Movement Disorders

Mary Quiceno, M.D.

Neurology
 Hypokinetic & Hyperkinetic
Movement Disorders
 Parkinson’s disease  Tremor
 Parkinson’s Plus  Dystonia
Syndromes  Myoclonus
– PSP  Chorea
– MSA
 Tics
– SND
 Akathisia
– OPCA
– CBD  Stereotypy

– AD w/Lewy bodies  RLS

– LBD
Basal Ganglia
What is Parkinson's Disease?
 Parkinsonism is the name given
to a collection of symptoms and
signs consisting of:
– Tremor
– Rigidity
– Bradykinesia
– Unsteady gait
 Parkinsonism
 Many neurological disorders have
features of parkinsonism.

 When parkinsonism occurs without

any other neurological abnormalities,
and there is no recognizable cause of
it, the disorder is termed Parkinson's
disease
– after the English physician who first
described it fully in 1817.
 Evaluation by a neurologist is
important for several reasons:
All tremors are not Parkinson’s
disease.
– There are many causes of tremor. It should not be assumed that
someone has PD unless the tremor has all the features of the tremor
that is known to occur in PD and other causes of tremor have been
excluded.

Parkinsonism is a symptom of
many disorders.
– There are a variety of disorders in which parkinsonism occurs without
obvious cause, but these disorders usually have additional features
that distinguish them from classic PD. Such a distinction is important
because the long-term outlook may differ and the treatment options
may be different.
 Parkinsonism
 Exclusion criteria for PD
– Neuroleptics
– Toxin exposure (MPTP, CO, Mn, Methanol)
– Encephalitis
– Stroke
– Head injuries
– Early and severe dementia or autonomic
dysfunction
– Levodopa non-responder
 Drug-induced Parkinsonism
 More common in  New and Old
elderly and women Antipsychotics
– Risperdal
– Haldol
 Symmetric onset of
bradykinesia, tremor,  Benzamides
and/or rigidity – Reglan
 Phenothiazines
 Onset within a few – Compazine
days to 3 months in – Phenergan
90% of affected
patients  Others causing mainly
postural tremors:
 Stop drug, try – Lithium
anticholingeric therapy – Depakote
– Amiodarone
 How is Parkinson's Disease
Treated?
 A number of treatment approaches help
patients with Parkinson's disease.
– General lifestyle modifications (rest and
exercise)
– Dietary considerations
– Physical therapy and speech therapy
– Medications and surgery
 Replacethe dopamine, increase the lifetime of the
dopamine at the synapse, or stimulate the dopamine
receptors.
 Medications for Parkinson's
disease
 Levodopa (carbidopa/levodopa; Sinemet)
– Reduces the symptoms.
– Carbidopa prevents peripheral break down of
levodopa.
 Minimum of 75 mg/d to avoid nausea.
– Treatment over a number of years may lead to
variability in an individual's response to
treatment, called "motor fluctuations."
– Another form of motor fluctuation is
uncontrolled writhing movement of the body or
a limb, which is called "dyskinesia."
 40% will develop motor fluctuations within six years
of treatment.
Drug Targets
 DA is made from
the amino acid L-
tyrosine.
 DA is inactivated
after release by
reuptake.
 It can be
repackaged or
degraded by MAO-
A & B and COMT.
 Levodopa
 Levodopa is rapidly absorbed from the small intestine. Most patients
experience improvement in symptoms about 30 minutes after a dose, and
the benefit lasts about 3-5 hours.

 Food (in particular, protein-rich food) delays absorption of levodopa. Instruct

patients to take levodopa 1 hour before meals.
 Levodopa is also available in a "controlled-release" (CR or SR) formulation.
Controlled release levodopa provides a longer duration of action by
increasing the time it takes for the gastrointestinal tract to absorb levodopa.
However, CR only allows 70% of the levodopa to be absorbed by the
gastrointestinal tract
 Levodopa preparations
– Standard release preparations
carbidopa/levodopa (Sinemet®): 10/100, 25/100, or 25/250 tablets
– Extended release preparations
levodopa/carbiopa (Sinemet CR®): 25/100 or 50/200 tablets

 Side effects include nausea, vomiting, dry mouth, dyskinesias, and

dizziness. In some individuals, levodopa may cause confusion,
hallucinations, or psychosis.
 Catechol-O-methyl transferase
(COMT) inhibitors
 Like carbidopa, COMT inhibitors prevent the breakdown of
levodopa which prolongs the duration of action of a dose of
levodopa.

 COMT inhibitors may be prescribed when an individual experiences

"wearing off," particularly when dopamine agonists (see below)
are not tolerated.

 Entacapone (Comtan®)--available in the United States and many

other countries.
200 mg tablets usually given with each dose of levodopa.
 Side effects include diarrhea, vivid dreams, visual hallucinations,
drowsiness, urine discoloration, and dyskinesias. Fulminant
hepatic failure has been reported in are patients receiving
tolcapone (Tasmar®).
 Combined carbidopa, levodopa
and entacapone
 This preparation combines all 3 medications in one pill,
which may be more convenient but may not be as flexible
as taking the medications individually.

 Doses:
– Stalevo® 50: 50 mg levodopa, 12.5 mg carbidopa, and 200
mg entacapone
– Stalevo® 100: 100 mg levodopa, 25 mg caridopa and 200 mg
entacapone
– Stalevo® 150: 150 mg levodopa, 37.5 mg carbidopa, and 200
mg entacapone

 Side effects of this combined preparation are the same as

for levodopa and entacapone and include: diarrhea, vivid
dreams, visual hallucinations, drowsiness, urine
discoloration and dyskinesias.
 Dopamine agonists

 They may be used in place of levodopa or

in combination with it.

 Cause less motor fluctuations.

 More likely to cause a number of side

effects (such as nausea, somnolence, sleep
attacks, postural hypotension,
hallucinations, neuropsychiatric disorders,
and lower extremity edema), particularly
in patients over 70 and those with baseline
cognitive deficits.
 Dopamine agonists
 Bromocriptine and pergolide (Permax ®) are ergot
derivatives.
– May rarely cause retroperitoneal, pulmonary and
pericardial fibrosis.
– Many reports of significant cardiac valve dysfunction
requiring replacement due to pergolide.

 Pramipexole (Mirapex ®) and ropinirole (Requip ®) are not

ergot compounds.
– Can be used in early Parkinson's disease and reduce the
severity of symptoms.
– One side effect is daytime sleepiness and "sleep
attacks." Although this may occur with all of the
dopamine agonists (and levodopa), it was first
appreciated in people treated with pramipexole.
 Dopamine agonists
 The response to a particular dopamine
agonist is idiosyncratic.

 If one dopamine agonists does not offer

benefit or causes bothersome side effects,
another agonist may be tried.

 Treatment with dopamine agonists often

begins at a very low dose. The dose is
increased at intervals (depending on the
agent) until benefit occurs.
The case for starting treatment with
a dopamine agonist
 Less dyskinesias
– 10%-20% versus 31%-45% during the first 2 to 5 years of
treatment.
 Less wearing off
– 24% versus 38%.

 Dopamine agonists may slow the progression of Parkinson's

disease.
– During a 4 year study of patients with early PD treated with
levodopa or pramipexole, those patients treated with
pramipexole may experience neuroprotection of dopamine-
releasing neurons as demonstrated by SPECT.
– Those treated with ropinirole lost less fluorodopa signal than those
treated with levodopa over the course of the study as documented
by PET scanning.

 Trade off: More frequent side effects (drowsiness,

hallucinations, generalized swelling and leg swelling).
 Other medications
 Amantadine
– Reduces fatigue and tremor and dyskinesias.
– Amantadine (Symmetrel®) as 100 mg capsules or in liquid form.
– Side effects may include difficulty concentrating, confusion, insomnia,
nightmares, agitation, headache, hallucinations, edema and livedo reticularis.

 Anticholinergic medications
– Reduce tremor and/or rigidity.
– Benztropine mesylate (Cogentin®): 0.5 mg, 1 mg, 2 mg tablets or
Trihexyphenidyl (Artane®): 2 mg and 5 mg tablets as well as liquid form.
– Side effects may include dry mouth, blurred vision, sedation, delirium,
hallucination, constipation, and difficulty urinating.

 Selegiline
– MAO-B (monoamine oxidase B) inhibitor prolonging the action of dopamine in
the brain. It also has a mild antidepressant effect.
– Eldepryl®: 5 mg capsule.
– Side effects may include heartburn, nausea, dry mouth, insomnia and dizziness.
Confusion, nightmares, hallucinations, and headache occur less frequently and
should be reported to your doctor.
 Rasagiline (Agilect ®)
– Soon to be released DA (MAO-B inhibitor) taken once daily in doses of 0.5 or 1
mg.
 Deep Brain Stimulation
 Unlike lesion procedures, DBS leaves electrodes in place in the
brain to deliver continuous stimulation.

 Adjusting the stimulator and medications after electrode

implantation is a major time commitment on the part of the
neurological team and patient.

 Risks for DBS procedures include surgical risks (hemorrhage,

infection) as well as hardware complications. These include leads
breaking, electrode malfunction, stimulator failure and battery
failure.

 Subthalamic Deep Brain Stimulation (DBS) improves dyskinesias

and off time. It allows for a reduction in medication.

 Neuropsychiatric adverse events have been increasingly reported.

– Depression
– Suicide
Deep Brain Stimulation
 Essential Tremor
 Typically a postural tremor, but it may be
accentuated by goal-directed movements
and may be present at rest.
 Flexion-extension movements at the wrist
or adduction-abduction movements of the
fingers or pronation-supination seen.
 Alcohol ameliorates tremor.
 Often there is a family history.
 No features of PD present.
 Check thyroid.
 Videos

– Parkinsonism
– Tardive dyskinesia
– UPDRS
Progressive Supranuclear Palsy
 ALL OF THESE FEATURES
– Onset at age 40 or later
– Progressive course
– Bradykinesia
– Impaired vertical gaze (voluntary downgaze <15o)
 PLUS THREE OF THESE FEATURES
– Frequent falls as an early manifestation
– Prominent axial rigidity
 (neck rigidity > limb rigidity)
 Neck hyperextended
– Early dysarthria
– Dysphagia
– Lack of tremor
 May see frontal lobe dementia
 Multiple Systems Atrophy
 Three presentations:
– Shy-Drager Syndrome
 Akinetic,
rigid parkinsonism with early and
prominent autonomic dysfunction (urinary
incontinence, postural hypotension, upper
airway obstruction, arrhythmias).
– Striatonigral Degeneration
 Akinetic, rigid parkinsonism unresponsive to
L-dopa.
– Olivopontocerebellar Atrophy
 Parkinsonism and cerebellar ataxia.
 Corticobasal Ganglionic Degeneration

 Rigid-bradykinetic parkinsonism with

cortical signs:
– Apraxia
– Cortical sensory loss
– Alien hand phenomenon

 Asymmetric onset, dystonic limb

postures, myoclonus, and L-dopa
unresponsiveness are features
 Lewy Body Dementia &
Alzheimer’s disease with Lewy Bodies

 Pathologically Lewy bodies can be seen

with AD pathology or they can cause a
dementia by themselves.

 LBD = dementia, fluctuating level of

awareness, visual hallucinations,
parkinsonism, and sensitivity to
neuroleptics

 It is common to see parkinsonism develop

in patients with AD.
 Myoclonus

 Sudden, shock-like muscle contractions

 Random and irregular
 Common manifestations:
– Action myoclonus
 Induced by voluntary movement
 Seen with metabolic abnormalities, metabolic
encephalopathy, lithium toxicity, CJD…
– Lance-Adams syndrome
 Action myoclonus seen after cerebral anoxia
– Asterixis
 negative myoclonus (brief lapses of posture) seen in
metabolic encephalopathy