运动障碍疾病PPT
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❖ Lewy body is present in the remaining cells(cytoplasmic
inclusion body,胞浆内嗜酸性包涵体）
病理
正常脑
PD 脑
➢ 含色素的黑质致密部DA能神经元变性\缺失
Parkinson病黑质致密部DA神经元内的Lewy体
HE染色
改良Bielschowsky银染 显示含α-突触核蛋白\泛素沉积
3.适当的辅助检查
➢有助于运动障碍性疾病的诊断
➢如血铜、尿铜和血清CP测定，CT/MRI示双豆状核区信 号异常，对WD的诊断有重要价值
➢PET或SPECT显示纹状体DA转运载体（DAT）功能降低， DA合成减少和D2型DA受体活性改变，对PD诊断颇有意 义
➢基因分析对确诊某些遗传性运动障碍疾病有决定意义
❖ Tremor: often appear as the first sign.
Characters: 4~6Hz, conspicuous at rest, increase at times of emotional stress, improves during voluntary activity, stop during sleep, begin from hand , “N” progression.
characterized by rest tremor, bradykinesia, rigidity, abnormal gait and posture
流行病学（Epidemiology）
➢Parkinson’s disease afflicts 1000/100000 people in people older than 65 ➢The disorder occurs in all races but is somewhat more prevalent among Caucasians ➢Men are affected slightly more often than women ➢Symptoms of PD may appear at any age, but the average age of onset is 60. It is rare in people younger than 30 and risk increases with age
Parkinson disease’s--Clinical findings
▪ Bradykinesia: slowness and reduction of voluntary movement, difficult to initiate, masked face, hypophonia, micrographia.
帕金森病
(Parkinson Disease)
Parkinson’s disease---conception
Also called paralysis agitans.
a common degeneration disease in nervous system
becomes increasingly common with advancing age
⑤ 家族史
➢亨廷顿病、良性遗传性舞蹈病、特发性震颤、扭转痉挛、 抽动-秽语综合征等有遗传性
2.详细的体检
➢可了解运动障碍症状的特点 ➢可明确有无其他神经系统症状体征 ➢如静止性震颤、铅管样或齿轮样肌强直提示PD ➢角膜K-F环提示肝豆状核变性 ➢亨廷顿病和肝豆状核变性等除运动障碍外，常伴精 神和智能损害
✓严重舞蹈症或偏侧投掷症如急性起病提示可能为血管 性病因，缓慢隐袭起病可能为神经变性疾病
③病程
➢对诊断有帮助，如小舞蹈病通常在起病6个月内缓解， 与儿童期起病的其他舞蹈病不同
④ 药物史和疾病史
➢吩噻嗪类及丁酰苯类可引起运动障碍 ➢某些疾病如风湿热、甲状腺疾病、SLE、真性红细胞增多 症等可伴有舞蹈样动作
General Conception
Two types of symptoms
Muscular hypotonus associated with hyperkinesia
Muscular hypertonus characterized with hypokinesia
运动障碍性疾病的症状
Myerson征: 反复叩击眉弓上缘→持续眨眼 反应(正常人不持续)
辅助检查
①生化检测: 高效液相色谱(HPLC)检测CSF HVA↓
②基因检测: 用DNA印迹技术(southern blot)\PCR \DNA序列分析检查家族性PD基因突变
③PET、SPECT检测: 早期可显示脑内DAT功能显 著 ↓ , DA递质合成↓, 可早期诊断和病情监测
oxidated
MPP+
mitochondrion in
substantia nigra
neuronal death
➢ Genetic factor: alpha-synuclein gene -----
susceptibility
病因与发病机制
PD发病可能与多种因素有关, 多种发病机制参与
环境因素
锥体外系的功能
Function of the extrapyramidal system
➢调节肌张力
Regulate muscle tone
➢协调肌肉活动
Coordinate muscular activities
➢保持正常体位和产生习惯性、节律性动作
Maintain normal body posture and produce habitual and rhythmic movement
Parkinson’s disease---Etiology
➢ Aging: over middle aged persons
➢ Environmental toxin: MPTP(1-Methyl-4-
phenyl-1,2,3,6-tetrahydropyridine) in astrocyte
Parkinson disease’s--Clinical findings
▪ Other features: Myerson’s sign, oily face, intractable constipation, postural hypotension, cognitive disturbance, hallucination, depression
协调不同肌群动作, 调节肌张力
PD: 黑质-纹状体系统多巴胺含量显著减少(＞80%)
DA↓
ACh功能相对亢进
神经生化改变 与症状成正比
肌张力↑, 运动↓
Parkinson disease’s---Clinical findings
Over middle aged & insidious onset and gradual progression.
④血、CSF检查无异常, CT\MRI检查无特征性所见
辅助检查
125I-β-CIT 示踪DA转运体PET成像
基线
22月
34月
46月
PD脑纹状体DAT功能逐渐显著降低
Diagnosis
Parkinson disease is a clinical diagnosis. No laboratory biomarkers exist for the condition, and findings on routine magnetic resonance imaging and computed tomography scans are unremarkable.
Parkinson’s disease---Biochemistry
L- tyrosine (blood) TH L-Dopa DDC DA
MAO and COMT
HVA
Nigrostriatal pathway is the most important.
dopamine depletion
subthalamus corpus striatum substantia nigra basal ganglia
大 脑 横 切 面
基底节神经联系环路
基底节 3个主要神经环路
◙ 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
◙ 黑质-纹状体环路:
黑质与尾状核、壳核间往返联系纤 维
扭转痉挛torsion spasm
运动减少 hypokinesia 肌强直 rigidity 震颤麻痹 trembling palsy
部位 locus
纹状体和/或苍白球 striatum and/or pallidus
黑质 substanti nigra
运动障碍性疾病的诊断路径
1.详尽的病史
① 发病年龄
▪ Abnormal gait and posture: flexed posture; difficult to get up, start walking, turn or stop. Shuffling gait and absence of the arm swing. Festinating gait(late sign).
Parkinson disease’s---Clinical findings
Rigidity: lead pipe / cogwheel phenomenon. Minimal rigidity: move the contralateral limb, head dropping test, road mark sign
运动障碍疾病
Movement Disorders
Extrapyramidal Disorders
General Conception: The dysfunction of basal ganglia putamen globus pallidus lentiform nucleus caudate nucleus
Symptom of the movement disorders
肌张力降低-动作增多综 合征
hypotonia-hyperkinetic syndrome
肌张力增高-动作减少综合 征
hypertonia-hypokinetic syndrome
表 现 舞蹈症 chorea manifestation 手足徐动症 athetosis
dopaminergic nigrostriatal system
Extrapyramidal Pathway
TH酪氨酸羟化酶 ，DDC多巴脱羧酶，MAO单胺氧化酶，COMT儿茶酚氧位甲基转移酶 HVA高香草酸
生化病理
黑质纹状体神经递质系统
DA
ACh
DA与ACh递质系统 相互拮抗, 维持平衡
调节正常的基底节环路功能
Clinical diagnosis requires the presence of 2 of 3 cardinal signs:
Resting tremor Rigidity Bradykinesia
帕金森病的临床诊断标准
➢常可提示病因 ✓婴儿幼儿期起病可能为脑缺氧、产伤、核黄疸或遗传因素 ✓少年期出现震颤很可能是Wilson病 ➢有助于判断预后 ✓原发性扭转痉挛在儿童期起病远较成年起病严重 ✓老年发病的迟发性运动障碍较成年发病更严重
② 起病方式
➢常可提示病因
✓儿童青少年肌张力障碍急性起病可能药物不良反应， 缓慢起病多为原发性扭转痉挛、肝豆状核变性等
遗传因素
生理奋氨基酸
黑质DA 能神经元
死亡
床 症
细胞凋亡
状
Parkinson’s disease---Pathology
❖ loss of at least 50% 0f melanin-containing cells in the substantia nigra
◙ 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
基底节的基本神经元环路
皮质-皮质环路的两条投射路径
直接通路
兴奋大脑皮层
纹状体→内侧苍白球/黑质网状部
间接通路
抑制大脑皮层
纹状体→外侧苍白球→丘脑底核→内侧苍白 球/黑质网状部
皮质-皮质环路是基底节实现其运动调节功能的主要 结构基础，而两条通路的活动平衡对实现正 常运动功能至关重要。
inclusion body,胞浆内嗜酸性包涵体）
病理
正常脑
PD 脑
➢ 含色素的黑质致密部DA能神经元变性\缺失
Parkinson病黑质致密部DA神经元内的Lewy体
HE染色
改良Bielschowsky银染 显示含α-突触核蛋白\泛素沉积
3.适当的辅助检查
➢有助于运动障碍性疾病的诊断
➢如血铜、尿铜和血清CP测定，CT/MRI示双豆状核区信 号异常，对WD的诊断有重要价值
➢PET或SPECT显示纹状体DA转运载体（DAT）功能降低， DA合成减少和D2型DA受体活性改变，对PD诊断颇有意 义
➢基因分析对确诊某些遗传性运动障碍疾病有决定意义
❖ Tremor: often appear as the first sign.
Characters: 4~6Hz, conspicuous at rest, increase at times of emotional stress, improves during voluntary activity, stop during sleep, begin from hand , “N” progression.
characterized by rest tremor, bradykinesia, rigidity, abnormal gait and posture
流行病学（Epidemiology）
➢Parkinson’s disease afflicts 1000/100000 people in people older than 65 ➢The disorder occurs in all races but is somewhat more prevalent among Caucasians ➢Men are affected slightly more often than women ➢Symptoms of PD may appear at any age, but the average age of onset is 60. It is rare in people younger than 30 and risk increases with age
Parkinson disease’s--Clinical findings
▪ Bradykinesia: slowness and reduction of voluntary movement, difficult to initiate, masked face, hypophonia, micrographia.
帕金森病
(Parkinson Disease)
Parkinson’s disease---conception
Also called paralysis agitans.
a common degeneration disease in nervous system
becomes increasingly common with advancing age
⑤ 家族史
➢亨廷顿病、良性遗传性舞蹈病、特发性震颤、扭转痉挛、 抽动-秽语综合征等有遗传性
2.详细的体检
➢可了解运动障碍症状的特点 ➢可明确有无其他神经系统症状体征 ➢如静止性震颤、铅管样或齿轮样肌强直提示PD ➢角膜K-F环提示肝豆状核变性 ➢亨廷顿病和肝豆状核变性等除运动障碍外，常伴精 神和智能损害
✓严重舞蹈症或偏侧投掷症如急性起病提示可能为血管 性病因，缓慢隐袭起病可能为神经变性疾病
③病程
➢对诊断有帮助，如小舞蹈病通常在起病6个月内缓解， 与儿童期起病的其他舞蹈病不同
④ 药物史和疾病史
➢吩噻嗪类及丁酰苯类可引起运动障碍 ➢某些疾病如风湿热、甲状腺疾病、SLE、真性红细胞增多 症等可伴有舞蹈样动作
General Conception
Two types of symptoms
Muscular hypotonus associated with hyperkinesia
Muscular hypertonus characterized with hypokinesia
运动障碍性疾病的症状
Myerson征: 反复叩击眉弓上缘→持续眨眼 反应(正常人不持续)
辅助检查
①生化检测: 高效液相色谱(HPLC)检测CSF HVA↓
②基因检测: 用DNA印迹技术(southern blot)\PCR \DNA序列分析检查家族性PD基因突变
③PET、SPECT检测: 早期可显示脑内DAT功能显 著 ↓ , DA递质合成↓, 可早期诊断和病情监测
oxidated
MPP+
mitochondrion in
substantia nigra
neuronal death
➢ Genetic factor: alpha-synuclein gene -----
susceptibility
病因与发病机制
PD发病可能与多种因素有关, 多种发病机制参与
环境因素
锥体外系的功能
Function of the extrapyramidal system
➢调节肌张力
Regulate muscle tone
➢协调肌肉活动
Coordinate muscular activities
➢保持正常体位和产生习惯性、节律性动作
Maintain normal body posture and produce habitual and rhythmic movement
Parkinson’s disease---Etiology
➢ Aging: over middle aged persons
➢ Environmental toxin: MPTP(1-Methyl-4-
phenyl-1,2,3,6-tetrahydropyridine) in astrocyte
Parkinson disease’s--Clinical findings
▪ Other features: Myerson’s sign, oily face, intractable constipation, postural hypotension, cognitive disturbance, hallucination, depression
协调不同肌群动作, 调节肌张力
PD: 黑质-纹状体系统多巴胺含量显著减少(＞80%)
DA↓
ACh功能相对亢进
神经生化改变 与症状成正比
肌张力↑, 运动↓
Parkinson disease’s---Clinical findings
Over middle aged & insidious onset and gradual progression.
④血、CSF检查无异常, CT\MRI检查无特征性所见
辅助检查
125I-β-CIT 示踪DA转运体PET成像
基线
22月
34月
46月
PD脑纹状体DAT功能逐渐显著降低
Diagnosis
Parkinson disease is a clinical diagnosis. No laboratory biomarkers exist for the condition, and findings on routine magnetic resonance imaging and computed tomography scans are unremarkable.
Parkinson’s disease---Biochemistry
L- tyrosine (blood) TH L-Dopa DDC DA
MAO and COMT
HVA
Nigrostriatal pathway is the most important.
dopamine depletion
subthalamus corpus striatum substantia nigra basal ganglia
大 脑 横 切 面
基底节神经联系环路
基底节 3个主要神经环路
◙ 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
◙ 黑质-纹状体环路:
黑质与尾状核、壳核间往返联系纤 维
扭转痉挛torsion spasm
运动减少 hypokinesia 肌强直 rigidity 震颤麻痹 trembling palsy
部位 locus
纹状体和/或苍白球 striatum and/or pallidus
黑质 substanti nigra
运动障碍性疾病的诊断路径
1.详尽的病史
① 发病年龄
▪ Abnormal gait and posture: flexed posture; difficult to get up, start walking, turn or stop. Shuffling gait and absence of the arm swing. Festinating gait(late sign).
Parkinson disease’s---Clinical findings
Rigidity: lead pipe / cogwheel phenomenon. Minimal rigidity: move the contralateral limb, head dropping test, road mark sign
运动障碍疾病
Movement Disorders
Extrapyramidal Disorders
General Conception: The dysfunction of basal ganglia putamen globus pallidus lentiform nucleus caudate nucleus
Symptom of the movement disorders
肌张力降低-动作增多综 合征
hypotonia-hyperkinetic syndrome
肌张力增高-动作减少综合 征
hypertonia-hypokinetic syndrome
表 现 舞蹈症 chorea manifestation 手足徐动症 athetosis
dopaminergic nigrostriatal system
Extrapyramidal Pathway
TH酪氨酸羟化酶 ，DDC多巴脱羧酶，MAO单胺氧化酶，COMT儿茶酚氧位甲基转移酶 HVA高香草酸
生化病理
黑质纹状体神经递质系统
DA
ACh
DA与ACh递质系统 相互拮抗, 维持平衡
调节正常的基底节环路功能
Clinical diagnosis requires the presence of 2 of 3 cardinal signs:
Resting tremor Rigidity Bradykinesia
帕金森病的临床诊断标准
➢常可提示病因 ✓婴儿幼儿期起病可能为脑缺氧、产伤、核黄疸或遗传因素 ✓少年期出现震颤很可能是Wilson病 ➢有助于判断预后 ✓原发性扭转痉挛在儿童期起病远较成年起病严重 ✓老年发病的迟发性运动障碍较成年发病更严重
② 起病方式
➢常可提示病因
✓儿童青少年肌张力障碍急性起病可能药物不良反应， 缓慢起病多为原发性扭转痉挛、肝豆状核变性等
遗传因素
生理奋氨基酸
黑质DA 能神经元
死亡
床 症
细胞凋亡
状
Parkinson’s disease---Pathology
❖ loss of at least 50% 0f melanin-containing cells in the substantia nigra
◙ 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
基底节的基本神经元环路
皮质-皮质环路的两条投射路径
直接通路
兴奋大脑皮层
纹状体→内侧苍白球/黑质网状部
间接通路
抑制大脑皮层
纹状体→外侧苍白球→丘脑底核→内侧苍白 球/黑质网状部
皮质-皮质环路是基底节实现其运动调节功能的主要 结构基础，而两条通路的活动平衡对实现正 常运动功能至关重要。