好病史或檢查排除繼發(fā)性帕金森癥病理學(xué)主要特徵是黑質(zhì)紋狀體多巴胺能通路受損隨著疾病進(jìn)展，其他腦區(qū)也發(fā)生退化，產(chǎn)生非多巴胺能、非運(yùn)動(dòng)性癥狀41運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024非運(yùn)動(dòng)癥狀LancetNeurol2006神經(jīng)精神癥狀抑鬱、淡漠、焦慮、興趣缺失、注意力缺失幻覺、妄想、錯(cuò)覺癡呆強(qiáng)迫行為（可由藥物引起）和重複性行為意識模糊、陣發(fā)性譫妄（可由藥物引起）驚恐發(fā)作睡眠障礙不寧腿綜合征和週期性肢體運(yùn)動(dòng)快速動(dòng)眼（REM）睡眠行為障礙和REM無張力狀態(tài)非REM睡眠相關(guān)運(yùn)動(dòng)障礙日間過度嗜睡生動(dòng)夢境失眠睡眠呼吸障礙感覺癥狀疼痛感覺異常嗅覺障礙自主神經(jīng)癥狀膀胱功能障礙：尿急、夜尿增多、尿頻出汗直立性低血壓因直立性低血壓而摔倒性功能障礙性欲亢進(jìn)/變態(tài)（有可能由藥物引起）勃起功能障礙眼幹胃腸道癥狀（與自主神經(jīng)癥狀相重疊）流涎味覺缺失吞咽困難和窒息返流、嘔吐噁心便秘排便不盡大便失禁其他癥狀疲勞等42運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024診斷標(biāo)準(zhǔn)（UK腦庫）反復(fù)的腦卒中病史，伴階梯式進(jìn)展的帕金森癥狀反復(fù)的腦損傷史確切的腦炎病史動(dòng)眼危象在癥狀出現(xiàn)時(shí)，正在接受神經(jīng)安定劑治療1個(gè)以上的親屬患病病情持續(xù)性緩解發(fā)病三年後，仍是嚴(yán)格的單側(cè)受累核上性凝視麻痹小腦征早期即有嚴(yán)重的自主神經(jīng)受累早期即有嚴(yán)重的癡呆，伴有記憶力，語言和行為障礙錐體束征陽性（Babinski征+）MRI/CT掃描可見顱內(nèi)腫瘤或交通性腦積水用大劑量左旋多巴治療無效（除外吸收障礙）MPTP接觸史一種阿片類鎮(zhèn)痛劑的衍生物步驟1-診斷帕金癥表現(xiàn)步驟2-排除標(biāo)準(zhǔn)步驟3-支持性診斷標(biāo)準(zhǔn)運(yùn)動(dòng)減少：隨意運(yùn)動(dòng)在始動(dòng)時(shí)緩慢，疾病進(jìn)展後，重複性動(dòng)作的運(yùn)動(dòng)速度及幅度均降低。至少符合下述一項(xiàng)：肌肉強(qiáng)直靜止性震顫4-6Hz姿勢不穩(wěn)（非原發(fā)性視覺，前庭功能，腦功能及本體感受功能障礙造成）確診帕金森病需要至少符合3個(gè)以上(含3個(gè))單側(cè)起病靜止性震顫逐漸進(jìn)展發(fā)病後多為持續(xù)性的不對稱性受累對左旋多巴的治療反應(yīng)非常好（70-100%）嚴(yán)重的左旋多巴導(dǎo)致的異動(dòng)癥左旋多巴的治療效果持續(xù)5年以上（含5年）臨床病程10年以上（含10年）符合步驟1帕金森綜合征診斷標(biāo)準(zhǔn)的患者，若不具備步驟2中的任何一項(xiàng)，同時(shí)滿足步驟3中三項(xiàng)及以上者即可臨床確診為帕金森病。臨床診斷43運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024帕金森病量表–Hoehn-Yahr分期I期

1.

癥狀和體征僅位於單側(cè)

2.

癥狀輕微

3.

癥狀使患者行動(dòng)不便但並未致殘

4.

通常表現(xiàn)為一個(gè)肢體震顫

5.

患者的親友可發(fā)覺患者的姿勢，運(yùn)動(dòng)和麵部表情發(fā)生變化II期

1.

癥狀為雙側(cè)性

2.

極低程度的殘疾

3.

姿勢和步態(tài)受影響III期

1.

肢體動(dòng)作顯著遲緩

2.

步行或站立時(shí)的平衡受到輕度損害

3.

中度、廣泛性的功能障礙

IV期

1.

嚴(yán)重癥狀

2.

仍可步行有限的距離

3.

肌強(qiáng)直和運(yùn)動(dòng)遲緩

4.

無法獨(dú)立生活

5.

震顫癥狀可能輕於較早期階段V期

1.

惡病質(zhì)期

2.

完全病殘期

3.

不能站立或行走

4.

需要持續(xù)護(hù)理MovDisord.200444運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024帕金森病的量表

——帕金森病統(tǒng)一評分量表（UPDRS）精神、行為和情緒共4個(gè)問題，主要針對非運(yùn)動(dòng)癥狀分別關(guān)於智力的、思維障礙的、抑鬱的和動(dòng)力日常生活活動(dòng)（確定“開或關(guān)”期）共13個(gè)問題，幾乎都是關(guān)於運(yùn)動(dòng)癥狀的有兩個(gè)關(guān)於流涎（自主神經(jīng)功能）和感覺方面的問題運(yùn)動(dòng)檢查共14個(gè)問題，主要針對運(yùn)動(dòng)癥狀治療的併發(fā)癥異動(dòng)癥：4個(gè)問題臨床波動(dòng)：4個(gè)問題其他併發(fā)癥：3個(gè)問題，關(guān)於厭食、噁心、嘔吐和睡眠的問題

總分共為199分，199分表示完全殘疾，0分表示無殘疾MovDisord200345運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024帕金森病的鑒別診斷原發(fā)性帕金森病帕金森病：大約占75%特發(fā)性震顫繼發(fā)性帕金森癥

-藥物引發(fā)：可達(dá)20%多巴胺阻滯劑：強(qiáng)效神經(jīng)安定劑、

甲氧氯普胺腦積水代謝（肝）性腦病、甲狀旁腺疾病腦部結(jié)構(gòu)性病變：腫瘤、梗死或出血毒素（一氧化碳、MPTP）感染帕金森疊加綜合征路易體癡呆多系統(tǒng)萎縮（橄欖體橋小腦萎縮、Shy-Drager綜合征、紋狀體黑質(zhì)變性）進(jìn)行性核上性麻痹皮質(zhì)基底節(jié)變性46運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024帕金森病病程ParkinsonismandRelatedDisorders2010帕金森病時(shí)間軸臨床發(fā)病20年前驅(qū)癥狀20年疾病期癥狀嗅覺減退便秘膀胱功能障礙睡眠障礙肥胖抑鬱Ⅲ平衡障礙病理腸壁神經(jīng)層嗅球腦神經(jīng)Ⅹ藍(lán)斑尾狀核巨細(xì)胞網(wǎng)狀核黑質(zhì)杏仁核馬特奈基底核腳橋核顳葉TECCA-2神經(jīng)層丘腦核前額皮層第三感覺聯(lián)合區(qū)第二、然後第一運(yùn)動(dòng)感覺區(qū)交感神經(jīng)系統(tǒng)Braak分級Ⅰ單側(cè)震顫肌強(qiáng)直運(yùn)動(dòng)不能Ⅱ雙側(cè)發(fā)?、舻揭蕾囁苏J(rèn)知功能衰退Ⅴ坐輪椅或臥床癡呆Hoehn&Yahr分期47運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024藥物治療多巴胺能類藥物左旋多巴左旋多巴卡比多巴左旋多巴芐絲肼COMT抑制劑（恩他卡朋、托卡朋）多巴胺受體激動(dòng)劑非麥角類普拉克索羅匹尼羅羅替戈汀吡貝地爾麥角類 選擇性MAO-B抑制劑司來吉蘭雷沙吉蘭非多巴胺能類藥物抗膽鹼能藥物苯海索苯托品金剛烷胺48運(yùn)動(dòng)障礙和帕金森病英文版課件5/9/2024L-Dopa左旋多巴=levodopaSymptomaticreliefofmovementdeficits(tremor,rigidity,akinesia)isprovidedbysystemicadministrationofL-DOPA,adopamine