Movement Disorders

Mary Quiceno, M.D. Neurology

Hypokinetic & Hyperkinetic Movement Disorders

Parkinsons disease  Parkinsons Plus Syndromes


PSP MSA SND OPCA CBD AD w/Lewy bodies LBD

Tremor  Dystonia  Myoclonus  Chorea  Tics  Akathisia  Stereotypy  RLS



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 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 longmay 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 non-

DrugDrug-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

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.

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 LLtyrosine.  DA is inactivated after release by reuptake.  It can be repackaged or degraded by MAOMAOA & 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. 3Food (in particular, protein-rich food) delays absorption of levodopa. proteinInstruct patients to take levodopa 1 hour before meals. Levodopa is also available in a "controlled-release" (CR or SR) formulation. "controlledControlled 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.

CatecholCatechol-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 (Comtan)--available 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, attacks, 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 10%31%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 dopaminedopamine-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 MAOthe 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 (MAOmg.

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 goaland may be present at rest.  Flexion-extension movements at the wrist Flexionor adduction-abduction movements of the adductionfingers or pronation-supination seen. pronation 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 o Impaired vertical gaze (voluntary downgaze <15 )

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 Shy Akinetic,

rigid parkinsonism with early and prominent autonomic dysfunction (urinary incontinence, postural hypotension, upper airway obstruction, arrhythmias). rigid parkinsonism unresponsive to

Striatonigral Degeneration
 Akinetic,

L-dopa.

Olivopontocerebellar Atrophy
 Parkinsonism

and cerebellar ataxia.

Corticobasal Ganglionic Degeneration

 Rigid-bradykinetic Rigid-

parkinsonism with

cortical signs:
Apraxia Cortical sensory loss Alien hand phenomenon
 Asymmetric

onset, dystonic limb postures, myoclonus, and L-dopa Lunresponsiveness are features

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.

Myoclonus
Sudden, shock-like muscle contractions shock Random and irregular  Common manifestations:


Action myoclonus
Induced by voluntary movement  Seen with metabolic abnormalities, metabolic encephalopathy, lithium toxicity, CJD


Lance-Adams syndrome Lance

Action myoclonus seen after cerebral anoxia negative myoclonus (brief lapses of posture) seen in metabolic encephalopathy

Asterixis