早期帕金森病診斷及治療新進(jìn)展-中山大學(xué)第一醫(yī)院神經(jīng)內(nèi)科+徐評議

徐評議中山大學(xué)附屬第一醫(yī)院神經(jīng)內(nèi)科早期帕金森病診斷及治療新進(jìn)展共同特點(diǎn):老年,進(jìn)行性發(fā)展,特定腦區(qū)和特定癥狀中樞神經(jīng)退行性病帕金森病、老年性癡呆、多系統(tǒng)萎縮等

不同腦區(qū)退行性變特定遞質(zhì)代謝障礙中老年，隱匿，癡呆、震顫麻痹、運(yùn)動(dòng)障礙和病理性肌萎縮等共同特征-不同區(qū)間神經(jīng)元胞體或胞核內(nèi)出現(xiàn)不同成份的異常蛋白沉積，神經(jīng)元變性凋亡中樞神經(jīng)退行性病InPD,theintracellularinclusionbodiescalledLewe’sbodyinmidbrainisaGoldenstandardforconfirmeddiagnosisofPD;whileamyloidplaquesandphosphoredtautanguesarepathologicalhallmarkerforAlzheimer’sdisease.Lewe’sbodydiseaseiswildlyspreadincortex,andmidbrain;inMSA,theneuronallossismainlypresentinnigro,striatum,pon,cellebrum,andspinalcordandvagusnuclei.中樞神經(jīng)退行性病的病理機(jī)制Over70proteinshavebeenidentifiedinLewybodies

-Crystallin;

-Synuclein

Calcium-calmodulin-dependentproteinkinaseIICalbindinD28K;Chondroitinsulfate;ChromograninAClusterin/apolipoproteinCochaperoneCterminusofHsp-70-interactingproteinComplementproteins(C3d,C4d,C7,andC9);Cyclin-dependentkinase5Cytochromec;DJ-1;Dorfin;14-3-3proteinGelsolin-relatedamyloidproteinFinnishtypeHeat-shockproteins27,40,70,60,90,and110P;hosphorylatedIkBa;LipidsMAP-2;MAP-5/MAP-1b;MitochondriaMulticatalyticproteinase;MxAproteinNEDD8;Neurofilaments;NFkBOmi/HtrA2P35nck5a;p62/sequestosomePael-R;ROC1;SphingomyelinCu/Znsuperoxidedismutase;MnsuperoxidedismutaseSynapticvesicle-specificprotein;Synphilin-1;Synaptophysin;TauTorsinA;Tubulin;TyrosinehydroxylaseUbiquitin;UbiquitinC-terminalhydroxylase

Shults,

PNAS2006;103:1661Savittetal,JCI,2006;116:1744帕金森病的臨床病程早期標(biāo)記的發(fā)現(xiàn)期TolosaEetal,LancetNeurology2006中樞神經(jīng)變性病的不同臨床特征吞咽困難發(fā)音困難凝視麻痹失用步態(tài)不穩(wěn)跌倒強(qiáng)直運(yùn)動(dòng)遲緩震顫癡呆植物神經(jīng)功能障礙帕金森背景發(fā)病情況:我國帕金森病(PD)＞200萬↑.ZhangZ,etal.

Lancet.2005無癥狀前10～20年，黑質(zhì)多巴胺(DA)神經(jīng)元大量變性病理發(fā)展：發(fā)病機(jī)制:基因/環(huán)境/老化可能與大多數(shù)PD相關(guān)替代療法5～年后逐漸失效,難以控制的不良反應(yīng);且DA神經(jīng)元持續(xù)變性,需發(fā)展新的治療方法，干預(yù)疾病發(fā)展治療現(xiàn)狀:發(fā)病機(jī)制不清:環(huán)境因素、遺傳易感、老年背景結(jié)果分析:Initialclinicaldiagnosiswithin5yrsofdiseaseonsetwascorrectin65%ofcases

Afterameandurationof12yrs,thefinaldiagnosisofPDbytheclinicianwasconfirmedatautopsyin76%ofcasesWiththeuseofstandardclinicalcriticalcriteriasuchastheUKParkinson’sDiseaseBrainBankCriteria,accuracyofaclinicaldiagnosisofthediseasecanbeimproved10%.(Jankovicetal,ArchNeurol2000;57:369;Hughesetal,JNeurolNeurosurg1992,55:181;Rajputetal,CanJNeurolSci1991;18:275-278)病理性標(biāo)志LossofnigralcellsPresenceofLewybodiesDepositionofreactivemicrogliaandotherinflammatorycellsShults,PNAS2006;103:1661存在問題:病理診斷標(biāo)準(zhǔn)LBD并非PD特有的特征，見于許多其他疾病；隨年齡增加LBD也增多<80%之PD有LBD，但都有多巴胺能神經(jīng)元減少遺傳性帕金森征中， 有臨床特征類似PD，但是病理檢查無LBD(PARK2);

或有LBD的病理特征，但是臨床表現(xiàn)不典型(PARK4)難以排除能導(dǎo)致其他帕金森征的病理證據(jù)方