Download GRS8NeurologyPart2 - Geriatrics Care Online

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NEUROLOGIC
DISEASES AND
DISORDERS
PART 2
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OBJECTIVES
Know and understand:
•
How to distinguish Parkinson disease from other
common movement disorders
•
The indications for medical, nonpharmacologic, and
surgical treatment of movement disorders
•
How to recognize and treat tardive movements
•
The work-up and treatment of epilepsy in older adults
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TOPICS COVERED
• Movement Disorders
 Parkinson Disease
 Multiple System Atrophy
 Progressive Supranuclear Palsy
 Chorea
 Drug-induced Movement Disorders
 Essential Tremor
• Epilepsy
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MOVEMENT DISORDERS
• Result of dysfunction of the basal ganglia or the
extrapyramidal motor system, not weakness or sensory
deficits
• Classified as:
 Hyperkinesias (excessive movement)
 Hypokinesias (paucity of movement)
• A particular movement disorder may be characterized
by several types of involuntary movements
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PARKINSON DISEASE (PD)
• Reduction in brain dopamine levels caused by cell death
in substantia nigra results in motor symptoms
• Characteristic features:

Tremor at rest

Postural instability

Bradykinesia

Mood abnormalities

Rigidity

Cognitive impairment

Freezing

Dementia (in subset)
• Pathologic hallmark is the Lewy body, an intracellular
inclusion found in the substantia nigra and other areas
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CLUES TO A DIAGNOSIS OF PD
• Bradykinesia and rigidity are asymmetric
• Tremor occurs at rest (typically asymmetric)
• Tremor decreases with active, purposeful
movement
• True extrapyramidal rigidity is noted (not just
stiffness)
NONPHARMACOLOGIC
THERAPY FOR PD
• Regular exercise program
• Physical therapy:
 To restore confidence in walking and
maintaining balance
 To teach management of freezing episodes
 To select a cane or walker, if needed
• Home visit by an occupational therapist to plan
placement of assistive devices
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LEVODOPA FOR PD
•
Has best risk-benefit ratio for motor symptoms
•
Converted to dopamine in both the CNS and the
periphery
•
To reduce peripheral conversion, combine with
carbidopa
•
Addition of COMT or MAO-B inhibitors are an adjunct
used to reduce “on-off” phenomenon later in illness
•
To decrease the risk of dyskinesias with higher doses
of levodopa (eg, >400 mg/day), a dopamine agonist
can be combined with levodopa
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DOPAMINE AGONISTS FOR PD
• Cautious titration period required
• Warn patients of risk of sudden sleep attacks,
orthostatic dizziness, and impulse control problems
• Can be introduced when response to levodopa
becomes variable
• Effective for restless leg syndrome symptoms
• Once-a-day formulations are available
OTHER THERAPIES FOR MOTOR
SYMPTOMS OF PD (1 of 2)
Selegiline (MAO-B inhibitor)
• Inhibits oxidative metabolism of dopamine
• Delays need for other antiparkinsonian agents
• Dosage is 5 mg twice a day (8 AM and noon)
Amantadine (glutamate antagonist)
• Mild anticholinergic; promotes dopamine release
• Particularly useful for treating tremor
• Usual dosage is 100 mg 2 to 3 times daily
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OTHER THERAPIES FOR MOTOR
SYMPTOMS OF PD (2 of 2)
Entacapone (COMT inhibitor)
• Inhibits peripheral conversion of levodopa
• Used as adjunct to decrease “on-off” phenomenon
Rasagiline (selective MAO-B inhibitor)
• Approved by the FDA as early monotherapy or
adjunct therapy
• Appeared to slow symptom progression in delayedstart trial
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MANAGING CONFUSION
AND PSYCHOSIS IN PD
• Confusion and psychosis are common side effects of
antiparkinsonian agents
• Simplify PD medications and lower overall dose of
dopaminergic medications
• Anticholinergics, enzyme inhibitors and dopamine
agonists provide the least PD benefit relative to their
CNS toxicity
• Clozapine and quetiapine have fewer extrapyramidal
side effects than other antipsychotic agents
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SURGICAL TREATMENT OF PD
• For patients whose PD symptoms are no longer
controlled by medical therapies due to motor fluctuations
and side effects, including dyskinesias
• Response to dopaminergic medications is best predictor
of response to deep brain stimulation (DBS)
 Globus pallidus or subthalamic nucleus are the best
DBS targets
 PD-related dementia is a contraindication
 DBS is most commonly performed in pts <80 yr
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MULTIPLE SYSTEM ATROPHY (MSA)
• 3 clinical syndromes: olivopontocerebellar atrophy
(MSA-C), Shy-Drager syndrome (MSA-A), striatonigral
degeneration (MSA-P)
• Parkinsonism (akinetic-rigid) plus autonomic symptoms,
cerebellar signs, sometimes myoclonus
• Orthostatic hypotension is often the most disabling
symptom, and symptoms of autonomic dysfunction can
be severe
• Compared with PD, autonomic dysfunction is more
severe, response to dopaminergic medications is less
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TREATMENT OF MSA
• Nonpharmacologic treatment of autonomic and
orthostatic symptoms
• Midodrine, fludrocortisoneOL and pyridostigmineOL can
be used treat orthostatic hypotension
 But can cause supine hypertension—monitor
orthostatic BPs, elevate head of bed at night
• Levodopa may initially help motor symptoms but often
worsens orthostatic hypertension
OL =
off-label
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PROGRESSIVE SUPRANUCLEAR PALSY
(1 of 2)
• Progressive impairment of voluntary gaze, especially
vertical gaze
• Small, brief saccadic-appearing eye movements every few
seconds on fixation; fixed facial expression due to facial
dystonia
• Severe postural instability
• Rigidity, especially at neck and trunk; bradykinesia,
dysarthria, dysphagia
• Cognitive impairment and personality changes
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PROGRESSIVE SUPRANUCLEAR PALSY
(2 of 2)
• Usual onset is during late 50s or early 60s
• Progresses rapidly
 Marked incapacity in 3 to 5 years
 Death within 10 years
• No fully effective treatment available
• Levodopa may partially reduce rigidity, but improvement
is generally transient
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CHOREA
• Flowing, continuous, random movement that flits from
one part of the body to another; arises from
dysfunction of the striatum
• Cause: Huntington’s disease (HD) is the most
common; also drugs, stroke, and age (senile chorea)
• Tx: dopamine depleter or dopamine receptor blockers
 Tetrabenazine—FDA-approved for HD; associated with
depression, parkinsonism, QT prolongation at higher doses
 Typical or atypical antipsychotics (off-label)—associated with
tardive dyskinesia, parkinsonism, metabolic syndrome
DRUG-INDUCED
MOVEMENT DISORDERS
• Antipsychotics can cause acute dystonia; treat severe
cases with IV diphenhydramine or lorazepam
• Reversible movement disorders can occur with:
 Lithium
 Antipsychotics
 Theophylline
 Estrogen
 Valproic acid
 Antiepileptics
 Antiemetics
 Dopamine replacement
therapy in PD
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TARDIVE MOVEMENT PHENOMENA
• Chronic and irreversible; older age and duration of
antipsychotic treatment are risk factors
• May begin weeks or months after initiation of drug;
outcome improved if offending drug can be stopped
• Treatment includes trihexyphenidyl, baclofenOL,
tetrabenazineOL, or clozapineOL
• Botulinum toxinOL injections are an option for severe
cases of dystonia (eg, neck jerking or sustained eye
closure)
OL =
off-label
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ESSENTIAL TREMOR
• Present when the limbs are in active use
• Common in the arms, head and/or voice; may also
include the chin, tongue, and legs
• Amplitude varies: tremor sometimes mild or absent,
other times severe
• May interfere with activities of daily living
• Family history is common, tremor improved with alcohol
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TREATMENT OF ESSENTIAL TREMOR
• Initial therapy includes β-blockers or primidoneOL
• Second-line drugs include gabapentinOL, topiramateOL,
mirtazapineOL, benzodiazepinesOL
• Response is variable and tremor is rarely reduced to
asymptomatic levels
• Severe, medically refractory tremor may be treated with
deep brain stimulation (DBS)
OL =
off-label
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EPILEPSY
• Seizures are classified by cortex involvement: partial or
generalized
• Partial seizures are subclassified:
 Simple partial: no impaired consciousness, usually
focal rhythmic motor twitching
 Complex partial: alteration of consciousness and
often amnesia for the event; automatisms and other
motor events may occur
• Generalized seizures in older adults are almost always
convulsive (“grand mal”)
COMMON UNDERLYING CAUSES OF
SEIZURES IN OLDER ADULTS
• Vascular disease
• Space-occupying lesions
• Brain trauma
• Alcohol withdrawal
• Neurodegenerative disease
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WORK-UP OF
NEW-ONSET SEIZURES (1 of 2)
• Look for underlying treatable cause
• Characterize the seizure/localize its source
• Prolonged delirium, especially in presence of
focal neurological signs and no obvious cause,
may indicate non-convulsive status epilepticus
• Elicit signs of a focal lesion or a metabolic
disturbance (eg, uremia, hepatic failure)
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WORK-UP OF
NEW-ONSET SEIZURES (2 of 2)
• Blood urea nitrogen; serum levels of sodium,
glucose, magnesium, calcium; liver function
tests
• MRI of brain with and without contrast, or head
CT with and without contrast
• Electroencephalography
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TREATMENT OF EPILEPSY (1 of 5)
• A low dose of antiepileptic drugs (AEDs) is often
necessary due to age-related changes in renal
and hepatic function
• Increase dosage gradually
• Free levels of some AEDs (eg, phenytoin) need
to be monitored because aging causes reduced
synthesis of albumin, decreased protein binding,
and increased free drug levels
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TREATMENT OF EPILEPSY (2 of 5)
• Instead of focusing on blood levels, follow:
 Reduction in seizure frequency
 Reduction in seizure severity
 Onset of side effects
• Maximizing monotherapy with second AED should
precede add-on therapy
• Consider discontinuing AED if patient is seizure-free for
several years and EEG is normal
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TREATMENT OF EPILEPSY (3 of 5)
Drug
Dosage,
mg
Target
blood level,
mcg/mL
Comments (Metabolism, Excretion)
Carbamazepine
200–600
bid
4–12
Many drug interactions; mood stabilizer;
thrombocytopenia, SIADH, leukopenia (L,K)
Gabapentin
300–600
tid
n.a.
Used as adjunct to other agents; good for
neuropathic pain; adjust dose on basis of
creatinine clearance (K)
Lamotrigine
100–300
bid
2–4
Can cause a fatal rash and must be titrated
slowly; when used with valproic acid, begin at
25 mg every other day and titrate to 25–100
mg bid over several weeks; prolongs PR
interval (L, K); lower risk of cognitive side
effects
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TREATMENT OF EPILEPSY (4 of 5)
Drug
Dosage,
mg
Target
blood level,
mcg/mL
Comments (Metabolism, Excretion)
Levetiracetam
500–1500
bid
n.a.
Adjust dose on basis of creatinine clearance
(K); low risk of cognitive side effects; can be
titrated quickly, but may cause irritability
Oxcarbazepine
300–1200
bid
n.a.
Leukopenia; hyponatremia (L)
Phenobarbital
30–60
bid–tid
20–40
200–300
qd
5–20 (see
notes page
of this slide)
Phenytoin
Many drug interactions; not recommended
for use in older adults (L)
Many drug interactions; potential for gingival
hypertrophy and osteoporosis with longterm use; exhibits nonlinear
pharmacokinetics (L)
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TREATMENT OF EPILEPSY (4 of 5)
Drug
Dosage,
mL
Target blood
level,
mcg/mL
Comments (Metabolism, Excretion)
Pregabalin
50–200
bid–tid
n.a.
Indicated as adjunct therapy for partial-onset
seizures only; not well studied in older adults
(K); used for neuropathic pain
Tiagabine
2–12
bid–tid
n.a.
Adverse-event profile in older adults less well
described (L)
Topiramate
25–100
qd–bid
n.a.
May affect cognitive functioning at high doses
(L, K)
Valproic acid
250–750
tid
50–100
Zonisamide
100–400
qd
n.a.
Can cause weight gain, tremor, elevated
LFTs, and thrombocytopenia requiring
monitoring; several drug interactions; mood
stabilizer (L)
Anorexia; contraindicated in patients with
sulfonamide allergy
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SUMMARY
• Parkinson disease may be recognized by
an insidious onset of asymmetrical tremor,
associated with rigidity and bradykinesia
• Tardive movement phenomena are most
common with antipsychotic therapy
• Common causes of late-life seizure include
vascular disease, new mass lesions,
alcohol withdrawal, and neurodegenerative
diseases such as Alzheimer disease
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CASE 1 (1 of 3)
• A 78-year-old man comes to the office because he has
lost consciousness 3 times in the past month.
• History includes Parkinson disease and stable angina.
• Medications include aspirin and carbidopa-levodopa.
• Tilt table test is positive for autonomic dysfunction.
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CASE 1 (2 of 3)
Which of the following is the most appropriate
treatment?
A. Increase current dosage of carbidopa-levodopa.
B. Initiate midodrine.
C. Initiate prednisone.
D. Discontinue aspirin; initiate clopidogrel.
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CASE 1 (3 of 3)
Which of the following is the most appropriate
treatment?
A. Increase current dosage of carbidopa-levodopa.
B. Initiate midodrine.
C. Initiate prednisone.
D. Discontinue aspirin; initiate clopidogrel.
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CASE 2 (1 of 4)
• A 66-year-old man comes to the office because he has
difficulty getting to sleep and frequent awakenings.
• He feels fatigued during the day and reports excessive
daytime sleepiness.
• He has twice fallen asleep at inappropriate times: once
while working on the computer and once while eating a
meal.
• His wife has noticed no snoring, nocturnal apnea, signs
of vivid dreams, or abnormal nighttime movement.
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CASE 2 (2 of 4)
• History includes Parkinson disease for 10 years, which is
well controlled with levodopa in small doses.
• The patient has had a sleep study and does not have
obstructive sleep apnea.
• The patient is counseled on sleep hygiene and is warned
to refrain from dangerous activities because of his
hypersomnolence.
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CASE 2 (3 of 4)
Which of the following is the most appropriate
next step to manage his hypersomnolence?
A. Prescribe modafinil.
B. Prescribe gabapentin.
C. Recommend melatonin.
D. Prescribe methylphenidate.
E. Increase dosage of levodopa.
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CASE 2 (4 of 4)
Which of the following is the most appropriate
next step to manage his hypersomnolence?
A. Prescribe modafinil.
B. Prescribe gabapentin.
C. Recommend melatonin.
D. Prescribe methylphenidate.
E. Increase dosage of levodopa.
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GRS8 Slides Editor:
Annette Medina-Walpole, MD, AGSF
GRS8 Chapter Author:
Daniel L. Murman, MD, MS, FAAN
GRS8 Question Writer:
Peter J. Whitehouse, MD, PhD
Medical Writers:
Reidenbach
Managing Editor:
Beverly A. Caley
Andrea N. Sherman, MS
Copyright © 2013 American Geriatrics Society
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