Parkinson's Disease : Trying to Find the Cause

by Food and Drug Administration (FDA)

(Page 3 of 3)

Parkinson's disease affects slightly more men than women and more whites than blacks in the United States. About three-quarters of all patients develop the disease between 50 and 65, though one person in seven develops it earlier, in the 30s or 40s. An estimated 1.5 million Americans have the disorder, according to the Parkinson's Disease Foundation.

The question of whether the disease has a genetic factor has been debated for years. Studies of both identical and fraternal twins, in which one twin had Parkinson's disease, showed that the unaffected twin had about the same frequency of the disorder as found in the general population.

"There is no definitive data to support whether Parkinson's is or is not hereditary," says Thomas Chase, M.D., chief, experimental therapeutics branch, National Institute of Neurological Disorders and Stroke, Bethesda, Md. "The mainstream thinking is that most Parkinson disease cases look as though they do not have any hereditary component whatsoever, on the face of it. The twin studies support that view ....

"But one can't be absolutely sure that there is no hereditary component in ordinary [idiopathic] Parkinson's disease, because there are two or three families around the world where Parkinson's is clearly hereditary."

A recent study of two large families from the same small town in southern Italy revealed that 41 family members in four generations, including members who emigrated to the United States, have had a particularly serious form of the disease. Genealogical studies of the two families showed a common ancestor dating to the early 1700s.

"Fortunately, these cases are exceedingly rare," says Chase. "So when a patient asks if Parkinson's can be inherited, the answer is the chance is one in a million."

Other experts debate whether Parkinson's disease has an environmental cause. The occurrence of the condition in couples married for many years, presumably eating the same diet in the same environment — in many cases in institutions — is exceptionally low. However, one researcher found that residents of three adjacent kibbutzim (community settlements) in Israel have five times the incidence of Parkinson's disease found in neighboring areas. Until recently, all three kibbutzim used drinking water from the same well, possibly contaminated by a nearby junkyard with rusting automobiles and tractor parts. Other researchers have also noted a higher risk of Parkinson's disease among rural populations who use well water.

Some, such as Donald M. Calne, D.M., University of British Columbia, argue that Parkinson's disease is not a specific disease entity, but rather a syndrome that may have either a genetic or environmental cause, depending on the particular case. Professor C.D. Marsden of the National Hospital for Nervous Diseases, London, U.K., writes in The Lancet (April 21, 1990): "A more complex theory is that the development of Parkinson's disease may be due to a combination of exposure to an environmental toxin with an inherited inability to adequately dispose of such a toxin."

The possibility that a virus or other infectious agent is responsible has been proposed, but sophisticated techniques have so far been unsuccessful in finding any such agent.

About 85 percent of patients who develop tremor, rigidity, slowness of movement, and minor signs have ordinary (or idiopathic — of no known cause) Parkinson's disease. Other patients with the same symptoms for which the cause is known have symptomatic or secondary parkinsonism. Parkinsonism can be induced by a variety of causes. One type is caused by drugs that block the dopamine receptors in the brain. The chief offenders are the antipsychotic drugs, such as Haldol, Thorazine, Loxitane, Stelazine, Mellaril, Prolixin, Compazine, Orap, and others of this class. Fortunately, these symptoms disappear when the drugs are withdrawn or the dose is lowered. (Benzodiazepine, or minor, tranquilizers such as Valium and Librium do not cause parkinsonism.)

The drug reserpine is prescribed in low doses to combat high blood pressure; in high doses, however, reserpine depletes dopamine in the brain and causes parkinsonism. Its effects are also reversible when use is discontinued.

Other chemicals are also implicated. In 1977, a young chemist in California synthesized a street narcotic that was contaminated with a byproduct known as MPTP. After several injections, he developed a tremor and was unable to move or speak. When he died in 1978 of a drug overdose, the autopsy showed irreversible damage to the brain's dopamine-producing systems.

In a study conducted in the province of Quebec, Canada, researchers found a strong correlation between the use of herbicides chemically related to MPTP, such as paraquat, and the development of Parkinson's disease. In one area where these types of herbicides were heavily used, the incidence of parkinsonism was seven times higher than in neighboring areas with low herbicide use.

Certain occupations are associated with the destruction of the dopamine-producing cells of the brain. Mechanics exposed to carbon monoxide, welders and miners exposed to manganese, and people in contact with mercury or carbon disulfide in rubber manufacture, for example, may have symptoms resembling those of parkinsonism.

Brain tumors, head injuries, strokes, tuberculosis, syphilis, subdural hematoma, degenerative diseases such as Alzheimer's, hereditary diseases (Huntington's chorea and Wilson's disease), or any other condition that damages the cells of the substantia nigra, may cause some degree of parkinsonism, but these cases are rare.

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