Parkinson Disease

I

Introduction

Parkinson Disease, disorder of the nervous system that affects muscle control. Marked by trembling of the arms and legs, muscular rigidity, and poor balance, Parkinson disease is slowly progressive, worsening over time. Eventually symptoms may cause problems with walking or talking and, in some people, difficulty thinking. Physicians do not know how to cure Parkinson disease, but drug therapy or surgery may alleviate some of the most troubling symptoms. The disease is named for British physician James Parkinson, who first described it in 1817. In a report describing six patients, Parkinson called the disorder paralysis agitans, Latin words that mean “shaking palsy.”

The National Parkinson Foundation based in Miami, Florida, estimates that 1.5 million people in the United States are affected with Parkinson disease, although estimates are difficult to make because symptoms of the disease are often mistaken for the normal effects of aging or are attributed to other diseases. Parkinson disease occurs in people all over the world, with the incidence in men slightly higher than in women. Caucasians have a higher incidence of the disease than people of other races. People most commonly develop Parkinson disease around the age of 60, and the incidence rises with age. However, at least 10 percent of cases occur in people under age 40, and a rare form of the disease affects teenagers.

Parkinson disease may initially be mistaken for one or more of a group of nervous system diseases collectively known as parkinsonism (also known as Parkinson Plus diseases), all of which have certain symptoms in common. Unlike most cases of Parkinson disease, most forms of parkinsonism develop from an identifiable cause, such as exposure to certain chemicals, drugs, or viruses. Often initially diagnosed as Parkinson disease, parkinsonism diseases do not respond to the drug therapies that treat Parkinson disease symptoms effectively. Physicians have also noted that the changes in the nervous system in people who have parkinsonism differ from those in patients who have Parkinson disease.

II

Cause

Parkinson disease develops as a part of the brain known as the substantia nigra degenerates. The substantia nigra is located in the midbrain, halfway between the cerebral cortex and the spinal cord. In healthy people, the substantia nigra contains certain nerve cells, called nigral cells, that produce the chemical dopamine. Dopamine travels along nerve cell pathways from the substantia nigra to another region of the brain, called the striatum. In the striatum, dopamine activates nerve cells that coordinate normal muscle activity. In people with Parkinson disease, nigral cells deteriorate and die at an accelerated rate, and the loss of these cells reduces the supply of dopamine to the striatum. Without adequate dopamine, nerve cells of the striatum activate improperly, impairing a person’s ability to control movement.

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A study published in 2000 found that people with Parkinson disease have a decreased number of nerve fibers in the heart. These results suggest that the disease affects nerves in organs outside the brain and may explain symptoms common in people with Parkinson disease, such as a drop in blood pressure when a person stands up, constipation, and difficulty urinating.

Scientists do not understand the mechanisms underlying nerve cell death in Parkinson disease. Most researchers believe that Parkinson disease results from a combination of factors involving genetics, environmental agents, and abnormalities in cellular processes.

A

Genetics

Studies suggest that genetic makeup may place a person at higher risk for developing Parkinson disease. Fifteen percent of people with Parkinson disease have one or more family members who also have the disease. In studies of families in which members from at least three generations have been diagnosed with the disease, scientists have identified three genes that, when mutated, may play a role in the development of Parkinson disease. Genes provide coded instructions for the manufacture of proteins. One of the suspect genes codes for a protein called alpha-synnuclein. A second gene codes for a protein called parkin, and a third gene codes for a protein belonging to a family of proteins known as ubiquitin. Researchers still do not understand the function of alpha-synnuclein, but parkin and ubiquitin may play a role in cleaning up abnormal deposits of proteins in the cell. When the genes that produce these proteins are mutated, parkin and ubiquitin are unable to prevent protein deposits from building up. The accumulation of these deposits may play a role in nigral cell degeneration.

A recent study among identical twins also suggests that genetics plays a role in Parkinson disease. In the study, doctors found that if one twin developed the disease before age 50, the chance was higher that the other twin would develop the disease if the twins were identical than it was if they were fraternal. Identical twins have the same genetic makeup, whereas the genes of fraternal twins are as different as those of any two siblings. This study suggests that the identical twins both have a gene that places them at risk for the disease.

B

Environmental Factors

Given the obvious symptoms associated with Parkinson disease, such as tremor and imbalance, it is odd that the first description of the disease did not appear until 1817. Some researchers propose that the disease may have been uncommon before the Industrial Revolution, the period starting in the 18th century when machinery began replacing manual labor. The increased number of patients diagnosed with the disease today may be related to the presence of an environmental toxin (poisonous chemical) released as a byproduct from machines and other technology. Alternatively, the higher incidence of the disease may be related to increasingly longer life spans that enable people to reach an age when the physical effects of Parkinson disease become more apparent.

Scientists have yet to identify a particular drug or toxin that causes Parkinson disease, although they have identified a number of drugs, chemicals, and viruses that cause diseases that resemble Parkinson disease. The chemical MPTP, a byproduct created in the synthesis of certain illicit drugs, is linked to the development of a disease in some drug abusers that closely resembles Parkinson disease. People who use some common garden pesticides and insecticides also seem to have a higher incidence of Parkinson disease, although a direct link between Parkinson disease and these chemicals has not yet been established. Certain people may develop parkinsonism if they are exposed to other agents, including carbon monoxide, cyanide, manganese, certain tranquilizers, and some rare viruses, or if they suffer head injuries or strokes. These parkinsonism diseases may be initially mistaken for Parkinson disease.