TUTOR’S GUIDE

CASE 4

PARKINSON

27 & 31 Oktober 2014

Faculty of Medicine
Universitas Padjadjaran Bandung
2014-2015

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 PARKINSON
Title of Case : Case of Mr. Perry Martin
Block Title : Neurobehavioral and Sense System
Week Schedule : 2 Meetings
Week Theme : Basal Ganglia and extrapyramidal system
Trigger Case : Parkinson

GLO : At the end of the course the student will be able to describe:
- Anatomy, physiology and neurotransmitter related to movement regulation
(basall ganglia and extrapyramidal system)
- Definition of Parkinsonism and Parkinson Disease (PD)
- Classification and etiology of Parkinsonism
- Pathology and etio-pathogenesis of PD
- Pathophysiology of PD
- Clinical feature and staging of PD
- Diagnosis and differential diagnosis of PD
- Management of PD
- Course and prognosis of PD
- Medico-legal aspect of PD

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PAGE I

You are medical student attending examination of a patient, Mr. Perry Martin at
outpatient clinic of Hasan Sadikin Hospital.
Mr. Perry Martin, 61 years old, came to the outpatient clinic of Hasan Sadikin Hospital,
accompanied by his nephew. He stated that his uncle has had difficulty bringing a glass
of water due to tremor and also initiating movement, he moves slowly. Frequently he
complained that his extremities were rigid, he walked with small steps and stood
posture. These symptoms have been appeared since 1 year ago and deteriorated
slowly.

Question:
 What are Mr. Perry Martin’s problems?
 Generate hypothesis and state the rationale for each
 What are further information do you need to improve or disprove your hypothesis?

Tutor Guide Page 1

Identify Mr. Perry’s problems:

 difficulty bringing a glass of water due to tremor
 difficulty initiating movement
 moves slowly
 extremities were rigid
 walked with small steps and stood posture
 symptoms have been appeared since 1 year ago (at age 60 years old) and
deteriorated slowly.

List of hypothesis:
1. Movement disorder: Tremor, moves slowly (brady-kynesia), rigidity, walked with small
steps and stood posture.
2. Disturbance of basal ganglia/ cerebellum/ extra pyramidal system

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Guiding question for Tutor:
1. What disorders associated with those signs and symptoms?
Disorders associated with those signs and symptoms are:
- Parkinsonism/ Parkinson disease
Parkinsonism
2. What are the definitions of Parkinsonism and Parkinson Disease (PD)?
- Definition:
Parkinsonism:
Parkinson Disease:
3. Describe the anatomy, physiology and neurochemistry/ neurotransmitter related to PD
(basal ganglia and extrapyramidal system)! What types of dopamin receptor do you
know?

PAGE II
Past History
 Mr. Perry has 4 siblings, 2 brothers and 2 sisters, and he is the youngest. One of his
sister suffered from resting tremor and rigidity on her extremities since she was 60
years old.
 He had no history of taking medication, head trauma, CNS infection, intracranial
tumor and intoxication. He also had no hypertension, diabetes, cardiac disease or
stroke.

Question:
 Identify Mr. Perry’s new problems
 How do these information change or confirm your hypothesis?
 What further information do you need to improve or disprove your hypothesis?

Tutor Guide Page 2

Identify Mr. Perry’s new problems
 One of his sister suffered from resting tremor and rigidity on her extremities since
she was 60 years old.
 He had no history of taking medication, head trauma, CNS infection, intracranial
tumor and intoxication (Etiologies of Secondary Parkinsonism).

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 He had no hypertension, di abetes, cardiac disease or stroke (Etiologies of
Secondary Parkinsonism).

Guiding question for Tutor

1. What are the classification and etiology of Parkinsonism?
2. How are the pathology and etiopathogenesis of PD?
3. What are the clinical features and staging of PD?
4. How are the pathomechanism/ pathophysiology of PD?
5. How do you diagnose PD? Can you describe the diagnostic criteria for PD?
6. What are differential diagnosis of PD ?

PAGE III
Physical Examination
- He looked composmentis, normal weight
- Blood pressure: 120/80 mmHg; Pulse rate = heart rate: 80 x / min, reguler, equal;
Respiration: 20 x / min
- Neurological examination:
- No abnormality of meningeal sign
- Cranial nerve: within normal limits
- Motor function: bilateral resting tremor especially right side, bradykinesia,
cogwheel sign +/+, mask face.
- Sensory function: within normal limits
- Autonom: within normal limits
- Deep tendon reflexes: within normal limits
- Pathological reflex: negative
- Postural reflexes: Pull test within normal limit

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Laboratory examination:
 Blood test: normal
 Urine test: normal
 Neuroimaging: Head CT Scan within normal limit

Question:
1. Identify Mr. Perry’s new problems
2. How do these information change or confirm your hypothesis?
3. How do you manage this patient?

Tutor Guide Page 3

Identify Mr. Perry’s new problems:
 Neurological examination:
- Cranial nerve: within normal limits
- Motor: bilateral resting tremor especially right side, bradykinesia, cogwheel
sign +/+ (tremor in passive ROM), mask face.
- Postural reflexes: Pull test within normal limit

Guiding question for Tutor:

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 1. Can you explain the management of PD?
2. What are the drugs that commonly used and how are its mechanism of action?
3. What drugs that always combined with levodopa and what is the reason?
4. When is dopaminergic therapy started and why?
5. Can you explain the course and prognosis of PD?
6. Can you explain the medicolegal aspect, BHP, PHOP and CRP of PD?

EPILOG
Because of his condition Mr. Perry Martin was treated with:
 L-Dopa/ Carbidopa 100/25 mg tablet three times daily
 Trihexyphenidil 2 mg tablet, initially ½ tablet two times daily and then the dose was
titrated.
 Physical therapy
Several weeks later, his condition were better and he could perform his activity daily
living almost normally. He has been continuously taking medication and physical
therapy.

PARKINSON’s DISEASE
(Tutor Guide)

Introduction:
Parkinson’s disease is one of the major causes of disability in the field of neurology. Incidence in
the U.S. from 4.5 to 21 / 100,000 population / year and 1% of the population aged> 55 years
suffer from this disease, with a ratio of male to female 3: 2.
It’s slowly progressing disease within 10-20 years, started to occur at the age of 40-50 years. 5%
of patients are young-onset Parkinson's Disease (Juvenile Parkinsonism) with onset age <40
years, in which many genetic factors play a role.
DEFINITION:

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Parkinsonism: is a syndrome consisting of tremor rest, rigidity, bradykinesia, and loss of
postural reflexes. Also called Parkinson's syndrome.
Parkinson's disease: It is a disease that is clinically characterized by tremor rest,
rigidity, bradykinesia, and loss of postural reflexes. Pathologically characterized by
degeneration of neuromelanin pigmented neurons, particularly in the substantia nigra pars
kompakta, who accompanied the eosinophilic cytoplasmic inclusions (Lewy bodies).
Also called: idiopathic or primary Parkinsonism.

KLASIFIKASI Dan ETIOLOGI PARKINSONISM

1. Primer or idiopathic (Idiopathic Parkinsonism)
- Called Parkinson's disease
- The etiology is unknown
- Most (75%) cases of Parkinson's include this group
2. Secondary or acquired (Symptomatic Parkinsonism)
→ Arise after exposure to illness or substance:
- Drug-induced: dopamine antagonists and depletors
Drugs that can cause Parkinsonism: phenothiazines, butirofenon, chlor promazine (CPZ),
prochlorperazine, haloperidol, metoclopramide, alfametildopa, calcium blockers (dialtiazem,
verapamil), captopril, vincristine, valproate, lithium, phenytoin, cytosine arabinose, alcohol
- Hemiatropi: Hemiparkinsonism
- Hidrosepalus: normal pressure hydrocephalus
- Hypoxia
- Infection: postencephalitic
- Metabolic: hipoparatiroid
- Toxins: Mn, CO, MPTP, cyanide
- Trauma: severe head trauma / repetitive
- Tumors
- Vascular: stroke, multiple cerebral infarcts

3. Parkinson Plus Syndrome

→ Symptoms of Parkinson's arise as comorbidity with other neurological disorders, ex:
- Cortical-basal ganglionic degeneration
- Dementia syndromes: Alzheimer's disease, Diffuse Lewy body disease
- Lytico-Bodig (Guamanian parkinsonism-dementia-ALS)
- Multiple system atrophy syndrome: Striatonigral degeneration, Shy-Drager syndrome,
sporadic olivopontocerebellar degeneration, motor neuron disease, parkinsonism

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 - Progressive pallidal atrophy
- Progressive supranuclear palsy

4. Hetedodegenerative disease
- Hallervorden-Spatz disease
- Huntington disease
- Lubag (X-linked dystonia-parkinsonism)
- Mitochondrial cytopathies with striatal necrosis
- Neuroacanthocytosis
- Wilson disease

ETIO-PATOGENESIS PP:
Many hypotheses, there are four processes that stand out:
- Accelerated Aging Theory: The death of dopaminergic neurons more quickly.
- Toxins: selective damaged dopamine neurons due intrinsic and extrinsic toxin (pesticides, heavy
metals, etc.).
- Genetics: Hereditary dominant pattern in some families.
- Peroxidation of free radicals: Widely recognised.
Oxidation of dopamine à Free radical (Fe)
Decreased protection mechanism à cell death

PATHOLOGY:

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Potongan Midbrain Normal (atas), dan Substansia Nigra pucat pada PP (bawah); Sel berpigmen
di substansia nigra normal (atas) dan pucat pada PP (bawah) serta Lewy bodies.

Sel berpigmen di substantia nigra:

Normal Pucat pada PP

Lewy Bodies:

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 H&E stain Imunoperoxidase ubiquitin

PATOFISIOLOGI:
- Defisit primer: Terjadi kehilangan neuron di substransia nigra pars kompakta yang
menghasilkan dopamin ke stritatum (kaudatus dan putamen). Manifestasi klinis terjadi akibat
kehilangan >60% neuron tersebut atau penurunan >80% dopamin di striatum .
- Gejala motorik timbul karena gangguan dalam sirkuit motorik ganglia basalis-talamokortikal.
- Konsep sederhana penyakit Parkinson :
- Traktus nigrostriatum untuk fungsi gerakan halus
- Perlu keseimbangan ko
mponen kolinergik yang berfungsi merangsang (stimulasi) dan komponen dopaminergik yang
berfungsi menghambat (inhibisi).
- Gejala timbul karena disproporsi fungsional kedua komponen di atas:
kolinergik yang meningkat atau dopaminergik yang melemah.

Dua teori kelainan pada ganglia basalis untuk terjadinya Parkinson:

1. Teori ketidakseimbangan saraf dopaminergik dengan saraf kolinergik
- Pengaruh dopaminergik dominan à gejala hiperkinesia

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 - Pengaruh kolinergik dominan à gejala hipokinesia

2. Teori ketidakseimbangan jalur langsung dan jalur tidak langsung

- Hiperaktifitas jalur langsung atau hipoaktifitas jalur tak langsung
à Output dari GPi dan SNr ke talamo korteks ¯¯ à Gerakan hiperkinesia
- Hipoaktifitas jalur langsung dan hiperaktifitas jalur tak langsung
à Output dari Gpi dan SNr à Gerakan hipokinesia

Anatomi Fungsional Ganglia Basal Normal

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Anatomi Fungsional PP

Keterangan:
D1/ D2 : Reseptor dopamin D1/ D2; SNc: Substansia Nigra pars compacta; SNr: Subst. Nigra
pars retikularis; Gpi: Globus Pallidus interna; Gpe: Globus Pallidus eksterna; STN: Nukleus
Sub Thalamicus, Thalamus VA/ VL: Thalamus Ventro Anterior/ Ventro Lateral; SC : Spinal
Cord

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GAMBARAN KLINIS:
 Gejala prodormal
- Tidak khas
- Lelah, letih, gangguan kepribadian sebelum muncul gejala motorik
- Motorik: kelemahan, gangguan kordinasi ringan à “permainan tenis jadi jelek”.
- Sering karena kekakuan salah satu tangan pasien berobat ke Ortopedi
- Gejala parkinsonism ringan seperti tremor intermiten pada 1 atau beberapa jari + rigiditas
asimetris à curigai gejala prodormal Parkinson.
 Gejala utama :
1. Tremor (T)
- Resting tremor – saat emosi bertambah
- Kasar 3-7 x/detik
- Pola : pill rolling
- Berawal dari tangan, dapat meluas ke kaki, bibir, dan seluruh badan.
2. Rigiditas (R)
- Hipertoni pada seluruh gerakan
- Fenomena roda bergigi (cogwheel phenomena)
3. Akinesia/Bradikinesia- Hipokinesia (A)
- Gerakan volunter – lambat dan sulit (t.u gerakan halus) seperti bicara, menulis,
mengancing baju, dll.
- Gerakan asosiatif berkurang – posisi jalan khas
- Gerakan spontan berkurang – wajah topeng
- Manifestasi lain, seperti : Hipomimia, hipofonia, kedipan mata berkurang,
gangguan konvergensi, up-ward gaze, perlambatan mengawali perintah gerak,
amplitudo makin berkurang, sulit bangun dari kursi atau berbalik di tempat tidur,
sulit melakukan dua aktifitas sekaligus
4. Ketidakstabilan Postur dan gait (P)
- Kurangnya keseimbangan atau perasaan unsteadiness pasien saat berdiri atau
berubah posisi badan.
- Sering bersamaan dengan gangguan gait→ Marche a petit pas.
- Sulit diatasi dan ditemukan pada stadium lanjut (stadium III keatas Hoehn &
Yahr).

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 - Awalnya isteri/ suami mengamati pasien kesulitan menjaga keseimbangan saat
memutar badan dengan cepat, terdorong atau tersandung ringan.
- Lanjut: sikap bungkuk, fleksi leher dan trunkal à titik gravitasi ke depan à mudah
jatuh ke depan (propulsi) atau ke belakang (retropulsi)
- Pull test: mundur lebih 2 langkah atau jatuh
Gejala nomor 1, 2, 3 disebut Gejala Kardinal Motorik/ Trias Gejala penyakit
Parkinson.
à Gejala bisa tunggal atau >1, a/simetris, uni/bilateral
 Gejala tambahan
- Kognitif/ neuropsikiatri : ansietas, bradifrenia, demensia, depresi, gangguan tidur
- Saraf kranial/ wajah : gangguan penglihatan, disartri, disfagi, refleks glabela (tanda
Myerson), muka topeng, gangguan penciuman, sialorhea,
- Muskuloskeletal : neuropati kompresi, distonia, deformitas tangan dan kaki, kiposkoliosis,
edema perifer
- Otonom: konstipasi, hipotensi ortostatik, hiperhidrosis, disfungsi seksusal (impotensi,
penurunan libido), gangguan berkemih (frekuency, hesitancy, urgency)
- Sensoris : Kram, nyeri, parestesi
- Kulit: seborea

STADIUM KLINIS ( HOEHN & YAHR)

Stadium I
 Unilateral
 Ekspresi wajah kurang
 Posisi fleksi pada lengan yang terkena, tremor, ayunan ¯
Stadium II
 Bilateral
 Postur bungkuk ke depan
 Gaya jalan lambat dengan langkah kecil
 Sukar membalikkan badan
Stadium III
 Gangguan gaya jalan menonjol
 Ketidak-stabilan postural, jarang jatuh
Stadium IV
 Disabilitas jelas

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  Berjalan terbatas tanpa bantuan
 Lebih cenderung jatuh
Stadium V
 Hanya berbaring atau duduk di kursi roda
 Tidak mampu berdiri/berjalan meski dibantu
 Bicara tak jelas, wajah tanpa ekspresi, jarang berkedip

DIAGNOSA PP
- Diagnosa pasti PP ditegakkan dengan pemeriksaan histopatologis. Untuk kepentingan praktis
diagnosa didasarkan pada gambaran klinis yang meliputi: riwayat panyakit, pemeriksaan
neurologi dan respon terhadap dopamin.
- Beberapa prediktor untuk diagnosa PP secara klinis antara lain: onset yang asimetri, adanya
tremor saat istirahat dan respon yang baik terhadap dopamine.
- Tidak ada pemeriksaan darah atau CT/ MRI yang khas untuk PP, tapi penyebab parkinsonism
sekunder dan penyakit degeneratif lainnya harus disingkirkan dulu sebelum menegakkan
diagnosa PP.
- Diagnosa PP cukup sulit pada stadium awal. Terdapat beberapa kriteria diagnosa yang
diusulkan:
- Kriteria Klinis - Kriteria dari Koller - Kriteria dari Gelb
 Kriteria Klinis
 Dua dari 3 gejala kardinal motorik : tremor, rigiditas, bradikinesia, ATAU
 Tiga dari 4 gejala utama: tremor, rigiditas, bradikinesia, ketidakstabilan postural
à Kesalahan diagnosa : 25% (London Brain Bank Study)
 Kriteria Koller
 Ada dua dari 3 tanda kardinal gangguan motorik : tremor istirahat/ postural, rigiditas,
bradikinesia, yang berlangsung satu tahun atau lebih.
DAN
 Respon terhadap terapi levodopa (mis. minimal 1000 mg/hari selama satu bulan) yang
diberikan sampai perbaikan sedang dan lama perbaikan satu tahun atau lebih.
 Kriteria Gelb
à Berdasarkan kelompok gejala klinis
Gejala klinis A (khas untuk penyakit Parkinson) :
 Tremor waktu istirahat
 Bradikinesia

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  Rigiditas
 Permulaan asimetris
Gejala klinis B (gejala dini tak lazim), diagnosa alternatif :
 Instabilitas postural menonjol pada tiga tahun pertama
 Fenomena tak dapat bergerak sama sekali (freezing) pada 3 tahun pertama
 Halusinasi yang tak ada hubungan dengan pengobatan dalam 3 tahun pertama
 Demensia sebelum gejala motorik atau pada tahun pertama
 Diagnosa POSSIBLE
- Paling sedikit 2 dari kelompok A atau
- Paling sedikit 1 dari kelompok A adalah tremor atau bradikinesia, dan atau tak
terdapat gejala kelompok B
- Gejala kurang dari 3 tahun disertai respon jelas terhadap levodopa atau dopamin
agonis
 Diagnosa PROBABLE
- Paling sedikit 3 dari 4 gejala kelompok A dan tidak terdapat gejala dari
kelompok B
- Lama penyakit paling sedikit 3 tahun
- Respon jelas terhadap levodopa atau dopamin agonis
 Diagnosa DEFINITE
- Memenuhi semua kriteria probable DAN
- Kepastian Histopatologis waktu otopsi

DIAGNOSA BANDING:
 Gejala klinis:
- Tremor : DD/ tremor oleh sebab lain
Hipertiroid, ansietas, kelelahan, alkoholism, obat asma, kelainan serebelar,
kelainan familial (senilitas, esensial) à Istirahat hilang, bergerak timbul
- Rigiditas: DD/ spastisitas ok/ lesi sistem ekstra piramidalàFenomena pisau lipat
- Bradikinesia :DD/ gait apraxia à pada Normal Pressure Hydocephalus (NPH)
 Penyakit-penyakit parkinsonisme yang lain:
- Parkinsonism sekunder: Bila stadium awal ada gangguan postur, disartri,
gangguan otonom atau demensia
- Parkinsonism lain: Bila respon terhadap levodopa buruk
Bila ditemukan gejala spesifik lain sesuai penyebabnya

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PENATALAKSANAAN PENYAKIT PARKINSON
Penatalaksanaan terdiri dari :
1. Penanganan Suportif
Penerangan pada pasien, dorongan emosi dan konseling profesional (hukum, finansial,
pekerjaan)
2. Terapi Medikamentosa
- Masih tetap merupakan pilihan utama
- Pemilihan obat berdasarkan stadium, munculan klinis, usia, profil efek samping obat
- Dengan terapi yang tepat saat ini + 50% pasien Parkinson dapat hidup tanpa disabilitas
yang berat selama 10 tahun.

Obat-obat yang dapat dipakai:

AGENT TYPICAL INITIAL DOSE DAILY DOSE/

USEFUL RANGE
Carbidopa/levodopa 25 to 100 mg twice a day or tds 200 to 1200 mg levodopa

Carbidopa/levodopa sustained release 50 to 200 mg twice a day 200 to 1200 mg levodopa

Pergolide 0.05 mg once a day 0.75 to 5.0 mg

Bromocriptine 1.25 mg twice a day 3.75 to 40 mg

Pramipexole 0.125 mg tds 1.5 to 4.5 mg

Selegiline 5.0 mg twice a day 2.5 to 10 mg

Amantadine 100 mg twice a day 200 mg

Trihexyphenidyl HCl 1 mg twice a day 2 to 15 mg

Algoritma terapi medikamentosa:

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3. Terapi operatif

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 - Dipertimbangkan jika terapi medikamentosa tidak memberikan perbaikan yang memuaskan
- Sebaiknya pasien yang masih muda <50 tahun
- Masih dapat berjalan tanpa bantuan, berespon terhadap antiparkinson tetapi sering timbul
komplikasi pengobatan
- Fungsi luhur yang masih intak
- Tidak ada gangguan sistemik yang berat
- Jenis tindakan operasi: Transplantasi jaringan fetus ke striatum otak, Thalamotomy,
Palidotomy, Deep Brain Stimulation
4. Terapi rehabilitasi:
Sesuai dengan kebutuhan pasien : Terapi fisik, terapi okupasi, terapi wicara, psikoterapi
5. Kelompok support
Parkinson club: Pasien Parkinson kumpul bersama-sama dan membagi pengalaman
mengatasi kesulitan-kesulitan akibat penyakit

PERJALANAN PENYAKIT DAN PROGNOSA:

- PP adalah penyakit degeneratif yang berjalan progresif lambat. Awitan insidious, umur 50-70
tahun. Degenerasi neuron terjadi 1 dekade sebelum gejala kardinal muncul.
- Sebelum penggunaan levodopa, mortalitas penderita PP 3x lebih tinggi dibanding populasi
normal. Dengan pemberian terapi dopamine, secara mendasar memberikan harapan hidup
yang normal dan angka kematian yang hampir sama dengan bukan penderita PP.
- Pada awalnya hampir semua penderita PP mendapat efek terapi levodopa yang sangat baik
sampai 4-6 tahun, selanjutnya sering terjadi komplikasi dari pengobatan berupa diskinesia
atau fluktuasi motorik ( on-off fenomena, wearing off fenomena). Oleh karena itu penggunaan
levodopa sebaiknya ditunda sampai timbulnya gangguan fungsional pada penderita PP,
terutama pada penderita < 60 tahun (lihat algoritma terapi medikamentosa).
- Pada stadium lanjut sering disertai gejala non motorik/ gejala tambahan seperti: depresi,
demensia, dll. Hal ini akan sangat berpengaruh pada kualitas hidup pasen dan perlu
dipertimbangkan aspek medicolegalnya.

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