1. Parkinson’s Disease
superKAT :)

2. Parkinsonism Neurological syndrome Combination of: 77% -PD
Rest tremors
Rigidity
Bradykinesia
77% -PD
12% -Parkinson plus syndromes
5% -Drug induced Parkinsonism
*not recognized early

3. Primary/idiopathic parkinsonism
Parkinson’s disease
Juvenile parkinsonism
Secondary
Infectious, drugs, toxins, vascular, trauma
Heredodegenerative parkinsonism
Huntington’s
Wilson
Multiple-system degeneration/ parkinsonism-plus
CBD (Cortical-Basal Ganglionic Degenration)
LBD (Lytico-Bodig)
Multisystem atrophy
PSP (Progressive Supranuclear Palsy)

4. Definition – Parkinson’s
Described by James Parkinson in 1817 as the “shaking palsy”
Chronic progressive disorder occurring in the Central Nervous System
Results from degeneration of dopamine-producing cells in the susbtantia nigra
susbtantia nigra
pars compacta – degenerate more
pars reticularis

5. 2nd most common neurodegenerative disease after Alzheimer’s disease
Age-related, progressive disorder
Dopamine, critical modulator of striatal output, is markedly decreased PD = control fine skillful movements

6. Prevalence PD is estimated to affect 100-180 in 100,000
Annual incidence of 4-20 per 100,000
Rising prevalence with age
Male: Female ratio is 3:2
M>F

7. Pathogenesis Neurogenerative
Loss of dopaminergic input to basal ganglia (extrapyramidal system)
Result in imbalance with dopamine and acetylcholine
Acetylcholine > Dopamine

8. Etiology Unknown Oxidative stress Proposed etiology Aging
Environmental toxins
Genetic susceptibility

9. Oxidative stress theory
Increased iron level
Lack of compensatory rise in isoferritins (iron-containing protein)
Increased aluminum levels
Reduced glutathione levels
Selective defect in complex I of mitochondrial respiratory chain
Evidence of oxidative damage to
Lipids, DNA, proteins, tyrosine-containing molecules

10. Oxidative stress
Mitochondrial dysfunction
Excitotoxicity

11. Genetics Young onset < 40yrs Juvenile onset < 20yrs
Parkin mutations: parkin gene
Mutations in the alpha synuclein and ubiquitin carboxy hydrolase: seen in autosomal dominant PD

12. Pathology
Loss of dopaminergic (DA) cells located in susbtantia nigra: most symptoms do not appear striata DA levels decline by at least 70-80%

13. Pathophysiology Degeneration of substantia nigra
Reduced production of dopamine

14. Clinical Manifestations
Bradykinesia – bumabagal
Tremor
Rigidity
*Stooped posture

15. Symptoms T- Tremors at rest R- Rigidity A- Akinesia/Bradykinesia
P- Postural instability

16. Tremors 4-6Hz Resting Disappears with voluntary movement
Disappears with sleep
Accentuated by stress/anxiety
Pill rolling
*Essential tremor & Physiology tremors 8-12 Hz and are kinetic and/or postural

17. Limb rigidity Resistance to passive movements of limbs
Involuntary hypertonia
Cogwheel

18. Bradykenisa
Decreased speed and amplitude of complex voluntary movements
Slowness and initiating and sustaining movement
Fragmented
Micrographia – lack of movement of the arm/difficulty
Tapping fingers
Twiddling

19. Postural instability Stooped, nanginginig ang kamay Shuffling gait
Righting reflex
equilibrium

20. Diagnosis Diagnosis depends on clinical findings
Tests(include imaging) are most often used to rule out etiology of secondary Parkinson’s disease
New technologies (PET scan) are used to visualize dopamin

21. Diagnosis
Presence of at least 2 of the 3 cardinal features of parkinsonism:
Tremor
Rigidity
Bradykinesia
Presence of at least 2 of the ff:
Marked response to levodopa
Asymmetry of signs
Asymmetry at onset
Evidence of disease progression

22. Stages Stage O – No clinical signs evident
Stage I – Unilateral involvement
Stage II – Bilateral
Stage III – Postural (minimal) problems
Stage IV – Postural with need of assistance
Stage V - Bedridden

23. Differential Diagnosis
DISEASE
HISTORY
PHYSICAL
Idiopathic Parkinson’s
gradual onset of tremor
gait disturbance
slowed movement
resting tremor
cogwheel rigidity
Drug induced parkinsonism
exposure to haloperidol or metoclopramide
similar to idiopathic PD
Essential Tremor
present for many years family history
tremor w/ arms raised
head involved
Multisystem atrophy
parkinsonism w/ autonomic system dysfunction
Orthostatic Hypotension
Hypotension
skin changes
Huntington’s disease
involuntary movement cognitive or behavioral problem
Chorea
loose tone
early dementia

24. Treatment Non-pharmacological approach Pharmacologic approach
Exercise, nutrition
Pharmacologic approach
Neuroprotective treatment
MAO B and Dopamine
4 classes:
Anticholinergic (for resting tremor)
Precursor of dopamine (carbidopa/levodopa)
Direct-acting dopamine agonist
Indirect-acting dopamine agonist

25. Drug therapy A. trycyclic antidepressants B. Beta blockers
C. Antihistamine

26. Factors Age Comorbidities Severity of symptoms Cognitive function
* For treatment plan

27. Management Treatment strategies Symptomatic relief
Levodopa
Amantadine
Anticholinergic
COMT inihibitors
Surgery
Symptomatic with neuroprotection
Dopamine agonist
MAO B inhibitors

28. Pharmacologic Options
Levodopa
Anticholinergic
Amantadine
Selegeline
Catechol-O-methyltransferase (COMT) Inhibitor
Dopamine Agonist

29. Levodopa Cabidopa-levodopa combination
Taken up by dopamine nerve terminals in the striatum
Converted to dopamine by dopa decarboxylase
Released and acts at the dopamine receptors

30. Levodopa Mainstay of therapy Produce immediate symptomatic response
Long-term use leads to dykinesias and motor response fluctuations
Development of nonlevodopa-responsive features (freezing, autonomic dysfunction)

31. ANTICHOLINERGIC Block muscarinic cholinergic receptors
Restore motor function
Trihexiphenidyl

32. Anticholinergic
Can be efficacious for tremors and dsystonia (agonist and antagonist acting simultaneously)
May be used as secondary pharmacologic option
Peripheral side effects – dry mouth, blurred vision, urinary retention, constipation
CNS side effects: confusion, memory loss

33. Amantadine Improves bradykinesia and tremor
Can be used as monotherapy or as adjunct therapy to levadopa
Antiparkinsonian MOA is not completely understood – indirect dopamine agonist
Restlessness, confusion, depression, nausea and hypotension
Used to treat influenza
Short term benefits

34. Selegeline Monoamine oxidase-B (MAO-B) inhibitor
Reduces dopamine metabolism

35. Selegeline Postulated to have neuroprotective effect
Reduce oxidative stress
Reduce free radical production
No benefit in producing
Nausea and hallucinations

36. Catechol-O-methyltransferase (COMT) Inhibitor
Increase the bioavailability of levadopa
Useful adjunct in early stage of PD and in patients w/ mild response fluctuations
Rare hepatocellular injury
Possible neurotoxicity in PD

37. Dopamine Agonist Binds to dopaminergic receptors
Restoration of effective neurotransmission

38. Dopamine Agonist Directly acting on the dopamine receptors
Postulated to provide neuroprotection
No conversion to dopamine
Do not produce toxic metabolites
Dec. endogenous dopamine turnover, decrease risk of oxidative stress
Monotherapy in early stage of PD – delay levodopa
Hypotension, nausea, vommiting and hallucinations

39. Dopamine Agonist Piribidel (Trivastal)
Pramipexole (Sifrol) – indicated for both early and advanced stages of PD; selectively binds to dopamine receptors and activate D2 receptor but with little or no affinity to the D1 receptor. Has greater affinity for D3 receptor than D2.
Ropinerole (Requip) – same as Pramipexole
Bromocriptine

40. Surgical Options Pallidotomy Thalamotomy Thalamic stimulation
Transplantation of fetal cells

41. Globus pallidus internus (Gpi) pallidotomy – resection of parts of Gpi.
Deep brain stimulation
Fetal nigral transplantation – not very successful

42. Nonpharmacologic Management
Early Stage
Advanced Stage
Education
-selective info
-aimed at promoting general health
Refer to PD organization
-problem oriented
Support
-emotional needs assessment
-support network assessment
-financial/occupational counseling
-Psychological counseling
-respite care
Exercise
-aerobics, stretching
-improves mood and mobility
-improves postural equilibrium reaction
-physiotherapy referral
-PD exercise group
-energy conservation techniques
Nutrition
-balanced diet
-fibers and fluids vs constipation
-calcium vs bone mass loss
-dietetic referral
-help preparing food
-meal deliveries

43. Secondary Effects of PD
Cardiovascular effects – orthostatic hypotension
GI tract – constipation, arrhythmia
Genitourinary effects – impotence, increase in urinary frequency
CN effects – hallucinations, depression, psychosis

44. Late Disabilities Levodopa-related disabilities
Toxicity
Dyskinesia
reduced response
motor fluctuations
Non-levodopa-related disabilities
Cognitive impairment
Dysphagia
speech and language disturbance
instability

45. Bleh
Urinary urgency
Urinary tension
Pain
Dysphonia
Panic attacks