Title: Movement Disorders
1Movement Disorders
- Mary Quiceno, M.D.
- Neurology
2Hypokinetic HyperkineticMovement
Disorders
- Parkinsons disease
- Parkinsons Plus Syndromes
- PSP
- MSA
- SND
- OPCA
- CBD
- AD w/Lewy bodies
- LBD
- Tremor
- Dystonia
- Myoclonus
- Chorea
- Tics
- Akathisia
- Stereotypy
- RLS
3Basal Ganglia
4What is Parkinson's Disease?
- Parkinsonism is the name given to a collection of
symptoms and signs consisting of - Tremor
- Rigidity
- Bradykinesia
- Unsteady gait
5Parkinsonism
- 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.
6Evaluation by a neurologist is important for
several reasons
- All tremors are not Parkinsons 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.
7Parkinsonism
- 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
8Drug-induced Parkinsonism
- More common in elderly and women
- Symmetric onset of bradykinesia, tremor, and/or
rigidity - Onset within a few days to 3 months in 90 of
affected patients - Stop drug, try anticholingeric therapy
- New and Old Antipsychotics
- Risperdal
- Haldol
- Benzamides
- Reglan
- Phenothiazines
- Compazine
- Phenergan
- Others causing mainly postural tremors
- Lithium
- Depakote
- Amiodarone
9How 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
- Replace the dopamine, increase the lifetime of
the dopamine at the synapse, or stimulate the
dopamine receptors.
10Medications 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.
11Drug 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.
12Levodopa
- 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 preparationscarbidopa/levodopa
(Sinemet) 10/100, 25/100, or 25/250 tablets - Extended release preparationslevodopa/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.
13Catechol-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).
14Combined 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.
15Dopamine 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.
16Dopamine 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.
17Dopamine 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.
18The 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).
19Other 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.
20Deep 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
21Deep Brain Stimulation
22Essential 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.
23Videos
- Parkinsonism
- Tardive dyskinesia
- UPDRS
24Progressive Supranuclear Palsy
- ALL OF THESE FEATURES
- Onset at age 40 or later
- Progressive course
- Bradykinesia
- Impaired vertical gaze (voluntary downgaze lt15o)
- PLUS THREE OF THESE FEATURES
- Frequent falls as an early manifestation
- Prominent axial rigidity
- (neck rigidity gt limb rigidity)
- Neck hyperextended
- Early dysarthria
- Dysphagia
- Lack of tremor
- May see frontal lobe dementia
25Multiple 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.
26Corticobasal 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
27Lewy Body Dementia Alzheimers 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.
28Myoclonus
- 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