PENYAKIT PARKINSON

UTOYO SUNARYO
RSUD Dr.MOHAMAD SALEH
KOTA PROBOLINGGO

PROBOLINGGO , 23 NOVEMBER 2005

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

MAKRO ANATOMI SUSUNAN

SARAF PUSAT

OTAK.
OTAK BESAR ( SEREBRUM).
OTAK KECIL ( SEREBELUM).
DIENSEFALON.

THALAMUS.

HIPOTHALAMUS
BATANG OTAK ( TRUNKUS SEREBRI).
- MESENSEFALON.
- PONS.
- MEDULA OBLONGATA.

MEDULA SPINALIS

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

GANGLIA BASALIS
1. Striatum (neostriatum & limbic striatum)
Neostriatum : - Putamen &
- Nucleus Caudatus
2. Globus Palidus (GP) : Interna & Externa.
3. Substansia Nigra (SN) :
- SNc : Pars Compacta
- SNr : Pars Reticular
4. Subthalamic Nucleus (STN)

CORTICAL MOTOR AREAS

THALAMUS

BASAL
GANGLIA
CEREBELLUM

BRAINSTEM

SPINAL
CORD

Ganglia Basalis dalam

Menciptakan Gerakan :
Stimulasi Korteks Motorik.
Melalui pintu masuk putamen

(di Striatum)
Keluar melalui Globus Palidus

internus
Menciptakan jalur direk dan indirek.

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

PATOFISIOLOGI PENYAKIT
PARKINSON
Ketidak seimbangan saraf
dopaminergik dan kolinergik
DA

AK AK = ASETIL KOLIN
DA = DOPAMIN

NORMAL
(AK=DA)

PENYAKIT PARKINSON
(AK>DA)

BRAIN
Ganglia basalis
Dopamin

Acetylcholin
MAO

Normal

MAO I ( selegiline )

Anticholinergic
Receptor

D2

Perokside

Dopamin

Radical H

Tissue
damage

Decarboxylase

Acetylcholin

Levodopa

(Trihexylphenidyl)

PD

BLOOD BRAIN BARIER

Levodopa

3 OMD
COMT Inhibitor
COMT

Dopamin Agonist

Decarboxylase

Ergot
(bromocryptin)

Non Ergot
(pramipexole )

Decarboxylase Inhibitor
(Benzeraside)
(carbidopa)
PERIFER

Dopamin

(entacapone)

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

EPIDEMIOLOGI
Prevalensi dari Penyakit Parkinson belum
diketahui secara pasti diperkirakan 1 %
dari jumlah penduduk antara usia 50 th
s/d 70 th dari pria atau wanita dengan ras
Kaukasian lebih banyak dibanding Afro
Amerika .
Poli saraf RS Dr Soetomo Sby : sekitar 190
pasien parkinson per tahun.

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

Parkinsons Disease
Definisi by James Parkinson 1817 :

Penyakit
Parkinson

T
R
A
P

Parkinsonisme

What is Parkinsons Disease?

Clinical
syndrome
manifesting
characteristically with parkinsonism
(bradikinesia, hipo/akinesia. rigidity,
tremors, and postural instability),
caused by significant dopaminergic
striatal denervation. (Wolters, 2007)
19

PENYAKIT PARKINSON
vs PARKINSONISM
PARKINSONISM
SINDROMA :
Tremor, Rigidity, Akinesia, Postural
instability (TRAP)

MACAM-MACAM PENYEBAB

PENYAKIT PARKINSON
Etiologi : Idiopatik
Degenerasi neuron di substansia nigra &
ada lewy bodies
80% Parkinsonism
Onset :

>50 TAHUN
PUNCAK 70 an TAHUN

PRIA : WANITA = 3 :2
Rata-rata 9 tahun meninggal tanpa
terapi

KLASIFIKASI PARKINSONISM

Parkinsonism Idiopatik / Primer

= Penyakit Parkinson=
Parkinsonism Simptomatik / Sekunder
Drugs Induced, Infectious, Head Trauma,
Tumor/paraneoplastik, Vascular, Toxins,
Metabolic, Hidrocephalus,Anoxic encephalopathy
Parkinsonism Plus
Dementia syndroma (Alzheimers Disease) ,
Multiple System Atrophy, Normal Pressure
Hydrocephalus, Progressive supranuclear palsy,
Corticobasal ganglionic degeneration, Hereditary
disorders.

Parkinsons Disease
ETIOLOGY:

Etiology dari Penyakit Parkinson belum

diketahui secara pasti , namun ada beberapa
faktor yang dapat meningkatkan Resiko
dari Penyakit Parkinson :

Parkinsons Disease
Faktor yang dapat menyebabkan
meningkatnya Resiko Penyakit Parkinson :
Aging , Gender ( Men) , and Ras ( White )
Riwayat Keluarga :
Trauma
Stress Emosional
Personality ( Shyness and Depressiveness)
Environmental Exposures
Metals ( Manganese , Iron )
Drinking unwell water
Farming
Herbicide and Pepticide exposure
MPTP ( methyl phenyl tetrahydropiridine)

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

PENYAKIT PARKINSON
GEJALA UTAMA (TRAP)

TREMOR

RIGIDITY

AKINESIA

POSTURAL INSTABILITY

Tremor

Resting tremor, postural tremor

Kasar, 3-7 getaran / detik
Tangan, kaki, badan, bibir

Rigidity

Cogwheel phenomenon

Leher, Lengan, Tungkai, Badan

Akinesia

Lama tidak bergerak atau lambat

(Bradikinesia)

Muka topeng, kurang berkedip

Postural Instability

Mudah terjatuh, propulsi

Pada stadium lanjut

Diagnosis
KRITERIA KLINIS

Dua dari 3 gejala kardinal (TRA)

Tiga dari 4 gejala utama (TRAP)

Responsif terhadap L-dopa

KRITERIA HUGHES
POSSIBLE
Tdpt salah satu gejala utama:
Tremor istirahat.
Rigiditas
Bradikinesia.
Kegagalan reflesk postural

KRITERIA HUGHES
PROBABLE
Bila terdapat kombinasi dua gejala utama
( termasuk kegagalan refleks postural)
DEFINITE
Bila terdapat kombinasi tiga dari empat
gejala.

TIGA FASE PARKINSON

DISEASE
1.

2.

3.

Preclinical stage at this PD-spesific

pathology is present with no clinical
signs at all and potential imaging and
biomarker abnormalities may be able
to detect these changes
Pre-motor extranigral pathology
causing symptoms
Motor PD classical nigral pathology
AAN 2012

GNM/Pre-motor
Penyakit Parkinson (PP)
Yang disepakati sebagai gejala dini PP
berdasar HistoPA dari Braak dkk:

Tolosa, E, et al. Neurology 2009 ( Suppl 2 ): S12-S20.

35

GNM lainnya
Gejala Non-Motor sebelum dan sesudah
dx. PP ditegakkan, sbb.:
Neuropsikiatri:
* gg. kognisi dan demensia
* apatis, ansietas, panik
* ilusi, delusi, halusinasi, dilirium
* ICDs (impulse control disorders)
* depresi.
36

GNM lainnya
Gangguan tidur:
* RBD (REM behavior disorders)
* EDS (excessive daytime sleepiness)
* RLS (restless legs syndrome)
* PLMS (periodic limb movement in sleep)
Gangguan sistem saraf otonom:
* hipotensi ortostatik
* OAB (overactive bladder)
* disfungsi ereksi
* hiperseks
37
* konstipasi
* drooling saliva

Progresifitas Parkinson
Disease

AAN 2012

PERJALANAN PENYAKIT
( Hoehn and Yahr )

Stadium 1: gejala dan tanda pada satu

sisi, terdapat gejala yg ringan, terdpt
gejala mengganggu ttp tdk
menimbulkan kecacatan, biasanya
tremor pd satu anggota gerak, gejala
yg timbul dapat dikenali orang terdekat.

Stadium 2 : terdapat gejala bilateral,

terdapat kecacatan minimal, sikap/cara
berjalan terganggu.
Stadium 3 : gerak tubuh nyata
melambat, keseimbangan mulai
terganggu saat berjalan/berdiri,
disfungsi umum sedang.

Stadium 4 : terdapat gejala yang lebih

berat, masih dpt berjalan hanya utk
jarak tertentu, rigiditas dan
bradikinesia, tdk mampu berdiri sendiri,
tremor dpt berkurang dibanding
stadium sebelumnya.

Stadium 5 : stadium kakhetik ( cachetic

stage ) , kecacatan total, tidak mampu
berdiri dan berjalan, memerlukan
perawatan tetap.

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

Brook D.J: Neuroimaging in Parkinsons Disease,Neuro RX 1: 243-254,2004

Marek K et al: ( 123 I )B CIT Spect Imaging Assesment of the rate of Parkinson Disease
Progression, Neurology 2001, 57:2089 -2054

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

NEUROPATOLOGI
DEGENERASI NEURON SUBSTANSIA
NIGRA.
o TERDAPAT LEWI BODY.

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

PENGOBATAN
FARMAKOLOGIS DIBAGI: (1)
NEUROPROTEKTIF.
1.1 MAOIs (Monoamin oxidase inhibitory )

Selegine.
Rasagiline.
Lazabernide.

1.2 Obat antiexcitatory.

NMDA Antagonis: remacemide,amantadine,riluzole .
Coenzyme Q10 dan nicotinamide.

PENGOBATAN
FARMAKOLOGIS DIBAGI : (2)
1.3 Faktor tropik.
GDNF.
GMI ganglioside.

1.4 Immunomodulator.
NSAID.
Immunophyllins.

1.5

Cyclosporine A, calpain inhibitor, caspase inhibitor.

PENGOBATAN
FARMAKOLOGIS DIBAGI : (3)
DOPAMINERGIK.
2.1 Prekursor dopamin.

o
o
o

Levodopa.
Levodopa CR
Levodopa cair.
Obat obat menaikkan kadar levodopa.
Levodopa + decarboxylase inhibitor.
Levodopa + COMT inhibitor.
Levodopa + selegilene.

PENGOBATAN
FARMAKOLOGIS DIBAGI: (4)
2.2 Agonis dopamin.
Derivat ergot: bromocriptin, pergolide, lisuride,
cabergoline.
Derivat non ergot: PRAMIPEXOLE, ropinirole,
talipexole, apomorfin, selegiline.

PENGOBATAN
FARMAKOLOGIS DIBAGI: (5)

NON DOPAMINERGIK.
ANTIKOLINERGIK: Trihexyfenidyl, benstropin.
GLUTAMAT ANTAGONIS: Amantadine, memantine.
ADENOSINE A2A ANTAGONIS.
GM 1 GANGLIOSIDE.

ALGORITMA
PENATALAKSANAAN
PENYAKIT PARKINSON

Konsensus POKDI
Gangguan Gerak
PERDOSSI 2003

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

UNIFIED PARKINSONS DISABILITY

RATING SCALE ( UPDRS )

Mentation, Behaviour and Mood.

Intelectual impairment.
Thought disorder.
Depresion.
Motivation initiative.

Activities of Daily Living.

Speech.
Salivation.
Swallowing.
Handwriting.
Cutting food-handling utensils.
Dressing.
Hygiene.
Turning in Beds-Adjusting Bed Clothes.
Falling-unrelated to freezing.
Walking.
Tremor.
Sensory Complaints related to Parkinsonism

UNIFIED PARKINSONS DISABILITY

RATING SCALE ( UPDRS ) cont

Motor Examination.
Speech.
Facial Expression.
Tremor at Rest.
Action or Postural Tremor.
Rigidity.
Finger Tab.
Hand Movement.
Rapid Alternating Movement.
Leg Agility.
Arising from Chair.
Posture.
Gait.
Postural Stability.
Body Bradykinesia.

UNIFIED PARKINSONS DISABILITY

RATING SCALE ( UPDRS )

TESTING FUNCTIONAL PERFORMANCE

IN PEOPLE WITH PARKINSON
DISEASE
Definitif skor setiap item : 0 - 5
Total skor
: 0 - 199
Skor
199 : Parkinson Berat.

OUTLINE

NEUROANATOMI.
NEUROFISIOLOGI.
NEUROPATOFISIOLOGI.
NEUROEPIDEMIOLOGI
BATASAN.
GEJALA KLINIS.
NEURORADIOLOGI.
NEUROPATOLOGI.
NEUROFARMAKOLOGI.
UNIFIED PARKINSONS DISABILITY RATING SCALE
( UPDRS )
LIVING WITH PARKINSON S DISEASE

UTOYO SUNARYO, NEUROLOGIST OF MOHAMAD SALEH MD HOSPITAL , PROBOL INGGO