Transcript Management of Late-Stage Parkinson`s Disease

Management of Late-Stage
Parkinson’s Disease
Part 5 of 7
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Parkinson’s Disease Slide Library Version 2.0 - All Contents Copyright © WE MOVE 2001
Late Complications
• Motor
– response fluctuations, dyskinesias, dystonia,
freezing, falls
• Behavioral/neuropsychological
– depression, sleep disorders, psychosis
• Autonomic
– orthostatic hypotension; hyperhidrosis,
constipation, impotence, urinary incontinence
or retention
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Stages in Decline of Response to LD
• I: Patient not aware of effect of individual dose
• II: Mid-afternoon loss of benefit
• III: Loss of sleep benefit; early-morning akinesia,
possible foot dystonia
• IV: Regular “wearing off” every 4 hours at first,
shortens with time
• V: Frequent wearing off, abrupt on-off,
unpredictable dose response
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LD Response Fluctuations
• Peripheral causes:
– delayed gastric emptying
– dietary protein
– short plasma half-life
• Central causes:
– pulsatile delivery to striatal receptors
– impaired storage capacity
– alteration of DA receptors
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Response Fluctuations: Treatment
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Increase LD dose
Increase DCI dose
Add dopamine agonist
Add COMT inhibitor
– reduce LD
– liver function monitoring
• Apomorphine rescue
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Peak Dose Dyskinesia or Dystonia
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Chorea more common than dystonia
May be worse on more affected side
May not be as disabling as akinesia/rigidity
Dose adjustments, add-ons:
– reduce LD dose, increase dose frequency
– convert to LD-CR
– reduce LD, add DA, COMT inhibitor, or MAOB inhibitor
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Off-period Dystonia
• Appears when LD level is low, especially
early AM
• w/ or w/o parkinsonism
• Dose adjustments, add-ons:
– more frequent LD dosing to avoid low plasma
levels
– add DA, COMT inhibitor, MAO-B inhibitor
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Wearing Off
• Regular and predictable decline in response
2-4 hours after LD dose
• Most common motor fluctuation
• Dose adjustments, add-ons:
– change to LD-CR, or increase LD frequency
– reduce LD, add DA or COMT inhibitor
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On-off Response
• Sudden and unpredictable off periods
unrelated to dosing schedule
• One of the hardest features to manage
• Dose adjustments, add-ons:
– reduce LD, add DA
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Other Motor Complications
• Diphasic dyskinesia
– dyskinesia at beginning and end of dose
– Dose adjustments, add-ons: add DA
• Drug failure
– late afternoon, probably related to poor gastric
emptying or absorption
– liquid preparations; increase gastric motility; decrease
dietary protein
– apomorphine rescue
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Freezing and Falls
• Freezing
– motoric block; at initiation of gait, turning, narrow
spaces
– use auditory, visual, proprioceptive cues
• Falls
– physical therapy evaluation
– cane, scooter, wheelchair may be necessary
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Cognitive Assessment
• Memory difficulties: 11-29% of PD patients
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Benign forgetfulness
Delirium
Alzheimer’s disease
Other dementias
• Evaluation
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Brain imaging
Lumbar puncture
EEG
Blood work for thyroid profile, vitamin B12, serology,
chemistry panel
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Psychosis
• Features
– Vivid dreams/nightmares, disorientation, hallucinations, delusional
thought
• Simplify medical regimen
– Stop unnecessary non-PD meds
– Stop: anticholinergic drugs, amantadine, selegiline, dopamine
agonists, COMT inhibitors
• Change from CR to standard carbidopa/levodopa
• Try atypical antipsychotic agents
• Try low-potency traditional antipsychotic agents
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Anti-psychotic Agents
• Molindone
– low-potency neuroleptic; may aggravate PD symptoms, but can
sometimes use 5-10 mg at HS
• Risperidone
– D3 antagonist; D1/D2 agonist; aggravates PD at doses > 3 mg/d.
• Olanzapine
– D4 antagonist. D1/D2 inhibition > 10 mg/d
• Quetiapine
– 5-HT1-2 antagonist. Dosage 25 - 500 mg/d
• Clozapine
– D4 antagonist; no confirmed aggravation of PD or causation of TD
– Fatal agranulocytosis in 9 patients; weekly CBC
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Depression
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Reported in 30-90% of PD patients
Difficult to discern from vegetative symptoms
Requires inquiry into depression symptoms
Usually responds quickly to medications
– Tricyclic agents
– Selective serotonin re-uptake inhibitors
• If ECT needed, will transiently improve PD
symptoms
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Anxiety/Restlessness
• Primary anxiety disorder: treat with
benzodiazepines
– Associated with “off-periods” or low-levodopa
levels: adjust levodopa dosing
• Restless Leg Syndrome: benzodiazepines,
narcotics, levodopa, dopamine agonists
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Sleep Disorders
• Insomnia
– careful history
– difficulty with sleep initiation: tricyclic agents, benzodiazepines,
diphenhydramine, chloral hydrate
– treat depression
– REM-behavioral disorder: clonazepam
• Excessive daytime sleepiness
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Correct poor sleep at night
Discontinue anticholinergics, amantadine
Reduce dopamine agonist, levodopa dosages if possible
selegeline; caffeine; methylphenidate 5-20 mgs/d
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Orthostatic Hypotension
• Light-headedness, dizziness, fatigue, shoulder or
neck pain, blood pressure drops when standing
• Taper anti-hypertensive agents
• Taper non-PD drugs
• Increase salt intake
• Compression stockings
• Fludrocortisone (0.1-0.4 mg/d)
• Midodrine (2.5 - 20 mg/d)
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Urinary Incontinence/Frequency
• Rule out urinary tract infection
• Bladder evaluation for
– detrusor hyperactivity
• oxybutinin 5 -30 mg/d; propanthaline 7.5 - 15 mg/d
– detrusor hypoactivity
• phenoxybenzamine; prazosin
• Urinary frequency
– avoid fluid pooling in feet
– DDAVP inhaler; tolterodine tartrate 2mg hs to 2mg tid
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Sexual Dysfunction
• Medical screening
– depression, anxiety, iatrogenic causes
• Endocrinologic evaluation
– prolactin, testosterone, lutenizing hormone,
thyroid screen
• Urologic evaluation
– yohimbine, sildenafil
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Nausea
• Levodopa-related: take with meals, add
carbidopa, add domperidone
• Other anti-PD medications: same.
– If no improvement: withdraw newest agent, reinitiate at minimal doses, slowly increase
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Excessive Sweating
• Usually levodopa related, and may be seen
at peak or trough dose drug levels
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reduce levodopa
add dopamine agonist or COMT inhibitor
add carbidopa
add Beta-blocker
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Faculty for the WE MOVE
Parkinson’s Disease Teaching Slide Set
Mark Stacy, MD
Barrow Neurological
Institute
Phoenix, Arizona, USA
Richard B. Dewey, Jr., MD
University of Texas
Southwestern Medical
Center
Dallas, Texas, USA
Charles H. Adler, MD, PhD
Mayo Clinic Scottsdale
Scottsdale, Arizona, USA
William G. Ondo, MD
Lisa M. Shulman, MD
Baylor College of Medicine Health Policy Fellow
Houston, Texas, USA
U.S. House of
Representatives
Washington, DC, USA
Rajesh Pahwa, MD
University of Kansas
Celia Stewart, PhD
Medical Center
Mount Sinai Medical
Kansas City, Kansas, USA Center
New York, New York, USA
Kathleen Albany, PT, MPH
WE MOVE
New York, New York,
USA
Ali H. Rajput, MD
Royal University Hospital
Saskatoon, Saskatchewan,
Canada
Reviewed by the Education Committee of the Movement Disorder Society
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