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Parkinson’s Disease (PD). Parkinson’s Disease Degenerative brain disease of elderly people, characterized by progressive motor difficulty. It causes significant.

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Presentation on theme: "Parkinson’s Disease (PD). Parkinson’s Disease Degenerative brain disease of elderly people, characterized by progressive motor difficulty. It causes significant."— Presentation transcript:

1 Parkinson’s Disease (PD)

2 Parkinson’s Disease Degenerative brain disease of elderly people, characterized by progressive motor difficulty. It causes significant disability and shortens life expectancy.

3 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

4 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

5 Survival in Parkinsonism Prior to Levodopa

6 Parkinson’s Disease Diagnosis Clinical criteria- The Triad: –Resting tremor –Cogwheel rigidity –Akinesia Asymmetry of tremor and rigidity

7 Parkinson’s Disease Presenting Symptoms –Tremor –Fatigue –Slowness –Gait difficulty –Frequent falls –Pain

8 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

9 Parkinson’s Disease Differential Diagnosis of Parkinsonism Drug induced Parkinsonism Depression Normal Pressure Hydrocephalus Vascular Lacunar States

10 Parkinson’s Disease Other degenerative diseases with Parkinsonian features. Progressive Supranuclear Palsy (PSP) Multi-System Atrophy (MSA) Lewy Body Dementia Wilson’s Disease

11 Parkinson’s Disease Diagnostic Tests: Brain imaging: CT and MRI Positron-emission Tomography (PET scan)

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13 Pathology of Parkinson’s Disease

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17 Pathophysiology of Parkinson’s Disease

18 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

19 Parkinson’s Disease Treatment-Replenishing of Dopamine: L-Dopa L-Dopa+Carbidopa ( Decarboxylase Inhibitor ) COMT Inhibitors

20 Diagram of LD Metabolism

21 Parkinson’s Disease L-Dopa Treatment: Most efficacious treatment. Helps all the symptoms of PD Improves functionality Extends life expectancy Generally well tolerated

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23 Survival in Parkinsonism Prior to Levodopa

24 Parkinson’s Disease Acute side-effects of L-Dopa treatment: Gastro-intestinal Psychosis Hypotension Arrhythmias

25 Parkinson’s Disease Chronic side-effects of L-Dopa treatment Failure of efficacy and shortened time On-Off Phenomena Dystonia ? Enhances progression of disease

26 Parkinson’s Disease Treatment- Increasing the release of Dopamine: Amantadine Adjunct or very early treatment Side-effect: Psychosis May reduce Dystonia

27 Parkinson’s Disease Treatment- Preventing Dopamine Breakdown: MAO-inhibitor –Selegeline

28 Parkinson’s Disease Treatment-Dopamine receptor agonists Ergot-Derived: –Bromocriptine –Pergolide Non-Ergot Derived –Ropinirole (Requipe) –Pramipexole (Sifrol)

29 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

30 Parkinson’s Disease Treatment- Anticholinergics: –Trihexyphenidyl –Biperiden (Long acting) More effective in the control of tremor Anti-cholinergic side effects May produce psychosis

31 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

32 When to Begin Therapy Definitive neuroprotective therapy not yet available Timing of symptomatic therapy is individual –degree of functional impairment –lifestyle of patient

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


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