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No standard treatment exists for the earliest symptoms of Parkinson's disease. In fact, the optimum time to begin treatment and even the best medication to use is controversial.

Some doctors may begin drug treatment at the first signs of the disease. Others may delay giving medications until symptoms become more pronounced. That's because the benefits of traditional Parkinson's medications diminish over time. Although drugs such as levodopa improve symptoms initially, long-term use frequently causes excessive, spasmodic movements (dyskinesia) and other side effects. For that reason, if your symptoms are mild, your doctor first may try lifestyle changes, such as diet, exercise and physical therapy.

Physical therapy can be extremely helpful for people with Parkinson's disease — both in the early stages and later, as the disease progresses. It can help improve mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, improving muscle strength can help you feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. For many people, working with a speech pathologist can help improve problems with speaking and swallowing.

When lifestyle changes are no longer enough, your doctor will likely recommend certain medications, either alone or in combination.

Medications
Medications are used to help manage problems with walking, movement and tremors by increasing the brain's supply of dopamine. However, your medication needs may change over time and the drug dosage and timing may require adjustment. For these reasons, you and your doctor will work together to design a program that best suits your needs, especially as the disease progresses. The medications used to treat Parkinson's disease include:

• Levodopa. Since its introduction in the 1960s, levodopa has been considered the gold standard drug therapy for Parkinson's disease. Levodopa is the formulation of a chemical found in plants and animals that is converted into dopamine by nerve cells in the brain. The increase in dopamine may reverse many of the disabling symptoms of Parkinson's disease, but as time passes, side effects may increase and you'll need adjustments of the doses.

• Treatment with dopamine itself isn't possible, because dopamine doesn't cross the body's blood-brain barrier. This is a meshwork of tightly packed cells in the walls of the brain's capillaries that screen out certain substances. Levodopa, on the other hand, does cross this barrier, but only a small amount actually reaches the brain. Combining levodopa with another drug, carbidopa (Sinemet), causes more levodopa to get to the brain and helps reduce some of the side effects of this therapy. Sinemet CR is a prolonged-release version of this drug.

• During early treatment, side effects from levodopa therapy are usually not a major problem. But as the disease progresses, the drug works less evenly. As a result, some people may experience involuntary movements (dyskinesia), especially when the medication is having its peak effects. Waxing and waning of the response to the drug (wearing off effects) also is common. This means that the time that each dose is effective begins to decrease, leading to more frequent doses. Other side effects may include hallucinations, a drop in blood pressure — especially when standing — and nausea. Still, levodopa often allows people with Parkinson's disease to extend the time they're able to lead relatively normal lives and in many cases is effective for a number of years.

• Dopamine agonists. Unlike levodopa, these drugs aren't changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though sufficient amounts of dopamine were present. Dopamine agonists are used both as adjuncts to levodopa therapy and also initially in early Parkinson's disease, especially in younger adults. The side effects of dopamine agonists are similar to those of levodopa. This class of drugs includes the older dopamine agonists, bromocriptine (Parlodel) and pergolide (Permax) and the newer drugs, pramipexole (Mirapex) and ropinirole (Requip). Avoid dopamine agonists if you already have experienced hallucinations or confusion.

• One clinical trial suggested that pramipexole may slow the progression of Parkinson's disease. Whether this truly occurs remains uncertain, but some physicians have chosen to begin early treatment with pramipexole based on the results of this study. Another clinical trial showed similar results for ropinirole, but these results remain somewhat controversial.

• Selegiline (Atapryl, Carbex, Eldepryl). This drug, used as an adjunct to levodopa therapy, helps prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. It does this by inhibiting the activity of the enzyme monoamine oxidase B (MAO-B) — the enzyme that metabolizes dopamine in the brain. At one time it was thought that this drug might slow the progression of Parkinson's disease, but this now appears not to be the case. Toxic reactions have occurred in some patients who took selegiline with the narcotic drug, meperidine (Demerol, Pethadol).

• COMT inhibitors. A newer class of drugs, COMT inhibitors prolong the effect of levodopa therapy by blocking an enzyme that breaks down dopamine in the liver and other organs. Tolcapone (Tasmar) is a potent COMT inhibitor that easily crosses the blood-brain barrier and in clinical trials reduced the amount of levodopa needed by 25 percent. But because Tasmar has been linked to liver damage and liver failure, the drug is normally used only in people who aren't responding to other therapies. Entacaopne is a COMT inhibitor that shares some of the properties of tolcapone but doesn't cross into the brain. It may help manage fluctuations in the response to levodopa in people with Parkinson's disease. 

• Anticholinergics. These drugs were the main treatment for Parkinson's disease before the introduction of levodopa. In general, they help control tremors in the early stages of the disease. Even so, they're only mildly beneficial and sometimes the benefits are offset by side effects such as dry mouth, nausea, urine retention — especially in men with an enlarged prostate — and severe constipation.

• Antcholinergics can also cause mental problems, including memory loss, confusion and hallucinations. A number of anticholinergic drugs, such as trihexyphenidyl (Artane) and benztropine (Cogentin), are available. The antihistamine diphenhydramine (Benadryl and antidepressants such as amitriptyline (Elavil) work much like anticholinergics and may be used in older adults who can't tolerate anticholinergics themselves.

• Amantadine (Symmetrel, Symadine). This antiviral drug may be prescribed for people in the latter stages of Parkinson's disease, especially if they have problems with involuntary movements induced by levodopa (dyskinesia). Side effects include swollen ankles and a purple mottling of the skin.

• If you're using medications for Parkinson's disease, it's extremely important not to stop taking them on your own. If you're troubled by side effects or any other problems, talk to your doctor.

Surgery
Surgical procedures were once commonly used to treat Parkinson's disease but fell out of favor with the advent of levodopa and other drug therapies. Now, surgical approaches are being re-evaluated. The following procedures may be an option when symptoms can't be controlled with medications:

• Thalamotomy. This procedure has been used for years to reduce tremor in people with Parkinson's disease, although it's not generally helpful for other aspects of parkinsonism. Thalamotomy involves the destruction of small amounts of tissue in the thalamus — a major brain center for relaying messages and transmitting sensations. The surgery can cause slurred speech and sometimes lack of coordination when performed on both sides of the brain. For that reason, it's usually done on only one side of the brain, with the benefits confined to one side of the body.

• Pallidotomy. There has been renewed interest in pallidotomy since improved imaging techniques have allowed surgeons to pinpoint the areas to be treated with greater precision. In this procedure, an electric current is used to destroy a small amount of tissue in the pallidum (globus pallidus), a part of the brain responsible for many symptoms of Parkinson's disease. Pallidotomy may improve tremors, rigidity and slowed movement by interrupting the neural pathway between the globus pallidus and the thalamus. It's especially helpful in countering the involuntary movements caused by drug therapy.

• Although pallidotomy has been helpful for some aspects of Parkinson's disease in certain people, it's not a cure, and in many cases benefits may not last. In addition, the surgery carries a number of risks, including slurred speech, disabling weakness and vision problems, especially when performed on both sides of the body.

Movement problems, such as a tremor, associated with Parkinson's, are primarily caused by inadequate levels of a chemical (dopamine) that transmits messages from the substantia nigra to other parts.

• Deep brain stimulation. In 1997 the FDA approved a new brain implant device that can help control the disabling shaking and trembling caused by Parkinson's disease. The deep brain stimulator consists of a pacemaker-like unit implanted in the chest that transmits electric impulses through a wire to tiny electrodes in the subthalamic nucleus — a structure located deep within the brain that controls many aspects of motor function. The pulses appear to interrupt signals that may play a role in causing tremors. Potential risks exist with the deep brain stimulator, including infection caused by the wire connecting the electrode to the stimulator and the need to perform minor surgery to change the unit's battery. Nevertheless, simulation within the subthalamic nucleus may markedly improve Parkinson's symptoms for many people. The device can also be placed in the thalamus for tremor control or the globus pallidus to produce effects similar to pallidotomy.

Experimental treatments
Although researchers continue to work to develop new drug treatments for Parkinson's disease, great interest also exists in finding a way to replace the dopamine-producing cells in the substantia nigra. One approach has been fetal cell transplantation — a procedure in which fetal cells are implanted into the brains of people with Parkinson's.

Unfortunately, one large study, published in the March 8, 2001, issue of the New England Journal of Medicine, reported that as many as 15 percent of study participants receiving transplanted fetal cells later developed severe involuntary movements (dyskenesias) as a result of too much dopamine.

In addition, the use of fetal cells raises a number of moral and ethical issues that won't be easily resolved. The answer, many researchers believe, is the use of embryonic stem cells.

Stem cells are the parent cells of all tissues in the body. To date, researchers have been able to capture and culture undifferentiated human stem cells in the laboratory. The hope is that researchers may one day be able to direct these cells to become specific types of cells — such as dopamine-producing neurons — that can be used to treat disease. Stem cells used in research are derived from embryos that were produced in a laboratory to treat infertility and are used only with the informed consent of the donors.

Researchers are also investigating genes that code proteins responsible for producing dopamine, drugs that block the action of glutamate — an amino acid that destroys nerve cells — and the role of the antioxidant coenzyme Q-10 in stopping the progression of Parkinson's disease.

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