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
Cardinal Characteristics
Resting tremor
Bradykinesia
Rigidity
Postural instability
Beware the Old Man (or woman)Difficulty initiating movement (akinesia)Small amplitude movements (hypokinesia)Reduced motor velocity (bradykinesia)Loss of postural reflexesStooped body posture
Additional Signs & SymptomsMicrographia
Masked face
Slowing of ADLs
Stooped, shuffling gait
Decreased arm swing when walking
Additional Signs and SymptomsDifficulty arising from a chair
Difficulty turning in bed
Hypophonic speech
Non-Motor SymptomsNeuropsychiatric
DepressionAnhedoniaAttention deficitHallucinationsDelusionsObsessional behaviorCognitive disorder
Sleep disordersRestless legsPeriodic limb
movementsREM behavior disorderExcessive daytime
somnolenceVivid dreamingNon-REM sleep-related
movement disordersInsomnia
Non-Motor SymptomsAutonomic symptoms
Bladder urgency, nocturia, frequency
SweatingOrthostatic hypotensionHypersexualityErectile impotence
hypotestosterone state
GI symptomsSialorrheaAgeusiaDysphagiaRefluxVomitingNauseaConstipationFecal incontinence
Non-Motor SymptomsSensory
PainParesthesiaOlfactory disturbance
OtherFatigueDiplopiaBlurred visionSeborrheaWeight loss
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
What Happened?
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
Atypical ParkinsonismEarly onset of, or rapidly progressing,
dementiaRapidly progressive courseSupranuclear gaze palsyUpper motor neuron signsCerebellar signs—dysmetria, ataxiaUrinary incontinenceEarly symptomatic postural hypotension
Progressive supranuclear palsySupranuclear downgaze palsy, square wave
jerksUpright posture/frequent fallsPseudobulbar emotionalityFurrowed brow/stare
Corticobasal degenerationUnilateral, coarse tremorLimb apraxia/limb dystonia/alien limb
Multiple system atrophyShy-Drager syndrome
Autonomic insufficiency—orthostasis, impotenceStriatonigral degeneration
Tremor less prominentOlivopontocerebellar atrophy
Cerebellar signs
Diffuse Lewy Body DiseaseEarly onset of dementiaDelusions and hallucinationsAgitation
Alzheimer’s diseaseDementia is the primary clinical syndromeRest tremor is rare
Hydrocephalus-induced ParkinsonismNormal pressure hydrocephalusClinical triad:
parkinsonism/gait disorderurinary/fecal incontinencedementia
Drug Classes in PDDopaminergic agents
LevodopaDopamine agonists
COMT inhibitors MAO-B inhibitorsAnticholinergicsAmantadine
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
Levodopa (cont’d)Rapid peripheral decarboxylation to
dopamine without a decarboxylase inhibitor (DCIs: carbidopa, benserazide)
Side effects: nausea, postural hypotension, dyskinesias, motor fluctuations
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
Treatment OptionsPreventive treatment
No definitive treatment availableSymptomatic treatment
PharmacologicalSurgical
Non-motor managementRestorative—experimental only
TransplantationNeurotrophic factors
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
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
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
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)
DAs: Common Adverse EffectsNausea, vomitingDizziness, postural hypotensionHeadacheDrowsiness & somnolenceDyskinesiasConfusion, hallucinations, paranoia
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
Initial Therapy: The Elderly PatientShorter treatment horizonLower risk of long-term complicationsHigher likelihood of comorbiditiesCarbidopa/Levodopa: well tolerated, effectiveUse adjunctive medications cautiouslyAvoid sedating medications
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
Levodopa: Guidelines in Early PDStart low and increase slowlyTitrate dosage to efficacy (~200-600 mg/day)Immediate releaseControlled releaseAcute side effects: nausea, dizziness,
somnolence
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
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
Surgical Treatments for Parkinson’s DiseaseAblative
thalamotomypallidotomy
Electrical stimulationVIM thalamus, globus pallidus internus, sub-
thalamic nucleusTransplant
autologous adrenal, human fetal, xenotransplants, genetically engineered transplants
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
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
Other Parkinson’s Meds
MAO Inhibitorsrasagaline selegilene
zydis carbidopa/levodopa
rotigotine patch
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