1. Parkinson’s Disease Angela Duncan June 2010

2. Why I Chose This Subject Common neurodegenerative disorder 120-230/100 000 in Scotland Expected increase of 25-30% in next 25 yrs Complex condition which changes with time Huge social impact Uncertainty amongst GP’s re prescribing New SIGN guideline this year

3. ClinicalBackground PD-syndrome consisting of bradykinesia plus at least one of rigidity, resting tremor and postural disorder Parkinsonism-broader term but could be different aetiology from PD Average time from diagnosis to death is 13 years

4. Pathophysiology Motor system-fine balance of inhibitory and excitatory inputs of basal ganglia and cerebellum Cerebellar output is excitatory, basal ganglia is inhibitory

5. Pathophysiology Apoptosis of dopaminergic neurons in substantia nigra-leads to decrease in inhibition Disruption of signals to motor cortex via thalamus Smooth, coordinated movement is lost

6. Diagnosis Is Difficult As is progressive disorder-can be hard in initial stages to diagnose accurately Poor specificity-advise pt & family this Recommendation that diagnosis should be made by a hospital clinician in SIGN Also useful way of getting MDT involved

7. Differential Diagnosis Progressive supranuclear palsy Multi-system atrophy Alzheimer’s disease Lewy body dementia

8. Clues in Differentiating Up to 20% of those with PD have one relative affected 30-50% have depressive symptoms 17% hallucinate 80% have ANOSMIA-may precede onset of PD

9. Investigations Routine use of imaging not recommended Functional imaging most useful where there is uncertainty SPECT cheapest Can potentially detect very early disease as you can lose up to ~50% of dopamine receptors before showing signs of PD

11. Drug therapy Does not slow or prevent disease progression Improves quality of life 5-10% respond poorly to all medications Trying to stimulate the dopaminergic system and control the resulting excitation in cholinergic pathways

12. Levodopa Available for ~40 years Given with Dopa-decarboxylase inhibitor Co-beneldopa (Madopar) or Co-careldopa (Sinemet) Often get disabling dyskinesias at about 8 years of use Therefore often kept in reserve, especially in younger patients

13. Levodopa Helps bradykinesia and rigidity (not really tremor) Small dose increments every few days 6-18 months to see improvement Nausea/flushing/sweating/neuropathy On-off effect End of dose deterioration

14. Dopamine Agonists Ropinorole, Pramipexole, Pergolide Bromocriptine/Cabergoline now avoided due to cardiac valvulopathy and pleural, pericardial and retroperitoneal fibrosis Again-incremental increases Similar s/e profile, less motor complications but less improvement

15. Dopamine Agonists If you initiate this you must tell patient about impulse control disorders and excessive daytime somnolence Hypotension particularly in first few days of treatment Good evidence in advanced PD to improve off time-transdermal Rotigotine Amantadine-weak dopamine agonist

16. However… Increasing Dopamine Agonists often worsens hallucinations Patient preference

17. Other Treatments COMT inhibitors Entacapone provide some benefit in reducing off time MAO-B inhibitors Buccal selegiline or rasagiline can help motor complications (less commonly used) Severe PD-can admit for subcutaneous Apomorphine infusion New treatments-dopamine pump if others fail

18. Antimuscarinics Orphenadrine-helps drooling Often drooling is more unpleasant for family & they are delighted if you can improve this Procyclidine Best in drug-induced Parkinsonism s/e control

19. Other Features to Be Aware of Depression-Citalopram (or Amitriptyline) Dementia in ~30% with late disease Treat as per dementia guideline Psychosis-low dose Clozapine or Quetiapine if monitoring impractical

20. Contacts Parkinson’s Disease Society (Scottish Office) Forsyth House, Lomond Court, Castle Business Park Stirling FK9 4TU Tel: 01786 433811 Helpline: 0808 800 0303 Email: pds.scotland@parkinsons.org.uk Website: www.parkinsons.org.uk/scotland Younger Parkinson’s Network Tel: 01656 663 284 E-mail: alunmorgan@btinternet.com Website: www.yap-web.net