Initial Diagnosis and Initial Diagnosis and Management of Parkinson’s Management of Parkinson’s

DiseaseDiseaseJay K. Johnson, D.O.

ObjectivesObjectives

Be familiar with how to make the Be familiar with how to make the diagnosis of Parkinson’s diseasediagnosis of Parkinson’s disease

Be aware of some of the differential Be aware of some of the differential diagnostic considerations of patient diagnostic considerations of patient who present with Parkinsonismwho present with Parkinsonism

Understand the current medical and Understand the current medical and surgical options for Parkinson’s surgical options for Parkinson’s diseasedisease

Parkinson’s Disease Parkinson’s Disease DiagnosisDiagnosis

Rest tremor – Often unilateralRest tremor – Often unilateral RigidityRigidity Akinesia or bradykinesiaAkinesia or bradykinesia Postural instability Postural instability

The usual criteria for a clinical The usual criteria for a clinical diagnosis of Parkinson’s disease diagnosis of Parkinson’s disease requires at least 2 of these 4 features.requires at least 2 of these 4 features.

Parkinson’s Disease Parkinson’s Disease Non-motor symptomsNon-motor symptoms

Depression and DementiaDepression and Dementia Autonomic symptoms – constipation, Autonomic symptoms – constipation,

orthostatic hypotension, detrusor orthostatic hypotension, detrusor muscle hyperactivitymuscle hyperactivity

Sleep disorders – RLS, EDS, Sleep Sleep disorders – RLS, EDS, Sleep fragmentation, REM behavior sleep fragmentation, REM behavior sleep disorderdisorder

AnosmiaAnosmia

Parkinson’s Disease Parkinson’s Disease DiagnosisDiagnosis

Features most suggestive of Features most suggestive of Parkinson’s disease include Parkinson’s disease include asymmetric or unilateral onsetasymmetric or unilateral onset

Tremor at restTremor at rest Good response to levodopaGood response to levodopa

Parkinson’s Disease Parkinson’s Disease Suspect an Alternative Suspect an Alternative

DiagnosisDiagnosis Rapidly progressive courseRapidly progressive course Lack of dopaminergic responseLack of dopaminergic response Early postural instabilityEarly postural instability Cerebellar signsCerebellar signs Early autonomic featuresEarly autonomic features Pyramidal signsPyramidal signs Rapidly progressing or early dementiaRapidly progressing or early dementia Supranuclear gaze palsy, slowed Supranuclear gaze palsy, slowed

saccadessaccades

Parkinson’s Disease Parkinson’s Disease Suspect an Alternative Suspect an Alternative

DiagnosisDiagnosis Early fallsEarly falls Symmetry of motor manifestationsSymmetry of motor manifestations Lack of tremorLack of tremor

Treatment of Parkinson’s Treatment of Parkinson’s DiseaseDisease

Neuroprotective Neuroprotective SurgicalSurgical SymptomaticSymptomatic Non-pharmacologicNon-pharmacologic

Treatment of Parkinson’s Treatment of Parkinson’s Disease Neuroprotective Disease Neuroprotective

At present there are no proven At present there are no proven neruoprotective therapiesneruoprotective therapies

Minocycline, creatine, caffeine, Minocycline, creatine, caffeine, coenzyme Q 10, estrogen, coenzyme Q 10, estrogen, pramipexole, ropinirole, rasagiline, pramipexole, ropinirole, rasagiline, GPI 1485, GM-1 ganglioside are GPI 1485, GM-1 ganglioside are currently in clinical trials (NINDS)currently in clinical trials (NINDS)

Treatment of Parkinson’s Treatment of Parkinson’s Disease Surgical Disease Surgical

It will often reduce “off” time and It will often reduce “off” time and dyskinesiadyskinesia

Indicated in advanced patients who Indicated in advanced patients who are not being helped with there are not being helped with there current therapy and have a current therapy and have a significantly reduced level of functionsignificantly reduced level of function

Surgery does not cure and doesn’t Surgery does not cure and doesn’t help symptoms that aren’t or haven’t help symptoms that aren’t or haven’t responded to dopaminergic therapyresponded to dopaminergic therapy

Treatment of Parkinson’s Treatment of Parkinson’s Disease SymptomaticDisease Symptomatic

LevodopaLevodopa MAO B inhibitorsMAO B inhibitors Dopamine agonists (ergot and non-Dopamine agonists (ergot and non-

ergot)ergot) COMT inhibitorsCOMT inhibitors Anticholinergic agentsAnticholinergic agents AmatadineAmatadine

Treatment of Parkinson’s Treatment of Parkinson’s Disease LevodopaDisease Levodopa

The most effective drug in the The most effective drug in the treatment of Parkinson’s diseasetreatment of Parkinson’s disease

It helps the symptom of bradykinesia It helps the symptom of bradykinesia and rigidity best, will often help the and rigidity best, will often help the tremor as welltremor as well

Postural instability responds the leastPostural instability responds the least It is combined with a decarboxylase It is combined with a decarboxylase

inhibitor inhibitor

Treatment of Parkinson’s Treatment of Parkinson’s Disease LevodopaDisease Levodopa

Immediate-release Immediate-release carbidopa/levodopa (Sinemet) – carbidopa/levodopa (Sinemet) – 10/100, 25/100, 25/25010/100, 25/100, 25/250

Parcopa is a immediate –release Parcopa is a immediate –release formulation that dissolves under the formulation that dissolves under the tongue.tongue.

Sinemet CR is a controlled release Sinemet CR is a controlled release formulation – 25/100 and 50/200formulation – 25/100 and 50/200

Treatment of Parkinson’s Treatment of Parkinson’s Disease Levodopa – Dosing Disease Levodopa – Dosing

Treatment is usually started with Treatment is usually started with 25/100 immediate release ½ to 3 per 25/100 immediate release ½ to 3 per day.day.

Most patients get a response at 300-Most patients get a response at 300-600mg per day of levodopa600mg per day of levodopa

Controlled release levodopa Controlled release levodopa preparations usually require 30% preparations usually require 30% more to achieve a clinically similar more to achieve a clinically similar effect effect

Treatment of Parkinson’s Treatment of Parkinson’s Disease Levodopa – Adverse Disease Levodopa – Adverse

effectseffects Confusion, hallucinations, delusions, Confusion, hallucinations, delusions,

agitation, psychosis.agitation, psychosis. Nausea, dizziness, headache, Nausea, dizziness, headache,

orthostatic hypotensionorthostatic hypotension Motor fluctuations Motor fluctuations

Treatment of Parkinson’s Treatment of Parkinson’s Disease MAO B inhibitorsDisease MAO B inhibitors

Selegiline – Eldepryl (5mg AM )Selegiline – Eldepryl (5mg AM ) Rasagiline – Azilect (0.5mg – 1.0mg)Rasagiline – Azilect (0.5mg – 1.0mg) Selegiline orally dissolving tablet - Selegiline orally dissolving tablet -

Zelapar (1.25-2.5mg) Zelapar (1.25-2.5mg)

Treatment of Parkinson’s Treatment of Parkinson’s Disease MAO B inhibitorsDisease MAO B inhibitors

Typically don’t produce a significant Typically don’t produce a significant functional benefit. But is often used functional benefit. But is often used early in the disease course.early in the disease course.

These agents serve as an adjunct These agents serve as an adjunct with levodopa. They may lessen with levodopa. They may lessen development of motor fluctuations. development of motor fluctuations. Dyskinesias are not affectedDyskinesias are not affected

Treatment of Parkinson’s Treatment of Parkinson’s Disease MAO B inhibitorsDisease MAO B inhibitors

Mortality was not increased in patients Mortality was not increased in patients taking these agentstaking these agents

Nausea, headache, confusion probably Nausea, headache, confusion probably by enhancing the effects of levodopaby enhancing the effects of levodopa

PDR warns against the use of these PDR warns against the use of these agents with tricyclics and SSRI’sagents with tricyclics and SSRI’s

Unlike nonselective MAO inhibitors Unlike nonselective MAO inhibitors these agents don’t precipitate these agents don’t precipitate hypertensive crisis in patient who ingest hypertensive crisis in patient who ingest high tyramine foodshigh tyramine foods

Treatment of Parkinson’s Treatment of Parkinson’s Disease MAO B inhibitorsDisease MAO B inhibitors

SSRI’s and the risk of the serotonin SSRI’s and the risk of the serotonin syndrome is very rare if present at syndrome is very rare if present at the standard doses of the current the standard doses of the current MAO B drugsMAO B drugs

Sertraline is probably the safest SSRI Sertraline is probably the safest SSRI to use. TCA’s are often used as well to use. TCA’s are often used as well but be careful about anticholinergic but be careful about anticholinergic side effectsside effects

Treatment of Parkinson’s Treatment of Parkinson’s Disease Dopamine AgonistsDisease Dopamine Agonists

Bromocriptine Bromocriptine PergolidePergolide PramipexolePramipexole RopiniroleRopinirole Apomorphine - InjectableApomorphine - Injectable

Treatment of Parkinson’s Treatment of Parkinson’s Disease Dopamine AgonistsDisease Dopamine Agonists

These are synthetic agents that These are synthetic agents that directly stimulate the dopamine directly stimulate the dopamine receptorreceptor

They were initially developed for They were initially developed for adjunctive therapy with levodopa but adjunctive therapy with levodopa but can be used as initial therapycan be used as initial therapy

They are very effective for use in They are very effective for use in patients who develop motor patients who develop motor fluctuations and dyskinesias fluctuations and dyskinesias

Treatment of Parkinson’s Treatment of Parkinson’s Disease Dopamine AgonistsDisease Dopamine Agonists

Most patients who initially start on Most patients who initially start on agonists will need to be on levodopa agonists will need to be on levodopa at some point.at some point.

Pergolide (Permax) has been taken off Pergolide (Permax) has been taken off the market, voluntarily by the the market, voluntarily by the manufacturermanufacturer

Oral dopamine agonist need to be Oral dopamine agonist need to be started slowly and the effect is not started slowly and the effect is not quick.quick.

Treatment of Parkinson’s Treatment of Parkinson’s Disease Dopamine AgonistsDisease Dopamine Agonists

Patients on dopamine agonists may Patients on dopamine agonists may develop impulse control problemsdevelop impulse control problems

The adverse effects of dopamine agonist The adverse effects of dopamine agonist are similar to levodopa. Peripheral are similar to levodopa. Peripheral edema is more common with agonistsedema is more common with agonists

Elderly and demented patients are more Elderly and demented patients are more susceptible to psychiatric side effectssusceptible to psychiatric side effects

Warn patients about “sleep attacks”Warn patients about “sleep attacks”

Treatment of Parkinson’s Treatment of Parkinson’s Disease Dopamine AgonistsDisease Dopamine Agonists

Dopamine dysregulation syndrome – Dopamine dysregulation syndrome – a cyclical mood disorder with a cyclical mood disorder with hypomania and possible manic hypomania and possible manic psychosispsychosis

Impulse control disorders including Impulse control disorders including hypersexuality and pathologic hypersexuality and pathologic gambling may occurgambling may occur

Treatment of Parkinson’s Treatment of Parkinson’s Disease COMT InhibitorsDisease COMT Inhibitors

Tolcapone (Tasmar)Tolcapone (Tasmar) Entacapone (Comtan)Entacapone (Comtan) Entacapone/carbidopa/levodopa Entacapone/carbidopa/levodopa

(Stalevo)(Stalevo)

Treatment of Parkinson’s Treatment of Parkinson’s Disease COMT InhibitorsDisease COMT Inhibitors

These drugs are ineffective when These drugs are ineffective when used aloneused alone

Used mainly in patients with wearing Used mainly in patients with wearing off off

Tolcapone is associated with Tolcapone is associated with hepatotoxicity and is rarely used in hepatotoxicity and is rarely used in the U.S.the U.S.

Treatment of Parkinson’s Treatment of Parkinson’s Disease AnticholinergicsDisease Anticholinergics

Trihexyphenidyl (Artane)Trihexyphenidyl (Artane) Benzotropine (Cogentin)Benzotropine (Cogentin)

Treatment of Parkinson’s Treatment of Parkinson’s Disease AnticholinergicsDisease Anticholinergics

Most useful in patients with tremor Most useful in patients with tremor predominate Parkinson's disease and predominate Parkinson's disease and age less than 65age less than 65

Do not use in patients with a Do not use in patients with a DementiaDementia

Treatment of Parkinson’s Treatment of Parkinson’s Disease Amantadine Disease Amantadine

Probably has multiple mechanisms of Probably has multiple mechanisms of actionaction

Is used to treat symptoms of akinesia, Is used to treat symptoms of akinesia, rigidity, and tremor. rigidity, and tremor.

Is often used to treat dyskinesias in Is often used to treat dyskinesias in patients already on levodopapatients already on levodopa

Side effects include livedo reticularis, Side effects include livedo reticularis, ankle edema, confusion and ankle edema, confusion and hallucinationshallucinations

SummarySummary

Treatment of Parkinson’s Treatment of Parkinson’s Disease RecommendationsDisease Recommendations

Either Carbidopa/Levodopa immediate Either Carbidopa/Levodopa immediate release or a dopamine agonist can be release or a dopamine agonist can be used as initial therapy in patients who used as initial therapy in patients who are functionally impaired.are functionally impaired.

Levodopa preparations are the most Levodopa preparations are the most effective agents for the treatment of effective agents for the treatment of Parkinson's diseaseParkinson's disease

It is reasonable to initiate therapy with It is reasonable to initiate therapy with a dopamine agonist in younger patientsa dopamine agonist in younger patients

Treatment of Parkinson’s Treatment of Parkinson’s Disease RecommendationsDisease Recommendations

Pergolide (Permax) should be avoided Pergolide (Permax) should be avoided Anticholinergics can be used in Anticholinergics can be used in

younger (65 or less) tremor younger (65 or less) tremor predominate patients.predominate patients.

MAO B inhibitors produce a MAO B inhibitors produce a symptomatic benefit that is mild and symptomatic benefit that is mild and these agents are often used early in these agents are often used early in the treatment of Parkinson patients.the treatment of Parkinson patients.

Treatment of Parkinson’s Treatment of Parkinson’s Disease RecommendationsDisease Recommendations

Surgery for Parkinson's disease is a Surgery for Parkinson's disease is a reasonable treatment in selected reasonable treatment in selected patientspatients