Parkinson’s Disease
台北榮總神經內科 主治醫師
陽明大學神經學科副教授
李宜中
History
 The disease was first
described in 1817 by
James Parkinson
Clinical Diagnosis Of PD
 Resting tremor
 Rigidity
 Bradykinesia
 Posture instability
2 of 4 major signs
Stages of Parkinson's disease
 Stage I (mild or early disease): unilateral
involved.
 Stage II: Both sides of the body are affected.
 Stage III (moderate disease): Both sides
involved with postural instability.
 Stage IV (advanced disease): requiring
substantial help in walking and turning.
 Stage V (severe): Restricted to a bed or chair.
Epidemiology of PD
 The most common movement disorder
affecting 1-2 % of the general population over
the age of 65 years.
 The second most common neurodegenerative
disorder after Alzheimer´s disease (AD).
 Prevalence rates in men are slightly higher
than in women; reason unknown, though a
role for estrogen has been debated.
Risk factors of PD
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Age - the most important risk factor
Positive family history
Male gender
Environmental exposure: Herbicide and pesticide
exposure, metals (manganese, iron), well water, farming,
rural residence, wood pulp mills; and steel alloy
industries
Race
Life experiences (trauma, emotional stress, personality
traits such as shyness and depressiveness)?
An inverse correlation between cigarette smoking and
caffeine intake in case-control studies.
Non-motor features of PD
 Neuropsycholgochiatric
 Depression
 Apathy
 Sleep disorder
 Insomnia
 Daytime sleepiness
 REM sleep disorders
 Anxiety
 Autonomic dysfunction
 Executive
dysfunction
 dementia
 Orthostatic hypotension
 Constipation
 Urogenital dysfunction
Autonomic dysfunction in PD
 Not only occurs in late stage of PD
 May as a early sign in AD
 Medications for PD may exacerbate symptoms of
autonomic dysfunction
Signs and symptoms of
autonomic dysfunction of PD
System
manifestations
Cadiovascular
Orthostatic hypotension
Gastrointestinal
Constipation, dysphagia, diarrhea
Urinary bladder
Nocturia, frequency, urgency,
incontinence, retention
Sudomotor
ANHIDROSIS, HEAT INTOLERANCE
Sexual
Erectile and ejaculatory failure
Ocular
Aniscoria, Horner’s syndrome
Respiratory
Stridor, apneic episode, inspiratory gasps
Pathology of PD
Neuropathology of PD
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Eosinophilic, round intracytoplasmic inclusions called
lewy bodies and Lewy neurites.
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First described in 1912 by a German
neuropathologist - Friedrich Lewy.
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Inclusions particularly numerous in the substantia
nigra pars compacta.
Lewy bodies
Neuropathology of PD: Lewy bodies
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Not limited to substantia nigra only; also found in the locus
coeruleus, motor nucleus of the vagus nerve, the
hypothalamus, the nucleus basalis of Meynert, the cerebral
cortex, the olfactory bulb and the autonomic nervous system.
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Confined largely to neurons; glial cells only rarely affected.
Functional neuroanatomy of PD
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Substantia nigra: The major origin of the dopaminergic
innervation of the striatum.
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Part of extrapyramidal system which processes
information coming from the cortex to the striatum,
returning it back to the cortex through the thalamus.
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One major function of the striatum is the regulation of
posture and muscle tonus.
Pathophysiology of PD
Secondary parkinsonism
 續發性(secondary）巴金森氏症是因一些疾病或物
質造成類似巴金森氏病的症狀，其相關原因可能有
 腦炎
 腦動脈硬化(cerebral ateriosclerosis):多為老年人。
 藥物：reserpine, neuroleptics, metoclopromide,
prochloperazine, flunarizine
 中毒：一氧化碳、錳、MPTP等。
 頭部外傷、職業拳手症
 腫瘤
 其他神經退化性疾病：如progressive
supramuclear palsy, striatonigral degenerateion,
Huntington’s disease, Wilson’s disease等。
Pharmacogical mangement
Treatment of Parkinson‘s disease
in the 1860‘s -Dr. J. M. Charcot‘s
Rocking chair
Neurochemistry of PD
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Late 1950s: Dopamine (DA) present in mammalian
brain, and the levels highest within the striatum.
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1960, Ehringer and Hornykiewicz: The levels of DA
severely reduced in the striatum of PD patients.
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PD symptoms become manifest when about 50-60 %
of the DA-containing neurons in the substantia nigra
and 70-80 % of striatal DA are lost.
Dopamine synthesis
Pharmacological treatment of PD
初期使用L－dopa之副作用
 腸胃症狀
 噁心、腹痛、食慾減退、嘔吐
 心臟血管症狀
 心悸、暈眩、心律不整、姿勢性低血壓
 腦功能症狀
 注意力不集中、焦慮、興奮、幻覺、幻想
 其他症狀
 性慾增加、尿變紅、皮膚疹
長期使用L-dopa之副作用
 藥效減低
 藥效時間減短
 不自主動作
 On-off 現象
Long-term complications of
levodopa
Motor fluctuation
• Weaning-off phenomenon
• On-off phenomenon
Dyskinesia
• Chorea
• dystonia
Flucturations in levodopa
treatment
Levodopa related motor
flucturation
Dyskinesia in levodopa
treatment
Pharmacological treatment of PD
Surgical mangement
巴金森氏病的手術治療方式
 立體定位手術
 神經細胞損害方式
 蒼白球燒灼術
 視丘燒灼術
 視丘下核燒灼術
 腦部深層刺激術
 蒼白球刺激術
 視丘刺激術
 視丘下核刺激術
 組織植入手術
 胚胎移植
 腎上腺移植
 培養細胞移植
Motor circuitry of basal ganglion
Deep brain stimulation
Pre-deep brain stimulation
Post-Deep brain stimulation
Indication of Deep brain
stimulation
• Advanced Parkinson's disease
• Who have shown benefit from levodopa therapy
• Whose symptoms are not adequately controlled
by medications.
• Patients should be carefully screened for other
movement disorders, which may not respond to
Deep brain stimulation.
• Deep brain stimulation has not been shown to
improve symptoms that do not respond also to
levodopa.
Potential surgical risks
• Paralysis, coma, death
• Intracranial hemorrhage
• Leakage of cerebral fluid surrounding the brain
• Seizure
• Infection
• Allergic response to implanted materials
• Temporary or permanent neurological
complications
• Confusion or attention problems
• Pain at the surgery sites
Side effects of deep brain
stimulation
• Tingling sensation (paresthesia)
• Worsening of symptoms
• Speech problems (dysarthria, dysphasia)
• Dizziness or lightheadedness (disequilibrium)
• Facial and limb muscle weakness or partial
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paralysis (paresis)
Abnormal, involuntary muscle contractions
(dystonia, dyskinesia)
Movement problems or reduced coordination
Jolting or shocking sensation
Numbness (hypoesthesia)
Important Points
 巴金森氏病的典型症狀為: 手抖、行動緩慢、肢體
僵硬.
 巴金森氏病的主要病理變化發生在Substantia
nigra.
 巴金森氏病與Dopamine 的缺乏相關.
 Lewy bodies是在巴金森氏病中，發生病理變化的
神經細胞內中所發生的異常蛋白質堆積所形成，
其主要成分為α-synuclein.