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PARKINSONSDISEASE::

EVALUATION,REHABILITATION
ANDTREATMENT
BradleyR.ErtelMD
ReneeErtelPuleoPharm.D.
MercyHospitalofSouthBuffalo

DISCLOSURES
None

OBJECTIVES
DiscussthepathophysiologyofParkinsonsDisease(PD)
DefinespecificmovementdisordersassociatedwithPD
Discusspharmacologicalandnonpharmacological
treatments

DEFINITIONSOFMOVEMENTDISORDERS
Neurologicaldysfunctionsinwhichthereexistseither:
Hyperkinesia:excessivemovement
Hypokinesia:paucityofvoluntaryandautomaticmovements

Notassociatedwithweaknessorspasticity

EXAMPLESOFHYPERKINESIA
Akathisia:Restlessness,anxiety,innertension
Athetosis:Slow,writhing,involuntarymovementsthatareusuallydistal
Ballismus:Violent,involuntarymovementsinvolvingonesideofbody
Chorea:Brief,repetitive,jerky,involuntarymovements
Dystonia:Repetitive,twistingmovementsleadingtoabnormalposture

MOREEXAMPLESOFHYPERKINESIA
Hemifacial spasm:Irregular,involuntarymusclecontractionsononesideoftheface
Myoclonus:Brief,shocklikemuscularcontractionsthatcanberegularorarrhythmic
RestlessLegSyndrome:Urgetomovethelegstorelieveunpleasantsensations
Tics:Sustained,nonrhythmic,rapid,andstereotypedmusclecontractions
Tremor:Rhythmicandoscillatingmovements

EXAMPLESOFHYPOKINESIA
ParkinsonsDisease
SecondaryParkinsonism

Meningitis
AIDS
Reglan
MPTP

ParkinsonsPlusSyndromes
ShyDrager:Autonomicdysfunction
Olivopontocerebellar atrophy:Ataxiaanddysarthria

PARKINSONSDISEASE
Progressivedisorderofthebasalgangliaduetolossof
dopaminergiccellsinthesubstantianigra
Hyperactivityofcholinergicneuronsinthecaudatenuclei
Imbalancedcholinergic/dopaminergic transmission

INCIDENCEANDEPIDEMIOLOGY
PrevalenceRate:200per100,000
Rareforindividuals<40yearsofage
1%forindividuals>60yearsofage
2%forindividuals>85yearsofage
Men>Women
Incidencerate:20per100,000(annually)
TheNationalParkinsonsFoundationestimatesthatupto1.5million
Americanshavethedisease
Approximately50,000newcasesarediagnosedeachyear
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CLINICALFEATURESOFPARKINSONS
DISEASE
Restingtremor
Leadpiperigidity
Cogwheelrigidity
Bradykinesia /MaskedFacies
Posturalinstability
Festinating(shuffling)gait
Freezingphenomenon
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RESTINGTREMORS

Suppressedbyactivity
orsleep
Intensifiedbystressor
fatigue(pillrolling)

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RIGIDITY

Leadpipe

Smoothresistancetopassive
movementthatis
independentofvelocity

Cogwheel

Ratchetingthroughrangeof
motionduetosubtletremor
superimposedonrigidity
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BRADYKINESIA

Upperextremities
Beginsdistallywith
decreasedmanualdexterity
offingers
Typing
Tyingshoelaces
Buttoningshirt

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BRADYKINESIA

Lowerextremities
Legdragging
Shufflingfeet
Difficultystandingupfromachair
Difficultygettingoutofacar

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MASKEDFACIES

Occurswhen
bradykinesiaaffects
themusclesoffacial
expression

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POSTURALINSTABILITY

Slumpedover
Protractedshoulders
Flexedhips
Flexedknees

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DIAGNOSISOFPARKINSONSDISEASE
Primarilyclinical
Twogroupsofsymptoms
Minimalornoresttremor(predominantrigidityandakinesia)
Resttremorpredominant
Theuseoflaboratoryorneuroimagingisforexclusionary
purposesandatypicalcases
Routineelectrodiagnostic studieswillnotaidindiagnosisofPD

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STAGESOFPARKINSONSDISEASE
Early
Mild
Moderate
Severe
Late
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STAGESOFPARKINSONSDISEASE
EARLY

Nofunctionalimpairment
Mildsymptoms
Unilateraltremors
Familymembersdetectpoorposture,lossofbalance,andabnormalfacialexpressions

MILD
Bilateralsymptoms
Difficultyambulatingandmaintainingbalance
DifficultycompletingADL
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STAGESOFPARKINSONSDISEASE
MODERATE

Multiplemedications
Occupationalandsocialactivitiesaffected
Inabilitytowalkorstandstraight
Noticeableslowingofmovements

SEVERE

Medicationsideeffects
Resistancetotherapies
Reducedqualityoflife
UnabletoperformADL
Cannotliveindependently
Decreasedtremors(mechanismunknown)

LATE

DependentinADL,wheelchairorbedbound
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PROGNOSISOFPARKINSONSDISEASE
Tremorpredominantpatientsprogressmoreslowlythan
patientswithbradykinesiaasthepredominantcomplaint
Bradykinesiaismoredisablingthantremors
Akinesia canindicateamorerapidlyprogressingdisease
process
Lifeexpectancyisvariable,butsignificantlyimprovedwith
medicalmanagement
Dysphagiaisthemostimportantriskfactorassociatedwith
earlydemise
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PROGNOSISOFPARKINSONSDISEASE
PositivePrognosticIndicators
Earlytremor
Rigidity
FamilyhistoryofParkinsons
Disease

NegativePrognosticIndicators
Bradykinesia
Akinesia
Posturalinstability
Gaitdysfunction
Cognitivedeficits
Lateageofonset
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PARKINSONSDISEASE
PETscanshighlightthelossof
dopaminestoragecapacityin
Parkinsonsdisease.Inthescanofa
diseasefreebrain,madewith[18F]
FDOPAPET (leftimage), theredand
yellowareasshowthedopamine
concentrationinanormalputamen,a
partofthemidbrain.Comparedwith
thatscan,asimilarscanofaParkinsons
patient (rightimage) showsamarked
dopaminedeficiencyintheputamen.

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PARKINSONSDISEASE
BCMJ,Vol.43,No.3,April2001,
page(s)142147

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IMPAIRMENTSINPARKINSONSDISEASE
Gait
Bladder
Orthostatichypotension
Pain
Gastrointestinal
Cognition
Depression
PsychosisandHalluciniations
Sleep
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GAIT
Canresultfromdiseaseor
secondarytomedications
Inefficient
Compromisedbybradykinesia,
poorposture,andfearoffalling
2Stereotypicalpatterns
Freezing:Inabilitytoinitiate
gaitafterstopping
Festination:Rapidshuffling
stepswithadditionaltrunk
flexion
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BLADDER
Mostcommonabnormality:nocturia
Urgency
Frequency
Detrusorhyperreflexia
Treatment
Timedvoidingwhileawake
Intermittentcatheterization
Anticholinergics
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ORTHOSTATICHYPOTENSION
Duetoautonomicdysfunction
fromsympatheticdenervation
Magnifiedbyintravascular
volumedepletionduetopoor
fluidintake
Elderly:Considercardiovascular
diseaseandothercausesof
hypotension,suchas
medications

Treatment
Avoidwarmbathsandheavymeals
Avoidstrainingwhiledefecating
AvoidValsalva maneuver
Compressionlegstockings
Abdominalbinders
Ariseslowlyfromaseatedposition
Pauseinasittingpositionbeforearising
fromasupineposition
Tilttabletest
Antihypertensivemedicationmanagement
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PAIN
Primarycentralprocesses
Secondarytootherconditions
Achingpaininaffectedlimb
MostcommoncauseofpaininPDlimbrigidity
Restlesslegsyndrome
Headaches
Treatment
Pharmacologicalandnonpharmacological
Increasemobilityandflexibility
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GASTROINTENSTINAL
Swallowing
Decreasedlingualcontroland
boluspropulsion
Duetoabnormalitiesinstriated
muscleunderDAcontroland
smoothmuscleunderautonomic
control

Nutrition
Restrictproteinconsumption
VitaminB6supplementation

Decreasedgastricemptying
Earlysatiety
Nausea/vomiting
Reglan worsensdyskinesia
Decreasedperistalsisand
GERDheartburn

Constipation
Alteredsympatheticinnervation of
GItract
Decreasedmobilityandhydration
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COGNITION
Psychomotorretardation,memorydifficulty,and
alteredpersonality
Anatomicandpathologicbasisisnotunderstood
Dementiaoccurslateinthedisease
Riskfactors
Laterageofonset
Longersymptomduration
Hallucinations
Depressivesymptoms
Familyhistoryofdementia
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DEPRESSION
MostcommonpsychiatricdisturbanceseeninPD
Independentofdiseaseseverityandduration
FeaturesofdepressionandParkinsonsare
similar
Deficitsinserotonergictransmission
Decreasednorepinephrineanddopamine
Treatment
Counseling
TCA
SSRI

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PSYCHOSIS/HALLUCINATIONS
Visualhallucinationsarethemostcommonpsychiatric
symptominPDpatients

Psychosis
UnderlyingLewy Bodydisease
Antiparkinson drugs(Dopamineagonists)
Generallyresolveswhenmedicationsarediscontinued
Singlegreatestreasonfornursinghomeplacementin
patientswithPD
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SLEEP
Rankedasoneofthemosttroublesomenonmotor
symptomsinearlyandlatePD
Mostcommonsleepdisturbances:Sleep
fragmentationandearlymorningawakening
Mostcommonetiologies

Nocturia
Difficultyturningoverinbed
Cramps
Vividdreams
Nightmares
Pain(mostcommonlyneckorback)
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SURGICALTREATMENTOF
PARKINSONSDISEASE

DESTRUCTIVESURGERY
Thalamotomy
Surgicaldestructionofspecificcellsinthethalamus
Restrictscontralateraltremor

Pallidotomy
Permanentablationofaportionoftheglobus pallidus
Indications
Dyskinesias
Stiffness
Freezing
Noteffectiveforcontrollingtremors

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DEEPBRAINSTIMULATION(DBS)
DBStargets:Thalamus,Globuspallidus interna,andSTN
Highfrequencystimulationinvolvesplacinganelectrodeintothetargeted
brainareaunderelectrophysiologic guidance
Electrodeisconnectedtoapulsegenerator,whichisactivatedand
deactivatedbypassingamagnetovertheapparatus
Theprecisemechanismofactionisunknown,butDBSispurportedtowork
byresettingabnormalfiringpatternsinthebrain
Associatedwithfewercomplicationsthanthalamotomy
Isreplacingthalamotomy astheprocedureofchoiceforParkinsons
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TYPESOFDEEPBRAINSTIMULATION
Subthalamic
Reducestremor,rigidity,andbradykinesia
Reducesantiparkinsonian medicationsbyhalf
MostcommonsurgicalprocedureforParkinsonsDisease

Thalamic
Reducescontralateraltremor
Worsensbradykinesia,rigidity,andgait
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DEEPBRAINSTIMULATION

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PHARMACOLOGICAL
TREATMENT

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PHARMACOLOGICALAGENTSFORPD
Carbidopa/Levodopa
DopamineAgonists
MonoamineoxidaseB(MAOB)inhibitors
CatecholOmethyltransferase (COMT)inhibitors
Amantadine
Anticholinergic agents
Botulinum Neurotoxin(Botox)
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CARBIDOPA/LEVODOPA
Carbidopa/Levodopa (Sinemet)
Carbidopa/Levodopa ODT(Parcopa)
Carbidopa/Levodopa CR(Sinemet CR)
MechanismofAction

Levodopa isthemetabolicprecursorofdopamine
Levodopa crossesthebloodbrainbarrier,whereitisconvertedtodopamine
Treatsbradykinesia,rigidity,andtremor

Adversereactions

GI:anorexia,n/v
Cardiovascular:arrhythmiaandorthostatichypotension
Psychiatric:mooddisorders,sleepdisturbances,hallucinations,anddelusions
Controlledbyadjustingdoseandfrequency

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CARBIDOPA/LEVODOPA DOSING
Immediaterelease
Initial:Carbidopa25mg/levodopa 100mgPOTID
Foodtoreducenausea
Orallydisintegratingdoesnotrequirewater

Sustainedrelease
Carbidopa50mg/levodopa 200mgPOBID
Decreasedoseinelderly
Donotcrush
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DOPAMINEAGONISTS
Pramipexole(Mirapex)

Apomorphine(Apokyn)

Bromocriptine (Parlodel)

Ropinirole (Requip)

Rotigotine(Neupro)
MechanismofAction
Exactunknown;stimulatedopaminereceptors
Treatbradykinesia andrigidity
Reduceofftime

AdverseReactions
Somnolence,edema,n/v,hypotension,hallucinations,andperipheraledema
Pulmonaryfibrosiswithbromocriptine

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DOPAMINEAGONISTDOSING
Pramipexole
Initial:0.125mgPOTID
Foodtoreducenausea
Adjustforrenalimpairment

Ropinirole
Initial:0.25mgPOTID,Max:24mg/day

Rotigotine

Apomorphine
0.06mg/kgrescuesubcutaneous
injection

Bromocriptine
Initial:1.25mgPOBID
Foodtoreducenausea

Transdermalpatchapplieddaily
Initial:2mg/24hr(early),4mg/24hr
(advanced)
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MAOBINHIBITORS
Selegiline (Eldepryl)
Selegiline ODT(Zelapar)
Rasagiline (Azilect)
MechanismofAction

SelectivelyinhibitsMAOBfrombreakingdowndopamine
Maybeneuroprotective
Treatmotorfluctuations
Reduceofftime

AdverseReactions

Headache,nausea,hypertensionwith>400mgtyramine
Insomniawithselegiline
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MAOBINHIBITORDOSING
Selegiline
5mgPOBIDwithbreakfastandlunch
10mgPOdailyinthemorning
Dosedecreaseinelderly

Rasagiline
1mgPOdaily
Dosedecreaseinmildhepaticimpairment
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COMTINHIBITORS
Entacapone(Comtan)
Tolcapone (Tasmar)
MechanismofAction
Usedinconjunctionwithcarbidopa/levodopa
SelectivelyinhibitsperipheralCOMT
Treatmotorcomplications

AdverseReactions
Increasedlevodopa adversereactions,brownorangeurine

BlackBoxWarning
Hepatotoxicity withtolcapone
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COMTINHIBITORDOSING
Entacapone
200mgwitheachdoseofcarbidopa/levodopa
Max:1600mg/day

Tolcapone
Initial:100mgPOTID

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COMBINATIONPRODUCT
Carbidopa/Levodopa/Entacapone (Stalevo)
Substituteforpatientsalreadystabilizedonequivalent
dosesofeachcomponent

Complication
Neuroleptic MalignantSyndrome(NMS)isassociatedwith
dosereductionsandwithdrawaloflevodopa preparations
Musclerigidity,fever,instability,anddelirium

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AMANTADINE (SYMMETREL)
MechanismofAction
Stimulatesdopaminereleaseandinhibitsglutamate
neurotransmission
Treatsdyskinesia andtremor

AdverseReactions
Edema,dizziness,confusion,andlivedo reticularis

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AMANTADINE (SYMMETREL)DOSING
Initial:100mgBIDifsoletherapy,oncedailyif
combination
Adjustforrenalimpairment

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ANTICHOLINERGIC DRUGS
Benztropine (Cogentin)
Trihexyphenidyl (Artane)
MechanismofAction
Antagonizeacetylcholinereceptors
Goal:regainbalancebetweendopamineandacetylcholine
Treattremoranddystonia

AdverseReactions
Drymouth,blurredvision,constipation,andurinaryretention
Moreserious:forgetfulness,sedation,depression,andanxiety
Trihexyphenidyl:glaucoma,needophthalmicexam
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ANTICHOLINERGIC DOSING
Benztropine
Initial:0.56mg/dayin12divideddoses
Dosedecreaseinelderly

Trihexyphenidyl
Initial:12mg/dayin2divideddoses
Max:515mg/dayin34divideddoses

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BOTULINUM NEUROTOXIN(BOTOX)
Treatment
Cervicaldystonia,blepharospasm,focalupperextremitydystonia,laryngeal
dystonia,essentialtremor,andsialorrhea

MechanismofAction
Blocksthereleaseofacetylcholineattheneuromuscularjunction
Localizedmuscleweakness

AdverseReactions
Local;onlyimpactsareasintowhichitisinjected

Limiteddurationofaction
Reinjectionevery34months
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TREATMENTOFIMPAIRMENTS
Gait:reducepharmacology
Bladder: anticholinergics oralphablockers
Orthostatichypotension: midodrine
Pain: symptomatictreatment
Gastrointestinal: polyethyleneglycol
Cognition: reducepolypharmacy
Depression:TCA&SSRI
PsychosisandHallucinations:reducedopamineagonists
Sleep:melatonin

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CONCLUSIONS
Parkinsonsdiseaseresultsfromadopamine/acetylcholine
transmissionimbalance
PDisahypokinetic movementdisorder
ThereareavarietyofdebilitatingimpairmentsassociatedwithPD
Thereareseveralpharmacologicalandnonpharmacological
treatmentsforPDanditscorrespondingimpairments
ThereisnocureforPD,butmanagingthesymptomsofthedisease
canleadtoanimprovedqualityoflife
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REFERENCES
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Elsevier.2007
Chou,KelvinMD.ClinicalManifestationsofParkinsonsDisease.www.uptodate.com.Ed.
HowardHurtig MD.July25,2014.
Delisa,JoelMD.PhysicalMedicineandRehabilitation:PrinciplesandPractice(FifthEdition).
Philadelphia.LippincottWilliamsandWilkins.2010.

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REFERENCES
Suchowersky,O."PracticeParameter:Neuroprotective StrategiesandAlternativeTherapies
forParkinsonDisease(an EvidencebasedReview):ReportoftheQualityStandards
SubcommitteeoftheAmericanAcademyofNeurology." Neurology 66.7(2006):97682.
Web.
Trail,Marilyn,ElizabethProtas,andEugeneC.Lai. Neurorehabilitation inParkinson'sDisease:
AnEvidencebasedTreatmentModel.Thorofare,NJ:SLACK,2008.Print.
Wells,BarbaraG."Parkinson'sDisease." PharmacotherapyHandbook.NewYork:McGrawHill
MedicalPub.Division,2009.62936.Print.
Zesiewicz,T.A.,K.L.Sullivan,I.Arnulf,K.R.Chaudhuri,J.C.Morgan,G.S.Gronseth,J.
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