Parkinsonism by Dr.Tapas Tripathi

1. Parkinsonism
Moderator : Dr. Prem Kumar
Presented By : Dr. Mohd. Junaid khan

2. Parkinsonism is a generic term that is used to define a syndrome manifest
as bradykinesia with rigidity and/or tremor. It has a differential
diagnosis (Table 435-2) that reflects damage to different components
of the basal ganglia. Among the different forms of parkinsonism, PD is the
most common (approximately 75% of cases).

3. Parkinsonism is a clinical syndrome characterized by motor
symptoms like bradykinesia,tremor and rigidity.
Classification of theParkinsonism
 Primary parkinsonism (Parkinson’s disease)
• Sporadic/Idiopathic
• Genetic
 Parkinsonism-plus syndromes (Atypical parkinsonism)
• Progressive supranuclear palsy (PSP)
• Multiple system atrophy(MSA)
• Cerebellar type (MSA-c)
• Parkinsons type(MSA-p)
• Cortical-basal ganglionic degeneration(CBGD)
• Frontotemporal dementia(FTD)

4.  Secondary parkinsonism (environmental etiology)
• Drugs induced(Antipsychotic medications,
Reserpine, Tetrabenazine)
• Postencephalitic(infection)
• Toxins: MPTP
, cyanide,CO, Mn, hexane
• Heavy metal (iron, manganese)
• Vascular
• Brain tumors
• Head trauma
• Normal-pressure hydrocephalus
• Liver failure

5. OTHER NEURODEGENERATIVE DISORDER
•Wilsons disease
•Huntingtons disease
•Neurodegenaration with brain iron accumulation
•SCA 3 (spinocerebellar ataxia)
•Fragile x-associated ataxia-tremor parkinsonism.
•Prion disease
•Dystonia-parkinsonism (DYT3)
•Alzheimers disease with parkinsonism

6. Anatomy Of Basal Ganglia
PARKINSON'S DISEASE 6
This Photo by Unknown Author is licensed under CC BY-SA-NC

7. COMPONENTS OF BASAL GANGLIA
• CAUDATE NUCLEUS
• PUTAMEN
• GLOBUS PALLIDUS INTERNA AND
EXTERNA
• SUBTHALAMIC NUCLEI
• SUBSTANTIA NIGRA
•(PARS COMPACTA AND RETICULATA)
•INPUT NUCLEI : STRAITUM
•OUTPUT NUCLEI : SUBSTANTIA
NIGRA PARS RETICULATA AND
GLOBUS PALLIDUS INTERNA

9. Functions Of Basal Ganglia
PARKINSON'S DISEASE 9
• Planning and modulation of movement pathways
• Reward processing and motivation
• Decision making
• Cognition

10. DIRECT BASAL GANGLIA PATHWAY
MOTOR
CORTEX
GPi
THALAMUS
VA/VL
FACILITATION OF
MOVEMENT
SNp
STRAITUM
SNc
EXCITATORY CONNECTIONS(RED ARROWS)
INHIBITORY CONNECTIONS(BLUE ARROWS)

11. INDIRECT BASAL GANGLIA
PATHWAY
MOTOR
CORTEX
GPe
THALAMUS
VA/VL
INHIBITION OF
MOVEMENT
GPi
STRAITUM
SNc
EXCITATORY CONNECTIONS(RED ARROWS)
INHIBITORY CONNECTIONS(BLUE ARROWS)
SUBTHALAMIC
NUCLEUS

13. PARKINSON'S DISEASE 13
Parkinson’s disease (PD)
• Second most common age-related neurodegenerative disease.
• Results due to reduction in the striatal dopamine content due to damage
of nigrostriatal pathway.
• Its cardinal clinical features were first described by the English physician
James Parkinson in 1817.
• James Parkinson was a general physician who captured the essence of
this condition based on a visual inspection of a mere handful of patients,
several of whom he only observed walking on the street and did not
formally examine.

14. Etiology
Idiopathic Genetic
Parkinson’s disease

15. Idiopathic
• Ageing
 Usual occurrence in late middle age, and
increases in its prevalence at older ages
 Loss of striatal dopamine and dopamine of cells in
the SN with age

16. Genetic factors
PD may be multifactorial in etiology with genetic
contributions.
The younger the age of symptom onset, the more likely genetic
factors play a dominant role.

18. Pathogenesis
Three major mechanisms in dopaminergic neuron
loss
 Mitochondrial dysfunction
 Oxidative and nitrosative stress
 Ubiquitin proteosome system dysfunction

21. PARKINSON'S DISEASE 21
PATHOLOGY
• Pathologically, the hallmark features of PD are degeneration of
dopaminergic neurons in the substantia nigra pars compacta (SNc),
reduced striatal dopamine, and intraneuronal proteinaceous inclusions
in cell bodies and axons that stain for α synuclein (known as Lewy bodies
and Lewy neurites, collectively as Lewy pathology)

22. PARKINSON'S DISEASE 22

23. Clinical Features &
Diagnosis of Parkinsonism

24. Motor symptoms
Non-motor symptoms

25. Motor symptoms
Characterized by Four cardinal features :
Bradykinesia (or Hypokinesia)
Tremor at rest
Rigidity
Postural instability

26. Bradykinesia
Slowness of movements with a progressive loss of
amplitude or speed.
Difficulty with planning, initiation and
execution of movements.

27. Clinical Manifestations of Bradykinesia
Difficulties with tasks requiring fine motor
control:
Loss of spontaneous movements andgesturing
Hypomimia (decreased facial expression)
MASK LIKE FACE
Decreased spontaneous blinking
Hypophonia
Micrographia
Sialorrhoea

30. Why Bradykinesia in Parkinsonism??
“Driving while stepping on the brakes”

31. Mechanism of action
BRADYKINESIA
TREMOR
RIGIDITY
POSTURAL
INSTABILITY
DEGENRATION
IN OTHER
BASAL GANGLIA
NUCLEI
INCLUSION
BODIES (LEWY
BODIES)
DEVELOP IN
NIGRAL CELLS
REDUCED
DOPAMINERGIC
OUTPUT FROM
SN
NEURONS IN SUBTHALAMIC NUCLEUS BECOMES MORE
ACTIVE THAN USUAL IN INHIBITING ACTIVATION OF
MOTOR CORTEX
BRADYKINESIA
DEPLETION OF PIGMENTED DOPAMENERGIC NEURONS IN
SNc

32. Rest Tremor
Tremor : Rhythmical & involuntary shaking,
trembling or quivering movements of the muscles.
Rest tremor ( 4 - 6 Hertz) :
Maximal when the limb is at rest
Disappears with voluntary movement and sleep
Alternating contraction of agonist and antagonist
muscles at a rapid pace
Usually Unilateral at onset

33. Involves the hands, lips, chin, jaw and legs .
“Pill-rolling”
Tremor:

34. Rigidity
Increased muscle tone felt during examination by
passive movement
Both the agonist and antagonist muscles are
involved
Rigidity :
Cogwheelrigidity
Lead-piperigidity

35. Postural instability
Stooped Posture
UNIVERSAL FLEXION :
Extreme neck flexion,
Extreme anterior truncal flexion (camptocormia) &
Flexion of elbows and knees.

36. Festinating / Shuffling Gait:
i) Difficulty to initiate walking
ii) Shortened stride
iii) Reduced arm swing
iv) Rapid small steps (shuffling)
RUNNING AFTER THE CENTRE OFGRAVITY
Freezing phenomenon
Myerson sign: glabellar tap absent

37. Non-motor symptoms
Neuropsychiatric
Depression &Anxiety disorders
Apathy
Autonomic disturbance (dysautonomia)
Urinary dysfunction
Constipation
Sensory symptoms
pain
Restless legs syndrome
Olfactory dysfunction

38. Sleep disturbances
REM behavior disorder
Excessive day time drowsiness
Cognitive impairment
Dementia : In >80% of patients after 20 years of
Disease
• Neuronal degeneration with Lewy pathology 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
nonmotor clinical features

40. Atypical Parkinson
• Atypical parkinsonism refers to a group of neurodegenerative conditions
that are usually associated with more widespread pathology than found in
PD (e.g., degeneration of striatum, globus pallidus, cerebellum, and
brainstem, as well as the SNc).
• These conditions include multiple system atrophy , progressive supranuclear
palsy and corticobasal syndrome . As a group, they tend to present with
parkinsonism (rigidity and bradykinesia) but manifest clinical differences
from PD reflecting their more widespread pathology.
• These include early involvement of speech and gait, absence of rest tremor,
lack of motor asymmetry, poor or no response to levodopa, and a more
aggressive clinical course. In the early stages, some cases may show a
modest benefit from levodopa and can be difficult to distinguish from PD,
but the diagnosis becomes clearer as the disease evolves over time

41. • Neuroimaging of the dopamine system is usually not helpful, as striatal
dopamine depletion can be seen in both PD and atypical parkinsonism.
By contrast, metabolic imaging of the basal ganglia/thalamus network
(using 2-F-deoxyglucose) may be helpful, showing a pattern of decreased
activity in the GPi with increased activity in the thalamus, the reverse of
what is seen in PD.

42. PARKINSON'S DISEASE 42
• Multiple system atrophy(Shy Dragger Syndrome)
• Bradykinesia, Rigidity(More symmetric motor invlovement)
• + Autonomic insufficiency features
• Orthostatic / postural hypotension is seen (recurrent falls )
• Neurogenic Bladder
• Constipation /diarrhea
• + Cerebellar features (MSAc): Gait apraxia
• Intentional tremors are seen
• MRI Brain :MSA-P iron deposition in the straitum and MSA-C
cerebellar atrophy with a characteristic Hot Cross bun sign in pons

43. MRI findings in MSA

44. MRI findings in MSA

45. PARKINSON'S DISEASE 45
Progressive supranuclear palsy(PSP)
• Due to tau protein deposition inside the neuronal cytoplasm
• Clinical features:
• Symmetric Axial rigidity
• Jerky toppling gait
• Recurrent falls
• Recurrent spilling of food on clothes ( due to eyelid apraxia ),slow
saccades
• Hyperextension of neck
• Downgaze paresis

46. PSP Neuro-Ophthalmological features
Vertical Supranuclear gaze Plasy
Downward > Upward
Horizontal Slow saccade
Convergence: Lost
Total Gaze palsy

47. MRI findings
in PSP

48. CBD
1. Unilateral Onset
2. Dystonia in arm
4. Rigidity & Bradykinesia
5. Limb apraxia / Useless arm
6. Alien Limb Phenomenon
7. Myoclonus (Stimulus Sensitive)

49. MRI findings in CBD

50. Signs PD PSP MSA CBD
Symmetry + +++ +++ _
Axial Rigidity + +++ ++ +
Palsy Vertical Gaze + +++ + +
Postural instability + +++ +++ +
Autonomic
features
+- + +++ -
L Dopa response
Early
+++ + + -
L Dopa response
late
++ - + -
Limb dystonia
Alien limb
- - - +++
MRI findings + ++ ++ +++

51. Diagnosis of Parkinsonism
Diagnosis is primarily clinical, based on history
and examination
Confirmatory diagnosis : Histological
demonstration of the intraneuronal Lewy
bodies on autopsy.
CT scan & MRI exclude other causes.

52. Examination of signs
Bradykinesia :
Ask patient to do repetitive movements as
quickly and as possible
• opening and closing the hand
• tapping thumb and index fingers
• or tapping the foot on the ground
Rest tremor:
Differentiate from the intentional tremor seen in
cerebellar disease
Best observed while the patient is focused on a
particular mental task.

53. Rigidity:
 Increased resistance to passive movements
Postural stability
 The “Pull test” is performed in order to assess
postural stability

54. UK Parkinson’s Disease Society Brain Bank’s
clinical criteria for the diagnosis of probable
Parkinson’s disease
Step 1
 Bradykinesia
 At least one of the following criteria:
• Rigidity
• Rest tremor (4–6 Hz )
• Postural instability (not caused by primary
visual, vestibular, cerebellar or
proprioceptive dysfunction)
Step 2
 Exclude other causes of parkinsonism

55. Step 3
 At least three of the following supportive
(prospective) criteria:
• Unilateral onset
• Rest tremor
• Progressive disorder
• Persistent asymmetry
• Severe levodopa induced chorea (dyskinesia)
• Clinical course of 10 years or more

57. Management of
Parkinsonism

58. No definitecure
Relief of cardinal signs- rigidity, tremor , &
akinesia
Correction of mood changes
Treatment of other symptoms such as
depression,sleep disturbance .
Treatment of cause when possible

59. Management
General
Measures
Drug Therapy Surgery

60. 1.General Measures
Physiotherapy
Speech therapy
Dietary controls

61. Physiotherapy
Helps to reducerigidity
Corrects abnormalposture
Improves walking , turning
& balance

62. Speech therapy
Helpful in patients where
dysarthria and dysphonia
interferes communication

63. Dietary controls
Include high-fiber diet
Choose foods low in saturated
fat and cholesterol.
Avoid high protein diet

64. Drug Therapy
Does not prevent disease progression but
improves quality of life
Drug therapy
Dopaminergic
activity
Cholinergic
activity

65. Classification of drugs
Drugs affecting Dopaminergic system
 Dopamine precursors: Levodopa
 Peripheral decarboxylase inhibitors: Carbidopa
 MAO-B Inhibitors: Selegiline, rasagiline.
 COMT Inhibitors: Tolcapone, entacapone.
 Dopamine releasing drugs:Amantadine
Dopamine receptor agonists:Bromocriptine, pergolide, cabergoline,
ropinirole, rotigotine,pramipexole.
Drugs affecting Cholinergic system
 Central anticholinergic:Trihexyphenidyl,Benztropine,
Biperidine, procyclidine.
 Antihistaminics: Promethazine

69. Levodopa
‘Gold-standard' treatment for Parkinson's..
Therapautic benefit is nearly complete in early stages
but declines as disease advances(“Wearing-off effect”)
1-2% cross BBB
Improves cardinal signs- tremor, rigidity and akinesia.

70. Side Effects
At the initiation of therapy
 Nausea, vomiting, hypotension, cardiac arrhythmias,
angina, taste alteration.
Avoided by gradual titration
Long-term complications
 Dyskinesias
 Behavioural effects: hallucination, psychosis
 On–off effect
 Wearing-off effect
(“on” episodes when the drug is working and “off” episodes when parkinsonian
features return)

71. PARKINSON'S DISEASE 71

72. LEVODOPA+ CARBIDOPA

73. Dopamine agonist
Ergot derivatives:
(e.g., bromocriptine, pergolide, cabergoline) and were associated with
ergot-related side effects, including cardiac valvular damage.
 Second generation of nonergot dopamine agonists :
(e.g., pramipexole, ropinirole, rotigotine)
Side effect:
oNausea,vomiting, and orthostatic hypotension.
o Hallucinations and cognitive impairment are more than levodopa so use
cautiosly in age more than 70
oSedation with sudden unintended episodes of falling asleep while driving a
motor vehicle have been reported.

74. MAO-B INHIBITORS
 Monotherapy in early disease.
Reduced “off” time when used as an adjunct to levodopa in patients with
motor fluctuations.

75. COMT INHIBITORS:
 Levodopa with a COMT inhibitor reduces “off” time and prolongs “on” time.
Two COMT inhibitors have been approved, tolcapone and entacapone.

76. Anticholinergic drugs:
Their major clinical effect is on tremor, although it is not certain that this benefit is
superior to what can be obtained with agents such as levodopa
and dopamine agonists. Still, they can be helpful in individual
patients with severe tremor.
Their use is limited particularly in the elderly, due to their propensity to induce a
variety of side effects including urinary dysfunction, glaucoma, and particularly
cognitive impairment.

77. Treatment approaches to newly diagnosed PD

78. Surgery
Deep Brain Stimulation
Thalamotomy
Pallidotomy
Neural Transplantation

79. REVIEW AND
CONCLUSION!

80. PARKINSONISM
CASE 1
Mr Poudel, 65 years old
man
Difficulty in walking and
speaking , tremor in left
hand and leg
Sleep disturbances

81. Rx:
Levodopa 250 mg+ carbidopa25mg
Medication reduced his symptoms but did not stop
the disease from getting worst.
His loss of mobility and speech impairment
limited his social interactions.
He and his wife also have had to give up many of
their retirement travel plans.

82. THANK U SIR