3. oIntroduction
ď It is a progressive neurological condition
ď Results from the degeneration of dopamine-
producing neurons in the substantia nigra
ď Afflicted 25,000 people in Malaysia
ď Various types of Parkinsonâs disease
ď Risk factors:
ďMiddle aged and increased risk with age
ďHereditary
ďMen (1.5 times more)
ďEnvironmental exposure to toxins
4. Symptoms
ď 4 major symptoms:
ďRigidity â muscles are tensed and contracted
ďResting tremor â trembling which is most obvious
when the patient is at rest or when stressed
ďBradykinesia â slowness in initiating movement
ďLoss of postural reflexes or instability â poor
balance and coordination
ď Non-motor symptoms
ďAnxiety disorders, depression, sleep disturbances,
orthostatic hypotension, olfaction dysfunction,
dysphagia, sialorrhoea, dementia, psychosis and
visual hallucinations
5. Diagnosis and Treatment
ď Diagnosis:
ďNeurological examination
ďAutopsy of brain to find lewy bodies (trademark
characteristic)
ďJudgement of physicians
ď Treatment:
ďMedications
ďDiet
ďExercise, physical and speech therapy
ďSurgery
ďś Cryothalamotomy
ďś Pallidotomy
ďś Deep brain stimulation
6. oCauses and Pathogenesis
ď Degradation of dopaminergic neuron.
ď Free radicals.
ď Neurotoxin - MPTP
ď Genetic factors.
7. Degradation of Dopaminergic Neuron
ď Substantia nigra pars compacta.
ď Death of neuron.
ď Symptoms of PD donât appear until 50-80% of the
neurons in the pars compacta have died.
ď Cause of death of neuron is not known.
8. Free Radicals
ď Unpaired electrons that can easily react with
surrounding molecules and destroy them.
ď Metabolism of dopamine by MAO produce
hydrogen peroxide.
ď Glutathione normally breaks down the hydrogen
peroxide quickly.
ď Reduced glutathione = loss of protection against
free radicals ď cell damage
9. Neurotoxin - MPTP
ď 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) â neurotoxin.
ď MPTP crosses the blood-brain barrier and
oxidized to 1-methyl-4-phenylpyridinium (MPP+)
by monoamine oxidase B (MAO)-B
ď MPP+ selectively enters dopamine neurons via
the dopamine transporter.
ď MPP+ inhibiting Complex I ď leads to cell death
via energy deficit.
10. Genetic Factors
⢠Mutation of SNCA genes in chromosome 4.
⢠2 types of alterations:
⢠Alanine is replaced with
threonine.
⢠Cause alpha-synuclein to
misfold.
⢠SNCA genes is
inappropriately duplicated
or triplicated.
⢠Extra copies of the gene
lead to an excess of alpha-
synuclein.
⢠Aggregate (Lewy bodies) and attract other protein.
⢠Clog neuron and impair the function of neuron.
11. oCase Study:
⢠70 year-old male
⢠Farmer
⢠Referred to a movement disorders outpatient clinic
12. Symptoms
1. Nondisabling intermittent resting tremor of left
hand
ď Result of pallidal dysfunction
ď Triggered by specific loss of dopa minergic
projections from retrorubral area
13. 2. Present of myerson
ď Eyes blinking when tapped on glabella (glabellar
reflex)
ď Involuntary reflex disorder
14. 3. Mild signs of asymmetrical cogwheel rigidity and
bradykinesia (left > right)
ď Cause to muscular aches and sensation of fatigue
ď Face become masklike, opened mouth, drooling
and reduced blinking
ď Underscaling of movement commands in internally
generated movements
ď Reflect the role of the basal ganglia in selecting
and reinforce appropriate patterns of cortical
activity during movement preparation and
performance
15. 4. Normal gait and balance and postural reflexes
ď Under activity in the left cerebellar hemisphere with
contrast of over activity in vermis
ď Associated with loss of lateral gravity shift in
parkinsonian gait
ď Loss of postural reflexes
ď No tendency of falling forward
ď No difficulty of walking, turning and stopping
16. Diagnostic Test
ď No specific test.
ď Usually based on present of symptoms.
ď Referral time should not be more than 6 weeks
and not exceed two weeks in severe case.
ď No specific lab test used for diagnosis.
ď Follow â up= every 6 to 12 months.
18. ďą Neurological examination
ďPatientâs medical and family history
ďObserve sign and symptoms present.
ďSuggested symptoms include:
ďś Bradikinesia
ďś Tremor
ďś Hypokinesia
ďś Rigidity
ďPatient had normal cognition and myerson sign is
present.
ďIntermittent mild tremor was observed as well as
cogwheel rigidity and bradykinesia.
19. ďą Oculomotor examination
ďTo check abnormalities of eye movement, generation,
and control.
ďNormal in patient.
ďą Single photon emission computed tomography
(SPECT)
ďShow dramatic (50%) loss of striatal uptake in patient
compared to normal individual.
ďąElectroencephalograms
ďRecord patientâs brain electrical activity.
21. Treatment
According to the case study the patient was on
initiation of treatment:In early-stage disease,
the pharmacological options for the treatment
of PD are multiple.
ď Levodopa:
ď is a medicine that the brain converts to dopamine.
ďis a medicine used to control symptoms
of Parkinson's disease and used at all stages of the
disease.
ďLevodopa does not slow the disease process, but it
improves muscle movement and delays severe
disability.
ďlong-term levodopa therapy within 5 to 10 years can
cause complication to occur such as Dyskinesia.
22. ď Dopamine agonist:
ďExample of drugs:pramipexole,ropinirole
ďdirectly stimulate the receptors in nerves in the
brain that normally would be stimulated
by dopamine.
ďused in the early stages of Parkinsonâs disease to
reduce symptoms.
ďeffective in people who have been newly diagnosed
with the disease (especially those younger than 60).
ďNot effective as levodopa in reducing symptom but
can prevent long term effect caused by levodopa.
23. ď Monoamine oxidase type B inhibitor
ďMAO-B is an enzyme in our brain that naturally
breaks down several chemicals in our brain
including dopamine.
ďPrevent the breakdown dopamine.
ďthey prevent the removal of dopamine between
nerve endings and enhance release of dopamine
from nerve cells.
ďExample of drug: Rasagiline and selegiline.
ďused in the early stages, to treat very mild
symptoms (such as resting tremor) and delay the
need for levodopa.
ďrasagiline or selegiline may be added to levodopa
treatment to reduce motor fluctuations , increase
the time of effect of the levodopa.
24. ď Amantadine
ď treat people who are in the early stages of
Parkinson's disease.
ď It is best used in people who have mild to moderate
symptoms.
ďcause greater amounts of dopamine to be released
in the brain.
ďcan be used with levodopa in the later stages of
Parkinson's disease to reduce dyskinesias.
25. ď Anticholinergic
ďExample of drugs: benztropine,biperiden
ďAnticholinergic medicines decrease levels of
acetylcholine to achieve a closer balance with
dopamine levels.
ďIn order to reduce the symptom.
27. ď Levodopa ( L-Dopa)
ďthe most effective antiparkinsonian medication.
ďâstart low, go slowâ approach, L-dopa can be started at
a dose of 50 mg daily (e.g., Âź tablet of MadoparÂŽ
200/50 mg) increasing every 3-7 days by 50 mg to an
initial maintenance dose of 50-100 mg 3x daily.
ď Selegiline ( Jumex and Selegos)
ďusual dose is 10 mg in the morning.
ďhas a mild antiparkinsonian effect.
28. ď Dopamine agonist
ďNext most potent class of drug after L-dopa.
Dopamine
agonist
Usual
Starting Dose
Maximum
recommende
d Dose
Piribedil
(Trivastal
Retard *)
25-50mg 300mg/d
Ropinirole
immidiate
release (
Requip *)
0.25mg 24mg/d
Ropinirole
Prolong
Release
(Requip PD*)
2mg 24mg/d
29. ď Anticholinergic agents
ď These include trihexyphenidyl or benzhexol (Apo-
TrihexÂŽ and BenzhexolÂŽ)(1 or 2 mg 2-3x daily) and
orphenadrine (NorflexÂŽ) (50 mg 2-3x daily).
ď Non-Pharmocologic Management
ďphysiotherapy: stretching and strengthening exercises
and balance training.
ďoccupational therapy: lifestyle adaptations and
assessment of safety in the home environment.
ďspeech therapy: rehabilitation techniques to strengthen
speech for improved communication.
ďDietitian: advice from them.
30. Conclusion
ď Patient has idiopathic Parkinsonâs disease
ď There is no cure but therapies are available
ď Treatments aim to:
ďPrevent clinical progression
ďImprovement of parkinsonism
ďDelay of motor complications
ď Complications: choking, falls and side effects of
drugs
ď Prognosis: normal life expectancy for treated
patients
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