Parkinson's Disease

In Parkinson's disease, some parts of the nervous system slowly and progressively degenerate.

The disease causes a tremor when muscles are at rest (resting tremor). Movements become slow and uncoordinated, and muscles become tight and rigid. The disease inevitably progresses, usually slowly.

Parkinson's disease affects about 1 out of 100 people over 65. It commonly begins between the ages of 50 and 79. It is twice as common among whites as among blacks.

In Parkinson's disease, the basal ganglia degenerate. The basal ganglia are clusters of nerve cells located at the base of the cerebrum, deep within the brain. They help make muscle movements smooth and coordinated. Like all nerve cells, those in the basal ganglia communicate with other nerve cells by releasing chemical messengers (neurotransmitters). The main neurotransmitter in the basal ganglia is dopamine. When nerve cells in the basal ganglia degenerate, less dopamine is produced. As a result, the basal ganglia cannot smooth out movements as they normally do. Tremor is thought to result from an imbalance: having too little dopamine and too much acetylcholine, another neurotransmitter.

Causes

Why brain cells in the basal ganglia degenerate is unknown. In only a few cases, the disease seems to run in families.

Other conditions that affect the basal ganglia can cause symptoms similar to those of Parkinson's disease. Any condition that causes these symptoms is considered parkinsonism.

Symptoms

Usually, Parkinson's disease begins subtly and progresses gradually. In many people, it begins with a coarse, rhythmic tremor in the hand while the hand is at rest. Typically, the fingers move as if rolling pills. The tremor decreases when the hand is moving purposefully and disappears completely during sleep. Emotional stress or fatigue may worsen the tremor. The tremor may eventually progress to the other hand, the arms, and the legs. The jaws may also be affected. The tremor may become less obvious as the disease progresses. In about one third of people with Parkinson's disease, a tremor is not the first symptom. In some people, a tremor never develops.

Early in Parkinson's disease, people may not be able to smell as well. Part of the reason may be that they have difficulty sniffing or taking a deep breath. Parkinson's disease affects muscles, including those used in breathing. Cells in the areas of the brain involved in smell may degenerate, affecting the brain's ability to identify smells. Although a reduced sense of smell may seem a minor problem, it can dampen the appetite, contributing to undernutrition.

Early in the disease, muscles become rigid. If the forearm is straightened out by another person, the movement may feel stiff or the forearm may move in jerks, like a ratchet. At first, one side of the body is often affected more.

People with Parkinson's disease move slowly and have difficulty starting movements. Gradually, walking becomes impaired. Taking the first step in walking becomes difficult. Once started, people with Parkinson's disease often shuffle and take short steps without swinging their arms as they walk. Some people have difficulty stopping or turning while walking. Sometimes people are in the middle of a movement, then suddenly and unpredictably freeze in place. As they walk, they may suddenly feel as if their feet are glued to the ground, and they cannot take another step. Because movement is difficult, people with Parkinson's disease move around less. Lack of movement makes muscles even stiffer. Muscles may ache and feel tired.

Often, the small muscles of the hands do not function normally. Thus, daily tasks, such as buttoning a shirt and tying shoelaces, become increasingly harder. Most people with Parkinson's disease have shaky, tiny handwriting (micrographia), because initiating and sustaining each stroke of the pen is difficult.

Sometimes movements become faster. For example, when walking, people may unintentionally quicken their steps, breaking into a short-stepped, stumbling run to avoid falling. They may talk faster, running words together in a mumble.

Posture becomes stooped, and the head tends to droop forward and rest on the chest. Balance becomes difficult to maintain, so that falling becomes more likely. When balance is lost, people often cannot move their feet or hands quickly enough to prevent or break a fall.

The face becomes less expressive because the facial muscles that control expression do not move. This lack of expression may be mistaken for depression. Or it may cause depression to be overlooked. Depression is common among people with Parkinson's disease. Eventually, the face can take on a blank stare with the mouth open, and the eyes may not blink often. People with Parkinson's disease often speak softly in a monotone and may stutter because they have difficulty articulating words. They may whisper.

Often, people with Parkinson's disease drool or choke because the muscles of the face and throat have become rigid or move slowly, making swallowing difficult. They may become malnourished and dehydrated. As the disease progresses, swallowing becomes increasingly difficult. Thus, aspiration pneumonia, which can be fatal, is more likely to develop.

Constipation and insomnia are common. In many people with Parkinson's disease, mental functions remain normal. But dementia develops in about half of people with Parkinson's disease.

Diagnosis

Doctors usually diagnose Parkinson's disease based on symptoms and the results of a physical examination. Mild disease may be difficult to diagnose, because it usually begins subtly. Also, older people may have parkinsonism or other problems that cause some of the same symptoms as Parkinson's disease, such as loss of balance, slow movements, muscle stiffness, and stooped posture.

Tests are rarely needed. However, when the diagnosis is unclear, positron emission tomography (PET) may help. This imaging procedure can often detect abnormalities in the brain that are characteristic of Parkinson's disease. Computed tomography (CT) and magnetic resonance imaging (MRI) cannot detect these abnormalities, but they may be done to look for another disorder that could be causing the symptoms. Sometimes, if the diagnosis is unclear, a person is given levodopa (commonly used to treat Parkinson's disease) for a brief time. The diagnosis of Parkinson's disease is likely if treatment with this drug results in improvement.

Treatment

Parkinson's disease cannot be cured. But drugs can usually control symptoms effectively for many years.

If another disorder or a drug is causing the symptoms, treating the disorder or discontinuing the drug is more effective than taking additional drugs.

General measures: Continuing to do as many daily activities as possible and following a program of regular exercise, such as walking, can help people stay mobile. Physical and occupational therapy can help people maintain or regain muscle tone and maintain range of motion. Therapists can also teach new ways to do activities that have become difficult (adaptive techniques). Therapists can teach ways to manage the unpredictable episodes of freezing when walking. They may recommend installing grab bars and railings to help prevent falls or using mechanical aids, such as a wheeled walker or a cane.

Eating fiber-rich foods (such as prunes), drinking plenty of fluids (particularly prune juice and other juices), and taking stool softeners (such as senna) can help keep bowel movements regular. These things should be done daily before constipation develops or becomes severe. Eating a nutritious diet is important.

Simple changes around the home can make the home safer. For example, removing throw rugs can prevent tripping. Installing railings in bathrooms, hallways, and other locations reduces the risk of falling. Daily tasks can be simplified, for example, by having buttons on clothing replaced with Velcro fasteners or buying shoes with such fasteners.

Drugs: No drug can cure Parkinson's disease or stop its progression. However, many drugs can make movement easier and enable people to function effectively for many years. Two or more drugs may be needed. People with Parkinson's disease must take these drugs for the rest of their life.

Taking levodopa can produce dramatic improvement in people with Parkinson's disease. This drug is taken by mouth and is most effective in reducing tremor and muscle rigidity. The drug enables many people with mild Parkinson's disease to return to a nearly normal level of activity and enables some people who are bedridden to walk again.

Levodopa is converted to dopamine in the basal ganglia. Thus, this drug partially compensates for the decrease in dopamine production. Levodopa is almost always given with carbidopa. Carbidopa prevents levodopa from being converted to dopamine before it reaches the brain. When the two drugs are given together, a lower dose of levodopa can be used, and some side effects of levodopa (nausea and flushing) are reduced.

To determine the best dose of levodopa for a particular person, doctors must balance control of the disease with the development of certain side effects, which may limit the amount of levodopa the person can tolerate. Side effects include involuntary movements of the mouth, face, and limbs and sometimes difficulty sleeping and nightmares.

After taking levodopa for 5 or more years, more than half of the people begin to have problems. These people alternate rapidly between responding well to the drug and not responding. This effect is called the on-off phenomenon. Within seconds, a person may change from being able to move (mobile) fairly well to being almost unable to move. Also, the period of improved mobility after a dose becomes shorter over time and may be accompanied by an increase in involuntary movements, such as writhing. Taking lower, more frequent doses controls these effects at first, but after several more years, these effects become hard to avoid.

Other drugs may benefit some people, particularly if levodopa is not tolerated or does not control symptoms well. Drugs that mimic the actions of dopamine (dopamine agonists), such as bromocriptine, pramipexole, and ropinirole, may be useful and are often used before levodopa. Selegiline, a type of antidepressant called a monoamine oxidase inhibitor (MAOI), prevents the breakdown of dopamine, thereby prolonging dopamine's action in the body. Tolcapone and entacapone appear to be useful as supplements to levodopa, but they are not helpful when taken alone. They also prevent the breakdown of dopamine.

Some drugs with anticholinergic effects, such as benztropine and trihexyphenidyl, can reduce the severity of tremors. These drugs can be used early in Parkinson's disease. They can also be used later to supplement levodopa. But these drugs can cause many troublesome side effects in older people.

Amantadine, a drug sometimes used to treat influenza, may be used as a supplement to levodopa or alone.

If depression develops, antidepressants are usually used.

Surgery: When symptoms are severe (late in the disease), surgery is sometimes done. In a pallidotomy, a tiny area in one of the basal ganglia on one side of the brain is surgically destroyed. This procedure can greatly reduce the "off" part of the on-off phenomenon and the involuntary movements due to years of levodopa therapy. In deep brain stimulation, tiny electrodes are implanted in the basal ganglia. They stimulate the area, often producing similar improvements.

Several experimental procedures are being studied. In one, nerve cells that produce dopamine are taken from human fetal tissue and implanted in the brain of a person with Parkinson's disease. These cells form connections with other nerve cells and produce dopamine, thus supplying the missing neurotransmitter.

Outlook

Usually, Parkinson's disease progresses slowly, and people can function for many years. But Parkinson's disease is progressive, and people eventually need help with normal daily activities, such as eating, bathing, dressing, and going to the toilet. Some people are incapacitated within 5 years. Caregivers can benefit from learning about the physical and psychologic effects of Parkinson's disease and about ways to enable people to function as well as possible. Because such care is tiring and stressful, caregivers may benefit from support groups.

Eventually, most people with Parkinson's disease become severely disabled and immobile. They may be unable to eat, even with help. If dementia develops, the situation is more difficult. Before people with Parkinson's disease are incapacitated, they should prepare advance directives, indicating what kind of medical care they want at the end of life. For example, they should state whether they want tube feedings or aggressive treatment for common problems that develop, such as aspiration pneumonia.

See the sidebar What Is Parkinsonism?

See the table Drugs Used to Treat Parkinson's Disease.