帕金森病綜合診斷

1、帕金森病診斷,北京協(xié)和醫(yī)院 張振馨,6/14/2019,1,帕金森綜合癥(Parkinsonism)診斷標(biāo)準(zhǔn)：,具有下列四種癥狀和體征中的二種(TRAP)靜止性震顫、僵直、運(yùn)動(dòng)減少或無(wú)(A)、慢(B)、幅度小姿勢(shì)反射的障礙,6/14/2019,2,帕金森綜合癥的誤診原因,四大主癥的確認(rèn)查體不標(biāo)準(zhǔn)震顫僵直I級(jí)，假陽(yáng)性其他：老年、抑郁、纏足和其他骨關(guān)節(jié)病診斷標(biāo)準(zhǔn)的限制,6/14/2019,3,良性震顫,Goetz C

2、G, et al.1995;1(4):47,6/14/2019,4,Final Neurological Evaluation in Beijing, Xian, Shanghai, 2001,Non-PD Parkinsonism N=132?N=9 N=117? N=6,Parkinsonism excluded N=665N=643 N=7 N =15,Parkinson’s Disease N=272+

3、1,Non-Parkinsonism N=1,839,Initial Evaluation in 1997,Non-PD Parkinsonism N=130,,Lost243Died 276,Parkinsonism excludedN=8,205,Re-study N=12,401+2,Re-study N=1,188,Negative symptom questionnaire N=27,213,Re

4、sponse N=29,454,Parkinson’s Disease N=277* N=17 N=6 N=252* N=2,Positive symptom questionnaire N=2,241,Parkinsonism excluded N=27,212,Eligible N=31,318,Non-response N=1,864,Neurological exam N=2,241,Neurological exam

5、 N=27,212+1,Lost3,323Died 873,Follow_up Survey,? For Non-PD Parkinsonism non-follow-up n=49, traced=62.3 %,* For PD non-follow-up n=75 traced=72.5 %,94%,64.4%,45.6%,33.8%,43.7%,56.3%,66.2%,6/14/2019,5,臨床

6、診斷的準(zhǔn)確性,22年中，65例尸檢，59例神經(jīng)病理檢查。生前臨床最初診斷PD43例，隨訪11.7年，臨床最后診斷PD41例死后病理證實(shí)31(76%)。(Rajput,et al. 1991),6/14/2019,6,病理檢查確認(rèn)臨床誤診為PD的原因,6/14/2019,7,神經(jīng)病理診斷59例,6/14/2019,8,疑似特發(fā)性帕金森病的 主要的特發(fā)性帕金森綜合癥,6/14/2019,9,Clinical Diagn

7、osis of IPD: difficult, particularly in early cases,Between IPD and other parkinsonian syndrome.Clinically diagnosed IPD: 100 casesPathologically confirmed: 76 cases(Hughes AJ, et al. 1992),6/14/2019,10,Clinical Feat

8、ures of IPD: particularly in early cases,The highest positive predictive values:tremorasymmetry of symptoms at onsetgood clinical response to L-dopa,6/14/2019,11,Clinical Features of IPD:

9、 particularly in early cases,At the onset of the symptomatic phase, the clinical response to L-dopa is not yet availableA sufficient dosage (1000 mg/day), [withdrawing levodopa over 1-2 days] an improvedment in

10、 the motor score of 30% or more indicates “dopa-sensitivity”,6/14/2019,12,Clinical Features of IPD:,蜜月后出現(xiàn)波動(dòng)、異動(dòng)典型的搓丸狀震顫，強(qiáng)烈提示IPD可以無(wú)震顫，或只有姿勢(shì)性震顫植物神經(jīng)癥狀不常見，或僅輕、中度眼動(dòng)正常認(rèn)知功能正常，某些人在晚期出現(xiàn)癡呆,6/14/2019,13,減少誤診的措施,診斷標(biāo)準(zhǔn)化詳細(xì)病史采集內(nèi)科

11、體檢神經(jīng)系統(tǒng)查體實(shí)驗(yàn)室檢查電生理影象學(xué)核醫(yī)學(xué)診斷標(biāo)準(zhǔn),6/14/2019,14,帕金森病診斷標(biāo)準(zhǔn) Calne et al：,臨床可能:以上頭三種癥狀和體征中的任何一種，震顫必須是新近(3 Yrs)發(fā)生、可靜止性或姿勢(shì)性臨床很可能: (2 or As)以上四癥狀和體征中的任何兩種,或TRA三癥狀中任何一種并且呈不對(duì)稱臨床肯定:(3 or 2+As)以上四癥狀和體征中的任何三種, 或以上任何兩種,并且任何一種呈不對(duì)稱,6

12、/14/2019,15,帕金森病診斷標(biāo)準(zhǔn) Calne et al：,早期僅有不對(duì)稱步態(tài)或一手苯拙,有助診斷臨床可能的PD:伴隨減少, 手指阻抗, Meyerson 征強(qiáng)直的肢體,無(wú)錐體束征,無(wú)力握反射很可能排除PD:早期出現(xiàn)癡呆和植物神經(jīng)功能紊亂病程早期姿勢(shì)不穩(wěn),出現(xiàn)摔倒共濟(jì)失調(diào)和錐體束征一側(cè)扭轉(zhuǎn)痙攣,下運(yùn)動(dòng)神經(jīng)原征動(dòng)眼危象、核上性上下視和側(cè)視麻痹突然發(fā)病,病程有緩解, 階梯性進(jìn)展發(fā)病前抗精神病藥治療或暴露于藥物或毒

13、物,腦炎史,6/14/2019,16,帕金森病診斷標(biāo)準(zhǔn) Calne et al：,其他: 進(jìn)行性的病程對(duì)左旋多巴反應(yīng)良好無(wú)多系統(tǒng)萎縮的表現(xiàn)無(wú)繼發(fā)性始金森綜合征臨床診斷PD病理符合76%, 24%為其他原因parkinsonism不能確診時(shí):每隔數(shù)月后再查體直至確診,6/14/2019,17,帕金森病運(yùn)動(dòng)和非運(yùn)動(dòng)癥狀,運(yùn)動(dòng)步態(tài)和軸位姿勢(shì)軸位上的姿勢(shì)改變?cè)诖采戏砝щy步態(tài)緩慢，拖步慌張步態(tài)上、下肢遠(yuǎn)端癥狀小

14、字癥精細(xì)動(dòng)作損害靜息性震顫足趾扭轉(zhuǎn)痙攣,頭部癥狀面具臉說(shuō)話猶豫、語(yǔ)調(diào)低平及構(gòu)音障礙瞬目減少眼球調(diào)節(jié)障礙強(qiáng)迫性閉眼吞咽困難流涎,6/14/2019,18,帕金森病運(yùn)動(dòng)癥狀和非運(yùn)動(dòng)癥狀,非運(yùn)動(dòng)性,精神和睡眠？發(fā)生于疾病前的人格改變抑郁焦慮非常逼真的夢(mèng)斷續(xù)的睡眠感覺麻木和刺痛感感覺異常：如溫?zé)岣徐o坐不能：感覺不安嗅覺缺失視覺集中敏感性受損,植物神經(jīng)直立性低血壓胃腸運(yùn)動(dòng)受損膀胱功能障礙體溫調(diào)節(jié)

15、障礙瞳孔對(duì)光反射減弱脂溢性皮炎體重減輕性功能障礙,6/14/2019,19,帕金森癥的分類,特發(fā)帕金森癥:帕金森病繼發(fā)帕金森癥藥源性帕金森癥多巴胺受體阻斷劑(抗精神病藥)多巴胺耗竭劑(利血平)鋰劑鹽酸氟桂利嗪、桂利嗪、鹽酸地爾硫卓偏側(cè)萎縮，偏側(cè)帕金森癥腦積水正常顱壓性腦積水非交通性腦積水,低氧血癥感染霉菌感染艾滋病胞漿玻璃樣包含體病亞急性硬化性腦炎腦炎后遺癥CJD代謝性 低鈣性帕金森癥 慢

16、性肝腦變性,6/14/2019,20,帕金森癥的分類,副瘤性 精神性的 腦脊髓空洞形成 外傷性 毒物MPTP中毒CO中毒錳中毒蘇鐵素美沙酮二硫化碳二硫化物,腫瘤血管性多灶性梗塞賓斯萬(wàn)格癡呆,6/14/2019,21,帕金森癥的分類,帕金森疊加綜合癥皮層基底神經(jīng)節(jié)變性癡呆綜合癥Alzheimer‘s 病皮層彌漫性路易體病Pick’s 病關(guān)島 PD-D-ALS,多系統(tǒng)萎縮綜合癥紋狀體黑質(zhì)變性Sh

17、y-Drager 綜合癥散發(fā)性O(shè)PCA運(yùn)動(dòng)神經(jīng)元病疊加帕金森進(jìn)行性蒼白球萎縮進(jìn)行性核上性麻痹,6/14/2019,22,帕金森癥的分類,遺傳變性疾病Ceroid-lipofuscinosis格-施-沙病哈-施病舞蹈病Lubag(Filipino X-linked dystonia-parkinson) 共濟(jì)失調(diào)病線粒體細(xì)胞病變合并紋狀體壞死神經(jīng)棘紅細(xì)胞癥，舞蹈樣運(yùn)動(dòng)棘紅細(xì)胞癥家族性O(shè)PCA丘腦性癡呆綜合癥肝

18、豆?fàn)詈俗冃?6/14/2019,23,UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria,帕金森病的UK腦庫(kù)臨床診斷標(biāo)準(zhǔn),6/14/2019,24,步驟1-帕金森癥狀的診斷,運(yùn)動(dòng)減少：隨意運(yùn)動(dòng)在始動(dòng)時(shí)緩慢，疾病進(jìn)展后，重復(fù)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(shì)不穩(wěn)（非原發(fā)性視覺，前庭功能，腦功能及本

19、體感受功能障礙造成）,6/14/2019,25,步驟2-排除非帕金森病的診斷無(wú)不典型的體征,有動(dòng)眼危象病情持續(xù)性緩解發(fā)病3年后，仍是嚴(yán)格的單側(cè)受累核上性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(yǔ)言和執(zhí)行障礙,6/14/2019,26,步驟2-帕金森病的排除標(biāo)準(zhǔn),錐體束征陽(yáng)性（Babinski +）用大劑量左旋多巴治療無(wú)效（除外吸收障礙）其他病因(繼發(fā)帕金森癥)反復(fù)的腦卒中發(fā)作史，伴帕金森特征

20、的階梯狀進(jìn)展反復(fù)的腦損傷史確切的腦炎病史,6/14/2019,27,步驟2-帕金森病的排除標(biāo)準(zhǔn),在癥狀出現(xiàn)時(shí)，應(yīng)用精神抑制藥物1個(gè)以上的親屬患病CT掃描可見顱內(nèi)腫瘤或交通性腦積水接受過(guò)MPTP（1甲基4苯基1，2，3，6四氫吡啶，一種阿片類鎮(zhèn)痛劑的衍生物，對(duì)黑質(zhì)細(xì)胞有特異性毒性）,6/14/2019,28,步驟3-帕金森病的支持性診斷標(biāo)準(zhǔn),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)病后多為持

21、續(xù)性的不對(duì)稱性受累對(duì)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）,6/14/2019,29,Proposed diagnostic criteria,Criteria AResting Tre.，Rigid.，Brady.，Asymm.Criteria B (Suggestive of alternative Diagnoses)

22、Atypical signs at onset (1st 3 years)Supranuclear gaze palsy, slowing of vertical saccadesSevere symptomatic dysautonomia unrelated medicationCriteria CSubstantial and sustained L-dopa or Dopamine agonist response,6/

23、14/2019,30,Proposed diagnostic criteria,Possible IPDCriteria A 2/4, (One is T or B)Criteria B, absence & Criteria C, presenceProbable IPDCriteria A 3/4, (One is T or B)Criteria B, absence & Criteria C, prese

24、nceDefinite IPDHistopathological confirmation,6/14/2019,31,帕金森病病理診斷標(biāo)準(zhǔn),①多巴胺能神經(jīng)元減少 (>50%)和黑質(zhì)中存在膠質(zhì)細(xì)胞②在黑質(zhì)或藍(lán)斑中至少存在一個(gè)路易小體(在這些區(qū)域的3~4張病理切片，不重疊 )③沒有能產(chǎn)生其他帕金森癥的病理證據(jù),6/14/2019,32,血管病所致的帕金森綜合征,符合PDS的診斷標(biāo)準(zhǔn)有明確的血管病臨床證據(jù):高血壓、情感失禁

25、和假性球麻痹、步態(tài)僵硬、病程中有確切的中風(fēng)史，廣泛的椎體系體征。突然發(fā)病、癥狀非進(jìn)行性或階梯性進(jìn)展,CT或 MRI發(fā)現(xiàn)梗塞灶于基底節(jié)。步基寬，表情、語(yǔ)音正常，無(wú)伴隨減少,6/14/2019,33,藥物誘導(dǎo)的帕金森綜合征診斷標(biāo)準(zhǔn),①符合PDS的診斷標(biāo)準(zhǔn)②癥狀出現(xiàn)前6個(gè)月內(nèi)有服用抗精神病藥（如吩塞嗪、丁酰苯類藥物）或多巴胺能拮抗劑（如氟利桂嗪）的歷史③第一次使用這些藥物前無(wú)帕金森綜合征的病史和體征,6/14/2019,34,與藥物誘

26、導(dǎo)的關(guān)系,藥物,抗精神病藥:酚噻嗪 丁酰苯 噻噸，硫蒽 苯甲酰胺酶 利血平,抗組胺劑:苯海拉明，氯苯吡胺， 暈海寧（茶苯海明）， 減食欲劑， 右旋苯丙胺，安非拉酮,其它類: α-甲基多巴 鋰劑鹽酸氟桂嗪、腦益嗪、鹽酸地爾硫卓硫酸苯乙肼鹽酸哌替啶丙戊酸鈉甲醇，乙醇多巴胺耗竭劑

27、 Ca離子拮抗劑胺碘酮,6/14/2019,35,與藥物誘導(dǎo)的關(guān)系,藥物,劑量: higher dose, total dose時(shí)間: begin within a few days with neuroleptics, 50-70% by one month, 90% within 3 months Some never do, irrespective of the dose or

28、 duration遺傳: HLA-B44?臨床前期,6/14/2019,36,臨床表現(xiàn),Hubble JP. In: Watts RL, Koller WC, eds. Movement disorders: Neurologic principles and practice 1997,1. milder, a prolonged exposure for dopamine depletors2. Older age wit

29、h a family history of essential tremor for Ca-entry blockers3. Cogwheel rigidity for some taking Lithium4. Blindness, dementia, parkinsonian symptoms for methanol poisoning5. Tremor, coarse rotatory jaw tremor for ami

30、odarone6. Mild personality, cognitive, mild P to sever P+D syndrome for valproate * 12mo 7. Tremor for Chinese herbs,6/14/2019,37,Parkinson-Plus,SMA，PSP，CBDSMA-PP only：SND 占50%P>C ：SND為主， 占30%

31、MSA-P > MSA-C (c only, c>p) SND，Shy-drager，sOPCAAge at onsetIPD: 60, 5%<40; MSA: 53; PSP: 63; CBD: 40-60,6/14/2019,38,MSA-P,30%早期對(duì)L-DOPA有效震顫占2/3,只有9%是搓丸狀Dysautonomia 廣泛受累97%，尿失禁71%、尿貯留27%，大便失禁2%，姿勢(shì)性頭昏6

32、8%5年內(nèi)發(fā)展迅速，發(fā)病癥狀對(duì)稱，姿勢(shì)不穩(wěn)少見Laryngeal stridor 喉鳴(嗯)睡眠呼吸暫仃, REM睡眠行為障礙肌陣攣 冷手征(cold hands sign，不見于IPD)情感釋放攣縮：多見于MSA或CBD，少見IPD,6/14/2019,39,Striatonigral degeneration,少動(dòng)-僵直、姿勢(shì)平衡早期發(fā)生言語(yǔ)、吞咽困難，喉鳴最終明顯錐體束受損L-dopa 治療無(wú)反應(yīng)小腦共濟(jì)失調(diào)

33、、自主神經(jīng)功能不良,6/14/2019,40,符合神經(jīng)病理標(biāo)準(zhǔn)的12例PSP臨床特征,發(fā)病至死亡平均5.3年早期發(fā)生嚴(yán)重平衡障礙(倒),嚴(yán)重小字凝視麻痹，早期未查1/2，查不到占1/3，瞼痙攣軸、對(duì)稱少(重面具臉9/12)、僵(項(xiàng)、坐下)、構(gòu)音障礙（假球）不對(duì)稱1/2，無(wú)L-dopa反應(yīng)7/10，無(wú)震顫認(rèn)知障礙7/12，額葉：人格、記憶提取、力握、重復(fù)言語(yǔ)無(wú)直立低血壓步基寬5，運(yùn)動(dòng)魯莽，肌緊張不全，肌陣攣、午蹈樣、共濟(jì)

34、生前臨床診斷8/12,6/14/2019,41,PSP 臨床特征,Initially: gait difficulty 62%Mental changes 22%Initially complaints:Slowness and stiffness of movementAbrupt fallsPoor vision, dysphagia or dysarthria,6/14/2019,42,PSP 臨床特征,Tremor

35、, 10-15%Responds poorly to L-dopaEarly effective, 10% No cardiovascular autonomic dysfuctionNo dystoniaNo myoclonic,6/14/2019,43,CBD,L-dopa無(wú)效上視麻痹無(wú)植物神經(jīng)功能不良不對(duì)稱 (經(jīng)典)jerk粗大震顫肌陣攣肌緊張不全僵直- 運(yùn)動(dòng)不能(akinesia)alien lim

36、b失用皮層感認(rèn)知 variability affect,6/14/2019,44,DLB,Early onset of dementiaearly hallucinations (visual) and delusionFluctuating cognition, variation in alertness and attentionSymmetrical parkinsonism, No tremor, No dyski