Parkinson's disease is a progressive neurodegenerative disorder caused by loss of dopamine-producing neurons in the substantia nigra. It affects around 1% of the population over age 60, with symptoms including tremors, rigidity, bradykinesia, and postural instability. The pathology involves damage to neurons in the substantia nigra and presence of Lewy bodies containing alpha-synuclein protein aggregates. As the disease progresses, Lewy pathology spreads from the midbrain to other areas, resulting in additional motor, autonomic, and cognitive symptoms.

1. PARKINSON’S DISEASE:
A
PATHOPHYSIOLOGICAL
PERSPECTIVE
Dr. Vishnu R Nair,
PharmD, RPh, Dip. (Nutrition),
Dip. (Psychotherapy),
Assistant Professor,
NIMS Institute of Pharmacy.

2. DEFINITION:
PD  slow, progressive, neurodegenerative
disease, due to lack of dopamine in the brain.

3. EPIDEMIOLOGICAL
STATISTICS:
Disease affects at least 1% of population
worldwide
People greater than 60 years of age 
most affected!
Incidence: 4.5-21 cases per 1,00,000
population
Prevalence: 18-328 cases per 1,00,000
population
1.5 times more common in men than
women!
Approximately 15% of patients with PD
 have a first-degree relative with the
disease.

4. ETIOLOGY/ RISK
FACTORS:
Involves the following factors:
Genetic predisposition
Mutations in genetic composition:
 Increased expression of the following 
causes mitochondrial damage  causes
oxidative stress  production of free
radicals  leads to parkinsonism:
1.LRRK-2 [Leucine-rich repeat kinase-
2]
2.Parkin
3.PTEN-induced putative kinase-1
[PINK1]
Aging

5. Chronic exposure to pesticides
Living in rural area
Drinking well-water exposed to toxic
elements
Drug-induced parkinsonism:
 Any drug that reduces dopamine
level in body  can cause
Parkinsonism:
1. Metoclopramide
2. 1st generation antipsychotics
3. Cinnarizine
4. Promethazine.

6. NORMAL PHYSIOLOGY:

7. Basal ganglia  regulates voluntary
movement.
Basal ganglia  consists of:
1. Substantia nigra (very imp!!)
2. Striatum (very imp!!)
3. Globus pallidus (very imp!!)
4. Subthalamic nucleus
Substantia nigra  consists of 2
parts:
1.SNc (Substantia nigra pars
compacta)
2.SNr (Substantia nigra pars
reticulata)

8. Neurons that project from SNc to the
striatum  known as nigrostriatal
pathway
Striatum  conveys signals to SNr, via
dopamine1 (D1) & dopamine2 (D2)
pathways.
SNr  receives signals from striatum
 conveys processed signals to
thalamus  regulates activities of
motor cortex.
In short  information passes (via DA
neurons) in the following sequence:
SNc  striatum  SNr  thalamus 
motor cortex.

9. PATHOPHYSIOLOGY OF
PARKINSONISM:
Major damage  occurs in substantia
nigra (especially SNc)!
Pathological features include:
Loss of SNc neurons  reduced
activity of dopamine-producing
neurons
Presence of Lewy bodies in
neurons.
WHAT ARE LEWY BODIES?
Cytoplasmic filamentous
aggregates, which consist of a
protein “alpha-synuclein”
Look like “HALOS” when
examined in brain tests.

10. Lewy bodies, and their progressive
effects on brain.

11. Location of LEWY BODIES 
determine the clinical
manifestations of PD.
Lewy bodies  originate in enteric
nervous system & olfactory system 
progress with time to the brain.
With progression of Lewy pathology in
the midbrain (SNc)  motor features
appear!
In advanced stages of PD  Lewy
pathology spreads to cortex  leads to
mood, cognitive & behavioural effects!

12. CLINICAL PRESENTATION
OF PARKINSONISM:
PARAMETER FEATURES NOTED
GENERAL
FEATURES
 Bradykinesia (reduced
movement)
 Resting tremor
 Rigidity
 Postural instability.
MOTOR
SYMPTOMS
 Hypokinesia
 Reduced manual
dexterity

13.  Difficulty in arising from
a seated position
 Dysarthria (slurred
speech)
 Dysphagia (difficulty in
swallowing)
 Festinating gait
(tendency to pass from a
walking to a running
pace)
 “freezing” at initiation
of movement
 Hypomimia (reduced
facial animation)
 Hypophonia (reduced
voice volume)
 Micrographia
AUTONOMIC &
SENSORY
SYMPTOMS
 Bladder dysfunction
 Constipation

14.  Diaphoresis
 Fatigue
 Olfactory impairment
 Orthostasis
 Sexual dysfunction
 Seborrhea
 Sialorrhea (drooling)
MENTAL
STATUS
CHANGES
 Anxiety
 Apathy
 Bradyphrenia
(slowness of thought
process)
 Cognitive impairment
 Depression
 Hallucination/psychosis
SLEEP
DISTURBANCES
 Insomnia
 Excessive daytime
sleepiness

15.  REM sleep behaviour
disorder.

17. PARKINSONIAN FEATURES...IN
SHORT!

18. To easily remember the clinical
manifestations of Parkinsonism……
Remember the code: TRAP-SOAP-MAD!
Motor symptoms  TRAP:
Motor symptom
mnemonic
Code meaning
T Tremor at rest
R Rigidity (stiffness)
A Akinesia/
bradykinesia
P Postural instability &
gait abnormalities

19. Non-motor symptoms  SOAP:
Non-motor
symptom
mnemonic
Code meaning
S Sleep disturbances:
 Insomnia
 REM sleep behavioural
disorder
O Other symptoms:
 Fatigue
 Vision problems
 Seborrhoea
A Autonomic symptoms:
 Drooling
 Constipation
 Sexual dysfunction
 Urinary problems
 Sweating
 Orthostatic hypotension
 Dysphagia
P Psychological symptoms:
 Anxiety

20.  Psychosis
 Cognitive impairment
 Depression
 Suicidal tendency
Response fluctuations  MAD:
Response fluctuation
mnemonic
Code meaning
M
Motor fluctuations:
 Freezing
 Delayed reaction
A
Akathisia
D
Dyskinesias:
 Dystonia
 Chorea

21. THANKYOU!!!