How is PD diagnosed & treated?

In rare cases, where people have a clearly inherited form of PD, researchers can test for known gene mutations as a way of determining an individual’s risk of developing the disease. However, this genetic testing can have far-reaching implications and people should carefully consider whether they want to know the results of such tests.

Treating PD

Currently, there is no cure for PD, but medications or surgery can often provide improvement in the motor symptoms.

Drug Therapy

Medications for PD fall into three categories:

1. Drugs that increase the level of dopamine in the brain. The most common drugs for PD are dopamine precursors—substances like levodopa that cross the blood-brain barrier and are then changed into dopamine. Other drugs mimic dopamine or prevent or slow its breakdown.
2. Drugs that affect other neurotransmitters in the body to ease some of the symptoms of the disease. For example, anticholinergic drugs interfere with production or uptake of the neurotransmitter acetylcholine. These can be effective in reducing tremors.
3. Medications that help control the non-motor symptoms of the disease, or the symptoms that don’t affect movement. For example, people with PD-related depression may be prescribed antidepressants.

Symptoms may significantly improve at first with medication but can reappear over time as PD worsens and drugs become less effective.

Medications

Levodopa-Carbidopa—The cornerstone of PD therapy is the drug levodopa (also known as L-dopa). Nerve cells can use levodopa to make dopamine and replenish the brain’s reduced supply. People cannot simply take dopamine pills because dopamine does not easily pass through the blood-brain barrier, which is a protective lining of cells inside blood vessels that regulate the transport of oxygen, glucose, and other substances in the brain.

People are given levodopa combined with another substance called carbidopa. When added to levodopa, carbidopa prevents the conversion of levodopa into dopamine except for in the brain; this stops or diminishes the side effects due to dopamine in the bloodstream. Levodopa-carbidopa is often very successful at reducing or eliminating the tremors and other motor symptoms of PD during the early stages of the disease. People may need to increase their dose of levidopa gradually for maximum benefit. Levodopa can reduce the symptoms of PD but it does not replace lost nerve cells or stop its progression.

Initial side effects of levodopa-carbidopa may include:

• Nausea
• Low blood pressure
• Restlessness
• Drowsiness or sudden sleep 

Side effects of long-term or extended use of levodopa may include:

• Hallucinations and psychosis
• Dyskinesia, or involuntary movements such as mild to severe twisting and writhing

Later in the course of the disease, people with PD may begin to notice more pronounced symptoms before their first dose of medication in the morning and between doses as the period of effectiveness after each dose begins to shorten, called the wearing-off effect. People experience sudden, unpredictable “off periods,” where the medications do not seem to be working. One approach to alleviating this is to take levodopa more often and in smaller amounts. People with PD should never stop taking levodopa without their physician’s input, because rapidly withdrawing the drug can have potentially serious side effects. 

Dopamine agonists—These mimic the role of dopamine in the brain and can be given alone or with levodopa. They are somewhat less effective than levodopa in treating PD symptoms but work for longer periods of time. Many of the potential side effects are similar to those associated with the use of levodopa, including drowsiness, sudden sleep onset, hallucinations, confusion, dyskinesias, edema (swelling due to excess fluid in body tissues), nightmares, and vomiting. In rare cases, they can cause an uncontrollable desire to gamble, hypersexuality, or compulsive shopping. Dopamine agonist drugs include apomorphine, pramipexole, ropinirole, and rotigotine. 

MAO-B inhibitors—These drugs block or reduce the activity of the enzyme monoamine oxidase B, or MAO-B, which breaks down dopamine in the brain. MAO-B inhibitors cause dopamine to accumulate in surviving nerve cells and reduce the symptoms of PD. These medications include selegiline and rasagiline. Studies supported by the NINDS have shown that selegiline (also called deprenyl) can delay the need for levodopa therapy by up to a year or more. When selegiline is given with levodopa, it appears to enhance and prolong the response to levodopa and thus may reduce wearing-off. Selegiline is usually well-tolerated, although side effects may include nausea, orthostatic hypotension, or insomnia. The drug rasagiline is used in treating the motor symptoms of PD with or without levodopa.

COMT inhibitors—COMT stands for catechol-O-methyltransferase and is another enzyme that breaks down dopamine. The drugs entacapone, opicapone, and tolcapone prolong the effects of levodopa by preventing the breakdown of dopamine. COMT inhibitors can decrease the duration of “off periods” of one’s dose of levodopa. Side effects may include diarrhea, nausea, sleep disturbances, dizziness, urine discoloration, abdominal pain, low blood pressure, or hallucinations. In a few rare cases, tolcapone has caused severe liver disease, and people taking tolcapone need regular monitoring of their liver function.

Amantadine—This antiviral drug can help reduce symptoms of PD and levodopa-induced dyskinesia. It can be prescribed alone in the early stages of the disease and can be used with an anticholinergic drug or levodopa. After several months, amantadine’s effectiveness wears off in up to half of the people taking it. Amantadine’s side effects may include insomnia, mottled skin, edema, agitation, or hallucinations. Researchers are not certain how amantadine works in PD, but it may increase the effects of dopamine.

Anticholinergics—These drugs, which include trihexyphenidyl, benztropine, and ethopropazine, decrease the activity of the neurotransmitter acetylcholine and can be particularly effective for tremor associated with PD. Side effects may include dry mouth, constipation, urinary retention, hallucinations, memory loss, blurred vision, and confusion.

When recommending a course of treatment, a doctor will assess how much the symptoms disrupt the person’s life and then tailor therapy to the person’s particular condition. Since no two people will react the same way to a given drug, it may take time and patience to get the dose right. Even then, symptoms may not be completely alleviated.

Medications to treat motor symptoms of PD

Surgery

Before the discovery of levodopa, surgery was an option for treating PD. Studies in the past few decades have led to great improvements in surgical techniques, and surgery is again considered for people with PD for whom drug therapy is no longer sufficient.

Pallidotomy and Thalamotomy

The earliest types of surgery for PD involved selectively destroying specific parts of the brain that contribute to PD symptoms. Surgical techniques have been refined and can be very effective for the motor symptoms of PD. The most common lesion surgery is called pallidotomy. In this procedure, a surgeon selectively destroys a portion of the brain called the globus pallidus. Pallidotomy can improve symptoms of tremor, rigidity, and bradykinesia, possibly by interrupting the connections between the globus pallidus and the striatum or thalamus. Some studies have also found that pallidotomy can improve gait and balance and reduce the amount of levodopa people require, thus reducing drug-induced dyskinesias.

Another procedure, called thalamotomy, involves surgically destroying part of the thalamus; this approach is useful primarily to reduce tremor.

Because these procedures cause permanent destruction of small amounts of brain tissue, they have largely been replaced by deep brain stimulation for treatment of PD. However, a method using focused ultrasound from outside the head is being tested because it creates lesions without the need for surgery.

Deep Brain Stimulation

Deep brain stimulation (DBS) uses an electrode surgically implanted into part of the brain, typically the subthalamic nucleus or the globus pallidus. Similar to a cardiac pacemaker, a pulse generator (battery pack) that is implanted in the chest area under the collarbone sends finely controlled electrical signals to the electrode(s) via a wire placed under the skin. When turned on using an external wand, the pulse generator and electrodes painlessly stimulate the brain in a way that helps to block signals that cause many of the motor symptoms of PD. (The signal can be turned off using the wand.) Individuals must return to the medical center frequently for several months after DBS surgery in order to have the stimulation adjusted very carefully to give the best results. DBS is approved by the U.S. Food and Drug Administration (FDA) and is widely used as a treatment for PD.

• DBS is primarily used to stimulate one of three brain regions: the subthalamic nucleus, the globus pallidus interna, or the thalamus. Stimulation of either the globus pallidus or the subthalamic nucleus can reduce tremor, bradykinesia, and rigidity. Stimulation of the thalamus is useful primarily for reducing tremor.
• DBS does not stop PD from progressing, and some problems may gradually return. While the motor function benefits of DBS can be substantial, it usually does not help with speech problems, “freezing,” posture, balance, anxiety, depression, or dementia.
• DBS is generally appropriate for people with levodopa-responsive PD who have developed dyskinesias or other disabling “off” symptoms despite drug therapy. DBS has not been demonstrated to be of benefit for “atypical” parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy, or post-traumatic parkinsonism, which also do not improve with Parkinson’s medications.

Complementary and Supportive Therapies

A wide variety of complementary and supportive therapies may be used for PD, including:

A healthy diet—At this time there are no specific vitamins, minerals, or other nutrients that have any proven therapeutic value in PD. The National Institute of Neurological Disorders and Stroke (NINDS) and other components of the NIH are funding research to determine if caffeine, antioxidants, and other dietary factors may be beneficial for preventing or treating PD. A healthy diet can promote overall well-being for people with PD just as it would for anyone else. Eating a fiber-rich diet and drinking plenty of fluids also can help alleviate constipation. A high protein diet, however, may limit levodopa’s absorption.

Exercise—Exercise can help people with PD improve their mobility, flexibility, and body strength. It also can improve well-being, balance, minimize gait problems, and strengthen certain muscles so that people can speak and swallow better. General physical activity, such as walking, gardening, swimming, calisthenics, and using exercise machines, can have other benefits. People with PD should always check with their doctors before beginning a new exercise program.

Alternative approaches that are used by some individuals with PD include:

Coping with PD

While PD usually progresses slowly, eventually daily routines may be affected—from socializing with friends to earning a living and taking care of a home. These changes can be difficult to accept. Support groups can help people cope with the disease’s emotional impact. These groups can provide valuable information, advice, and experience to help people with PD, their families, and their caregivers deal with a wide range of issues, including locating doctors familiar with the disease and coping with physical limitations. A list of national organizations that can help people locate support groups in their communities appears at the end of this information. Individual or family counseling may also help people find ways to cope with PD.

People with PD may also benefit from being proactive and finding out as much as possible about the disease in order to alleviate fear of the unknown and to take a proactive role in maintaining their health. Many people with PD continue to work either full- or part-time, although they may need to adjust their schedule and working environment to accommodate their symptoms.

Outlook

The average life expectancy of a person with PD is generally the same as for people who do not have the disease. Fortunately, there are many treatment options available for people with PD. However, in the late stages, PD may no longer respond to medications and can become associated with serious complications such as choking, pneumonia, and falls.

Because PD is a slow, progressive disorder, it is not possible to predict what course the disease will take for an individual person.