Parkinson’s disease

C ortex

P refrontalInsular

C ingulateS ensoryMotor

S uppl. MotorP remotor

P remotorP refrontal

S triatum

D 2 D 1Thalamus

VA /VL

+ = exc itatory

- = inhibitory

B rainstemS C

S N c

S N r

G P i

S TN

G Pe

-

+

+

+-

-

---

-

+

++

+

+

+

N ormal

Function Anatomy of Parkinson’s Disease

C ortex

P refrontalInsular

C ingulateS ensoryMotor

S uppl. MotorP remotor

P remotorP refrontal

S triatum

D 2 D 1Thalamus

VA /VL

+ = exc itatory

- = inhibitory

B rainstemS C

S N c

S N r

G P i

S TN

G Pe

-

-

++

++++

-

---

--

+

++

+

+

+ - -

Parkinson’s D isease

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) PDAgeEnvironment

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 levodopaThe metabolism of levodopa

左 旋 多 巴 左 旋 多 巴 LevLevodopaodopa

33 － 氧－ 甲 基 多 － 氧－ 甲 基 多 巴巴 ( 3- OMD)( 3- OMD)

多 巴 胺 多 巴 胺 DopaDopaminemine

左 旋 多 巴 左 旋 多 巴 LevodopaLevodopa

33 － 氧－ 甲 基 － 氧－ 甲 基 多 巴多 巴 ( 3- OMD)( 3- OMD)

甲 氧 基－ 络 胺 甲 氧 基－ 络 胺 (3-MT)(3-MT)

二 羧 基－ 苯－ 乙 酸 二 羧 基－ 苯－ 乙 酸 (DOPAC)(DOPAC)

高 香 草 酸 高 香 草 酸 (HVA)(HVA)

多 巴 胺 多 巴 胺 (Dopamine)(Dopamine)

COMTX X

COMT

COMTCOMT

COMTCOMTMAOMAO

MAOMAO

X

X

X

多 巴 脱 羧 酶 DDC

多 巴 脱 羧 酶 DDC

Tolcapone

Tolcapone

Tolcapone

TolcaponeTolcapone

外 周

脑 内

载 体

苄 丝 肼 卡 比 多 巴

Clinical manifestations

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 examination1.The HVA dose in cerebrospinal fluid a

nd urine.2. Southern blot 、 PCR 、 DNA analysi

s3. PET 、 SPECT

Diagnosis

It’s usually not difficulty to diagnose PD accor

ding to the age at onset, symptoms and cours

e of the disease. The coherence of PD clin

ical diagnosis is 85% with the pathology.

Differential diagnosis 1.Secondary Pakinsonism 2.Major depression (MD) 3.Essential tremor (ET) 4.Other nervous system degeneration diseas

e with the PD sympotom 5.Diffuse Lewey body disease (DLBD) 6.Hepatolenticular degeneration (HLD) 7.Huntington’s disease (HD)

Differential diagnosis8.Multiple system atrophy (MSA):

① Striatonigral degeneration (SND) ②Shy-Drager syndrome (SDS) ③Olivoponcerebellar 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 :

①L-Dopa ② Compound L-Dopa ：

madopar Sinemet madopar dispersible Sinemet CR

L-Dopa and the complication

EffectEffect

complicationcomplication

Course of the Course of the diseasedisease

5 years5 years

wearing-off

on-off phenom

enon

Dyskim

sia G

ait freezin

g

DA depositDA deposit 2.0 1.37

Co

gn

itive

d

isord

er

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 treatments2.Surgery

The most common methods : Stereotaxic thalamotomy Pallidotomy Deep brain stimulation (DBS)

3.Transplantation of fetal dopamine neurons or gene therapy.

4.Neurologic rehabilitation.