parkinson’s disease (pd). parkinson’s disease degenerative brain disease of elderly people,...
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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
Parkinson’s Disease
• Diagnosis
• Clinical criteria- The Triad:– Resting tremor– Cogwheel rigidity– Akinesia
• Asymmetry of tremor and rigidity
Parkinson’s Disease
• Presenting Symptoms– Tremor– Fatigue– Slowness– Gait difficulty– Frequent falls– Pain
Parkinson’s Disease
• 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
• 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)
Main Biochemical Abnormality
• Marked striatal DA depletion– “Striatal dopamine deficiency syndrome”
• 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
Parkinson’s Disease
• L-Dopa Treatment:
• Most efficacious treatment.
• Helps all the symptoms of PD
• Improves functionality
• Extends life expectancy
• Generally well tolerated
Parkinson’s Disease
• Acute side-effects of L-Dopa treatment:
• Gastro-intestinal
• Psychosis
• Hypotension
• Arrhythmias
Parkinson’s Disease
• 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- Increasing the release of Dopamine:
• Amantadine• Adjunct or very early
treatment• Side-effect: Psychosis• May reduce Dystonia
Parkinson’s Disease
• Treatment-Dopamine receptor agonists
• Ergot-Derived:– Bromocriptine– Pergolide
• Non-Ergot Derived– Ropinirole (Requipe)– Pramipexole (Sifrol)
Parkinson’s Disease
• 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 L-
Dopa• 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