PARKINSON DISEASE

s e lly m ar isd in a, S p .S
Dr .
1. Definisi Parkinsonism, Parkinson Disease
2. Patofisiologi Parkinson Disease
3. Gejala klinis Parkinson Disease
4. Diagnosis Parkinson Disease
5. Tata laksana Parkinson Disease
 Basal ganglia
subcortical nuclei:
caudate, putamen &
globus pallidus are
named corpus striatum
Caudate &putamen are
named striatum
globus pallidus &
caudate putamen are named
lentiform nuclei
putamen
globus pallidus

MOVEMENT
DISORDER
PPT. Movement Disorders and Extrapyramidal System Sibel Ertan, MD
Dept. of Neurology
Parkinsonism

• Parkinsonism: combination of the following six cardinal features:

– tremor at rest,
– bradykinesia,
– rigidity,
– loss of postural reflexes,
– flexed posture, and
– freezing (motor blocks).

• The four major characteristics of parkinsonism :

tremor, rigidity, akinesia, and postural disturbances (TRAP ).
Bradley's Neurology in Clinical Practice Seventh Edition © 2016, Elsevier
 The many causes of parkinsonism are divided into four
categories:
1. Idiopathic (%77.7): Etiologi tidak jelas, paling sering
dijumpali, berhubungan dengan MPTP (1 methyl 4 phenyl
1,2,3,4 tetrahidropyridine ) --> Parkinson Disease
2. Parkinson-plus syndromes (%12.2)
3. Symptomatic (secondary) (%8.2)
4. Heredodegenerative diseases (%0.6)
 The core biochemical pathology in parkinsonism is
“decreased dopaminergic neurotransmission in the
basal ganglia”

• Degeneration of the nigrostriatal dopamine system

• Degeneration of the striatum with loss of dopamine receptors
• Drug induced parkinsonism as the result of blockade of dopamine rece
ptors.
Nigral Dopaminergic Neuron Terminals and
Striatal Receptors

Parkinson’s Drug-induced
Parkinson-plus
Disease Parkinsonizm
Syndromes

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Parkinson’s disease

1817: James Parkinson

“Shaking Palsy”

1960: Dopaminergic neuronal

loss in substantia nigra
1960: Levodopa
1982: MPTP (ABD, California)
(toxic substance in
synthetic heroin)
After 1982: Experimental
models
2005: Etiopathogenesis ?

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Parkinson’s disease (primary parkinsonism)

• PD makes up approximately 80% of cases of

parkinsonism.
• Mean age at onset in both sexes is 55 years
(range:20-80).
• Over 60 yrs of age risk of Parkinson’s disease is %1
• Male/female = 3/2.
• Prevalence  160/100.000 and incidence 20/100.000/yr.
• The cause of PD is unknown.

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 Parkinson’s disease (primary parkinsonism)
• Degeneration of the neuromelanin-containing
neurons in the brain stem, especially in
substantia nigra pars compacta and in the
locus ceruleus.
• Many of the surviving neurons contain
eosinophilic cytoplasmic inclusions known as
Lewy bodies.
• By the time symptoms appear, the substantia
nigra already has lost about 60% of
dopaminergic neurons and the dopamine
content in the striatum is about 80% less than
normal.

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PATOPHYSIOLOGY

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 NORMAL

SEREBRAL KORTEKS

Glu Glu Glu

STRİATUM AK GABA
D1 D2
SS
P Mad. ENK. Glu VA/VL
DA
GABA Glu
TALAMUS
GABA

Glu GABA
Glu
SNpc GPe STN Glu
GABA

Glu
GABA GABA

GPi/SNpr GABA
M. Spinalis Glu

PPN
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PARKINSON

SEREBRAL KORTEKS

Glu Glu Glu

STRİATUM AK GABA
D1 D2/ENKEFALİN
SS
P Mad. DİNORFİN
VA/VL
GABA
TALAMUS
DA GABA

STN GABA
SNpc GPe GABA

GABA
Glu
Glu

GPi/SNpr GABA
M. Spinalis

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CHOREA HUNTINGTON

SEREBRAL KORTEKS

Glu Glu
Glu
STRİATUM AK GABA
D1 D2
SS
P Mad. ENK. VA/VL
DA
GABA
TALAMUS
GABA

GABA
Glu STN
SNpc GPe GABA

Glu
GABA

GPi/SNpr GABA

M. Spinalis

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Parkinson’s Disease - Symptomatology

Motor abnormalities
•Early: unaware of any motor deficit.
•PD is typically asymmetrical, especially early in the course (sometimes A pa
inful shoulder )
•Tremor: Static  postural, 3-7 Hz, (hand, arm, foot, leg, tongue, chin, lip)
•Rigidity
•Bradykinesia
– reduction in facial expression (often misinterpreted as depression),
– a reduction in arm swing while walking, and a slowing of activities of daily living, mos
t notably dressing, feeding, and walking.

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• micrographia
• Dressing tasks are often difficult.
• Hygiene becomes impaired, disability is greater if the dominant arm is mo
re affected; shaving, brushing teeth, and other repetitive movements usua
lly are affected the most.
• hypophonia
• speech may be festinating ; that is, it gets faster and faster (tachyphemia).
• speech disturbances: stuttering and palilalia
• nasal quality of the voice, quite distinctive from the hypophonic monotone
of PD
• excessive salivation and drooling.
• Getting in and out of a chair or car, climbing in and out of the bathtub may
cause problems
• misinterpret from “weakness.”
• Generalized loss of energy and easy fatigability
• Walking becomes slowed and shuffling, with flexion of the knees and a na
rrow base.
• When involvement is asymmetrical, one leg may drag behind the other.
• Turns include multiple steps (turning en bloc).
• a tendency to advance more and more rapidly with shorter an
d shorter steps (festination),
• freezing phenomenon, or motor block.
– initiates walking (start hesitation),
– turning (especially in an enclosed space),
– attempts to walk through an enclosed area or a narrow passage such
as a doorway or walking in or out of an elevator.
– poor postural stability, the tendency to fall forward or to the side while
turning.
Cognitive, Autonomic, and Sensory Abnormalities

• Dementia
• Depression.
• Bradyphrenia, describes the slowness of thought processes and inattentiveness
• constipation
• Bladder complaints such as frequency, nocturia, and the sensation of incomplete bladder
emptying
• orthostatic hypotension
• rapid eye movement (REM) sleep behavior disorder
• excessive greasiness of the skin and seborrheic dermatitis, characteristically seen over t
he forehead, eyebrows, and malar area.
Examination and Clinical Signs
• The facial expression, low-volume voice, tremor, poverty of movement, sh
uffling gait, and stooped posture
• Loss of facial expression ( hypomimia )
• Blink frequency usually is reduced
• Primitive reflexes, including the inability to inhibit blinking in response to ta
pping over the glabella (Myerson sign) and palmomental reflexes
• Tremor "resting"
– Patients should be observed with hands resting on their laps or thighs,
and they should be instructed to hold their arms in an outstretched posi
tion or in a horizontal position with shoulders abducted, elbows flexed,
and hands palms-down in front of their faces in the so-called “wing-bea
ting position”.
• Rigidity is an increase in muscle tone, usually equal in flexors
and extensors and present throughout the passive range of mo
vement.
– Contrasts with the clasp-knife phenomenon
– Cogwheel phenomenon, appreciated by placing one hand over the mu
scles being tested (e.g., placing the left thumb over the biceps and the
remaining fingers over the triceps while flexing and extending the elbo
w with the right hand).  
• Akinesia and bradykinesia are appreciable on examination in
several ways.
– Automatic movements (gesturing with hands while speaking, crossing
and uncrossing the legs, and repositioning the body in the chair diminis
h) are absent.
– The performance of rapid, repetitive, and alternating movements such
as finger tapping, opening and closing the fist, pronation-supination of t
he forearm, and foot tapping is slow, with a gradual reduction in amplit
ude and eventual cessation of movement ( freezing ).
– hesitation in initiating movement and arrests in ongoing movement.
– Watching the patient write (micrographia), writing and drawing show a ten
dency to fatigue, with a further reduction in size as the task proceeds and
a concomitant action tremor.
– The head usually tilts forward and the body becomes stooped, kyphosis
– The arms become flexed at the elbows and wrists, with varying postural d
eformities in the hands, the most common being flexion at the metacarpo
phalangeal joints and extension at the interphalangeal joints, with adducti
on of all the fingers and opposition of the thumb to the index finger ( striat
al hand ),
– Variable foot deformities, (hammer toe-like disturbances), extension of the
great toe ( striatal foot )
• Postural instability
– As patients rise from a sitting position, poor postural stability,
slowness, narrow base, and not repositioning the feet often c
ause them to fall back into the chair
• may require several attempts, push off the arms of the chair, or nee
d to be pulled up by an assistant.
– Gait disturbances : lack of arm swing, shortened and later sh
uffling stride, freezing in the course of walking (especially wh
en initiating gait and when approaching a door frame or a po
tential obstruction or a chair).
– Turn en bloc, propulsion and retropulsion may occur falls
– Walking often exacerbates a rest tremor in patients with PD.
– To assess postural instability, the pull test.
– Standing behind the patient, the examiner pulls the patient backward
by the shoulders, carefully remaining close behind to prevent a fall
– Once postural reflexes are impaired, there may be retropulsion or mul
tiple backward steps in response to the postural perturbation.
– Later there is a tendency to fall en bloc without retropulsion or even n
ormal attempts to recover or to cushion the fall.
 Clinical Staging of PD According
0- Asymptomatic to Hoehn-Yahr Scale
1- Unilateral involvement
2- Bilateral involvement
3- Involvement of postural reflexes,
imbalance and falls
Mild-moderate morbidity
4- Needs continious support
5- Bedridden

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Diagnosis of PD

 Based on clinical
findings and signs
 No radiologic “marker”
 No laboratory “marker”
• Diagnosis:
– definite parkinsonism: at least two of these features must
be present, with one of them being resting tremor or bradyki
nesia;
– probable parkinsonism : consists of resting tremor or brad
ykinesia alone;
– possible parkinsonism : includes at least two of the remain
ing four features.
Parkinson’s disease Treatment

• Treatment is aimed at controlling symptoms because no

drug or surgicl approach unequivocally prevents
progression of PD.
• Treatment is lifelong.
• Treatment includes pharmacotherapy, physiotherapy and
surgery.

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 Parkinson’s disease
(primary parkinsonism)
Medications Treatment

Dopamine precursor: levodopa (LD)±carbidopa or benserazide

Dopamine agonists: bromocriptine, pergolide, pramipexole, ropinirole,
apomorphine, cabergoline, pribedil.
Catecholamine-O-methyl transferase inhibitors: tolcapone and entacapone.
Dopamine releaser, NMDA receptor antagonist: Amantadine.
Monoamine oxidase type B inhibitor: selegiline. rasagiline
Anticholinergics: trihexyphenidyl, benztropine, biperidene
Antihistaminics: diphenhydramine, orphenadrine, phenindamine

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 Parkinson’s disease
(primary parkinsonism)
Treatment
Surgery

Ablative surgery:Thalamotomy, pallidotomy.

Restorative surgery:Embryonic dopaminergic tissue
transplantation
Deep brain stimulation:Thalamic stimulation, pallidal
stimulation, subthalamic stimulation, PPN

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 Parkinson’s disease (primary
parkinsonism)
• LD is the most effective drug, BUT 75% of patients have Treatment
serious complications after 5 years of LD therapy.
• Younger patients, in particular, are more likely to show
response fluctuations.
• DOPA-SPARING STRATEGY: Other antiparkinsonian
drugs should be used first to delay the introduction of
LD.
• Selegiline delays the need for LD therapy by an average
of 9 months.

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Adverse events and side effects of L-Dopa

 Noisea, vomiting
 Postural hypotension
 Psychosis: Hallucinations
delusions

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 Late Complications of L-Dopa
Motor Complications
1. “wearing-off” End of dose phenomenon (predictable)
2. “On-off” fluctuations (unpredictable)
3. Dyskinesias:
- Chorea (“on” period)
- Dystonia (“on” or “of” period)

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38

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Thank you

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