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Parkinson’s Disease . Sophie Mitchell . Neurodegeneration. ACUTE Stroke Cerebral Ischaemia Acute brain injury Spinal cord injury. CHRONIC Alzheimers Disease Parkinsons disease Multiple sclerosis Huntington’s disease ALS. Epidemiology Aetiology Pathology Clinical Features
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Parkinson’s Disease Sophie Mitchell
Neurodegeneration ACUTE Stroke Cerebral Ischaemia Acute brain injury Spinal cord injury CHRONIC Alzheimers Disease Parkinsons disease Multiple sclerosis Huntington’s disease ALS
Epidemiology • Aetiology • Pathology • Clinical Features • Differentials/’Parkinsonism’ • Investigations/Diagnosis • Management/Drugs
Epidemiology • Age of onset • Prevalence • Disease progression 45-60 years 0.5-1% over 60’s, 2nd most common ND Increases with age Progressive
Risk Factors • Male sex (1.5 ×) • Personality? • Non-smokers • Family history (2×) genetics (DJ1, PINK1, Parkin, Synuclein mutations) • Exposure to pesticides • Manganese, copper • Head injury
Pathological Changes Lewy bodies: alpha synuclein ubiquitin Degeneration of corpus striatum & basal ganglia Loss of neurons in substantianigra
Mitochondrial dysfunction Free radicals Oxidative stress apoptosis Ubiquitin system dysfunction Inadequate clearance of misfolded proteins accumulation Increased aggregation of a-synuclein Space occupying lesions Disruption of vesicular transport
Clinical Features Triad: 1. Resting tremor 2. Rigidity 3. Bradykinesia
What about non-motor symptoms? • Hypomimia mask-like face • Loss of smell (olfactory bulb) • Seborrheoa scalp/face • Constipation • Bladder symptoms • Bulbar symptoms dysarthria/dysphagia • Pain • Fatigue (hypothalamus) • Mental and cognitive disturbance depression(frontal cortex/limbic system)
Differentials • Alzheimer's • Huntingdon's • Dementia with Lewy bodies • Essential tremor • Multi-infarct dementia • Progressive supranuclear palsy • Repeated head injury • Drugs (antipsychotics) & toxins
Diagnosis • Clinical history and examination, and response to drugs • Rule out other causes of parkinsonism • PET scanning? • Post mortem (Lewy bodies)
Management • Drug therapies • Specialist nurse, physio, OT, speech therapist, dietician, psychiatrist, rehab, social services… • Deep brain stimulation • Pallidotomy (globuspallidus) • Palliative • Stem cell grafts, neurotrophic factor infusions, gene therapy…
Are these drugs good enough? • Wearing off • Increased reliance over time • Side effects PH, psych, n & v, dyskinesias…. • ….Levadopa + PDI Carbidopa & Domperidone • QOL now vs. the future? • Arresting neurodegeneration or postponing it?