1. Initial Diagnosis and Management of Parkinson’s Disease
Jay K. Johnson, D.O.

2. Objectives
Be familiar with how to make the diagnosis of Parkinson’s disease
Be aware of some of the differential diagnostic considerations of patient who present with Parkinsonism
Understand the current medical and surgical options for Parkinson’s disease

3. Parkinson’s Disease Diagnosis
Rest tremor – Often unilateral
Rigidity
Akinesia or bradykinesia
Postural instability
The usual criteria for a clinical diagnosis of Parkinson’s disease requires at least 2 of these 4 features.

4. Parkinson’s Disease Non-motor symptoms
Depression and Dementia
Autonomic symptoms – constipation, orthostatic hypotension, detrusor muscle hyperactivity
Sleep disorders – RLS, EDS, Sleep fragmentation, REM behavior sleep disorder
Anosmia

5. Parkinson’s Disease Diagnosis
Features most suggestive of Parkinson’s disease include asymmetric or unilateral onset
Tremor at rest
Good response to levodopa

6. Parkinson’s Disease Suspect an Alternative Diagnosis
Rapidly progressive course
Lack of dopaminergic response
Early postural instability
Cerebellar signs
Early autonomic features
Pyramidal signs
Rapidly progressing or early dementia
Supranuclear gaze palsy, slowed saccades

7. Parkinson’s Disease Suspect an Alternative Diagnosis
Early falls
Symmetry of motor manifestations
Lack of tremor

8. Treatment of Parkinson’s Disease
Neuroprotective
Surgical
Symptomatic
Non-pharmacologic

9. Treatment of Parkinson’s Disease Neuroprotective
At present there are no proven neruoprotective therapies
Minocycline, creatine, caffeine, coenzyme Q 10, estrogen, pramipexole, ropinirole, rasagiline, GPI 1485, GM-1 ganglioside are currently in clinical trials (NINDS)

10. Treatment of Parkinson’s Disease Surgical
It will often reduce “off” time and dyskinesia
Indicated in advanced patients who are not being helped with there current therapy and have a significantly reduced level of function
Surgery does not cure and doesn’t help symptoms that aren’t or haven’t responded to dopaminergic therapy

11. Treatment of Parkinson’s Disease Symptomatic
Levodopa
MAO B inhibitors
Dopamine agonists (ergot and non-ergot)
COMT inhibitors
Anticholinergic agents
Amatadine

12. Treatment of Parkinson’s Disease Levodopa
The most effective drug in the treatment of Parkinson’s disease
It helps the symptom of bradykinesia and rigidity best, will often help the tremor as well
Postural instability responds the least
It is combined with a decarboxylase inhibitor

13. Treatment of Parkinson’s Disease Levodopa
Immediate-release carbidopa/levodopa (Sinemet) – 10/100, 25/100, 25/250
Parcopa is a immediate –release formulation that dissolves under the tongue.
Sinemet CR is a controlled release formulation – 25/100 and 50/200

14. Treatment of Parkinson’s Disease Levodopa – Dosing
Treatment is usually started with 25/100 immediate release ½ to 3 per day.
Most patients get a response at mg per day of levodopa
Controlled release levodopa preparations usually require 30% more to achieve a clinically similar effect

15. Treatment of Parkinson’s Disease Levodopa – Adverse effects
Confusion, hallucinations, delusions, agitation, psychosis.
Nausea, dizziness, headache, orthostatic hypotension
Motor fluctuations

16. Treatment of Parkinson’s Disease MAO B inhibitors
Selegiline – Eldepryl (5mg AM )
Rasagiline – Azilect (0.5mg – 1.0mg)
Selegiline orally dissolving tablet - Zelapar ( mg)

17. Treatment of Parkinson’s Disease MAO B inhibitors
Typically don’t produce a significant functional benefit. But is often used early in the disease course.
These agents serve as an adjunct with levodopa. They may lessen development of motor fluctuations. Dyskinesias are not affected

18. Treatment of Parkinson’s Disease MAO B inhibitors
Mortality was not increased in patients taking these agents
Nausea, headache, confusion probably by enhancing the effects of levodopa
PDR warns against the use of these agents with tricyclics and SSRI’s
Unlike nonselective MAO inhibitors these agents don’t precipitate hypertensive crisis in patient who ingest high tyramine foods

19. Treatment of Parkinson’s Disease MAO B inhibitors
SSRI’s and the risk of the serotonin syndrome is very rare if present at the standard doses of the current MAO B drugs
Sertraline is probably the safest SSRI to use. TCA’s are often used as well but be careful about anticholinergic side effects

20. Treatment of Parkinson’s Disease Dopamine Agonists
Bromocriptine
Pergolide
Pramipexole
Ropinirole
Apomorphine - Injectable

21. Treatment of Parkinson’s Disease Dopamine Agonists
These are synthetic agents that directly stimulate the dopamine receptor
They were initially developed for adjunctive therapy with levodopa but can be used as initial therapy
They are very effective for use in patients who develop motor fluctuations and dyskinesias

22. Treatment of Parkinson’s Disease Dopamine Agonists
Most patients who initially start on agonists will need to be on levodopa at some point.
Pergolide (Permax) has been taken off the market, voluntarily by the manufacturer
Oral dopamine agonist need to be started slowly and the effect is not quick.

23. Treatment of Parkinson’s Disease Dopamine Agonists
Patients on dopamine agonists may develop impulse control problems
The adverse effects of dopamine agonist are similar to levodopa. Peripheral edema is more common with agonists
Elderly and demented patients are more susceptible to psychiatric side effects
Warn patients about “sleep attacks”

24. Treatment of Parkinson’s Disease Dopamine Agonists
Dopamine dysregulation syndrome – a cyclical mood disorder with hypomania and possible manic psychosis
Impulse control disorders including hypersexuality and pathologic gambling may occur

25. Treatment of Parkinson’s Disease COMT Inhibitors
Tolcapone (Tasmar)
Entacapone (Comtan)
Entacapone/carbidopa/levodopa (Stalevo)

26. Treatment of Parkinson’s Disease COMT Inhibitors
These drugs are ineffective when used alone
Used mainly in patients with wearing off
Tolcapone is associated with hepatotoxicity and is rarely used in the U.S.

27. Treatment of Parkinson’s Disease Anticholinergics
Trihexyphenidyl (Artane)
Benzotropine (Cogentin)

28. Treatment of Parkinson’s Disease Anticholinergics
Most useful in patients with tremor predominate Parkinson's disease and age less than 65
Do not use in patients with a Dementia

29. Treatment of Parkinson’s Disease Amantadine
Probably has multiple mechanisms of action
Is used to treat symptoms of akinesia, rigidity, and tremor.
Is often used to treat dyskinesias in patients already on levodopa
Side effects include livedo reticularis, ankle edema, confusion and hallucinations

31. Summary

32. Treatment of Parkinson’s Disease Recommendations
Either Carbidopa/Levodopa immediate release or a dopamine agonist can be used as initial therapy in patients who are functionally impaired.
Levodopa preparations are the most effective agents for the treatment of Parkinson's disease
It is reasonable to initiate therapy with a dopamine agonist in younger patients

33. Treatment of Parkinson’s Disease Recommendations
Pergolide (Permax) should be avoided
Anticholinergics can be used in younger (65 or less) tremor predominate patients.
MAO B inhibitors produce a symptomatic benefit that is mild and these agents are often used early in the treatment of Parkinson patients.

34. Treatment of Parkinson’s Disease Recommendations
Surgery for Parkinson's disease is a reasonable treatment in selected patients