Parkinson_s Disease Case Presentation

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



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



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



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



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.



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)



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



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



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



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









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



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



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.



PharmacotherapyPharmacotherapy

LevodopaLevodopa

Dopamine agonistsDopamine agonists

COMT inhibitorsCOMT inhibitors Amantadine Amantadine

Anticholinergics Anticholinergics

SelegilineSelegiline





LevodopaLevodopa

LL--Dopa (Larodopa by Roche)Dopa (Larodopa by Roche)

Introduced in the late 1960sIntroduced in the late 1960s

³Gold Standard´³Gold StandardĆrosses 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





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 effectóff effect´³On³On--off effectóff effect´





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)



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



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



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.



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



COMT InhibitorsCOMT Inhibitors

Entacapone (Comtan)Entacapone (Comtan)

Tolcapone (Tasmar)Tolcapone (Tasmar)



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



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



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




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.




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.




Selegiline HCL(Eldepryl)Selegiline HCL(Eldepryl)




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.



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



GraftingGrafting

Suprarenal to brain transplantationSuprarenal to brain transplantation

Fetal tissue transplantationFetal tissue transplantation

Cell culture transplantationCell culture transplantation



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



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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Parkinson_s Disease Case Presentation

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