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

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

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.

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

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

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

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

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

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)

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

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

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

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

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 300-600mg per day of levodopa Controlled release levodopa preparations usually require 30% more to achieve a clinically similar effect

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

Treatment of Parkinson’s Disease MAO B inhibitors Selegiline – Eldepryl (5mg AM ) Rasagiline – Azilect (0.5mg – 1.0mg) Selegiline orally dissolving tablet - Zelapar (1.25-2.5mg)

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

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

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

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

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

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.

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”

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

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

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.

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

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

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

Summary

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

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.

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