PARKINSON DISEASE

Devyani Diah Wulansari

OUTLINES
1. Clinical Overview
2. Symptoms
3. Common Form Of Parkinsonism
4. Clinical Diagnosis
5. Ethiology
6. Pathophysiology
Parkinson Disease

• The most common form of parkinsonism is idiopathic PD, first

described by james parkinson in 1817 as paralysis agitans, or the
“shaking palsy.”
• The pathological hallmark of pd is the loss of the pigmented,
dopaminergic neurons of the substantia nigra pars compacta, with
the appearance of intracellular inclusions known as lewy bodies.
• Progressive loss of dopamine containing neurons is a feature of
normal aging; however, most people do not lose the 70-80% of
dopaminergic neurons required to cause symptomatic pd.
Common Form
Of
Parkinsonism
Clinical Overview

Muscular
Bradykinesia
Rigidity

Postural
Resting Tremor
Instability
Symptoms
Motor Symptoms Motor Symptoms
• Hypokinetic Movements • Flexed Posture / Menekuk
• Decreased Manual Dexterity • “Freezing” At Initiation Of Movement
(ketangkasan ↓) • Hypomimia (Reduced Facial
• Difficulty Arising From A Seated Position Animation)
• Diminished Arm Swing During • Hypophonia (Reduced Voice Volume)
Ambulation
• Micrographia
• Dysarthria (Slurred Speech / cadel)
• Dysphagia (Difficulty With Swallowing)
• Festinating Gait (Tendency To Pass From
A Walking To A Running Pace)
Micrographia
Symptoms
Autonomic and Sensory Symptoms Mental Status Changes
• Bladder Dysfunction
• The patient experiences anxiety, apathy
• Constipation (kurang emosi), bradyphrenia (slowness
• Diaphoresis/ keringat dingin of thought processes), cognitive
• Fatigue impairment, depression, and
• Olfactory Impairment / penciuman terganggu hallucinosis/psychosis.
• Orthostatic Intolerance
• Pain
• Paresthesia / kesemutan
• Paroxysmal Vascular Flushing
• Seborrhea / bersisik
• Sexual Dysfunction
• Sialorrhea (Drooling) / air liur
Symptoms
Sleep Disturbances
• Excessive daytime sleepiness
• Insomnia
•Obstructive sleep apnea / henti
nafas
•Rapid eye movement (REM)
•Sleep behavior disorder.
Laboratory Tests Diagnostic Tests
• No laboratory tests are • Genetic testing is not
available to diagnose PD routinely helpful.
• Neuroimaging may be useful
for excluding other diagnoses.
• Medication history ( drug-
induced Parkinsonism)
Tremor
• Most commonly in the hands, sometimes
with a characteristic pill-rolling motion.
• Less commonly, tremor may involve the
jaw or legs.
• Resting tremor often begins unilaterally
and becomes bilateral with disease
progression.
• Stressful or emotional situations often
increase the tremor amplitude and
severity.
• Usually, tremor is absent during sleep.
Although resting tremor is visibly
Rigidity
• Increased muscular resistance to passive range of motion
• Affects the upper and lower extremities, and occasionally the Neck
• If tremor is present in the affected extremity, the rigidity is associated
with Hypomimia
BRADYKINESIA
• Hypokinesia is decreased movement /
bradykinesia (slowness of movement) /
akinesia (absence of movement).
• Dexterity may impair tasks such as
hand clapping, finger tapping, and
handwriting / micrographia
• Freezing
 Etiology
• The cause of Parkinson’s disease is
unknown for most patients.
• The disease is correlated with
destruction of dopaminergic
neurons in the substantia nigra
with a consequent reduction of
dopamine actions in the corpus
striatum, parts of the basal ganglia
system that are involved in motor
control.
Dopamine Metabolism
• In the Fenton reaction, H2O2 accepts an electron
from ferrous iron (Fe2+) to produce ferric iron
(Fe3+) and the hydroxyl radical (HO*).
• Fe3+ is reduced back to Fe2+ by another molecule
of H2O2, forming a hydroperoxyl radical (HOO*).
• The radicals damage cell membranes and
organelles (eg, mitochondria) and also induce
apoptotic signaling.
• (COMT, catechol-Omethyltransferase; DOPAC, 3,4-
dihydroxyphenylacetic acid; GSH, glutathione;
GSSG, glutathione disulfide; H+, proton; H2O,
water; HVA, homovanillic acid; L-AAD, L-aromatic
amino acid decarboxylase; OH−, the hydroxide ion;
MAO-B, monoamine oxidase B.).
Functional Circuity
Between The
Cortex, Basal
Ganglia And
Thalamus
• Gpe, globus
pallidus externa;
• GPi, globus pallidus
interna;
• SNc, substantia
nigra pars
compacta;
• SNr, substantia
nigra pars reticulata;
• STN, subthalamic
nucleus.
Pathophysiology
• The dopaminergic deficit in PD
arises from a loss of the neurons in
the substantia nigra pars compacta
that provide innervation to the
striatum (caudate and putamen).
• The current understanding of the
pathophysiology of PD is based on
the finding that the striatal DA
content is reduced in excess of 80%.
This paralleled the loss of neurons
from the substantia nigra,
suggesting that replacement of DA
could restore function
Homeostasis

D1

D2
Parkinson Disease

D1

D2
• Gpe, globus
pallidus externa;
• GPi, globus pallidus
interna;
• SNc, substantia
nigra pars
compacta;
• SNr, substantia
nigra pars reticulata;
• STN, subthalamic
nucleus.
 SARAF Tiroksin

DOPAMINERGIK L-DOPA

Dopamin
Stimulasi

Vesikel

Reseptor
Dopaminergik

EFEK DOPAMINERGIK
AGONIS DOPAMIN Tiroksin

L-DOPA
Obat Agonis Dopamin

Dopamin

Vesikel

Reseptor Reseptor
Dopaminergik Dopaminergik

EFEK DOPAMINERGIK
EFEK DOPAMINERGIK

R-β1
R-D1 R-α1

Stimulasi kardiak Dilatasi renal Vasokonstriksi

R-D2

Inhibitor motilitas pencernaan Efek emetik

 Levodopa
DOPAMIN (L-Dopa) DOPAMIN
DDC DDC

Vesikel

Reseptor Reseptor
Dopaminergik Dopaminergik

Efek Dopaminergik Efek Dopaminergik

Sentral Perifer
 Levodopa
(L-Dopa) DOPAMIN
DDC

Vesikel

Sawar Darah Otak

Reseptor Reseptor
Dopaminergik Dopaminergik

Efek Dopaminergik
Perifer
Postclass Engaged Learning Activity
1. Pada kondisi Parkinson, terjadi penurunan transmisi dopaminergik.
Mengapa hal ini menyebabkan hambatan pada jalur langsung dan terjadi
overaktivasi pada jalur tidak langsung pada ganglia basal?
2. Terjadinya degenerasi pada substansia nigra pars compacta pada
Parkinson, akan mengakibatkan overaktivasi pada jalur tak lansung dan
meningkatnya transmisi glutaminergik di nucleus subthalamus. Jelaskan
hubungan antara transmisi glutaminergik dan GABAergik di substansia
nigra pars reticulata dan globus palidus internal sehingga bisa
menghasilkan efek inhibitory pada cortex
3. Apa yang dimaksud dengan Lewy Bodies dan kaitannya dengan
parkinson
4. Berikan prediksi mekanisme dan reseptor sebagai target terapi Parkinson