See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/241827581

Movement Disorders: Overview and Treatment Options

Article · April 2005

CITATIONS READS

4 6,445

2 authors, including:

Bruce R Ransom
The Chinese University of Hong Kong
253 PUBLICATIONS   20,215 CITATIONS   

SEE PROFILE

All content following this page was uploaded by Bruce R Ransom on 02 April 2014.

The user has requested enhancement of the downloaded file.

 CONTINUING EDUCATION CREDIT
Movement Disorders:
Overview and Treatment Options
Ali Samii, MD, and Bruce R. Ransom, MD, PhD
Educational Objectives
■ Review the terminology used to describe movement
disorders.
■ Discuss individual movement disorder syndromes,
including essential tremor, Parkinson’s disease, dystonia,
myoclonus, chorea, tic disorders, tardive dyskinesia and
akasthisia, restless limbs syndrome, and Wilson’s disease.
■ Review current treatment options for individual
movement disorders.
Introduction
The area of movement disorders is a subspecialty of neurol-
ogy focusing on a variety of conditions that are characterized
by hypokinetic, hyperkinetic, or abnormally coordinated move-
ments. These conditions include tremor,
parkinsonism, dystonia, myoclonus,
chorea, ballismus, ataxia, tic disorders,
dyskinesia, akathisia, restless limbs, and
others. The term “movement disorders”
may be used to refer to either abnormal
movements or to syndromes that cause
these abnormal movements.
The classification of movement disorders is based on phe-
nomenology, individual syndromes, or etiology. In this article,
we will first review the terminology used to describe movement
disorders, then briefly discuss individual movement disorder
syndromes. The focus of this article is on treatment options.
Terminology
A tremor is a rhythmic oscillation of a body part by alternat-
ing or synchronous contraction of agonist and antagonist mus-
Dr. Samii is Associate Professor and Dr. Ransom is Warren Magnuson
Professor and Chair, both in the Department of Neurology at the Univer-
sity of Washington School of Medicine in Seattle, Washington. Dr. Samii
is Director of the Seattle Parkinson Disease Research, Education and
Clinical Center (PADRECC) at the Seattle Veterans Affairs Puget Sound
Health Sciences Center. Dr. Ransom is a member of P&T’s editorial board.
228 P&T® • April 2005 • Vol. 30 No. 4
cles.1 Usually, the hands are involved, but the head, jaw, voice,
tongue, and the lower limbs may also be affected.
A resting tremor occurs while a limb is not active or when it
is at complete rest against gravity. The resting tremor in Parkin-
son’s disease (PD) affects the upper limbs asymmetrically.
An action tremor, such as that seen in essential tremor (the
most common movement disorder), can be:
• postural, as when a limb maintains position against grav-
ity (e.g., with the hands in the outstretched position).
• intention (terminal), as observed in the finger-to-nose-to-
finger test.
• task-specific (observed while a person is performing a cer-
tain activity, such as writing).
Parkinsonism is a nonspecific term that refers to a combina-
tion of signs seen in PD. These include tremor, rigidity,
bradykinesia, and postural instability. PD is defined more
specifically, with gradations of diagnostic
certainty (Table 1).2
Dystonia is an abnormal sustained mus-
cle contraction causing twisting or turn-
ing around one or multiple joints.3 It may
affect the neck (cervical dystonia or torti-
collis), eyelids (blepharospasm), limbs,
trunk, or vocal cords (spasmodic dysphonia). Dystonia can be
focal, segmental, or generalized. “Writer’s cramp” is a focal
hand dystonia. With segmental dystonia, an entire limb or
trunk is involved. Generalized or multifocal dystonia affects
multiple body parts.
Myoclonus may be “positive” or “negative.” Positive myo-
clonus is a sudden, brief muscle contraction; a negative myo-
clonus (e.g., asterixis) is an interruption of muscle contraction
in the extended arm and wrist that causes inhibition of the ac-
tivated muscle.4
Chorea, meaning “dance” in Greek, resembles exaggerated
fidgetiness. The movements are usually generalized and pur-
poseless. In mild cases, chorea may be blended into natural
movements and may appear purposeful.
Choreoathetosis refers to slow and writhing movements.
Ballismus is a large-amplitude, sometimes violent, proximal
chorea. It usually occurs acutely on one side of the body
(hemiballismus) after an infarct in the contralateral subthala-

mic nucleus (STN) or with STN stimulation for the treatment
of PD.
Ataxia refers to impaired motor coordination that is usually
related to disorders of the cerebellum or its connections with
the brain and spinal cord. It is characterized by slurred speech,
nystagmus, dysmetria (undershooting or overshooting a tar-
get with trajectory limb movements), poor dexterity, and a
wide-based gait. There are no proven drug treatments for
ataxia caused by primary degenerative cerebellar syndromes.
The therapy for secondary ataxia syndromes (e.g., toxic/meta-
bolic, drug-induced, paraneoplastic, or Wilson’s disease) would
involve treatment of the primary condition.
Tics are temporarily suppressible, abnormal movements or
vocalizations.5 Simple motor tics are isolated, brief, sudden
movements that involve one body part. Complex motor tics may
involve more than one body part and may have a component
of dystonia, other complex movements, or even obscene ges-
tures (copropraxia). A simple vocal tic may be a grunt or a
throat clearing. Complex vocal tics are more elaborate vocal-
izations, words or phrases, even profanity (coprolalia).
Dyskinesia literally means “abnormal movement.” However,
the term has evolved to refer to abnormal drug-induced invol-
untary movements, usually choreatic, dystonic, or a com-
bination of both. Dyskinesia in PD patients results from the
long-term complications of levodopa therapy.6 Tardive dys-
Table 1 Diagnosis of Idiopathic Parkinson’s
Disease (PD)
Clinical Diagnostic Criteria
Clinically possible PD
• One of asymmetrical resting tremor, asymmetrical
rigidity, or asymmetrical bradykinesia
Clinically probable PD
• Any two of asymmetrical resting tremor, asymmetrical
rigidity, or asymmetrical bradykinesia
Clinically definite PD
• Criteria for clinically probable PD
• Definitive response to antiparkinson medications
Exclusion Criteria
• Exposure to drugs that can cause parkinsonism, such as
neuroleptic agents, some antiemetic medications, tetra-
benazine, reserpine, flunarizine, and cinnarizine
• Cerebellar signs
• Corticospinal tract signs
• Eye-movement abnormalities other than slight limita-
tion of upward gaze
• Severe dysautonomia
• Early moderate-to-severe gait disturbance or dementia
• History of encephalitis, recurrent head injury, or a fam-
ily history of PD in two or more family members
• Evidence of severe subcortical white-matter disease,
hydrocephalus, or other structural lesions on magnetic
resonance imaging that might explain parkinsonism
CONTINUING EDUCATION CREDIT
kinesia refers to choreodystonic movements secondary to the
long-term use of neuroleptic or antiemetic medications that
have dopamine antagonist activity.7
Akathisia is excessive motor activity that is intended to
relieve a sensation of inner restlessness, which occurs either
acutely or as a late complication of neuroleptic medications.8
Patients display agitation, with an inability to remain seated,
and are usually shifting their weight, or pacing.
Restless limbs syndrome occurs as a distressing desire to
move the limbs (usually the legs) while sitting or lying down.
The disorder is relieved by walking. Symptoms worsen in the
evening, and periodic limb movements may occur during
sleep.9
Treatment of Movement Disorder Syndromes
Essential Tremor
Essential tremor is a prevalent movement disorder.10 The
tremor is present during action, and the hands, head, and
voice are affected to variable degrees. A family history is pos-
itive in most patients, with a dominant inheritance pattern and
variable penetrance.11 The occurrence of a family history is
more common if the patient’s relatives are examined. 12
Tremors are worsened by caffeine, stress, and associated
medical disorders, such as hyperthyroidism, and they are
relieved by alcohol.
Medical Therapy
The initial medication for essential tremor is usually either
primidone (Mysoline®, Xcel) or propranolol (e.g., Inderal®,
Wyeth).13 The starting dose of primidone is 50 mg at bed-
time, with the doses gradually increasing up to 750 mg daily.
Side effects include somnolence, fatigue, cognitive problems,
and ataxia. Propranolol should be started at 10 mg daily and
titrated as tolerated to 320 mg daily. Adverse drug effects
(ADEs) include bradycardia, hypotension, fatigue, broncho-
spasm, depression, and impotence.
Primidone and propranolol can be administered together.
Topiramate (Topamax®, Ortho-McNeil), gabapentin (Neu-
rontin®, Pfizer), and the benzodiazepines (e.g., diazepam
[Valium®, Roche]) may also relieve tremors. Injections of bot-
ulinum toxin may also be helpful.14,15
Surgical Options
Thalamotomy
When severe essential tremor is intractable to medical ther-
apy, unilateral thalamotomy (surgical destruction of a small
part of the thalamus) improves the contralateral tremor. Bilat-
eral thalamotomy is rarely performed, because it can result in
cognition and gait disturbances.
Deep-Brain Stimulation
Although the exact mechanism of deep-brain stimulation is
unknown, the technique is thought to suppress neuronal activ-
ity in the target (in this case, the same part of the thalamus that
would be destroyed in thalamotomy) by stimulating it at high
frequency. Thalamic deep-brain stimulation is considered safer
Vol. 30 No. 4 • April 2005 • P&T® 229
 CONTINUING EDUCATION CREDIT
than thalamotomy,16 presumably because there is no signifi-
cant destruction of brain tissue, the effects are considered re-
versible, and the degree to which the target is suppressed can
be adjusted.
Serious surgical complications include symptomatic brain
hemorrhage (usually fewer than 3% of patients) and death
(fewer than 1%).
Parkinson’s Disease
The cardinal features of PD are resting tremor, rigidity, and
bradykinesia. Postural instability is sometimes considered a
cardinal feature, but this is a nonspecific finding that is usually
absent in early PD, especially in younger patients. Nonmotor
features may occur in PD, including autonomic dysfunction,
cognitive and psychiatric changes, sensory symptoms, and
sleep disturbances. The diagnostic criteria for PD have become
more rigorous with gradations of diagnostic certainty (Table
1).17,18
The prevalence of PD in industrialized countries is esti-
mated at 0.3% of the general population; approximately 1% of
people over 60 years of age are affected.19,20 The prevalence is
slightly higher in men than in women.21 The mean age of
onset is about 60 years,22 but 5% of patients experience their
first symptom before age 40.23
The etiologic mechanism of PD is unknown, but aging,
environmental factors, and a genetic predisposition probably
all play a role.24 The recent discovery of several genetic loci
related to familial PD has led to the hypothesis that failure of
the ubiquitin–proteasome system and protein misfolding are
the final common pathways in the pathogenesis of PD.25
Medical Therapy
There is no unequivocal neuroprotective agent currently
available for PD. Vitamin E was not beneficial in a large multi-
center trial in patients with early PD.26 The efficacy of selegi-
line (Eldepryl®, Watson), a monoamine oxidase-B (MAO-B)
inhibitor, in delaying the initiation of levodopa is at least par-
tially a consequence of symptomatic relief of motor symptoms
rather than neuroprotection.27
Patients with early PD who were treated for a year with
rasagiline (Teva Pharmaceuticals), another MAO-B inhibitor,
showed less functional decline than patients whose treatment
with rasagiline was delayed for six months.28 The issue of
possible neuroprotection by MAO-B inhibitors remains un-
resolved.
One pilot study suggested that high-dose coenzyme Q10
might slow symptom progression in early PD.29 These results
have yet to be confirmed in larger studies with longer follow-
up periods.
Controlled trials of dopamine agonists versus levodopa in
early PD using functional imaging of the dopaminergic system
have claimed a slower rate of disease progression in PD
patients who were started on dopamine agonists.30,31 How-
ever, these results are are still being debated, in part because
of issues surrounding the accuracy of functional neuro-
imaging techniques as markers of disease progression.32
230 P&T® • April 2005 • Vol. 30 No. 4
In a controlled trial of intraventricular infusion of glial cell
line–derived neurotrophic factor (GDNF) in PD patients,
GDNF did not improve motor symptoms.33 In an open-label
study, five PD patients who received GDNF infusions via
catheters directly into the putamen improved after a year.34 A
larger controlled trial of bilateral intraputamenal GDNF infu-
sion sought to confirm these findings, but no benefits over
placebo were observed.35
Treatment is initiated when motor symptoms cause dis-
ability. Anticholinergic agents are rarely used in younger
patients, in whom tremor is the major symptom. The more
definitive treatment of early PD consists of either a dopamine
agonist or levodopa. Because dopamine agonists cause less
dyskinesia than levodopa,36,37 they are usually the initial ther-
apy for younger patients. Side effects of dopamine agonists
include nausea, hypotension, leg edema, vivid dreams, hallu-
cinations (especially in elderly people with cognitive deficits),
somnolence, and sleep attacks.38
Dopamine agonists have less antiparkinson efficacy than
levodopa does, but agonist monotherapy can sometimes
control motor symptoms for the first two to five years. The non-
ergot agonists, such as pramipexole (Mirapex®, Pfizer) and
ropinirole (Requip®, GlaxoSmithKline) may help to prevent
rare ergot-related retroperitoneal, pulmonary, and cardiac
valve fibrosis.
Levodopa remains the most potent antiparkinson drug and
is the backbone of therapy throughout much of the course of
the disease.2 It is the preferred initial drug in older adults and
in those with cognitive deficits or serious comorbid condi-
tions. Levodopa is combined with carbidopa (e.g., Sinemet®,
Bristol-Myers Squibb) or benserazide (e.g., Parlopa® in
Canada) to prevent peripheral conversion to dopamine by
dopa-decarboxylase.
Side effects of levodopa are similar to those of dopamine
agonists, although somnolence, hallucinations, and leg edema
are less common. Complications of long-term levodopa ther-
apy include motor fluctuations, including “end-of-dose wearing-
off ” and “on–off” phenomena, and dyskinesia.39 Dividing
protein intake throughout the day may help to reduce motor
fluctuations.
Controlled-release forms of levodopa may provide a longer
duration of benefit, but their absorption is more unpredictable
than immediate-release levodopa. Catechol-O-methyl trans-
ferase (COMT) inhibitors, such as entacapone (Comtan®,
Novartis) and tolcapone (Tasmar®, Roche), prolong the half-
life of circulating levodopa and improve end-of-dose wearing-
off.40 Tolcapone is more potent, but its use has declined signif-
icantly because of a few cases of fatal liver failure.41 Dyskinesia
can be alleviated with a lower levodopa dosage but at the
expense of worsening motor symptoms. In patients with motor
fluctuations and dyskinesia, adding a dopamine agonist to
levodopa may help reduce motor fluctuations. It may also allow
for levodopa reduction, which in turn alleviates dyskinesia.
The subcutaneously injectable dopamine agonist apo-
morphine is useful for rapid treatment of “off” periods in PD.42
However, given the severity of apomorphine-induced nausea,

premedication with domperidone (Motilium™, Janssen) or
trimethobenzamide (Tigan®, King) is needed. Amantadine
(Symmetrel®, Endo) may also suppress dyskinesia, possibly
by N-methyl-D-aspartate (NMDA) receptor antagonism.43
Nonmotor Symptoms
Nonmotor symptoms in PD may occur as part of the disease
or as complications of treatment. These include depression,
constipation, sleep disturbance, psychosis, cognitive impair-
ment, orthostatic hypotension, drooling, and urinary urgency.
Depression in PD is usually treated with a selective serotonin
reuptake inhibitor (SSRI).44 No controlled head-to-head stud-
ies have suggested that one SSRI is superior to another in PD.
The aggressive use of multiple modalities (e.g., stool soften-
ers, increased fiber intake, and suppositories) is indicated for
treating constipation.
Disorders of sleep in PD patients include daytime somno-
lence, sleep attacks, night-time awakenings caused by
overnight bradykinesia, rapid-eye movement (REM) behavior
disorder, and restless limbs or periodic limb movements.45
Daytime somnolence and sleep attacks may be associated
with dopamine agonists, and the agonist may have to be dis-
continued.46
Overnight bradykinesia and restless limbs syndrome may
be alleviated with a bedtime dose of long-acting levodopa,
sometimes with entacapone, or a dopamine agonist. Clon-
azepam (Konopin®, Roche) is effective in treating REM behav-
ior disorder.
Psychosis in PD patients is thought to be mostly drug-
induced, and it occurs more frequently in patients with demen-
tia. Dopamine agonists are more likely than levodopa to cause
hallucinations.38
First, the agonist or anticholinergic agent should be discon-
tinued, and the lowest dose of levodopa should be used. Adding
an atypical neuroleptic drug may be necessary. Quetiapine
fumarate (Seroquel®, AstraZeneca) is the more popular atyp-
ical neuroleptic agent in therapy for PD. It causes fewer extra-
pyramidal ADEs than risperidone (Risperdal®, Janssen) or
olanzapine (Zyprexa®, Eli Lilly), and there is no need for
weekly or biweekly measurements of the complete blood count
(CBC), as would be required with clozapine (Clozaril®, Novar-
tis).47 Open-label studies have suggested that dementia and
psychosis in PD may be treated with central cholinesterase in-
hibitors.48
Rivastigmine tartrate (Exelon®, Novartis) has been effec-
tive for dementia with Lewy bodies49 and in treating the demen-
tia associated with PD.50 Another small randomized, controlled
study showed that donepezil (Aricept®, Esai/Pfizer) improved
cognition in PD patients.51 Memantine (Namenda®, Forest),
proven to be effective in moderate-to-severe Alzheimer’s de-
mentia,52 has not been evaluated in a large, controlled study
for dementia in PD, but it may prove to be useful.
Treatment options for hypotension include reducing the
dosage of antiparkinson medications, increasing the salt and
fluid intake, and adding fludrocortisone acetate (Florinef®,
CONTINUING EDUCATION CREDIT
King) or midodrine (ProAmatine®, Shire). Drooling may be
reduced by the peripheral anticholinergic agent glycopyrrolate
(Robinul®, First Horizon), but this drug may worsen consti-
pation. Injection of botulinum toxin into the salivary glands
reduces drooling.53
Urinary urgency may be treated with peripheral anticholin-
ergic agents, such as oxybutynin (Ditropan®, Ortho-McNeil)
and tolterodine tartrate (Detrol®, Pfizer) or with alpha-adren-
ergic blocking agents, such as prazosin (Minipress®, Pfizer)
and terazosin (Hytrin®, Abbott). Unfortunately, the former
agents worsen constipation and the latter agents exacerbate
hypotension.
Surgical Options
Deep-Brain Stimulation
For more than a decade, deep-brain stimulation of “hyper-
active” nuclei has been used to help relieve motor symptoms
in PD patients with severe motor fluctuations and dyskinesia.
High-frequency stimulation of deep-brain targets presumably
reduces neural activity in the tissue surrounding the electrode
contact.
The suppression of the target induced by this technique can
be sculpted by adjustments of the electrode configuration,
stimulation intensity, pulse width, and frequency. Bilateral
stimulation of the internal globus pallidus (GPi) or the subthal-
amic nucleus (STN) helps to relieve PD motor symptoms.54
Some researchers claim that bilateral STN stimulation is
superior to bilateral GPi stimulation in PD patients because it
allows a reduction in antiparkinson medications,55 but the
debate continues regarding the optimal stimulation target for
PD. A large randomized, multicenter study comparing bilateral
STN to bilateral GPi stimulation is currently under way.
The adverse effects of deep-brain stimulation include brain
hemorrhage, infarct, seizures, and death. Other complications
include breakage of the leads, various hardware failures, mal-
function of the pulse generator, and infected hardware. Side
effects from the stimulation itself include gait disturbances and
worsening dyskinesia, paresthesias, cognition, mood, and
speech. The stimulation-related side effects may be reversible
by adjusting stimulation parameters.
The key to a successful outcome is appropriate patient selec-
tion.56 Surgical patients must have clinically definitive PD with
documented motor improvement after levodopa therapy. All
attempts to optimize drug therapy must have failed to relieve
motor fluctuations or dyskinesia. Patients should not have
dementia, untreated psychiatric conditions, or serious medical
illnesses. Dedication and commitment from patients and their
families are essential for maintaining frequent follow-up visits.
Restorative (Transplantation) Therapy
In the first randomized sham surgery-controlled study of
fetal mesencephalic tissue transplantation, younger patients
showed some improvement in the “medication-off” state, but
many patients experienced disabling dyskinesia.57 The second
randomized, controlled study found no significant motor im-
provement.58 Most transplant recipients developed dyskinesia
Vol. 30 No. 4 • April 2005 • P&T® 231
 CONTINUING EDUCATION CREDIT
Table 2 Drug Therapy for Movement Disorders
Condition Medication
Essential tremor Propranolol (beta blocker)
Primidone (anticonvulsant)
Topiramate (anticonvulsant)
Parkinson disease Immediate-release carbidopa/
(motor symptoms) levodopa (levodopa is a precur-
sor to dopamine, and carbidopa
blocks conversion of levodopa
to dopamine in the periphery)
Controlled-release
carbidopa/levodopa
Ropinirole (non–ergot-derived
dopamine agonist)
Pramipexole (non–ergot-
derived dopamine agonist)
Pergolide (ergot-derived
dopamine agonist)
Entacapone (catechol-O-methyl
transferase inhibitor)
Tolcapone (catechol-O-methyl
transferase inhibitor)
Selegiline (selective monoamine
oxidase-B inhibitor)
Trihexyphenidyl (central
anticholinergic agent)
Amantadine (N-methyl-D-
aspartate receptor inhibitor)
Apomorphine (non–ergot-
derived injectable dopamine
agonist)
Parkinson disease
(non-motor symptoms)
REM behavior Clonazepam (benzodiazepine)
disorder
Psychosis Quetiapine (antipsychotic agent) 12.5–200 mg daily
Clozapine (antipsychotic agent)
232 P&T® • April 2005 • Vol. 30 No. 4
Dose Range
30–180 mg daily
50–500 mg daily
25–200 mg daily
25/100 or 25/250 from 1/2 Nausea, somnolence, dyskinesia,
tablet t.i.d. to as high as hypotension, hallucinations
tolerated, depending on
motor symptoms
25/100 and 50/200 1/2
tablet t.i.d. to as high as
tolerated
0.25 mg t.i.d. to 5 mg q.i.d. Nausea, more somnolence than levodopa,
0.125 mg t.i.d.–1.5 mg
q.i.d.
0.05 mg t.i.d.–1 mg q.i.d.
200 mg with each dose
of carbidopa/levodopa
100 mg t.i.d.
5 mg b.i.d.
2–10 mg daily
100 mg b.i.d.–t.i.d.
1–6 mg SQ injection
for severe "off" episodes
0.25–3 mg
12.5–100 mg daily
Side Effects
Hypotension, bradycardia, fatigue,
impotence, bronchospasm, depression
Somnolence, cognitive impairment
Somnolence, cognitive impairment,
weight loss, paresthesias
Nausea, somnolence, dyskinesia,
hypotension, hallucinations
less dyskinesia than levodopa, sleep at-
tacks, leg edema, hallucination, hypotension
Nausea, more somnolence than levodopa,
less dyskinesia than levodopa, sleep at-
tacks, leg edema, hallucination, hypotension
Same as ropinirole and pramipexole,
plus cardiac valve, retroperitoneal and
pulmonary fibrosis
Exacerbates levodopa’s side effects;
diarrhea and bright-orange urine
Exacerbates levodopa’s side effects;
diarrhea, rare liver failure (liver enzyme
monitoring required)
Nausea, insomnia, interaction with other
monoamine oxidase inhibitors
Dry mouth, dry eyes, constipation,
hypotension, cognitive impairment,
urinary retention
Nausea, hypotension, hallucinations,
confusion, edema
Severe nausea, abdominal cramps, yawning,
somnolence, hallucinations, hypotension
Residual daytime somnolence, impaired
cognition, worsening of sleep apnea
Somnolence, worsening of motor
symptoms, confusion
Same as quetiapine plus possible
agranulocytosis requiring frequent
blood count measurements
 CONTINUING EDUCATION CREDIT

Table 2 Drug Therapy for Movement Disorders, continued

Condition Medication Dose Range Side Effects

Dementia Rivastigmine (central 1.5–6 mg b.i.d. Nausea and abdominal cramps
cholinesterase inhibitor)
Donepezil (central 5–10 mg daily Nausea and abdominal cramps
cholinesterase inhibitor)
Galantamine (central 4–12 mg b.i.d. Nausea and abdominal cramps
cholinesterase inhibitor)

Levodopa- and Domperidone (peripheral 10–20 mg with each dose No common side effects
dopamine agonist- dopamine antagonist) of carbidopa/levodopa
induced nausea or dopamine agonist
Levodopa-induced Carbidopa alone (Lodosyn®) 25 mg with each dose of No common side effects
nausea carbidopa/levodopa
Depression SSRIs Depends on drug SSRI adverse effects vary among individual
drugs
Orthostatic Fludrocortisone 0.1–0.3 mg daily Hypertension, edema, fluid retention
hypotension (mineralocorticoid)
Midodrine (peripheral alpha- 10–30 mg daily Hypertension, piloerection, urinary
agonist) retention
Drooling Glycopyrrolate (peripheral 2–8 mg daily Dry mouth, dry eyes, constipation,
anticholinergic agent) hypotension, urinary retention
Botulinum toxin injections 20–100 units Dry mouth, difficulty chewing
or swallowing
Urinary urgency Peripheral anticholinergic agents Depends on drug Dry mouth, dry eyes, constipation,
(e.g., tolterodine, oxybutynin) hypotension, urinary retention
Alpha-adrenergic blocking Depends on drug Hypotension
agents (e.g., prazosin, terazosin)
Dystonia Trihexyphenidyl 2–10 mg daily Dry mouth, dry eyes, constipation,
hypotension, cognitive impairment,
urinary retention
Benztropine (central 2–8 mg daily Dry mouth, dry eyes, constipation,
anticholinergic agent) hypotension, cognitive impairment,
urinary retention
Carbidopa/levodopa Smaller doses than Nausea, somnolence, dyskinesia,
for Parkinson’s disease hypotension, hallucinations

Botulinum toxin injections Depends on body part Depends on body part injected
for focal dystonia injected
Myoclonus Valproic acid (anticonvulsant) 500–2,000 mg daily Somnolence, cognitive impairment, tremor,
hair loss, weight gain, thrombocytopenia,
elevated ammonia
Clonazepam 1–4 mg daily Somnolence, cognitive impairment, fatigue
Levetiracetam (anticonvulsant) 500–3,000 mg daily Somnolence, cognitive impairment, fatigue
Primidone 50–500 mg daily Somnolence, cognitive impairment, fatigue

Vol. 30 No. 4 • April 2005 • P&T® 233

 CONTINUING EDUCATION CREDIT

Table 2 Drug Therapy for Movement Disorders, continued

Condition Medication Dose Range Side Effects

Chorea Neuroleptic (antipsychotic) Depends on drug Somnolence, cognitive impairment,
agents parkinsonism, plus others
Reserpine (monoamine 0.1–1.0 mg daily Hypotension, depression, parkinsonism
depleter)
Tetrabenazine (monoamine 12.5–100 mg daily Hypotension, depression, parkinsonism
vesicular transporter inhibitor)
Tic disorder Clonidine (central alpha- 0.1–0.4 mg daily Hypotension
adrenergic agonist)
Neuroleptic agents (quetiapine, Depends on drug Somnolence, cognitive impairment,
risperidone, olanzapine, dystonic reaction, parkinsonism, tardive
pimozide, haloperidol) dyskinesia
Reserpine and tetrabenazine Depends on drug Hypotension, depression,
parkinsonism

Tardive dyskinesia Stop the offending drug first — —

Dystonic dyskinesia Trihexyphenydil or benztropine Depends on drug Dry mouth, dry eyes, constipation,
only hypotension, cognitive impairment,
urinary retention
Clozapine or quetiapine Depends on drug Somnolence, confusion, and
agranulocytosis with clozapine

Reserpine or tetrabenazine Depends on drug Hypotension, depression,

parkinsonism

Akathisia Stop the offending drug first — —

No definitive drug therapy — —
(see text)
Restless limbs Ropinirole 0.25–3 mg qhs, or more Nausea, somnolence, leg edema,
often hypotension, hallucinations

Pramipexole 0.125–1.5 mg qhs, Nausea, somnolence, leg edema,

or more often hypotension, hallucinations

Controlled-release 50/200 1/2 tablet qhs, Nausea, hypotension, somnolence

carbidopa/levodopa or more often

Gabapentin (anticonvulsant) 300–600 mg qhs or more Somnolence, cognitive impairment,

often fatigue

Clonazepam 0.25 mg–1 mg qhs Somnolence, cognitive impairment,

or more often fatigue

Wilson’s disease Zinc acetate (blocks copper 50 mg t.i.d. Gastrointestinal upset and rarely
absorption) pancreatitis
Trientene (heavy metal 250 mg t.i.d. or q.i.d. Initial neurological worsening, bone mar-
chelator) row suppression, proteinuria, dermatitis
Penicillamine (heavy metal 250 mg t.i.d. or q.i.d. Similar to trientene
chelator)
b.i.d. = twice daily; q.i.d. = four times daily; mg = milligrams; qhs = at bedtime; REM = rapid-eye movement; SQ = subcutaneous;
SSRI = selective serotonin reuptake inhibitor; t.i.d. = three times daily.

234 P&T® • April 2005 • Vol. 30 No. 4


that persisted after the withdrawal of dopaminergic therapy.
Therefore, at present, fetal nigral transplantation is not a treat-
ment option for PD. The negative results from fetal tissue
transplantation have dampened the enthusiasm for stem-cell
therapy. At present, there are no large-scale stem-cell human
clinical trials for PD.
Other Movement Disorders
Dystonia
Dystonia may be classified by the body part affected or by
its etiology, including genetic forms.3,59
Dopa-responsive dystonia is a rare genetic disorder that
begins in childhood. Dystonia usually starts in one leg. There
is a diurnal fluctuation, and patients respond dramatically to rel-
atively low doses of levodopa.60
Drug-induced dystonia may occur acutely or as a tardive
phenomenon from exposure to neuroleptic agents, antiemetic
therapy, and promotility drugs with dopamine antagonist activ-
ity, such as prochlorperazine (Compazine®, GlaxoSmith
Kline), promethazine (Phenergan®, Wyeth) and metoclo-
pramide (Reglan®, Wyeth). Patients must avoid the offending
drug and similar drugs in the future, and they should use
centrally acting anticholinergic agents, such as benztropine
mesylate (Cogentin®, Merck) orally or intravenously.
Although focal dystonias may be treated initially with anti-
cholinergic agents, benzodiazepines, or muscle relaxants,
these drugs are somewhat ineffective at doses that would not
cause side effects. Therefore, botulinum toxin injections are
the first line of therapy for most focal dystonias, including tor-
ticollis, blepharospasm, and focal limb dystonia. In selected
cases, electromyographic guidance helps to localize the mus-
cles targeted for injection.
Treatment of generalized dystonia is more challenging,
because botulinum toxin cannot be injected at high doses in
multiple body parts. Anticholinergic agents, benzodiazepines,
muscle relaxants, and anticonvulsants are frequently used.
Other options for managing severe generalized dystonia
include intrathecal baclofen (Lioresal®, Novartis),61 tetra-
benazine (Xenazine™ or Nitroman®, Prestwick),62 and reser-
pine. 63 Tetrabenazine and reserpine act as monoamine
“depleters” and may cause depression, hypotension, and drug-
induced parkinsonism. Bilateral pallidal deep-brain stimulation
is effective in severe cases of generalized dystonia.64
Myoclonus
Myoclonus can be classified according to its site of origin,
its etiology, or the body part involved.4 Although the exact site
of myoclonus is difficult to determine, cortical, subcortical
(brainstem), and spinal (including propriospinal) types of myo-
clonus are described.
Physiological myoclonus occurs in normal subjects and
includes jerking movements during sleep as well as anxiety-
induced or exercise-induced myoclonus.
In essential myoclonus, there is no known cause and there
are no gross neurological deficits.
In symptomatic myoclonus, a progressive or static enceph-
CONTINUING EDUCATION CREDIT
alopathy exists, and myoclonus is one of the clinical signs.
In cortical myoclonus, the sensorimotor cortex is the site of
origination;65 therefore, cortical myoclonus is a fragment of
epilepsy, and its treatment frequently involves anticonvulsant
agents. The most commonly used drugs are valproic acid,
clonazepam, and primidone. Levetiracetam (Keppra®, UCB
Pharma) has emerged as an effective antimyoclonic drug,66
and it may also alleviate negative myoclonus, which has tradi-
tionally proved challenging to treat.67
Chorea
Chorea can be obser ved in patients with Huntington’s
disease, benign hereditary chorea, endocrine-mediated dis-
orders (e.g., hyperthyroidism), or autoimmune-mediated
disorders (e.g., Sydenham’s chorea and lupus). Chorea is a
major component of levodopa-induced dyskinesia in PD and
neuroleptic-induced tardive dyskinesia.
Therapy for chorea begins with treating the underlying con-
dition or reducing or stopping the drug that is potentially caus-
ing it. The next step depends on the cause.
In PD patients with levodopa-induced choreatic dyskinesia,
drug adjustments are necessary (see “Medical Therapy” on
page 230).
In neuroleptic-induced choreatic tardive dyskinesia, the
offending neuroleptic agent should be discontinued. If the
patient requires antipsychotic therapy, an atypical neuroleptic
agent should be used. Clozapine has proved the most effica-
cious among the neuroleptic drugs in alleviating tardive dysk-
inesia; however, it may cause agranulocytosis, and CBC mon-
itoring is necessary.68
Anticholinergic medications are not effective in alleviating
chorea. In Huntington disease, treatment of chorea begins
with a neuroleptic agent, but monoamine-depleting agents
may also be used. Benzodiazepines may help suppress chorea
in a variety of disorders.
Ballismus, a condition in which the limbs fling violently and
involuntarily, is rare. It usually occurs as hemiballismus, with
only one side affected, after an infarct in the contralateral STN.
The violent nature of ballismus dissipates over time, and the
movements become choreatic. Its treatment is similar to that
for chorea.
Tic Disorders
Tourette syndrome is a neuropsychiatric disorder character-
ized by motor and vocal tics.5 Depression and obsessive-
compulsive traits are common in Tourette syndrome and in tic
disorders in general. Therefore, treating the underlying psy-
chiatric conditions is extremely important in conjunction with
treating the movement disorder.69
Two classes of drugs are usually used as first-line therapy
to suppress tics: alpha2-adrenergic agonists and neuroleptic
agents.70 Guanfacine (Tenex®, A. H. Robbins) and clonidine
(Catapres®, Boehringer Ingelheim) are two alpha2-adrenergic
agonists that are less effective than neuroleptic drugs in sup-
pressing tics, but they have better side-effect profiles. Cloni-
dine is commonly used in the U.S. with a starting dose of 0.1
Vol. 30 No. 4 • April 2005 • P&T® 235
 CONTINUING EDUCATION CREDIT
mg daily in adults. The dose may be slowly increased to 0.4 mg
daily, and patients should be monitored for hypotension.
Haloperidol (Haldol®, Ortho-McNeil)and pimozide (Orap®,
Gate) have been the most commonly used neuroleptic agents
for the treatment of tics. However, atypical neuroleptic drugs
(e.g., risperidone, olanzapine, and quetiapine) have been also
used. The benzodiazepines and even cannabis have also been
used with variable success.
Monoamine-depleting drugs (e.g., reserpine and tetra-
benazine) suppress tics, but they should be used in conjunc-
tion with close monitoring for side effects.
For patients with dystonic tics, muscle relaxants, anticholin-
ergic agents, and other treatment modalities for dystonia,
including botulinum toxin injections, are used. Neuroleptic
therapy, which is frequently used to suppress myoclonic tics,
should be avoided in those with dystonic tic disorders.
Tardive Dyskinesia and Akathisia
Tardive dyskinesia is typically choreatic, dystonic, or a com-
bination of the two. It is usually a late complication of neuro-
leptic therapy, but it may occur rarely after repeated exposure
to promotility or antiemetic agents that have dopamine antag-
onist activity.68 Of course, it is best to prevent tardive syn-
dromes by using the lowest dose of an atypical antipsychotic
agent for the shortest possible duration.
Once tardive dyskinesia is present, its treatment can be
challenging. The data supporting the use of vitamin E and
benzodiazepines are weak, although the sedative and anxi-
olytic effects of the benzodiazepines may suppress abnormal
movements.
There are no large-scale head-to-head studies comparing
atypical neuroleptic agents among themselves. Clozapine and
quetiapine are associated with the lowest reported cases of tar-
dive dyskinesia.68 Therefore, the offending neuroleptic agent
should first be stopped. If the patient requires neuroleptic
treatment, quetiapine should be tried initially. However, if psy-
chosis prevails or tardive dyskinesia deteriorates, clozapine
therapy with CBC monitoring may be necessary.
Centrally acting anticholinergic drugs, such as benztropine
or trihexyphenidyl (Artane®, Lederle) may alleviate dystonic
dyskinesia, but they do little for choreatic dyskinesia.
Monoamine-depleting agents may also be used in intractable
cases of tardive dyskinesia.62
Neuroleptic-induced akathisia is characterized by dysphoria
and motor restlessness.8 Treatment of akathisia begins with
discontinuation of the offending neuroleptic agent. If the
patient requires neuroleptic therapy, using the lowest dose of
an atypical antipsychotic agent, preferably quetiapine, is rec-
ommended. A number of drugs, including beta blockers, anti-
cholinergics, clonidine, amantadine, and even opiates, have
been somewhat successful in alleviating akathisia.
Restless Limbs Syndrome
Restless limbs syndrome is a common disorder with a preva-
lence of 5% to 15% in Western countries.9 It is characterized by
a distressing desire to move the legs, with motor restlessness
236 P&T® • April 2005 • Vol. 30 No. 4
brought on by rest. Symptoms worsen in the evenings and at
night, and patients experience periodic limb movements dur-
ing sleep. Although the syndrome is sometimes observed in
patients with peripheral neuropathy, most of the time it is not
accompanied by neuropathy.
There is an association between restless limbs and a defi-
ciency of brain dopamine and iron deficiency.71 Therefore,
checking iron and ferritin levels is part of the evaluation for this
movement disorder.
If iron deficiency is detected, it should be evaluated (with an
anemia workup) and treated with iron supplementation. If a
sleep study reveals sleep apnea together with periodic limb
movements during sleep, the apnea should be treated.
Symptomatic treatment of restless legs and limb movements
during sleep usually begins with a dopamine agonist, such as
pramipexole or ropinirole.72 Dopamine agonists have longer
durations of action compared with levodopa, and one or two
evening or bedtime doses may suffice.
If dopamine agonists are not well tolerated, a controlled-
release formulation of carbidopa/levodopa should be tried
next, and the dose should be titrated as tolerated. Other adjunct
medications include gabapentin, benzodiazepines, and low-
potency opiates as a last resort.
Wilson’s Disease
Wilson’s disease is a rare autosomal recessive disorder of
copper metabolism that causes a buildup of the mineral in the
liver, brain, eye, and other organs. It is a disease of children,
adolescents, and young adults.73 The neurological manifesta-
tions include large-amplitude tremor, dystonia, chorea, and
ataxia.74
Neurological manifestations may occur in the absence of
hepatic disease. The diagnosis depends on a high index of sus-
picion, a low serum ceruloplasmin level, and high urinary
excretion of copper.
Medical therapies include (1) reducing copper in the diet
(foods such as shellfish, liver, mushrooms, some legumes,
chocolate, soy, bran, and avocado), (2) supplementing with
zinc, and (3) using chelating agents such as penicillamine or
trientine. In cases of chronic hepatic failure, liver transplanta-
tion is an option.
Conclusion
Advances in the treatment of PD and other movement dis-
orders continue to provide new strategies in symptomatic
management of motor and nonmotor symptoms. Atypical
neuroleptic agents have significantly reduced the incidence of
tardive dyskinesia. Newer or rediscovered older drugs, as
well as functional neurosurgery, have provided better relief of
motor fluctuations in PD. However, definitive neuroprotection
and effective restorative therapy for degenerative diseases
remain elusive. Neuroimaging techniques need to be refined
to enhance our ability to follow disease progression at the cel-
lular level. Future drug therapy for PD is focusing as much on
neuroprotection as on alleviating motor symptoms.

References
1. Elble RJ. Physiologic and essential tremor. Neurology 1986; 36(2):
225–231.
2. Samii A, Nutt JG, Ransom BR. Parkinson’s disease. Lancet 2004;
363(9423):1783–1793.
3. Langlois M, Richer F, Chouinard S. New perspectives on dystonia.
Can J Neurol Sci 2003(30 Suppl 1):S34–S44.
4. Rivest J. Myoclonus. Can J Neurol Sci 2003(30 Suppl 1):S53–S58.
5. Marcus D, Kurlan R. Tics and its disorders. Neurol Clin 2001;
19(3):735–758, viii.
6. Luquin MR, Scipioni O, Vaamunde J, et al. Levodopa-induced
dyskinesias in Parkinson’s disease: Clinical and pharmacological
classification. Mov Disord 1992;7(2):117–124.
7. Llorca PM, Chereau I, Bayle FJ, Lancon C. Tardive dyskinesias
and antipsychotics: A review. Eur Psychiatry 2002;17(3):129–138.
8. Chung WS, Chiu HP. Drug-induced akathisia revisited. Br J Clin
Pract 1996;50(5):270–278.
9. Schapira AH. Restless legs syndrome: An update on treatment
options. Drugs 2004;64(2):149–158.
10. Louis ED. Clinical practice: Essential tremor. N Engl J Med 2001;
345(12):887–891.
11. Watner D, Jurewicz EC, Louis ED. Survey of essential tremor
patients on their knowledge about the genetics of the disease. Mov
Disord 2002;17(2):378–381.
12. Louis ED, Ford B, Frucht S, et al. Mild tremor in relatives of
patients with essential tremor: What does this tell us about the
penetrance of the disease? Arch Neurol 2001;58(10): 1584–1589.
13. Chen JJ, Swope DM. Essential tremor: Diagnosis and treatment.
Pharmacotherapy 2003;23(9):1105–1122.
14. Jankovic J, Schwartz K, Clemence W, et al. A randomized, dou-
ble-blind, placebo-controlled study to evaluate botulinum toxin
type A in essential hand tremor. Mov Disord 1996;11(3):250–256.
15. Brin MF, Lyons KE, Doucette J, et al. A randomized, double-
masked, controlled trial of botulinum toxin type A in essential
hand tremor. Neurology 2001;56(11):1523–1528.
16. Pahwa R, Lyons KE, Wilinson SB, et al. Comparison of thalamo-
tomy to deep brain stimulation of the thalamus in essential tremor.
Mov Disord 2001;16(1):140–143.
17. Ward CD, Gibb WR. Research diagnostic criteria for Parkinson’s
disease. Adv Neurol 1990;53:245–249.
18. Calne DB, Snow BJ, Lee C. Criteria for diagnosing Parkinson’s dis-
ease. Ann Neurol 1992(32 Suppl):S125–S127.
19. Rajput AH. Frequency and cause of Parkinson’s disease. Can J
Neurol Sci 1992;19(1 Suppl):103–107.
20. de Rijk MC, Launer LJ, Berger K, et al. Prevalence of Parkinson’s
disease in Europe: A collaborative study of population-based co-
horts. Neurologic Diseases in the Elderly Research Group. Neu-
rology 2000;54(11 Suppl 5): S21–S23.
21. Lai BC, Schulzer M, Marion S, et al. The prevalence of Parkinson’s
disease in British Columbia, Canada, estimated by using drug
tracer methodology. Parkinsonism Relat Disord 2003;9(4):233–238.
22. Inzelberg R, Schechtman E, Paleacu D. Onset age of Parkinson
disease. Am J Med Genet 2002;111(4):459–460; author reply, 461.
23. Golbe LI. Young-onset Parkinson’s disease: Part 1. A clinical
review. Neurology 1991;41(2):168–173.
24. Huang Z, de la Fuente-Fernandez R, Stoessl AJ. Etiology of Parkin-
son’s disease. Can J Neurol Sci 2003(30 Suppl 1):S10–S18.
25. McNaught KS, Olanow CW, Halliwell B, et al. Failure of the ubiq-
uitin–proteasome system in Parkinson’s disease. Nat Rev Neurosci
2001;2(8):589–594.
26. The Parkinson Study Group. Effects of tocopherol and deprenyl
on the progression of disability in early Parkinson’s disease.
N Engl J Med 1993;328(3):176–183.
27. Schulzer M, Mak E, Calne DB. The antiparkinson efficacy of
deprenyl derives from transient improvement that is likely to be
symptomatic. Ann Neurol 1992;32(6):795–798.
28. A controlled, randomized, delayed-start study of rasagiline in
early Parkinson disease. Arch Neurol 2004;61(4):561–566.
29. Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10
in early Parkinson disease: Evidence of slowing of the functional
decline. Arch Neurol 2002;59(10):1541–1550.
CONTINUING EDUCATION CREDIT
30. Dopamine transporter brain imaging to assess the effects of
pramipexole vs. levodopa on Parkinson disease progression.
JAMA 2002;287(13):1653–1661.
31. Whone AL, Watts RL, Stoessl AJ, et al. Slower progression of
Parkinson’s disease with ropinirole versus levodopa: The REAL-
PET study. Ann Neurol 2003;54(1):93–101.
32. Brooks DJ, Frey KA, Marck KL, et al. Assessment of neuroimag-
ing techniques as biomarkers of the progression of Parkinson’s
disease. Exp Neurol 2003(184 Suppl 1):S68–S79.
33. Nutt JG, Burchiel KJ, Comella CL, et al. Randomized, double-blind
trial of glial cell line–derived neurotrophic factor (GDNF) in PD.
Neurology 2003;60(1):69–73.
34. Gill SS, Patel NK, Hotton GR, et al. Direct brain infusion of glial
cell line–derived neurotrophic factor in Parkinson disease. Nat
Med 2003;9(5):589–595.
35. Lang AE, Gill S, Brooks D, et al. Multicenter, double-blind, ran-
domized, placebo-controlled, phase 1/2 trial (RCT) of bilateral
intraputamenal (IPu) infusion of glial cell line–derived neuro-
trophic factor (GDNF) in levodopa-responsive Parkinson’s disease
(PD): Preliminary results. Ann Neurol 2004;56(5):17A.
36. Pramipexole vs. levodopa as initial treatment for Parkinson dis-
ease: A randomized controlled trial. Parkinson Study Group.
JAMA 2000;284(15):1931–1938.
37. Rascol O, Brooks DJ, Korczyn AD, et al., A five-year study of the
incidence of dyskinesia in patients with early Parkinson’s dis-
ease who were treated with ropinirole or levodopa. 056 Study
Group. N Engl J Med 2000;342(20):1484–1491.
38. Etminan M, Gill S, Samii A. Comparison of the risk of adverse
events with pramipexole and ropinirole in patients with Parkin-
son’s disease: A meta-analysis. Drug Saf 2003;26(6):439–444.
39. Nutt JG. Motor fluctuations and dyskinesia in Parkinson’s disease.
Parkinsonism Relat Disord 2001;8(2):101–108.
40. Schapira AH, Obeso JA, Olanow CW. The place of COMT
inhibitors in the armamentarium of drugs for the treatment of
Parkinson’s disease. Neurology 2000;55(11 Suppl 4):S65–S68;
discussion, S69–S71.
41. Assal F, Spahr L, Hadengue A, et al. Tolcapone and fulminant hep-
atitis. Lancet 1998;352(9132):958.
42. Factor SA. Literature review: Intermittent subcutaneous apomor-
phine therapy in Parkinson’s disease. Neurology 2004;62(6 Suppl
4):S12–S17.
43. Verhagen Metman L, Del Dotto P, van den Munckhof P, et al.
Amantadine as treatment for dyskinesias and motor fluctuations
in Parkinson’s disease. Neurology 1998;50(5):1323–1326.
44. McDonald WM, Richard IH, DeLong MR. Prevalence, etiology,
and treatment of depression in Parkinson’s disease. Biol Psychi-
atry 2003;54(3):363–375.
45. Stacy M. Sleep disorders in Parkinson’s disease: Epidemiology
and management. Drugs Aging 2002;19(10):733–739.
46. Etminan M, Samii A, Takkouche B, et al. Increased risk of som-
nolence with the new dopamine agonists in patients with Parkin-
son’s disease: A meta-analysis of randomised controlled trials.
Drug Saf 2001;24(11):863–868.
47. Fernandez HH, Trieschmann ME, Friedman JH. Treatment of
psychosis in Parkinson’s disease: Safety considerations. Drug
Saf 2003;26(9):643–659.
48. Burn DJ, McKeith IG. Current treatment of dementia with Lewy
bodies and dementia associated with Parkinson’s disease. Mov
Disord 2003(18 Suppl 6):S72–S79.
49. McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in
dementia with Lewy bodies: A randomised, double-blind, placebo-
controlled international study. Lancet 2000;356(9247):2031–2036.
50. Emre M, Aarsland D, Albanese A, et al. Rivastigmine for demen-
tia associated with Parkinson’s disease. N Engl J Med 2004;
351(24):2509–2518.
51. Aarsland D, Laake K, Larsen JP, et al. Donepezil for cognitive
impairment in Parkinson’s disease: A randomised controlled
study. J Neurol Neurosurg Psychiatry 2002;72(6):708–712.
52. Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment
in patients with moderate to severe Alzheimer disease already
receiving donepezil: A randomized controlled trial. JAMA 2004;
291(3):317–324.
Vol. 30 No. 4 • April 2005 • P&T® 237
 CONTINUING EDUCATION CREDIT
53. Lipp A, Trottenberg T, Schink T, et al. A randomized trial of bot-
ulinum toxin A for treatment of drooling. Neurology 2003;
61(9):1279–1281.
54. Deep-brain stimulation of the subthalamic nucleus or the pars
interna of the globus pallidus in Parkinson’s disease. N Engl J Med
2001;345(13):956–963.
55. Moro E, Scerrati M, Romito LM, et al. Chronic subthalamic nu-
cleus stimulation reduces medication requirements in Parkin-
son’s disease. Neurology 1999;53(1):85–90.
56. Lozano AM. Surgery for Parkinson’s disease. The five W’s: why,
who, what, where, and when. Adv Neurol 2003;91:303–307.
57. Freed CR, Greene PE, Kordower JH, et al. Transplantation of
embryonic dopamine neurons for severe Parkinson’s disease.
N Engl J Med 2001;344(10):710–719.
58. Olanow CW, Goetz CG, Kordower JH, et al. A double-blind con-
trolled trial of bilateral fetal nigral transplantation in Parkinson’s
disease. Ann Neurol 2003;54(3):403–414.
59. Bressman SB. Dystonia genotypes, phenotypes, and classification.
Adv Neurol 2004;94:101–107.
60. Furukawa Y. Update on dopa-responsive dystonia: Locus hetero-
geneity and biochemical features. Adv Neurol 2004;94:127–138.
61. Albright AL, Barry MJ, Shafton DH, et al. Intrathecal baclofen for
generalized dystonia. Dev Med Child Neurol 2001;43(10):652–657.
62. Jankovic J, Orman J. Tetrabenazine therapy of dystonia, chorea,
tics, and other dyskinesias. Neurology 1988;38(3):391–394.
63. Rojas VM, Davies RK. Reserpine treatment of comorbid Tourette’s
disorder and tardive dystonia. J Clin Psychiatry 1999;60(10):
709–710.
64. Kiss ZH, Doig K, Eliasziw M, et al. The Canadian multicenter trial
of pallidal deep brain stimulation for cervical dystonia: Prelimi-
nary results in three patients. Neurosurg Focus 2004;17(1):E5.
65. Mima T, Nagamine T, Nishitani N, et al. Cortical myoclonus: Sen-
sorimotor hyperexcitability. Neurology 1998;50(4):933–942.
238 P&T® • April 2005 • Vol. 30 No. 4
66. Schauer R, Singer M, Saltuari L, et al. Suppression of cortical myo-
clonus by levetiracetam. Mov Disord 2002;17(2):411–415.
67. Gelisse P, Crespel A, Genton P, et al. Dramatic effect of levetirac-
etam on epileptic negative myoclonus. Acta Neurol Scand 2003;
107(4):302–303.
68. Fernandez HH, Friedman JH. Classification and treatment of
tardive syndromes. Neurologist 2003;9(1):16–27.
69. Jankovic J. Tourette’s syndrome. N Engl J Med 2001;345(16):
1184–1192.
70. Leckman JF. Tourette’s syndrome. Lancet 2002;360(9345):
1577–1586.
71. Allen R. Dopamine and iron in the pathophysiology of restless legs
syndrome (RLS). Sleep Med 2004;5(4):385–391.
72. Silber MH, Ehrenberg BL, Allen RP, et al. An algorithm for the
management of restless legs syndrome. Mayo Clin Proc 2004;
79(7):916–922; erratum, 79(10):1341.
73. El-Youssef M. Wilson disease. Mayo Clin Proc 2003;78(9):
1126–1136.
74. Robertson WM. Wilson’s disease. Arch Neurol 2000;57(2):
276–277.
Disclosure
Dr. Ransom has no financial relationships to disclose.
Dr. Samii has indicated the following relationships: grant/
research support: Allergan, Medtronics. Speaker’s Bureau:
Boehringer-Ingelheim (unpaid).
 CONTINUING EDUCATION CREDIT

Continuing Education for Physicians and Pharmacists

P&T ® 2005;30(4):228–238
ACPE Program # 079-999-05-016-H01
Expiration Date: April 30, 2006
TOPIC: Movement Disorders: Over view and Treatment Options

CME Accreditation
This activity has been planned and implemented in accordance with the Essential Areas
and Policies of the Accreditation Council for Continuing Medical Education (ACCME)
through the joint sponsorship of Jefferson Medical College and MediMedia USA, Inc.

Jefferson Medical College of Thomas Jefferson University, as a member of the Consor-

tium for Academic Continuing Medical Education, is accredited by the Accreditation Council for Continuing Medical Educa-
tion to sponsor continuing medical education for physicians. All faculty/authors participating in continuing medical education
activities sponsored by Jefferson Medical College are expected to disclose to the activity audience any real or apparent con-
flict(s) of interest related to the content of their article(s). Full disclosure of these relationships appears on the last page of the
article.

Continuing Medical Education Credit

This CME activity is designed to assist physicians and other health care professionals who are P&T committee members in
making formulary decisions. Its goal is to increase participants’ ability to recognize and treat important medical problems.

Jefferson Medical College designates this continuing medical education activity for a maximum of one Category 1 credit
toward the Physician’s Recognition Award (PRA) of the American Medical Association. Each physician should claim only
those credits that he/she actually spent in the educational activity.

This credit is available for the period of one year from the date of publication.

Although forms will be processed when received, certificates for CME credits will be issued every six months, in February
and August. Interim requests for certificates can be made by contacting the Jefferson Office of Continuing Medical Education
at (215) 955-6992 or by going online to http://jeffline.tju.edu/jeffcme/.

Continuing Pharmacy Education Credit

The Department of Health Policy, Thomas Jefferson University Hospital, is approved by the Accreditation Council
for Pharmacy Education (ACPE) as a provider of continuing pharmaceutical education and complies with the
Criteria for Quality for continuing pharmaceutical education programming. This program (079-999-05-016-H01) is
acceptable for 1.0 hour of continuing education credit (0.1 CEUs) in states that recognize ACPE-approved pro-
viders. Statements of Credit indicating hours/CEUs will be mailed within six to eight weeks to participants who completed
this activity and submitted a completed evaluation with payment.

How to Apply for CE Credit

1. Each CE article is prefaced by learning objectives for participants to use to determine whether the article relates to their
individual learning needs.
2. Read the article carefully, paying particular attention to the tables and other illustrative materials.
3. Complete the questions and fill in the answers on the evaluation form on the next page.
4. Complete the CE Registration and Evaluation Form. Type or print your full name and address in the space provided,
and evaluate the activity as requested. In order for the form to be processed, all information must be complete
and legible.
5. Payment of $10 per exam is required for processing and maintenance of records. Make checks payable to P&T®. This
processing fee is non-refundable.
6. Send the completed form, answer sheet, and $10 payment to:
Department of Health Policy
Thomas Jefferson University
Attn: Continuing Education Credit
1015 Walnut Street, Suite 115
Philadelphia, PA 19107
7. Be sure to mail the Registration, Evaluation Form, and $10 payment within one year of the date of publication. After that
date, this article will no longer be designated for credit and forms cannot be processed.

Vol. 30 No. 4 • April 2005 • P&T® 239

 CONTINUING EDUCATION CREDIT
Continuing Education Questions for Physicians and Pharmacists
TOPIC: Movement Disorders: Over view and Treatment Options
ACPE Program # 079-999-05-016-H01
CE Evaluation: Select the one best answer to each of the following questions, and record your response on the
examination answer sheet. Complete the additional requested information. Forward the answer sheet, with appro-
priate payment, to the Department of Health Policy,Thomas Jefferson University Hospital, at the address indicated.
A certificate of completion will be mailed within six to eight weeks of receipt of your exam/payment. (A minimum
test score of 70% is required.)
Multiple Choice
Select the one correct answer.
1. Select the false statement concerning terminology
related to movement disorders:
a. Action tremor can be postural, intention, or task-specific.
b. Signs seen in Parkinson’s disease include tremor, rigidity,
bradykinesia, and postural instability.
c. Negative myoclonus is a sudden, brief muscle contraction,
whereas positive myoclonus is an interruption of muscle
contraction in the extended arm and wrist that causes
inhibition of the activated muscle.
d. Chorea resembles exaggerated fidgetiness.
2. Concerning movement disorders, select the false
statement:
a. “Writer’s cramp” is a focal hand dystonia.
b. The term choreoasthetosis refers to slow and writhing
movements.
c. Impaired motor coordination, ballismus, is characterized by
slurred speech, nystagmus, dysmetria, poor dexterity, and a
wide-based gait.
d. Dyskinesia in patients with Parkinson’s disease results from
the long-term complications of levodopa therapy.
3. The following statement is false for the treatment of
essential tremor:
a. The starting dose for primidone is 50 mg at bedtime, with
doses gradually increasing up to 750 mg daily.
b. Side effects associated with primidone include somnolence,
fatigue, cognitive problems, and ataxia.
c. Propranolol should be started at 50 mg daily and titrated as
tolerated to 320 mg daily.
d. Topiramate, gabapentin, benzodiazepine, and botulinum toxin
may help relieve tremor.
4. Which of the following statements is true regarding
neuroprotective agents for Parkinson’s disease?
a. There is no unequivocal agent available at this time.
b. Coenzyme Q10 may slow symptom progression in early
Parkinson’s disease.
c. Vitamin E was not beneficial in a large multicenter trial in
patients with early Parkinson’s disease.
d. all of the above
5. Which of the following statements concerning
dopamine agonists is false?
a. Dopamine agonists cause less dyskinesia than levodopa.
b. Dopamine agonists have more antiparkinson efficacy than
levodopa does.
c. Dopamine agonists may be used as monotherapy for the first
few years of Parkinson’s disease.
d. The side effects of dopamine agonists include nausea and
hypotension.
240 P&T® • April 2005 • Vol. 30 No. 4
6. Which of the following statements is true concerning
pharmaceutical treatments of nonmotor symptoms of
Parkinson’s disease?
a. Memantine was found to be effective in treating dementia
associated with Parkinson’s disease in large studies.
b. Risperidone is associated with fewer extrapyramidal adverse
drug effects compared with quetiapine in patients with
Parkinson’s disease.
c. Drooling and urinary urgency can be treated with peripheral
anticholinergic agents.
d. Levodopa is more likely than dopamine agonists to induce
hallucinations.
7. Regarding dystonia, which statement is incorrect?
a. Botulinum toxin injections are the first line of therapy for
most focal dystonias.
b. Focal dystonias may first be treated effectively with anti-
cholinergic agents, benzodiazepines, or muscle relaxants at
any dose with no insurgence of side effects.
c. Botulinum toxin is not appropriate for the treatment of
generalized dystonia.
d. Anticholinergic agents, benzodiazepines, muscle relaxants,
and anticonvulsants are frequently used to treat generalized
dystonia.
8. Which of the following statements is incorrect?
a. In patients with cortical myoclonus, the most commonly
used drugs are valproic acid, clonazepam, and primidone.
b. Benzodiazepines may help to suppress chorea in a variety of
disorders.
c. Anticholinergic medications are very effective in alleviating
chorea.
d. Clozapine has the most proven efficacy among neuroleptic
agents in alleviating tardive dyskinesia; however, it may cause
agranulocytosis, and blood count monitoring is necessary.
9. Which of the following classes of drugs is/are used to
treat tic disorders?
a. alpha2-adrenergic agonists
b. neuroleptic agents
c. benzodiazepines
d. all of the above
10. Regarding restless limbs syndrome, which statement is
incorrect?
a. There is an association between restless limbs and a
deficiency of brain dopamine and iron.
b. Symptomatic treatment of the syndrome begins with
dopamine agonists.
c. First-line medications include gabapentin and benzo-
diazepines.
d. If dopamine agonists are not well tolerated, a controlled-
release formulation of carbidopa/levodopa should be tried
next.
 Pharmacy and Therapeutics
CE Registration and Evaluation Form
Date of publication: April 2005
Title: Movement Disorders: Over view and Treatment Options
Authors: Ali Samii, MD, and Bruce R. Ransom, MD, PhD
Submission deadline: April 30, 2006 A Peer-Reviewed Journal for Managed Care
and Hospital Formulary Management

ACPE Program # 079-999-05-016-H01

Registration
Name: ____________________________________________________________ Degree: ____________________________________
Street address: ______________________________________________ Last 4 Digits of Social Security No. (Web ID): __________
City: ___________________________________ State: _________ Zip:__________ Telephone: _____________________________
E-mail Address: _______________________________________ Check one: ■ Physician ■ Pharmacist ■ Other
Time needed to complete this CE activity in hours: ■ 0.5 hr ■ 1 hr ■ 1.5 hr ■ 2 hr ■ Other _________________________

Certification: I attest to having completed this CE activity. ___________________________________________________________

Signature (required) Date _______________

Answer Sheet
Please fill in the box next to the letter corresponding to the correct answer
1. a ■ b ■ c ■ d ■ 6. a ■ b ■ c ■ d ■
2. a ■ b ■ c ■ d ■ 7. a ■ b ■ c ■ d ■
3. a ■ b ■ c ■ d ■ 8. a ■ b ■ c ■ d ■
4. a ■ b ■ c ■ d ■ 9. a ■ b ■ c ■ d ■
5. a ■ b ■ c ■ d ■ 10. a ■ b ■ c ■ d ■

Evaluation
Rate the extent to which: Very High High Moderate Low Very Low
1. Objectives of this activity were met ■ ■ ■ ■ ■
2. You were satisfied with the overall quality of this activity ■ ■ ■ ■ ■
3. Content was relevant to your practice needs ■ ■ ■ ■ ■
4. Participation in this activity changed your ■ ■ ■ ■ ■
knowledge/attitudes ■ ■ ■ ■ ■
5. You will make a change in your practice as a result ■ ■ ■ ■ ■
of participation in this activity
6. This activity presented scientifically rigorous, ■ ■ ■ ■ ■
unbiased, and balanced information
7. Individual presentations were free of commercial bias ■ ■ ■ ■ ■
8. Adequate time was available for Q&A ■ ■ ■ ■ ■
9. Which ONE of the following best describes the impact of this activity on your performance:
■ This program will not change my behavior because my current practice is consistent with what was taught.
■ This activity will not change my behavior because I do not agree with the information presented.
■ I need more information before I can change my practice behavior.
■ I will immediately implement the information into my practice.
10. Will you take any of the following actions as a result of participating in this educational activity (check all that apply)
■ Discuss new information with other professionals ■ Consult the literature
■ Discuss with industry representative(s) ■ Participate in another educational activity
■ Other ____________________________________ ■ None
Send the completed form and $10 payment (make checks payable to P&T) to: Department of Health Policy, Thomas Jefferson
University, Attn: Continuing Education Credit, 1015 Walnut Street, Suite 115, Philadelphia, PA 19107.

Vol. 30 No. 4 • April 2005 • P&T® 241

View publication stats