Transcript
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SUMAIYA SALIM, M.D.
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Classification
y Hypokinesias - typified byslownessand/orpaucityofmovement, eg. parkinsonism.
y Hyperkinesias - abnormalinvoluntarymovements,eg. chorea, dystonia, myoclonus, stereotypes, tics,tremors.
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Hypokinesias
y Bradykinesia - slownessofmovement andimpairedinitiation/paucityofmovement (akinesia).
y Rigidity- cogwheeling- increasedresistance topassive movement.
y Posturalinstability- propulsion, retropulsion.
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Hyperkinesias- Chorea
y Chorea - continuous, abrupt, rapid, brief,unsustained, irregular, random, DANCE-LIKE
movementswhichflowfrom one bodypart toanother.Maybeincorporatedintosemipurposeful activities.Motorimpersistance isacommonfeature - difficultymaintainingsustainedcontractionssuchas tongueprotrusion.
y Athetosis isacontinuousstream ofslow, sinuous,writhing movements, typicallyofthehandsandfeet
y Ballism thrashing motions
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Hyperkinesias - Dystoniay Dystonia - involuntary, sustained (tonic)or
intermittent (spasmodic, clonic), patterned,repetitive musclecontractionswhichfrequentlycause twisting (torticollis), flexingorextending(writerscramp, retrocollis), andsqueezing(blepharospasm)orabnormalposture. Maybe task-specific.
yFocal, segmental, generalized, multifocalandhemidystonia
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Hyperkinesias - Myoclonusy Lightning-like movementssecondaryTO
y briefsuddencontractions (positive myoclonus)
y or muscleinhibition (negative myoclonus). Asterixis:one typeofnegativemyoclonus
y Focal, segmental, multifocal, generalized.
y Cortical, brainstem (reticular), andspinal
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Hyperkinesias - Stereotypies
y Involuntaryorsemi-voluntary(unvoluntary)patterned, repetitive, coordinated, rhythmic,
purposeless thoughseeminglypurposefulorritualistic movement, postureorutterance.
y Examplesincludefoot tapping, bodyrocking, orcomplexrituals.
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Hyperkinesias-Tics
y Relativelybrief, repetitive, nonrhythmic,y movements (motor tics)y sounds (phonic/vocal tics).
y Premonitorysensations - maybelocalized (burning,tension, tightness)orfeelingofanxiety, an urge
y Suppressible toadegree. suppressible yet irresistibley Simple motor tics - sudden, brief, meaningless
movementsinvolveonlyonegroupofmuscles (eyeblinking, head jerkingorshouldershrugging. simple
phonic tic can bealmost anysoundornoise (throatclearing, sniffing, orgrunting)y Complex motor tic - clusterofmovementsandapppear
coordinated. (pullingat clothes, touchingpeople). Vocal echolalia, coprolalia
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Hyperkinesias -Tremorsy Involuntary, rhythmic, oscillatorymovementsabout
a joint secondarytoalternatingorsynchronous
contractionsofantagonist muscles.y Rest - fullysupportedagainst gravity.
y Action - duringvoluntarycontractions.
y Postural, Kinetic (initial, dynamic, terminalor
intention), task- orposition-specific, isometric.
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Anatomy - Basal Ganglia
y 6pairednuclei - caudatenucleus, putamen, globuspallidus, nucleusaccumbens, subthalamicnucleus
andsubstantianigra.y lenticularnucleus - lenslike - putamenandglobus
pallidus.
y GPiand SNr behaveassinglefunctionalunit.
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Anatomy - Basal Ganglia
y striatum - caudateandputamen - composedofstriosomes (limbicsystem projectshere), matrix
(neocorticalfibersproject here).y putamen - motor - receivesinput from
somatosensory, motorandpremotorareas.
y caudate - emotionalandcognitiveprocesses -
posteriorparietaland temporal, frontalassociationareasproject here.
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Anatomy - Basal Gangliay Functions to modulate theamplitudeandvelocityof
movement andin thepreparationfor movement.
ySeediagramsforproposed basalgangliacircuitryinnormalsandin Parkinsonsdisease
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Cortex
PrefrontalInsular
CingulateSensoryMotor
Suppl. MotorPremotor
PremotorPrefrontal
Striatum
D2 D1 ThalamusVA/VL
+ = excitatory
- = inhibitory
BrainstemSC
SNc
SNr
GPi
STN
GPe
-
+
+
+ -
-
--
-
-
+
++
+
+
+
Normal
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Cor ex
re ron ansu ar
Cingu a eensoryo or
upp o orre o or
re o orre ron a
riatu
2 1Thalamus
L
+ = excitatory
= inh ibitory
rainstemSC
SNc
SNri
STN
GPe
++
++++
+
++
+
+
+
Parkinsons isease
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Clinical Features/Cardinal Signs
y 1817: James Parkinson AnEssayon the Shaking Palsy
y
Diagnosis requires 2 of 3:y Bradykinesia
y Rigidity
y Tremor (primarily at rest)
y Othersigns: Maskedface, hypovolemic speech,swallowingdifficulty, micrographia, flexedposture,shufflinggait, start hesitancyandfreezing
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Onsety Insidious, unilateralprogressing to bilateral
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Classification of Parkinson Syndromes in a
Community
y Idiopathic PD ~ 85%ofall PS cases
y Neuroleptic-inducedparkinsonism (DIP)7% - 9%
y Vascularparkinson syndrome ~ 3%y PS due to MPTP, CO, Mn, recurrent head traumais
extremelyrare
y Nonewcasesofpostencephalitic parkinsonism since
1960s
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Epidemiology of Parkinson Syndrome
y Incidence:
- 5-24/100000worldwide (USA/Canada 300/100000)-IncidenceofPS/PD risingslowlywithagingpopulation
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Prevalence
y 57-371/100t. worldwide (USA/Canada 300/100t.)
y 35%-42%ofcasesundiagnosedat anytime
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Onset
y mean PS 61.6years; PD 62.4 years
y rare beforeage 30; 4-10%cases beforeage 40
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Pathology of Parkinsons Disease
y Markedstriatal DAdepletion
Striatal dopaminedeficiencysyndrome
y At death, DAloss > 90%
y
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Parkinsons Disease Risk Factors
y Definite: Oldage
y Highlylikely: MZ co-twinwithearly-onset PD
y Probable: Positivefamilyhistoryy Possible:Herbicides, pesticides, heavymetals,
proximitytoindustry, ruralresidence, wellwater,repeatedhead trauma, etc.
y Possibleprotectiveeffect: Smoking
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Cause of PD
y Unknownin most cases;not acceleratedagingy GenesAD inheritanceveryrare; mutationunknown
mutationofAlphasynucleingene (chromosome 4q)identifiedinonelarge Italian (Contursi)and5 Greekautosomaldominant families
mutationofparkingeneinautosomal-recessive juvenileparkinsonism
y EnvironmentMajorityofcases believedcaused byenvironmentalfactor (s)
but noneidentifiedsofary Genesplusenvironment?
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Early Signs and Symptoms
y CardinalCharacteristics (Requires 2 of3):
y Resting tremor
yBradykinesia
y Rigidity
Andoftenassociatedwith Posturalinstability
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Early Signs and Symptoms
Others
y Micrographia
y
Maskedfacey SlowingofADLs
y Stooped, shufflinggait
y Decreasedarm swingwhenwalking
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Additional Signs and Symptoms
y Difficultyarisingfrom achair
y Difficultyturningin bed
y Hypophonicspeechy Sialorrhea
y Lossofthesenseofsmell
y Foot dystonia
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Clues Suggesting Atypical Parkinsonism
y Earlyonset of, orrapidlyprogressing, dementia
y Rapidlyprogressivecourse
y Supranuclear gazepalsy(impairedverticalgaze,bradykinesia, posturalinstability, frequent falls,incontinence)
y Upper motorneuronsigns (suggestiveofstrokes)
y Cerebellar signsdysmetria, ataxiay Urinaryincontinence (NPH)
y Earlysymptomaticposturalhypotension
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Hereditary disorders associated with
parkinsonism
y Wilsonsdisease
y Huntingtonsdisease
y Dentatorubro-pallidoluysianatrophy(DRPLA)y Machado-Josephdisease (SCA-3)
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Differential Diagnosis of PDy Drug-induced
y Toxin-induced
y Metabolicy Structurallesions (vascularparkinsonism, etc.)
y Hydrocephalus
y Infections
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Drug-Induced Parkinsonism
y Crucial toruleout, since most casesarereversible
y Careful medicationhistorylist drugnames
y Commonoffendingdrug types
y Antipsychotics :haloperidol, chlorpromazine,thioridizine, perphenazine, risperidone, olanzapine
y Antiemeticsmetoclopramide, prochlorperazine
y Dopaminedepletorsmethyldopa, reserpine,
tetrabenaziney Combinationdrugse.g., Triavil (amitriptyline,
perphenazine)
y Treatment: Stopoffending medication
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Metabolic and Infectious Causes of
Parkinsonism
y Metabolicy Oftenreversible
y Hypo- orhyper-thyroidism
y Hypo- orhyper-parathyroidism
y Liverfailure
y Centralpontine myelinolysis
y Infectiousy Post-encephaliticy Creutzfeldt-Jakob disease
y Infectious masses
y HIV
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Toxin-induced Parkinsonism
y MPTP
y Carbon monoxide
y Manganesey Cyanide
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Structural Lesions Causing Parkinsonism
y Acuteorsubacuteonset
y Othersignshemiparesis, hyperreflexia, aphasia,
sensoryloss, seizuresy Brain tumor
y Infectious mass
y Aneurysm
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Vascular Parkinsonism
y Abrupt onset, usuallyunilateral
y Step-wiseornoprogression
y Othersignshemiparesis, aphasia, hyperreflexiay Infarctsonneuroimaginghelpfulinconfirming
diagnosis
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Hydrocephalus-induced Parkinsonism
y Can becommunicatingorobstructive
y Normalpressurehydrocephalusidiopathic
y Clinical triad:y parkinsonism/gait disorder
y urinary/fecalincontinence
y dementia
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Parkinsons Disease vs. Essential Tremory Essential tremorshould be tremorwithnoothersigns
ofparkinsonism
y Bothcanhaveakineticandrest component
y Kinetic tremorcaninterferewith RAM
y Cogwheelrigiditycan befoundinET
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TreatmentOptions
y Preventive treatment -- Nodefinitiveavailable
y Symptomatic treatmenty
Pharmacologicaly Surgical
y Non-motor management
y Restorativeexperimentalonlyy Transplantationy Neurotrophic factors
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Drug Classes in PD
y Dopaminergic agents
y Levodopa
y
Dopamineagonistsy COMT inhibitors
y MAO-Binhibitors
y Anticholinergics
y Amantadine
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Levodopa
y Most effectivedrugforparkinsonian symptoms
y First developedin thelate1960s;rapidlybecame
thedrugofchoicefor PDy Largeneutralaminoacid;requiresactive transport
across thegut-bloodand blood-brain barriers
y Rapidperipheraldecarboxylation todopamine
without adecarboxylase inhibitor (DC
Is:carbidopa, benserazide)
y Sideeffects:nausea, posturalhypotension,dyskinesias, motorfluctuations
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Diagram of LD Metabolism
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Levodopa-Induced Dyskinesiasy Manifestationofexcessivedopaminergic
stimulationy Typicallylateeffect, andwithhigherdosesy Narrowingoftherapeuticwindowy Rarein LD-naivepatientson DA monotherapyy Most commonis peakdosedyskinesia
disappearswithdosereductiony Choreiform, ballisticanddystonic movementsy Most patientsprefersomedyskinesiasover the
alternativeofakinesiaandrigidity
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Dopamine Agonists: Distinguishing Features
y Directlystimulatedopaminereceptorsy No metabolicconversion; bypasses
nigrostriatalneuronsy Noabsorptiondelayfrom competitionwith
dietaryaminoacidsy Longerhalf-life thanlevodopay Monotherapyoradjunct therapyy Maydelayorreduce motorfluctuations &
dyskinesiasassociatedwithlevodopay Maybeneuroprotective
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DAs: Common Adverse Effects
y Nausea, vomitingy Dizziness, posturalhypotensiony Headachey Dizzinessy Drowsiness & somnolencey Dyskinesiasy Confusion, hallucinations, paranoiay Erythromelalgia; pulmonary&retroperitonealfibrosis;pleuraleffusion & pleuralthickening; Raynaudsphenomena. Maybe morecommonwithergotoline DAs
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Apomorphine
y D1/D2 agonist
y Parenteraldelivery(s.c., i.v., sublingual, intranasal,rectal)
y Rapid offperiodrescue 2-5 mgs.c.;peninjectionsystems
y Treatment ofunpredictable, frequent motorfluctuations
continuouss.c. infusionvia mini-pumpy SE:nausea, vomiting, hypotension
trimethobenzamide 250 mg t.i.d.
domperidone 20 mg t.i.d.;not availablein U.S.
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Anticholinergics
y Dopaminergic depletion cholinergicoveractivityy Initiallyusedin the1950sy Effective mainlyfor tremorandrigidityy Commonagents (Start low, goslow):
y Trihexyphenidyl: 2-15 mg/day
y Benztropine:1-8 mg/dayy Ethopropazine:10-200 mg/day
y Sideeffects: Drymouth, sedation, delirium,confusion, hallucinations, constipation, urinaryretention
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Amantadine
y Antiviralagent; PD benefit foundaccidentallyy Tremor, bradykinesia, rigidity& dyskinesiasy Exact mechanism unknown;possibly:
y enhancingreleaseofstoreddopamine
y inhibitingpresynaptic reuptakeofcatecholamines
y dopaminereceptoragonismy NMDAreceptor blockade
y Sideeffectsautonomic, psychiatricy 200-300 mg/day
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EarlyManagement of Parkinsons Disease
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Initial Therapy: Patient Considerationsy Riskofacutedrugintolerance
y Riskoflong-term drug-relatedcomplications
yPolypharmacy
y Comorbidities, especiallydementia
y Patientslifestyle, responsibilities
y Cost ofmedications
y Functionalvs. chronologicalage
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Initial Therapy: The Elderly Patienty Shorter treatment horizon
y Lowerriskoflong-term complications
y
Higherlikelihoodofcomorbiditiesy Levodopa:well tolerated, effective
y Useadjunctive medicationscautiously
y Avoidsedating medications
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Initial Therapy: The Young Patient
y Long-term treatment horizon
y Increasedriskoflong-term complications
y
Increasedpatient responsibilitiesy Dopamineagonist monotherapy
y Levodopa-sparingstrategies
y Putativeneuroprotectivestrategies
y Roleoflevodopaisnot adequatelydefined
:
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Complaint?
SymptomsSymptoms Clinical optionClinical option
No functional impairmentNo functional impairment Delay TherapyDelay Therapy
Mild symptomsMild symptoms Amantadine, SelegilineAmantadine, Selegiline
TremorTremor AnticholinergicAnticholinergic
DepressionDepression AntidepressantAntidepressant
AnxietyAnxiety AnxiolyticAnxiolytic
Functionally disablingFunctionally disabling
symptomssymptoms
Levodopa, DopamineLevodopa, Dopamine
agonist, COMT inhibitoragonist, COMT inhibitor
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Levodopa: Guidelines in Early PD
y Start lowandincreaseslowlyy Titratedosage toefficacy(~200-600 mg/day)y Immediaterelease-morerapidonset-shorterdurationofbenefit-genericavailabley Controlledrelease-longerdurationofbenefit-somepatientspreferlessfrequent dosingy Acutesideeffects:nausea, dizziness, somnolence
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Dopamine Agonists: Guidelines in Early PD
y Effectiveas monotherapyy Lesssymptomatic benefit thanlevodopay Maydelayneedforlevodopaapprox. 12 months
dataup to >3 yearshas beenpresentedy Start lowandincreaseslowlyy Titrate toefficacy-bromocriptine7.5-30 mg/day-pergolide1.5-4.5 mg/day-pramipexole1.5-4.5 mg/day-ropinirole 3-24 mg/dayy Acute SEs:nausea, dizziness, somnolence, confusion
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Dopamine Agonists:Adjunctive Use with L-
dopa
y Bromocriptine, pergolide, pramipexole, ropinirole
y Agonist choiceis moreart thanscience
y Reducelevodopadosagewhenadding theagonist
y Failureofonedoesnot predict failureofanother
y Agonists maybeswitchedeithergraduallyorrapidlytoacomparabledosage
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Managing Early Complications:
AlteredMental States
y Confusion, sedation, dizziness, hallucinations,delusions
y
ReduceoreliminateC
NS-activedrugsoflesserpriorityanticholinergics sedatives
amantadine musclerelaxants
hypnotics urinaryspasmodics
y ReducedosageofDA, COMT inhibitor, or LD
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Late Complications
y Motor
-responsefluctuations, dyskinesias, dystonia, freezing,falls
y Behavioral/neuropsychological
-depression, sleepdisorders, psychosis
y Autonomic
-orthostatichypotension;hyperhidrosis, constipation,impotence, urinaryincontinenceorretention
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LD Response Fluctuationsy Peripheralcauses:
-delayedgastricemptying
-dietaryprotein
-short plasmahalf-life
y Centralcauses:
-pulsatiledeliverytostriatalreceptors
-impairedstoragecapacity-alterationofDAreceptors
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Response Fluctuations: Treatment
y Increase LD dose
y Increase DCI dose
y
Adddopamineagonisty AddCOMT inhibitor
-reduce LD
-liverfunction monitoring
y Apomorphinerescue
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Cognitive Assessment
y Memorydifficulties:11-29%ofPD patients
-Benignforgetfulness
-Delirium
-Alzheimersdisease-Otherdementias
y Evaluation
-Brainimaging
-Lumbarpuncture-EEG
-Bloodworkfor thyroidprofile, vitaminB12, serology,chemistrypanel
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Psychosis
y Features Vividdreams/nightmares, disorientation,hallucinations, delusional thought
y Simplifymedicalregimen Stopunnecessarynon-PD meds Stop:anticholinergicdrugs, amantadine,selegiline, dopamineagonists, COMT inhibitors
y Changefrom CR tostandard
carbidopa/levodopay Tryatypicalantipsychoticagentsy Trylow-potencytraditionalantipsychotic
agents
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Anti-psychotic Agents
y Molindonelow-potencyneuroleptic; mayaggravate PD symptoms, but cansometimesuse5-10 mgat HS
y Risperidone
D3 antagonist; D1/D2 agonist;aggravates PD at doses > 3 mg/d.y Olanzapine
D4 antagonist. D1/D2 inhibition > 10 mg/dy Quetiapine5-HT1-2 antagonist. Dosage 25 - 500 mg/d
y ClozapineD4 antagonist;noconfirmedaggravationofPD orcausationofTDFatalagranulocytosisin 9 patients;weeklyCBC
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Depression
y Reportedin 30-90%ofPD patients
y Difficult todiscernfrom vegetativesymptoms
y Requiresinquiryintodepressionsymptoms
y Usuallyrespondsquicklyto medications
Tricyclicagents
Selectiveserotoninre-uptakeinhibitors
y
IfEC
T needed, will transientlyimprove PD symptoms
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Anxiety/Restlessness
y Primaryanxietydisorder: treat with benzodiazepines
-Associatedwith off-periodsorlow-levodopalevels:
adjust levodopadosingy Restless Leg Syndrome: benzodiazepines, narcotics,
levodopa, dopamineagonists
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Sleep Disorders
y Insomnia
-carefulhistory
-difficultywithsleepinitiation: tricyclicagents,
benzodiazepines, diphenhydramine, chloralhydrate- treat depression
-REM-behavioraldisorder:clonazepam
y Excessivedaytimesleepiness
-Correct poorsleepat night-Discontinueanticholinergics, amantadine
-Reducedopamineagonist, levodopadosagesifpossible
-selegeline;caffeine; methylphenidate5-20 mgs/d
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Orthostatic Hypotension
y Light-headedness, dizziness, fatigue, shoulderorneckpain, bloodpressuredropswhenstanding
y Taperanti-hypertensiveagents
y Tapernon-PD drugsy Increasesalt intake
y Compressionstockings
y Fludrocortisone (0.1-0.4 mg/d)
y Midodrine (2.5 - 20 mg/d)
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Urinary Incontinence/Frequencyy Ruleout urinarytract infection
y Bladderevaluationfor
-detrusorhyperactivity
oxybutinin5 -30 mg/d;propanthaline7.5 - 15 mg/d
-detrusorhypoactivity
phenoxybenzamine;prazosin
y
Urinaryfrequency-avoidfluidpoolinginfeet
-DDAVP inhaler; tolterodine tartrate 2mghs to 2mg tid
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Sexual Dysfunction
y Medicalscreening
-depression, anxiety, iatrogeniccauses
y
Endocrinologicevaluation-prolactin, testosterone, lutenizinghormone, thyroidscreen
y Urologicevaluation
-yohimbine, sildenafil
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Nausea
y Levodopa-related: takewith meals, addcarbidopa, adddomperidone
y Otheranti-PD medications:same.
-Ifnoimprovement:withdrawnewest agent, re-initiateat minimaldoses, slowlyincrease
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Excessive Sweating
y Usuallylevodoparelated, and maybeseenat peakortroughdosedruglevels
-reducelevodopa
-adddopamineagonist orCOMT inhibitor
-addcarbidopa
-addBeta-blocker
The Surgical Treatment of Parkinsons
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The Surgical Treatment of Parkinsons
Disease
y Ablative
-thalamotomy
-pallidotomyy Electricalstimulation
-VIM thalamus, globuspallidusinternus, sub-thalamicnucleus
y Transplant-autologousadrenal, humanfetal, xenotransplants,geneticallyengineered transplants
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Deep Brain Stimulation (DBS)
y Highfrequency, pulsatile, bipolarelectricalstimulation
y Stereotacticallyplacedinto target nucleus
y Can beactivatedanddeactivatedwithanexternalmagnet
y Exact physiologyunknown, but higherfrequencies
mimiccellularablation, not stimulation
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Adjustable Features
y Voltage (1-7volts)
y Pulsewidth (65-450 msec)
y
Frequency(130-180Hz)y Polarity
y Leadlocation (4 leads, each1.5 mm apart)
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Cell Transplants
y Autologousadrenal transplants
-Noefficacy
y Allogenichumanfetal transplants
-Initialencouragingclinicalresults
y Xenogenicfetal transplant (porcineand bovine)
-Preliminaryresultspending
y
Geneticallyengineeredcells-Researchongoing
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Human Fetal Transplants
y Efficacy
-Encouragingpreliminaryresultsinyoung PD pts
-PET studiesconsistent withcellfunctioning
-Autopsies (2)showcellsurvival
y Problems
-4-10embryos
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Problems That May Respond to
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Problems That May Respond to
Nonpharmacological Approaches
y ADL difficultiesy Motor, balance, posture, gait, mobilityy Speechandswallowing:hypophonia,
sialorrhea, dysphagiay Inadequatenutritiony Sleepdisturbancey Autonomicdysfunction:painandconstipationy Skin breakdowny Sexualdysfunctiony Depression
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Nonpharmacologic Treatments
y Patient/caregivereducation
y Physical therapy
y Exercise
y Occupational therapy
y Speech/language therapy
y Diet andnutrition
y Psychosocialinterventions
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Physical Therapy: Goals
y Maintainorincreaseactivitylevel
y Decreaserigidityand bradykinesia
y
Facilitate movement andflexibility;optimizegaity Maximizegross motorcoordinationand balance
y Maximizeindependence, safety, function
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Physical Therapy: Features
y Exercise:e.g., walking (1+ mile/day), swimming, golf,dancing
y Stretchingandstrengthening
y Exaggeratedorpatterned movements
y highstepping, weight shifting, repetition, verbalcues
y Mobilityaids, orthotics, adaptivefootwear
y Transfer techniques
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Occupational Therapy: Features
y Patient andcaregivereducation
goalsofprogram
transfers, tasksimplification, positioning, etc.y Homeexerciseprogram
y Homeandworkplace modifications
y Adaptiveequipment
y Upperextremitysplinting
Adaptive Equipment and
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Adaptive Equipment and
Environmental Modifications
y Customizefordisability, budgety Seating:wheelchairs, cushions, lateralsupports,
etc.y Toilet andhygeine: tub/showerseat, grab bars,etc.
y Feeding:wide-handledutensils, sipcups, etc.y Clothing:velcro, pullovers, shoehorns, etc.y Bed:rails, hospital bed, trapeze, etc.y Equipment: bookholders, large-buttonphone,
keyholders, etc.y Considerdoorsills, throwrugs, otherobstructions
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Speech and Communication Problems
y Maybeoneofthefirst symptomsofPD
y Characterized by:
-soft voiceandimprecisearticulation
-burstsofrapidspeechalternatingwithperiodsofsilence
-lossofinflection
y Can besignificant foremployment
y Dyskinesias mayworsen
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Speech-Language TherapyOptions
y Oftenunderutilized
y Earlytherapyespeciallyeffective
y
At-homeexercises; modificationofdailyactivitiesy Emphasisoncontrolofrespirationandvoice
production
y Amplificationdevicesrarelyuseful
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Techniques to Improve Speech
y Increaseloudness
y Face thelistenerdirectly
y Emphasizekeywords
y Useshort sentences
y Range-of-motionexercisesfor musclesofspeech
y Breathingexercises
y Attendspeech therapy
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Nutritional Risk Factors
y Inactivity
y Foodpreparationproblems
y
Dyskinesiaandfeedingproblemsy Chewingandswallowingproblems
y Increased metabolicneeds
y Medication-relateddietaryrestrictions
y Drugsideeffects:anorexia, nausea, vomiting,constipation
y Depressionanddementia
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Dietary Recommendations
y Eat a balancediet, includingallfoodgroups
y Consumesufficient calories to maintainweight
y C
onsumeadequatefiberandfluids toavoidconstipation
y Takevitamin D andcalcium toprevent osteoporosis
y Reduceprotein to minimum dailyallowance
-concentrateinevening meal
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Miscellaneous Concerns
y Seborrheicdermatitis
-shampoosorlotionswithketoconazole, selenium,pyrithionezinc
y Driving
-assessregularlyforreactionspeed, judgment, mentalstatus
-retakedrivers test
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Education, Support and Counseling
y Patient/caregivereducation:newsletters,Webresources
y Support groups:patient, caregivers
-maybeappropriate towait fordisabilityprogression
-early-onset patients maydesireseparategroup
y Counseling
-bothpatient andcaregiver/family;assessneedsseparately
-anxiety, grief, guilt, anger, isolation, depression
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Community Resources
y Socialworkerintervention:
Social Securityoffice
Medicare, Medicaidy In-homeprograms
MealsonWheels, homevisiting, etc.
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Epidemiologyy Onset is typicallybetween theagesof25and 45years
(range 370years)withaprevalenceoftwo toeightcasesper100,000.
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Etiologyy HD iscaused byanincreasein thenumberof
polyglutamine (CAG)repeats (>40)in thecodingsequenceoftheHuntingtongenelocatedon theshort arm ofchromosome 4. Thegeneencodes thehighlyconservedcytoplasmicproteinhuntingtin.
y Intraneuronalinclusionscontainingaggregatesof
ubiquitinand the mutant proteinhuntingtinarefoundinnucleiofneuronsin thestriatum andcerebralcortex.
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PATHOLOGY AND PATHOGENESISy Impairedglucose metabolism in thecaudatenucleus,
precedingvisibleatrophy
y excessofdopamine (incontrast to Parkinsondisease)
y disturbancesin the metabolism ofotherneurotransmitters (norepinephrine, glutamicaciddecarboxylase, cholineacetyltransferase, GABA,acetylcholine, andsomatostatin)
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CLINICAL FEATURESy The mentaldisorderassumesseveralsubtleformslong
before the moreobviousdeteriorationofcognitivefunctions becomesevident. Inapproximatelyhalfthe
cases, slight andoftenannoyingalterationsofcharacterare thefirst toappear. Patients begin tofindfault witheverything, tocomplainconstantly, and tonagother membersofthefamily
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CLINICAL FEATURESy Theabnormality of movement isat first slight and
most evident in thehandsandface;often thepatient ismerelyconsidered to befidgety, restless, or "nervous."
Slownessofmovement ofthefingersandhands, areducedrateoffinger tapping, anddifficultyinperformingasequenceofhand movementsareearlymotorsigns. Graduallytheseabnormalities becomemorepronounceduntil theentire musculatureis
implicatedwithchorea.
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Diagnosisy It isnowpossible toconfirm orexclude thediagnosis
byanalysisofDNAfrom a bloodsample. Thepresenceofgreater than 39 to 42 CAG repeatsat theHuntington
locusessentiallyconfirmsitspresence
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Huntington's Disease: Treatmenty Treatment involvesa multidisciplinaryapproachwith
medical, neuropsychiatric, social, andgeneticcounselingforpatientsand theirfamilies
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Huntington's Disease: Treatmenty Dopamine-blockingagents maycontrol thechorea but
aregenerallynot recommended becauseoftheirside-effect profileandpotential toaggravate motor
symptoms, and because thechorea tends to beself-limitedandisusuallynot disabling.
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Huntington's Disease: Treatmenty Depressionandanxietycan begreaterproblems, and
patientsshould be treatedwithappropriateantidepressant andantianxietydrugsand monitored
for maniaandsuicidalideations.y Psychosiscan be treatedwithatypicalneuroleptics
suchasclozapine (50600 mg/d), quetiapine (50600mg/d), andrisperidone (28 mg/d)
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Huntington's Disease: Treatmenty Thereisnoadequate treatment for thecognitiveor
motordecline. Aneuroprotective therapythat slowsorstopsdiseaseprogressionis the majorunmet medical
needinHD. Antiglutamateagents, bioenergetics,caspaseinhibitors, inhibitorsofproteinaggregation,intracerebraldeliveryofneurotrophicfactors, andtransplantationoffetalstriatalcellsareallareasofactiveresearch, but nonehasasyet been
demonstrated tohaveadisease-modifyingeffect.
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