3. oIntroduction
It is a progressive neurological condition
Results from the degeneration of dopamine-
producing neurons in the substantia nigra
Afflicted 25,000 people in Malaysia
Various types of Parkinson’s disease
Risk factors:
Middle aged and increased risk with age
Hereditary
Men (1.5 times more)
Environmental exposure to toxins
4. Symptoms
4 major symptoms:
Rigidity – muscles are tensed and contracted
Resting tremor – trembling which is most obvious
when the patient is at rest or when stressed
Bradykinesia – slowness in initiating movement
Loss of postural reflexes or instability – poor
balance and coordination
Non-motor symptoms
Anxiety disorders, depression, sleep disturbances,
orthostatic hypotension, olfaction dysfunction,
dysphagia, sialorrhoea, dementia, psychosis and
visual hallucinations
5. Diagnosis and Treatment
Diagnosis:
Neurological examination
Autopsy of brain to find lewy bodies (trademark
characteristic)
Judgement of physicians
Treatment:
Medications
Diet
Exercise, physical and speech therapy
Surgery
Cryothalamotomy
Pallidotomy
Deep brain stimulation
6. oCauses and Pathogenesis
Degradation of dopaminergic neuron.
Free radicals.
Neurotoxin - MPTP
Genetic factors.
7. Degradation of Dopaminergic Neuron
Substantia nigra pars compacta.
Death of neuron.
Symptoms of PD don’t appear until 50-80% of the
neurons in the pars compacta have died.
Cause of death of neuron is not known.
8. Free Radicals
Unpaired electrons that can easily react with
surrounding molecules and destroy them.
Metabolism of dopamine by MAO produce
hydrogen peroxide.
Glutathione normally breaks down the hydrogen
peroxide quickly.
Reduced glutathione = loss of protection against
free radicals cell damage
9. Neurotoxin - MPTP
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) – neurotoxin.
MPTP crosses the blood-brain barrier and
oxidized to 1-methyl-4-phenylpyridinium (MPP+)
by monoamine oxidase B (MAO)-B
MPP+ selectively enters dopamine neurons via
the dopamine transporter.
MPP+ inhibiting Complex I 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
Result of pallidal dysfunction
Triggered by specific loss of dopa minergic
projections from retrorubral area
13. 2. Present of myerson
Eyes blinking when tapped on glabella (glabellar
reflex)
Involuntary reflex disorder
14. 3. Mild signs of asymmetrical cogwheel rigidity and
bradykinesia (left > right)
Cause to muscular aches and sensation of fatigue
Face become masklike, opened mouth, drooling
and reduced blinking
Underscaling of movement commands in internally
generated movements
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
Under activity in the left cerebellar hemisphere with
contrast of over activity in vermis
Associated with loss of lateral gravity shift in
parkinsonian gait
Loss of postural reflexes
No tendency of falling forward
No difficulty of walking, turning and stopping
16. Diagnostic Test
No specific test.
Usually based on present of symptoms.
Referral time should not be more than 6 weeks
and not exceed two weeks in severe case.
No specific lab test used for diagnosis.
Follow – up= every 6 to 12 months.
18. Neurological examination
Patient’s medical and family history
Observe sign and symptoms present.
Suggested symptoms include:
Bradikinesia
Tremor
Hypokinesia
Rigidity
Patient had normal cognition and myerson sign is
present.
Intermittent mild tremor was observed as well as
cogwheel rigidity and bradykinesia.
19. Oculomotor examination
To check abnormalities of eye movement, generation,
and control.
Normal in patient.
Single photon emission computed tomography
(SPECT)
Show dramatic (50%) loss of striatal uptake in patient
compared to normal individual.
Electroencephalograms
Record patient’s 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.
Levodopa:
is a medicine that the brain converts to dopamine.
is a medicine used to control symptoms
of Parkinson's disease and used at all stages of the
disease.
Levodopa does not slow the disease process, but it
improves muscle movement and delays severe
disability.
long-term levodopa therapy within 5 to 10 years can
cause complication to occur such as Dyskinesia.
22. Dopamine agonist:
Example of drugs:pramipexole,ropinirole
directly stimulate the receptors in nerves in the
brain that normally would be stimulated
by dopamine.
used in the early stages of Parkinson’s disease to
reduce symptoms.
effective in people who have been newly diagnosed
with the disease (especially those younger than 60).
Not effective as levodopa in reducing symptom but
can prevent long term effect caused by levodopa.
23. Monoamine oxidase type B inhibitor
MAO-B is an enzyme in our brain that naturally
breaks down several chemicals in our brain
including dopamine.
Prevent the breakdown dopamine.
they prevent the removal of dopamine between
nerve endings and enhance release of dopamine
from nerve cells.
Example of drug: Rasagiline and selegiline.
used in the early stages, to treat very mild
symptoms (such as resting tremor) and delay the
need for levodopa.
rasagiline or selegiline may be added to levodopa
treatment to reduce motor fluctuations , increase
the time of effect of the levodopa.
24. Amantadine
treat people who are in the early stages of
Parkinson's disease.
It is best used in people who have mild to moderate
symptoms.
cause greater amounts of dopamine to be released
in the brain.
can be used with levodopa in the later stages of
Parkinson's disease to reduce dyskinesias.
25. Anticholinergic
Example of drugs: benztropine,biperiden
Anticholinergic medicines decrease levels of
acetylcholine to achieve a closer balance with
dopamine levels.
In order to reduce the symptom.
27. Levodopa ( L-Dopa)
the most effective antiparkinsonian medication.
“start low, go slow” approach, L-dopa can be started at
a dose of 50 mg daily (e.g., ¼ tablet of Madopar®
200/50 mg) increasing every 3-7 days by 50 mg to an
initial maintenance dose of 50-100 mg 3x daily.
Selegiline ( Jumex and Selegos)
usual dose is 10 mg in the morning.
has a mild antiparkinsonian effect.
28. Dopamine agonist
Next 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. Anticholinergic agents
These include trihexyphenidyl or benzhexol (Apo-
Trihex® and Benzhexol®)(1 or 2 mg 2-3x daily) and
orphenadrine (Norflex®) (50 mg 2-3x daily).
Non-Pharmocologic Management
physiotherapy: stretching and strengthening exercises
and balance training.
occupational therapy: lifestyle adaptations and
assessment of safety in the home environment.
speech therapy: rehabilitation techniques to strengthen
speech for improved communication.
Dietitian: advice from them.
30. Conclusion
Patient has idiopathic Parkinson’s disease
There is no cure but therapies are available
Treatments aim to:
Prevent clinical progression
Improvement of parkinsonism
Delay of motor complications
Complications: choking, falls and side effects of
drugs
Prognosis: normal life expectancy for treated
patients
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