Gangguan Gerak, Parkinson- Koas New

transcript

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

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

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 )

Dopamin

Receptor

Dopamin Agonist

Ergot (bromocryptin)

Non Ergot (pramipexole)

Levodopa

Dopamin

Decarboxylase

Decarboxylase Inhibitor

(Benzeraside)(carbidopa)

COMTCOMT Inhibitor

(entacapone)

BLOOD BRAIN BARIER

PHERIFER

Decarboxylase

LEVODOPAPRECURSOR OF DOPAMINE

• REPLACEMENT OF DEPLETED TRANSMITTER

• COMPLICATION OF CHRONIC THERAPYTHE “ON-OFF” REACTION, DYSKINESIAS,

AND VISUAL HALLUCINATIONS

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)

• 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

• 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

THERAPEUTIC ALGORITHMFOR MANAGEMENT

OF PARKINSON’S DISEASE

(SEE TEXT)

• 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

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

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

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

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)

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

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

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

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:

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

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

Dopamine

Levodopa

Dopamine

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

Gangguan Gerak, Parkinson- Koas New

Documents