Parkinsonism is a clinical syndrome characterized by symptoms such as tremors, rigidity, and bradykinesia, first described by James Parkinson in 1817 and more commonly seen in individuals over 65 years old. The disease is primarily linked to dopamine deficiency due to degeneration in the substantia nigra, leading to impaired motor control and various other symptoms, including cognitive decline. Multiple System Atrophy (MSA) is a progressive disorder with features of parkinsonism and autonomic dysfunction, distinguished into two categories based on predominant symptoms.

1. Parkinsonism
Dr. Varun SJ Doctor of Pharmacy,

2. INDEX
• History
• Definition
• Causes
• Risk factors
• Symptoms
• Pathophysiology
• Important questions with answers

3. It is a clinical syndrome characterized
by
diminished facial expression,
stooped posture,
slowness of voluntary movement,
festinating gait,
rigidity and
a “pill – rolling” tremor

4.  First described in 1817 by an English
physician, James Parkinson, in “An Essay
on the Shaking Palsy.”
 The famous French neurologist, Charcot,
further described the syndrome in the late
1800s
Parkinson Disease

5. • It is a degenerative disorder of the CNS
• The most common movement disorder
affecting 1-2 % of the general population
over the age of 65 years.
• Parkinson's disease is the most common
form of parkinsonism

6. What causes PD
May be combination of factors involving
genetics, environmental agents,& abnormalities
in cellular process.

7. Risk Factors Age - the most important risk factor
Develops around age 50
* incidence rises with age
* affects 1-2% of population > age 65
 Positive family history
 Male gender
Higher incidence in men (62%) compared to women (38%)
 Environmental exposure: Herbicide and pesticide exposure, metals
(manganese, iron), well water, farming, rural residence, wood pulp
mills; and steel alloy industries
 Life experiences (trauma, emotional stress, personality traits such as
shyness and depressiveness)

8. Three cardinal symptoms:
 resting tremor
 bradykinesia
(generalized
slowness of
movements)
 muscle rigidity
Symptoms worsen as
disease progresses

9.  Resting tremor: Most common first
symptom, usually asymmetric and most
evident in one hand with the arm at rest.
can occur in head, face, jaw, & leg

10. • Bradykinesia: Difficulty with daily
activities such as writing, shaving,
using a knife and fork, and opening
buttons; decreased blinking, masked
facies, slowed chewing and
swallowing.

11. • Rigidity: Muscle tone increased in
both flexor and extensor muscles
providing a constant resistance to
passive movements of the joints;
stooped posture, anteroflexed head,
and flexed knees and elbows.

12. Postural manifestations –
■ postural instability
■ rigidity
■ stooped

13. Additional Symptoms
 Dysfunction of the autonomic nervous system:
Impaired gastrointestinal motility, bladder
dysfunction, sialorrhea, excessive head and neck
sweating, and orthostatic hypotension.
 Depression: Mild to moderate depression in 50 %
of patients.
 Cognitive impairment: Mild cognitive decline
including impaired visual-spatial perception and
attention, slowness in execution of motor tasks,
and impaired concentration in most patients; at
least 1/3 become demented during the course of the
disease.

14. Parkinson’s Disease – Stages of Symptoms
Stage Symptoms
One Unilateral
Tw o Bilateral
No balanc e impairment
Three Balanc e impairment
Mild to mod erate d isease
Physic ally ind ependent
Four Severe d isability
Still able to w alk & stand unassisted
Five Wheelc hair-bound or bed rid d ened
unlessassisted

15. Parkinson’s Disease - Pathophysiology
Question: What causes the movement problems of PD?
Answer: Deficiency of the brain chemical dopamine
occurs in the basal ganglia.
The Basal Ganglia is an area deep inside the cortex of
the brain that coordinates normal muscle activity.

16. • Question: What causes the dopamine
deficiency?
• Answer: Degenerative changes in the
substantia nigra and striatum portions of the
basal ganglia reduce dopamine production.
Cross section of striatum
Substantia nigra

17. Cells degenerate in substantia nigra (Sn)
Substantia nigra destroyed
Dopamine decreases
Muscle cell activation decreases
Movement control decreases
Parkinson’s Disease - Pathophysiology
Healthy
Sn
PD Sn

18. Pathophysiology
• Imbalance of dopamine and acetylcholine
• Loss of 80 to 90% of dopaminergic production
in the substantia nigra
• Lewy Bodies

19. • Lewy bodies are abnormal aggregates of
protein that develop inside nerve cells in
Parkinson's disease (PD). They are
identified under the microscope when
histology is performed on the brain.
• Lewy bodies appear as spherical masses
that displace other cell components.
There are two morphological types:
classical (brain stem) Lewy bodies and
cortical Lewy bodies.

20. • A classical Lewy body is an eosinophilic
cytoplasmic inclusion that consists of a dense
core surrounded by a halo of 10-nm wide
radiating fibrils, the primary structural
component of which is alpha-synuclein.
• In contrast, a cortical Lewy body is less well
defined and lacks the halo. Nonetheless, it is
still made up of alpha-synuclein fibrils.

21. Morphology
• Macroscopic findings : substantiua nigra - pallor
• Microscopic examination:
 loss of pigmented, catecholaminergic neurons
 Lewy bodies found in remaining neurons

22. • Multiple system atrophy (MSA) is a progressive
neurodegenerative disorder characterized by
symptoms of autonomic nervous system failure such
as fainting spells and bladder control problems,
combined with motor control symptoms such as
tremor, rigidity, and loss of muscle coordination.
• MSA affects both men and women primarily in their
50s
Multiple System Atrophy

23. MSA = OPCA + SDS + SND
• Olivopontocerebellar atrophy (OPCA)
• Shy-Drager syndrome (SDS)
• Striatonigral degeneration (SND)

24. • The disease tends to advance rapidly
over the course of 9 to 10 years, with
progressive loss of motor skills,
eventual confinement to bed, and
death.
• There is no remission from the
disease. There is currently no cure

25. Multiple System Atrophy
• Neurodegenerative disorders affecting
multiple neural systems
• Characterized by the presence of glial
cytoplasmic inclusions (GCIs), typically
within the cytoplasm of
oligodentrocytes.
• α Synuclein is the major component of
the inclusion – synucleinopathy

26. • Unlike PD with (α synuclein inclusion) no
mutations in the gene for this synaptic protein
• (A53T, A30P and E46K) – MUTATED GENES
SPECIFIC FOR PD

27. • Definition of categories of MSA: The 2
categories of MSA are (1) with predominant
parkinsonism (MSA-P) and (2) with cerebellar
features (MSA-C).
• MSA-P is the category of MSA where
extrapyramidal features predominate. The term
striatonigral degeneration, parkinsonian variant
is sometimes used.
• MSA-C is the category when cerebellar ataxia
predominates. It is sometimes termed sporadic
olivopontocerebellar atrophy.
• The designation to a category MSA-P or MSA-C
depends on the dominant feature at the time of
evaluation, which can change with time.

28. Clinical Features
• Two principal symptoms
are parkinsonism and autonomic dysfunction,
particularly orthostatic hypotension.
• When these are present in relative isolation,
the syndromes may be referred to as
striatonigral degeneration and Shy Drager
syndrome respectively.

29. • Parkinsonism (akinesia and rigidity) can be
related to degree of cell loss from the
substantia nigra and striatum
• Ataxia - with changes in the circuits involving
the pons, cerebellum and inferior olive.
• autonomic symptoms - with loss from the
catecholaminergic nuclei of the medulla and
the intermediolateral cell column of the spinal
cord.

30. Morphology
• Macroscopic examination – atrophy of the
cerebellum, including the cerebellar peduncles,
pons, medulla, substantia nigra and striatum
• These brain regions shows neural loss as well
as cytoplasmic and nuclear inclusions
• These inclusions contains a synuclein, ubiquitin
and α B crystallin.