Home > Encyclopedia of Nursing & Allied Health > Parkinson's Disease

Definition

Parkinson's disease (PD) is a progressive movement disorder marked by tremors, rigidity, slow movements (bradykinesia), and postural instability. It occurs when, for unknown reasons, cells in one of the movement-control centers of the brain begin to die.

Description

Usually beginning in a person's late 50s or early 60s, PD causes a progressive decline in movement control, affecting the ability to control initiation, speed, and smoothness of motion. Symptoms of PD are seen in up to 15% of those between the ages 65–74, and almost 30% of those between the ages 75–84.

Genetic profile

Most cases of PD are sporadic. This means that there is a spontaneous and permanent change in nucleotide sequences (the building blocks of genes). Sporadic mutations also involve unknown environmental factors in combination with genetic defects. The abnormal gene (mutated gene) will form an altered end-product or protein. This will cause abnormalities in specific areas of the body where the protein is used. Some evidence suggests that the disease is transmitted by autosomal dominant inheritance. This implies that an affected parent has a 50% chance of transmitting the disease to any child. This type of inheritance is not commonly observed. The most recent evidence links PD with a gene that codes for a protein called alpha-synuclein. Further research is attempting to fully understand the relationship with this protein and nerve cell degeneration.

Demographics

PD affects approximately 500,000 people in the United States, both men and women, with as many as 50,000 new cases being diagnosed each year.

Causes and symptoms

Causes

The immediate cause of PD is degeneration of brain cells in the area known as the substantia nigra, one of the movement control centers of the brain. Damage to this area leads to the cluster of symptoms known as parkinsonism. In PD, degenerating brain cells contain Lewy bodies, which help identify the disease. The cell death leading to parkinsonism may be caused by a number of conditions, including infection, trauma, and poisoning. Some drugs given for psychosis, such as haloperidol (Haldol) or chlorpromazine (Thorazine), may cause parkinsonism. When no cause for nigral cell degeneration can be found, the disorder is called idiopathic parkinsonism, or Parkinson's disease. Parkinsonism may be seen in other degenerative conditions, known as the parkinsonism plus syndromes, such as progressive supranuclear palsy.

The substantia nigra, or black substance, is one of the principal movement control centers in the brain. By releasing the neurotransmitter known as dopamine, it helps to refine movement patterns throughout the body. The dopamine released by nerve cells of the substantia nigra stimulates another brain region, the corpus striatum. Without enough dopamine, the corpus striatum cannot control its target muscles. Ultimately, the movement patterns of walking, writing, reaching for objects, and other basic programs cannot operate properly, and the symptoms of parkinsonism are the result.

There are some known toxins that can cause parkinsonism, most notoriously a chemical called MPTP, found as an impurity in some illegal drugs. Parkinsonian symptoms appear within hours of ingestion and are permanent. MPTP may exert its effects through generation of toxic molecular fragments called free radicals. Reducing free radicals has been a target of several experimental treatments for PD using antioxidants.

It is possible that early exposure to some as-yetunidentified environmental toxin or virus leads to undetected nigral cell death, and that PD then becomes manifest as normal age-related decline brings the number of functioning nigral cells below the threshold needed for normal movement. It is also possible that, for genetic reasons, some people are simply born with fewer cells in their substantia nigra than others, and develop PD again as a consequence of normal decline.

Symptoms

The identifying symptoms of PD include:

• Tremors, usually beginning in the hands, often occurring on one side before the other. The classic tremor of PD is called a pill-rolling tremor, because the movement resembles rolling a pill between the thumb and forefinger. This tremor occurs at a frequency of about three per second.
• Slow movements (bradykinesia) occur, which may involve slowing down or stopping in the middle of familiar tasks such as walking, eating, or shaving. This may include freezing in place during movements (akinesia).
• Muscle rigidity or stiffness, occurring with jerky movements replacing smooth motion.
• Postural instability or balance difficulty occurs. This may lead to a rapid, shuffling gait (festination) to prevent falling.
• In most cases, there is a typical facial expression called masked face, characterized by little facial expression and decreased eye-blinking.

In addition, a wide range of other symptoms may often be seen, some beginning earlier than others:

• depression
• speech changes, including rapid speech without inflection changes
• problems with sleep, including restlessness and nightmares
• emotional changes, including fear, irritability, and insecurity
• incontinence
• constipation
• handwriting changes, with letters becoming smaller across the page (micrographia)
• progressive problems with intellectual function (dementia)

Diagnosis

The diagnosis of Parkinson disease involves a careful medical history and a neurological exam to look for characteristic symptoms. There are no definitive tests for PD, although a variety of lab tests may be done to rule out other causes of symptoms, especially if only some of the identifying symptoms are present. Tests for other causes of parkinsonism may include brain scans, blood tests, lumbar puncture, and x rays.

Treatment

There is no cure for Parkinson disease. Most drugs treat only the symptoms of the disease, although one drug, selegiline (Eldepryl), may slow degeneration of the substantia nigra.

Exercise, nutrition, and physical therapy

Regular, moderate exercise has been shown to improve motor function without an increase in medication for a person with PD. Exercise helps maintain range of motion in stiff muscles, improve circulation, and stimulate appetite. An exercise program designed by a physical therapist has the best chance of meeting the specific needs of a person with PD. A physical therapist may also suggest strategies for balance compensation and techniques to stimulate movement during slowdowns or freezes.

Good nutrition is important to maintenance of general health. A person with PD may lose some interest in food, especially if depressed, and may have nausea from the disease or from medications, especially those known as dopamine agonists. Slow movements may make it difficult to eat quickly, and delayed gastric emptying may lead to a feeling of fullness without having eaten much. Increasing fiber in the diet can improve constipation, soft foods can reduce the amount of needed chewing, and a prokinetic drug such as cisapride (Propulsid) can increase the movement of food through the digestive system.

People with PD may need to limit the amount of protein in their diets. The main drug used to treat PD, L-dopa, is an amino acid, and is absorbed by the digestive system by the same transporters that pick up other amino acids broken down from proteins in the diet. Limiting protein, under the direction of a physician or nutritionist, can improve the absorption of L-dopa.

No evidence indicates that vitamin or mineral supplements can have any effect on the disease other than in their improvement of general health. No antioxidants used to date have shown promise as a treatment except for selegiline, an MAO-B inhibitor. A large, carefully controlled study of vitamin E demonstrated that it could not halt disease progression.

Drugs

The pharmacological treatment of Parkinson disease is complex. While there are a large number of drugs that can be effective, their effectiveness varies among individuals, disease progression, and the length of time the drug has been used. Dose-related side effects may preclude the use of the most effective dose, or require the introduction of a new drug to counteract them. There are five classes of drugs currently used to treat PD.

DRUGS THAT REPLACE DOPAMINE. One drug that helps replace dopamine, levodopa (L-dopa), is the single most effective treatment for the symptoms of PD. L-dopa is a derivative of dopamine, and is converted into dopamine by the brain. It may be started when symptoms begin, or when they become serious enough to interfere with work or daily living.

L-dopa therapy usually remains effective for five years or longer. Following this, many persons develop motor fluctuations, including peak-dose dyskinesias (abnormal movements such as tics, twisting, or restlessness); rapid loss of response after dosing (known as the on-off phenomenon); and unpredictable drug response. Higher doses are usually tried, but may lead to an increase in dyskinesias. In addition, side effects of L-dopa include nausea and vomiting, and low blood pressure upon standing (orthostatic hypotension), which can cause dizziness. These effects usually lessen after several weeks of therapy.

ENZYME INHIBITORS. Dopamine is broken down by several enzyme systems in the brain and elsewhere in the body, and blocking these enzymes is a key strategy to prolonging the effect of a dose of dopamine. The two most commonly prescribed forms of L-dopa contain a drug to inhibit the amino acid decarboxylase (an AADC inhibitor), one type of enzyme that breaks down dopamine. These combination drugs are Sinemet (L-dopa plus carbidopa) and Madopar (L-dopa plus benzaseride). Controlled-release formulations also aid in prolonging the effective interval of an L-dopa dose.

The enzyme monoamine oxidase B (MAO-B) inhibitor selegiline may be given as add-on therapy for L-dopa. Research indicates selegiline may have a neuroprotective effect, sparing nigral cells from damage by free radicals. Because of this, and the fact that it has few side

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KEY TERMS

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AADC inhibitors—Drugs that block the amino acid decarboxylase; one type of enzyme that breaks down dopamine. Also called DC inhibitors, they include carbidopa and benserazide.

Akinesia—A loss of the ability to move; freezing in place.

Bradykinesia—Extremely slow movement.

COMT inhibitors—Drugs that block catechol-O-methyltransferase, an enzyme that breaks down dopamine. COMT inhibitors include entacapone and tolcapone.

Dopamine—A chemical in the brain (neurotransmitter) that helps send signals that control movement.

Dyskinesia—An abnormal involuntary movement. Dyskinesias are common late in PD as L-dopa therapy becomes less effective.

MAO-B inhibitors—Inhibitors of the enzyme monoamine oxidase B. MAO-B helps break down dopamine; inhibiting it prolongs the action of dopamine in the brain. Selegiline is an MAO-B inhibitor.

Orthostatic hypotension—A sudden decrease in blood pressure upon sitting up or standing. May be a side effect of several types of drugs.

Substantia nigra—One of the movement control centers of the brain.

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effects, it is also frequently prescribed early in the disease before L-dopa is begun. Entacapone (Comtan) and tolcapone (Tasmar), two inhibitors of another enzyme system called catechol-O-methyltransferase (COMT), have recently been approved for use and marketed. They effectively treat PD symptoms with fewer motor fluctuations and decreased daily L-dopa requirements.

DOPAMINE AGONISTS. Dopamine works by stimulating receptors on the surface of corpus striatum cells. Drugs that also stimulate these cells are called dopamine agonists, or DAs. DAs may be used before L-dopa therapy, or added on to avoid requirements for higher L-dopa doses late in the disease. DAs available in the United States as of 2001, include bromocriptine (Permax, Parlodel), pergolide (Permax), pramipexole (Mirapex), cabergoline (Dostinex), and ropinirole (Requip). Other dopamine agonists in use elsewhere include lisuride (Dopergine) and apomorphine. Side effects of all the DAs are similar to those of dopamine, plus confusion and hallucinations at higher doses.

ANTICHOLINERGIC DRUGS. Anticholinergics maintain dopamine balance as levels decrease. However, the side effects of anticholinergics (dry mouth, constipation, confusion, and blurred vision) are usually too severe in older individuals or in persons with dementia. In addition, anticholinergics rarely work for very long. They are often prescribed for younger people who have predominant shaking. Trihexyphenidyl (Artane) is the most commonly prescribed drug.

DRUGS WHOSE MODE OF ACTION IS UNCERTAIN. Amantadine (Symmetrel) is sometimes used as an early therapy before L-dopa is begun, and as an add-on later in the disease. Its anti-parkinsonian effects are mild, and are not seen in many persons. Clozapine (Clozaril) is effective, especially against psychiatric symptoms of late PD, including psychosis and hallucinations.

Surgery

Two surgical procedures are used for treatment of PD that cannot be controlled adequately with drug therapy. In PD, a brain structure called the globus pallidus (GPi) receives excess stimulation from the corpus striatum. In a pallidotomy, the GPi is destroyed by heat that is delivered by long thin needles inserted under anesthesia. Electrical stimulation of the GPi is another way to reduce its action. In this procedure, fine electrodes are inserted to deliver the stimulation, which may be adjusted or turned off as the response dictates. Other regions of the brain may also be stimulated by electrodes inserted elsewhere. In most persons, these procedures lead to significant improvement for some motor symptoms, including peak-dose dyskinesias. This allows a person to receive more L-dopa, since these dyskinesias are usually responsible for any upper limit on the L-dopa dose.

A third procedure, transplant of fetal nigral cells, is still highly experimental. Its benefits to date have been modest, although improvements in technique and surgical candidate selection are likely to increase successful outcomes.

Alternative treatment

Currently, the best treatments for PD involve the use of conventional drugs such as levodopa. Alternative therapies, including acupuncture, massage, and yoga, can help relieve some symptoms of the disease and loosen tight muscles. Alternative practitioners have also applied herbal and dietary therapies, including amino acid supplementation, antioxidant (vitamins A, C, E, selenium, and zinc) therapy, B vitamin supplementation, and calcium and magnesium supplementation to the treatment of PD. Persons using these therapies in conjunction with conventional drugs should check with their doctor to avoid the possibility of adverse interactions. For example, vitamin B₆ (either as a supplement or from foods such as whole grains, bananas, beef, fish, liver, and potatoes) can interfere with the action of L-dopa when the drug is taken without carbidopa.

Prognosis

Despite medical treatment, the symptoms of Parkinson's disease worsen over time, and become less responsive to drug therapy. Late-stage psychiatric symptoms are disease often the most troubling. These include difficulty sleeping, nightmares, intellectual impairment (dementia), hallucinations, and loss of contact with reality (psychosis).

Health care team roles

A physician usually makes an initial diagnosis of Parkinson's disease. Treatment is often managed by a family physician or internist. Neurologists may be asked for consultations. Occasionally, neurosurgeons perform surgery in the treatment of parkinsonism. Clinical nutritionists and physical therapists may assist in managing persons with PD. Nurses provide bedside care in the hospital, and administer the frequent patient neurologic evaluations. They also provide patient and family education about the diagnosis and home management.

Prevention

There is no known way to prevent Parkinson's disease.

L. Fleming Fallon, Jr., MD, DrPH