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Parkinson Disease (cont.)

Parkinson Disease Causes

The challenge that remains is to discover how these neurons are destroyed to cause Parkinson disease.

Many theories have been put forward, but most researchers believe that Parkinson disease is not due to a single culprit but rather a combination of both genetic susceptibility and environmental stresses causing brain cell death.
Studies have found that living in a rural area, drinking well water, or being exposed to pesticides, herbicides, or wood pulp mills may increase your risk for developing Parkinson disease.
It has been demonstrated that 5-10% of people with PD have a genetic tendency. A recent study identified a specific gene mutation in a group of people who were related. Although this gene mutation is not responsible for all causes of PD, this finding may give scientists the opportunity to develop an animal model to gain insight into PD.
Currently, one of the most promising theories is the oxidation hypothesis.
- It is thought that free radicals may play a role in the development of Parkinson disease. Free radicals are chemical compounds with a positive charge that are created when dopamine is broken down by combining it with oxygen.
- This breakdown of dopamine by an enzyme called monoamine oxidase (MAO) leads to the formation of hydrogen peroxide.
- A protein called glutathione normally breaks down the hydrogen peroxide quickly. If the hydrogen peroxide is not broken down correctly, it may lead to the formation of these free radicals that then can react with cell membranes to cause cell damage and something called lipid peroxidation (when the hydrogen peroxide interacts with lipids [fat soluble substances] in the cell membrane).
- In PD, glutathione is reduced, which may mean that you have a loss of protection against the formation of these free radicals.
- Also, iron is increased in the brain and may help form free radicals.
- In addition, lipid peroxidation is increased in Parkinson disease.
- The association of Parkinson disease with increased dopamine turnover, decreased mechanisms (glutathione) to protect against free radical formation, increased iron (which makes it easier to create free radicals), and increased lipid peroxidation helps support the oxidation hypothesis.
- If this hypothesis turns out to be correct, it still does not explain why or how a loss of the protective mechanism occurs. An answer to this question may not be required. If the theory is correct, drugs may be developed to stop or delay these events.
Although the cause of Parkinson disease is not known, some people have symptoms of PD that may have an identifiable cause. In this case, the syndrome is known as parkinsonism or secondary PD.
It is thought that although primary parkinsonism, or Parkinson disease, is the most common type seen by neurologists, parkinsonism that is caused by drugs is probably far more common than reported and accounts for about 4% of all cases of parkinsonism.
- A change in the level of dopamine, whether by brain cell loss or drug use, can create the symptoms of PD.
- Interestingly, people who experience drug-induced parkinsonism may actually have a higher risk of developing PD later in life.
- A number of medications can cause parkinsonism by lowering dopamine levels. These are referred to as dopamine receptor antagonists or blockers.
- Nearly all antipsychotic or neuroleptic medications such as chlorpromazine (Thorazine), haloperidol (Haldol), and thioridazine (Mellaril) can induce the symptoms of parkinsonism.
- The medication valproic acid (Depakote), a widely use antiseizure medication, may also cause a reversible parkinsonism.
- Medications such as metoclopramide (Octamide, Maxolon, Reglan), which is used to treat certain stomach disorders such as peptic ulcer disease, are capable of causing parkinsonism or making it worse.
- Antidepressants known as selective serotonin-reuptake inhibitors may cause symptoms similar to parkinsonism.
Central to all these medications is their ability to alter the concentration of dopamine in the central nervous system.
Therefore a careful review of a medication list and ruling out of other causes such as brain tumors, stroke, infections, toxins, AIDS, and hydrocephalus must occur before the absolute diagnosis of Parkinson disease is made.