parkinsonism update

1. DR RAMDHAN KR KAMAT
PG (3rd year)
JLNMCH, Bhagalpur

2. History & epidemiology
- Introduction and Conclusion
Anatomy & physiology
Pathology of Parkinsonism
Clinical features & diagnosis of Parkinsonism
Management of Parkinsonism
Pathology of Alzheimer’s disease
Clinical Feature & Diagnosis of Alzheimer’s
Management Of Alzheimer’s Disease

3. 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 449-2) 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).

4. 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)

5.  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

6. 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

9. Neurodegenerative diseases
Parkinson’s Disease
Alzheimer’s Disease
Huntington’s Disease
Amyotrophic lateral sclerosis (ALS)
SpinocerebellarAtaxia

11. Case Presentation

12. Began to experience tremors and stiffness of his left
arm while he walked
Changes in his posture and unusual movements of
his left arm.
Sleep disturbances
Gait problems- stooped posture
Symptoms gradually worsened with time
Case 1
Mr Anil chaudhry, 65 years old man, a retired
university professor……

13. Case 2
Mrs Meena devi, 76 years old woman
Lived alone for several years
Brought to the neurological department, by
her daughter, memory impairment
General and neurological examinations-
normal
Speech – highly anomic , paraphasic
Unable to provide birth month, year, current
year
Cognitive domain – below average

14. HISTORY & EPIDEMIOLOGY

15. History of Parkinson’s
Disease
First clear medical description: James
Parkinson in An Essay on the Shaking Palsy
(1817)
Jean-Martin Charcot-
 Influential in refining and expanding this
early description & in disseminating
information internationally
 Named the disorder as Parkinson’s disease

16. William Gowers- Slight male predominance of
the disorder, joint deformities typical of the
disease.
Richer and Meige
Babinski - Babinski sign
Brissaud
Greenfield and Bosanquet- Clear delineation of
the brain stem lesions

17. Epidemiology of Parkinson’s
disease
Prevalence
 Crude prevalence –India - 328 per 100,00
Incidence
 Crude annual incidence rates- 1.5 per 100,000
population (China) in 1986 to 14.8 (Finland)
through 1968 to 1970.

18. Gender differences
 Slightly more common in men than in women
 Male to female ratio- 1.2:1 to 1.5:1
Geographic distribution
 Crude prevalence
• China - 15 per 100,000
• India - 328 per 100,000
• Mississippi, USA - 131 per 100,000
• Argentina - 657 per 100,000

19. Ethnic distribution
 White people in Europe and North America have a
higher prevalence, around 100 to 350 per 100,000
population.
 Asians in Japan & China and Africans have lower rates,
around one-fifth to one-tenth of those in whites.

20. Age Distribution
 Less common before 50 years of age & increases steadily
with age thereafter up to the ninth decade.
 ~1 in every 200 persons aged 60–69 had PD in the United
States (US) and Western Europe.
 For people in their 70’s, this increased to ~1 person with
PD in every 100 people,
 For people in their 80’s, ~1 in every 35 had PD

22. Incidence
 “Every four seconds, a new case of
dementia occurs somewhere in the world.”
 Cohort longitudinal studies provide rates
between 10 and 15 per thousand.
 Advancing age -primary risk factor
 Women- higher risk of developing AD
particularly in the population older than 85

24. Basal Ganglia

25. GRAY MATTER(COLLECTION)
•CORPOUS STRATUM
•AMYGDALOID
•CLAUSTRUM
•SUBTHALAMIC NUCLEI
•SUBSTANTIANIGRA

26. Corpus
striatum
Lentiform
nucleus
Globus
pallidus
putamen
Caudate
nucleus

27. Corpus
striatum
Lentiform
nucleus
Globus
pallidus
putamen
Caudate
nucleus
Neostraitum or
straitum
Paleostraitum

30. /striatum

38. Cognition(caudate circuit)
eg:A person seeing a lion approach ????
FUNCTIONS
Executes Learned Patterns of Motor Activity
eg:writing of letters of the alphabet.
hammering nails,
shooting a basketball through a hoop,

39. Control of movement
Nigrostriatal
pathway
Indirect
pathway
Direct
Pathway
Planning of movement

45. PATHOLOGY OF
PARKINSON’S DISEASE

46. Etiology
Idiopathic Genetic
Parkinson’s disease
Results due to reduction in the striatal dopamine content
due to damage of nigrostriatal pathway.

48. PARKINSON’S DISEASE
Neurodegenerative disorder which
affects the extrapyramidal system.

50. 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

51. 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
At least ten single gene mutations identified

52. Mutations in gene coding Alpha synuclein and
LRRK2 (leucine rich repeat kinase 2) - Autosomal
dominant PD
Mutations in gene coding Parkin,DJ-1and PINK1-
Autosomal recessive PD

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

56. Morphology
Macroscopic:
Pallor or depigmentation of neurons in substantia
nigra and locus ceruleus

57. Microscopic
Loss of pigmented ,catecholaminergic neurons
Intraneuronal Lewy bodies within the
pigmented neurons of the substantia nigra.
Lewy bodies are cytoplasmic eosinophilic round
to elongated inclusions that often have a dense
core sourrounded by halo.
Lewy bodies are composed of Alpha –synuclein

58. NORMAL PARKINSONS DISEASE

60. Clinical Features &
Diagnosis of Parkinsonism

61. Motor symptoms
Non-motor symptoms

62. Motor symptoms
Characterized by Four cardinal features :
Bradykinesia (or Hypokinesia)
Tremor atrest
Rigidity
Posturalinstability

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

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

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

69. 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

70. Involves the hands, lips, chin, jaw and legs .
“Pil l-rolling”
Tremor:

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

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

74. Festinating / Shuffling Gait:
i) Difficulty to initiate walking
ii) Shortened stride
iii) Reduced arm swing
iv) Rapid small steps (shuffling)
RUNNING AFTER THE CENTRE OF GRAVITY
Freezing phenomenon

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

76. Sleep disturbances
REM behavior disorder
excessive day timedrowsiness
Cognitive impairment
Dementia : In >80% of patients after 20 years of
disease

81. 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.

82. 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.

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

84. 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

85. 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

88. Management of
Parkinsonism

89. 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

90. Management
General
Measures
Drug Therapy Surgery

91. 1.General Measures
Physiotherapy
Speech therapy
Dietary controls

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

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

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

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

96. 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

100. 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.

101. 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)

102. LEVODOPA+ CARBIDOPA

103. 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)
Dopamine agonist
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.

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

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

106. 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.

107. Treatment approaches to newly diagnosed PD

108. Surgery
Deep Brain Stimulation
Thalamotomy
Pallidotomy
Neural Transplantation

109. REVIEW AND
CONCLUSION!

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

111. 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.

112. THANK U SIR