Transcript Parkinson’s Disease (PD)

Parkinson’s Disease (PD)
Parkinson’s Disease
• Degenerative brain disease of elderly
people, characterized by progressive motor
difficulty. It causes significant disability and
shortens life expectancy.
Parkinson’s Disease
• Epidemiology
• Age is the most important risk factor
• Increasing prevalence with longevity
– Affects 0.3% of population
– And 1% of people above 60 years of age
• Affects around 1 million people in N. America
• World-wide distribution
• Largely under-diagnosed, so under-estimated
Mortality in PD
• Reduced life expectancy
– Mean survival after onset ~ 15 years
– longer in non-demented PD cases
– longer with L-dopa use
• The most common causes of death:
– pulmonary infection/aspiration, urinary tract
infection, pulmonary embolism and
complications of falls and fractures
Survival in Parkinsonism Prior to
Levodopa
Parkinson’s Disease
• Diagnosis
• Clinical criteria- The Triad:
– Resting tremor
– Cogwheel rigidity
– Akinesia
• Asymmetry of tremor and rigidity
Parkinson’s Disease
• Presenting Symptoms
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Tremor
Fatigue
Slowness
Gait difficulty
Frequent falls
Pain
Parkinson’s Disease
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Other clinical features:
Stooped posture
Shuffling and festinating gait
Poor arm swing
Expressionless face
Monotonous slurred speech
Small hand-writing
Poor balance
Parkinson’s Disease
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Differential Diagnosis of Parkinsonism
Drug induced Parkinsonism
Depression
Normal Pressure Hydrocephalus
Vascular Lacunar States
Parkinson’s Disease
• Other degenerative diseases with
Parkinsonian features.
• Progressive Supranuclear Palsy (PSP)
• Multi-System Atrophy (MSA)
• Lewy Body Dementia
• Wilson’s Disease
Parkinson’s Disease
• Diagnostic Tests:
• Brain imaging: CT and MRI
• Positron-emission Tomography (PET scan)
Pathology of Parkinson’s Disease
Pathophysiology of
Parkinson’s Disease
Main Biochemical Abnormality
• Marked striatal DA depletion
– “Striatal dopamine deficiency syndrome”
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At death, DA loss > 90%
<50% DA loss is asymptomatic
~70% DA loss for symptom manifestations
Severity of DA loss best correlates with
bradykinesia in PD
Parkinson’s Disease
• Treatment-Replenishing of Dopamine:
• L-Dopa
• L-Dopa+Carbidopa (Decarboxylase Inhibitor)
• COMT Inhibitors
Diagram of LD Metabolism
Parkinson’s Disease
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L-Dopa Treatment:
Most efficacious treatment.
Helps all the symptoms of PD
Improves functionality
Extends life expectancy
Generally well tolerated
Survival in Parkinsonism Prior to
Levodopa
Parkinson’s Disease
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Acute side-effects of L-Dopa treatment:
Gastro-intestinal
Psychosis
Hypotension
Arrhythmias
Parkinson’s Disease
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Chronic side-effects of L-Dopa treatment
Failure of efficacy and shortened time
On-Off Phenomena
Dystonia
? Enhances progression of disease
Parkinson’s Disease
• Treatment•
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Increasing the release
of Dopamine:
Amantadine
Adjunct or very early
treatment
Side-effect: Psychosis
May reduce Dystonia
Parkinson’s Disease
• Treatment- Preventing Dopamine Breakdown:
• MAO-inhibitor
– Selegeline
Parkinson’s Disease
• Treatment-Dopamine receptor agonists
• Ergot-Derived:
– Bromocriptine
– Pergolide
• Non-Ergot Derived
– Ropinirole (Requipe)
– Pramipexole (Sifrol)
Parkinson’s Disease
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Dopamine Agonists:
Effective, especially early in the disease
Allow the reduction of L-Dopa dose
Less Dyskinesia
• Prevent the long term side-effects of L-Dopa
Parkinson’s Disease
• Treatment- Anticholinergics:
– Trihexyphenidyl
– Biperiden (Long acting)
• More effective in the control of tremor
• Anti-cholinergic side effects
• May produce psychosis
Parkinson’s Disease
• Treatment Strategies:
• Start with Dopamine agonists or enzyme inhibitors
• Add the lowest dose of L-Dopa with disease
progression
• Add adjunctive medications to reduce dose of LDopa
• Add Anti-cholinergics if tremor in prominent
When to Begin Therapy
• Definitive neuroprotective therapy not yet
available
• Timing of symptomatic therapy is
individual
– degree of functional impairment
– lifestyle of patient
Parkinson’s Disease
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Surgical Treatment (Ablative):
Thalamotomy
Pallidotomy
Sub-thalamotomy
Deep Brain Stimulation (DBS):
Thalamic (for tremor)
Internal Globus Pallidum.
Subthalamic nucleus.