Gangguan Gerak, Parkinson- Koas New
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Transcript of Gangguan Gerak, Parkinson- Koas New
GANGGUAN GERAK DAN PENYAKIT PARKINSONTinjauan Umum
SISTEM MOTORIK
1. Sistem piramidal 2. Sistem ekstrapiramidal
3. Serebelum
Interaksi ketiganya menghasilkan gerak
Types of Movements
● Automatic movement Learned motor behaviors performed without conscious effort
(walk, speak)● Voluntary movement Intentional planned or self initiated, or externally triggered● Involuntary movement Not suppressible (tremor, myoclonus)● Semi-voluntary (un-voluntary) movement induced by inner sensory stimulus, move to suppress
unpleasant sensation, suppressible for short time (tic, akathisia, RLS)
GANGGUAN SISTEM MOTORIK
Lumpuh1. Sistem piramidal Kejang2. Sistem ekstrapiramidal Gangguan gerak
3. Serebelum Gangguan koordinasi (ataksia)
Extrapyramidal System
FacilitationPhysiology: function by Suppression
FacilitatePathophysiology: failure to Extrapyramidal dysfunction Suppress
MOVEMENT DISORDER
MOVEMENT DISORDER
DefinitionMovement disorder Is a neurological syndrome in which there iseither an excess of movement, or a paucity of voluntary andAutomatic movement. Unrelated to weakness or spasticity
It is a term for: 1. A physical sign 2. Describing a specific syndrome / condition
The Origin of Movement Disorders
1. Basal ganglia - Cerebral Globus pallidus, Caudate nucleus, Putamen - Diencephalon Subthalamic nucleus - Mesencephalon Substantia nigra
2. Non-basal ganglia a. Cerebellum b. Cerebral cortex c. Brainstem
3. Peripheral ? (Hemifacial spasm)
Specific Site for Specific MD
1. Basal Ganglia - Substantia nigra Bradykinesia, rest tremor - Subthalamic nucleus Ballism - Caudate nucleus Chorea - Putamen Dystonia
2. Non-ganglia basal - Cerebellum ataxia, dysmetria, intention tremor, progressive myoclonic ataxia - Brainstem reticular reflex myoclonus, hyperekplexia, palatal myoclonus, ocular myoclonus - Cerebral cortex cortical reflex myoclonus - Limbic structure + basal ganglia (?) tics
Classification of Movement disorders
Extrapyramial Dysfunction
Failure to Facilitate Failure to Suppress
HYPOKINESIA HYPERKINESIA (“Involuntary movement”)- Akinesia/Bradykinesia - Rigidity - Dyskinesia – Myoclonus- Diminished postural response - Tremor - Tics- Freezing - Chorea - Akathesia - Athetose - Hyperekplexia
No Weakness ! ! - Dystonia - Stereotypy
Pattern and Type of Movement HYPERKINESIA
● Tremor rhythmic, alternating agonist and antagonist , sinusoidal, regular Type: essential, rest, action trremor ● Chorea (“dance”) rapid, forceful, semipurposeful● Ballism large amplitude choreic movements of proximal parts of limbs ● Athetosis slow, writhing, mostly distally● Dystonia involuntary, sustained muscle contraction, causing repetitive twisting movement and
abnormal posture - focal, segmental, generalized● Myoclonus sudden brief shock-like involuntary movement from: muscle contraction (positive myoclonus) or muscle inhibition (negative myoclonus)
Pattern and Type of Movement
HYPERKINESIA (cont’d)● Tics -abnormal movement (motor tics) or abnormal sounds (phonic tics), or both (Tourette’s syndrome) - abrupy, brief moments - preceded by urge ● Akathesia feeling of inner restlesness leading to complex stereotyped movements, which may
reduce the sensation● Stereotypy - coordinated movements that repeat themselves continually and identically - not preceded by urge - In tardive dyskinesia● Restless leg syndrome - urge to move the limb with uncomfortable sensations
Pattern and Type of Movement
HYPOKINESIA● Rigidity - increased tone throughout all directions of movement. - Flexor > extensor - “lead pipe”/”plastic”, “cogwheel” phenomenon● Bradykinesia slowness of movement● Freezing - motor act halted transiently (several seconds) - Includes: start hesitation, turning hesitation, destination hesitation● Apraxia - inability to perform complex learned voluntary movement - not due to weakness, spasticity, rigidity, sensory loss
PERANAN SEREBELUM (otak kecil) INTEGRASI FUNGSI SENSORIMOTOR
GANGGUAN KOORDINASI
MEKANISME REFLEKS‘LENGKUNG REFLEKS’
RESEPTOR – AFEREN – PUSAT – EFEREN – EFEKTOR
REFLEKS PADA INDIVIDU DEWASA:GERAK OTOT SKELETAL YANG BANGKIT
SEBAGAI JAWABAN ATAS SUATU RANGSANGAN
• REFLEKS FISIOLOGIS• REFLEKS PATOLOGIS
PARKINSON’S DISEASE
ETIOLOGY
IDIOPATHIC
RISK FACTORS(MULTIFACTORIAL)
• AGING• RACE
• GENETIC• ENVIRONMENT
PATOPHYSIOLOGY
BASAL GANGLIAEXTRAPYRAMIDAL SYSTEM
DOPAMINERGIC VS CHOLINERGIC
DIRECT PATHWAY VS
INDIRECT PATHWAY
Substrat anatomi utama pada PD
DIAGNOSTIC APPROACH
• CLINICALLY POSSIBLETHE PRESENCE OF ANY ONE OF THE SALIENT FEATURES: TREMOR (RESTING); RIGIDITY; BRADYKINESIA; IMPAIRMENT OF POSTURAL REFLEXES
• CLINICALLY PROBABLECOMBINATION OF ANY TWO CARDINAL FEATURES (INCLUDING IMPAIRED POSTURAL REFLEXES); ALTERNATIVELY, ANY ONE OF THE FIRST THREE IF ASYMMETRICAL
• CLINICALLY DEFINITEANY COMBINATION OF THREE OF THE FOUR FEATURES; ALTERNATIVELY, ANY TWO WITH ONE OF FIRST THREE DISPLAYING ASYMMETRY
DIAGNOSIS
Vascular PD
MODIFIED HOEHN AND YAHR STAGING
• STAGE 0 = NO SIGNS OF DISEASE• STAGE 1 = UNILATERAL DISEASE• STAGE 1.5= UNILATERAL PLUS AXIAL
INVOLVEMENT• STAGE 2 = BILATERAL DISEASE,
WITHOUT IMPAIRMENT OF BALANCE• STAGE 2.5= MILD BILATERAL DISEASE,
WITH RECOVERY ON PULL TEST• STAGE 3 = MILD-TO-MODERATE BILATERAL DISEASE;
SOME POSTURAL INSTABILITY; PHYSICALLY INDEPENDENT
PROGNOSTIC FACTORS
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GOAL OF THERAPY:TO REVERSE
THE FUNCTIONAL DISABILITY
• ABOLITION OF ALL SYMPTOMS AND SIGNS IS NOT CURRENTLY POSSIBLE EVEN WITH HIGH DOSES OF MEDICATION
• TREATMENT IS INDIVIDUALIZED
• PATIENT AND PHYSICIAN PLAYS A MAJOR ROLE IN THERAPEUTIC DECISIONS
B R A I NGanglia basalis
Acetylcholin Normal
Dopamin
Acetylcholin PD
Perokside Radical H
Tissue damage
Anticholinergic
(Trihexylphenidyl)
MAO MAO I ( selegiline )
D2
Dopamin
Receptor
Dopamin Agonist
Ergot (bromocryptin)
Non Ergot (pramipexole)
Levodopa
Levodopa
Dopamin
Decarboxylase
Decarboxylase Inhibitor
(Benzeraside)(carbidopa)
3 OMD
COMTCOMT Inhibitor
(entacapone)
BLOOD BRAIN BARIER
PHERIFER
Decarboxylase
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LEVODOPAPRECURSOR OF DOPAMINE
• REPLACEMENT OF DEPLETED TRANSMITTER
• COMPLICATION OF CHRONIC THERAPYTHE “ON-OFF” REACTION, DYSKINESIAS,
AND VISUAL HALLUCINATIONS
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ADDITIONAL AND DISTINCTLY DIFFERENT PHARMACOLOGIC
ADVANCES
• CARBIDOPA
• CONTROLLED RELEASE CARBIDOPA/LEVODOPA
• DOPAMINE AGONIST
• INHIBITOR OF CATECHOL-O- METHYL TRANSFERASE (COMT)
• MONOAMINE OXIDASE TYPE B (MAO-B)
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• CARBIDOPA (INHIBITOR OF DOPA DECARBOXYLASE) COMBINED WITH LEVODOPA, REDUCES PERIPHERAL DECARBOXYLATION OF LEVODOPA TO DOPAMINE
• CONTROLLED RELEASETO PROLONGE LEVODOPA’S 90-MINUTES HALF-LIFE
• DOPAMINE AGONISTUSED AS PHARMACOLOGICALLY SUBSTITUTES FOR CARBIDOPA/LEVODOPA IN EARLY DISEASE
TO PROVIDE SUPPLEMENTATION IN LATER STAGES
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• INHIBITORS OF CATECHOL-O-METHYL TRANSFERASE (COMT)INCREASE THE AMMOUNT OF LEVODOPA CROSSING THE BLOOD BRAIN BARRIER
• MONOAMINE OXIDASE TYPE B (MAO-B)INHIBITORS TO SLOW DOPAMINE’S METABOLIC BREAKDOWN
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THERAPEUTIC ALGORITHMFOR MANAGEMENT
OF PARKINSON’S DISEASE
(SEE TEXT)
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• INITIAL DECISION :WHETHER ANY PHARMACOTHERAPY IS NEEDED
• NO CONCLUSIVE EVIDENCETHAT TREATMENT IS HELPFUL BEFORE SYMPTOMS START TO AFFECT THE PATIENT’S LIFEEARLY STAGE : MAY BE BETTER LEFT UNTREATED IF IT DOES NOT LIMIT MOTOR FUNCTION
• DECISION IS MADE ON THE BASIS OF HOW SYMPTOMS ARE AFFECTING INDIVIDUAL PATIENTS
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CHOICE:INTRODUCE LEVODOPA
OR ANOTHER ANTIPARKINSONIAN AGENT
• DEVELOPMENT OF COMPLICATION ASSOCIATED WITH LONG-TERM USE OF LEVODOPA
• OTHER ANTIPARKINSONIAN DRUGS SHOULD BE CONSIDERED FIRST TO DELAY THE INTRODUCTION OF LEVODOPA
• LEVODOPA IS APPROPRIATE IF THE PATIENT’S SYMPTOMS ARE STARTING TO INTERFERE WITH HIS OR HER ACTIVITIES
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PATIENTS WITH MILD SYMPTOMSMAY BE TREATED IN OTHER WAYS
CHOICES INCLUDE :
INTRODUCING SELEGILINE FOR ITS POSSIBLE
NEUROPROTECTIVE BENEFIT
INITIATING TREATMENT WITH ANTICHOLINERGIC DRUG, AMANTADINE,
OR A DOPAMINE AGONIST AGENT
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SELEGILINE (L-DEPRENYL)AS AN ADJUNCT TO CARBIDOPA/LEVODOPA
FOR PATIENTS WHO EXHIBIT DETERIORATION IN RESPONSE TO LEVODOPA
• SHOWN TO PROLONG THE SYMPTOMATIC BENEFIT OF LEVODOPA
• IMPROVEMENT OF MOTOR SCORES AFTER THE INITIATION OF THE DRUG AND DETERIORATION OF SCORES ON ITS WITHDRAWL
• MAY HAVE SOME NEUROPROTECTIVE EFFECT• STATISTICALLY REDUCED DISABILITY COMPARED TO PLACEBO
WAS FOUND EVEN AMONG DEPRENYL PATIENTS WHO INITIALLY HAD NO IMPROVEMENT IN MOTOR SCORES
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SELEGILINE MONOTHERAPY
• SELEGILINE’S NEUROPROTECTIVE EFFECTS
• LEVODOPA TREATMENT TOXICITY WILL BE REDUCED BY SELEGILINE INHIBITION OF MAO-B OXIDATION OF DOPAMINE
• APPROPRIATE CANDIDATES FOR SELEGILINE MONOTHERAPY:
- EARLY-STAGE PATIENTS WITHOUT DISABLING SYMPTOMS- YOUNG PATIENTS (< 65 YEARS OF AGE)
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ANTICHOLINERGICS
• TO BE EFFECTIVE FOR THE SYMPTOMS OF TREMOR, ALTHOUGH RIGIDITY AND BRADYKINESIA ARE NOT MUCH ALTERED
• SHOULD BE USED WITH CAUTION IF AT ALL IN THE ELDERLY SINCE THEY HAVE A POOR THERAPEUTIC INDEX AND HIGH TOXICITY
• NUMBER OF SIDE EFFECTS
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AMANTADINEFOR PATIENTS WHOSE EARLY SYMPTOMS DO NOT
RESPOND TO ANTICHOLINERGICS
• AN ANTI VIRAL AGENTPRECISE MECHANISM OF ACTION REMAINS TO BE DEFINEDRELEASES DOPAMINE FROM PERIPHERAL NEURAL STOAGE SITES;
SIMILAR ACTION ON THE RESIDUAL, INTACT DOPAMINERGIC TERMINALS IN THE STRIATUM OF PARKINSONIAN PATIENTS
• REPORTED ACTIONS :- RELEASE OF DOPAMINE FROM CENTRAL NEURON- DELAY OF DOPAMINE UPTAKE BY NEURAL CELLS- BLOCKADE F NMDA RECEPTORS- ANTICHOLINERGIC EFFECTS
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DOPAMINE AGONISTS
• LONG HALF-LIFE ASSOCIATED WITH LESS RISK OF DEVELOPING DYSKINESIA
• USE OF THESE COMPOUNDSPRIOR THE LEVODOPA INITIATION IN EARLY DISEASE TO AVOID OR DELAY THE PRODUCTION OF DYSKINESIA, ESPECIALLY IN PATIENTS WHO ARE YOUNG
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DEVELOPMENT OF DYSKINESIA
• DEPEND ON DISEASE SEVERITY AND THE HALF-LIFE OF THE DOPAMINERGIC AGENT
• ENOUGH DOPAMINE TERMINALS TO REGULATE DOPAMINE RELEASE AND PROVIDE POSTSYNAPTIC DOPAMINE RECEPTOR WITH RELATIVELY PHYSIOLOGIC DOPAMINE STIMULATION
• MORE ADVANCED DISEASE:
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NOT ENOUGH DOPAMINE TERMINALS TO REGULATE DOPAMINE RELEASE
FLUCTUATION IN STRIATAL LEVODOPA THE RESULTING EXPOSURE OF STRIATAL RECEPTORS
TO ALTERNATING HIGH AND LOW CONCENTRATIONS OF DOPAMINE ----
INDUCE THE POSTSYNAPTIC CHANGES THAT LEAD TO THE DEVELOPMENT OF DYSKINESIA & MOTOR COMPLICATIONS
INITIAL MONOTHERAPY: USEFUL IN YOUNGER PATIENTS WHO ARE MORE PRONE TO THE EARLY DEVELOPMENT
OF LEVODOPA-RELATED CLINICAL FLUCTUATIONS
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INHIBITORS OFCATECHOL-O-METHYLTRANSFERASE
ADDITION OF CARBIDOPA TO LEVODOPA INCREASES THE AMMOUNT OF DRUG AVAILABLE TO CROSS THE BLOOD-BRAIN BARRIER
LEVODOPA IS METABOLIZED IN THE GUT AND LIVER BY COMT
COMT INHIBITORY AGENTS PREVENT THE BREAKDOWN ; PROLONGING THE HALF-LIFE OF LEVODOPA, INCREASING ITS TRANSPORT INTO THE BRAIN TO RISE DOPAMINE LEVELS
COMT inhibitionLevodopa plus DDCI Levodopa plus DDCI plus COMT inhibitor
BBB = blood brain barrierDDC = DOPA-decarboxylaseDDC = DOPA-decarboxylase inhibitorCOMT = Catechol-O-methyl transferase 3-OMD = 3-O-methyldopa
Peripheral CentralPeripheralCentral
Dopamine
Levodopa
3-OMD
COMT
BBB
DDC
3-OMD
Levodopa
Dopamine
COMT
DDC
Dopamine
Levodopa
3-OMD
COMT
BBB
DDC
3-OMD
Levodopa
Dopamine
COMT
DDC
Kaakkola S, et al. General properties and clinical possibilities of new selective inhibition of cathecol-O-methyl transferase. Gen. Pharmacol 1994a; 25: 813 - 824.
Akinesia
• The absence of movement• Facial characteristics: decreased blinking, a
reptillian 'stare,' or an immobile or mask-like face (hypomimia)
• Gradual softening of the voice (hypophonia).
Bradykinesia
• the slowness of movement : – micrographia– Impaired movements result :
• difficulty turning in bed, • standing up from sitting in a chair• getting out of a car.
– Festinating increasing in velocity
Postural Imbalance
• A symptom that manifest itself in the inability of a patient to balance or remain steady
Clinical Tests of Balance Used by Physical Therapists
Standing
Feet apart Feet together Stride stance Tandem stance Single-limb stance Romberg Test
• Perturbation of standing balance by self-initiated movements Response to externally generated perturbations
Arm raises Step test Functional reached
Sternal push Postural stress
Pastor, Marsden, and
Day Test
• Ability to maintain balance during functional tasks
Berg Balance Scale "Get up and go" test Gait Tinetti MobilityIndex
Subcomponents of
functional assessment scales such as Barthel index, Functional Independence Measure, and Webster Scale
• Ability to integrate sensory
Sensory organization information to maintain
Tersebut di bawah ini adalah instrumen / perasat yang berkaitan dengan diagnostik
Penyakit Parkinson
• Hoehn and Yahr Staging of Parkinson’s Disease
• Kriteria Hughes
• Unified Parkinson’s Disease Rating Scale
• MMSE
Tersebut di bawah ini adalah instrumen / perasat yang berkaitan dengan pemilihan medikamentosa pada pengobatan awal
Penyakit Parkinson
• Hoehn and Yahr Staging of Parkinson’s Disease
• Kriteria Hughes
• Unified Parkinson’s Disease Rating Scale
• MMSE
Tersebut di bawah ini adalah hal-hal yang merupakan pertimbangan pemilihan medikamentosa
pada pengobatan awal Penyakit Parkinson
• Usia
• Berat-ringannya gambaran klinis
• Lamanya menderita
• Kemungkinan komplikasi obat jangka panjang
Komplikasi penggunaan jangka panjang levodopa terjadi berkaitan dengan:
Stadium penyakit Tingginya penggunaan dosis pengobatan Pulsatilitas kadar levodopa dalam plasma
Waktu paruh levodopa yang pendek Peranan Mono Amine Oxidase -B
Peranan Catechol-O-Methyl Transferase Kerusakan struktur dan fungsi reseptor dopamin
Pertimbangan untuk digunakannya Dopamine Agonists
• Stimulasi langsung pada reseptor dopamin
• Tidak memerlukan konversi presinaptik
• Tidak ada kompetisi di usus maupun sawar darah otak
• Dimungkinkan aktivasi terhadap reseptor selektif
• Dimungkinkan adanya sejumlah jalur pemberian