Movement Disorders

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Movement Disorders

• Mary Quiceno, M.D.
• Neurology

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Hypokinetic 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

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Basal Ganglia
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What is Parkinson's Disease?

• Parkinsonism is the name given to a collection of
  symptoms and signs consisting of
• Tremor
• Rigidity
• Bradykinesia
• Unsteady gait

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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.

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Evaluation 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.

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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

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Drug-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

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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
• Replace the dopamine, increase the lifetime of
  the dopamine at the synapse, or stimulate the
  dopamine receptors.

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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.

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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.

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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 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.

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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).

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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.

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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.

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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.

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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.

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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).

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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.

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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

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Deep Brain Stimulation
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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.

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Videos

• Parkinsonism
• Tardive dyskinesia
• UPDRS

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Progressive 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

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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.

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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

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Lewy 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.

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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