Treating Parkinson's Disease
There is no cure for Parkinson's disease. But a number of medications can ease symptoms and improve a patient's quality of life. In some patients, surgery to implant a deep brain stimulator is the treatment of choice when drugs have failed or side effects are intolerable. In addition, patients can do much to manage the disease themselves—and feel better—by exercising to increase their flexibility and eating a carefully planned diet to avoid the malnourishment that often comes with difficulty swallowing.
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Drugs
No drug can stop or slow the progression of Parkinson's disease, though a few are being studied and show promise. But many drugs help patients move more easily and function well for years. The two main categories of drugs operate in different ways on the brain:
Dopamine replacement. Most medications on the market compensate for the loss of dopamine in the brain by introducing levodopa, a substance that is chemically very similar to the body's natural neurotransmitter. Taken by mouth, levodopa is converted to dopamine in the brain's basal ganglia and acts like dopamine in the brain's movement centers. Levodopa can produce dramatic results, especially in reducing rigidity and tremor and improving movement. People with mild symptoms can return to near normal. Levodopa is generally taken in combination with carbidopa, which keeps the levodopa from being broken down in the digestive tract before it reaches the brain. It also permits a lower dose of levodopa and reduces side effects, which can include nausea and flushing.
After taking levodopa drugs for five years or more, many people find that the effectiveness begins to wear off, and more than half suffer "on-off syndrome," in which they rapidly cycle between being fairly mobile and being severely impaired as dopamine levels in the brain fluctuate. Taking lower, more frequent doses can control on-off syndrome for a while, but even this strategy begins to lose its effectiveness after 15 to 20 years. At this point, surgery might be considered.
Dopamine agonists. These drugs are not converted into dopamine but rather stimulate the dopamine receptors in the brain and mimic the effects of dopamine at these receptors. This helps compensate for the depletion of the neurotransmitter. Dopamine agonists are often prescribed for younger patients who are in the early stages of the disease because they can alleviate symptoms and delay the need for levodopa—and thus the eventual "on-off" syndrome (and unpredictable fluctuations in symptoms) that occurs after years on that drug. Dopamine agonists are also used in combination with levodopa when the effectiveness of levodopa treatment wanes and a higher dosage induces side effects.
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Dopamine-replacement medications
Sinemet is one of the most widely prescribed treatments for Parkinson's disease. It has two main active ingredients, levodopa (which turns to dopamine in the brain) and carbidopa (which prevents the levodopa from breaking down before reaching the brain). Side effects that may occur include nausea, vomiting, diarrhea, lightheadedness and dizziness, and sleepiness. Sinemet may turn your urine, sweat, and saliva a dark-brown or red color, which is not harmful. If you experience sudden involuntary movements on the drug, you may need a lower dose.
Patients on Sinemet take a dose of entacapone (Comtan) at the same time. This drug has no effect on Parkinson's symptoms itself, but it inhibits an enzyme that breaks down the levodopa in Sinemet, thus extending the effect of each dose. Comtan may produce side effects such as diarrhea, confusion, and hallucinations, and it tends to make urine brownish-orange.
Stalevo contains three active ingredients: levodopa, carbidopa, and entacapone. Side effects may include diarrhea, nausea, dizziness, drowsiness, and insomnia. If you experience sudden involuntary movements, you may need a lower dose. Patients taking the combination should be advised that, occasionally, saliva, urine, or sweat may turn a dark-brown or reddish color, and garments may even become discolored.
Dopamine agonists
These drugs stimulate the dopamine receptors in the brain and mimic the effects of dopamine, helping to compensate for the depletion of the neurotransmitter. This class of drugs includes:
Mirapex and Requip. These dopamine agonists are used alone in the early stages of Parkinson's disease or in combination with levodopa therapy (Sinemet) in later stages. In some patients, they cause a drop in blood pressure when the person rises to a standing position, and they may cause hallucinations or confusion and involuntary movements. If so, the dosage may need to be changed. Other side effects include drowsiness, nausea, vomiting, and swelling of the legs. It's important to let your doctor know of any side effects.
Apokyn. This drug is injected under the skin on an "as-needed" basis to treat "off" episodes when the muscles suddenly become frozen. It acts quickly to improve mobility and is used along with, not in place of, other medications. Apokyn is first tried in the doctor's office so the response can be monitored. If the drug is well tolerated, the patient is given a prescription for use at home. Side effects may include nausea and vomiting, daytime sleepiness, sudden uncontrolled movements, dizziness, and low blood pressure.
Other medications
Amantadine is an antiviral drug that for unknown reasons helps alleviate the rigidity and slowness of movement associated with Parkinson's disease. It may increase levels of dopamine in the brain, and it may lower levels of acetycholine, another neurotransmitter involved in movement. Stiffness and tremors can occur when the two neurotransmitters are out of balance.
Side effects are unusual, though some people note difficulty falling asleep; agitation; trouble concentrating; dry mouth; swelling of the legs, hands or feet; blurred vision; dizziness; or skin mottling. In rare cases, patients experience confusion or hallucinations.
Selegiline, or L-deprenyl, belongs to a class of medications called selective monoamine oxidase inhibitors. It is effective against mild Parkinson's symptoms and can delay the need for levodopa. The drug acts by inhibiting the metabolism of dopamine, thus allowing it to remain in an active state longer. Side effects include nausea, dizziness, abdominal pain, and confusion.
Selegiline is often used with levodopa early in the course of the disease to prevent or slow progression. Though such neuroprotective properties have been shown in laboratory studies, claims that selegiline can delay the natural progression of Parkinson's in patients have not been proved.
Artane and Cogentin are examples of anticholinergics, drugs that are sometimes used in younger patients with severe tremor. The drugs can also help control drooling but are relatively ineffective against other symptoms. Elderly patients are often intolerant of common anticholinergic side effects such as cognitive impairment (specifically loss of short-term memory), dry mouth, and urinary retention.
Surgery
Although medications are very effective for treating Parkinson's disease, in many cases they lose efficacy over time. Patients may need increasing doses or more frequent dosing intervals. Many patients develop abnormal involuntary movements (dyskinesia), which can occur when medication concentrations are at their peak. In addition, increasingly wide fluctuations can occur, with dyskinesia during "on" periods and severe rigidity and slowness of movement during "off" times. For patients with these symptoms, surgery can sometimes offer dramatic improvement.
Until the 1970s, destructive brain surgery was the only available treatment option for Parkinson's patients. Pallidotomy (destruction of a part of the brain known as the globus pallidus) and thalamotomy (destruction of a portion of the thalamus, a relay area in the brain) were moderately effective in relieving rigidity and tremor but did not improve all the symptoms of Parkinson's. These procedures fell out of favor with the introduction of Sinemet. However, it was soon realized that patients developed side effects and loss of efficacy after long-term treatment with medication, and surgery was reintroduced as an effective treatment once medical treatment began to fail.
In the 1980s, neurosurgeons discovered that stimulation of certain brain regions could be more effective and safer than destructive procedures. Deep brain stimulation (DBS) was rapidly adopted throughout the United States and the rest of the world and is now the main surgical technique used for the treatment of movement disorders. Sometimes called a "brain pacemaker" because of its similarity to a cardiac pacemaker, DBS delivers electrical stimulation to the brain via a thin insulated wire, or lead. This lead has four electrodes at the end, which the neurosurgeon uses to precisely target specific areas in the brain, depending on the nature of the particular patient's disability. Continuous stimulation of these brain regions blocks the signals that cause the disabling motor symptoms of Parkinson's disease.
Good candidates for DBS are patients who respond well to the levodopa drug Sinemet, have developed intolerable side effects, and have no serious medical or cognitive difficulties that might increase the risks of surgery. Implanting DBS carries the same risks associated with any brain surgery: intracranial hemorrhage, leakage of cerebrospinal fluid around the brain, infection, seizure, stroke, confusion and attention problems, and speech difficulties.
In many cases, DBS can improve tremor, rigidity, slowness of movement, and gait by 60 to 80 percent. In addition, patients are able to decrease medication intake by an average of 60 percent. Unfortunately, DBS does not improve cognitive function or dementia.
Implanting the deep brain stimulators
DBS can help many of the symptoms of Parkinson's, including tremor, rigidity, and slowness of movement. An advantage is that, unlike medication, the stimulator is "on" all the time, so most patients find relief from the "on-off" syndrome common with drug treatment. Most patients with an implanted stimulator can reduce their medication significantly—often cutting dosages in half. In addition, patients often find relief from drugs' side effects, including the involuntary movements sometimes caused by medication.
Both sides of the brain are implanted with the deep brain stimulation devices, so that both sides of the body are treated for optimum symptom control. Components of the device include:
- The lead, a thin, insulated coiled wire with four electrodes at the end. The neurosurgeon places these electrodes in the thalamus (most effective for the treatment of tremor, but less effective for other symptoms of Parkinson's), the subthalamic nucleus (effective for all the symptoms of Parkinson's, but sometimes associated with an increased risk of cognitive difficulties postoperatively), or the internal globus pallidus (often somewhat less effective than subthalamic stimulation, but perhaps with less risk of cognitive problems), depending on the patient's needs.
- The neurostimulator, a device containing a battery and microelectronic circuitry that is implanted under the skin near the collarbone and generates electrical signals that are delivered to the targeted structures in the brain.
- The extension, an insulated wire that is passed under the skin of the head, neck, and shoulder to connect the lead to the implanted neurostimulator.
The surgery may take place in two parts, with each side of the brain completed on a separate day, or it may all be accomplished in one operation. The patient is awake during the procedure, in order to assist the surgical team in determining the best target for the electrodes. At the beginning of the procedure, the patient is given some sedation and local anesthetic. An opening is made in the skull, and a hair-fine wire (microelectrode) is inserted to the target point while the surgical team listens to the signals transmitted by brain cells along the path of insertion. The patient's arms and legs are usually moved passively to test for brain cell response, allowing the surgical team to precisely locate the target in the brain.
Once the optimal target is determined, the DBS lead is introduced. A small electric current is transmitted through the lead, and tests are conducted to gauge how well the stimulation is working. The patient may be asked questions and asked to perform certain tasks, such as counting or moving his fingers or toes, to help the neurosurgeon test the stimulation.
The neurostimulator is usually placed under general anesthesia in a separate procedure. Programming of the deep brain stimulators takes place three to four weeks later, after which medications will usually be decreased or potentially even stopped.
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