锥体外系疾病(运动障碍性疾病)优质课件.pptx

1、锥体外系疾病（运动障碍性疾病）锥体外系疾病（运动障碍性疾病）运动障碍（锥体外系）疾病,主要表现为随意运动迟缓，不自主运动、肌张力障碍、姿势步态障碍等运动症状。肌力、Extrapyramidal diseases mainly impair the regulation of voluntary motor activity（sluggish），involuntary movement，myodystonia，without 感觉及小脑功能不直接受影响。运动障碍疾病源于基底节功能紊乱。directly affecting strength,sensation,or cerebellar func

2、tion.Movement disorders result from dysfunction of deep subcortical gray matter structures termed the basal ganglia.解剖：解剖：AnatomyAnatomy:基底节：尾状核、豆状核（壳核、苍白球）、屏状核和杏仁复合体（丘脑底核与黑质为相关结构）。Basal ganglia:caudate nucleus,lentiform nucleus(putamen,globus pallidus),claustrum and amygdaloid complex.新纹状体：壳核、尾状核。N

3、eostriatum:putamen,caudate.旧纹状体：苍白球Paleostiratum:globus pallidus古纹状体：杏仁复合体Archistriatum:amygdaloid complex相关结构：红核、黑质、丘脑底核、中脑间质核、大脑皮质的4、6区。Dependency structure:red nucleus(corpus rubrum),substantia nigra,mid brain interstitial nucleus,4 and 6 regions of cerebral cortex神经环路神经环路：Neuronal circuitryNeuro

4、nal circuitry:1.皮质-皮质环路：大脑-皮质-尾状核、壳核-内侧苍白球-丘脑-大脑皮质(直接通路,间接通路)1.Corticortical loop:cerebral cortex-caudate,putamen-the internal segment of the globus pallidus-thalamus-cerebral cortex(direct path,indirect path)2.黑质-纹状体环路：黑质与尾状核、壳核之间的往返联系纤维2.Nigrostriatal loop:connecting the substantia nigra,caudate a

5、nd putamen3.纹状体-苍白球环路：尾状核、壳核-外侧苍白球-丘脑底核-内侧苍白球3.Striaropallidal loop:projects from the caudate and putamen to the external segment of the globus pallidus,then to the subthalamic nucleus,and finally to the internal segment of globus pallidus.书本简约：大脑皮质-基底核-丘脑-大脑皮质神经递质神经递质：乙酰胆碱（Ach）、多巴胺(DA)、去甲肾上腺素(NE)、5

6、-羟色胺(5-HT)、-氨基丁酸(GABA)、谷氨酸等。Neurotransmitter(NT):acetylcholine,dopamine,noradrenaline,5-hydroxytryptamine(serotonin),gamma-aminobutyric acid,aminoglutaminic acid,etc.椎体外系症状肌张力异常：高或低运动迟缓异常不自主运动：震颤、舞蹈、投掷、徐动。临床分类：临床分类：Clinical classification:1运动过多：震颤、肌张力障碍、舞蹈症、手足徐动症、抽搐1.hypercinesia:tremor,dysmyotonia,

7、chorea,posthemiplegic chorea,tic2运动减少：帕金森病和帕金森综合征。2.hypokinesia:Parkinsons disease and Parkinsons syndrome3.其他疾病：共济失调、肝豆状核变性。3.Other diseases:ataxia,Kinnier-Wilson syndrome治疗原则：治疗原则：Therapeutic principleTherapeutic principle:病因治疗、药物治疗、神经外科治疗、个体化原则。Etilogical treatment，drug treatment，neurosurgical th

8、erapy,individualized treatment 帕金森病帕金森病 (agitans paralysis;paralysis agitans;Parkinsons disease;PD)帕金森病又名震颤麻痹，是一种常见的中老人神经系统变性疾病 Parkinsons disease,also named Paralysis agitans,is a kind of frequent nervous system degenerative disease.65岁以上人群(北京、西安、上海）患病率1.7%,男性居多。The morbidity rate is 1.7%in the pop

9、ulation of above 65 years old.以黑质多巴胺能神经元变性缺失和以黑质多巴胺能神经元变性缺失和路易小体形成为特征。临床上表现路易小体形成为特征。临床上表现静止性震颤、运动迟缓、肌强直和静止性震颤、运动迟缓、肌强直和姿势步态异常。姿势步态异常。Characteristic loss and Characteristic loss and degeneration of dopamine degeneration of dopamine neurons in the substantia nigra.neurons in the substantia nigra.The

10、lewy bodies forming.The lewy bodies forming.Present symptoms are static Present symptoms are static tremor,bradykinesia,myotonia,tremor,bradykinesia,myotonia,posture and walking disordersposture and walking disorders.病因病因：etiological factor:病因不明。发病可能与以下因素有关：etiology unknown.The factors bellow possib

11、ly relates the onset:1.年龄老化：主要发病为中老年人，但只是促发因素（多巴胺含量减少80%）。Ageing:it mainly attacks aged people,but the ageing is only the precipitating factor.2.环境因素：MPTP使ATP生成减少，自由基生成，氧化应激反应，导致多巴胺能神经元变性死亡。Environmental factor:The MPTP reduces the generation of ATP,preciptitates the generation of free radical and i

12、ncreases the oxidative stress,which results in the regeneration and death of dopamine neurons.3.遗传因素：约10%-15%病人有阳性家族史，多呈常染色体显性遗传。Hereditary factor:about 10%-15%percent patients have the family history,and most of them belong to autosomal dominant inheritance.4.多因素：病机病机:Pathogenesis:1.氧化应激氧化应激氧自由基、羟自

13、由基、兴奋性氨基酸。目前氧自由基、羟自由基、兴奋性氨基酸。目前认为是多因素作用的结果。认为是多因素作用的结果。1.Oxidation stress:1.Oxidation stress:free radical,hydroxy radical,free radical,hydroxy radical,excitatory amino acids.Recently the excitatory amino acids.Recently the occurence of this disease is considered occurence of this disease is consider

14、ed as the effective result of multiple as the effective result of multiple factorsfactors 2.腺粒体功能缺陷腺粒体功能缺陷减少减少ATPATP合成合成,增加氧自由基的生成增加氧自由基的生成.2.2.Mitochondrial disfunctionMitochondrial disfunctionThe ATP synthesis reduce,The ATP synthesis reduce,oxidated free radical increase.oxidated free radical inc

15、rease.3.泛素泛素-蛋白酶体功能异常蛋白酶体功能异常-突触核蛋白过度表达突触核蛋白过度表达,出现出现lewylewy小体小体.泛素、蛋白酶体亚单位、泛素羧基水解酶泛素、蛋白酶体亚单位、泛素羧基水解酶L1L1、ParkinParkin等等蛋白过度表达和聚集。蛋白过度表达和聚集。3.Disfunction of ubiquitin-proteasome 3.Disfunction of ubiquitin-proteasome systemsystem The over expression of The over expression of-synuclein synuclein indu

16、ce the formation of induce the formation of lewy body.lewy body.病理与生化病理病理与生化病理：Pathology and biochemical pathology:1.病理：含色素的神经元变性、缺失，尤以黑质致密部DA能神经元为著。出现路易小体,苍白小体。1.pathology:The loss and degeneration of pigmentosus neurons,especial the dopamine neurons in the substantia nigra.The lewy bodies and pale

17、 bodies can be seen also.该二小体尚可在老年痴呆、共济失调、毛细血管扩张症和哈-斯二氏病见到。These two bodies also can be seen in senile dementia,ataxia,telangiectasia and Hallervoeden-spatz disease.Braak延髓背核、前嗅核、脑桥、中脑、新皮质2.生化病理：多巴胺与乙酰胆碱作为生化病理：多巴胺与乙酰胆碱作为纹状体中两种重要的神经递质系统，功纹状体中两种重要的神经递质系统，功能互相拮抗，它们的平衡在该病的发病能互相拮抗，它们的平衡在该病的发病起重要作用。起重要作用。

18、2.Biochemical pathology:As two 2.Biochemical pathology:As two important neurotransmitters in important neurotransmitters in striatum,DA and Ach functionally striatum,DA and Ach functionally antagonize each other,playing antagonize each other,playing very important roles in very important roles in Pa

19、rkinsons Disease.Parkinsons Disease.PD 患者黑质-纹状体通路变性，纹状体DA含量显著降低（减少70%以上），Because the degeneration of substantia nigra-striatum pathway,the content of DA in striatum remarkably decrease(over 80 percent),造成Ach系统功能相对亢进，导致基底节输出过多，丘脑-皮质反馈活动受到过度抑制，the acetylcholine system exerts a excitatory effect,which

20、results in the over output of basal ganglia,the inhibition of the feed backing activity of thalamus opticus-cortex,其对皮质的易化作用受到削弱，因此产生肌张力增高、动作减少等运动症状。and the impairment of facilitation effect to cortex,so the movement disorder symptoms appear,such as hypermyotonia,and reduction of movement临床表现临床表现：Cl

21、inical findings:Clinical findings:1.40岁少，大部分60岁以后发病。65岁1%-2%。1.symptoms occur mostly in the age of 50,or older.2.起病隐袭，缓慢发展，逐渐加剧。2.insidious onset,slow development,gradual aggravation3.主要症状为静止性震颤、肌张力增高、运动迟缓等。首发症状：60-70%震颤，12%步行障碍，10%肌强直，10%运动迟缓。3.present symptoms are static tremor,hypermyotonia,brady

22、kinesia.First symptoms:tremor 60-70%,walking disorder 12%,myotonia 10%,bradykinesia10%.65-70%从一侧上肢开始，渐波及同侧下肢，对侧上肢与下肢。25-30%从一侧下肢开始。(1)震颤:静止性，紧张加剧，搓丸样动作,每秒4-6次These symptoms 65-70%start from one side upper extremity,gradually to same side lower extremity,then the opposite side extremities.(1)Tremor:s

23、tatic,it increases with emotional stress,the fingers appear the pill-rolling-like action.4-6 times per sec.(2)肌强直:铅管样，齿轮样强直。路标现象。(2)Rigidity:lead pipe-like,cogwheel rigidity.A road sign phenomenon.(3)运动迟缓:随意动作减少，面具脸，声调低缺少变化。写字过小征。(3)Bradykinesia:voluntary action decreases,mask-like face,hypophonia,m

24、icrographia(handwriting reduces in size and becomes spidery)(4)姿势步态异常：慌张步态等。Abnormal gait and posture:such as the festinating gait.,4.非运动症状：Non-motor symptoms（1）感觉症状：嗅觉减退、麻木疼痛Hyposmia,numbness,restless leg syndrome.(2)自主神经功能障碍：Autonomic nervous dysfunction流口水，多汗，脂颜，便秘，性功能减退、排尿障碍、体位性低血压 dribbling,col

25、liquative sweating,lipoids face,constipation,sexual dysfunction,urination disorder,postural hypotension(3)精神障碍 mental disorder 认知功能减退、抑郁、幻觉hypofunction of cognition,depression，hallucination hallucination（4 4）睡眠障碍）睡眠障碍 sleeping disorder sleeping disorder 不宁腿综合征（不宁腿综合征（restless leg symdrome)restless l

26、eg symdrome)辅助检查辅助检查：Ancillary examinationAncillary examination1.生化检测：高效液相色谱示脑脊液与尿液中高香草酸、5-羟吲哚乙酸降低。1.biochemical detection:high performance liquid chromatogram shows increased homovanillic acid(HVA)and decreased 5-hydroxyindole acetic acid in cerebral spinal fluid and urine.2.基因检测：少数家族性患者有基因突变。2.gen

27、ic detection:gene mutations were found in a few familial patients.3.功能显象：PET 与SPECT可发现患者脑内 DAT功能显著降低，且可早期发现，D2型DA 受体活性 3.Functional image:with PET and SPECT method,the DAT function in brain was detected to be significantly decreased in patients in early stage,the activity of D2 type receptor was在疾病早

28、期超敏，后期降低，以及DA递质合成减少。对PD的诊断与监测均有价值。supersensitive in early stage,then decreased with the decreased synthesis of DA transmitter.This phenomenon is valuable for the diagnosis and monitoring of PD.4.其他 嗅棒测试，经颅超声，心脏间碘苯甲胍闪烁照相术。诊断诊断：Diagnosisiagnosis根据年龄、临床表现、病程发展、左旋多巴有效。According to age,clinical manifesta

29、tion,course of disease，the L-dopa is effective.一般诊断：1.中老年发病，缓慢进行性病程。2.四主征（静止性震颤、肌强直、运动迟缓、姿势步态异常）中必备运动迟缓，其余至少一项。3.左旋多巴治疗有效。4.无眼外肌麻痹、小脑体征、体位性低血压、锥体系损害和肌萎缩等。2006年中华医学会神经病学分会制定的标准（见课文）鉴别诊断鉴别诊断：Differential diagnosisDifferential diagnosis1.继发性PD：均有明显的病因可寻。1.Secondary PD:usually there are evident etiologi

30、cal factors（1）脑炎后帕金森综合征：甲型脑炎后，罕见。乙型脑炎、爱滋病。(1)Postencephalitic parkinsonism:post-encephalitis A,hardly seen.encephalitis B,AIDS.（2）药物或中毒性帕金森综合征：神经安定剂（酚噻嗪类，丁酰苯类）、利血平、灭吐灵、甲基多巴、锂、氟桂嗪、(2)medical or toxical parkinsonism:neuroleptic(phenothiazines,butyrophenones),reserpine,paspertin,methyldopa,lithium(Li),

31、flunarizine,脑益嗪。MPTP、锰、二硫化碳，一氧化碳中毒后遗症等。cinnarizine.The sequela of MPTP,manganese(Mn),carbon bisulfide,carbon monoxide poisoning.（3）动脉硬化性帕金森综合征：病史、锥体束征、高血压等可资鉴别。(3)arteriosclerosis parkinsonism:the differentiation depends on the medical record,pyramid sign,and hypertension.（4）外伤性：病史可鉴。(4)Traumatic pa

32、rkinsonism:according to the medical history.2.伴发帕金森表现的其他神经变性疾病（帕金森迭加综合征）：The other neurodegenerative diseases accompanying parkinsonism(parkinsonism plus)（1）进行性核上性麻痹：垂直凝视不能，假性球麻痹，锥体束征，震颤不明显，对多巴反应差。(1)Progressive supranuclear palsy:unable vertical steady fixation,supranuclear paralysis,pyramid sign,m

33、ild tremor,poor dopa reaction.（2）多系统萎缩：(2)multiple system atrophy(MSA)*纹状体黑质变性：病理征、晕厥。striatonigral degeneration:pathological sign,faint*Shy-Drager综合征：直立性低血压（差距40以上），性功能障碍，晕厥为主。Shy-Drager symptom：postural hypotension（difference over 40 mmHg）,sexual disturbance,faint.*橄榄脑桥小脑萎缩：小脑症状、锥体束征、脊髓症状。影象学可提供证据

34、。Olive pons cerebellar atrophy:cerebellar symptom,pyramid sign,cord symptom.Evidences can be found with imageology(3)帕金森综合征-痴呆-ALS复合体：Parkinsons syndrome-ALS(amyotrophic lateralizing sclerosis)complex(4)皮质基底节变性：额顶叶限局性萎缩、气球样皮质细胞肥大、黑质色素脱失和 corticobasal degeneration（CBD）：fronto-parietal lobes focal atr

35、ophy;balloon-like cortic cells hypertrophy,pigment loss in substantia nigra and 广泛的神经元丧失。可有肢体失用症，多巴类药及其激动剂有效。General loss of neurons.There may be limbs parectropia.Medication such as dopa alike and dopa-excitomotor will be effective （5）偏侧萎缩/偏侧帕金森综合征：病侧出现症状，同侧常有轻度萎缩。左旋多巴有效。Hemiatrophy/hemiparkinsonis

36、m:hemilatera symptom and mild atrophy.Levodopa is effective.3.遗传性帕金森综合征3.Heritage parkinsonism（1）弥散性路易体病：60岁以上，早期的痴呆、幻觉、肌阵挛、步态障碍，对左旋多巴反应差。(1)Diffuse lewy body disease:above 60 years old,early dementia,illusion,myoclonus,gait disorder,poor reaction to levodopa.（2）肝豆状核变性：年龄小、肝损、角膜K-F环，血清铜、铜蓝蛋白、铜氧化酶活性降

37、低，尿铜增加。(2)Kinnier-Wilson syndrome:young,liver injured,cornea K-F sign.serum copper and copper-protein are decreased,and the activity of copper oxidase is decreased also.Urine copper is increased.（3)亨廷顿舞蹈病：家族史、痴呆、遗传学检查(3)Humtingtons chorea:family history,dementia,test of genetics4.抑郁症：不具有肌强直与运动迟缓，抗抑郁

38、制剂有效。4.Depressive disorder:without myotonia and bradykinesia,anti-depressive medication is effective5特发性震颤：震颤以姿势性与运动性，年龄早，饮酒或用心得安可缓解。无肌强直与运动迟缓。1/3有家族史。5.Essential tremor:posture and motility tremor,young,relieving after drink or administrating propranolol,without myotonia and bradykinesia.1/3 have f

39、amily history.治疗治疗：treatment:treatment:原则：综合治疗、药物为主、减轻症状、延缓进程、提高生存质量。Goal:relieving symptom,postponing process,enhancing living quality一、药物治疗（一）方法(原则）：1.依个体情况选择治疗（年龄、病情、药物反应等）Approach:The choice of therapies depends on the individual condition(age,state of illness,and the reaction to medication)2.细水

40、长流，不求全效细水长流，不求全效3.3.掌握时机掌握时机4.“low”and“slow4.“low”and“slow”（二）治疗药物 1.抗胆碱能药物：针对震颤，安坦：1-2毫克，每日3次。有胆碱能副作用，青光眼与前列腺肥大禁用。60岁，认知下降不用。Anticholinergic agents:antan,1-2mg,Tid.Side effect:cholinergic effect,the uses in glaucoma and prostatic hypertrophy are forbidden 2.金刚烷胺：促进DA合成与释放，减少DA再吸收，早期患者可与安坦合用或单用。副作用：

41、浮肿、不宁。肾功能不全、癫痫、溃疡、肝病慎用。哺乳期妇女禁用。0.1 2次/天Amantadine:facilitating the synthesis and releasing of DA,reducing the resorption of DA,it can be used in the early stage of disease combined antan or not.Side effect:swollen,restless.Cautious in renal inadequacy,epilepsy,ulcer and liver disease.Women in lactat

42、ion are forbidden.3.多巴胺能药物(替代疗法）3.Dopaminergic drugs（Alternative treatment)左旋多巴+多巴脱羧酶抑制剂levodopa plus dopa decarboxylase-inhibitors1）复方左旋多巴：美多巴（加 卞丝肼，4：1），息宁（信尼麦，加甲基多巴）。Compound L-dopa:madopar(plus benserazide),sinemet(plus methyldopa)用药时机：年老患者可早期选用。Administration opportunity:aged patients may be us

43、ed in early stage of disease2）其他特殊制剂：复方左旋多巴控释剂，弥散型美多巴，左旋多巴甲酯及乙酯用药方法：由小到大Administration method:the dosage increases gradually副作用：周围性为恶心、低血压，心律失常。中枢性为症状波动、运动障碍、精神症状等。Side effect:peripheral side effects:nausea,hypotension,arrhythmia.Central side effect:fluctuated symptom,motor disorder,psychiatric symp

44、tom,etc.禁用：前列腺肥大、窄角型青光眼、严重肝肾功能不全。Forbidden:prostatic hypertrophy,narrow angle glaucoma,severe liver and renalInadequacy.长期及大剂量使用可出现：long-term and large dosage will cause:4.DA受体（DR)激动剂：麦角类：溴隐亭、培高利特（协良行）。非麦角类：普拉克索、吡贝地尔（泰舒达）。早初期用。DA receptor agonist:Bromocriptine,pergolide，Pramipexole Dihydrochloride，P

45、iribedilSR.5.儿茶酚-氧位-甲基转移酶抑制剂(COMT)：托卡朋100mg,tid;恩托卡朋 100-200mg,tid or qid。Catechol-o-methyltransferases:Tolcapone,entacapone,etc.6.单胺氧化酶B抑制剂（MAO-B）：B型单胺氧化酶抑制剂应用较广。常用丙炔苯丙胺（司来吉兰），每次5毫克，1-2次/天，晨服。不良反应：兴奋、失眠、幻觉、妄想和胃肠不适。Monoamine oxidase inhibitor(MAOI):MAO-B is generally used.Selegiline frequently used,

46、5mg,1-2 time per day morning.adverse effect:Exciting,insomnia,illusion,delusion and upset gastro-intestinal7.其他：抗组胺药、神经营养因子、免疫调节剂、抗氧化剂、自由基清除剂等。Others:antihistamine drug,neurotrophic factor,immunomodulator,antioxidant,free radical scavenger帕金森病帕金森病Hoehn-Yahr（修正）分级量表修正）分级量表 l l级：单侧肢体疾病级：单侧肢体疾病 1 15 5级

47、：单侧肢体合并躯干级：单侧肢体合并躯干(轴轴)症症 2 2级：双侧肢体症状但无平衡障碍级：双侧肢体症状但无平衡障碍 2 25 5级：轻度双侧肢体症状，能从后拉测试中级：轻度双侧肢体症状，能从后拉测试中恢复恢复 3 3级：轻至中度双侧症状，不能从后拉测试中恢复，级：轻至中度双侧症状，不能从后拉测试中恢复，姿势不稳，转弯变姿势不稳，转弯变 慢，许多功能受到限制，但慢，许多功能受到限制，但能自理能自理 4 4级：重度病残，不需要帮助仍能站立和行走级：重度病残，不需要帮助仍能站立和行走 5 5级：坐轮椅或卧床，完全依赖别人帮助级：坐轮椅或卧床，完全依赖别人帮助（三）早期治疗（Hoehn-Yahr 1-

48、2.5级）首选药原则1）早发型：无智能减退时，选择：非麦角类DR激动剂；MAO-B抑制剂；金刚烷胺；复方左旋多巴；恩他卡朋双多巴片。不一定按顺序。2）晚发型，或伴智能减退：首选复方左旋多巴，可添加DR激动剂、MAO-B抑制剂或COMT抑制剂。尽量不用抗胆碱药。（四）中晚期治疗（Hoehn-Yahr 3-5级）1.运动并发症的治疗1）症状波动的治疗：*剂末恶化：A.复方左旋多巴日总量不变，增加服药次数。或每次剂量不变，增加服药次数。B.换用控释剂。C.加用长半衰期DR激动剂。D.COMT抑制剂。E.MAO-B抑制剂。F.避免饮食影响。G.手术治疗：DBS.2）异动症的治疗:*剂峰异动症：A.减少

49、每次复方左旋多巴的剂量；B.在A的基础上，加用DR激动剂或COMT抑制剂；C.加用金刚烷胺；D.加用非典型抗精神病药，如氯氮平；E.将复方左旋多巴控释剂换为常释剂。*双相异动症（剂初与剂末）：A.针对剂初：复方左旋多巴控释剂换为常释剂，最好水溶剂；B.加用长半衰期的DR激动剂或COMT抑制剂（延长清除半衰期）。2.姿势平衡障碍的治疗：训练。药物效果不理想。3.非运动症状的治疗：1）感觉障碍：嗅觉减退、疼痛、麻木、不安腿综合征等。原因较多，具体分析，针对用药。2）自主神经功能障碍：便秘、排尿障碍与体位性低血压等。排尿障碍给奥昔布宁、莨菪碱。体位性低血压可给米多君、多潘立酮等。3）精神障碍：抑郁和

50、或焦虑、幻觉、认知障碍、痴呆等。需要鉴别是否药物诱发，如考虑药物依次停药：抗胆碱药、金刚烷胺、MAO-B抑制剂、DR激动剂、复方左旋多巴；如不理想需考虑疾病所致。幻觉妄想：给氯氮平、奥氮平、喹硫平等。抑郁焦虑：SSRI、DR激动剂、易激惹者可给予劳拉西泮、地西泮等。认知障碍或痴呆：利伐斯明、多奈哌齐、加兰他敏、石杉碱甲、美金刚等。4)睡眠障碍：失眠、快速眼动期睡眠行为异常（RBD)、白天过度嗜睡(EDS)等。夜间药量不足，翻身困难引起：调整药物。司来吉兰或金刚烷胺宜在早、中服用。RBD可给氯硝西泮；EDS可与认知功能减退有关，也可与DR激动剂或左旋多巴有关，调整药物，减量或改控释剂。二、外科治