What is Parkinson's Disease?

Parkinson's disease or Parkinsonism is named for the English physician James Parkinson. His description of the various manifestations of the disease was published in 1817, in a work entitled "An Essay on the Shaking Palsy." He used the terms" shaking palsy" or "paralysis agitans" to describe a group of related symptoms, which he carefully observed and recorded. It is now known that this neurological disorder is caused by damage to certain areas of the brain. The main symptoms of the disease are tremor while at rest and abnormal movements of the arms and legs while standing or walking. These are accompanied by a number of other symptoms, including speech problems, a stiff, bent-over position, insomnia, and constipation.

All related disorders are attributed to a malfunction of the basal ganglia (which contain a rich array of neurotransmitters and receptors controlling muscular movements) and of the substantia nigra (where dopamine is produced). Dopamine is one of the brain chemicals involved in the control of physical movement, and Parkinsonism is characterized by dopamine depletion. Secondary Parkinsonism, in which symptoms are of a passing nature, is due to temporary dopamine depletion, induced most commonly by antipsychotic drugs.

Cause

The basal ganglia control movements of the muscles, muscle tone, balance, coordination of groups of muscles that oppose each other, and the change of state necessary for muscles to go from rest to motion. Control from this section of the brain also enables some muscles to remain at rest while others are in action. In a healthy state, signals pass from the motor cortex of the brain to the reticular formation and spinal cord and then to the various muscles that are to undergo contraction. At the same time, other signals follow a different pathway through the basal ganglia, where the nerve signal is dampened (subdued or toned down) so that the resulting contraction does not become jerky (too sudden or quick). Dopamine, found in the basal ganglia, is the neurotransmitter responsible for the dampening effect of the motor signal. If the dampening effect should become too strong, then another neurotransmitter, acetylcholine, counteracts the effects of the dopamine, thus maintaining a balance in the force of the signals sent to the muscle.

In Parkinson's disease, degeneration of the basal ganglia, along with damage to the dopamine-producing cells of the substantia nigra, hampers the proper functioning of the nerve pathway that controls movements of the muscles. The muscles become excessively tense, a condition that gives rise to tremor and a rigid joint action. The movements of the body also begin to slow down as a result of this malfunction. Drug treatments are designed to increase the level of dopamine or inhibit the release of acetylcholine, which counteracts dopamine.

Damage to the basal ganglia may be caused by an environmental factor, such as an unknown toxic chemical. Another supposition is that an early viral infection causes the degeneration. Parkinsonism may follow encephalitis or other forms of brain injury. In 1997, researchers located a specific gene defect which seems to be responsible for some familial cases of Parkinson's disease.

The disease is not contagious, and while it generally affects older people, there are also cases of juvenile Parkinsonism. Cases involving younger people who had used street drugs of unknown composition and developed full-blown symptoms of the disease as a result have been reported. Some of these cases were favorably treated with implantations of dopamine-producing tissues from fetal brain cells.

Incidence and symptoms

In the United States there are about one million people who suffer from Parkinson's disease (1 person in 100 over the age 60), and each year 50,000 new cases are reported. The elderly are most vulnerable to the condition, with men showing a greater tendency toward the disease than women. In about 15% of cases, symptoms of the disease begin to show when patients are in their 40s, but the majority of cases occur somewhat later. Parkinson's disease is most prevalent in people between the ages of 70 and 80. Those who smoke seem to show a lower incidence of the disorder. While there is no cure for the disease and the factors responsible for the brain damage are not fully understood, the mechanism of brain-cell deterioration and the brain chemicals involved has been carefully studied.

At the beginning of the illness, one side of the body may begin to exhibit symptoms. Eventually, however, the disorder spreads to both sides of the body. At first there are signs of difficulty in walking and other basic movements of the body, such as turning, rising from a seated position, standing, and sitting down. These movements seem labored and become difficult to perform. Body movements slow down, and they are executed very carefully with much deliberation. The muscles at rest are so tense that they become rigid. Simple facial movements become difficult to execute because of this rigidity of muscle tone. The face begins to look like a mask. Walking movements become altered. Instead of the natural arm swing, the arms hang limply at the side. The patient shuffles while walking, and sideways turns of the head are replaced by whole body movements.

Tremor is one of the characteristic signs of Parkinsonism, but not all patients actually display that symptom. While it is immediately obvious and recognizable, tremor is not necessarily more of a disability than the other symptoms of the disorder. Tremor occurs while the patient is at rest and is reflected mostly in the hands, in spasms entailing a rolling motion of various fingers. Other parts of the body may also be involved in the tremor, notably the lips and the head. While the Parkinson's patient is involved in some task, the tremor may relent for a short period of time.

Some patients undergo a general decline of mental ability (dementia). They begin to forget recent events, get lost in a known neighborhood, or fail to comprehend what is going on about them. The skin becomes excessively oily, a condition known as seborrhea, particularly in the areas of the face and scalp. Blood pressure may also begin to fluctuate over a wide range, and these fluctuations create further difficulties in treatment. Toward the later stages of the disease, when all of these symptoms are present, some patients become totally helpless.

Diagnosis

Only a postmortem examination provides conclusive evidence of Parkinsonism, while a live clinical neurological examination may present difficulties in diagnosis. Certain symptoms readily show the presence of the disease, such as tremor, slow body movements, and the inability to perform joint motor activities. There are, however, other conditions that can be mistaken for Parkinsonism because they are also characterized by the tremor syndrome and certain other symptoms.

While the exact cause of Parkinsonism can only be determined at autopsy, a clinical diagnosis when the patient is still alive allows doctors to prescribe the most effective treatment. The physician begins a diagnosis with the patient's general medical history along with a careful examination. In the absence of certain symptoms of the disease, an experienced physician may be able to exclude Parkinson's disease and search for other causes of neurological impairment, such as tumors of the brain, especially in the cerebellum which controls balance. A CAT scan is used to determine the presence or absence of brain tumors. The appearance of tremor is carefully studied to determine whether or not it qualifies as a symptom of Parkinsonism. New diagnostic methods allow physicians to target the affected brain areas precisely. An analysis of cerebrospinal fluid along with magnetic resonance imaging (MRI) can reveal damage to areas of the brain like the substantia nigra. An increase in lipid (fat) oxidation in the substantia nigra suggests that free radicals are damaging nerve cells producing dopamine. If that is the case, antioxidants and scavengers that destroy free radicals may improve the symptoms.

Treatment

There are organizations that can give families help in learning how to manage the illness in its early stages. Exercise is important along with special aids to help movement. Drug therapy is important in later stages of the disease when symptoms become debilitating if left untreated. The drug treatment is complex because dosages have to be carefully regulated and different combinations of drugs have to be used.

Despite certain severe side effects, the drug levodopa (l-dopa) is currently used as the most effective medication in the treatment of Parkinson's disease. Some of the adverse side effects are disorders of the digestive system, hemorrhage, disturbances in heart rhythm, depression, confusion, possible psychotic reactions, and delirious episodes. The extent of these reactions appears to be dependent on the amount of medication used. In some patients the mask-like facial expression gives way to distorted facial expressions, and other unusual body movements may result from the use of the drug.

A combination drug called Sinemet composed of levodopa and carbidopa (a drug that alleviates levodopa's side effects) is given in careful dosages often requiring changes in the amount taken. Patients respond differently to this combination drug. Some will be able to take it hourly, others just three times daily.

For all of its adverse side effects, l-dopa has helped many sufferers from Parkinsonism to deal with their illness. Other drugs, which are not as effective but do have fewer side effects, are sometimes used for milder cases of Parkinson's disease. Two such drugs are bromocriptine and amantadine. Anticholinergic drugs are used to deal with tremor. These drugs can be used alone or in combination with l-dopa. Sometimes they are used to help diagnose a questionable condition. They are not noted for providing important long-term relief.

In order to replace the dopamine in 100 Parkinson's disease patients, Swedish and American doctors have used brain cells from fetal brains for brain implantation. Although the results of this experimental procedure were highly favorable, there has been resistance against this form of treatment because the brain cells were taken from aborted fetuses. Adrenal tissue that produces dopamine is now being used for experimental purposes instead.

Surgerical procedures to inactivate certain areas of the brain have sometimes been helpful in restoring movement for some younger Parkinsonism patients who have stopped responding to various medical therapies. Two such procedures are the thalamotomy and the palidotomy. While symptoms may be dramatically relieved, the outcome of the treatment is still being studied. Another surgical intervention involves implanting a device to provide electrical stimulation to areas of the brain deprived of dopamine. Still more research is being done to find a substance which could potentially prevent the cells within the substantia nigra from dying.

Further Reading

Dauphin, Sue. Parkinson's Disease: the Mystery, the Search, and the Promise. Tequesta, Florida: Pixel Press, 1992.

Duvoisin, Roger. Parkinson's Disease: a Guide for Patient and Family. New York: Raven Press, 1991.

Lang, A. E. "Motor disorders symptomatology." In Neurology in clinical practice, edited by W. G. Bradley, et al. Boston: Butterworth-Heinemann, 1991, pp. 315-316.

Jordan P. Richman

KEY TERMS

Basal ganglia--Groups of nerve cells located within the white matter of each cerebral hemi sphere. They are important for coordinating signals along the motor pathways of the central nervous system.

CAT scan--Computerized axial tomographic scanning, also called CT scanning, which uses diagnostic x rays and a computer to give crosssectional images at different angles of the brain and other parts of the body.

Dementia--Impairment of mental functioning due to illness or aging.

Dopamine--Neurotransmitter essential for proper movement functions of the body.

Levodopa (l-dopa)--Precursor to dopamine, used as drug for Parkinson's disease because, unlike dopamine, it can cross the brain blood barrier.

MRI--Magnetic resonance imaging, a nonxray imaging technique used to diagnose the brain and other parts of the body.

Substantia nigra--A layer of deeply pigmented nerve cells in the brain containing dopamine producing cells.

Tremor--Involuntary shaking movements of the hands while at rest produced in Parkinson's disease by a lack of dopamine.

Record Number: A30434767

SOURCE:
Gale Encyclopedia of Science.  June 2001 pNA.

Full Text: COPYRIGHT 2001 Gale Group