Transcript Clinical Slide Set. Parkinson Disease

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© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
in the clinic
Parkinson
Disease
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
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© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
What symptoms should prompt a clinician to
consider a diagnosis of Parkinson disease?
 Tremor at rest (frequency: 3–7 Hz )
 In hands; may also occur in legs, lips, jaw, tongue
 Bradykinesia (generalized slowness of movement)
 Patient may feel weakness, incoordination, tiredness
 Includes dragging the legs; shuffling; feeling unsteady
 Rigidity (increased resistance to passive joint movement)
 “Cogwheel rigidity”: ratchet-like pattern of catch and
release as examiner moves patient’s limb thru ROM
 “Lead-pipe rigidity”: smooth resistance thru ROM
 Affects any part of body and contributes to pain, stiffness
 Features typically start on one side… then spread to other
 Initially affected side more severely affected
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
What should clinicians ask patients when
evaluating them for Parkinson disease?
 Tremor at rest, bradykinesia, stiffness (rigidity)
 Decreased volume of speech (hypophonia)
 Smaller handwriting (micrographia)
 Drooling or excess saliva in the mouth
 Difficulty turning over in bed
 Changes in posture (especially stooping), changes in gait
 Constipation
 Anxiety, depression
 Olfactory dysfunction or REM sleep behavior
 Exposure to drugs that cause parkinsonism but not PD itself
 Family history (1st-degree relative with PD = 2-fold higher risk)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
What should clinicians do during the
physical exam of patients with possible PD?
 Neurologic examination
 ? decreased eye blinking, ? diminished expression
 Tremor: check with patient sitting, hands resting on lap
 When patient does mental calculation or repetitive
movement of contralateral limb: ? tremor
 Bradykinesia
 With rapid and repetitive movement—does slowing occur?
 Movements less coordinated as PD progresses
 Rigidity
 Passively manipulate limbs
 Have patient do repetitive maneuvers w/ contralateral limb
 Ask patient to stand up from chair without using the arms
 Assess postural stability with “pull” test
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
How does the clinician establish a
diagnosis of Parkinson disease?
 Diagnosis is clinical
 Depends on the history & physical exam
 Bradykinesia plus tremor or rigidity should be present
 Asymmetrical onset with persistent asymmetry as
disease progresses (initially symptomatic side remains
more severely affected)
 Sustained clinical improvement with levodopa or
dopamine agonist highly supportive of diagnosis
 Rule out signs of alternative condition (see next slide)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
Features Suggesting Another Diagnosis
 History encephalitis
 History repeated head injury
 History recurrent strokes +
stepwise progression of
parkinsonism
 History oculogyric crisis
 Dementia preceding or concurrent
with onset of parkinsonism
 Cerebellar signs
 Autonomic dysfunction
 Spasticity, hyperreflexia, or
Babinski responses
 Current or recent use of
dopaminergic blockers or
depletors
 Apraxia
 Structural abnormality on brain
imaging
 Abrupt symptom onset or
sustained spontaneous remission
 Supranuclear gaze palsy
 Unilateral features after 3 y
 Frequent falls early in disease
 Symmetrical motor signs
 Impaired sensation with intact
primary sensory systems
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
What tests should be considered in the
evaluation of possible Parkinson disease?
 Brain MRI (or CT, if contraindicated)
 If diagnosis uncertain
 May show abnormalities explaining cause for symptoms
(severe vascular changes, tumor, hydrocephalus)
 PET scan and SPECT scan
 May detects abnormalities of dopaminergic system
 SPECT: differentiates parkinsonism from essential tremor
 ? Wilson disease (patients <40yo with parkinsonism)
 To rule-out: measure serum ceruloplasmin; order 24-h
urinary copper test; check for Kayser-Fleischer rings (eyes)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
What other conditions should be
considered in the differential diagnosis?
Parkinson disease with known genetic cause

LRRK2-associated Parkinson disease

Autosomal recessive juvenile parkinsonism

Autosomal-dominant Parkinson disease
Other conditions
 Multiple system atrophy
 Progressive supranuclear palsy
 Corticobasal degeneration
 Dementia with Lewy bodies
 Essential tremor
 Vascular parkinsonism
 Normal pressure hydrocephalus
 Dopa-responsive dystonia
 Medication-induced or toxin- or
metabolic-related parkinsonism
 Post-traumatic or psychogenic
parkinsonism
 Post-encephalitic parkinsonism
 Parkinsonism from tumor, subdural
hematoma, or infection
 Wilson disease, Alzheimer
dementia
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
When should a specialist be consulted for
the diagnosis of Parkinson disease?
 Refer all patients with early symptoms to neurologist
 Guides diagnosis
 Helps rule-out atypical parkinsonian syndromes
 Consider PD or movement disorders specialist
 May diagnose more accurately than general neurologist
 Not necessarily more cost-effective or more acceptable to
patients
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
CLINICAL BOTTOM LINE: Diagnosis…
 Consider Dx when rest tremor, bradykinesia, or rigidity present
 Conduct thorough history and neurologic examination
 Pay attention to medications that may cause parkinsonism
 Base diagnosis on clinical findings
 MRI & SPECT imaging may help rule out differential Dx
 Consult neurologist if atypical signs or symptoms present
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
Is there any role for exercise or diet
modifications?
 Exercise
 Modestly benefits motor & functional outcomes
 Regular activity needed to maintain gains
 Diet
 Adequate fiber and hydration to reduces constipation
 Calcium & vitamin D important to reduce risk for bone loss
 Low-protein diet may reduce “on-off” phenomenon
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
When should drug therapy be started?
 No medication is available that slows disease
progression
 Start treatment when symptoms limit patient’s
activities
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
What drugs should be used for initial
treatment and how should they be chosen?
 Levodopa
 Most effective medication for motor symptoms
 Complications long-term (dyskinesia + “wearing-off”)
 Often initial treatment used in patients >70 years; all
patients eventually require levodopa
 Dopamine agonist (pramipexole, rotigotine, ropinirole)
 May delay motor complications when used as initial Rx
 Often initial treatment in patients <50 years
 Anticholinergics and MAO-B inhibitors
 Prevent dopamine breakdown
 No consensus: initial Rx for those between 50-70 years
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
How should pharmacotherapy be adjusted
as motor symptoms worsen?
 Increase dopaminergic medications as symptoms worsen
 Dyskinesia
 Don’t treat if it doesn’t disturb patient
 Reduce levodopa, add amantadine or dopamine agonist
 Carbidopa-levodopa: try decreased dose at shorter intervals
 Wearing off
 COMT inhibitors: prolong levodopa’s therapeutic effect
 Alternative: selegiline (MAO-B inhibitor)
 Other strategies: add dopamine agonist, increase levodopa
dosage or frequency of administration
 Apomorphine: rescue therapy until next levodopa dose
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
How should clinicians manage the adverse
effects of pharmacotherapy?
 Nausea (from carbidopa-levodopa, dopamine agonists)
 Often mild; taking medication with food may alleviate
 Additional carbidopa may help
 If persistent, domperidone may be effective
 Metoclopramide and prochlorperazine block dopamine
receptors and worsen parkinsonism (don’t use)
 Excessive sleepiness (from dopamine agonists)
 Discontinue all meds that may contribute to sleepiness
 Teach good sleep hygiene
 Evaluate patients for underlying sleep disorders
more…
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
 Peripheral edema (from amantadine or dopamine agonists)
 Doesn’t always need treated, especially if mild
 Disappears when offending medication discontinued;
reducing dose won’t help
 Impulse control disorders (from dopamine agonists)
 Occur in ≈14% of treated patients
 Ask all patients about these behaviors
 If treatment needed, reduce or discontinue offending
medication (worsening motor symptoms may require
return to original dose)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
What are the nonmotor symptoms?
 Sleep disorders
 Neuropsychiatric complications
 GI symptoms
 Symptoms of autonomic dysfunction
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
How should sleep problems be managed?
 Educate patients about proper sleep hygiene
 Discontinue drugs that inhibit sleep initiation, if possible
 Decrease evening fluid intake / prescribe anticholinergic
 Treat anxiety / depression
 XR carbidopa-levodopa: for tremor, difficulty turning over
 Levodopa or dopamine agonists: for restless leg syndrome
 Mechanical devices: for obstructive sleep apnea
 Clonazepam: for REM sleep behavior disorder
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
How should clinicians manage
neuropsychiatric complications?
 Depression
 Under-recognized: PD features overlap with somatic features
 SSRIs often used (due to favorable adverse effect profile)
 Apathy
 Can occur independently; distinguish from depression
 Anxiety
 More anxiety during “off ” periods, less during “on” periods
 May help to adjust medications to prolong “on” times
more…
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
 Psychosis (especially visual hallucinations)
 Treat reversible causes (infection, metabolic disturbance)
 Consult neurologist for reducing/eliminating Parkinson meds
 If pharmacotherapy warranted: use cholinesterase inhibitor
 If antipsychotic necessary: use clozapine or quetiapine only
 Cognitive impairment (especially of executive function)
 Can present in early stages of Parkinson disease
 Treat any reversible causes; then try cholinesterase inhibitor
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
How should gastrointestinal symptoms be
managed?
 Dysphagia
 Refer patient to speech pathologist
 Order modified barium swallow with videofluoroscopy
 Adjust medications to improve “on” time, if appropriate
 Teach safe swallowing techniques; consider changing diet
 Constipation
 Modify diet, use bulking agents, stool softeners, laxatives
 Consider domperidone / tegaserod
 Consider Isosmotic macrogol electrolyte solution
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
How should symptoms of autonomic
dysfunction be managed?
 Urinary symptoms
 Rule-out bladder infection
 Reduce evening fluid intake
 Try timed voiding to lessen urgency, incontinence
 For storage symptoms: solifenacin or darifenacin; consider
anticholinergics (may contribute to cognitive impairment)
 Options: desmopressin, botulinum toxin in bladder muscle
 Urodynamic studies, referral to urologist may be warranted
 Orthostatic hypotension
 Increase salt and fluid intake; try small, frequent meals
 Use high-compression stockings
 If neurogenic: fludrocortisone; midodrine (pyridostigmine
less effective, but doesn’t exacerbate supine hypertension)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
When should a specialist be consulted?
When should is hospitalization warranted?
 Consult neurologist: at least annually
 May lower morbidity and mortality
 Hospitalize: when symptoms can’t be managed on
outpatient basis
 Psychosis (hallucinations, delirium)
 Significant mood disturbances (mania or depression)
 Profound fluctuations in mobility
 Frequent or serious falls
 Infections (UTI, aspiration pneumonia)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
Which surgical interventions are effective?
 Lesioning therapies (thalamotomy, pallidotomy)
 Effective for treating symptoms
 But irreversible, and may cause AEs, esp bilateral lesions
 Deep-brain stimulation (current practice)
 Of subthalamic nucleus or globus pallidus interna:
alleviates tremor, bradykinesia, rigidity; increases “on”
time; reduces wearing off & dyskinesia
 Of ventralis intermedius nucleus: disables tremor only
 For major motor fluctuations + dyskinesia Rx can’t control
 For severe, isolated, disabling tremor
 Inappropriate for atypical parkinsonian syndromes
 Inappropriate if dementia or untreated depression present
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
What is the prognosis of a patient with
Parkinson disease?
 Unpredictable: Progression varies by individual
 Progressive neurologic disorder
 Tremor-dominant: tends to progress more slowly + have
less cognitive impairment
 Akinetic-rigid: tends to progress more quickly + have
more cognitive impairment
 Many patients live with minimal functional impairment for
substantial period (due to dopaminergic Rx)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.
CLINICAL BOTTOM LINE: Treatment…
 Refer patients to a neurologist for co-management
 Begin drug Rx when symptoms cause functional impairment
 Start with levodopa / dopamine agonists / MAO-B inhibitors
(depending on severity, motor complications, age, drug AEs)
 Adjust drug regimen + add other agents as PD progresses
 Treat nonmotor symptoms
 Sleep disorders, neuropsychiatric complications, GI
symptoms, autonomic dysfunction
 Encourage regular exercise to maintain physical functioning
 Consider deep-brain stimulation when substantial motor
fluctuations, dyskinesia, or disabling tremor can’t be managed
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (3): ITC2-1.