parkinson_s disease case presentation
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8/3/2019 Parkinson_s Disease Case Presentation
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Parkinson¶s DiseaseParkinson¶s Disease
Review of Pathophysiology,Review of Pathophysiology,
Diagnosis, & Current TherapyDiagnosis, & Current Therapy
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Historical PerspectiveHistorical Perspective
Dr. James Parkinson (1755Dr. James Parkinson (1755--1828)1828)
18171817
³involuntary tremulous motion´³involuntary tremulous motion´
³pass from a walking to a running pace´³pass from a walking to a running pace´
³shaking palsy´³shaking palsy´
London homeLondon home
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EpidemiologyEpidemiology
Average incidence is 20 per 100,000 in Average incidence is 20 per 100,000 inNorth AmericaNorth America
1 Million affected in the United States1 Million affected in the United States50,000 new cases per year 50,000 new cases per year
Cost estimated to exceed $5.6 BillionCost estimated to exceed $5.6 Billion
annuallyannually
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EpidemiologyEpidemiology
Average age of onset 62.5 Average age of onset 62.5
Men and women affected equallyMen and women affected equally
Genetic LinkGenetic Link African African--Americans and Asians less likely Americans and Asians less likelythan Caucasians to develop Parkinson¶sthan Caucasians to develop Parkinson¶s
Caffeine and smoking shows someCaffeine and smoking shows someprotective effectsprotective effects
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Case ExampleCase Example
JJ is a 66 y/o Caucasian man who underwent surgicalJJ is a 66 y/o Caucasian man who underwent surgicalmanagement for spinal stenosis and was admitted for management for spinal stenosis and was admitted for rehabilitation. JJ has a past history of Parkinson¶s,rehabilitation. JJ has a past history of Parkinson¶s,hypertension, coronary artery disease, GERD, andhypertension, coronary artery disease, GERD, and
depression. Upon admission appropriate measuresdepression. Upon admission appropriate measureswere taken for pain management and aforementionedwere taken for pain management and aforementionedmedical conditions. JJ¶s surgical management andmedical conditions. JJ¶s surgical management andrehabilitation was complicated by advanced Parkinson¶s.rehabilitation was complicated by advanced Parkinson¶s.During his stay advances were made in his strength,During his stay advances were made in his strength,
endurance, and ADL¶s. JJ was discharged and willendurance, and ADL¶s. JJ was discharged and willreceive assistive care from his wife. Overall, the care for receive assistive care from his wife. Overall, the care for JJ was appropriate and followed standard of careJJ was appropriate and followed standard of carepractices.practices.
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Medication ProfileMedication Profile
Carbidopa/Levodopa (Sinemet) 25/100/poCarbidopa/Levodopa (Sinemet) 25/100/po--6times daily6times daily--(Parkinson's)(Parkinson's)Lansoprazole (Prevacid) 30mg/poLansoprazole (Prevacid) 30mg/po--ACBR ACBR--(GERD)(GERD)Baclofen (Lioresal) 10mg/poBaclofen (Lioresal) 10mg/po--qhsqhs--(Parkinson's Dystonia)(Parkinson's Dystonia)Quinine sulfate (Quinidine) 260mg/poQuinine sulfate (Quinidine) 260mg/po--qhsqhs--(Muscle Cramps)(Muscle Cramps)Quetiapine (Seroquel) 25mg/poQuetiapine (Seroquel) 25mg/po--qhsqhs--(Hallucinations)(Hallucinations)
Ropinirole (Requip) 1mg/poRopinirole (Requip) 1mg/po--1mg5Xdaily&2mgq6am1mg5Xdaily&2mgq6am--(Parkinson's)(Parkinson's)Docusate Sodium (Colace) 100mg/poDocusate Sodium (Colace) 100mg/po--bidbid--(Constipation)(Constipation)Metoprolol (Lopressor) 50mg/poMetoprolol (Lopressor) 50mg/po--qdqd--(Hypertension)(Hypertension)Calcium Carbonate (Tums) 500mg/poCalcium Carbonate (Tums) 500mg/po--1000mgbid1000mgbid--(Calcium supplement)(Calcium supplement)Oxaprozin (Daypro) 600mg/poOxaprozin (Daypro) 600mg/po--qdqd--(Osteoarthritis)(Osteoarthritis)Propoxyphen/APAP (Darvocet NPropoxyphen/APAP (Darvocet N--100) 100mg/650mg/po100) 100mg/650mg/po--1q4hprn1q4hprn--(Pain(Pain
Management)Management)Bethanechol (Urecholine) 10mg/poBethanechol (Urecholine) 10mg/po--20mgprn20mgprn--(Urinary Retention)(Urinary Retention)Docusate SodDocusate Sod--Casanthranol (Pericolace) 100mg/30mg/poCasanthranol (Pericolace) 100mg/30mg/po--qdprnqdprn--(Constipation)(Constipation)Bisacodyl Supp (Ducolax) 10mg/pr Bisacodyl Supp (Ducolax) 10mg/pr--qodprnqodprn--(Constipation)(Constipation)
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PathogenesisPathogenesis
Four TheoriesFour Theories
Oxidative damageOxidative damage
Impaired protectionImpaired protection
Environmental toxinsEnvironmental toxins
MPTPMPTP--MethylMethyl--phenyl tetrahydropyridinephenyl tetrahydropyridine
Genetic predispositionGenetic predisposition
Mutations in the gene for the protein alphaMutations in the gene for the protein alpha--synuclein located on chromosome 4synuclein located on chromosome 4
Accelerated aging Accelerated aging
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PathophysiologyPathophysiology
Imbalance of dopamine and acetylcholineImbalance of dopamine and acetylcholine
Loss of 80 to 90% of dopaminergicLoss of 80 to 90% of dopaminergic
production in the substantia nigraproduction in the substantia nigraLewy BodiesLewy Bodies
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Diagnostic FeaturesDiagnostic Features
Four Cardinal SignsFour Cardinal Signs
T remor T remor
R igidityR igidity A kinesian and bradykinesia A kinesian and bradykinesia
P ostural instabilityP ostural instability
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Characteristic ProblemsCharacteristic Problems
MicrographiaMicrographia--small handwritingsmall handwriting
HypomimiaHypomimia--decreased facial animationdecreased facial animation
HypophoniaHypophonia--soft speechsoft speechDysarthriaDysarthria--unclear pronunciationunclear pronunciation
DyspneaDyspnea--labored breathinglabored breathing
FestinationFestination--Shuffling gaitShuffling gait
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DiagnosisDiagnosis
Bradykinesia must be present with at least two of theBradykinesia must be present with at least two of thefollowing: limb muscle rigidity, resting tremor (abolishedfollowing: limb muscle rigidity, resting tremor (abolishedwith movement), or postural instability.with movement), or postural instability.Need to eliminate secondary causes;Need to eliminate secondary causes; PostencephaliticPostencephalitic DrugDrug--InducedInduced ToxicToxic StrokeStroke TraumaTrauma NeoplasmNeoplasm Other neurodegenerative conditionsOther neurodegenerative conditions
Wilson¶s diseaseWilson¶s disease Alzheimer¶s Alzheimer¶sLewy Body dementiaLewy Body dementia
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Hoehn and Yahr Staging of Hoehn and Yahr Staging of
Severity of Parkinson¶s DiseaseSeverity of Parkinson¶s DiseaseStageStage DescriptionDescription
00 No clinical signs evidentNo clinical signs evident
II Unilateral involvementUnilateral involvement
IIII Bilateral involvement but no postural abnormalitiesBilateral involvement but no postural abnormalities
IIIIII Bilateral involvement with mild postural imbalance onBilateral involvement with mild postural imbalance onexamination or history of poor balance or falls; patient leadsexamination or history of poor balance or falls; patient leadsindependent lifeindependent life
IVIV Bilateral involvement with postural instability; patient requiresBilateral involvement with postural instability; patient requiressubstantial helpsubstantial help
VV Sever, fully developed disease; patient restricted to bed or Sever, fully developed disease; patient restricted to bed or wheelchair wheelchair
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Schwab & England Activities of Schwab & England Activities of
Daily Living ScaleDaily Living Scale100% Completely independent. Able to do all chores without slowness,100% Completely independent. Able to do all chores without slowness,difficulty or impairment. Essentially normal. Unaware of any difficultydifficulty or impairment. Essentially normal. Unaware of any difficulty
80% Completely independent in most chores. Takes twice as long.80% Completely independent in most chores. Takes twice as long.Conscious of difficulty and slownessConscious of difficulty and slowness
60% Some dependency. Can do most chores, but exceeding slowly60% Some dependency. Can do most chores, but exceeding slowlyand with much effort. Error; sometimes impossibleand with much effort. Error; sometimes impossible
40% Very dependent. Can assist with all chores, but few alone40% Very dependent. Can assist with all chores, but few alone
20% Nothing alone. Can be slight help with some chores.20% Nothing alone. Can be slight help with some chores.
0% Cannot swallow, bladder and bowel not functioning, Bed0% Cannot swallow, bladder and bowel not functioning, Bed--ridden.ridden.
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PharmacotherapyPharmacotherapy
LevodopaLevodopa
Dopamine agonistsDopamine agonists
COMT inhibitorsCOMT inhibitors Amantadine Amantadine
Anticholinergics Anticholinergics
SelegilineSelegiline
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LevodopaLevodopa
LL--Dopa (Larodopa by Roche)Dopa (Larodopa by Roche)
Introduced in the late 1960sIntroduced in the late 1960s
³Gold Standard´³Gold Standard´Crosses the bloodCrosses the blood--brain barrier brain barrier
Adverse effects such as nausea, vomiting, Adverse effects such as nausea, vomiting,
postural hypotension, involuntarypostural hypotension, involuntarymovements, restlessness, and cardiacmovements, restlessness, and cardiacarrhythmiasarrhythmias
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LevodopaLevodopa
Today LToday L--dopa/carbidopa (Sinemet) used almostdopa/carbidopa (Sinemet) used almostexclusivelyexclusivelyInitial dose of 25/100mg ½ QD for 7 days,Initial dose of 25/100mg ½ QD for 7 days,increase by ½ tab daily for 7 days until up to 1increase by ½ tab daily for 7 days until up to 1tablet TID. Extended release dosed astablet TID. Extended release dosed as25/100mg QD and titrated up to TID over a25/100mg QD and titrated up to TID over amonths time. Maximum dose of Lmonths time. Maximum dose of L--dopa isdopa is800mg/day.800mg/day.
Adverse effects minimized with carbidopa Adverse effects minimized with carbidopa³End³End--of of--dose wearingdose wearing--off effect´off effect´³On³On--off effect´off effect´
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Dopamine AgonistsDopamine Agonists³Synthetic Dopamine´³Synthetic Dopamine´
Bromocriptine Mesylate (Parlodel)Bromocriptine Mesylate (Parlodel)
Pergolide Mesylate (Permax)Pergolide Mesylate (Permax)Pramipexol (Mirapex)Pramipexol (Mirapex)
Ropinirole HCL (Requip)Ropinirole HCL (Requip)
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Dopamine AgonistsDopamine Agonists
Monotherapy or combinationMonotherapy or combination
Are particulary usefull for: Are particulary usefull for: Prolonging the effective treatment period in patients withProlonging the effective treatment period in patients with
deteriorating response.deteriorating response.
Delaying the onset of LDelaying the onset of L--dopa therapy. Particularly in younger dopa therapy. Particularly in younger patients.patients.
Treating patients who cannot tolerate high doses of LTreating patients who cannot tolerate high doses of L--dopa.dopa.
Associated with more side effects than L Associated with more side effects than L--dopadopa
Potential adverse effects include somnolence,Potential adverse effects include somnolence,
dyskinesias, nausea, vomiting, orthostatic hypotension,dyskinesias, nausea, vomiting, orthostatic hypotension,nightmares, hallucinations, confusion, dizzinessnightmares, hallucinations, confusion, dizziness
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Ergot Agonist DosingErgot Agonist Dosing
Bromocriptine (Parlodel)Bromocriptine (Parlodel) Initial 1.25mg QDInitial 1.25mg QD--BIDBID
Titrate 1.25mg to 2.5mg/d every weekTitrate 1.25mg to 2.5mg/d every week
Average dose <30mg/day. Some patients may require up to Average dose <30mg/day. Some patients may require up to
120mg/day120mg/day
Pergolide (Permax)Pergolide (Permax) 13 times more potent than bromocriptine13 times more potent than bromocriptine
Initial 0.05mg/d for 2 days, increasing by 0.1 to 0.15mg/d every 3Initial 0.05mg/d for 2 days, increasing by 0.1 to 0.15mg/d every 3
days over a 12 day perioddays over a 12 day period May increase by 0.25mg every 3 days until symptoms areMay increase by 0.25mg every 3 days until symptoms are
eliminated or adverse effects occur eliminated or adverse effects occur
Mean dose 3mg/dMean dose 3mg/d
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Nonergot Agonist DosingNonergot Agonist Dosing
Pramipexole (Mirapex)Pramipexole (Mirapex) Monotherapy or AdjunctMonotherapy or Adjunct Initial dose of 0.125 mg TID and increased every 5 toInitial dose of 0.125 mg TID and increased every 5 to
7 days as tolerated up to 3 to 4.5mg/d7 days as tolerated up to 3 to 4.5mg/d Higher doses are not more effective than 1.5mg/d andHigher doses are not more effective than 1.5mg/d and
are associated with more side effectsare associated with more side effects Mean 27% reduction of LMean 27% reduction of L--DopaDopa Decrease dose with renal function impairmentDecrease dose with renal function impairment Drugs that are secreted by the cationic transportDrugs that are secreted by the cationic transport
system may decrease the clearance of pramipexolesystem may decrease the clearance of pramipexoleby 20%. These include cimetidine, diltiazem,by 20%. These include cimetidine, diltiazem,quinidine, quinine, ranitidine, triamterene, andquinidine, quinine, ranitidine, triamterene, andverapamil.verapamil.
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Nonergot Agonist DosingNonergot Agonist Dosing
Ropinirole (Requip)Ropinirole (Requip) Monotherpy or AdjunctMonotherpy or Adjunct
Initial dose of 0.25mg TID and increased by 0.25mg TID on aInitial dose of 0.25mg TID and increased by 0.25mg TID on aweekly basis. After the fourth week doses may be increased byweekly basis. After the fourth week doses may be increased by
1.5mg/d up to 9mg/d. Further adjustment may be obtained by1.5mg/d up to 9mg/d. Further adjustment may be obtained by3mg/d increases up to 24mg/day3mg/d increases up to 24mg/day
Mean 19% reduction of LMean 19% reduction of L--dopadopa
Drugs that inhibit or induce CYP1A2 will affect the clearance of Drugs that inhibit or induce CYP1A2 will affect the clearance of ropinirole. Inhibitors such as cimetidine, ciprofloxacin,ropinirole. Inhibitors such as cimetidine, ciprofloxacin,clarithromycin, diltiazem, enoxacin, erythromycin, fluvoxamine,clarithromycin, diltiazem, enoxacin, erythromycin, fluvoxamine,
mexiletine, norfloxain, omeprazole, ritonavir, andmexiletine, norfloxain, omeprazole, ritonavir, andtroleandomycin. Inducers such as carbamazepine,troleandomycin. Inducers such as carbamazepine,phenobarbital, phenytoin, and rifampin.phenobarbital, phenytoin, and rifampin.
If therapy is stopped, discontinue over seven daysIf therapy is stopped, discontinue over seven days
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COMT InhibitorsCOMT Inhibitors
Entacapone (Comtan)Entacapone (Comtan)
Tolcapone (Tasmar)Tolcapone (Tasmar)
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COMT Inhibitor DosingCOMT Inhibitor Dosing
Entacapone (Comtan)Entacapone (Comtan)
Adjunct therapy Adjunct therapy
Initial dose of 200mg with each dose of Initial dose of 200mg with each dose of levodopa up to 8 times dailylevodopa up to 8 times daily
Decrease of LDecrease of L--dopa may be necessarydopa may be necessary
Exacerbation of LExacerbation of L--dopa side effects , diarrhea,dopa side effects , diarrhea,
urine discoloration, abdominal painurine discoloration, abdominal pain
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COMT Inhibitor DosingCOMT Inhibitor Dosing
Tolcapone (Tasmar)Tolcapone (Tasmar) Adjunct therapy Adjunct therapy
Initial 100mg TID up to 200mg TIDInitial 100mg TID up to 200mg TID
More potent and longer acting thanMore potent and longer acting thanentacaponeentacapone
Decrease LDecrease L--dopa by 25 to 50%dopa by 25 to 50%
Exacerbation of LExacerbation of L--dopa side effects, diarrhea,dopa side effects, diarrhea,urine discoloration, liver toxicity.urine discoloration, liver toxicity.
Monitor LFTs every 2 weeks for 1 year, everyMonitor LFTs every 2 weeks for 1 year, every4 weeks for 6 months, then every 8 weeks4 weeks for 6 months, then every 8 weeks
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Amantadine Amantadine
Amantadine HCL (Symmetrel) Amantadine HCL (Symmetrel)
Inhibits dopamine recaptureInhibits dopamine recapture
Blocks acetylcholine and glutamate receptorsBlocks acetylcholine and glutamate receptors
Dose 100mg BID to TIDDose 100mg BID to TID Caution in renal failure patientsCaution in renal failure patients
Currently used to reduce choreic movementsCurrently used to reduce choreic movements
Narrow therapeutic rangeNarrow therapeutic range
Unpleasant side effects such as nausea, dizziness,Unpleasant side effects such as nausea, dizziness,confusion, hallucinations, nightmares, dry mouthconfusion, hallucinations, nightmares, dry mouthperipheral edema, and livedo reticularisperipheral edema, and livedo reticularis
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Anticholinergics Anticholinergics
Trihexyphenidyl HCL (Artane)Trihexyphenidyl HCL (Artane)
Benztropine Mesylate (Cogentin)Benztropine Mesylate (Cogentin)
Monotherapy or adjunctMonotherapy or adjunct Predopaminergic therapyPredopaminergic therapy
Long touted as most effective for reducingLong touted as most effective for reducingtremor tremor
Use Limited by side effects especially in theUse Limited by side effects especially in theelderly.elderly.
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Anticholinergics Anticholinergics
Trihexyphenidyl HCL (Artane)Trihexyphenidyl HCL (Artane) Initial dose of 1mg and increase by 2 mg every 3 to 5 days until 6Initial dose of 1mg and increase by 2 mg every 3 to 5 days until 6
to 10 mg/day. Usually given TID with meals or QID with mealsto 10 mg/day. Usually given TID with meals or QID with mealsand at bedtime.and at bedtime.
Possible adverse effects include dry mouth, blurred vision,Possible adverse effects include dry mouth, blurred vision,somnolence, hallucinations, memory impairment, confusion,somnolence, hallucinations, memory impairment, confusion,urinary retention, and constipation.urinary retention, and constipation.
Benztropine Mesylate (Cogentin)Benztropine Mesylate (Cogentin) Initial dose of 0.5 to 1 mg at bedtime. Increase by 0.5mg every 5Initial dose of 0.5 to 1 mg at bedtime. Increase by 0.5mg every 5
to 6 days up to a total daily dosage of 6mg.to 6 days up to a total daily dosage of 6mg.
Possible adverse effects include dry mouth, blurred vision,Possible adverse effects include dry mouth, blurred vision,somnolence, hallucinations, memory impairment, confusion,somnolence, hallucinations, memory impairment, confusion,urinary retention, and constipation.urinary retention, and constipation.
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SelegilineSelegiline
Selegiline HCL(Eldepryl)Selegiline HCL(Eldepryl)
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SelegilineSelegiline
Selegiline HCL (Eldepryl)Selegiline HCL (Eldepryl) Monotherapy or adjunctMonotherapy or adjunct MOAMOA--inhibits monoamine oxidaseinhibits monoamine oxidase--B (MAOB (MAO--B)B) Inhibition of MAOInhibition of MAO--A does not occur A does not occur Dosage of 5 mg BID with breakfast and lunchDosage of 5 mg BID with breakfast and lunch When used as monotherapy delays the need of LWhen used as monotherapy delays the need of L--
dopa by an average of nine months.dopa by an average of nine months. Possible adverse effects include nausea, dizziness,Possible adverse effects include nausea, dizziness,
abdominal pain, confusion, and exacerbation of Labdominal pain, confusion, and exacerbation of L--
dopa side effectsdopa side effects Controversial theory of decreased rate of neuronalControversial theory of decreased rate of neuronal
death due to a reduction of free radicals.death due to a reduction of free radicals.
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Surgical OptionsSurgical Options
Pallidotomy and Pallidal StimulationPallidotomy and Pallidal StimulationThalamotomy and Thalamic StimulationThalamotomy and Thalamic Stimulation Introduced in 1950Introduced in 1950 Pallidotomy improves tremor, rigidity, andPallidotomy improves tremor, rigidity, and
bradykinesiabradykinesia Thalamotomy relieves tremor, rigidity, but notThalamotomy relieves tremor, rigidity, but not
bradykinesiabradykinesia Neurosurgical treatment came to a end with theNeurosurgical treatment came to a end with the
introduction of Lintroduction of L--dopa in late 1960sdopa in late 1960s Resurgence of neurosurgical intervention with theResurgence of neurosurgical intervention with the
failure of pharmacological treatments after 10 to 15failure of pharmacological treatments after 10 to 15years of disease progressionyears of disease progression
Two methods: Ablation and deep brain stimulationTwo methods: Ablation and deep brain stimulation
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GraftingGrafting
Suprarenal to brain transplantationSuprarenal to brain transplantation
Fetal tissue transplantationFetal tissue transplantation
Cell culture transplantationCell culture transplantation
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Under InvestigationUnder Investigation
Implantable pumpsImplantable pumps
Implantable capsules containingImplantable capsules containing
dopaminedopamine--producing cellsproducing cellsNew medications to target one of the fiveNew medications to target one of the fiveindividual brain receptors for dopamineindividual brain receptors for dopamine
Continued genetic researchContinued genetic research
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ReferencesReferences
Cosgrove, G. Rees, Eskandar, Emad N., Shinobu, Leslie A. ³Surgical Treatment of ParkinsonCosgrove, G. Rees, Eskandar, Emad N., Shinobu, Leslie A. ³Surgical Treatment of ParkinsonDisease.´ JAMA December 26, 2001;286:3056Disease.´ JAMA December 26, 2001;286:3056--3059.3059.Dipiro, Joseph T., ed.Dipiro, Joseph T., ed. Pharmacotherapy Fourth Edition.Pharmacotherapy Fourth Edition. Stamford, Connecticut: Appleton &Stamford, Connecticut: Appleton &Lange, 1999.Lange, 1999.³Early Parkinson¶s Disease: Dopamine Agonists Have Increasingly Important Role in Symptom³Early Parkinson¶s Disease: Dopamine Agonists Have Increasingly Important Role in SymptomManagement.´ Drug Ther Perspect 2001;17(17):5Management.´ Drug Ther Perspect 2001;17(17):5--9.9.Faulkner, Thomas P. ³Parkinson¶s Disease.´ 7 December 1999.Faulkner, Thomas P. ³Parkinson¶s Disease.´ 7 December 1999.http://www.onu.edu/user/FS/tfaulkner/parkinso.htmlhttp://www.onu.edu/user/FS/tfaulkner/parkinso.html 23 May 2002.23 May 2002.Hermanowiez, Neal. ³Management of Parkinson¶s Disease.´ Postgraduate MedicineHermanowiez, Neal. ³Management of Parkinson¶s Disease.´ Postgraduate Medicine2001;110(6):152001;110(6):15--2828Korczyn, Amos D. ³Hallucinations in Parkinson¶s Disease.´ Lancet 2001;358(9287):1031Korczyn, Amos D. ³Hallucinations in Parkinson¶s Disease.´ Lancet 2001;358(9287):1031--1032.1032.Lindvall, Olle. ³Stem Cell Transplantation.´ Lancet 2001;358(Supplement);s47.Lindvall, Olle. ³Stem Cell Transplantation.´ Lancet 2001;358(Supplement);s47.Nicholl, David. ³Parkinson¶s Disease.´ 22 April, 1998.Nicholl, David. ³Parkinson¶s Disease.´ 22 April, 1998.http://medweb.bham.ac.uk/http/depts/clin_neuro/teaching/tutorials/parkinsons/parkinsons1http://medweb.bham.ac.uk/http/depts/clin_neuro/teaching/tutorials/parkinsons/parkinsons1... 27... 27May, 2002.May, 2002.Ninds. ³Parkinson¶s DiseaseNinds. ³Parkinson¶s Disease--Hope Through Research.´Hope Through Research.´
http://accessible.ninds.nih.gov/health_and_medical /pubs/parkinson_disease_htr.htmhttp://accessible.ninds.nih.gov/health_and_medical /pubs/parkinson_disease_htr.htmReferenced on 5/27/02.Referenced on 5/27/02.Stephenson, Joan. ³Exposure to Home Pesticides Linked to Parkinson Disease.´ JAMA June 21,Stephenson, Joan. ³Exposure to Home Pesticides Linked to Parkinson Disease.´ JAMA June 21,2000;283(23):30552000;283(23):3055--3058.3058.
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