Parkinsons Disease PD Parkinsons Disease Degenerative brain disease

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