Parkinson's Disease Lecture

1. Parkinson’s Disease(PD)

2. Objectives
• Overview of PD
• Treatment of PD and complications

3. History
• 1817: James Parkinson reported 6 of his patients, named it ”paralysis
agitans” or “shaking palsy”
• 1865: other physicians called it “Parkinson’s Disease”
• 1912: Brain biopsy ”Lewy bodies”
• 1919: Substantia nigra was identified to be the structure involved

5. • 1967: Levodopa was first used for symptomatic treatment
• 50 years remained as mainstay of treatment

6. Epidemiology
• World wide incidence
• Slightly more in men than women
• Frequency increases with age
• In the US, 1% of people over age 60

7. Cause
• Idiopathic
• 5-10% genetic
• Environmental causes: pesticides, heavy metals, rural living increase
risk
• Smoking and caffeine decrease risk

8. Diagnosis
• Definitive: autopsy
• Clinical criteria:
• History and PE
• Cardinal motor features
• Exclusion criteria
• Supportive features
• ～82% diagnostic accuracy

9. 3 Cardinal Motor Features
• Bradykinesia
• Tremors
• and/or rigidity
• 2 out of 3 must be present to make diagnosis

10. Bradykinesia
• “slow movement”
• Smaller movement
• Examples: facial expression, smaller handwriting, “shuffling gait”

12. Tremor
• Resting tremor, i.e. tremor at rest
• Not everyone have tremors
• Hands, legs, jag, chin, tongue

14. Rigidity
• Not similar to stiffness
• Part of our clinical exam
• “cog-wheel rigidity”

15. Other motor symptoms
• Postural reflexes (imbalance)
• Freezing
• Drooling
• Changes in Speech
• Swallowing

16. Non-motor symptoms
• Behavioral (depression, anxiety, hallucinations)
• Autonomic (lightheadedness, constipation)
• Sleep (restless legs, dream enactment)
• Cognition
• Pain
• other

17. Course/Progression
• Everyone is different
• In general, slowly progressive

19. Clinical Stages
• Prodromal/Premotor
• Early
• Middle
• Late

20. Premotor
• Constipation
• Sense of smell
• Dream enactment
• Mood

21. Early Stage
• One side of the body
• Good response to treatment

22. Mid-later stages
• Motor complications
• Response to medication
• Fluctuations/wearing off
• Falls
• Freezing
• Dyskinesias

23. • Motor fluctuations
• “off” and “on”
• Medications take longer to kick in, wear off earlier

25. Mid-later stages
• Non-motor
• Speech, swallowing
• Hallucinations
• Cognition
• Autonomic symptoms

26. • A 55 year old male came to the OPD because his wife noticed change
in his facial expression and he doesn’t swing his has when walking.
There was also an incident that he had punched his wife during sleep
while dreaming he was being attacked by an enemy. He is not aware
of these symptoms. The resident diagnosed his with Parkinson’s
disease. What will be your initial treatment?

27. • Unfortunately, there is no commercially available treatment to
prevent progression of the disease at this stage.

28. 3 Years later
• Patient came back in the clinic complaining of trouble of tying his
shoe laces and other tasks with his left hand. His walking became
slow and have trouble keeping up with her wife when they are at the
mall. He consulted because it has become bothersome and
concerning. What will be your treatment?

29. Treatment
• Mainstay:
• “replace” the dopamine in the brain
• Carbidopa/Levodopa

30. Carbidopa/Levodopa
Regular Controlled Release (CR): Sinemet 25/100, 25/250; Parkimet;
Tidomet 50/200, 25/100, 25/250; Sinedin

31. Dopamine Agonists
• Bromocriptine
• Ropinirole
• Pramipexole
• Rotigotine

32. • 6 years after giving Sinemet, the patient complained that his
medications are not working anymore unlike in the past several years.
He feels better when he takes the meds but his movements are still
slow. After a few hours, he becomes slower and slower, feels rigid and
have a progress into tremors. He is asking you another what to do
next.

33. What to do with motor complications
• Lack of effect
• Fluctuations/waning off
• Side effect of treatment: dyskinesia, lightheadedness, hallucinations

34. Motor fluctuations
• Increase dopaminergic dose
• Increase amount each dose
• Give more frequently
• Add dopamine agonist

35. Motor fluctuations
• Decrease the breakdown of dopamine
• Add COMT inhibitor
• Entacapone
• Carbidopa/levodopa/entacapone (Stalev)

36. Motor fluctuations
• Decrease dopamine breakdown
• Add MAO-B inhibitor
• Rasagiline
• Selegiline
• Safinamide

37. Rescue therapies
• Apomorphine injections: onset 10minutes, lasts for 90minutes
• Nausea and vomiting
• Inhaled levodopa: Inbrija
• Onset is 10+ minutes, lasts 60minutes
• Cough, nausea

38. Levodopa-induced dyskinesia
• Decrease dopaminergic medications
• Amantadine
• Extended release amantadine

40. • What if meds are still wearing off and meds are not effective or
cannot increase meds (ie, dyskinesias/side effects)
• Consider surgical treatments
• Deep brain stimulation
• Levodopa intestinal gel