1. Parkinson’s Disease

2. Content
 Introduction
 Cause and pathogenesis
 Case Study:
Symptoms
Diagnosis
Treatment
Conclusion

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.

17.  Suggested method include:
Neurologic examination
Oculomotor examination
Electroencephalograms (EEG)
Single photon emission computed tomography
(SPECT)

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.

20. Single photon emission computed tomography
(SPECT)

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.

26. Treatment In Malaysia
Decision pathway for the initiation of
medication

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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