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PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia, SC 29224 (803) 422-2985

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Page 1: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 2: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Cardinal Characteristics

Resting tremor

Bradykinesia

Rigidity

Postural instability

Page 3: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Beware the Old Man (or woman)Difficulty initiating movement (akinesia)Small amplitude movements (hypokinesia)Reduced motor velocity (bradykinesia)Loss of postural reflexesStooped body posture

Page 4: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Additional Signs & SymptomsMicrographia

Masked face

Slowing of ADLs

Stooped, shuffling gait

Decreased arm swing when walking

Page 5: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,
Page 6: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,
Page 7: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Additional Signs and SymptomsDifficulty arising from a chair

Difficulty turning in bed

Hypophonic speech

Page 8: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,
Page 9: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Non-Motor SymptomsNeuropsychiatric

DepressionAnhedoniaAttention deficitHallucinationsDelusionsObsessional behaviorCognitive disorder

Sleep disordersRestless legsPeriodic limb

movementsREM behavior disorderExcessive daytime

somnolenceVivid dreamingNon-REM sleep-related

movement disordersInsomnia

Page 10: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Non-Motor SymptomsAutonomic symptoms

Bladder urgency, nocturia, frequency

SweatingOrthostatic hypotensionHypersexualityErectile impotence

hypotestosterone state

GI symptomsSialorrheaAgeusiaDysphagiaRefluxVomitingNauseaConstipationFecal incontinence

Page 11: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Non-Motor SymptomsSensory

PainParesthesiaOlfactory disturbance

OtherFatigueDiplopiaBlurred visionSeborrheaWeight loss

Page 12: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,
Page 13: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 14: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

What Happened?

Page 15: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 16: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,
Page 17: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Atypical ParkinsonismEarly onset of, or rapidly progressing,

dementiaRapidly progressive courseSupranuclear gaze palsyUpper motor neuron signsCerebellar signs—dysmetria, ataxiaUrinary incontinenceEarly symptomatic postural hypotension

Page 18: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Progressive supranuclear palsySupranuclear downgaze palsy, square wave

jerksUpright posture/frequent fallsPseudobulbar emotionalityFurrowed brow/stare

Page 19: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Corticobasal degenerationUnilateral, coarse tremorLimb apraxia/limb dystonia/alien limb

Page 20: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Multiple system atrophyShy-Drager syndrome

Autonomic insufficiency—orthostasis, impotenceStriatonigral degeneration

Tremor less prominentOlivopontocerebellar atrophy

Cerebellar signs

Page 21: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Diffuse Lewy Body DiseaseEarly onset of dementiaDelusions and hallucinationsAgitation

Alzheimer’s diseaseDementia is the primary clinical syndromeRest tremor is rare

Page 22: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Hydrocephalus-induced ParkinsonismNormal pressure hydrocephalusClinical triad:

parkinsonism/gait disorderurinary/fecal incontinencedementia

Page 23: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,
Page 24: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Drug Classes in PDDopaminergic agents

LevodopaDopamine agonists

COMT inhibitors MAO-B inhibitorsAnticholinergicsAmantadine

Page 25: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 26: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Levodopa (cont’d)Rapid peripheral decarboxylation to

dopamine without a decarboxylase inhibitor (DCIs: carbidopa, benserazide)

Side effects: nausea, postural hypotension, dyskinesias, motor fluctuations

Page 27: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 28: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Treatment OptionsPreventive treatment

No definitive treatment availableSymptomatic treatment

PharmacologicalSurgical

Non-motor managementRestorative—experimental only

TransplantationNeurotrophic factors

Page 29: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 30: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 31: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 32: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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)

Page 33: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

DAs: Common Adverse EffectsNausea, vomitingDizziness, postural hypotensionHeadacheDrowsiness & somnolenceDyskinesiasConfusion, hallucinations, paranoia

Page 34: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 35: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Initial Therapy: The Elderly PatientShorter treatment horizonLower risk of long-term complicationsHigher likelihood of comorbiditiesCarbidopa/Levodopa: well tolerated, effectiveUse adjunctive medications cautiouslyAvoid sedating medications

Page 36: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 37: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Levodopa: Guidelines in Early PDStart low and increase slowlyTitrate dosage to efficacy (~200-600 mg/day)Immediate releaseControlled releaseAcute side effects: nausea, dizziness,

somnolence

Page 38: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 39: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 40: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Surgical Treatments for Parkinson’s DiseaseAblative

thalamotomypallidotomy

Electrical stimulationVIM thalamus, globus pallidus internus, sub-

thalamic nucleusTransplant

autologous adrenal, human fetal, xenotransplants, genetically engineered transplants

Page 41: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 42: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 43: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

Other Parkinson’s Meds

MAO Inhibitorsrasagaline selegilene

zydis carbidopa/levodopa

rotigotine patch

Page 44: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,

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

Page 45: PARKINSON’S DISEASE Diagnosis & Treatment Options University of South Carolina School of Medicine March 27, 2014 Dale R.Hamrick, MD PO Box 23656 Columbia,