1. Parkinson ’ s disease

4. Function Anatomy of Parkinson ’ s Disease

6. Parkinson ’ s disease (PD),which is also called paralysis agitans ， is a common degenerative disease of the nervous system in middle and old-age. PD is a clinical disease dominated by four important signs:  tremor at rest  bradykinesia  rigidity  postural instability and gait difficulty

7. Etiology

8. Primary (Idiopathic) PD  Age  Environment  MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine)  Heredity  P4502D2 gene  а-synuclein gene  Parkin gene

9. Secondary (Acquired, symptomatic) PD  Post-encephalitic Pakinsonism  Drugs-induced or toxins-induced Pakinsonism  Vascular Pakinsonism

10. Pathology

12. Pathophysiology

13. The metabolism of levodopa The metabolism of levodopa 左 旋 多 巴 Levodopa 左 旋 多 巴 Levodopa 3 － 氧－ 甲 基 多 巴 ( 3- OMD) 多 巴 胺 Dopamine 左 旋 多 巴 Levodopa 3 － 氧－ 甲 基 多 巴 ( 3- OMD) 3 － 氧－ 甲 基 多 巴 ( 3- OMD) 甲 氧 基－ 络 胺 (3-MT) 甲 氧 基－ 络 胺 (3-MT) 二 羧 基－ 苯－ 乙 酸 (DOPAC) 二 羧 基－ 苯－ 乙 酸 (DOPAC) 高 香 草 酸 (HVA) 高 香 草 酸 (HVA) 多 巴 胺 (Dopamine) 多 巴 胺 (Dopamine) COMT X X COMT COMT MAO MAO X X X 多 巴 脱 羧 酶 DDC 多 巴 脱 羧 酶 DDC Tolcapone Tolcapone 外 周 外 周 脑 内 脑 内 载 体 载 体 苄 丝 肼卡 比 多 巴 苄 丝 肼卡 比 多 巴

15. Clinical manifestations

16.  1. tremor  2 rigidity  lead-pipe phenomenon  cogwheel phenomenon  head dropping test  road market phenomenon  3, bradykinesia  4 postural instability and gait difficulty :  Festination gait

17. Clinical manifestations Some patient may have the other non- motor manifestations of PD such as autonomic dysfunction, personality changes,dementia, depression and visual hallucination, but usually don ’ t serious.

18. Laboratory examination  1.The HVA dose in cerebrospinal fluid and urine.  2. Southern blot 、 PCR 、 DNA analysis  3. PET 、 SPECT

19. Diagnosis It ’ s usually not difficulty to diagnose PD according to the age at onset, symptoms and course of the disease. The coherence of PD clinical diagnosis is 85% with the pathology.

20. Differential diagnosis  1.Secondary Pakinsonism  2.Major depression (MD)  3.Essential tremor (ET)  4.Other nervous system degeneration disease with the PD sympotom  5.Diffuse Lewey body disease (DLBD)  6.Hepatolenticular degeneration (HLD)  7.Huntington ’ s disease (HD)

21. Differential diagnosis  8.Multiple system atrophy (MSA):  ① Striatonigral degeneration (SND)  ② Shy-Drager syndrome (SDS)  ③ Olivoponcerebellar atrophy (OPCA)  9.Progressive supraneuclear palsy (PSP)  10.Corticalbasal degeneration (CBGD)

22. Treatment

23. 1.Drug  (1)Anticholinergic drugs:  Adam: 1~2mg tid P.O.  (2) Amantadine

24. 1.Drug  (3) Levodopa and Compound levodopa :  ① L-Dopa  ② Compound L-Dopa ：  madopar  Sinemet  madopar dispersible  Sinemet CR

25. L-Dopa and the complication Effect complication Course of the disease 5 years wearing-off on-off phenomenon Dyskimsia Gait freezing DA deposit 2.01.37 Cognitive disorder 1.47

26. Side-effects of L-Dopa  Peripheral ： nausea, vomit, hypotension, arrhythmia  Central ：  Motor fluctuation:  (1) wearing-off  (2) on-off phenomenon  Dyskimsia :  (1) peak-dose dyskimsia  (2) biphasic dyskinesia  (3) dystonia  Psychiatric sympotoms

27. 1.Drug  Dopamine agonists, DAs :  Bromocriptin  Pergolide  Lisuride  Trastal SR  Apomorphine  Bromocriptin : have large agonism to D2 receptor but small antagonism to D1 receptor  Pergolide : have agonism to both D1 and D2 receptor

28. 1.Drug  (5)Monoamine oxidase type B （ MAO-B ） :  Deprenyl  (6)Catechol O-methyltransferase (COMT) inhibitors:  Tacapone  Entacopone

29. Other treatments  2.Surgery The most common methods :  Stereotaxic thalamotomy  Pallidotomy  Deep brain stimulation (DBS)  3.Transplantation of fetal dopamine neurons or gene therapy.  4.Neurologic rehabilitation.