Parkinson ’ s disease
Function Anatomy of Parkinson ’ s Disease
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
Etiology
Primary (Idiopathic) PD Age Environment MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) Heredity P4502D2 gene а-synuclein gene Parkin gene
Secondary (Acquired, symptomatic) PD Post-encephalitic Pakinsonism Drugs-induced or toxins-induced Pakinsonism Vascular Pakinsonism
Pathology
Pathophysiology
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
Clinical manifestations
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
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.
Laboratory examination 1.The HVA dose in cerebrospinal fluid and urine. 2. Southern blot 、 PCR 、 DNA analysis 3. PET 、 SPECT
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.
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)
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)
Treatment
1.Drug (1)Anticholinergic drugs: Adam: 1~2mg tid P.O. (2) Amantadine
1.Drug (3) Levodopa and Compound levodopa : ① L-Dopa ② Compound L-Dopa : madopar Sinemet madopar dispersible Sinemet CR
L-Dopa and the complication Effect complication Course of the disease 5 years wearing-off on-off phenomenon Dyskimsia Gait freezing DA deposit Cognitive disorder 1.47
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
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
1.Drug (5)Monoamine oxidase type B ( MAO-B ) : Deprenyl (6)Catechol O-methyltransferase (COMT) inhibitors: Tacapone Entacopone
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.