Parkinson's disease is a brain disorder that occurs when certain nerve cells in the substantia nigra die or become impaired, reducing dopamine levels. The key signs are tremors, slow movement, rigidity, and difficulty with balance. It is caused by the loss of dopamine-producing cells and presence of Lewy bodies. While there is no cure, treatment aims to manage symptoms through dopamine replacement and other drugs, as well as physical and speech therapy.

1. parkinsonism
shwethaBy
Dr.SHWETHA.A.P

2. Also called :
• Parkinson's Syndrome
• Atypical Parkinson's
• Secondary Parkinson's

3. INTRODUCTION
Parkinsonism is a clinical definition of
variety of underlying pathologies that can
cause parkinson’s like symptom .
There are a number of disorders that can
produce the symptoms referred to as
Parkinsonisms. Parkinson’s is one of the
parkinsonian disorders.

4. Studied & discovered by James Parkinson (1817) in his essay
on the shaking palsy.
Pathology was not well understood until the early 20th century.
In 1919, Tretiakoff observed that the most critical abnormality
in pd was the loss of neurons in the substantia nigra pars
compacta of the midbrain.
In the 1950s,the importance of dopamine and its depletion
from the basal ganglia as the key to understanding the
pathophysiology and pathologic biochemistry of pd was
discovered.

5. Essay on the shaking palsy –
James Parkinson 1817
“involuntary tremulous
motion , with lessened
muscular power, in part not
in action and even when
supported ;with a propensity
to bend the trunk forward,
and to pass from a walking to
a running pace , the senses
and intellect being uninjured

6. causes
•Parkinson's disease (PD) is the most common
cause of parkinsonism,
•A wide-range of other aetiologies may lead to a
similar set of symptoms, including
1. Some toxins
2. A few metabolic diseases
3. Its most common cause is as a side effect of
medications,mainly neuroleptic antipsychotics
4. Antidepressants

7. • Impaired release of dopamine - Idiopathic parkinsonism.
• Drug depleting dopamine store - reserpine, tetrabenzine
• Toxin damaging dopaminergic neuron
• Viral infection- Encephalitis ,Japanese encephalitis
• Trauma-repeated head injury[punch drunk syndrome]
• Miscellaneus-wilson disease,huntingtion’s disease
Causes

8. CLASSIFICATION
Primary = Idiopathic = Parkinson’s Disease
Secondary = Acquired = Parkinsonism

9. CLINICAL DEFINITIONS
(Lewy bodies = aggregation of protein alpha-synuclein in brain neurons)
Parkinsonism Parkinson Disease
1. Resting tremor
2. Bradykinesia
3. Cogwheel rigidity
4. Impaired postural
reflexes
5. PD can be one among the
parkinsonian disorder &
many other.
6. Won’t respond to
dopamine replacement
therapy.
Parkinsonian symp. plus
1. Asymmetric onset
2. DOPA responsive
3. Absence of Saccadic
problems & Early, severe
orthostasis
4. Lewy bodies in SN
5. Respond to dopamine
replacement therapy

10. Demonstration of Parkinsonian Gait

11. 1. Parkinson’s disease
Also called Parkinson Disease, Parkinson's, Idiopathic
Parkinsonism, Primary Parkinsonism, PD , Hypokinetic
Rigid Syndrome/HRS, or Paralysis Agitans
•2nd most commonest neurodegenerative disease.
•Affects men and women of all races, all occupations,
and all countries
•Mean age of onset is about 60 years, but cases can be
seen in patients in their 20s, and even younger

12. Parkinson’s disease is a chronic progressive
degenerative disorder of the CNS caused by an
imbalance b/w dopaminergic & cholinergic activity in
the brain due to degeneration of dopaminergic neurons
resulting in depleted levels of dopamine in the brain
leading to motor function disorder & various other extra
pyramidal symptoms.
DEFINITION

13. Parkinson's Defined
•Parkinson disease is a brain disorder.
•It occurs when certain nerve cells (neurons) in a part
of the brain called the substantia nigra die or become
impaired.
•Normally, these cells produce a vital chemical known
as dopamine. Dopamine allows smooth, coordinated
function of the body's muscles and movement.
•When approximately 80% of the dopamine-producing
cells are damaged, the symptoms of Parkinson disease
appear.
In short

14. Causes of Parkinson’s
 Genetics –
 15 – 25% of people with Parkinson's report having a relative
with the disease .
 The vast majority of Parkinson's cases are not directly
inherited, but researchers have discovered several genes that
can cause the disease in a small number of families.
 Environmental Factors – Epidemiological research has
identified several factors that may be linked to PD,
including
• Rural living,
• Well water,
• Herbicide use
• Exposure to pesticides.
There is though no evidence to prove there is environmental factors that cause
Parkinsons.

15. CLINICAL FEATURES
Cardinal Features Other Motor Features Nonmotor Features
• Bradykinesia
• Rest tremor
• Rigidity
•Gait disturbance/postural
instability
•Micrographia
•Masked facies
(hypomimia)equalize
•Reduced eye blink
•Soft voice (hypophonia)
•Dysphagia
•Freezing
• Anosmia
• Sensory disturbances (e.g.,
pain)
• Mood disorders (e.g.,
depression)
• Sleep disturbances
• Autonomic disturbances
• Orthostatic hypotension
• Gastrointestinal
disturbances
• Genitourinal disturbances
• Sexual dysfunction
• Cognitive
impairment/Dementia

16. C/F
TREMORS(4-6hz) RIGIDITY
Tremors[pill rolling] at
rest,
 Decreases on action.
 Usually first in
finger/thumb.
Coarse flexion/extension
of finger[pill rolling &
drum beating]
-Cog wheel type especially in
upper limb {stiffness in all
direction of movement}.
- Plastic type {lead type}
mostly appreciated in
legs.(hypertonicity felt in a parkinsonian
limb throughout the range of movements of a
joint.)
- In trunk rigidity manifest by
flexed& stooped posture

17. C/F
HYPOKINESIA
Characterized by poverty & slowness of movement. Slowness in
initiating movement.
Hand writing : Micrographia
Gait - Patient walk with short step , with a tendency to run{as
they are catching their own centre of gravity}-festinating gait
General –
• Expressionless face with staring look with infrequent blinking.
• Monotonus speech.
• Dementia & depression in advance stage

18. EPIDEMIOLOGY OF PD
Increased risk Decreased risk
1. Pesticide exposure
2. Pre-menopausal
oopherectomy
3. Familial aggregation
1. Smoking
2. Coffee
3. High plasma urate

19. Pathologic definitions (20th Century)
• Lewy bodies within
damaged substantia nigra
(and other brainstem
pigmented nuclei)
• “Incidental” Lewy bodies
represent pre-clinical
Parkinson’s disease

20. ANATOMICAL
•The basal ganglia,( a group of "brain structures" )innervated by the
dopaminergic system, are the most seriously affected brain areas in PD
•main pathological characteristic of PD is cell death in the substantia
nigra and, more specifically, the ventral (front) part of the pars compacta,
affecting up to 70% of the cells by the time death occurs
•Macroscopic alterations can be noticed on cut surfaces of the brainstem,
where neuronal loss can be inferred from a reduction
of melanin pigmentation in the substantia nigra and locus coeruleus
PATHOLOGY

21. • Histopathology (microscopic anatomy) of the substantia nigra and
several other brain regions shows neuronal loss and lewy bodies in
many of the remaining nerve cells.
•Neuronal loss is accompanied by death of astrocytes(star-
shaped glial cells) and activation of the microglia(another type of
glial cell)
•Lewy bodies are a key pathological feature of pd
(A lewy body (stained brown) in a brain cell of
the substantia nigra in parkinson's disease. The
brown colour is positive immuno -
histochemistry staining for alpha-synuclein)

23. PATHOLOGY
• Pathology begins in the peripheral autonomic nervous system,
olfactory system, and dorsal motor nucleus of the vagus nerve in
the lower brainstem, and then spreads in a sequential manner to
affect the upper brainstem and cerebral hemispheres.
• Dopamine neurons are affected in midstage disease.
• Several studies suggest that symptoms reflecting nondopaminergic
degeneration such as constipation, anosmia, rapid eye movement
(rem) behavior sleep disorder, and cardiac denervation precede the
onset of the classic motor features of the illness.

24. PATHOLOGY
• Degeneration of dopaminergic neurons in the substantia nigra
pars compacta (snc), reduced striatal dopamine, and
intracytoplasmic proteinaceous inclusions known as lewy
bodies .
• Neuronal degeneration with lewy body formation can also
affect cholinergic neurons of the nucleus basalis of meynert
(NBM), norepinephrine neurons of the locus coeruleus (LC),
serotonin neurons in the raphe nuclei of the brainstem, and
neurons of the olfactory system, cerebral hemispheres, spinal
cord, and peripheral autonomic nervous system.
• This "nondopaminergic" pathology is likely responsible for the
nondopaminergic clinical features

25. SIGNS AND TESTS
 The healthcare provider may be able to diagnose
secondary parkinsonism based on the patient's history,
symptoms, and physical examination.
 However, the symptoms may be difficult to assess,
particularly in the elderly.
 For example, the tremor may not appear when the
person is sitting quietly with the arms in the lap. The
posture changes may be similar to those caused by
osteoporosis or other changes associated with aging.
The lack of facial expression may be a sign of
depression.

26.  Examination may show increased muscle tone,
tremors of the Parkinson's type, and difficulty
initiating or completing voluntary movements.
Reflexes are usually normal.
 Tests are not usually specific for secondary
parkinsonism but may be used to confirm or rule
out other disorders that may cause similar
symptoms.

27. DIFFERENTIAL DIAGNOSIS
•Diagnosis is mainly clinical and is based on the clinical findings.
•Among the most common are
• Side effects of drugs (mainly the major tranquilizers such as
haloperidol),
• Strokes involving the basal ganglia,
• Degenerative disorders such as Progressive Supranuclear
Palsy (PSP), Corticobasal Ganglionic Degeneration,
Olivopontocerebellar Degeneration, Multiple System Atrophy,
and Huntington's Disease.

28. TREATMENT
presently no cure or prevention of Parkinson's
disease.
Treatment strategies
1. Conservative Approach
2. Neuroprotective Approach
3. Symptomatic Approach

29. Conservative approach
1. Avoid all drugs until symptoms are troublesome
2. When symptoms become troublesome start
amantadine and an anticholinergic
3. When symptoms become disabling introduce L-
Dopa or agonists at minimal doses

30. Neuroprotective approach
1. All newly diagnosed cases should be started
on Selegeline
2. When symptoms become disabling add
dopaminergic drugs

31. Symptomatic approach
• At diagnosis ,treatment immediately started
with dopaminergic drugs
• Treatment continually modified in order to
maintain maximum function for the maximum
amount of time

32. DRUG THERAPY
Drugs acting on dopaminergic system:
1. Dopamine precursors: L-dopa
2. Dopa decarboxylase inhibitors: carbidopa & benserazide
3. Dopamine agonists: bromocryptine, pergolide, peribidil,
ropinirole, pramipexole
4. Dopamine facilitators: amantadine
5. MAO-B inhibitor: selegiline
6. COMT-inhibitors: entacapone, tolcapone
Drugs acting on central cholinergic system:
1. Central anticholinergics: trihexiphenidyl, procyclidine, biperidin.
2. Central antihistaminics; orphenadrine, promethazine

33. PREVENTIVE TREATMENT
Amantadine or anticholinergic medications
Levodopa/carbidopa
Dopamine agonists
Vitamin E- has been suggested to lower the risk of PD risk.
Health Food- papaya and blueberries have been suggested
to slow nerve cell death.
**Neither one of these medications have provided
any real evidence that they slow down the progression of Parkinson’s
or manages symptoms.

34. PHYSICAL THERAPY
 Physical therapy is helpful in Parkinsonism. It
maintains muscle tone, flexibility, improves
posture and gait.
 Speech therapy and occupational therapy may help
promote function and independence, and may help
maintain skills and positive attitude and minimize
depression.

35. SURGERY
•Newest Version of surgery- DBS, (deep brain stimulation) this
was developed in 1990 and is the standard treatment.
Procedure
•Electrodes are inserted into the targeted brain region using MRI
and neurophysiological mapping to ensure that they are in the right
place.
•Next an impulse generator or IPG (similar to a pacemaker) is
implanted under the collarbone to provide an electrical impulse to a
part of the brain involved in motor function.
•Patients have a controller, which allows them to check the battery
and to turn the device on or off. An IPG battery lasts for three to
five years and is easy to replace under local anesthesia.

36. THANK YOU

37. Parkinson's Defined
•Parkinson disease is a brain disorder.
•It occurs when certain nerve cells (neurons) in a part
of the brain called the substantia nigra die or become
impaired.
•Normally, these cells produce a vital chemical known
as dopamine. Dopamine allows smooth, coordinated
function of the body's muscles and movement.
•When approximately 80% of the dopamine-producing
cells are damaged, the symptoms of Parkinson disease
appear.
In short

38. CLINICAL PRESENTATION
Altered body image
(depression)
Poor balance
Bradykinesia (slow
movement)
Bradyphrenia (slowness of
thought)
Constipation
Dribbling/drooling
Dyskinesias (involuntary
movements)
Dysphagia (difficulty
swallowing
Dystonia (pain spasms)
Excessive sweating (impaired
thermoregulation)
Hullucinations (visual)
Postural hypotension
Restless leg syndrome (leg
aches, tingle, or burn)
Rigidity
Sleep disturbance
Slurring/slowing of speech
Tremor

39. The key signs of Parkinson disease are:
• Tremor (shaking)
• Slowness of movement
• Rigidity (stiffness)
• Difficulty with balance
Other signs of Parkinson disease may include:
• Small, cramped handwriting
• Stiff facial expression
• Shuffling walk
• Muffled speech
• Depression

40. Demonstration of Parkinsonian Gait

41. PATHOLOGY
• The primary symptoms of Parkinson's disease result from greatly reduced
activity of dopamine-secreting cells caused by cell death in the pars
compacta region of the substantia nigra.
• There are five major pathways in the brain connecting other brain areas
with the basal ganglia. These are known as the motor, oculo-
motor,associative, limbic and orbitofrontal circuits, with names indicating
the main projection area of each circuit.
• All of them are affected in PD, and their disruption explains many of the
symptoms of the disease since these circuits are involved in a wide variety
of functions including movement, attention and learning. Scientifically, the
motor circuit has been examined the most intensively.

42. Additional Info :
DOPAMINE:
• It is a principle inhibitory NT in the brain whose distribution is restricted to
the dopaminergic neurons of substantia nigra (extra pyramidal motor
center), limbic system & hypothalamus.
• All catecholamine's most of dopamine secreted in the synapse is recaptured
by reuptake mechanism involving dopamine transporters. They are also
degraded by MAO & COMT.
ACETYLCHOLINE:
• It is an excitatory NT which is well distributed in various regions in the brain &
also secreted by the cholinergic neurons of the caudate nucleus in the basal
ganglia. Along with dopamine they together regulate the motor function.
• Ach is quickly degraded in the synapse by choline esterase enzyme.

43. Clinical definitions
Parkinsonism
1. Resting tremor
2. Bradykinesia
3. Cogwheel rigidity
4. Impaired postural
reflexes
5. Parkinson Disease
Parkinson Disease
Parkinsonian symp. Plus
1. Asymmetric onset
2. DOPA responsive
3. Absence of
1. Saccadic problems
2. Early, severe
orthostasis
4. Lewy bodies in SN

44. LEVODOPA
• Levodopa has been the most widely used treatment
for over 30 years.
• L-DOPA is converted into dopamine in the
dopaminergic neurons by dopa decarboxylase
• .Since motor symptoms are produced by a lack of
dopamine in the substantia nigra, the administration
of L-DOPA temporarily diminishes the motor
symptoms

45. TOLCAPONE
• Inhibits the COMT enzyme, which degrades dopamine, thereby prolonging
the effects of levodopa.
• Used to complement levodopa
• Possible side effects such as liver damage
DOPAMINE AGONISTS
•Bind to dopaminergic post-synaptic receptors in the brain have similar effects to
levodopa.
• were initially used for individuals experiencing on-off fluctuations and dyskinesias
as a complementary therapy to levodopa;
• They are now mainly used on their own as an initial therapy for motor symptoms
with the aim of delaying motor complications.
• When used in late pd they are useful at reducing the off periods.

46. MAO-B inhibitors (selegiline and rasagiline)
• Increase the level of dopamine in the basal ganglia by blocking its
metabolism.
• They inhibit monoamine oxidase-b (mao-b) which breaks down dopamine
secreted by the dopaminergic neurons.
• The reduction in mao-b activity results in increased l-dopa in the striatum.
• Used as monotherapy
• Improve motor symptoms and delay the need for levodopa in early disease,
• Produce more adverse effects
• Less effective than levodopa.

47. Other surgical methods
1. Unilateral thalamotomy -- can be used to reduce tremor.
2. Unilateral Pallidotomy is an effective technique for reducing contralateral
levodopa induced dyskinesias.
3. Unilateral deep brain stimulation of the thalamus for tremor may also be of
benefit for tremor.
4. Neural transplantation is no longer felt to be effective treatment.
5. Gamma knife -- thallamotomy or pallidotomy can be performed with
focussed radiation