September 2008

Dr. Ted Rothstein

Click here to read Dr. Rothstein’s excellent article for American Scientist magazine entitled, “The Neglected Side of Parkinson’s Disease”.

Parkinson disease (PD) is named after James Parkinson who published a monograph in 1817 entitled “An Essay on the Shaking Palsy”. His conclusions were based on his observations of 6 people, and he noticed that the symptoms they had in common were tremors, bent forward posture and a festinating gait which he described as, “to pass from a walking to a running pace.”

• 200 out of every 100,000 people
• rare amongst people under 50 years of age (5% – 10%)
• 1% over 60 years of age
• 2% over 85 years of age
• more common with men than with women
• Parkinson disease will become more common as the population ages

Two different kinds of symptoms:
1) dopaminergic (related to dopamine levels): resting tremor, rigidity, slowness of movement, walking disorder, poker face, reduced blink, low volume, small handwriting
2) nondopaminergic (not related to dopamine): decreased sense of smell, constipation, drooling, choking, difficulty swallowing, depression, insomnia, forgetfulness, urgency in urination

It has been noted that people who suffer from constipation could be at higher risk for PD. In the Hawaiian Heart Study, involving 8,000 Japanese Americans on Oahu, they found that those men who had 3 or less bowel movements per week were at 5 fold risk of PD 20 years later.

Lewy bodies are named after Friedrich Lewy and are abnormal protein inclusions. They can be found in the colon years before they appear in the brain – hence the relationship to constipation and PD.
Lewy body disease is as a result of more protein and symptoms include more dementia, hallucinations and behavioral outbursts than PD.

Biochemical Basis – there is a depletion of the neurochemical dopamine.
At 50% loss there are no symptoms
At 70% loss there are early symptoms.
Late symptoms appear after a loss of 90% of dopamine

Medications can replace dopamine or stimulate dopamine receptors.
PET scans show dopamine levels in the brain.

Etiology of PD
specific cause is unknown
genetic cases – to date there 15 genetic mutations have been identified. These first came to light in a 1997 article in Nature magazine
Genetic factors are more common with young onset PD
Environmental factors are more common in those over 50 years old. These can include exposure to insecticides and drinking well water in rural   areas.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is an experimental toxin. It is a byproduct of Demerol synthesis and damages the mitochondria   resulting in diminished energy in the cells. People who took what they believed was Demerol but was in fact MPTP experienced Parkinson symptoms.   Because MPTP can cause Parkinson symptoms, it is used in research on animals.

Toxins affect cell structure. Proteasomes, are like a cellular garbage disposal for proteins. When these proteins aren’t disposed of they accumulate to become Lewy bodies and “gum up the works”. It would be ideal if medicine could find a way to stimulate the proteasomes to deal with the proteins and/or break up the Lewy bodies.

Stages of PD
early – no functional impairment
mild – honeymoon period
moderate – multiple drugs, occupational & social activities affected
severe – side effects from drugs (especially Levadopa), resistant to therapy, reduced quality of life
late – dependent in activities of daily living (ADLs) wheelchair or bed bound

Rasagiline (Azilect®)
George Washington University participated in a study to see if rasagiline could delay progression of PD and they are pleased with the results. There   was less deterioration although it did not affect the symptoms.

Levadopa monotherapy
• Has been the standard treatment since the 1960’s
• Is the most effective for reversing symptoms
• Side effects include dyskinesia (involuntary movement)
• Initially it lasts 6-8 hours but as the disease progresses it can last   3-4 hours or less and dyskinesias increase
• Side effects are possibly caused by the up and down levels of dopamine that are delivered with pills. When dopamine is produced naturally in the   brain, it is a steady dose.
• Diskinesias are a major source of disability.

Surgical options
Deep brain stimulation (DBS) offers a dramatic improvement in symptoms.
It is suitable for people who initially respond to Levadopa, are still having symptoms despite maximum therapy and have true PD. There can be no   mental health issues.
It reduces tremors, rigidity and slowness of movement. Levadopa levels can be reduced resulting in less dyskinesias.

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