During my 1st &2nd year of residency period , i used to teach Anatomy and Orthopaedics for foreign undergraduate medical students. At last year i taught Neurology for one batch. so i posted some of my collections for competely educational purpose coz i believe in knowledge ...inseted of deleting these ppts , they may me useful for others so i shared it ....

1. PARKINSON’S DISEASE
Dr. sunil pahari, 3rd year resident ,
Yangtze university , hubei , china

2. TOPICS TO BE DISCUSSED
1. Definition
2. Epidemiology
3. Etiology
4. Risk factor
5. Types
6. Signs and Symptoms
7. Pathophysiology
8. Staging
9. Complications
10. Diagnosis
11. Pharmacotherapy

3. DEFINITION
 Parkinson’s disease (PD) is a slow, progressive,
neurodegenerative disease of the extrapyramidal
motor system.
 Dopamineneurons in the substantia nigra are
primarily affected, and degeneration of these
neurons causes a disruption in the ability to
generate body movements.

4. EPIDEMIOLOGY
 PD already the second most common neurodegenerative disease of
mid-to-late life in developed countries, will become increasingly
prevalent in developed countries in this century.
 In United States (US) and Western Europe.
 An estimate of approximately 10million people worldwide are living
with Parkinson’s Disease.
Age Incidence
60 – 69year ~1 in 200
70’s ~1 in 100
80’s ~1 in 35

5. PREVALENCE OF PARKINSON’S DISEASE

7. ETIOLOGY
1. Age – more than 60years.
2. Positive family history and Race.
3. Environmental Exposure: Herbicide and pesticide exposure, metals(
manganese,iron) and steel alloy industries.
4. Exposure to MPTP (1- methyl-4-phenyl-1,2,3,6 tetrahydropyridine), a
potent neurotoxin.
5. Environmental factors such as rural living,drinking well water.
6. Life experiences (trauma,emotional stress).
7. An INVERSE correlation between cigarette smoking and caffeine intake
in case-control studies.

8. RISK FACTOR
 Age. Young adults rarely experience Parkinson's
disease. It ordinarily begins in middle or late life, and the
risk increases with age. People usually develop the
disease around age 60 or older.
 Heredity. Having a close relative with Parkinson's
disease increases the chances that you'll develop the
disease. However, your risks are still small unless you
have many relatives in your family with Parkinson's
disease.
 Sex. Men are more likely to develop Parkinson's
disease than are women.
 Exposure to toxins. Ongoing exposure to herbicides
and pesticides may put you at a slightly increased risk of
Parkinson's disease.

9. TYPES
1. Primary or Idiopathic Parkinsonism
 The cause of the disease is unknown.
 Predominantly affecting the individuals over 60years of age.
 Over the years the dopaminergic neurons degenrate due to
H2O2 and free radicals such as O2-(superoxide) and OONO-
(Peroxynrite).
2. Secondary or Drug Induced Parkinsonism
• There is no degeneration as seen in above case, but the
decrease ion dopamine is drug induced.

10. SIGNS AND SYMPTOMS

11. SIGNS AND SYMPTOMS (SSS)
1. Increased muscular stimuation leading
to involuntary tremors which occurs
when the person sits or even at
rest(resting tremors).
2. Typical pill rolling movement of fingers
and nodding of head
3. Bradykinesia- Difficulty and slowness of
movements.
4. Rigidity of muscles leading to masked
appearance of face.
5. Jerk during voluntary movements.

12. 6. Aphonia- loss of volunatry control of muscles of
mouth and larynx leadint to loss of speech.
7. Posture and Gait:
- Gait is characterized by short steps,with feet
barely leaving the groung,producing an audible
shuffling noise.
- Stooping posture- forward flexed posture
- Dystonia- Abnormal, sustained, painful twisting
muscle contractions,often affecting the foot and
ankle.
8. Excessive secretion of salivary glands i.e sialorrhoea
and sebaceous glands
i.e seborrhoea
9. Absence of control over movements of eye.
10. Memory Disorder, loss of personal interest, loss of
reasoning and orientation.

13. PATHOPHYSIO
LOGY

14. PATHOPHYSIOLOGY
 The dopaminergic neuron from substantia nigra pars compacta
act on excitatory D1 receptors in the striatum and causes
excitation of the striatal neurons in the direct pathway.
 The excitation is neutralized when the dopaminergic neurons
from the substantia nigra pars compacta act on inhibitory D2
receptors in the stratum and cause the inhibition of the striatal
neurons in the indirect pathway.
 In direct pathway, the globus pallidus medial is innervated via
ihibitory GABAergic neurons from the striatum.
 Similarly, the neurotransmission from this region to the thalamus
is also carried out by inhibitory GABAergic neurons.
 However,the nervous innervation from the thalamus to the
cortex is via the excitatory glutaminergic neurons which results
in voluntary movements

15.  In the indirect pathway,similar to the direct pathway,the nervous
innervation from the striatum to globus pallidum lateral from these
regions to subthalmic nucleus is through inhibitory GABAergic
neurons.But the transmission from the subthalmic nucleus to globus
pallidus medial is through excitatory glutaminergic neurons.
 The basic difference between two pathways is the type of innervation to
the two mentioned regions(globus pallidus medials and substantia nigra
par reticulus).
 In direct pathway the innervation is inhibitory while in indirect pathway it
is excitatory in nature.
 Hence any alterations in the innervation to the globus pallidus medial
and substantia nigra par reticulata ultimately affect the
neurotransmission to the cortex, which results in either enhancement or
suppression of voluntary movements.

16.  Physiologically,dopamine causes the activation of direct
pathway and inhibition of indirect pathway.
 This results in excitation of cortex,leading to voluntary
movements.
 In parkinsonism,where the dopamine gets depleted due to
destrution of dopaminergic neurons,the direct pathway get
suppressed while the indirect pathway get overstimulated.This
leads to decreased excitatory outflow to the motor cortex
resulting in the suppression of voluntary movements

17.  Clinical features don’t emerge until >60-80% dopamine lost.
 Compensatory changes include hyperactivity in remaining neurones
(increased transmitter turnover), increase in dopamine receptors;
receptor supersensitivity.
 Other pigmented nuclei also affected (locus ceruleus and raphe).
Also cortex and other structures affected.
 Characteristic histological inclusion in affected neurons are
eosinophilic cytoplasmic inclusions in nigral cells called the Lewy
Bodies.

18.  Basal Ganglia
 Controls movement
 Dopamine
 Inhibitory
neurotransmitter in the
basal ganglia
 Acetylcholine
 Excitatory
neurotransmitter in the
basal ganglia
 Without dopamine, inhibitory
influences are lost and
excitatory mechanisms are
unopposed 
 Neurons of basal ganglia
are over stimulated 
 Excess muscle tone,
tremors & rigidity

19. HOEHN AND YAHR STAGING OF PARKINSON'S
DISEASE
1. Stage 1: Mild signs and symptoms on one side only, not disabling but
friends notice.
2. Stage 2: Symptoms are bilateral, minimal disability, posture and gait
affected
3. Stage 3: Significant slowing, dysfunction that is moderately severe
4. Stage 4: Severe symptoms, walking limited, rigidity, bradykinesia,
unable to live alone
5. Stage 5: Cachectic, complete invalidism, unable to stand, walk, require
nursing care

20. COMPLICATIONS
 Thinking difficulties.
 Depression and emotional changes..
 Swallowing problems. .
 Sleep problems and sleep disorders.
 Bladder problems
 Constipation
You may also experience:
 Smell dysfunction.
 Fatigue
 Pain.
 Sexual dysfunction

21. DIAGNOSIS
1. Neurological History
2. Response to levodopa
3. Imaging and Laboratory examination
4. Physical Examination

22. There are no standard diagnostic tests for Parkinson’s.
1. Neurological History
 The doctor looks to see if your expression is animated.
 Your arms are observed for tremor, which is present either when they are at
rest, or extended.
 Is there stiffness in your limbs or neck?
 Can you rise from a chair easily?
 Do you walk normally or with short steps, and do your arms swing
symmetrically? The doctor will pull you backwards.
 How quickly are you able to regain your balance?
2. Response to levodopa
 A person’s good response to levodopa (which temporarily restores dopamine
action in the brain) may support the diagnosis.
DIAGNOSIS

23. The main role of any additional testing is to exclude other diseases that imitate
Parkinson’s disease, such as stroke or hydrocephalus.
3. Imaging and Laboratory examination
a. Blood test - usually to rule out any other condition, such as abnormal thyroid
hormone levels or liver damage.
b. MRI or CT scan - to check for signs of a stroke or brain tumor. If there is/was no
stroke or brain tumor, most MRI or CT scans of people with Parkinson’s disease
will appear normal.
c. PET (positron emission tomography) scan –
this imaging test may sometimes detect low
levels of dopamine in the brain.

24. 4. Physical Examination:
 Two of the four main symptoms must be present - for a neurologist to
consider a Parkinson’s disease diagnosis, the patient must have two
of the four main symptoms.
 They must be present over a specific period.
 The four main symptoms are:
 Tremor or shaking
 Bradykinesia - slowness of movement
 Rigidity (stiffness) of the arms, legs or trunk
 Postural instability - balance problems and possible falls

25. MANAGEMENT
1. Pharmacotherapy
2. Non-Pharmacotherapy
3. Surgery

26. ANTI-PARKINSONS DRUG
1.Dopaminergic drugs
a. Dopamine precursor
b. Peripheral Decarboxylase Inhibitors
c. Dopamine agonist
i). Ergot derivatives
ii). Non- ergot derivatives
d. MAO-B Inhibitors
e. Dopamine facilitator
f. COMT iInhibitors
2.Anticholinergic Drugs
a. Anti-cholinergics
b. Anti-histamines

27. 1. Dopaminergic drugs
a. Dopamine preacursor
- Levodopa
b. Peripheral Decarboxylase Inhibitors
- Carbidopa
- Benserazide
c. Dopamine agonist
i). Ergot derivatives
- Bromocriptine
- Pergolide
- Lisuride
- Carbergolin
ii). Non- ergot derivatives
- Piribedil
- Ropinirole
- Pramipexole Apomorphine
- Rotigotine

30. d. MAO-B Inhibitors
- Seleginine
- Rasagiline
e. Dopamine facilitator
- Amantadine
f. COMT Inhibitors
- Entacapone
- Tolcapone

31. 2.Anticholinergic Drugs
a. Anti-cholinergics
- Trihexyphenidyl
- Benztropine
- Procyclidine
- Biperiden
b. Anti-histamines
- Diphenhydramine
- - Orphenadrine
- - Promethazine

33. LEVODOPA
 Well absorbed from gut, but > 90% is decarboxylated to
dopamine peripherally in GIT& blood vessels & only a small
proportion reaches the brain (dopamine does not readily cross
BBB). Therefore combined with peripheral decarboxylase
inhibitor that does not cross the blood-brain barrier along with L-
DOPA.
 Peripheral decarboxylase inhibitors, carbidopa & benserazide,
are available as combination preparations with levodopa, as
Sinemet & Madopar, respectively.

34. CARBIDOPA
 Is a structural analogue of L-dopa.
 Inhibits the conversion of L-dopa to dopamine in peripheral
tissue
 Carbidopa is highly ionized at physiological pH and does not
cross the blood-brain barrier, so it does not inhibit the
formation of dopamine in CNS
 It reduces GI and cardiovascular side effects of L-dopa and
enables about 75% reduction in dosage of L-dopa
 L-dopa-carbidopa sustained release combination designed to
reduce “wearing off” effect

36. Drug Dose MOA Diagram
Dopaminergic
drugs
a. Dopamine
preacursor
- Levodopa
I: 125
mg BD
M:
8 g/day
Levodopa increases
dopamine levels in the
brain leading to the
stimulation of dopamine
receptors.
b. Peripheral
Decarboxylase
Inhibitors
- Carbidopa
Initial:
25mg
tab TD
Max: 8
tab/day
Inhibits the conversion of
L-dopa to dopamine in
peripheral tissue
c. Dopamine agonist
-Bromocriptine
1 mg
initially,
sed to
2.5
mg ,TD
up to 30
mg/day.
Bromocriptine is a
dopamine D2 and D3-
agonist which works by
activating postsynaptic
dopamine receptors

37. Drug Dose MOA Diagram
MAO-B
Inhibitors
- Seleginine
10 mg/day
in single or
divided
doses
Selegiline increases
dopaminergic activity by
intervening with the re-
uptake of dopamine at
the synapse. It also
irreversibly inhibits the
MAO-B which is involved
in the metabolism of
dopamine.
Dopamine
facilitator
- Amantadine
100 mg/day,
up to 100
mg twice
daily Max:
400 mg/day.
Amantadine is a weak
dopamine agonist
possessing
antimuscarinic
properties. It alters
dopamine release and
re-uptake. It also
noncompetitively
antagonises N-methyl-D-
aspartate.

38. Drug Dose MOA Diagram
COMT
Inhibitors
- Entacapone
PO 200 mg w/
each
levodopa/dopa
decarboxylase
inhibitor dose.
Max: 200 mg
Entacapone is a selective,
reversible, peripheral
inhibitor of COMT, an
enzyme involved in the
metabolism of dopamine
and levodopa.
Anticholinergics
- Bromocryptine
Initial: 1
mg/day in
divided
doses,
gradually up
to 6-10
mg/day
Trihexyphenidyl is a
tertiary amine
antimuscarinic, which
competitively inhibits
the effects of
acetylcholine at the
muscarinic receptors of
autonomic effector
sites

39. Anticholinergics
Benztropine (Cogentin),
trihexyphenidyl (Artane)
Dry mouth, dry eyes,
constipation,
hypotension, cognitive
impairment, urinary
retention
Useful for symptomatic
control of Parkinson’s
disease (benefits are
mild to moderate);
associated with more
adverse effects than
other drugs
Carbidopa/levodopa
Immediate- and
sustained-release
carbidopa/levodopa
(Sinemet)
Nausea, somnolence,
dyskinesia, hypotension,
hallucinations
Levodopa is the most
effective medication and
remains the primary
treatment for
symptomatic
Parkinson’s disease; no
added benefit for motor
complications with
sustained-release
versus immediate-
release preparations
ADRs Indications

40. COMT inhibitors
Entacapone
(Comtan)
Diarrhea; exacerbates
levodopa adverse effects;
bright orange urine
Useful for managing motor
fluctuations (“wearing-off”
effect) in patients taking
levodopa; levodopa dose may
need to be reduced if
dyskinesia appears
Tolcapone (Tasmar) Diarrhea; exacerbates
levodopa adverse effects;
rare liver failure (liver
function monitoring
needed)
Dopamine agonists
Bromocriptine
(Parlodel)
Nausea, headache,
dizziness
Useful for early and advanced
disease
Pergolide (Permax) Somnolence;
hallucinations; nausea;
edema; fibrosis of cardiac
valves, lung, and
retroperitoneum;
retroperitoneal and
pulmonary fibrosis
Useful for the initial treatment of
parkinsonism and as adjunct
therapy in patients taking
levodopa

41. MAO-B inhibitors
Selegiline (Eldepryl) Nausea, insomnia, drug
interactions with other
MAO inhibitors/tyramine
Useful for symptomatic
control of Parkinson’s
disease (benefits are mild
to moderate) and as
adjuvant therapy for
patients with Parkinson’s
disease and motor
fluctuations
Rasagaline (Azilect) Weight loss, hypotension,
dry mouth, drug
interactions with other
MAO inhibitors/tyramine
NMDA receptor inhibitor
Amantadine (Symmetrel) Nausea, hypotension,
hallucinations, confusion,
edema
Useful for treating akinesia,
rigidity, tremor, dyskinesia

42. SURGERY
1. Deep brain stimulation
2. Pallidotomy
3. Thalamotomy

43.  Deep brain stimulation
Affects movement by using electrical impulses to stimulate a
target area in the brain. The electrical impulses are generated by
wire electrodes surgically placed in the brain. Deep brain
stimulation may be used in addition to therapy with levodopa or
other drugs when drugs alone do not control symptoms
adequately.
It does not destroy brain tissue and has fewer risks than older,
more destructive surgical methods, such as pallidotomy and
thalamotomy.

44.  Pallidotomy involves the precise destruction of a
very small area in the deep part of the brain (the
globus pallidus) that causes symptoms.
 Thalamotomy involves the precise destruction of
very small area in the deep part of the brain (the
thalamus) that causes symptoms.

45. NON- PHARMACOLOGICAL TREATMENT
Healthy eating
 Eat a nutritionally balanced diet that contains plenty of fruits, vegetables
and whole grains. Eating foods high in fiber and drinking an adequate
amount of fluids can help prevent constipation that is common in
Parkinson's disease.
 A balanced diet also provides nutrients, such as omega-3 fatty acids, that
may be beneficial for people with Parkinson's disease.
Exercise
 Exercising may increase your muscle strength, flexibility and balance.
Exercise can also improve your well-being and reduce depression or
anxiety.
 Try not to move too quickly.
 Aim for your heel to strike the floor first when you're walking.
 If you notice yourself shuffling, stop and check your posture.
 It's best to stand up straight.
 Look in front of you, not directly down, while walking.
.

46. Avoiding falls
 In the later stages of the disease, you may fall more easily.
 The following suggestions may help:
 Make a U-turn instead of pivoting your body over your feet.
 Keep your center of gravity over your feet without leaning or
reaching.
 Avoid carrying things while you walk.
 Avoid walking backward.
Daily living activities
 Daily living activities — such as dressing, eating, bathing and
writing — can be difficult for people with Parkinson's disease. An
occupational therapist can show you techniques that make daily
life easier

47. THANK YOU!!!