Parkinson’s Disease

JANE 07120110017

Preceptor : Dr. dr. Yusak Siahaan, SpS, FIPP

BAB IPENDAHULUAN

• Penyakit neurodegenerative yang bersifat

kronis dan progresif yang ditandai dengan

adanya gangguan gerakan motorik maupun

non motorik.

• Berkaitan dengan usia

• Penyakit terbanyak ke 2 setelah Alzheimer

• Mempengaruhi kualitas hidup penderita

(disability) maupun keluarga.

1817

by James Parkinson, a

British physician.

“The Shaking Palsy”

1919

Konstantine Tretiakoff, Russia Neuropatologist

“Kesamaan lesi di substansia nigra.”

1960

Ehringer and Hornykiewicz

”The levels of dopamin severely reduced in the

striatum of PD patients.”

BAB IIPEMBAHASAN

I.DEFINISI

Suatu penyakit neurodegeneratif pada basal ganglia

Nigrostriatal dopaminergic deficiency

II. EPIDEMIOLOGI

• Inggris 20 per 100,000

• US 1 juta kasus, 50,000 kasus baru per tahun

• Onset usia rata-rata = 61 tahun

• Early onset = 40 tahun

• Laki-laki : Perempuan = 3 : 2

• African-Americans & Asians < Caucasians

Insidensi Parkinson’s Disease

Age

Inci

den

ce /

10

0 00

0

PD di Indonesia

• Exact data remain unknown

• IDI, 2003 20 per 100,000 penduduk

• RSCM, 2005 219 kasus per tahun

• Surabaya 10 kasus per tahun

per 100,000 inhabitants

III. FAKTOR RESIKO

• USIA meningkat diatas usia 60 tahun

• Genetik riwayat keluarga (+)

• Jenis kelamin laki-laki

• Environmental toxin exposure metal, herbisida,

pestisida

• Ras : Caucasians

• Riwayat trauma kepala

IV. ETIOLOGI

• No definite single etiology is confirmed for primary PD

• May result a complex interaction of environmental toxic

factors, genetic susceptibility traits & aging

USIA

GENETIK

GEOGRAFIS

LINGKUNGAN-Xenobiotik pestisida, herbisida-Pekerjaan paparan metal -Infeksi virus influeza intrautero-Trauma kepala-Stress dan depresi stres oksidatif

V. KLASIFIKASI

1. Parkinson primer (idiopatik/paralisis agitans)

- Paling sering 7 dari 8 kasus parkinson

- Genetik

- Penyebab belum jelas

2. Parkinson sekunder (simtomatik)

a. Neurodegeneratif disorder

- Disorder asociated with alpha-synuclein

- Disorder asociated with primary amyloid

- Disorder asociated with amyloidopathies

b. Genetik

- Wilson disease, Prion disease, Huntington disease, Fragile X permutation, X linked dystonia

c. Miscellaneous

- Vascular parkinsonism (atherosclerosis, amyloid angiopathy), cerebral palsy, normal pressured hidrosefalus

d. Repeated head trauma

e. Infeksi (CJD, Neurosifilis, Postensephalitis PD)

f. Metabolik (hipoparatiroid)

g. Multiple sclerosis

h. Neoplastik

i. Drugs

j. Toxins (methanol, CO, carbondisulfida)

Degenerasi dopaminergic nigrostriatal pathway

Anatomi Basal Ganglia

DOPAMINE

- Neurotransmitter excitatoric

- Diproduksi di beberapa tempat, termasuk ventral

tegmental area dan substansia nigra(terbanyak)

- Fungsi di otak :

1. Mengatur perilaku dan fungsi kognitif

2. Aktivitas motorik

3. Motivasi dan reward system

4. Prolactine inhibitor

5. Mengatur tidur, mood, perhatian

- Memiliki 5 reseptor : D1, D2, D3, D4, D5

Dopamine Synthesis

• Dopaminergic pathway adalah jalur neuron di otak

yang mentransmisikan neurotransmiter dopamin

dari 1 regio otak ke regio lainnya.

• EMPAT dopaminergic pathways :

1.Mesolimbic pathway

2. Mesocortical pathway

3. Nigrostriatal pathway

4. Tuberoinfundibular pathway

DOPAMINERGIC PATHWAYS

Nigrostriatal Pathway

• Jalur yang memproyeksikan dopamine dari

substansia nigra ke striatum.

• Fungsi : Motor Control

• Degenerasi pathway ini Parkinson’s Disease

Motor / Basal Ganglia Pathway

1. Direct Pathway2. Indirect Pathway

Direct Pathway

Indirect Pathway

Dopaminergic nigrostriatal

pathway

Parkinson’sDIRECTPathway

Parkinson’sINDIRECT Pathway

VI. PATOFISIOLOGI

Etiologi

Degenerasi basal ganglia

Loss 80-90% dopamine production di substansia nigra

Degenerasi dopaminergic nigrostriatal pathway

No transmisi dopamine dari substansia nigra ke striatum

Imbalance NT dopamine dan acethylcoline

Motor DIRECT pathway

Motor INDIRECT pathway

Motor Activity

4 cardinal symptomps Parkinson Disease

Tremor

Rigidity

Akinesia / Bradykinesia

Postural Instability

T

R

A

P

PREMOTOR PHASE

- Gejala awal nonspecific

-Depresi, konstipasi, lelah, penurunan daya penciuman, gangguan tidur,

TREMOR

• Resting tremor paling sering, 70% kasus

• Hanya bergetar ketika sedang beristirahat hilang ketika melakukan

sesuatu dan sewaktu tidur

• Dapat terjadi pada 1/lebih ekstrimitas, biasanya asimetris tangan,

kaki, jari-jari, kelopak mata, bibir, lidah semakin berat jadi bilateral

• ↑↑ ketika cemas, lelah dan kurang tidur

• Characteristic ‘pill-rolling’ movement

(seperti menghitung uang logam)

• Frekuensi 4-5 cycles per second

RIGIDITY

• Kekakuan (kaki, tangan, leher)

> 90% cases

• Cogwheel rigidity fenomena roda gerigi

gerakan terpatah-patah

• Gerakan jadi tidak halus seperti break dance

BRADYKINESIA

• Gerakan menjadi serba lambat.

• Penyebab disability tersering 80 - 90%

• Kesulitan bangun dari posisi duduk/tempat tidur

• Kesulitan melakukan pekerjaan sehari-hari, seperti

mengenakan baju, mengkancingkan baju, mengunyah

makanan, memegang alat makan

• Frekuesi berkedip berkurang

• Refleks menelan berkurang air liur sering keluar

• Micrographia tulisan semakin mengecil dan rapat

• Hypomimia penurunan ekspresi wajah

• Hypophonia suara menjadi monoton kecil halus seperti

bisikan lambat

- Karena bradikinesia dan rigiditas otot pernafasan, pita suara, otot laring

• Dysarthria unclear pronunciation

Today is sunny day in Toronto

Postural Instability

• Indikasi progresifitas penyakit menjadi advance stage.

• Kombinasi efek of rigidity & bradykinesia

• Due to loss of postural reflexes positional adjustments

difficulties

• Examination ‘The Pull Test’

Parkinsonian Gait

• PD penyakit ke 2 tersering selain stroke yang menyebabkan

gangguan gait.

• Langkah menjadi lebih kecil-kecil, menggeser dan cepat

marche a petit pas

stadium lanjut : kepala difleksikan ke dada, bahu membungkuk ke

depan, punggung melengkung bila berjalan

• Penurunan ayunan tangan karena kaku penurunan joint motion

• Kesulitan memulai berjalan

• Kesulitan untuk memutar balik ketika berjalan (memerlukan lebih

dari 3 langkah)

• Stooped Posture stand in general flexion (trunk is

flexed forward)

10 m walk test

• The patient asked to perform straight line walking

• Measurement of gait speed, step length, and step frequency

• Self-initiated gait can improved with external cues, attention an sensory stimulation, as well as levodopa treatment

Time UP and GO• The patient asked to

stand up and walk forward for 3 meters, turn around and return back to his / her chair

• Evaluate: turning, gait initiation and termination

Test gait :

Freezing

• Motor block penyebab utama jatuh

• Tiba- tiba berhenti ditempat saat mau mulai

melangkah / sedang berjalan / berputar balik

ragu-ragu untuk memulai langkah

Gejala nonmotor PDNeuropsychiatric dysfunction Mood disorders : depresi

Apathy, anhedonia, gangguan tidur

Frontal executive dysfunction

Dementia and psychosis

Sleep disorders Sleep fragmentation and insomnia

REM sleep behavior disorders (RBD)

Periodic limb movements in sleep (PLMS) / Restless

legs syndrome (RLS)

Excessive daytime somnolence

Autonomic dysfunction Orthostatic hypotension

Urogenital dysfunction

constipasion

Sensory symptom and pain Olfactory dysfunction, visual dysfunction

Abnormal sensations

Pain

VIII. DIAGNOSIS (Hughes)

• POSSIBLE ONE of the following is present : tremor (either

resting or postural), rigidity, or bradykinesia

• PROBABLE TWO of the major features (TRAP) are present;

or if resting tremor, rigidity or bradykinesia are asymmetric

• DEFINITE THREE of the major features are present; or if

two of the features are present with one of them presenting

asymmetrically

NINDS Diagnosis Criteria for PD(National Institute of Neurological Disorders & Stroke)

• Group A features (characteristic of PD)

– Resting tremor

– Bradykinesia

– Rigidity

– Asymmetric onset

• Group B features (suggestive or alternative diagnosis)

– Features usual early in clinical course

– Prominent postural instability in first 3 years after symptom onset

– Freezing phenomenon in first 3 years

– Hallucinations unrelated to medications in the first 3 years

– Dementia preceding motor symptom or in first year

– Supranuclear gaze palsy (other than restriction of upward gaze) or slowing vertical saccades

– Severe, symptomatic dysautonomia unrelated to medications

– Documentation of condition know to produce parkinson’s and plausibly connected to the patients symptom s

(such as suitably located focal brain lesion or neuroleptic use within the past 6 month

• Criteria for definite PD

– All criteria for probable PD are met; and

– Histopathological confirmation of diagnosis is obtained at autopsy

• Criteria for probable PD

– At least three of the four features in group A are present; and

– None of the features in group B is present (note: symptom duration ≥ 3 years is

necessary to meet this requirement); and

– Substansial and sustained response to levodopa or dopamine agonist has been

documented

• Criteria for possible PD

– At least two of the four features in group A are present, and least one of these is

tremor or bradykinesia; and

– Either none of the features in group B is present or symptom have been present

≤ 3 years and none of the features in group B is present; and

– Either substansial and sustained respond to levodopa or a dopamine agonist has

been documentented or the patient has not had an adequat trial of levodopa or

dopamin agonist

Hoehn and Yahr Staging of Severity of Parkinson’s Disease

Stage Description

0 No clinical signs evident

I Unilateral involvement

II Bilateral involvement but no postural abnormalities

III Bilateral involvement with mild postural imbalance on examination or history of poor balance or falls; patient leads independent life

IV Bilateral involvement with postural instability; patient requires substantial help

V Severe, fully developed disease; patient restricted to bed or wheelchair

Neuropathology of PD

• The loss of pigmented dopaminergic neurons in substansia

nigra pars compacta (SNpc)

• Ditemukan Lewy Bodies

Normal Brain PD Patient’s Brain

Lewy Bodies

IX. TATALAKSANA

• Non-pharmacologic therapy

• Pharmacologic therapy

• Surgical therapy

Non-Pharmacologic

• Exercise & physical therapy

• Speech therapy

• Nutrition eat high in fiber, drink plenty of fluids

• Education

• Support

Exercise & Physical Therapy

Walking & Turning

Back Stretch Seated March

Getting Up & Sitting Down

Body Twist

Getting Out of Bed

Pharmacologic Treatment

Surgical Therapy- Deep Brain Stimulation

• Bila gejala tidak

terkontrol dengan

farmakologi.

• Transplantation of fetal

nigral cells

• Thalamotomy

X. PROGNOSIS

Ad vitam : dubia ad malamAd Functionam : dubia ad malamAd Sanationam : dubia ad malam

• Kebanyakan pasien meninggal karena komplikasi sekunder seperti : pneumonia, tersedak, dan terjatuh

BAB IIIKESIMPULAN

Parkinson adalah penyakit neurodegeneratif yang bersifat kronis progresif, akibat degenerasi basal ganglia. Degenerasi basal ganglia ini mengakibatkan terjadinya penurunan kadar dopamin, sehingga terjadi ketidakseimbangan antara dopamin (NT excitatoric) dan acethylcoline (NT inhibitoric). Hal ini menyebabkan kelainan pada direct dan indirect pathway basal ganglia, sehingga terjadi penurunan motoric activity.

Gejala khas dari PD adalah resting tremor, rigidity, bradikinesia, dan postural instability. Selain gangguan motorik, ada pula gangguan non motorik seperti depresi, konstipasi, gangguan tidur, gangguan penciuman, dan lain-lain. Penyakit ini dapat didiagnosis menggunakan kriteria hughes atau NINDS, untuk mengetahui derajat keparahan parkinson dapat menggunakan kriteria Hoehn dan Yahr.

Tatalaksana parkinson yaitu dengan farmakologi, non farmakologi dan surgical. Prognosis dari penyakit ini adalah dubia ad malam.

FEATURE PARKINSON DISEASE ESSENTIAL TREMORAge of onset 55-75 10 - 80

Family history + / - ++

Frequency 4 – 6 Hz 5 - 10

Tremor characteristic Supinasi - pronasi Flexion - extention

Influence factorRestActionMental concentrationWritingWalkingAlcohol

IncreaseDecreaseDecreaseDecrease (micrographia)Increase-

DecreaseIncreaseIncreaseIncrease (tremulous)DecreaseDecrease

Postural tremor Re-emergent Without latency

Distribution other than limb Face, jaw, hips, chin Head, voice

Neuroimaging dopaminergic system

Marked dopaminergic deficits Mild

Mid brain sonography Marked hyper-echogenicity Mild

Neuropathology Nigrostriatal degeneration, lewy bodies

Mild cerebellar degeneration

Treatment Anticholinergic, dopaminergic drugs, DBS

Alcohol, beta blockers, primidone, topiramat, bagapentin, botox, DBS

Parkinson Disease vs Parkinsonism