Slide pendukung

Presentasi Kasus Movdis

AQI
Anatomi Dystonia Neurodegenerative Atypical Parkinsonism
Parkinson Disease
• Ganglia basalis • Definisi
• Dementia Lewy bodies DLB
• Epidemiologi, Gejala, Klasifikasi • History, Faktor Risiko, Insiden
• Fisiologi GB
• Spasmodic torticolis • MSA
• Pyramidal, ekstrapyramidal • Patogenesis, Etiology
• Manajemen
• Vaskularisasi GB • PSP
• Deep Brain Stimulation DBS
• Dopamine Aging, Preklinis PD
• Cerebellum • CBD
• Tools • Braak staging
• Fungsi cerebellum
• Gambar • DRUG INDUCED
Movement Disorder • Motor symptoms PD
Parkinsonism
• Tools Drug induced
• Pengertian dan Klasifikasi movdis
• Definisi
• Non motor PD
• Lokasi • Vaskular Parkinsonism
• Kriteria diagnostik • Scales & Scores
TREMOR • Synucleinopathies vs Tauopathies
• Clinical approach Imaging Parkinsonism
• Definisi • Klasifikasi
• Parkinson’s Disease
• Klasifikasi • Diagnosis banding • Manajemen, terapi
• PSP
• Cause, diagnosis Myoclonus • Differential diagnosis
• Sindroma • MSA
• Definisi
• Rekomendasi Imaging
• Tremor dystonia • Klasifikasi, treatment • CBD
Imaging Movement Disorder Chorea Others
• Hutington, Hemibalismus, Wilson
• CHOREA • Athetosis

• Causes, Clinical approach • Dyskinesia

ATAXIA Chorea
• Tipe Gait
• Ataxia • Huntington’s,
• TMS
Syndendham
• Sporadic
• Vascular, metabolic, drug
• Genetic
induced Chorea
• Evaluasi, Treatment
• Treatment
GANGLIA BASALIS
ANATOMI
• Disebut juga sistem striato-pallido-nigral
• Tidak memiliki definisi pasti secara anatomis
• Ganglia Basalis = N. Caudatus + N. Lentiformis + N.
Subthalamikus + Substantia Nigra

• Bagian reseptif : Putamen  menerima jaras dari

seluruh bagian korteks serebri dan substansia
nigra pars kompakta
• Bagian output : G.P. Internus dan Substansia Nigra
pars retikulata
• Jaras dari ganglia basalis diteruskan ke Thalamus
(N. Ventrolateral dan N. Ventromedial) Bersama
jaras dari Cerebellum dan korteks motorik
Anatomy Ganglia Basalis
Anatomi Ganglia Basalis
FISIOLOGI
 Basal ganglia berperan dalam “memperhalus” gerakan volunter.
 Basal ganglia melakukan inhibisi pada gerakan yang tidak diperlukan

JARAS EFEREN PUTAMEN

1. Direct Pathway
Putamen  G.P. Internus  Substantia Nigra pars Reticulata
Diaktifkan oleh neuron glutaminergik dari korteks sensorimotor
dan neuron dopaminergic dari s. nigra pars compacta

2. Indirect Pathway
Putamen  G.P. Externus  N. Subthalamic
Neuron GABA-ergik dari putamen
Direct & Indirect Pathway
Direct & Indirect Ganglia basalis
GANGLIA BASALIS

Substansia nigra
(neuron di pars kompakta)

Membentuk sinaps inhibitori

Striatum
D2 dopamin reseptor
(nukleus kaudatus dan putamen)
Membentuk sinaps eksitatori
D1 dopamin reseptor

Striatum
(nukleus kaudatus dan putamen)

Substansia nigra pars retikulata

mengirimkan akson keluar memodulasi gerakan

kepala dan mata
Patomekanisme Hiperkinetik dan Hipokinetik
Cortico-Basal Ganglia-Thalamo-Cortical
Circuit
Farmakologi - Neurotransmiter
Neurotransmitter yang bekerja pada Ganglia Basalis :
1. Glutamate : eksitatorik, dilepaskan dari korteks ke striatum dan dari N.
Subtalamik

2. GABA : inhibitorik, dilepaskan dari striatum, G.P, dan Subs. Nigra pars reticulata

3. Dopamin : peran paling besar, eksitatorik / inhibitorik tergantung reseptor

4. Asetilkolin

5. Serotonin
 UMN

Ganglia basalis

parkinson Chorea huntington

Cerebelum

Contoh lesi pada

sistem pengaturan
gerak
 Talamus

Melalui traktus
tegmental sentral

Nukleus olivari inferior

Korteks cerebelum kontralateral

Nukleus rubra

Sistem organisasi pada ganglia basalis meliputi beberapa lingkaran kompleks dari neuron
(termasuk banyak neuron inhibitorik)

Adanya kerusakan pada sistem ini ditandai dengan osilasi/alarm yang terjadi apabila sirkuit umpan
balik inhibitori rusak. Biasanya ditandai dengan gerakan abnormal yang berulang atau ritmik
 EXTRAPYRAMIDAL SYSTEM PYRAMIDAL SYSTEM

POSTURAL ACTIVITY NONPOSTURAL ACTIVITY

GROUP OF LARGE INDIVIDUAL MUSCLE

MUSCLES ADAPTATION SKILLED MOVEMENTS
(Smooth, precise, specific,
learned)

CIRCUIT MODULATION

LMN

Pyramidal & extrapyramidal

systems interact in harmony to
produce normal and coordinated NORMAL & COORDINATED
movement MOVEMENT
Sindroma Extrapiramidal

02/02/2023 Department of Neurology FKKMK UGM - Dr. Sardjito Hospital 24

 CLINICAL CORRELATION
RIGIDITY
DISORDER OF
THE EXTRAPYRAMIDAL SYST.
DYSKINESIA

RIGIDITY INCREASED OF THE TONUS

OF AGONIST AND ANTAGONIST
MUSCLES

PLASTIC COGWHEEL

RESISTANCE: + RESISTANCE: +
SMOOTH AND JERKY
CONTINUOUS (DISCONTINUOUS)

PASSIVE MOVEMENT
TEST
GEJALA KELAINAN GB
• Gejala negatif : Bradikinesia, hypokinesia, kelainan reflex postural

• Gejala positif : Tremor, rigiditas, dyskinesia, athetosis, ballismus,

dystonia.

• Gejala lain : Gangguan gait, fonasi, artikulasi, gangguan kognitif dan

perilaku
Vascularisasi Ganglia Basalis
Vascularisasi Ganglia Basalis
CEREBELLUM
 Cerebellum

1. Flocculonodular lobe 2. Anterior lobe 3. Posterior lobe

(archicerebellum) (paleocerebellum) (neocerebellum)
Cerebellum
D Cerebelum

Interkoneksi
Medula spinalis & brainstem

Korteks cerebri kontralateral

(kortikopontocerebelar)

Eferen cerebelar ke nukleus

rubra, formasio retikularis,
nukleus ventral talamus kontra
lateral

Fungsi :
Koordinasi gerakan motorik volunter
Kontrol keseimbangan dan tonus otot
Serebelum
• Secara anatomis tersusun atas dua hemisfer dan vermis yang terletak
di antaranya.
• Serebelum berhubungan dengan batang otak melalui tiga pedunkel
serebelum
• Secara fungsional terbagi menjadi 3 komponen
Vestibuloserebelum, Spinocerebelum, Serebroserebelum.
Anatomi Permukaan Serebelum
• Terletak di fossa posterior, permukaan superiornya diselubungi oleh
tentorium serebeli.
• Permukaan serebelum menampilkan banyak lekukan kecil yang
berjalan horizontal (folia) yang satu sama lain dipisahkan oleh fisura,
bagian sentral serebelum disebut vermis.
Tiga komponen utama serebelum
1. Vestibuloserebelum (Arkiserebelum)
-Merupakan bagian serebelum tertua.
-Terdiri atas flokulus dan nodulus (lobus flokulonodularis).
-Fungsi Menerima impuls dari aparatus vestibularis yang
membawa informasi mengenai posisi dan gerakan kepala.
-Output eferennya mempengaruhi fungsi motorik mata dan
tubuh sedemikian rupa sehingga ekuilibrium dapat
dipertahankan pada semua posisi dan pada semua gerakan.
 3. Serebroserebelum
(neoserebelum/pontoserebelum)
• Bagian Serebelum termuda dan bagian terbesar.
• Terbentuk dari dua hemisfer serebeli dan memiliki
hubungan fungsional yang erat dengan korteks
serebri yang berproyeksi kesini melalui nuklei
pontin. (Lobus posterior)
• Fungsi Meregulasi semua gerakan secara halus dan
tepat.
Lesi Vestibulocerebellum
• Gangguan fungsional lobus flokulonodularis atau nukleus fastigii:

1. Disekuilibrium

Pasien mengalami kesulitan berdiri tegak (astasia) dan berjalan (abasia), dan gaya berjalan pasien lebar-lebar
dan tidak stabil, menyerupai gaya berjalan orang yang sedang mabuk (ataksia trunkal).

2. Gangguan okulomotor, nistagmus

Gangguan kemampuan mempertahankan tatapan terhadap objek yang diam atau bergerak (lesi flokulus dan
paraflokulus) hasilnya gerakan mengejar sakadik dan gaze-evoked nystagmus.

Gaze-evoked nystagmus ketika mata bergerak ke sisi lesi serebellum dan menghilang bila pandangan
dipertahankan ke sisi tersebut. Bila mata diarahkan ke tengah, rebound nystagmus.

3. Heel-to-toe walking tidak dapat dilakukan.

 Lesi Spinocerebellum
• Lesi lobus anterior dan superior vermis : ataksia stance /postur berdiri tegak dan ataksia gait/gaya berjalan (lebih berat).

• Cara berjalan yang lebar dan tidak stabil, berdeviasi ke sisi lesi, kecenderungan jatuh di sisi lesi.

• Ataksia stance terlihat dengan tes Romberg.

• Jika lesi terbatas pada bagian superior vermis: tes telunjuk-hidung dan tes tumit-lutut –tulang kering masih dapat dilakukan
secara akurat.

• Lesi bagian inferior vermis : menyebabkan ataksia pada postur berdiri tegak (astasia) yang lebih berat dibandingkan ataksia gaya
berjalan. Pasien kesulitan untuk duduk dan berdiri dengan stabil dan pada tes romberg bergoyang secara perlahan kebelakang
dan kedepan tanpa kecendrungan ke arah tertentu.
Lesi Serebrocerebellum
A. Dekomposisi gerakan volunter

1. Dismetria : ketidakmampuan untuk menghentikan gerakan terarah pada suatu saat,

bermanifestasi dengan menggerakkan jari melewati lokasi target (past-pointing :
overshoot, hipermetria).

2. Dissinergia : hilangnya kerjasama yang tepat pada beberapa kelompok otot dalam
eksekusi gerakan tertentu, masing-masing kelompokotot berkontraksi tetapi tidak dapat
bekerjasama dengan kelompok otot lainnya secara sinergis.

3. Disdiadokokinesia : gangguan rapid alternating movement akibat kerusakan koordinasi

ketepatan waktu pada kelompok otot antagonis: gerakan seperti pronasi dan supinasi
tangan secara cepat menjadi lambat , terputus-putus dan tidak berirama.
4. Tremor intensional (tremor aksi)
Terutama terlihat pada gerakan terarah dan menjadi lebih berat ketika jari semakin dekat dengan target.

B. Rebound phenomenon
ketika pasien melawan tangan pemeriksa dengan kekuatan maksimum dan pemeriksa tiba-tiba
menarik tangannya, gerakan pasien tidak dapat dihentikan secara normal dan lengannya tiba-tiba
bergerak ke arah pemeriksa.

C. Hipotonia dan hiporefleksia

Pada lesi akut hemisfer serebeli, resistensi otot terhadap gerakan pasif menghilang dan dapat terjadi
postur abnormal (misal pada tangan). Refleks otot intrinsik juga menghilang pada otot yang hipotonik.

D. Slurred Speech
Terutama timbul akibat lesi paravermis dan menggambarkan gangguan sinergi otot-otot untuk
berbicara. Pasien berbicara lambat dan terbata-bata, dengan artikulasi yang buruk dan dengan
penekanan yang abnormal dan tidak bervariasi pada setiap suku kata.
Fungsi cerebellum

Koordinasi Postur
gerakan

Gaya berjalan Pengaturan tonus

Cerebellum
Zona vermal
- Menjaga keseimbangan
- Input melalui spinocerebellar
- Nukleus fastigial.
Zona paravermal
- Gerakan yang terampil
- Input melalui spinocerebellar
- Nukleus globosa & emboliform
Zona lateral
- Aktivitas motorik seluruh tubuh
-
Klinis pada kelainan cerebellar
- Inkoordinasi ataksik
- Disartria cerebellar
- Kelainan mata
- Gangguan gaya berjalan
- Hipotonus
PEMERIKSAAN

• Disdiadokokinesis • Dismetri : Finger to nose test

• Ataxia • Heel to shin test
• Nistagmus • Tandem gait
• Intention tremor • Romberg test
• Slurred Speech
• Hipotonia
• Past pointing test
• Tremor
• Rebound phenomen
Movement Disorder
 Pengertian Movement Disorder
MDs are neurological syndromes that involve impaired performance of voluntary
movements, dysfunction of posture, abnormal involuntary movements, normal
movements at inappropriate times.
not due to weakness or abnormal muscle tone, but may be accompanied by weakness
or abnormal tone.
 Most movement disorders are associated with pathologic alterations in the basal ganglia
or their connections.
 But disorders of the
• Cerebellum or its pathways
• Cerebral cortex
• Thalamus
• Brain stem
• Spinal cord
• Peripheral nerves
may also cause several movement disorders
Movement Disorder Classification: Pola gerakan
 Kekuatan Refleks Regang Gerakan
Lokasi Lesi Atrofi Tonus Kelainan
Volunter Otot Abnormal

Gangguan Gerak
Otot
(Miopati)
Kelemahan
(paretik)
dapat parah Hiporefleks Hipotonus tidak ada Miastenia gravis
Myotonia
kongeniltal
progressive
muscular
dystrophies

Motor end Kelemahan ringan Hiporefleks Hipotonus tidak ada

plate
Lower motor Kelemahan mungkin ada Hiporefleks atau Hipotonus Fasikulasi spinal muscular
neuron atau arefleks (flasid) dystrophy,
(termasuk kelumpuhan amyotropic
nervus lateral sclerosis,
perifer, poliomielitis
neuropati)
Upper motor Kelemahan ringan (disuse hiperrefleks, Hipertonik withdrawal
neuron atau atrofi) setelah terjadi (pisau lipat spasme, refleks
kelumpuhan lesi UMN yang atau abnormal
masif, refleks spastik)
dapat hilang cerebral palsy
sementara,
dengan
hipotonus dan
spinal syok
Sistem normal normal Hipotonus Hipotonus Ataksia,
cerebelar (pendulus) dismetria,
Ataksia
disdiadokokinesis,
kelainan gait
Ganglia normal normal normal Rigid Diskinesia
basalis (coghwheel) (misalnya :
chorea, atetosis, Parkinson
distonia, tremor,
hemibalismus)
Hypokinesias

• Akinesia/bradykinesia (parkinsonism)
• Apraxia
• Blocking (holding) tics
• Cataplexy and drop attacks
• Catatonia, psychomotor depression, and obsessional slowness
• Freezing phenomenon
• Hesitant gaits
• Hypothyroid slowness
• Rigidity
• Stiff muscles
Hyperkinesias

• Abdominal dyskinesias • Moving toes and fingers

• Akathitic movements • Myoclonus
• Ataxia/asynergia/dysmetria • Myokymia and synkinesis
• Athetosis • Myorhythmia
• Ballism • Paroxysmal dyskinesias
• Chorea • Periodic movements in sleep
• Dystonia • REM sleep behavior disorder
• Hemifacial spasm • Restless legs
• Hyperekplexia • Stereotypy
• Hypnogenic dyskinesias • Tics
• Jumping disorders • Tremor
Phenomenology Movement Disorder
LOKASI
• Many movement disorders are associated with
pathologic alteration in the basal ganglia or their
connection.
• Localizations are classicaly associated with specific
movement disorders:
• Substansia nigra with bradykinesia, rest tremor
• Subthalamic nucleus with ballismus,
• Caudate nucleus with chorea,
• Putamen with dystonia.
Klasifikasi Gangguan
Gerak: Lokasi Lesi
Klasifikasi
Gangguan Gerak:
Lokasi Lesi Spesifik
TREMOR
TREMOR
• Gerakan involunter dengan karakteristik getaran ritmis yang muncul akibat kontraksi
otot-otot yang berlawanan.
• “Ritmis” menjadi pembeda antara tremor dg gangguan gerak lainnya.
• Tremor dikelompokkan berdasarkan frekuensi, amplitude, lokasi, dan aktivasi posisional
Tremor
• Tremor adalah gerakan osilasi ritmik, selang-seling otot agonis dan
antagonis, sinusoidal, teratur.
• lnsiden dan prevalensi tremor meningkat seiring bertambah usia,
mengenai lebih dart 4% pasien usia lebih darl 65 tahun. Lebih dari 2/3
populasi yang mengalami tremor pada tangan mengalami kesulitan
dalam kehidupan seharl-harl, dan menyebabkan gangguan fungsional
dan sosial.
Tremor
Jenis Frekuensi Aktivasi Pemeriksaan Kausa
TREMOR
CAUSE OF TREMOR (1)
Rest tremor : PD, dug-induced parkinsonism, vascular parkinsonism,
PSP, MSA, spinocrebellar ataxia, psychogenic tremor
Postural tremor : enhanced physiological tremor, drugs, toxins,
metabolic disturbance, essential tremor, neuropathy, dystonia, task
specific tremors, PD, MSA, SCA orthostastic tremor, psychogenic
tremor.
Kinetic tremor : cerebellar disease, Holmes tremor, Wilson’s disease,
psychogenic tremor
CAUSE OF TREMOR (2)
Head tremor : ET,
dystonia, cerebellar
disease, third
ventricular cysts
Chin tremor :
Hereditary geniospasm,
PD
Jaw tremor : PD,
dystonia, ET
Palatal tremor : ET,
symptomatic with
ataxia.
CLINICAL APPROACH OF TREMOR

History
 Age at onset
 Body part affected
 Any precipitating factors at onset
 Drug exposure
 Progression : static or rapid
 Exacerbating factors e.g. writing
 Reliefing factors e.g. Alcohol
 Associated neurological symtoms e.g. slowness movement, incoordination, sensory
disturbance, limb weakness
 Associated systemic symptoms e.g. symptoms of hyperthyroid
 Family history
Examination
◦ Examine patient at rest
◦ Examine arms on posture
◦ Examine arms during
movement
◦ Ask the patient to write with
their dominant hand and
copy a spiral with both hand
◦ Examine for the neuroogical
signs : parkinsonism,
cerebellar signs, peripheral
neuropathy signs
◦ Examine for signs of systemic
disease : hyperthyroidism
 Resting Tremor Tremor Intensional
 Parkinson Disease Penyakit pada jaras cerebellar (dentate nuclei, interpositus nuclei,
Differensial  Sindrom Parkinsonian lain (jarang)
 Tremor midbrain (Holmes tremor):
dan superior cerebellar peduncle):
MS, trauma, tumor, vascular disease, WD, acquired
hepatocerebral degeneration, obat-obatan, toksin (e.g., mercury),
Diagnosis rest< postural< intensional
 WD ( termasuk degenerasi hepato cerebral) dll
 Tremor esensial
Tremor Tremor Postural Gangguan Gerakan Ritmik Lain-Lain
 Tremor fisiologis  Tremor psikogenik
 Tremor fisiologis yang berlebihan; faktor-faktor ini juga  Gerakan berirama pada distonia (tremor distonik, mioritmia)
dapat memperburuk bentuk lain dari tremor:  Mioklonus berirama (mioklonus segmental, misalnya palatal
o Stres, kelelahan, kecemasan, emosi atau myoclonus branchial, mioklonus spinal), mioritmia
o Endokrin: hipoglikemia, tirotoksikosis, pheochromocytoma  Mioklonus berosilasi
o Obat-obatan dan racun: adrenokortikosteroid -agonis,  Asteriksis
dopamin  Klonus
o agonis, amfetamin, litium, antidepresan trisiklik, neuroleptik,  Epilepsia parsialis continua
teofilin, kafein, asam valproat, alcohol withdrawal, merkuri  Hereditary chin quivering
("hatter’s shake"), timbal, arsenik, dll  Spasmus nutans
 Tremor esensial (familial atau sporadis)  Headbobbing dengan kista ventrikel ketiga
 Writing tremor primer dan tremor khusus tugas lainnya  Nistagmus
 Tremor ortostatik
 Dengan gangguan SSP lainnya:
o PD (tremor postural, tremor yang muncul kembali,
berhubungan dengan tremor esensial)
o Sindrom kaku-akinetik lainnya
o Distonia idiopatik, termasuk distonia fokal
o Dengan Neuropati perifer:
o Charcot-Marie-Tooth disease (called the Roussy-Levy
syndrome)
o Neuropati perifer yang lain
o Cerebellar tremor
 Gambaran Sindroma Tremor
Sindroma Tremor
Tremor Cerebellar
Enhanced Physiologic Tremor
Essential Tremor
Parkinsonian Tremor
Psychogenic Tremor
Gambaran Klinis
Tremor intensional atau postural, ipsilateral lesi, abnormal finger to finger test,
imbalance, abnormal heel to shin test, hypotonia
Postural tremor, low amplitude, use of exacerbating medication
Postural tremor, simetris, melibatkan tangan, eskstremitas bawah, kepala, suara,
riwayat keluarga, alcohol
Rest tremor, asimetris, berhubungan dengan anggota gerak distal, menurun
dengan gerakan volunteer, bradykinesia, instabilitas postural, rigiditas
Onset mendadak, remisi spontan, hilang dengan distraksim perubahan
karakteristik tremor
Action tremor
• Tremor yang muncul saat menggerakkan bagian tubuh

• Dibagi menjadi 2 :
• Goal-directed action tremor  Lesi cerebellar, ataxia
• Postural tremor : muncul saat ekstremitas dipertahankan pada posisi
tertentu, hilang saat relaksasi
• Enhanced Physiologic tremor
• Essential tremor
ENHANCED Physiologic tremor
• Secara fisiologis, tremor ada di dalam sistem motorik tetapi sangat
halus sehingga tidak terlihat
• Beberapa kondisi menyebabkan tremor fisiologis tersebut
membesar
• Frekuensi sama dengan tremor fisiologis (10Hz) tetapi dg
ampitudo yang lebih besar
• Pencetus : cemas, takut, gangguan metabolik (Hipertiroid,
hipoglikemi), withdrawal alcohol, efek kokain
• Muncul bukan akibat kelainan pada SSP tetapi akibat stimulasi dari
reseptor beta di otot
Essential tremor
• Jenis tremor paling banyak ditemukan
• Frekuensi 4-8 Hz
• Tidak berhubungan dengan lesi SSP
• Bersifal familial, muncul pada decade ke dua.
• Muncul asimetris

• Patofisiologi : Kontroversi. Gerakan berasal dari jaras olivocerebellar dan

terdapat peningkatan blood flow pada cerebellum
• Tatalaksana :
• 75% pasien membaik dg konsumsi alcohol.
• Beta adrenergic : propranolol 80 – 200mg/hari. ESO : kelelahan, DE, dan bronchospasme
• Botulinum toxin. ESO : kelemahan otot
PARKINSONIAN (REST) TREMOR
• Tremor yang tampak kasar, ritmis, frekuensi 3-5 Hz.
• Lebih sering ditemukan di tangan dan lengan bawah, jarang di kaki,
rahang, lidah dan bibir
• Muncul saat ekstremitas dalam posisi istirahat dan berkurang saat
terdapat gerakan intensional.
• Pada Parkinson, tremor yang muncul dalam bentuk fleksi-extensi jari dan
adduksi-abduksi ibu jari  pin rolling tremor
• Patofisiologi : Belum diketahui secara pasti. Kerusakan pada substansia
nigra pars compacta menyebabkan tremor pada 50% pasien
• Terapi : Obat antikolinergik (THP dan Benzthropin), beta-blocker diberikan
pada tremor yang lebih cepat frekuensinya.
Intention tremor
• Disebut juga ataxic tremor / cerebellar tremor / goal-directed tremor
• Selalu muncul bersamaan dengan ataxia cerebellar
• Tremor tidak muncul saat istirahat dan saat awal gerakan, tetapi muncul saat
gerakan halus dibutuhkan (ex. Finger to finger test)
GENIOSPASM
• Familial episodic tremor yang disebabkan mutasi kromosom 9
• Muncul pada dagu dan bibir bawah
• Mulai muncul saat anak-anak dan semakin parah seiring usia
PRIMARY ORTHOSTATIC TREMOR
• Tremor yang hanya muncul di kaki pada saat berdiri dan hilang
saat berjalan.
• Frekuensi 14-16 Hz sehingga sulit dilihat dan lebih mudah
ditemukan saat dipalpasi
• Disertai ketidakseimbangan saat berdiri

• Patofisiologi : Mielopathy
• Terapi : clonazepam, gabapentin, atau sodium valproat
psychogenic tremor
• Manifestasi dari histeria
• Biasanya tampak sebagai tremor sesisi pada sisi dominan,
bentuknysa tidak regular dan berupa action tremor
• Tremor menghilang saat pasien terdistraksi
• Fenomena “Chasing the tremor”
Palatal tremor
• Gerakan involunter ritmis pada palatum mole
• Essential palatal tremor : kontrsaksi berulang m.tensor veli palatini.
Pasien mengeluhkan bunyi “click” terus menerus. Palatal tremor tetap
muncul bahkan saat tidur
• Symptomatic palatal tremor : disebabkan lesi vascular / neoplasma /
demyelinisasi pada m.oblongata dan pons.

• Terapi : Clonazepam (0.25 – 0.5mg, dinaikkan bertahap hingga 3.0- 6.0

mg/hari); As. Valproat (250mg/hari, ditingkatkan hingga 1000mg/hari);
Gabapentin (hingga 2100mg)
TREMOR SYNDROMES
Tremor in Parkinson’s disease
◦ PD is the most common cause of rest tremor.
◦ Rest tremor : asymmetric, 3-4 Hz, moderate amplitude.
Typically involves the thumb and index finger –pill-
rolling. May involve other body parts, including legs,
jaw and chin.
◦ Postural tremor : asymmetric, 6-8 Hz, moderate
amplitude. Occurs immidiately on stretching out the
arms.
◦ Re-emergent tremor : asymmetric, 3-4 Hz, moderate
amplitude. Occurs in patients with rest tremor. When
they stretch their arms out in front of them there is no
tremor, but after a few second, a rest tremor recurs (re-
emerges) in the new potition.
• Tremor in Neurophatic
• Peripheral neuropathy can cause postural
tremor.
• Tremor is often seen in hereditary
sensorimotor neuropathy (HSMN) and
chronic inflamatory demyelinating
polyradiculoneuropathy (CIDP).
• Signs of pheripheral neuropathy are almost
always cleary present at the onset of the
tremor
• Treatment of the underlying neuropathy may
improve the tremor.
• Tremor in Cerebellar disease
• The most common cause of kinetic tremor
• This tremor is called “intention tremor”.
• Had tremor is often present
• Cerebellar signs are present, including
nystagmus, dysmetria, rebound, heel-shin
ataxia, ataxia gait.
• Cause: demyelination,
ischemic/haemorrhagic damage in
cerebellum, toxic effect of drugs and
degenerative disease affecting the
cerebellum.
Essential tremor (ET)
◦ Symmetrical postural tremor
◦ Often inherited in a autosomal dominan
◦ Onset is bimodal : childhood and senile
◦ Men and women are equally affected.
◦ Clinical features: 8-10 Hz, rarely present at rest, may
persist during movement, usually gradual onset,
tend to worsen slowly over time, head and voice
may occur., exacerbated by anxiety, relieved by
alcohol.
◦ It is due to the action of a abnormal central
oscillator, probably located in midbrain.
• Holmes tremor
• Tremor is present at rest, worse on posture and
much worse during movement.
• Named after the neurologist Gordon Holmes
(1876-1965)
• Synonyms include rubral tremor and midbrain
tremor.
• It is due to damage to cerebellar connections
within brainstem.
TREATMENT
• Treatment of tremor is purely symptomatic.
• It is essential to ask the patient if they feel that
their tremor is disabling enough for them to want
to try a treatment that may have side effects.
• For limb tremor, except in cases of parkinsonism,
can be used propanolol, clonazepam, primidone,
topiramate and gabapentine.
• Botolinum toxin may be helpful for task-specific
tremor.
TREMOR DYSTONIA
• Merupakan tremor yang terjadi pada bagian tubuh yang dlpengaruhi
distonia (tangan, kepaia, leher).
• Bersifat Irregular dan menyentak-nyentak ( jerky ) dengan frekuensi
bervariasi (< 7 Hz), biasanya menghilang saat istlrahat.
• Salah contoh tremor dlstonia adalah tortikolis spasmodik.
• Tremor dlstonia kepala serlngkali dldiagnosis sebagal titubasi atau
tremor senilis. Untuk membedakan, minta pasien untuk mengarahkan
kopala berlawanan dengan arah distonia, bila tremor memburuk 
tremor distonia.
• Etiologi belum diketahui, namun dlduga mellbatkan ganglia basalis.
Penatalaksanaan
• lnjeksi toksin botulinum :
• untuk tremor kepala (40-400 unit pada otot yang terkait)
• dan tangan (50-100 unit pada otot agonis / antagonis yang mengalami tremor).
• Jika tremor tldak membaik, dapat dlberikan :
• Antlkolinerglk (trihekslfenidil, baklofen) sebagal antidistonia
• Benzodiazepin.
• Alternatif lainnya, meliputi propanolol, primidon, L-dopa, neuroleptlk,
karbamazepln, dan tetrabenazin.
• Pada kasus tremor yang berat, dapat dllakukan DBS pada globus
• pallidus atau thalamus ventrolateral dan rhlzotomi dorsal selektlf.
DEFINITION
• Dystonia means a disturbance in muscle
tone.

• Dystonia defined as sustained muscle

contractions, producing twisting, repetitive
and patterned movements or abnormal
postures.
Dystonia
• Dystonia is characterized by involuntary, long-lasting muscle
contractions that produce bizarre movements and contorted
postures of the limbs. Like many other types of movement disorders
caused by basal ganglia disease, dystonia worsens with mental
concentration or emotional stress and improves during sleep. During
the intervals when dystonia is absent, the muscle tone on passive
movement of the affected limbs tends to be decreased.
DYSTONIA
• Gerakan involunter yang berupa gerakan spasme atau postur yang
tidak natural yang mengakibatkan tubuh seperti terpelintir
• Gerakan dapat berupa overextensi atau overfleksi tangan, inversi
kaki, fleksi lateral atau retrofleksi kepala, torsi tulang belakang
dengan lengkungan dan puntiran punggung, dan penutupan mata
secara paksa
• Dystonia dapat terjadi pada satu bagian tubuh tertentu maupun
generalisata
EPIDEMIOLOGY
• Dystonia is the most frequent movement
disorder, after PD and ET.
• Prevalence :
• 3.4/100,000 for generalized dystonia
• 29.5/100,000 for focal dystonia.
• One-third of all dystonia caused by
secondary dystonia.
SYMPTOMS
The symptoms of Task-specific dystonia
dystonia depend on the only arise during the
body part affected. performance of certain
Face : repetitive tasks such as writing,
blinking, tongue typing or playing
protrusion or jaw instruments.
clenching. Dystonia can be
Neck : sustained flexion, worsened by stress and
extension, or twisting anxiety, and it may be
postures of the neck relieved with relaxation
known as torticollis. and sleep.
CLASSIFICATION
Distribution
• Focal : blepharospasm,
oromandibular dystonia,
cervical dystonia, laryngea
ldystonia, and writer’s
cramp.
• Segmental : cranial dystonia Age at onset
or bibrachial dystonia. • Infancy (birth to 2 years)
• Multifocal • Childhood (3–12 years)
• Generalized • Adolescence (13–20 years)
• Hemidystonia • Early adulthood (21–40 years)
• Late adulthood (>40 years
 CLASSIFICATION – Etiology
• Inherited (dystonia forms of • Acquired (dystonia due to
proven genetic origin). a known specific cause).
• Autosomal dominant • Perinatal brain injury
• Autosomal recessive • Infection
• X-linked recessive • Drug
• Mitochondrial • Toxic
• Idiopathic (unknown cause). • Vascular
• Sporadic • Neoplastic
• Familial • Brain injury
• Psychogenic
 I. Keturunan atau didapat III. Sindrom hiperkinetik lain yang terkait dengan distonia
A. Keturunan (isolated) A. Gangguan tic dengan tics distonik
B. Keturunan (combined) B. Diskinesia paroksismal
Klasifikasi  
II. Distonia didapat (distonia karena sebab spesifik)
1. Diskinesia kinesigenik paroksismal (16p11.2–q12.1)
2. Diskinesia nonkinesigenik paroksismal (2q33–35)
etiologi  Parkinson disease
 Progressive supranuclear palsy
3. Diskinesia akibat aktivitas paroksismal (16p12–q12)
4. Diskinesia hipnogenik paroksismal (sebagian besar frontal)
Distonia  Multiple system atrophy
 Corticobasal degeneration
gangguan kejang lobus dengan gen yang terlokalisasi pada
20q13.2-13.3)
 Berhubungan dengan gangguan metabolic:  
1. Amino acid disorders IVFunctional/ Psikogenik
2. Gangguan lipid V Pseuodistonia
3. Kelainan Metabolik Lain Subluksasi Atlanto-aksial
 Cedera serebral perinatal dan kernikterus: Siringomielia
 Infeksi: ensefalitis virus, HIV Kelumpuhan saraf troklearis
 Lainnya: TBC, sifilis, tortikolis infeksi akut Tortikolis
 Obat-obatan: L-dopa dan agonis dopamin, obat penghambat Massa fossa posterior
reseptor dopamin, fenfluramine, antikonvulsan, flecainide,
ergot, penghambat kanal kalsium tertentu
 Toksin: magnesium, karbon monoksida, karbon disulfida,
sianida, metanol, disulfiram, asam 3-nitroproprionat,
sengatan tawon
 Metabolik: hipoparatiroidisme
 Lesi batang otak dan sumsum tulang belakang
 Tumor otak
 Malformasi arteriovenosa
 Trauma kepala dan operasi otak (thalamotomy)
 Trauma perifer (dengan kausalgia)
 Cedera listrik
DYSTONIA
• Dystonia Musculorum Deformans :
Mutasi gen DYT
• Idiopathic dystonia : Familial,
autosomal dominan
• Acute Generalized Dystonia : biasanya
efek obat neuroleptic, retrocollis
menjadi tanda khas
• Hemidystonia sangat jarang ditemukan,
disebabkan stroke pada putamen
kontralateral
Dystonia
• Focal dystonia: examples include blepharospasm, an involuntary
forced closure of the eyes due to contractions of the orbicularis oculi
muscle, and spasmodic torticollis, i.e., dystonic wry neck.
• Generalized dystonias, of which there are multiple types, affect all
muscle groups of the body to varying degrees. Patients suffering from
generalized dystonia are often most severely disturbed by the
dysarthria and dysphagia that usually form part of the syndrome: the
patient’s speech is hurried, and often barely intelligible. The precise
nature of the functional abnormality in the basal ganglia that gives
rise to dystonia is poorly understood at present
Dystonia
Blepharospasm
• The first described by
Talkow, 1870 in a 60-year-
old women.
• Prevalence is 5/500,000
• Woman: man = 3 : 1
• Age of onset 50 -70 years
old.
• Increased blinking and
intermittent involuntary
closure of the eyelids.
Spasmodic Torticolis
Torticolis spasmodique’
was introduced by
Desterac in 1901
The most of focal
dystonia
Prevalence is 18/100,000
Age of onset at 50-60
Stress increases the
dystonia, with relaxation
and ‘sensory trics’ may
improve the symptoms.
Oromandibular Dystonia
• Involve muscle of mouth, jaw and tounge.
• Dystonic movements may sometimes be evoked
by voluntary muscle contactions like talking or
laughing.
• OMD can be supressed by chewing, biting on a
object or potitioning a hand below the chin 
sensory trick.
• Meige’s syndrome is combined between OMD
and blepharospasm (Henry Meige in 1910).
Dystonia
TREATMENT
• Focal dystonias may be treated initially with anticholinergic agents,
benzodiazepines, or muscle relaxants.
• These drugs are somewhat ineffective at doses that would not cause side effects.
• Botulinum toxin injections are the first line of therapy for most focal dystonias,
including torticollis, blepharospasm, and focal limb dystonia.
• Treatment of generalized dystonia is more challenging, because botulinum toxin
cannot be injected at high doses in multiple body parts.
• Anticholinergic agents, benzodiazepines, muscle relaxants, and anticonvulsants
are frequently used.
DYSTONIA – Manajemen
• Focal dystonia : injeksi botulinum toxin pada otot yang terlibat

• Idiopatic chronic dystonia : antikolinergik, THP, benztropine

• General dystonia : Bedah stereotaktik pada GP dan N. Ventrolateral

thalamus memiliki hasil yg tidak dapat dipredikdsi, Deep Brain
Stimulation pada GP bilateral mengurangi 50% gejala selama 1 tahun
Candidacy
for DBS
UNIFIED DYSTONIA RATING SCALE
(UDRS)
TORONTO WESTERN SPASMODIC
TORTICOLLIS RATING SCALE
(TWSTRS)
Gambar
PARKINSONISM
Definisi
Penyakit Parkinson: Bagian dari Parkinsonism yang secara patologi ditandai
oleh degenerasi ganglia basalis terutama di substansia nigra pars kompakta yang
disertai adanya inklusi sitoplasmik eosinofilik (Lewy bodies).

Parkinsonism: Suatu sindroma yang ditandai oleh tremor waktu istirahat,

rigiditas, bradykinesia dan hilangnya reflex postural akibat penurunan kadar
dopamine dengan berbagai macam sebab.

Syamsudin, T. 2015. Penyakit Parkinson. In: Thamrin, S., Subagya &

Muhammad A. editor, Buku Panduan Tatalaksana Penyakit Parkinson
dan Gangguan Gerak Lainnya. 1st ed., Kelompok Studi Movement
Disorders Perhimpunan Dokter Spesialis Saraf Indonesia, Jakarta.

02/02/2023 Department of Neurology FKKMK UGM - Dr. Sardjito Hospital 134

PARKINSONISM - Definition
• Parkinsonism is a syndrome manifested by a combination of the following six
cardinal features: tremor at rest, bradykinesia, rigidity, flexes posture, loss of
postural reflexes and freezing.

• Combination of these signs is used to clinically define definite, probable and

possible parkinsonism.

• The most common form of parkinsonism is the idiopathic variety known as

Parkinson’s disease (PD)
PARKINSONISM – Diagnostic Criteria
1. tremor at rest
4. flexes posture
2. bradykinesia
5. loss of postural reflexes
3. rigidity
6. freezing

Definite Probable Possible

At least two of Feature 1 or 2 At least two of

these feature must alone is present features 3 to 6
be present, one of must be present
the being 1 or 2
Synucleinopathies vs Tauopathies
Synucleinopathies vs Tauopathies
 Klasifikasi Parkinsonism
1 Parkinson Disease IV Sekunder (acquired, simtomatik) Parkinsonism
 Parkinson Disease-sporadic  Infeksi: post ensefalitis, AIDS, subacute
 Parkinson Disease-hereditary (lihat tabel 23.1) sclerosing panencephalitis, Creutzfeldt–Jakob
Klasifikasi II Multisystem degenerations (“parkinsonism plus”)


Progressive supranuclear palsy
Multiple system atrophy (Shy-Drager syndrome):

disease, prion diseases
Obat-obatan: obat dopamine receptor

Parkinsonisme
blocking (antipsikotik , antiemetik) reserpine,
MSA-P striatonigral degeneration) tetrabenezine, methyldopa, lithium,
MSA-C (olivopontocerebellar atrophy)
flunarizine, cinnarizine)
 Lytico-Bodig disease, or amyotrophic lateral sclerosis and
parkinsonism-dementia complex of Guam  Toksin: MPTP, karbon monoksida, mangan,
 Degenerasi kortikobasal merkuri, karbon disulfide, methanol, etanol
 Progressive pallidal atrophy  Vaskular: penyakit multi infark
 Trauma: pugilistic encephalopathy disease
 Lainnya: abnormalitas paratiroid,
III Heredodegenerative parkinsonism   hipotiroidisme, degenerasi hepatoserebral,
 Dopa-responsive dystonia tumor otak, paraneoplastic, normal-pressure
 Huntington disease hydrocephalus, noncommunicating
 Wilson disease hydrocephalus, syringomesencephalia,
 Neurodegeneration denagn akumulasi iron pada otak (pantothenate hemiatrophyhemiparkinsonism,
kinase-associated neurodegeneration, also known as Hallervorden–  peripherally induced tremor and
Spatz disease dan aceruloplasminemia)  parkinsonism, psychogenic
 Olivopontocerebellar and spinocerebellar atrophies, including
Machado–Joseph disease
 Frontotemporal dementia with parkinsonism (FTDP)
 Gerstmann–Sträussler–Scheinker syndrome
 Familial progressive subcortical gliosis
 Lubag (X-linked dystonia-parkinsonism)
 Familial basal ganglia calcification
 Mitochondrial cytopathies with striatal necrosis
 Ceroid lipofuscinosis
 Familial parkinsonism with peripheral neuropathy
 Parkinsonian-pyramidal syndrome
 Neuroacanthocytosis
 Hereditary hemochromatosis
 Neuroferritinopathy
Klasifikasi Parkinsonism berdasarkan Proteinopathies
Diagnosis Banding Parkinsonism
Dementia with Lewy Body (DLB)
Idiopathic Parkinson’s Disease
Multiple System Atrophy (MSA)
Other Neurodegenerative
Parkinsonism Progressive Supranuclear Palsy
(PSP)

Corticobasal Syndrome (CBS)

Parkinsonism
Drug-induced Parkinsonism

Toxin

Vascular Parkinsonism
Secondary Parkinsonism
Normal Pressure Hydrocephalus

Wilson’s Disease
Other causes: posttraumatic,
postencephalitis, infection, tumor. Other Causes
Parkinsonism Sekunder
Parkinsonism Sekunder
Algoritma Parkinson Disorder
MYOCLONUS
DEFINITION
• Myoclonus is a brief electric shock-like jerks.
• Myoclonus is caused by brief activation of a
group of muscles, leading to a jerk of the
affected body part.
• This activation can rise from the cortex,
subcortex, spinal cord or nerve roots.
• Sometimes myoclonus produces a
temporary cessasion of muscle activity
(negative myoclonus).
• If this affects the legs, patient may fall.
CLASSIFICATION
• Clinical presentation Anatomic origin
• spontaneous, Cortical
• reflex myoclonus, Subcortical
• action-iduced, Spinal
• negative myoclonus Peripheral
• Distribution Etiology :
• generalized Physiological
• multifocal Essential
• segmental Epileptic
• focal Symptomatic
• Physiological myoclonus occurs in normal
subjects and includes jerking movements
during sleep as well as anxiety induced or
exercise-induced myoclonus.
• In essential myoclonus, there is no known
cause and there are no gross neurological
deficits.
• In symptomatic myoclonus, a progressive or
static encephalopathy exists, and myoclonus
is one of the clinical signs.
TREATMENT
• In cortical myoclonus, the sensorimotor cortex is
the site of origination.
• Cortical myoclonus is a fragment of epilepsy, and
its treatment frequently involves anticonvulsant
agents.
• The most commonly used drugs are valproic acid,
clonazepam, levetiracetam and primidone.
• Clonazepam is best treatment for propiospinal
myoclonus,
• Carbamazepine/tetrabenazine for segmental
myoclonus.
Parkinson’s Disease
PARKINSON’S DISEASE – History
• First Description of the
“Shaking Palsy” as a Clinical
Syndrome by James Parkinson
in 1817.
• Jean-Martin Charcot, 1867
• Proposes the eponymous
label “Parkinson’s disease”
• First effective treatment:
belladonna alkaloids
PARKINSON’S DISEASE – History
• Friedrich Heinrich Lewy, 1912
• Intracytoplasmic inclusions: the hallmark of Parkinson's
disease
• Constantin Trétiakoff, 1919
• Cell degeneration in the substantia nigra
• Herbert Ehringer and Oleh Hornykiewicz, 1960
• Dopamine deficiency in the striatum
• Cotzias and colleagues, 1967,1969
• Making levodopa clinically useful in patient with PD
Facts about PD
• Annual incidence: 60,000 new cases/yr
• Increase with age (3% population >65 years old)
• Slightly more common in men
• Mean age at onset: 60 years old
• 85% of patients are over 65 years old
Risk of PD
Increased risk
Decreased risk
•• Age
Caffeine intake
•• High Bodycigarettes
Smoking Mass Index
• Male gender
• Anti-oxidants in diet
• Family history
• Depression
• Environment factors
• rural living
• well-water drinking
• welding
• head injury
Incidence Prevalence
PATHOLOGY OF PD
• Two major neuropathologic findings in PD :
• Loss of pigmented dopaminergic neurons in the substantia nigra
• The presence of Lewy bodies

• Lewy bodies are concentric, eosinophilic, cytoplasmic inclusions with peripheral

halos and dense cores.

• Alpha-synuclein is a major structural component of Lewy bodies.

PATHOLOGY of PD – Macroscopy
PATHOLOGY of PD – Microscopy
• Loss of pigmented dopaminergic neurons
Normal Parkinson’s disease

Normal substantia nigra Degeneration of nigral cells

• Histopathological hallmark: Lewy bodies

158
Gibb WR, Lees AJ. Neuropathol Appl Neurobiol 1989;15:27-44.
ETIOLOGY OF PD
• Most cases of PD are
believed to be due to a
combination of genetic and
environmental factors.
• Environmental factors :
• Influenza epidemic- van
Economo’s disease
• Being raised on a farm with
weel water
• Pesticide/herbicide/
manganese exposure
• MPTP toxin exposure
• Factors that modify the risk :
• Physical exercise
• Cigarette smoking,
• Caffeine consumption,
• Some NSAIDs (ibuprophen, but not
ASA)
• Higher level of uric acid in pheripheral
blood.
 GENETIC FACTORS
Locus
Age of
Gene (Chromosomal Inheritance Clinical phenotype
onset
position)
-
PARK1 (4q21-q23) Young AD Similar to IPD, rapid progression
synuclein
Symptomatic improvement following
PARK2 (6q25.2-
Parkin Young AR sleep, mild dystonia, good response
q27)
to levodopa, slow progression
Similar to
UCHL1 PARK5 (4p14) AD Similar to IPD
IPD

PINK1 PARK6 (1p35-p36) Young AR Benign course, levodopa-responsive

DJ1 PARK7 (1p36) Young AR Levodopa-responsive

Similar to IPD (LRRK2 mutations are
Similar to
LRRK2 PARK8 (12q12) AD the commonest cause of either
IPD
familial or ‘sporadic’ PD)

(1p36, 1p32, and PARK9: spasticity, dementia and

PARK9, 10, AR supranuclear palsy
2q36-q37,
and 11 (PARK9)
respectively ) PARK10: similar to IPD

Abbreviations: AD, autosomal dominant; AR, autosomal recessive; IPD,

idiopathic Parkinson’s disease; LRRK2, leucine-rich repeat kinase 2; PARK2,
parkin-encoding gene; PINK1, PTEN induced putative kinase 1; UCHL1,
Farrer MJ. Nat Rev Genet 2006;7:306-18. ubiquitin carboxyl-terminal esterase L1; UPS, ubiquitin-proteasome system.
de Lau LM, Breteler MM. Lancet Neurol 2006;5:525-35. 160
PATHOGENESIS OF PD
ENVIRONMENTAL FACTORS GENETIC FACTORS

PARK1 (α-synuclein) a-Synuclein

Oxidative stress Mitochondria PARK2 (Parkin) Related proteins?
MPTP Complex I PARK5 (UCH-L1)
Pesticides ROS PARK6 (PINK1)
Herbicides PARK7 (DJ-1) Altered protein
Bacterial toxins PARK8 (LRRK2, dardarin) conformation
Other genes

Ubiquitin proteasome
system dysfunction?
Toxic injury
Apoptosis
Protein aggregates
(Lewy bodies:
Inflammation good or bad?)
Excitotoxicity

NIGRAL CELL DEATH

BenMoyal-Segal L, Soreq H. J Neurochem. 2006;97:1740-1755.

Dawson TM, Dawson VL. J Clin Invest. 2003;111:145-151. Mouradian MM. Neurology. 2002;58:179-185.
PATHOPHYSIOLOGY OF PD
• Basal Ganglia structure :
• Caudate nucleus
• Putamen
• Globus pallidus
• Subthalamic nucleus
• Substantia nigra
• Ventrolateral nucleus of the thalamus
Neurons use neurotransmittes connecting
the various structures of basal ganglia
(acetylcholine, GABA, substance P,
enkepalin, glutamat).
• Basal Ganglia Loop :
• Motor loop : control of movement
• Oculomotor loop : control of eye movement
• Lateral orbito-frontal loop : control of social behaviour
• Dorsolateral prefrontal loop : control of executive function, planning, working
memory
• Anterior cingulate loop : role unclear
• Basal ganglia are involved in much more than just movement.
• This explains the cognitive and psychiatric problems commonly experienced by
those with PD.
PATHOPHYSIOLOGY OF PD
In PD, neurons that produce dopamine damaged
Insufficient dopamine disturbs the balance between dopamine
and other transmitters.

This reduces dopaminergic stimulation of the striatum

Direct pathway activity is reduced and indirect pathway activity

is increased
This leads to an increase in Gp medial (internal) activity and
therefore inhibition of the thalamus and cortex.

This is hypothesized to lead to the slowness of movement seen

in PD
BASAL GANGLIA CIRCUITS – Normal vs PD
DOPAMINE AND AGING

Onset Diagnosis
Dopaminergic neuron loss in PD
Dopaminergic Neurons

Nonmotor
% Remaining

Motor

Sleep
Olfactory*
Mood
Autonomic system

Presymptomatic phase Early nonmotor symptoms Specific symptoms

Time (years)
*Olfactory dysfunction may predate clinical PD by at least 4 years.

 Approximately 60-80% of dopaminergic

Halperin et al. Neurotherapeutics. 2009;6:128-140.
neurons are lost before the motor signs
Lang. Neurology. 2007;68:948-952. of PD emerge.
Ross et al. Ann Neurol. 2008;63:167-173.
Karakteristik umum Parkinson disease
GEJALA Stadium Pre Klinik
MOTORIK
Stadium Premotor
GEJALA NON (hanya muncul beberapa gejala non motoric)
MOTORIK
Stadium Motorik
(muncul gejala motoric)
02/02/2023 Department of Neurology FKKMK UGM - Dr. Sardjito Hospital 172
BRAAK STAGING

Pathological changes in PD can be devided into 6 stages:

• 1 & 2: certain structure in the brainstem, but not yet the substastia nigra
• 3 & 4: spreads to the midbrain and basal ganglia
• 5 & 6: spread to the cortex

Olanow, C. W. et al. Neurology 2009;72:S1-S136

Diagram diagnosis Parkinson Disease sesuai Kriteria movement disorder society 2015
Kriteria Eksklusi Absolut

• Unequivocal cerebellar abnormal

• Downward vertical supranuclear gaze palsy, or selective slowing of downward vertical saccades.
• Demensia Frontotemporal atau afasia primer progresif dalam 5 tahun perjalanan penyakit
• Gambaran gejala Parkinson yang terbatas pada anggota gerak bawah selama lebih dari 3 tahun
• Kemungkinan drug-induced parkinsonism berdasarkan Riwayat pengobatan sebelumnya
• Tidak respon terhadap dosis tinggi levodopa meskipun derajat penyakit sedang – berat
• Unequivocal cortical sensory loss, clear limb ideomotor apraxia, atau progresif afasia. (CBD)
• Gambaran normal pada neuroimaging pada sistem presinaptik dopaminergik (tremor esensial)
• Penemuan kondisi alternatif yang dapat menyebabkan gejala Parkinson dan memungkinkan berhubungan
dengan gejala.
Red Flags
(1) Progresifitas yang cepat dari gangguan berjalan yang membutuhkan kursi roda dalam 5 tahun (PSP)
(2) Tidak terdapat perbaikan gejala atau tanda motoric lebih dari 5 tahun yang sudah diberikan terapi
(3) Disfungsi bulbar awal: disfonia berat atau disartia atau disfagia berat dalam 5 tahun pertama (MSA)
(4) Disfungsi pernafasan inspirasi : inspirasi stridor atau tanda pernafasan sering (MSA)
(5) Kegagalan fungsi otonom berat dalam onset 5 tahun.
(a) Orthostatic hypotension (MSA-A)
(b) Retensi urin berat atau inkontenensia yang tidak berkaitan dengan kondisi lain
(6) Kejadian jatuh berulang (>1x dalam setahun) dikarenakan gangguan keseimbangan dalam onset 3 tahun
(PSP/ MSA-C)
(7) Distonia atau kontraktur pada tangan atau kaki pada 10 tahun pertama (CBD)
(8) Tidak terdapat gejala non motoric dalam 5 tahun durasi penyakit termasuk : gangguan tidur, gangguan
otonom, hyposmia atau gangguan psikiatri.
(9) Gejala jaras pyramidal lain yang tidak dapat dijelaskan, namun tidak termasuk asimetris reflek pada plantar
ekstensor (NPH)
(10) Bilateral simetris parkinsonism (Vaskuler)
Kriteria pendukung

1. Respon yang bermakna pada terapi dopaminergik

a. perbaikan saat peningkatan dosis dan pemburukan saat dosis
diturunkan
b. ditandai adanya fluktuasi hilang timbul dan predictable end of dose
wearing off.
2. Levodopa-induced dyskinesia
3. Resting tremor pada salah satu lengan
4. kehilangan fungsi olfaktori atau cardiac sympathetic denervation
Diagnosis Parkinson Disorder
Anamnesis Parkinson
MOTOR SYMPTOMS OF PD
Tremor at rest
• The most common in early symptom (75%)
• Tremor begin in one arm at a 4-6 Hz.
• Pill-rolling finger movement.
• Rest tremor disappears with action or sleep
• Tremor increases with walking, anxiety,
mental activity and excitement.
• When tremor occur in isolation for many
years without bradykinesia or rigidity
(TREMOR-DOMINANT PD) , the
prognosis is better
Brady-/hypo-/akinesia
• Bradykinesia :
• slowed movement, e.g. walking
speed, slowed finger tapping
• Hypokinesia :
• small movement, e.g. small steps,
soft speech
• Akinesia :
• difficulty to initiating movement
/lack of movement, e.g. start
hesitation when getting up to
walk, freezing when walking
through doorway
Bradykinesia
• Bradykinesia can affect:
• Large voluntary movement :
• standing up, walking, turning in bed
• Fine voluntary movement :
• difficulty fastening button or cutting
food,
• smaller and more cramped writing
• Autonomic movement :
• constipation, dysphagia
• Automatic movement :
• reduced arm swinging,
• slow blingking, loss of facial expression
 Hipokinesia dan bradikinesia
• Bradikinesia disebabkan oleh
gangguan pada jaras cortico-
striato-pallido-thalamic.

• Contohnya pada :
• Parkinson disease : berkurangnya
dopamine
• Obat neuroleptic : blokade
reseptor dopamine
• Wilson disease : kerusakan GPI
Hipokinesia dan bradikinesia
• Hypokinesia = Poverty of movement
• Berkurangnya gerakan spontan pada bagian yang terkena dan kegagalan untuk
terlibat secara bebas dalam gerakan alami tubuh
• Gerakan alami tubuh : menengok saat melihat ke samping, berkedip, menelan
ludah
• Membedakan dg lesi jaras kortikospinal : Kekuatan otot normal

- Bradikinesia = Slowness of movement

- Lambat dalam memulai gerakan dan sepanjang proses gerakan

- Hypokinesia dan bradykinesia yang parah menyebabkan akinesia

Rigidity
• Increase of muscle tone when
the examiner moves the
patients limbs.
• This increased resistance to
passive movement is equal in
all directions.
• ‘Cogwheel phenomena’ .
• Rigidity of the passive limb
increases while another limb
is engaged in voluntary active
movement.
Stoop Posture
• Its begin in the arms and
spreads to involve the entire
body:
• the head is bowed,
• the trunk is bent forward,
• the back is kyphotic,
• the arms are held in front
of the body, and
• the elbows, hips, and
knees are flexed.

FIGURE 1. Parkinson patient body posture. A: Front view. B: Side view.

Loss of Postural Reflexes
• Not useful as diagnostic signs because it
appears several years into the disease
• Person who has lost postural reflexes
could fall
• No effective treatment
• The pull-test :
• examiner who stands behind the
patient, gives a sudden firm pull on
the shoulders and checks for
retropulsion.
• normal person can recover within one
two step.
Gangguan mempertahankan postur dan
keseimbangan
• Gangguan ini paling banyak ditemukan pada pasien dengan
Parkinson Disease
• Terjadi fleksi involunter pada trunkus, leher dan ekstremitas yang
memunculkan postur khas pada PD.
• Gangguan postur dan keseimbangan pada lesi ganglia basalis tidak
disebabkan pada lesi labirin, propriosepsi atau visual.
Freezing Phenomenon
• The feet seem as if glued to
the ground.
• Freezing occurs suddenly and
is transient, no more than
several seconds.
• Freezing occurs when :
• begin to walk (start
hesitation)
• attempt to turn while
walking,
• approach a destination
Rigiditas dan gangguan tonus

• Pada rigiditas, otot terus menerus kaku dan tegang.

• Terjadi kontraksi otot involunter yang terjadi terus menerus terutama saat
berjalan dan bahkan saat pasien beristirahat
• Rigiditas vs spastisitas, pada rigiditas :
• Resistensi terhadap gerakan pasif terjadi sejak awal  Lead-pipe rigidity vs clasp-knife
spasticity
• Reflex tendon tidak meningkat
• Rigiditas melibatkan flexor dan extensor
• Dibarengi cogwheel-phenomenon

• Rigiditas dapat ditemukan pada PD, Wilson disease, PSP, Fahr disease
Non motoric symptom Parkinson Disease
Non motoric symptom Parkinson Disease
Non-Motor Symptoms of PD(1)
Neuropsychiatric symptoms Autonomic symptoms
Depression, apathy, anxiety Bladder disturbances
Anhedonia Urgency
Attention deficit Nocturia
Hallucinations, illusions, delusions Frequency
Dementia Sweating
Obsessional behaviour (can be drug-induced) and Orthostatic hypotension
repetitive behaviour Falls related to orthostatic hypotension
Confusion Coat-hanger pain
Delirium (could be drug-induced) Sexual dysfunction
Panic attacks Hypersexuality (likely to be drug-
induced)
Sleep disorders Erectile impotence
Restless legs and periodic limb movements Dry eyes
REM sleep behaviour disorder
Non-REM sleep-related movement disorders
Excessive daytime somnolence
Vivid dreaming
Insomnia
Sleep-disordered breathing
196
Adapted from Chaudhuri KR, et al. Lancet Neurol 2006;5:235-45.
Non-Motor Symptoms of PD(2)
Gastrointestinal symptoms Sensory Symptoms
(overlap with autonomic symptoms) Pain
Drooling Paraesthesia
Ageusia Olfactory disturbance
Dysphagia and choking
Reflux, vomiting Other symptoms
Nausea Fatigue
Constipation Diplopia
Unsatisfactory voiding of bowel Blurred vision
Faecal incontinence Seborrhoea
Weight loss
Weight gain (possibly drug-
induced)

197
Adapted from Chaudhuri KR, et al. Lancet Neurol 2006;5:235-45.
Gejala non motorik pada Parkinson akibat perjalanan
penyakit atau berhubungan dengan terapi
Domain Gejala
Otonom Variasi tekanan darah dengan hipotensi ortostatik, takikardia, gangguan
berkemih (seperti urgensi, frekuensi), nocturia, disfungsi seksual,
hypersexual (seperti pada drug induced), paroxysmal sweating, Seborrhea,
Serostomia (mata kering), facial Hyperemia, midriasis, pallor.
Gastrointestinal Menetesekan air liur, agesia, disfagia, konstipasi, inkontenensia alvi,
(Sebagian berhubungan eructation, meteroismus
dengan disotonimia)
Sleep REM gangguan tidur (RBD), waktu tidur berlebihan, vivid dream, insomnia,
periodic limb movement (PLM), Restless legs syndrome (RLS)
Neuropsikiatri Gangguan kognitif ( mild cognitive impairment dan demensia), depresi,
anhedonia, apatis, anxiety, gangguan panik, delirium, halusinasi, ilusi,
delusi, impulse control disorder (ICD), Dopaminergic dysregulation
syndrome, dopamine agonist with drawl syndrome (DAWS).
Sensorik Nyeri, gangguan penciuman, gangguan penglihatan, visual diskriminasi
Miscellaneous Fatigue, diplopia, weight loss atau weight gain
Gejala non motor

Zesiewicz, T. A. 2019. Parkinson Disease. CONTINUUM: Lifelong Learning in

Neurology, 25(4), 896-918.
199
CLINICAL EVALUATION
SCALES AND SCORES
Hoehn and Yahr Staging
Stage One
1.  Signs/symptoms on one side only
2.  Symptoms mild
3.  Symptoms inconvenient but not
disabling
4.  Usually presents with tremor of one
limb
5.  Friends have noticed changes in
posture, locomotion and facial
expression
Stage Two
1.  Symptoms are bilateral
2.  Minimal disability
3.  Posture and gait affected
201
Stage Three
 1. Significant slowing movements
 2. Early impairment of equilibrium on
walking or standing
 3. Generalised dysfunction that is
moderately severe 
Stage Four
 1.  Severe symptoms 
 2.  Can still walk to a limited extent 
 3.  Rigidity and bradykinesia
 4.  No longer able to live alone
5.  Tremor may be less than earlier
Stage Five
 1.  Cachectic stage
 2.  Invalidism complete
3.  Cannot stand or walk
 4.  Requires constant nursing care
Modified Hoehn and Yahr Scale
 Schwab and England
Activities of Daily Living
• 100% – Completely independent. Able to do all chores without slowness, difficulty or
impairment.
• 90% – Completely independent. Able to do all chores with some slowness, difficulty or
impairment. May take twice as long.
• 80% – Independent in most chores. Takes twice as long. Conscious of difficulty and slowing.
• 70% – Not completely independent. More difficulty with chores. Three to four times as long on
chores for some. May take large part of day for chores.
• 60% – Some dependency. Can do most chores, but very slowly and with much effort. Errors.
Some chores impossible.
• 50% – More dependent. Help with 1/2 of chores. Difficulty with everything.
• 40% – Very dependent. Can assist with all chores, but do few alone.
• 30% – With effort, now and then does a few chores alone or begins alone. Much help needed.
• 20% – Nothing alone. Can do some slight chores with some help. Severe invalidity.
• 10% – Totally dependent, helpless.
• 0% – Vegetative functions such as swallowing, bladder and bowel function are not
functioning. Bedridden.

203 FJ, Donaldson MC, eds. Third Symposium of Parkinson’s Disease.

Gillingham
Edinburgh, Scotland: E&S Livingstone; 1969:152-7.
Unified Parkinson’s Disease Rating Scale
I. Mentation, Behaviour, Mood
• Non-motor symptoms with one question on intellect, one on
thought disorders, one on depression, and one on motivation
II. Activities of Daily Living (ADL)
• 13 questions, almost all about motor symptoms
• Two questions on salivation (autonomic function) and sensory
complaints
III. Motor Examination
• Motor symptoms
IV. Treatment Complications
• Yes/no questions on anorexia, nausea, vomiting and sleep

A total of 199 points are possible, with 199 representing total

disability and 0 meaning no disability
204 Disorder Society Task Force on Rating Scales
Movement
for Parkinson’s Disease. Mov Disord 2003;18:738-50.
 Instrumen untuk pemeriksaan umum, penilaian kualitas
hidup dan komplikasi pada penyakit parkinson
Instrumen Singkatan Pengukuran Tingkat Keparahan MCID Tips singkat
Hoehn and Yahr HYS Penilaian Umum Ringan : HYS 1 dan 2 Tersedia versi
Scale Sedang : HYS 3 modifikasi HYS
Berat : HYS 4 dan 5
Unified UPDRS Pemeriksaan Bagian II: 0.7 Pada kebanyakan
Parkinson’s umum, 4 skala (early PD), 2 poin kasus, jumlah
Disease Rating sub: (HYS 1&2), 3 poin skoring dihitung
Scale Bagian I: Mental, (HYS2.5-3) dengan
perilaku dan Bagian III: 2.4 penjumlahan
mood (early PD), 5 (HYS bagian I+II+III
Bagian II: aktivitas 1-3), 3.5
kehidupan sehari (advanced)
–hari
Bagian III:
pemeriksaan
motoric
Bagian IV:
komplikasi terapi

MCID, minimal clinically important difference

Instrumen Singkatan Pengukuran Tingkat Keparahan MCID Tips
singkat
Movement MDS- Penilaian umum, 4 Skoring : Perubahan Skor: Memecahk
Disorders UPDRS skala sub: Ringan Sedang Berat Perbaikan Perburukan an
Society- Bagian I: B I <10 11-21 >22 BI: -2.64 2.45 beberapa
Sponsored pengalaman non- BII <12 13-29 >30 BII -3.05 2.51 ambiguitas
Unified motor pada BIII < 32 33-58 > 59 BIII -3.25 4.63 dari
Parkinson’s kehidupan sehari- UPDRS;
Disease Rating hari subskala
Scale Bagian II: seharusnya
Pengalaman motoric ditafsirkan
pada kehidupan terpisah
sehari – hari
Bagian III:
Pemeriksaan
motoric
Bagian IV:
Komplikasi motorik

MCID, minimal clinically important difference

Instrumen Singkatan Pengukuran Tingkat Keparahan MCID Tips singkat
Parkinson’s PDQ-39 Penyakit-spesifik Perubahan Salah satu
Disease Kesehatan yang skoring: instrument paling
Questionnaire berhubungan Peningkatan -4.72 relevan
(39 items) dengan kualitas poin
hidup yang Perburukan 4.22
dikelompokkan poin
dalam 39 item ke
dalam 8 domain
yang membuat
indeks
kesimpulan
Parkinson’s PDQ-8 Penyakit-spesifik Penignkatan -5.94 Ini merupakan
Disease Kesehatan yang (range: -4.6 -10) versi singkat dari
Questionnaire (8 berhubungan Perburukan 4.91 PDQ-39
items dengan kualitas poin
hidup. Terdapat 8
pertanyaan untuk
membuat index
kesimpulan

MCID, minimal clinically important difference

Instrumen Singkatan Pengukuran Tingkat Keparahan MCID Tips singkat
Nonmotor NMSS Menilai 9 domain; Tidak ada atau ringan : 0- Terdapat juga
Symptoms Scale kardivaskular, 20 poin instrument
sleep/fatigue, Sedang : 21-40 poin skrining (NMSQ):
mood/kognitif, Berat : 41-70 poin NMSS yang
masalah persepsi, Sangat berat: > 71 poin menilai
atensi & memori, pemberatan dan
gastrointestinal- frekuensi
urinary, fungsi
seksual dan aneka
ragam
Parkinson’s PDSS-2 Kualitas tidur Tidak ada atau minal : 0- Peningkatan -3.44 PDSS-2 adalah
Disease Sleep keseluruhan; 3 10 poin poin versi
Scale 2nd version sub skala pada Ringan – sedang: 11-20 Perburukan 2.07 pembaharuan
masalah motoric poin poin dari PDSS yang
pada malam hari, Berat: > 20 poin asli
penyakit
Parkinson pada
malam dari dan
gangguan tidur.

MCID, minimal clinically important difference

Instrumen Singkatan Pengukuran Tingkat Keparahan MCID Tips singkat
Unified UDysRS Penilaian Bagian III: UDysRS
Dyskinesia keseluruhan pada Peningkatan 2.32 merupakan skala
Rating Scale dyskinesia: poin dyskinesia yang
Bagian I: Riwayat Perburukan 2.76 paling
ON-Diskinesia poin komprehensif
Bagian II: Riwayat
OFF-dystonia
Bagian III:
gangguan objektif
Bagian IV:
Disabilitas
objektif

MCID, minimal clinically important difference

 CLINICAL APPROACH TO PARKINSONISM
• History
• Age at onset : mean is about 60 in PD
• Occupation : any exposure risk to toxin, e.g. manganes in miners, pesticides in
farmers.
• Character of onset: acute or gradual
• Precipitant at onset: stroke, infection, hypoxia
• Progression: static, rapid, gradual progression
• Family history, if positif, what is the mode inheritance?
• Drug history, esp. dopamine receptor blocking drugs
• Pattern of motor symptoms: asymmetric? Is tremor present? Are legs the main
part of the body affected – lower body parkinsonism? Is there gait disturbance
and postural instability?
• Examination
• Head :
• observe for reduced facial expression, reduced blink rate, frontalis
overactivity
• check eye movements and saccades, limitation of vertical
• listen to speech and breathing (hypophonic speech, stridor)
• assess neck for rigidity
• Limbs :
• assess for rigidity, is it asymmetric?
• assess for resting and postural tremor,
• look for bradykinesia, note any asymmetric
• Arms : tap thumb and forefinger together, open and close fist, pronate and
supinate the arms
• Legs : tap the feet while sitting, lift the leg up and dwn, stamp the foot on the
ground as fast as possible
• look for cerebelar signs: dysmetria, rebound, ataxia
• Gait
• Watch the patient stand, is able to do unassisted?
• Note the posture : flexed, anterocollis, leaning to the side
• Assess gait initiation, step size, arm swing, presence of freezing
• Assess ability to turn round
• Assess heel-toe walking
• Assess postural instability: pull test
• Others
• Check blood pressure on lying or standing
• Check handwriting, cognitive assessment
DIAGNOSIS (1)

• The diagnosis of PD may be difficult in the early

stages1
• There is no diagnostic test for Parkinson disease
• UK PDS Brain Bank Criteria is a set of well-validated
criteria to assist in the clinical diagnosis of PD
• UK PDS Brain Bank Criteria have specificity and
sensitifity of 98,1% and 90,4%.

1. Olanow CW, et al. Neurology 2001;56(suppl 5):S1-S88. 2. Lang AE, Lozano AM. The New England Journal 1998; 339:1044-1053
DIAGNOSIS (2)

• Some tests can assist in the differential diagnosis of

PD but the error rate in diagnosis in specialist
movement disorders ranges from 10-20%.
• Most common alternative diagnosis are ET, drug-
induced parkinsonism, vascular parkinsonism PSP,
MSA, CBD.
UK PDS Brain Bank Criteria
Step 1. Diagnosing Parkinsonian syndrome
Bradykinesia and at least one of the following
• Muscular rigidity
• Resting tremor (4-6Hz)
• Postural instability unrelated to primary visual, cerebellar,
vestibular or propioceptive dysfunction
Step 2. Exclusion criteria of PD
History of stroke, trauma, encephalitis, drugs or toxin exposure,
presence of cerebral tumor or hydrocephalus on imaging, babinski
sign, cerebellar sign, gaze palsy early severe autonomic dysfunction or
dementia, negative response to large dose of levodopa, sustained
remission
Step 3. Supportive criteria of PD
3. Supportive criteria of PD
• Three or more required for diagnosing of definite PD
• Unilateral onset
• Resting tremor present
• Progressive disorders
• Persistent asymmetry affecting the side of onset most
• Excellent response to levodopa
• Severe levodopa induced chorea
• Levodopa response for over 5 years
• Clinical course of over 10 years
Recommendation of
Clinical Diagnostic
• UK PDS Brain Bank Criteria (Grade B)1
• PD should be suspected in people presenting with tremor, stiffness,
slowness, balance problems and/or gait disorders (Grade D;GPP)2

• Patients with suspected Parkinson’s disease should be referred

untreated to specialist in movement disorders to make the
diagnosis (Grade C3;Grade B2)

1
European Journal of Neurology, 2013
2
Canadian Journal of Neurological Sciences, 2012
3
Scottish Intercollegiate Guidelines Network, 2010

217
02/02/2023
Department of Neurology FKKMK UGM - Dr. Sardjito Hospital

Anindhita, T. & Wiratman, W. 2017. Penyakit Parkinson.

In: Eva, D., Dyah, T. & Ni Nengah, R.A. editor, Buku Ajar
Neurologi. 1st ed., Departemen Neurologi Fakultas
Kedokteran Universitas Indonesia, Jakarta.
220
Kelebihan dan Kekurangan Obat Parkinsonism
Kelebihan dan Kekurangan Obat
Parkinsonism
Obat Parkinson
Terapi MSA
Mekanisme Obat Parkinson
02/02/2023
Department of Neurology FKKMK UGM - Dr. Sardjito Hospital

Anindhita, T. & Wiratman, W. 2017. Penyakit Parkinson.

In: Eva, D., Dyah, T. & Ni Nengah, R.A. editor, Buku Ajar
Neurologi. 1st ed., Departemen Neurologi Fakultas
Kedokteran Universitas Indonesia, Jakarta.
228
 Anindhita, T. & Wiratman, W. 2017. Penyakit Parkinson.
In: Eva, D., Dyah, T. & Ni Nengah, R.A. editor, Buku Ajar
Neurologi. 1st ed., Departemen Neurologi Fakultas
Kedokteran Universitas Indonesia, Jakarta.

02/02/2023 Department of Neurology FKKMK UGM - Dr. Sardjito Hospital 229

02/02/2023
Department of Neurology FKKMK UGM - Dr. Sardjito Hospital

Anindhita, T. & Wiratman, W. 2017. Penyakit Parkinson.

In: Eva, D., Dyah, T. & Ni Nengah, R.A. editor, Buku Ajar
Neurologi. 1st ed., Departemen Neurologi Fakultas
Kedokteran Universitas Indonesia, Jakarta.
230
02/02/2023
Department of Neurology FKKMK UGM - Dr. Sardjito Hospital

Anindhita, T. & Wiratman, W. 2017. Penyakit Parkinson.

In: Eva, D., Dyah, T. & Ni Nengah, R.A. editor, Buku Ajar
Neurologi. 1st ed., Departemen Neurologi Fakultas
Kedokteran Universitas Indonesia, Jakarta.
231
 Manajemen berdasarkan stadium penyakit
o Pemberian terapi inisiasi segera diberikan saat diagnosis ditegakkan
o Oral levodopa merupakan gold standard therapy untuk Parkinson Disease, walaupun
sekitar 40% pemakaian levodopa untuk Parkinson disease dapat menyebabkan Levodopa
– Induced Dyskinesia (LID) setelah pemakaian 4 – 6 tahun.
o Pada usia muda dominan gejala motorik dapat dimulai dengan MAO B Inhibitor atau
dopamine agonis kemudian dapat ditambahkan levodopa.

A. Gejala motor dan non motor yang paling relevan mengarah kecurigaan tidak adekuat dalam control penyakit Parkinson
(diurutkan berdasarkan hal paling penting)
Motor
1. tingkat fluktuasi motor yang menyulitkan
2. Gejala “off” 2 jam per hari
3. Paling sedikit 1 jam per hari terjadi dyskinesia
4. Terdapat komplikasi motorik pada penggunaan dosis
multipel oral levodopa per hari
Non Motor
1a. Halusinasi/psikosis yang menyulitkan
1b. Fluktuasi gejala non motor
2a. Impuls control disorder
2b. Gangguan tidur pada malam hari pada level yang
merepotkan
3a. Depresi level yang menyulitkan
3b. Mengantuk di siang hari di level yang menyulitkan
B. Pendekatan pragmatis: pertanyaan
untuk pasien
Apakah gejala Anda cukup terkontrol?
Ketika Anda bangun di pagi hari,
apakah pergerakan anda baik? Jika
tidak, berapa lama waktu yang
dibutuhkan untuk
obat anda mulai bekerja?
Ketika obat anda mulai bekerja, apakah Wearing Off (gejala motor atau non
tetap efektif sampai dengan dosis
selanjutnya?, jika tidak, berapa lama
anda merasakan gejala?
Jika jawabannya TIDAK: potensial
bermasalah
Insufisiensi efek – dimungkingkan
pasien mengalami underdosed
Gejala OFF pada pagi hari yang
menyulitkan
motor)
Solusi masalah
1. Tingkatkan dosis dopamine agonis
2. Tingkatkan dosis levodopa
1. Konsumsi levodopa dosis pagi hari
pada saat bangun tidur.
2. Tingkatkan dosis dopamine agonis
(gunakan lebih pada sore)
3. Jika dosis levodopa pada pagi lebih
kurang efektif dibandingkan dengan
waktu lain – tingkatkan dosis
tunggal tersebut
1. Tingkatkan dosis dopamine agonis
2. Tingkatkan frekuensi dosis
levodopa
3. Tambahkan COMT Inhibitor
(entacapone, tolcapone)
4. Tambahkan MAO-B Inhibitor
(Selegiline, rasagiline)
B. Pendekatan pragmatis: pertanyaan
untuk pasien
Apakah efek dari obat yang dikonsumsi
membutuhkan waktu lama untuk
bereaksi atau anda benar – benar tidak
merasakan efek sama sekali?
Apakah anda merasakan Gerakan
involunter yang berlebihan Ketika obat
mulai bekerja?
Apakah kegiatan di malam hari dapat
diterima baik?
Jika jawabannya TIDAK: potensial Solusi masalah
bermasalah
Delayed “ON” 1. Indikasi penggunaan levodopa
Failed “ON” paling tidak 30-45 menit sebelum
atau setelah makan (tidak
bersamaan dengan makan)
2. Tambahkan prokinetic
(domperidone)
3. Eksklusi Helicobacter pylori dan
/atau SIBO syndrome
Diskinesia 1. Berikan levodopa dosis rendah dan
lebih sering
2. Tambahkan amantadine
Gejala “OFF” pada malam hari yang 1. Berikan segera levodopa pada saat
menyulitkan terbangun di malam hari
2. Tingkatkan dopamine agonis (pada
dosis di sore hari)
Karakteristik pasien penyakit Parkinson yang memenuhi syarat
mendapatkan terapi bantuan alat perangkat tingkat lanjut
Motor Non Motor Fungsi
1. Level yang menyulitkan pada 1. Fluktuasi Gejala Non motor Membutuhkan bantuan untuk
fluktuasi gejala motorik 2. Impulse control disorder beraktivitas kehidupan sehari –
2. Minimal 1 jam per hari gejala 3. Gangguan tidur malam hari hari, setidaknya beberapa kali
dyskinesia yang menyulitkan berat
muncul 4. Disfagia berat dan jatuh
3. Minimal 2 jam per hari untuk berulang
gejala “OFF” 5. mengantuk berat pada siang
4. Periode “OFF” postural hari
instability 6. Tingkat kecemasan yang
5. Distonia dengan nyeri merepotkan
6. Freezing gait selama waktu
“OFF”
7. Multiple dosis levodopa
dalam sehari
 Pendekatan multidisiplin dan tim di semua
tahap
Perawat khusus 1. Perawat khusus penyakit Parkinson
2. Sentral koordinasi pada multidisiplin tim
3. Selalu kontak dekat dengan pasien dan keluarganya
fisioterapi 1. Melatih postur, gait dan keseimbangan, mencegah jatuh; individual sesi rehabilitasi 2-3
kali dalam seminggu dapat menurunkan risiko jatuh
2. Mebantu pasien mempertahankan fungsi bernafas yang baik dan mengatasi nyeri.
Terapi bicara 1. Membantu mengatasi kesulitan komunikasi, Lee siilverman voice treatment
menunjukan dapat menurunkan gejala hipofonia dan diastria hipokinetik
2. Melatih otot ekspirasi untuk menurunkan kejadian aspirasi
3. Melatih ekspresi wajah
Terapis okupasi Melatih aktivitas fungsional sehari – hari dengan mencari cara untuk dapat Kembali bekerja,
melakukan hobi yang pada akhirnya bertujuan untuk menjaga tetap indipenden
Psikologi Menggali kondisi penderita melalui caregiver dan
kemungkinan adanya problem emosional akibat
penyakitnya.
Pekerja sosial Menganalisa kondisi social dan membantu menilai
psikososial
Mmemberikan bantuan dan informasi jika pasien diperlukan
untuk dilakukan nursing home
DIFFERENTIAL DIAGNOSIS OF
PARKINSONISM
Differential Diagnosis of Parkinsonism
Primary or idiophatic parkinsonism
Parkinson disease sporadic and familial
Secondary or symptomatic
parkinsonism
Drug-induced: dopamine antagonists and
depletors
Hemiatrophy-hemiparkinsonism
Hydrocephalus: NPH-Normotensive Pressure
Hydrocephalus
Hypoxia
Infectious: postencephalitic
Metabolic: parathyroid dysfunction
Toxin: Mn, CO, MPTP, cyanide
Trauma
Tumor
Vascular: multi-infarct state
Parkinson-plus syndromes
PSP-Progressive supranuclear palsy
CBD-Cortical-basal degeneration
MSA-Multiple system atrophy syndromes
   Striatonigral degeneration
   Shy-Drager syndrome
   Olivopontocerebellar degeneration
Dementia syndromes
   Alzheimer disease
   DLB-Diffuse Lewy body disease
   Frontotemporal dementia
Heredodegenerative diseases
Hallervorden-Spatz disease
Huntington disease
Neuroacanthocytosis
Wilson disease
PD vs. ET
Parkinson’s disease Essential tremor
• Resting tremor • Tremor with no other sign of
• parkinsonism
Clear asymmetry
• Presence of a head or voice tremor
• Presence of bradykinesia or rigidity
• Strong and usually autosomal
• Leg tremor
dominant family history
• Improvement with dopaminergic
• Improvement with alcohol
treatment

 Both PD and ET have a kinetic and rest component

 Kinetic tremor can interfere with rapid alternating movements
 Cogwheel rigidity is rare in ET

Deuschl G, et al. Mov Disord 1998;13(Suppl 3):2-23.

Chaudhuri KR, et al. J Neurol Neurosurg Psychiatry 2005;76:115-7.
Recommendation of Neuroimaging

• Transcranial sonography is recommended (Grade A)1

• MRI 1.5 T and SPECT recommended (Level A)1
• PET is insufficient evidence (Grade U)1,2
• TCS, CT Scan, MRI should not be routinely applied in the
diagnosis of idiopathic PD (Grade C)3

1
European Journal of Neurology, 2013
2
Canadian Journal of Neurological Sciences, 2012
3
Scottish Intercollegiate Guidelines Network, 2010

240
NEURODEGENERATIVE ATYPICAL
PARKINSONISM
Dementia Lewy Bodies
Dementia
Lewy Bodies
Multi System Atrophy

Patofisiologi MSA
 Multiple System Atrophy (MSA)

 Epidemiology
 Prevalence : 4 per 100,000
 Median age of onset is 55-60
 Males and females are equally affected
 Mean survival 6-9 years from symptom onset
 Pathology
 Hallmark is glial cytoplasmic inclusions contaning alfa synuclein in basal ganglia, cerebellar and
motor cortex.
 Clinical Features
 MSA-P : parkinsonism with signs of autonomic failure
 MSA-C : cerebellar signs occur with autonomic failure
 Usually poorly responsive to levodopa.
 Tend to exclude diagnosis of MSA : dementia, hallusination, positive family history, gaze paresis.
Multi System Atrophy:
Gejala MSA
Multi System Atrophy: Diagnosis MSA
Diagnosis MSA
Pemeriksaan Imaging MSA
Prognosis
Prognosis
Faktor Risiko MSA
Faktor Risiko MSA
Faktor Risiko MSA
Pathogenesis Alpha Synuclein
High IQ related to synucleopathy
Epidemiologi MSA
Genetik pada MSA
MSA
MSA
Pogressive Supranuclear Palsy (PSP)
 Epidemiology
 Prevalence of about 6/100,000
 Males and females are equally affected
 Median age of onset is 63, gradual onset
 Mean survival from symptom onset to death is 7 years,
 Pathology
 Hallmark is abnormal aggregates of tau protein.
 Neurofibrillary tangles are present in substantia nigra, subtalamic nucleus and
midbrain.
 Clinical Features
 Symmetrical parkinsonism, usually witout tremor;
 Reduced blink rate markedly;
 Apraxia of eyelid opening;
 Vertical supranuclear gaze palsy;
 Postural instability leadin to early falls;
 Dysarthria and dysphagia;
 Lack of levodopa response
FIGURE 116.1. Progressive supranuclear palsy. Oculocephalic maneuver demonstrates
intact reflex down gaze in a patient unable to look down voluntarily.
Progressive Supranuclear Palsy

• New-onset neurologic, cognitive, or behavioral deficits progress in

absence of other identifiable causes in a patient ≥40 years of age.
• The core clinical features:
1. early postural instability with falls
2. oculomotor deficits, especially slowing of vertical saccades followed by a vertical
gaze palsy
3. akinesia/parkinsonism
4. frontal lobe impairments, including speech and language problems and behavioral
change
5. lack of response to levodopa
Progressive Supranuclear Palsy

• No laboratory or imaging studies are diagnostic. Imaging can be supportive

if there is predominant midbrain atrophy on MRI, but the absence of this
feature does not rule out the diagnosis of PSP, especially in patients at the
earliest stages or presenting with a non-Richardson syndrome phenotype
• Neuropathologic examination remains the gold standard for its definitive
diagnosis. The pathologic diagnosis of PSP is based upon the identification of
neurofibrillary tangles in a distribution considered typical for PSP.
• The diagnosis requires a high density of neurofibrillary tangles and neuropil
threads in the basal ganglia and brainstem. As mentioned earlier, astrocytic
plaques and tau-positive tufts of abnormal fibers are highly characteristic of
typical PSP
Progressive Supranuclear Palsy

• Diagnostic criteria — In 2017, the Movement Disorder Society (MDS)

proposed new diagnostic criteria for PSP. The MDS-PSP criteria include the
following components:
1. Basic features (inclusion and exclusion criteria)
2. Four core functional domains (ocular motor dysfunction, postural
instability, akinesia, and cognitive dysfunction) as characteristic
manifestations of PSP
3. Supportive clinical features that increase diagnostic confidence
4. Operationalized definitions for the core features and supportive features
5. Four levels of diagnostic certainty
Progressive Supranuclear Palsy

Imaging findings:
• (IF1) Predominant midbrain atrophy or hypometabolism
• (IF2) Postsynaptic striatal dopaminergic degeneration

• The anterior-posterior diameter of the suprapontine midbrain was significantly

lower in patients with PSP than in patients with idiopathic Parkinson disease
• The average midbrain area of patients with PSP (56 mm2) was significantly lower
than in patients with Parkinson disease (103 mm2)
• The midbrain-to-pons ratio, measured from the anterior-posterior distance on
midsagittal MRI, was significantly reduced for patients with pathologically
confirmed PSP
Progressive Supranuclear Palsy
Inclusion and exclusion criteria
Inclusion:
• Sporadic occurrence
• Age 40 years or older at onset of first PSP-related symptom

Exclusion:
• unexplained impairment of episodic memory, suggestive of Alzheimer disease
• unexplained autonomic failure (eg, orthostatic hypotension suggestive of multiple system atrophy or Lewy body disease)
• unexplained visual hallucinations or fluctuations in alertness, suggestive of dementia with Lewy bodies
• unexplained multisegmental upper and lower motor neuron signs, suggestive of motor neuron disease (pure upper motor
neuron signs are not an exclusion criterion)
• Sudden onset or step-wise or rapid progression of symptoms, in conjunction with corresponding imaging or laboratory
findings, suggestive of vascular etiology, autoimmune encephalitis, metabolic encephalopathies, or prion disease
• History of encephalitis
• Prominent appendicular ataxia
• Identifiable cause of postural instability (eg, primary sensory deficit, vestibular dysfunction, severe spasticity, or lower
motor neuron syndrome)
 Progressive Supranuclear Palsy

Mandatory imaging exclusion criteria

• Severe cerebral leukoencephalopathy
• Relevant structural abnormality (eg, normal pressure or obstructive
hydrocephalus; basal ganglia, diencephalic, mesencephalic, pontine or
medullary infarctions, hemorrhages, hypoxic-ischemic lesions, tumors, or
malformations)
Progressive Supranuclear Palsy

The MDS-PSP criteria specify four levels of diagnostic

certainty
• Definite PSP, the gold standard, can be diagnosed only postmortem by
neuropathological examination.
• Probable PSP is diagnosed when clinical features with a high specificity
are present.
• Possible PSP is diagnosed in the presence of clinical features considered
to substantially increase the sensitivity for PSP.
PSP
PSP
Manajemen PSP
• Trial levodopa disarankan untuk pengobatan simptomatik pasien
dengan PSP yang memiliki parkinsonisme untuk menentukan respon.
Meskipun regimen bervariasi, banyak ahli merekomendasikan
pengobatan dengan levodopa 1000 mg sampai 1200 mg per hari
(sampai 300 mg per dosis) jika ditoleransi selama setidaknya satu
bulan. Varian PSP dengan parkinsonisme dominan (PSP-P) seringkali
awalnya responsif, sedangkan PSP klasik dengan sindrom Richardson
(PSP-RS) umumnya tidak responsif terhadap levodopa.
• Efek samping levodopa: halusinasi visual, diskinesia, distonia
oromandibular, dan apraxia pada kelopak mata yang terbuka
• Suntikan toksin botulinum dapat secara efektif mengobati berbagai bentuk distonia
fokal dan air liur.
• Amantadine dapat memberikan manfaat terapeutik sementara untuk gaya berjalan,
termasuk kekakuan, dan disfagia pada sebagian kecil kasus dan juga dapat
membantu meneteskan air liur dan diskinesia.
• Zolpidem dikaitkan dengan peningkatan fungsi motorik pada 2 dari 10 pasien
dibandingkan dengan plasebo atau levodopa.
• Amitriptyline telah dinilai pada beberapa pasien dengan hasil variabel untuk
peningkatan fungsi motorik.
• Penghambat kolinesterase telah digunakan untuk mengobati jenis demensia tetapi
tidak ada data yang memadai untuk menentukan apakah memiliki manfaat pada PSP
CBD
Cortical Basal Degeneration (CBD)
 Epidemiology
 Prevalence of about 5-7/100,000
 Median age of onset is 63
 Males and females are equally affected
 Mean time from symptom onset to death is 8 years
 Amost always a sporadic condition

 Pathology
 Widespread depotition of hyperphosphorylated tau protein in the brain,
especially in substantia nigra and fronto-parietal cortex

 Clinical Features
 Motor symptom : asymmetric rigidity and bradykinesia affecting one limb;
Progressive dystonia often also affects the limb; Alien limb phenomena
 Eye sign : horizontal saccades usually abnormal, difficulty in initiating saccades
 Cortical dysfunction : apraxia is cardinal clinical feature in CBD; cortical
sensory loss, and dementia
PSP vs. CBD

Differences :
 PSP - symmetric parkinsonism, vertical supranuclear gaze palsy,
postural instability at onset and early falls, axial rigidity, wide-
based/slow/unsteady gait
 CBD - asymmetric parkinsonism, horizontal saccades abnormal,
asymmetric cortical signs, dystonic posturing of unilateral limb,
alien limb phenomena

Similarities :
 Relatively rapid disease progression
 Speech and gait disturbance
 Poorly responsive to levodopa therapy
Drug-Induced
Parkinsonism
Drug-Induced
Parkinsonism:
Obat yang dapat
menginduksi
Obat yang dapat menginduksi
 Drug-Induced Parkinsonism

Clinical Features
 Caused by exposure to a dopamine-receptor blocking agent
within 6 months of the onset of symptoms,

 Elderly patients are most susceptible,

 Drugs include: antipsychotics, anti-emetics

 Mild cases can frequently recover after cessation of the

offending drug.
TOOLS Drug Induced
SAS Simpson-Angus Scale
SAS Simpson-Angus Scale
SAS Simpson-Angus Scale
ESRS Extrapyramidal Symptom Rating Scale
ESRS Extrapyramidal Symptom Rating Scale
ESRS Extrapyramidal Symptom Rating Scale
AIMS Abnormal Involuntary Movement Scale
AIMS Abnormal Involuntary Movement Scale
 Vascular Parkinsonism

Clinical Features
 Acute or subacute onset with stepwise evolution of akinesia
and rigidity
 Presence of risk factors for cerebrovascular disease
 Two or more basal ganglia infarcts or more widespread
subcortical white matter lesions evident on neuroimaging
 No rest tremor
 Prominent postural instability and gait disorder
IMAGING PARKINSONISM
MRI findings for differential diagnosis in symptomatic parkinsonism
Imaging pada Parkinsonism
Imaging pada Parkinson Disorder
• Absent Swallow Tail Sign  Parkinson Disease & Dementia Lewy Bodies

Absence of Nigrosome-1, within the posterior third of the

substantia nigra
- increased iron content or decreased neuromelanin content
with decreased iron storage capacity
Imaging pada Progressive Supranuclear Palsy (PSP)

• Atrofi dan T2 hipointensitas pada putamen, terutama pada bagian

posterior dan globus palidus.
• Atrofi midbrain -> menunjukkan gambaran penguin silhouette atau
hummingbird pada sagittal dan Mickey Mouse atau morning glory sign
pada axial
• Atrofi pada pedunculus serebelar posterior,
• Dilatasi ventrikel tertius
• Hiperintensitas periaqueductal pada T2
Imaging pada Progressive
Supranuclear Palsy (PSP)

• Hipointensitas pada
putamen bagian posterior
dan globus palidus T2
Imaging pada Progressive Supranuclear Palsy (PSP)
Imaging pada Progressive Supranuclear Palsy (PSP): Hummingbird Sign

Midsagittal T1-weighted MRI of the brain showing midbrain tegmental atrophy without pontine
atrophy, associated with widening of interpeduncular cistern giving the impression of head and
body of a humming bird
Imaging pada Progressive Supranuclear Palsy (PSP)

Morning glory flower sign

Axial T1-weighted MRI of the brain showing increased lateral concavity of the midbrain
tegmentum resembling morning glory. Red arrow in the pictorial representation explains
the lateral concavity.
Imaging pada Progressive Supranuclear Palsy (PSP)

Axial T1-weighted MRI of the brain showing selective atrophy of the midbrain
tegmentum with relative preservation of tectum and cerebral peduncles resembling the
head of Mickey Mouse
Imaging pada Progressive Supranuclear Palsy (PSP)

• Atrofi pada pedunculus serebeli superior. Pedunculu serebeli

media biasanya masih normal
Imaging MSA
Imaging pada Multiple System Atrophy (MSA)

• Atrofi dan T2 hipointensitas pada putamen dan hiperintensitas

marginal pada putamen
• Atrofi serebelum dan atrofi pedunculus serebeli dengan atau tanpa
peningkatan sinyal pada T2 atau FLAIR
• Atrofi pons
• Tanda silang pada pontine, hiperintens pada T2 (hot-cross bun sign)
Imaging pada Multiple
System Atrophy (MSA)

• Hipointensitas pada
putamen dan hiperintens
pada pinggiran putamen
pada gambaran T2
Imaging pada Multiple
System Atrophy (MSA)

• Hiperintens pada tampaka

pedunculus serebeli
media, terkadang tampak
sebagai atrofi
Imaging pada Multiple
System Atrophy (MSA)

• Hiperintens pada
tampakan pedunculus
serebeli media, terkadang
tampak sebagai atrofi
Imaging pada Multiple System Atrophy (MSA)

• Atrofi pons
Imaging pada Multiple System Atrophy (MSA)

• Hot-cross bun sign

Imaging pada Corticobasal Degeretion (CBD)

• Atrofi putamen dan hipointensitas pada T2

• Atrofi kortikal asimetris, terutama pada level korteks motor-sensorik
primer, terkadang diikuti dengan gambaran hiperintents pada FLAIR
Imaging CBD
• Hipointens pada T2 di
putamen
Imaging CBD

asymmetric cortical atrophy, terutama pada korteks

motorik, sensorik primer
Imaging CBD
Perbedaan imaging PD, PSP, MSA
Pusat Autonomic
Imaging Movement Disorders
Imaging pada Parkinson Disorder
• Absent Swallow Tail Sign  Parkinson Disease & Dementia Lewy Bodies

Absence of Nigrosome-1, within the posterior third of the

substantia nigra
- increased iron content or decreased neuromelanin content
with decreased iron storage capacity
Huntington Disease
Hemibalismus
Wilson Disease
Wilson Disease
CHOREA
DEFINITION
• Chorea itself comes from the Greek word choeria, which means “dance”.
• Chorea is defined as brief irregular purposeless movements that flit and
flow from one bofy part to another.

• When choreic movements are more severe, they are called ballism.
• Athetosis describes sinuous, slow movements affecting distal limbs,
particularly in the arms.
CHOREA
• Berasal dari Bahasa Yunani yang artinya “menari”
• Gerakan involunter, aritmis dengan tipe menyentak, cepat dan
forcible
• Gerakan tidak bertujuan, tetapi sering disamarkan oleh pasien
menjasi seolah-olah bertujuan
• Biasanya gerakannya terpisah, tetapi jika sangat banyak, mereka
menjadi konfluen dan kemudian menyerupai athetosis
• Chorea dapat dibedakan dari myoclonus terutama berdasarkan
kecepatan, gerakan myoclonus jauh lebih cepat
CHOREA
• Chorea merupakan gejala mayor dari
Huntington disease.
• Dentatorubropallidolusyan atrophy
berhubungan dengan acantocytosis.
• Sydenham chorea merupakan kondisi
autoimun yang berhubungan dengan
infeksi streptococcus, terutama pada
wanita
• Paranoplastic chorea berhubungan
dengan sejumlah kecil kasus Ca Paru.
Biasanya muncul bersamaan dengan
dystonia, ballismus dan athetosis.
• Chorea yang muncul unilateral
biasanya disebabkan infark lakunar
CHOREA
• Lokasi lesi yang menyebabkan chorea masih belum dapat dipastikan
• Chorea atau ballismus yang transient disebabkan infark pada striatum, lebih
tepatnya nucleus caudatus kontralateral.
• Huntington Chorea disebabkan adanya lesi pada nucleus caudatus dan
putamen
• Sydenham Chorea diakibatkan adanya kelainan pada striatum
CAUSES OF CHOREA
 Inherited/degenerative disoders : HD, HD-like syndromes,
Wilson’s disease, neuroacanthocytosis, ataxia telangectasia,
SCA, benign hereditary chorea.
 Autoimmune : SLE, Bechet’s syndrome, vasculitis, Hashimoto’s
thyroiditis, syndeham’s chorea, PANDAS.
 Infection :HIV, abscess, Creutzfeld –Jakop disease.
 Drugs : dopamine receptor blocking drugs, levodopa,
stimulans, oral contraceptive pill, anticonvulsants,
anticholinergics, Calsium antagonists
 Structural lesions : vascular, tumour, demyelination in basal
ganglia.
 Metabolic : thyroid disorders, glucose, sodium, calsium,
manesium, chorea gravidarum
CLINICAL APPROACH OF CHOREA

• History
• Age at onset
• Character of onset : acute or gradual
• Drug exposure : dopamine receptor blocking drugs
• Family history
• Other neurologic symtoms : incoordination (Wilson’s disease, Huntington’s disease,
sensory disturbance (neuroacanthocytosis)
• Psychiatric/ behaviour disturbance
• Examination
• Observe patient at rest with arms relaxed, outstretched and while walking
• Note distribution of chorea (e.g. facial, hemichorea)
• Neurological signs : eye movement disorders ( Huntington’s disease), UMN
signs (brain lesion, HD), cerebellar signs (Wilson’s disease, HD) peripheral
neuropathy (neuroacanthocytosis)
• Systemic signs : rash, arthropathy (SLE), signs of thyroid disease, sunflowers
cataracts (Wilson’s disease).
Huntington's Disease
• HD is a autosomal dominant degenerative disease characterized by
progressive behaviour disturbance, dementia, and movement disorders
usually chorea.
• Huntington’s Chorea was described by G Huntington in 1872.
• Prevalence : 4-8/100.000.
• Mean age of onset : 40 year-old
• Men and women equally.
• UMN signs may be present.
Sydenham's Chorea
• SC remains the most common cause worldwide of acute chorea in children
• The usual age at onset of SC is 8 - 9 years.
• SC is the prototype of chorea resulting from immune mechanisms.
• Chorea occurs in 26% of patients with rhematic fever.
• The pathogenesis of SC is thought to be related to the existence of
molecular mimicry between streptococcal and central nervous system
antigens.
Vascular Chorea
• Usually related to ischemic or hemorrhagic
lesion of the basal ganglia and adjacent white
matter in the territory of the middle or the
posterior cerebral artery
• Often characterized as hemichorea.
• Incidence : 1% of patients with acute stroke.
• Vascular chorea often comes into remission
spontaneously.
Metabolic Chorea
• Chronic acquired or non-Wilsonian hepatolenticular degeneration was the
first well-characterized metabolic cause of chorea.
• The clinical picture is combination of neurological and hepatic
manifestations.
• The neurological findings include apathy, somnolence, parkinsonism,
tremor, myoclonus, asterixis, and chorea.
• Other possible metabolic causes of chorea are hypoglycemia,
hyperthyroidism, renal failure, and ketogenic diet.
Drug-Induced Chorea
• Levodopa is the most common form.
• The other drugs related to induction of chorea:
• Antiepileptic agents (hydantoin, lamotrigine, valproic acid)
• Antihypertensive agents
• Calcium channel blockers (cinnarize, flunarizine)
• Neuroleptics, Anticholinergics, etc
TREATMENT
• Neuroleptics are the best accepted to controll
symptoms of HC such as clozapine, quetiapine
and olanzapine.
• In Syndeham chorea, the first choice is valproic
acid or carbamazepine.
• Vascular chorea may require treatment with
neuroleptics or dopamine depleter.
• In women with chorea gravidarum:
• neuroleptic drugs cannot be given because
they may harm the fetus.
• pregnant patients may be given a mild
benzodiazepine tranquilizer.
ATAXIA
ATAXIA
• The term ataxia, meaning without order, refer
to disorganized, poorly coordinated or clumsy
movement.
• Ataxia is the type clumsiness produced by
dysfunction of the cerebellum or cerebellar
pathways.
• The core symptoms are difficulty with balance
and gait, clumsiness of the hands and
dysarthria.
• Ataxia is devided into sporadic and genetic.
SPORADIC ATAXIA (1)

a. Degenerative : MSA, progressive myoclonic epilepsy which ataxia is tipically a

part of this syndrome.
b. Strokes : lesions of the cerebellum or cerebellar pathways.
 Ataxic hemiparesis : thalamic lesion and posterior limb of the internal capsule, upper basis
pontin and cerebral peduncle.
 Hemisensory loss and hemiataxia : thalamic lesion.
 Isolated gait ataxia : pontomedullary junctin lesion.
c. umor : medulloblastoma, meningioma, astrocytoma, cerebellopontine angle
schwannoma.
SPORADIC ATAXIA (2)

d. Toxic/metabolic : alcohol, hypoxia, vitamin deficiencies, drugs (phenitoin,

carbamazepine, lithium, barbiturates, cyclosporine, methotrexate, and 5-
flourouracil).
e. Paraneoplastic (tumors of lung, colon, prostate, breast, ovary and adnexa)
f. Autoimmune (stiff-person syndrome)
g. Infectious / post-infectious,
h. Demyeliniting (multple sclerosis)
i. Ataxia of non-cerebellar origin ( spinocerebellar tract lesions, Miller Fisher
form of GBS)
j. Other (hydrocephalus, Chiari malformation)
Genetic Ataxia – Dominant ataxia (1)
Autosomal Dominan Cerebellar ataxia (ADCA)
1. ADCA I : cerebellar syndrome plus pyramidal, extrapyramidal,
opthalmoplegia and dementia

2. ADCA II : cerebellar syndrome plus pigmentary maculopathy

3. ADCA III : largely a pure cerebellar syndrome plus mild pyramidal signs
Genetic Ataxia – Dominant ataxia (2)
Autosomal Dominan Episodic ataxia (ADEA)
a. ADEA-1 :
 The characterized by interictal myokymia, brief attacks of ataxia and
dysarthria lasting seconds to menite precipitated by exercise or startle.
 Onset is childhood aor early adolescence.
 The myokymia is prominent around the eyes, lips or in the fingers.
 The myokymia may respond to phenitoin and the ataxia to acetazolamide
Genetic Ataxia – Dominant ataxia (3)
b. ADEA-2 :
 Characterized by intermittent attacks of ataxia, dysarthria,
nause, vertigo, diplopia, and oscillopsia minutes to days.
 Episodes are provoked by stress and exercise, but not startle.
 About half of the patients also have migraine.
 The attacks may respond to acetazolamide and a-
aminopyridine.
c. ADEA-3
 Called periodid vestibiulo cerebellar ataxia.
 Characterized by ataxia, vertigo, gaze-evoked nystagmus
d. ADEA-4 :
 Characterized by vestibular ataxia, vertigo, tinnitus and
interictal myokymia.
 Attacks respond to acetazolamide.
Genetic Ataxia – Recessive ataxia (1)
a. Friedreich ataxia
 Most common cause of hereditary ataxia,
 Prevalence 1/50.000 persons,
 Age of onset before 20 years,
 Clinical feature: ataxia, dysarthria, sensory loss and corticospinal tract
signs with absent reflexes.
 Treatment : idebenone , coenzimeQ10, vitamin E.
Genetic Ataxia – Recessive ataxia (2)
b. Ataxia with vitamin E deficiency (AVED)
c. Ataxia teleangectasia
d. Spinocerebellar ataxia with axonal neuropathy
e. Autosomal recessive cerebellar ataxia type 1
f. Autosomal recessive cerebellar ataxia type 2
g. Familial cerebellar ataxia with muscle
coenzyme Q10 deficiency
EVALUATION OF THE ATAXIC PATIENT
• Good history and physical exam
• Laboratory test, including lipids and thyroid function
• Autonomic testing, sphincter EMG
• MRI
• Genetic testing
• Toxin screen
• Vitamin level (especially E)
• Paraneoplastic antibodies
TREATMENT
• There are NOT ANY EXCELLENT TREATMENT
• Several agents have been reported to show same ataxia
ameliorating effects.
• Amantadine for FA and olivopontocerebellar atrophy (OPCA)  no
functional improvement
• Thyrotropin releasing hormone (TRH)  small benefit
• L-5 hydroxytryptophan  high rate of gastrointestinal side effects.
• Buspirone  small benefit
• Ondansetron  little benefit
• Physostigmine  no benefit
• D-cycloserine, pirasetam, gabapentin  improvement
• Varenicline unclear
• Riluzole  significanly improvement
• Surgical or DBS  no benefit for ataxia.
ATHETOSIS
• Berasal dari Bahasa Yunani yang artinya “Tidak pasti”
• Kondisi tidak dapat mempertahankan posisi jari tangan, jari kaki, lidah atau
bagian tubuh lainnya.
• Gerakan involunter berupa gerakan tak bertujuan dengan karakteristik melintir
atau melenting secara lambat. Sering muncul pada jari, tangan, wajah, lidah.
• Sering muncul bersama chorea dan sulit dibedakan sehingga disebut
choreoatrhetosis
• Athetosis dapat ditemukan pada :
• Huntington disease
• Hepatic Encephalopathy pada dewasa
• Intoksikasi haloperidol
• Lesi vascular pada nucleus lentiformis atau thalamus
Dyskinesia
• Dyskinesias are involuntary, erratic, writhing movements of the face,
arms, legs or trunk. They are often fluid and dance-like, but they may
also cause rapid jerking or slow and extended muscle spasms. They
are not a symptom of Parkinson's itself. Rather, they are a
complication from some Parkinson's medications
Symptoms: Dyskinesia
• Levodopa-induced dyskinesia, which refers to abnormal, involuntary,
choreiform movements that may affect the limbs, head, and torso.
• Manifest with ballism, myoclonus, dystonia, or combination of these
movements.
• Classified as peak-dose dyskinesia, wearing-off or off-period
dyskinesia, or diphasic dyskinesia.
• Diphasic dyskinesia begins shortly after levodopa ingestion followed
by improvement in parkinsonian symptoms and dyskinesia and a
subsequent return of dyskinesia as dopamine levels decline
Zesiewicz, T. A. 2019. Parkinson Disease. CONTINUUM: Lifelong Learning in
Neurology, 25(4), 896-918.
02/02/2023 Department of Neurology FKKMK UGM - Dr. Sardjito Hospital 359
Tipe Gait
Tipe Gait
Tipe Gait
Transcranial magnetic stimulation (TMS)
Tujuan TMS
• Program Neurorestorasi yang dapat memperbaiki sebagian fungsi
syaraf dengan meningkatkan reorganisasi kortikal
• Repetitive Transcranial Magnetic Stimulation (rTMS)  menghasilkan
perubahan potensial terhadap rangsangan kortikal.
• Stimulasi TMS direkomendasikan untuk mendorong perubahan
fungsional pd pasien dengan cara menginduksi neuroplastisitas.
Efek TMS
• Medan magnet digunakan untuk • Efek TMS sebenarnya bukan efek
menembus struktur yang cukup langsung dari medan magnet
resisten (tulang kepala) namun bergantung pada medan
• Medan listrik untuk mengaktivasi listrik induksi dalam jaringan
neuron. syaraf.
• Medan magnet dihasilkan oleh
coil
• (Ricceri et al 2013)
Prinsip TMS
Indikasi TMS
Gangguan neurologis
Gangguan neuropsikiatrik
• Stroke
• Gangguan kecemasan
• Multiple sklerosis
• Skizofrenia
• Movement disorder
• Depresi
• Gangguan memori
• Mood disorder
• Gangguan berbahasa
• Nyeri kronis

Sebagai alat penelitian untuk menilai fisiologi otak manusia

Aplikasi terapi  gangguan neurologis dan kejiwaan
Kontraindikasi
• Perangkat metalik dekat letak koil
• Pacemakers
• Implan pompa jantung, cochlear implants
• Vp shunt
• Riwayat kejang atau riw epilepsi pada keluarga dekat
• Dalam pengobatan yang menurunkan ambang batas (anti depresan, stimulant)
• Pasien dengan fokal/general encephalopathy (tumor,iskemia, bleeding, meningitis, encephalitis)
posible to formation of an accidental seizure induction.
• Kehamilan, trauma kepala berat
• Riw penggunaan obat terlarang
• Stroke akut
• Riw pembedahan kepala
• Riw pengobatan terkait epilepsi maupun pasien dengan peningkatan tek intrakranial
Efek samping TMS
Sistemik Psikiatrik Neurologis

• nausea • anxiety • Local pain (scalp

• Arytmia (tu/ jika coil • Acute dysforia/crying muscle and superfisial
dekat pericardium) • Attack of laughter nerves, facial twitch)
• Muscle pain, (stimulasi di area • Headache, discomfort
contraction, athralgia broca) and local pain
• Erythema kulit • Suicidal ideation • Fatigue
• Induced mania • Dizziness
• Cognition positive
and negative result
• Hearing loss/tinnitus
• Induce accidental
seizure
Efek samping TMS
• Resiko bangkitan kejang (pada pasien dengan riw kejang maupun riw
keluarga kejang), hal tersebut diantisipasi dengan pegukuran motor
treshold dan pemberian stimulasi awal
• Nyeri kepala tipe tegang otot
• Gangguan pendengaran sementara
• Perubahan kognitif saat dilakukan stimulasi.
Teknik Penggunaan TMS
3 macam tekhnik :
• 1. Single-pulse TMS  TMS yang diberikan dalam satu waktu dan
terdiri dari satu stimulus, teknik ini menghasilkan respons yang baik
tetapi hanya berlangsung singkat.
• Pengulangan stimulus dapat lebih memperpanjang efek pada otak
• Lama efek setelah single-stimulus  30-60 menit
• Single-pulse digunakan untuk mapping output korteks motorik
Teknik Penggunaan TMS
2. Paired-Pulse TMS  yaitu TMS yang diberikan dalam stimulus
berpasangan atau lebih dari satu stimulus dan diantara stimulus
terdapat jeda/ interval
• Paired-pulse TMS dapat diberikan pada satu target kortikal
menggunakan satu kumparan atau pada dua daerah otak yang
berbeda menggunakan dua kumparan yang berbeda.
• Digunakan untuk mengukur fasilitasi intrakortikal dan inhibisi
intrakortikal.
Paired Associative Stimulation (PAS)
• Penggunaan TMS dengan paired-stimulation yang diikuti dengan
stimulus perifer
Tekhnik TMS
• Prinsip elektromaghnetik
• Kumparan (coil) diletakan diatas kepala pada M1.
• Kumparan tsb dialiri arus dan menghasilkan medan maghnet serta
menginduksi arus listrik yang dapat mencetuskan depolarisasi syaraf.
Stimulasi diberikan sepanjang jalannya serabut saraf, menggunakan
arus yang cukup kuat untuk menimbulkan depolarisasi.
Tekhnik TMS
• rTMS juga mengaktivasi sel-sel piramidal secara tidak langsung
(transinaptik) atau secara langsung melalui axon hillock.
• Pada penggunaan TMS operator dapat mengkontrol intensitas stimuli
dengan mengubah intensitas arus listrik yang mengalir pada
kumparan sehingga mengubah besarnya medan maghnet dan medan
listrik yang mengalir di otak.
• Fokus medan maghnet tergantung pada bentuk kumparan.
Efek TMS pada area motorik
Parameter TMS
• Resting Motor Treshold (RMT)
• Short interval cortical inhibition (SICI)
• Short latency afferent inhibiton (SAI)
• Cortical silent periode (CSP)
• Infracortical facilitation (ICF)
• Paired associative stimulation (PAS)
Modern Application
Even More Modern
ALAT TMS