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PENYAKIT PARKINSON

UTOYO SUNARYORSUD Dr.MOHAMAD SALEH

KOTA PROBOLINGGO

PROBOLINGGO , 23 NOVEMBER 2005

OUTLINE NEUROANATOMI. NEUROFISIOLOGI. NEUROPATOFISIOLOGI. NEUROEPIDEMIOLOGI BATASAN. GEJALA KLINIS. NEURORADIOLOGI. NEUROPATOLOGI. NEUROFARMAKOLOGI. UNIFIED PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

OUTLINE NEUROANATOMI. NEUROFISIOLOGI. NEUROPATOFISIOLOGI. NEUROEPIDEMIOLOGI BATASAN. GEJALA KLINIS. NEURORADIOLOGI. NEUROPATOLOGI. NEUROFARMAKOLOGI. UNIFIED PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

MAKRO ANATOMI SUSUNANSARAF 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 PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

GANGLIA BASALISGANGLIA BASALIS

1. Striatum (neostriatum & limbic striatum)Neostriatum : - Putamen &

- Nucleus Caudatus2. Globus Palidus (GP) : Interna & Externa.3. Substansia Nigra (SN) :

- SNc : Pars Compacta- SNr : Pars Reticular

4. Subthalamic Nucleus (STN)

CORTICAL MOTOR AREASCORTICAL MOTOR AREAS

THALAMUS BASALGANGLIA

CEREBELLUM

BRAINSTEM

SPINALCORD

THALAMUS BASALGANGLIA

CEREBELLUM

BRAINSTEM

SPINALCORD

Ganglia Basalis dalamMenciptakan Gerakan :Ganglia Basalis dalamMenciptakan Gerakan :

Stimulasi Korteks Motorik.

Melalui pintu masuk putamen

(di Striatum)

Keluar melalui Globus Palidus

internus

Menciptakan jalur direk dan indirek.

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 PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

PATOFISIOLOGI PENYAKITPARKINSON

““KetidakKetidak seimbanganseimbangan sarafsarafdopaminergikdopaminergik dandan kolinergikkolinergik””

DA AK

NORMAL(AK=DA)

PENYAKIT PARKINSON(AK>DA)

AK = ASETIL KOLINDA = DOPAMIN

B R A I NB R A I NGanglia basalis

Acetylcholin Normal

Dopamin

Acetylcholin PD

Perokside Radical HTissueTissue

damagedamage

Anticholinergic

(Trihexylphenidyl)

MAO MAO I ( selegiline )

D2

Dopamin

Receptor

DopaminDopamin AgonistAgonist

Ergot(bromocryptin)

Non ErgotNon Ergot((pramipexolepramipexole))

Levodopa

Levodopa

Dopamin

Decarboxylase

Decarboxylase Inhibitor(Benzeraside)(carbidopa)

3 OMD

COMTCOMT Inhibitor

(entacapone)

BLOOD BRAIN BARIER

PERIFER

Decarboxylase

OUTLINE NEUROANATOMI. NEUROFISIOLOGI. NEUROPATOFISIOLOGI. NEUROEPIDEMIOLOGI BATASAN. GEJALA KLINIS. NEURORADIOLOGI. NEUROPATOLOGI. NEUROFARMAKOLOGI. UNIFIED PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

EPIDEMIOLOGI

Prevalensi dari Penyakit Parkinson belumdiketahui secara pasti diperkirakan 1 %dari jumlah penduduk antara usia 50 ths/d 70 th dari pria atau wanita dengan rasKaukasian lebih banyak dibanding AfroAmerika .

Poli saraf RS Dr Soetomo Sby : sekitar 190pasien parkinson per tahun.

OUTLINE NEUROANATOMI. NEUROFISIOLOGI. NEUROPATOFISIOLOGI. NEUROEPIDEMIOLOGI BATASAN. GEJALA KLINIS. NEURORADIOLOGI. NEUROPATOLOGI. NEUROFARMAKOLOGI. UNIFIED PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

Parkinson’s Disease

Definisi by James Parkinson 1817 :

PenyakitParkinson

Parkinsonisme

TRAP

1919

What is Parkinson’s Disease?

Clinical syndrome manifestingcharacteristically with parkinsonism(bradikinesia, hipo/akinesia. rigidity,tremors, and postural instability),caused by significant dopaminergicstriatal denervation. (Wolters, 2007)

PARKINSONISM

SINDROMA :Tremor, Rigidity, Akinesia, Posturalinstability (TRAP)

MACAM-MACAM PENYEBAB

PENYAKIT PARKINSONPENYAKIT PARKINSONvsvs PARKINSONISMPARKINSONISM

Etiologi : IdiopatikDegenerasi neuron di substansia nigra &

ada lewy bodies80% Parkinsonism Onset :

>50 TAHUN PUNCAK 70 an TAHUN

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

terapi

PENYAKIT PARKINSONPENYAKIT PARKINSON

KLASIFIKASI PARKINSONISM Parkinsonism Idiopatik / Primer

= Penyakit Parkinson= Parkinsonism Simptomatik / Sekunder

Drugs Induced, Infectious, Head Trauma,Tumor/paraneoplastik, Vascular, Toxins,Metabolic, Hidrocephalus,Anoxic encephalopathy

Parkinsonism PlusDementia syndroma (Alzheimer’s Disease) ,Multiple System Atrophy, Normal PressureHydrocephalus, Progressive supranuclear palsy,Corticobasal ganglionic degeneration, Hereditarydisorders.

Parkinson’s Disease

ETIOLOGY:

Etiology dari Penyakit Parkinson belumdiketahui secara pasti , namun ada beberapafaktor yang dapat meningkatkan Resikodari Penyakit Parkinson :

Parkinson’s DiseaseFaktor yang dapat menyebabkanmeningkatnya 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 PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

TREMOR

RIGIDITY

AKINESIA

POSTURAL INSTABILITY

GEJALA UTAMA (TRAP)GEJALA UTAMA (TRAP)

PENYAKIT PARKINSONPENYAKIT PARKINSON

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

Dua dari 3 gejala kardinal (TRA)

Tiga dari 4 gejala utama (TRAP)

Responsif terhadap L-dopa

KRITERIA KLINISKRITERIA KLINIS

KRITERIA HUGHES

POSSIBLETdpt salah satu gejala utama:Tremor istirahat.RigiditasBradikinesia.Kegagalan reflesk postural

KRITERIA HUGHES

PROBABLEBila terdapat kombinasi dua gejala utama

( termasuk kegagalan refleks postural) DEFINITEBila terdapat kombinasi tiga dari empat

gejala.

1. Preclinical stage – at this PD-spesificpathology is present with no clinicalsigns at all and potential imaging andbiomarker abnormalities may be ableto detect these changes

2. Pre-motor – extranigral pathologycausing symptoms

3. Motor PD – classical nigral pathology

TIGA FASE PARKINSONDISEASE

AAN 2012

3535

GNM/Pre-motorPenyakit Parkinson (PP)

Yang disepakati sebagai gejala dini PPberdasar HistoPA dari Braak dkk:

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

3636

GNM lainnya

Gejala Non-Motor sebelum dan sesudahdx. PP ditegakkan, sbb.:Neuropsikiatri:

* gg. kognisi dan demensia* apatis, ansietas, panik* ilusi, delusi, halusinasi, dilirium* ICDs (impulse control disorders)* depresi.

3737

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* konstipasi * drooling saliva

Progresifitas ParkinsonDisease

AAN 2012

PERJALANAN PENYAKIT( Hoehn and Yahr )

Stadium 1: gejala dan tanda pada satusisi, terdapat gejala yg ringan, terdptgejala mengganggu ttp tdkmenimbulkan kecacatan, biasanyatremor pd satu anggota gerak, gejalayg timbul dapat dikenali orang terdekat.

Stadium 2 : terdapat gejala bilateral,terdapat kecacatan minimal, sikap/caraberjalan terganggu.

Stadium 3 : gerak tubuh nyatamelambat, keseimbangan mulaiterganggu saat berjalan/berdiri,disfungsi umum sedang.

Stadium 4 : terdapat gejala yang lebihberat, masih dpt berjalan hanya utkjarak tertentu, rigiditas danbradikinesia, tdk mampu berdiri sendiri,tremor dpt berkurang dibandingstadium sebelumnya.

Stadium 5 : stadium kakhetik ( cacheticstage ) , kecacatan total, tidak mampuberdiri dan berjalan, memerlukanperawatan tetap.

OUTLINE NEUROANATOMI. NEUROFISIOLOGI. NEUROPATOFISIOLOGI. NEUROEPIDEMIOLOGI BATASAN. GEJALA KLINIS. NEURORADIOLOGI. NEUROPATOLOGI. NEUROFARMAKOLOGI. UNIFIED PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

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

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

OUTLINE NEUROANATOMI. NEUROFISIOLOGI. NEUROPATOFISIOLOGI. NEUROEPIDEMIOLOGI BATASAN. GEJALA KLINIS. NEURORADIOLOGI. NEUROPATOLOGI. NEUROFARMAKOLOGI. UNIFIED PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

NEUROPATOLOGI

DEGENERASI NEURON SUBSTANSIANIGRA.

o TERDAPAT LEWI BODY.

OUTLINE NEUROANATOMI. NEUROFISIOLOGI. NEUROPATOFISIOLOGI. NEUROEPIDEMIOLOGI BATASAN. GEJALA KLINIS. NEURORADIOLOGI. NEUROPATOLOGI. NEUROFARMAKOLOGI. UNIFIED PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

PENGOBATANFARMAKOLOGIS 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.

PENGOBATANFARMAKOLOGIS DIBAGI: (2)

1.3 Faktor tropik.GDNF.GMI ganglioside.

1.4 Immunomodulator.NSAID.Immunophyllins.

1.5 Cyclosporine A, calpain inhibitor, caspase inhibitor.

PENGOBATANFARMAKOLOGIS DIBAGI: (3)

DOPAMINERGIK.2.1 Prekursor dopamin.

Levodopa.Levodopa CRLevodopa cair.Obat obat menaikkan kadar levodopa.

o Levodopa + decarboxylase inhibitor.o Levodopa + COMT inhibitor.o Levodopa + selegilene.

PENGOBATANFARMAKOLOGIS DIBAGI: (4)

2.2 Agonis dopamin.Derivat ergot: bromocriptin, pergolide, lisuride,cabergoline.Derivat non ergot: PRAMIPEXOLE, ropinirole,talipexole, apomorfin, selegiline.

PENGOBATANFARMAKOLOGIS DIBAGI: (5)

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

ALGORITMAPENATALAKSANAAN

PENYAKIT PARKINSON

Konsensus POKDIGangguan GerakPERDOSSI 2003

OUTLINE NEUROANATOMI. NEUROFISIOLOGI. NEUROPATOFISIOLOGI. NEUROEPIDEMIOLOGI BATASAN. GEJALA KLINIS. NEURORADIOLOGI. NEUROPATOLOGI. NEUROFARMAKOLOGI. UNIFIED PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

UNIFIED PARKINSON’S DISABILITYRATING 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 PARKINSON’S DISABILITYRATING SCALE ( UPDRS ) con’t

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 PARKINSON’S DISABILITYRATING SCALE ( UPDRS )

TESTING FUNCTIONAL PERFORMANCEIN PEOPLE WITH PARKINSONDISEASE

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 PARKINSON’S DISABILITY RATING SCALE

( UPDRS ) LIVING WITH PARKINSON’S DISEASE

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