PARKINSON'S DISEASE

• DEFINITION

Parkinson's disease develops gradually, often starting with a barely noticeable tremor in just one hand. But while tremor may be the most well-known sign of Parkinson's disease, the disorder also commonly causes a slowing or freezing of movement.

Friends and family may notice that your face shows little or no expression and your arms don't swing when you walk. Speech often becomes soft and mumbling. Parkinson's symptoms tend to worsen as the disease progresses.

While there is no cure for Parkinson's disease, many different types of medicines can treat its symptoms. In some cases, your doctor may suggest surgery.

• CAUSES

Many symptoms of Parkinson's disease result from the lack of a chemical messenger, called dopamine, in the brain. This occurs when the specific brain cells that produce dopamine die or become impaired. But researchers still aren't certain about what sets this chain of events in motion. Some theorize that genetic mutations or environmental toxins may play a role in Parkinson's disease.

• RISK FACTOR'S

Risk factors for Parkinson's disease include:

• Age. Young adults very rarely experience Parkinson's disease. It ordinarily begins in middle or late life, and the risk continues to increase with age.
• Heredity. Having one or more close relatives with Parkinson's increases the chances that you'll also develop the disease, although your risk is still less than 5 percent. Recent evidence suggests a crucial role for small contributions from many different genes that program brain architecture.
• Sex. Men are more likely to develop Parkinson's disease than women are.
• Exposure to toxins. Ongoing exposure to herbicides and pesticides puts you at slightly increased risk of Parkinson's.

• SYMPTOMS

The symptoms of Parkinson's disease vary from person to person. Early signs may be subtle and can go unnoticed for months or years. Symptoms typically begin on one side of the body and usually remain worse on that side. Parkinson's signs and symptoms may include:

• Tremor. The characteristic shaking associated with Parkinson's disease often begins in a hand. A back-and-forth rubbing of your thumb and forefinger, known as pill-rolling, is common. However, many people with Parkinson's disease do not experience substantial tremor.
• Slowed motion (bradykinesia). Over time, Parkinson's disease may reduce your ability to initiate voluntary movement. This may make even the simplest tasks difficult and time-consuming. When you walk, your steps may become short and shuffling. Or your feet may freeze to the floor, making it hard to take the first step.
• Rigid muscles. Muscle stiffness often occurs in your limbs and neck. Sometimes the stiffness can be so severe that it limits the range of your movements and causes pain.
• Impaired posture and balance. Your posture may become stooped as a result of Parkinson's disease. Imbalance also is common, although this is usually mild until the later stages of the disease.
• Loss of automatic movements. Blinking, smiling and swinging your arms when you walk are all unconscious acts that are a normal part of being human. In Parkinson's disease, these acts tend to be diminished and even lost. Some people may develop a fixed staring expression and unblinking eyes. Others may no longer gesture or seem animated when they speak.
• Speech changes. Many people with Parkinson's disease have problems with speech. You may speak more softly, rapidly or in a monotone, sometimes slurring or repeating words, or hesitating before speaking.
• Dementia. In the later stages of Parkinson's disease, some people develop problems with memory and mental clarity. Alzheimer's drugs appear to alleviate some of these symptoms to a mild degree.

• TEST'S & DIAGNOSIS

No definitive tests exist for Parkinson's disease, so it can be difficult to diagnose, especially in the early stages. And parkinsonism — the symptoms of Parkinson's disease — can be caused by many other types of problems. Examples include:

• Other neurological disorders. Essential tremor, dementia with Lewy bodies, multiple system atrophy and progressive supranuclear palsy each feature some symptoms common to Parkinson's disease.
• Drugs. Antipsychotic medications — such as chlorpromazine (Thorazine) and haloperidol (Haldol) — block dopamine, as do anti-nausea drugs like prochlorperazine (Compazine) or metoclopramide (Reglan). If you take any of these drugs, you may develop parkinsonism, although it is reversible when the drug is stopped.
• Toxins. Exposure to carbon monoxide, cyanide or certain other toxins can produce symptoms similar to Parkinson's disease.
• Head trauma. Both solitary head injuries and the repetitive variety of head trauma common in boxing have been linked to parkinsonism, although risks are small.
• Structural problems. Strokes or fluid buildup in the brain (hydrocephalus) may occasionally mimic Parkinson's disease.

A diagnosis of Parkinson's disease is based on your medical history and a neurological examination. As part of your medical history, your doctor will want to know about any medications you take and whether you have a family history of Parkinson's. The neurological examination includes an evaluation of your walking and coordination, as well as some simple hand tasks.

A diagnosis of Parkinson's is most likely if you have:

• At least two of the three cardinal Parkinson's symptoms — tremor, slowing of motion and muscle rigidity
• Onset of symptoms on only one side of the body
• Tremor more pronounced at rest, for example, when your hands are resting in your lap
• Strong response to levodopa, a Parkinson's drug

• TREATMENT'S

Your initial response to Parkinson's treatment can be dramatic. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms can usually still be fairly well controlled. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications. In some cases, surgery may be helpful.

Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. Taking dopamine itself is not helpful, because it is unable to enter your brain.

• Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance that we all have in our body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.

  As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). This then requires medication adjustments. Levodopa side effects include confusion, delusions and hallucinations, as well as involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control.

• 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 dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson's disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.

  This class includes pill forms of dopamine agonists, pramipexole (Mirapex) and ropinirole (Requip), as well as a patch form, rotigotine (Neupro). Pergolide (Permax) has been withdrawn from the market because of its association with heart valve problems. A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.

  The side effects of dopamine agonists include those of carbidopa-levodopa, although they're less likely to cause involuntary movements. However, they are substantially more likely to cause hallucinations, sleepiness or swelling. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that's out of character for you, talk to your doctor.

• MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — the enzyme that metabolizes dopamine in the brain. Side effects are rare but can include serious interactions with other medications, including drugs to treat depression and certain narcotics.
• Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it's normally used only in people who aren't responding to other therapies. Entacapone (Comtan) doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo.
• Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson's disease. A number of anticholinergic drugs, such as trihexyphenidyl and benztropine (Cogentin), are available. However, their modest benefits may be offset by side effects such as confusion and hallucinations, particularly in people over the age of 70. Other side effects include dry mouth, nausea, urine retention — especially in men with an enlarged prostate — and severe constipation.
• Antivirals. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include swollen ankles and a purple mottling of the skin.

Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson's disease. Physical therapy may be advisable and 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. A speech therapist or speech pathologist can improve problems with speaking and swallowing.

Surgery
Deep brain stimulation is the most common surgical procedure to treat Parkinson's disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrode.

Deep brain stimulation is most often used for people who have advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesias). Tremor is especially responsive to this therapy. Deep brain stimulation doesn't help dementia and may make that worse.

Like any other brain surgery, this procedure has risks — such as brain hemorrhage or stroke-like problems. Infection also may occur, requiring parts of the device to be replaced. In addition, the unit's battery beneath the skin of the chest wall must be surgically replaced every few years. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.