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– 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)

Pathology of Parkinson’s Disease

Pathophysiology of Parkinson’s Disease

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

Diagram of LD Metabolism

Parkinson’s Disease

• 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

• 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- 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

• 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

Parkinson’s Disease

• Surgical Treatment (Ablative):• Thalamotomy• Pallidotomy• Sub-thalamotomy• Deep Brain Stimulation (DBS):• Thalamic (for tremor)• Internal Globus Pallidum.• Subthalamic nucleus.