parkinson’s disease diagnosis & treatment options university of south carolina school of...
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PARKINSON’S DISEASEDiagnosis & Treatment Options
University of South CarolinaSchool of Medicine
March 27, 2014
Dale R.Hamrick, MDPO Box 23656
Columbia, SC 29224(803) 422-2985
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Cardinal Characteristics
Resting tremor
Bradykinesia
Rigidity
Postural instability
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Beware the Old Man (or woman)Difficulty initiating movement (akinesia)Small amplitude movements (hypokinesia)Reduced motor velocity (bradykinesia)Loss of postural reflexesStooped body posture
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Additional Signs & SymptomsMicrographia
Masked face
Slowing of ADLs
Stooped, shuffling gait
Decreased arm swing when walking
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Additional Signs and SymptomsDifficulty arising from a chair
Difficulty turning in bed
Hypophonic speech
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Non-Motor SymptomsNeuropsychiatric
DepressionAnhedoniaAttention deficitHallucinationsDelusionsObsessional behaviorCognitive disorder
Sleep disordersRestless legsPeriodic limb
movementsREM behavior disorderExcessive daytime
somnolenceVivid dreamingNon-REM sleep-related
movement disordersInsomnia
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Non-Motor SymptomsAutonomic symptoms
Bladder urgency, nocturia, frequency
SweatingOrthostatic hypotensionHypersexualityErectile impotence
hypotestosterone state
GI symptomsSialorrheaAgeusiaDysphagiaRefluxVomitingNauseaConstipationFecal incontinence
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Non-Motor SymptomsSensory
PainParesthesiaOlfactory disturbance
OtherFatigueDiplopiaBlurred visionSeborrheaWeight loss
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Epidemiology Incidence
5-24/ 105 worldwide (USA: 20.5/105)Incidence of PS/PD rising slowly with aging
populationPrevalence
57-371/105 worldwide (USA/Canada 300/105)35%-42% of cases undiagnosed at any time
Onsetmean PS 61.6 years; PD 62.4 yearsrare before age 30; 4-10% cases before age 40
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What Happened?
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Mortality in PSReduced life expectancy
Mean survival after onset ~ 15 yearslonger in non-demented PD caseslonger with L-dopa use
PD survival >MSA, PSPThe most common causes of death:
pulmonary infection/aspiration, urinary tract infection, pulmonary embolism and complications of falls and fractures
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Atypical ParkinsonismEarly onset of, or rapidly progressing,
dementiaRapidly progressive courseSupranuclear gaze palsyUpper motor neuron signsCerebellar signs—dysmetria, ataxiaUrinary incontinenceEarly symptomatic postural hypotension
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Progressive supranuclear palsySupranuclear downgaze palsy, square wave
jerksUpright posture/frequent fallsPseudobulbar emotionalityFurrowed brow/stare
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Corticobasal degenerationUnilateral, coarse tremorLimb apraxia/limb dystonia/alien limb
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Multiple system atrophyShy-Drager syndrome
Autonomic insufficiency—orthostasis, impotenceStriatonigral degeneration
Tremor less prominentOlivopontocerebellar atrophy
Cerebellar signs
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Diffuse Lewy Body DiseaseEarly onset of dementiaDelusions and hallucinationsAgitation
Alzheimer’s diseaseDementia is the primary clinical syndromeRest tremor is rare
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Hydrocephalus-induced ParkinsonismNormal pressure hydrocephalusClinical triad:
parkinsonism/gait disorderurinary/fecal incontinencedementia
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Drug Classes in PDDopaminergic agents
LevodopaDopamine agonists
COMT inhibitors MAO-B inhibitorsAnticholinergicsAmantadine
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LevodopaMost effective drug for parkinsonian
symptomsFirst developed in the late 1960s; rapidly
became the drug of choice for PDLarge neutral amino acid; requires active
transport across the gut and blood-brain barriers
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Levodopa (cont’d)Rapid peripheral decarboxylation to
dopamine without a decarboxylase inhibitor (DCIs: carbidopa, benserazide)
Side effects: nausea, postural hypotension, dyskinesias, motor fluctuations
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AmantadineAntiviral agent; PD benefit found accidentallyTremor, bradykinesia, rigidity & dyskinesiasExact mechanism unknown; possibly:
enhancing release of stored dopamineinhibiting presynaptic reuptake of
catecholaminesdopamine receptor agonismNMDA receptor blockade
Side effects —autonomic, psychiatric200-300 mg/day
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Treatment OptionsPreventive treatment
No definitive treatment availableSymptomatic treatment
PharmacologicalSurgical
Non-motor managementRestorative—experimental only
TransplantationNeurotrophic factors
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Levodopa-Induced DyskinesiasMost common is “peak dose” dyskinesia
disappears with dose reductionChoreiform, ballistic and dystonic movementsMost patients prefer some dyskinesias over
the alternative of akinesia and rigidity
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COMT InhibitorsNewest class of antiparkinsonian drugs:
tolcapone, entacaponePotentiate LD: prevent peripheral
degradation by inhibiting catechol O-methyl transferase
Reduces LD dose necessary for a given clinical effect
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COMT Inhibitors (cont’d)Helpful for both early and fluctuating
Parkinson’s diseaseMay be particularly useful for patients with
“brittle” PD, who fluctuate between off and on states frequently throughout the day
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Dopamine Agonists: Distinguishing FeaturesDirectly stimulate dopamine receptorsNo competition with dietary amino acidsLonger half-life than levodopaMonotherapy or adjunct therapyMay delay or reduce motor fluctuations &
dyskinesias associated with levodopaMay be neuroprotective“The Patch” – rotigotine (Neupro)
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DAs: Common Adverse EffectsNausea, vomitingDizziness, postural hypotensionHeadacheDrowsiness & somnolenceDyskinesiasConfusion, hallucinations, paranoia
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Clinical Decision-Making in Early PDDisease severity
degree of functional impairmentimpact on quality of life
Age of patientcomorbiditiesrisk of acute drug intolerancerisk of long-term complications
Neuroprotection
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Initial Therapy: The Elderly PatientShorter treatment horizonLower risk of long-term complicationsHigher likelihood of comorbiditiesCarbidopa/Levodopa: well tolerated, effectiveUse adjunctive medications cautiouslyAvoid sedating medications
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Initial Therapy: The Young PatientLong-term treatment horizonIncreased risk of long-term complicationsIncreased patient responsibilitiesDopamine agonist monotherapyLevodopa-sparing strategiesPutative neuroprotective strategiesRole of levodopa is not adequately defined
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Levodopa: Guidelines in Early PDStart low and increase slowlyTitrate dosage to efficacy (~200-600 mg/day)Immediate releaseControlled releaseAcute side effects: nausea, dizziness,
somnolence
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Managing Early Complications: Wearing Off/Mild DyskinesiaFor pts on DA monotherapy:
elevate dosage of agonistadd LD, w/ or w/o COMT inhibitor
For pts on LD:add DA, COMT inhibitor, or MAO inhibitorreduce LD dosageuse combination of immediate and CR
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Managing Early Complications: Altered Mental StatesConfusion, sedation, dizziness, hallucinations,
delusionsReduce or eliminate CNS-active drugs of
lesser priorityanticholinergics – sedativesamantadine – muscle relaxantshypnotics – urinary spasmodics
Reduce dosage of DA, COMT inhibitor, or LD
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Surgical Treatments for Parkinson’s DiseaseAblative
thalamotomypallidotomy
Electrical stimulationVIM thalamus, globus pallidus internus, sub-
thalamic nucleusTransplant
autologous adrenal, human fetal, xenotransplants, genetically engineered transplants
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Deep Brain Stimulation (DBS)High frequency,
pulsatile, bipolar electrical stimulation
Stereotactically placed into target nucleus
Exact physiology unknown, but higher frequencies mimic cellular ablation, not stimulation
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Psycho-Social Aspects of Parkinson's diseaseChronic, progressive,
incurableOff the wall curesDepression (like
stroke, assume they all are depressed)
Housing – the move to the NH
Children and their fears
Resuscitation issues
Artificial nutrition issues
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Other Parkinson’s Meds
MAO Inhibitorsrasagaline selegilene
zydis carbidopa/levodopa
rotigotine patch
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Hoehn and Yahr Staging
1. Unilateral disease only2. Bilateral mild disease,
with or without axial involvement
3. Mild-to-moderate bilateral disease, with first signs of deteriorating balance
4. Severe disease requiring considerable assistance
5. Confinement to wheelchair or bed unless aided
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