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What Are the Drug Treatments for Parkinson's Disease 
The goals of treatment for Parkinson's disease are to relieve disabilities and to balance the problems of the disease with the side effects of the medications. Treatment is very individualized for this complicated problem, and patients must 
work closely with physicians and therapists throughout the course of the disease to customize a program suitable for their particular and changing needs. Patients should never change their medications without consulting their physicians, and they should never stop taking their medications abruptly.


Treatments by Stage of Parkinson's Disease

Onset of Parkinson's Disease / Life-Style Changes
- (Exercise, Diet)
- Drugs
- Levodopa
- Anticholinergic Drugs
- Amantadine
- Selegiline
- Dopamine Agonists
- Catechol-O-Methyl Transferase Inhibitor 

Long-Term Maintenance Therapy Levodopa in combination with:
Selegiline
Dopamine Agonists
Catechol-O-Methyl Transferase Inhibitors 

Advanced Disease

Experimental Drugs

Surgical Procedures:
Pallidotomy, Thalamotomy, Radiosurgery, Neurostimulation,

Tissue Implantation 



Levodopa and General Guidelines for Treating the Stages of Parkinson's Disease
Onset of Parkinson's Disease. There is no standard method for treating the earliest symptoms. Before symptoms become disabling, some patients prefer trying lifestyle changes first, including exercise and diet. When the patient and physician determine that medication is necessary, the patient will start out with as low a dose as possible of any drug used.

Levodopa, or L-dopa, which is converted to dopamine in the brain, remains the gold standard for treating Parkinson's disease. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America.

The timing for its first administration in the development of the disease is controversial. Many physicians now initiate treatment with levodopa at the first sign of symptoms, particularly in people over 70. For younger people, who will require long-term treatment, physicians sometimes delay levodopa until symptoms become pronounced or after other drugs are no longer effective. Such physicians are responding to widely held beliefs that patients lose their response to the drug after a few years or that L-dopa may even become toxic over time. Careful reviews of studies indicate, however, that taking L-dopa for a long time does not harm remaining dopamine nerve cells, and in fact, may even promote recovery of those that are damaged. There is even some evidence that taking levodopa early in the course of the illness can prolong life. It is true that certain symptoms may become less responsive to L-dopa, but most patients, if not all, derive substantial benefit from the drug throughout their lives.

Levodopa, or L-dopa, is most effective against rigidity and slowness, but produces less benefit for tremor, balance, and gait. Dosages vary, although the preparation is usually taken in three or four divided doses per day. If the symptoms do not improve after two or three months, the physician should look for problems other than Parkinson's, although some Parkinson's patients may have abnormalities in other brain sites that do not respond to L-dopa. Sometimes patients are so depressed they cannot tell if the drug is beneficial or not, and only a series of physical examinations by the doctor will indicate that the drug is actually helping. In half of Parkinson's patients, levodopa significantly improves the quality of life for many years. One study indicated that women may be more sensitive than men to the effects of L-dopa, although this finding needs to be confirmed in further trials. The observation could also simply indicate that the disease progresses more swiftly in men.

The toxic effects of levodopa with or without carbidopa are considerable. Nausea and low blood pressure are the most common problems during the first few weeks, particularly if the initial dose is too high. The addition of extra supplements of carbidopa reduces this effect to some degree. Taking the drug with food can alleviate the nausea. It should be noted, however, that proteins interfere with intestinal absorption of levodopa, and some physicians recommend not eating any protein until nighttime in order to avoid this interference. To offset low blood pressure, the patient should drink lots of fluids and possibly increase salt intake. The drugs can affect other organs, sometimes producing disturbances of heart rhythm or gastrointestinal bleeding. Major impacts, however, are psychiatric. Patients taking levodopa, especially in combination with other drugs, can experience confusion, extreme emotional states, vivid dreams, visual and possibly auditory hallucinations, anxiety, and even psychosis. The drug may even unmask dementia that had not been previously noticed. Because psychiatric side effects often occur at night, some physicians recommend reducing or stopping the evening dose. It should be noted that levodopa provokes fewer psychiatric side effects than other drugs used for Parkinson's disease, including anticholinergics, selegiline, amantadine, and dopamine agonists [ see below ]. Some studies indicate that the drug clozapine (Clozaril), normally used in schizophrenia, may help offset the psychiatric side effects, but it too has some serious side effects and needs to be used with caution. (Newer, similar drugs, such as risperidone or olanzapine, that are alternatives to clozapine in schizophrenia, can actually worsen Parkinson's symptoms.)

Increasingly, however, drugs that can preserve residual dopamine are being used before L-dopa is even started. Strategies include starting out with such agents as monotherapy (single drugs) or starting earlier or later in combinations with L-dopa. Selegiline is the most common of these drugs and is currently the first choice for younger adults; studies indicate that it may postpone the need for L-dopa up to several months and that it slows down the progression of disability. Other drugs that are very promising for early onset Parkinson's include the dopamine agonists (ropinirole, pramipexole, pergolide, and bromocriptine) and catechol-o-methyl transferase (COMT) inhibitors. Studies indicate that both ropinirole and pramipexole slow the progression of the disease when it is in early stages and delay the need for L-dopa. In some cases they have controlled symptoms for more than three years. (A ten year study of patients who were given bromocriptine, an older dopamine agonist, in early stages reported no improvement in survival, but the effects of newer drugs are not yet known.) At one time, anticholinergics were the preferred drugs for initial therapy, but they have lost favor in the past few years because of side effects and because newer drugs are proving to be effective and tolerable. The drug amantadine stimulates dopamine release and may help early symptoms. Some studies suggest that this agent may lose effectiveness within about a year, however. [For a description of individual drugs, see Drugs Used for Parkinson's Disease, below.]

Long-Term Maintenance Therapy. Within four to six years of treatment with levodopa, the effects of the drug in many patients begin to last for shorter periods of time (called the wearing-off effect ), and most patients start to experience motor fluctuations. For instance, patients often first notice slowness (bradykinesia) or tremor in the morning before the next dose is due. Less commonly, some patients experience painful dystonia, muscle spasms that can cause sustained contortions of various parts of the body, particularly the neck, jaw, trunk, and eyes and possibly the feet. Patients must increase the frequency of levodopa doses. This puts them at risk for dyskinesia (the inability to control muscles) which usually occurs when the drug level peaks. Dyskinesia can take many forms, most often uncontrolled flailing of the arms and legs or chorea, rapid and repetitive motions that can affect the limbs, face, tongue, mouth, and neck. Dyskinesia is not painful, but it is very distressing. In about 15% to 20% of patients the fluctuations become extreme, a phenomenon known as the on-off effect , which consists of unpredictable, alternating periods, sometimes within minutes or seconds, of dyskinesia and immobility. The transition may follow such symptoms as intense anxiety, sweating, and rapid heartbeats.

One study found that within the first five years of therapy, about 20% of patients had predictable wearing-off periods, and at 15 years, 70% of patients had off periods or dyskinesia. About 30% however, experienced neither side effect after 20 years of levodopa. Debate is ongoing about whether the wearing-off effect and dyskinesia are due to progression of the disease, the prolonged exposure to dopamine, or both. Some experts believe that the brain's dopamine neurons become incapable of storing dopamine and when the levodopa wears off, little or no natural dopamine remains. Some studies have suggested that as levodopa is metabolized, it produces oxygen free radicals, which in turn accelerates dopamine degradation.

To reduce the effects of fluctuation and the wearing-off effect, it is important to maintain as consistent a level of dopamine as possible. To make matters more difficult, levodopa is poorly absorbed and may remain in the stomach a long time. A number of strategies are being developed to take care of these problems. Some patients take multiple small doses on an empty stomach, crushing the pills and mixing them with a lot of liquid. A liquid form of Sinemet may produce fewer fluctuations and a prolonged "on" time compared with the tablet. A prolonged release version of levodopa and carbidopa (Sinemet CR) is also available to control fluctuations for some people. Some evidence suggests that there is no actual difference in symptom control between the sustained and immediate release forms, but patients on Sinemet CR tend to experience a better quality of life.

In general, however, physicians are increasingly using combinations of levodopa and other drugs to reduce adverse effects. Selegiline is the most common combination drug and may delay the wearing-off effect for six months to a year, although some people have experienced a delay as long as two years. Selegiline does not have much impact on the on-off phenomenon itself. Other combination drugs are proving to be very effective; they include the dopamine agonists pramipexole and ropinirole and catechol-o-methyl transferase inhibitors. Some experts strongly recommend starting out with low doses of several drugs rather than high doses of a single one. [ See discussions of individual drugs, below.]

Advanced Disease. Eventually, symptoms such as stooped posture, freezing, and speech difficulties may not respond to drug treatment. Total unresponsiveness is unlikely, however, even after 20 years of treatment. Simply increasing the dose of levodopa or its frequency raises an unacceptable risk of the distressing side effects, including dyskinesia, confusion, and even hallucinations. Some physicians have tried hospitalizing patients, totally withdrawing the levodopa, and then readministering it, but benefits were seen for only a few months, and there were some dangerous risks to the process of withdrawal, including pneumonia and blood clots in the lungs. Surgical treatments, including pallidotomy, neurostimulation, and transplantation may help some patients. Research is ongoing to develop drugs and procedures that will manage advanced disease and possibly even reverse the process.


Descriptions of Other Drugs Used for Parkinson's Disease
Selegiline and Other Monoamine Oxidase Inhibitors. Selegiline (Eldepryl, Movergan), also known as deprenyl, is an antioxidant drug that blocks the enzyme monoamine oxidase B, which degrades dopamine. Selegiline (Eldepryl, Movergan), or deprenyl, is the drug most commonly used in early-onset disease and in combination with levodopa for maintenance. It may actually have nerve-protective properties. Of great concern is a long-term study and its 1998 update that found an increased risk of death after people had taken Sinemet combined with selegiline (particularly in the third and fourth years) compared to those taking Sinemet alone. In the group taking Sinemet, those who died had a higher rate of dementia and history of falls. Shedding some light on these negative results was another study that reported a high incidence of orthostatic hypotension in some people taking Sinemet plus selegiline. Orthostatic hypotension is an abrupt and sometimes severe drop in blood pressure after standing and could indicate changes in the blood vessels that might contribute to more serious complications. Some experts recommend that patients taking the drugs should be tested for orthostatic hypotension; those that show susceptibility should be withdrawn gradually. On the encouraging side, a recent analysis of five long-term studies found no increased mortality rate using the combination. It should be noted that other Parkinson's drugs, as well as lazabemide, a new MAO-B inhibitor, can also cause orthostatic hypotension. Selegiline has adverse interactions with nearly every antidepressant, some very serious. Patients suffering from depression should discuss all treatment options with their physician. People taking any monoamine oxidase inhibitor are at risk for high blood pressure if they consume tyramine-containing foods or beverages, including aged cheeses, most red wines, vermouth, dried meats and fish, canned figs, fava beans, and concentrated yeast products.

Dopamine Agonists. The drugs known as dopamine agonists are being used in early-onset Parkinson's to delay the administration of L-dopa and are also used in long-term maintenance either alone or in combination with levodopa. These drugs stimulate dopamine receptors in the substantia nigra, the part of the brain in which Parkinson's is thought to originate. Pramipexole (Mirapex) and ropinirole (Requip) are proving to be especially safe and effective for both initial sole therapy and in combination with L-dopa. Ropinirole allows lower dosages of L-dopa and may produce better "off" times than the use of L-dopa alone. Both pramipexole and ropinirole are proving to be effective as single agents and may induce a longer delay before onset of motor fluctuations and dyskinesias than L-dopa. Although comparable in effectiveness to bromocriptine, an older so-called ergot-derived dopamine agonist, ropinirole may have a more positive impact on daily functioning. Pramipexole appears to have antidepressant properties and helps reduce tremors, rigidity, and akinesia. Such drugs may even have actions that protect the nerves from further damage. Side effects of pramipexole and ropinirole vary but include nausea, constipation, headache, dyskinesia, hypotension, and nasal congestion. The drugs can also cause nightmares, hallucinations, and even psychosis. Of concern are reports of sudden sleep attacks, which can be very serious, particularly if patients are driving. Even more specific dopamine agonists are showing promise in early studies.

Older dopamine agonists, such as bromocriptine (Parlodel), pergolide (Permax), lisuride, and cabergoline (a long-acting agent not yet available in the US) are known as ergot-derived drugs and have more severe side effects than the newer dopamine agonists. Pergolide, however, is the most powerful of all dopamine agonists and a 1999 study reported that it can significantly improve symptoms in early stages as a single agent. Side effects in the study include nausea, dizziness, insomnia, and weight loss. Uncommon, but serious side effects have been reported with the use of ergot-derived drugs, including scarring on the outside of the lungs or other organs and skin abnormalities. Experts recommend periodic monitoring for these side effects for patients taking any ergot-derived dopamine agonist.

Apomorphine is a dopamine agonist used as a single daily injection. It is particularly effective when administered as a "rescue" drug in people experiencing on-off effects severe enough to require going off L-dopa for a few days. It causes vomiting, however, and needs to be used with domperidone, an anti-nausea drug. Other side effects are excitability and aggression. Patches, nasal sprays, and other forms of apomorphine are showing promise as alternatives to injections. Apomorphine may also be particularly helpful in alleviating nighttime symptoms, including pain and restless legs syndrome.

Catechol-O-Methyl Transferase Inhibitors. The catechol-O-methyl transferase (COMT) inhibitors, tolcapone (Tasmar) and entacapone (Comtan), increase concentrations of existing dopamine in the brain. They are proving to be particularly useful in early treatment and for long-term maintenance with levodopa. Both drugs improve motor fluctuations and have shown impressive results in improving "on" time and reducing the requirements for L-dopa. Side effects include occasional diarrhea and dyskinesia. Of concern, however, are reports of a few deaths from liver damage in patients taking tolcapone and the drug has been taken off the market in many countries. It is now recommended only for patients who do not have severe movement abnormalities and who cannot take other treatments. Whether entacapone has similar and serious effects is not yet known, but physicians should monitor liver function regularly in anyone taking a COMP inhibitor. Patients themselves should watch out for symptoms of liver damage, including jaundice (yellowish skin), fatigue, and loss of appetite. If the patient does not respond to the drug within three weeks, it should be withdrawn. No one should withdraw abruptly from these drugs.

Anticholinergic Drugs. Anticholinergics work best against tremor in the early stages, but are not as effective against bradykinesia and posture problems. They commonly cause dryness of the mouth (which can actually be an advantage in some people who experience drooling). Other side effects are nausea, urinary retention, blurred vision, and constipation. These drugs can also increase heart rate, worsen constipation, and cause urine retention in men with enlarged prostate. People with glaucoma should use these drugs cautiously. Anticholinergics can sometimes cause significant mental problems, including memory loss, confusion, and even hallucinations, which can be particularly problematic for elderly people with signs of existing dementia and people taking tricyclic antidepressants. Among the many anticholinergics are trihexyphenidyl (Artane, Trihexy), benztropine (Congentin), biperiden (Akineton), procyclidine (Kemadrin), and ethopropazine (Parisdol). Orphanadrine (Norflex) is a drug with anticholinergic properties but is also a muscle relaxant and does not cause urinary retention. Other drugs with anticholinergic properties, such as the antihistamine diphenhydramine (Benadryl) and tricyclic antidepressants, such as amitriptyline (Elavil, Endep) and doxepin (Adapin, Sinequan), may be used in combination therapies or for elderly people who cannot tolerate the more powerful drugs. These drugs have some side effects that are different from the anticholinergic agents, which should be discussed with the doctor. Withdrawal from anticholinergics or any drug used for Parkinson's disease should be gradual in order to avoid aggravating Parkinson symptoms.

Amantadine. Amantadine (Symadine, Symmetrel) stimulates the release of dopamine and may also be used for patients with early mild symptoms. According to some studies, it can also benefit patients in advanced stages who are unresponsive to other drugs. Possibly accounting for such benefits, researchers in 1999 found that amantadine increases certain factors in the immune system (interferon-gamma and interleukins 2 and 10) that may play a role in the disease process. Unlike the anticholinergics, it has some benefit against muscle rigidity and slowness. It is less powerful than levodopa and may lose its effectiveness after about half a year. It may also reduce motor fluctuations brought on by levadopa, however, and these benefits appear to persist for at least a year. Side effects are similar to those of anticholinergic drugs and also may include swollen ankles and mottled skin. Overdose can cause serious and even life-threatening toxicity. Patients with Parkinson's should not withdraw from this drug abruptly: in rare instances can cause acute delirium or a life-threatening condition called neuroleptic malignant syndrome. Pregnant or nursing women should not use this drug.


Experimental Agents
Investigators have been studying nicotine administration because of the observation that smokers appear to have a lower risk for Parkinson's disease. Studies on nicotine patches have been conflicting, however; although some suggest benefit, one 1999 study reported worsening motor control in patients who wore 35 mg patches. Of particular interest was the incidental discovery in 1999 that the unique antidepressant mirtazapine reduced tremors and dyskinesia in a small group of patients. This finding certainly warrants more study. A number of experimental drugs, including remacemide and riluzole, are being investigated for Parkinson's disease because they block the actions of glutamate, an amino acid that is a particularly potent nerve cell killer. Some of these drugs block a receptor group to glutamate called N-methyl-D-aspartate (NMDA). NMDA antagonists are showing some promise for reducing symptoms of Parkinson's disease, particularly tremor, include memantine and budipine. Another area of research is therapy that administers genes that code proteins responsible for producing dopamine or protect or even heal nerve cells damaged by Parkinson's disease. 

Miscellaneous Treatments
Botulism Toxin for Drooling. In search of a simple solution to the problem of drooling, scientists have reported that injections of very small amounts of botulinum toxin A effectively reduce saliva production and drooling. In such small amounts the toxin is safe.

Collagen Injections to Treat Voice Loss. A relatively simple procedure of injecting collagen appears to be a safe and effective method of improving the voice and speech disorders caused by Parkinson's disease. The procedure augments the collagen in the vocal fold, and was found in a preliminary 1999 study to significantly help 75% of those who had the injections.

Hormone Replacement Therapy. Studies indicate that taking hormone replacement therapy after menopause reduces the risk of developing Parkinson's. Other studies show that it may also reduce the severity of early-onset Parkinson's as well as dementia related to the disorder.



What Are Surgical Procedures for Parkinson's Disease 

Pallidotomy
Pallidotomy is a surgical procedure that may be appropriate for some patients when drug therapy no longer works. It was used years ago with very limited success and was abandoned when levodopa was introduced. Pallidotomy has been revived recently because of advances in imaging that allow new understanding about how motor information is processed in the brain and new techniques that allow surgeons to pinpoint the critical areas much more exactly. In some patients, surgery restores normal brain activity related to voluntary movement. It does not cure the disease, however, and its primary benefit is to allow people to continue on Sinemet without incurring its side effects. The procedure is irreversible. The neurosurgeon drills a small hole into the skull and inserts an electrode, which generates a current and heat to destroy small amounts of tissue in the globus pallidus, a part of the brain responsible for many Parkinson's symptoms, particularly those that develop after long-term use of levodopa. The patient is awake during the operation, which takes about six hours. The hospital stay averages two days. To date, the standard procedure involves one side of the brain (unilateral pallidotomy). A 1999 review of 10 studies reported that unilateral pallidotomy is relatively safe and effective but more experience is needed to determine the full benefits and long-term effects. Bilateral pallidotomy (surgery on both sides of the brain) is currently being researched. While some patients have reported good improvement with the procedure, it can cause a range of cognitive, behavioral, and emotional dysfunctions.

In general, appropriate candidates for unilateral pallidotomy are patients with advanced disease who no longer benefit from drug treatments. The best results occur in patients with medication-induced dyskinesias, rigidity, and tremor; surgery has less effect on balance, gait disorders, and voice volume. Some studies have reported, however, that voice volume improved considerably after surgery in some patients with mild problems, especially when it was performed on the patient's right side. In one study, about half of patients who could stand independently before the procedure reported better stability and fewer falls. The procedure does not restore the ability to stand independently in patients who could not do so before surgery. In another two-year study, dyskinesia significantly improved on the side of the body opposite to where the surgery occurred, as did tremor, bradykinesia, and rigidity, and such benefits persisted. To a lesser degree, these symptoms initially improved on the same side of the body as the surgery but were not sustained over time. About half of the patients went from being dependent to independent, particularly in being able to feed and dress themselves, and remained that way for the next two years.

Unfortunately, only about 5% to 10% of Parkinson's patients are candidates. The procedure is generally not recommended for people who do not respond to levodopa, who are very elderly, whose primary symptom is tremor, whose predominant symptoms are freezing and falling (especially during on-periods), who have serious medical or mental disorders, or those with parkinsonism (as opposed to idiopathic Parkinson's disease). Surgical experience is improving outcomes, but even in centers with high track records, serious and permanent complications occur in 1% to 3% of cases and include stroke, paralysis, numbness, and impaired peripheral vision, perhaps even blindness. Studies show that neuropsychologic problems such as a decline in memory capacity may also occur. The procedure can even be fatal. Patients should have the surgery performed only in centers that have experience with the procedure.


Thalamotomy
Thalamotomy uses the same techniques as in pallidotomy, but it is performed on the thalamus, which is a major brain center for relaying messages. Thalamotomy has been reported to significantly reduce or completely stop tremor in 80% to 90% of patients. It does not appear to have much effect on other symptoms. Complications are similar to pallidotomy, except there is no danger of vision loss.


Neurostimulation (Deep Brain Stimulation)
Procedures called neurostimulation, also called deep brain stimulation, use electric pulse generators to control symptoms. They are proving to be safe and effective alternatives to surgery. Appropriate candidates are similar to those for surgery. (Patients being given neurostimulation, however, should not have pacemakers.) Like pallidotomy and thalamotomy, neurostimulation is not a cure; on the other hand, it does not remove brain tissue and is reversible. Complications occur in 2% to 4% of operations. The most serious is bleeding, which can cause stroke. Of some concern, however, is a possible risk for hemorrhage during implantation, and some experts are not convinced of the safety of implanting a polyurethane device in the brain.

Neurostimulation of the Thalamus. Neurostimulation of thalamus helps patients with tremor and is proving to be as effective and safer than thalamotomy. One procedure (Activa Tremor Control System) surgically implants a tiny pulse generator near the collar bone that is connected to four electrodes that have been implanted in the thalamus of the brain. The generator delivers programmed pulses to the thalamus, which the patient can turn on and off using a magnet held over the skin. When the pulses are turned on, the tremor is suppressed. Studies are reporting improvement in tremor in up to 85% of patients, although only on one side of the body. (Double implants are being studied.) Long-term effects are still unknown, although studies are indicating that it is safe and effective. The generator must be replaced every three to five years, and the procedure is very expensive.

Neurostimulation of the Subthalamic Nucleus or Globus Pallidus. Investigators are also studying the use of pulse generators implanted in the globus pallidus or the subthalamic nucleus, which control symptoms of rigidity and involuntary motion. It is not yet clear which site offers the best target for symptom improvement, although early evidence indicates that subthalamus stimulation may be a better target for patients with advanced Parkinson's symptoms. Some studies on this approach have reported improved gait, walking ability, and less upper limb rigidity. (A test evaluating the effects of apomorphine may be a useful predictor of the best candidates for subthalamic stimulation.) Stimulation of both sides (bilateral neurostimulation) of the pallidus and subthalamus are also being investigated. Early results are promising.


Tissue Implantation
Experimental surgery is showing remarkable promise using fetal brain cells rich in dopamine implanted in the substantia nigra. Fetal cells are the best replacements available, since these early cells have the capacity to develop into every cell found in the adult. In implanted patients, these fetal cells produce dopamine. Implantation best improves rigidity, slow movements, and the on-off effect; it has no effect on tremor. It can reduce the need for medication by up to half, but it takes up to 6 months for improvement to occur. One 1999 study reported that the benefits were lasting for at least five years and 10-year follow-up on the few early patients reported that the implants were still working and producing dopamine. Improvement seems significant, however, only in patients under 60, most likely because their brain tissue is more responsive than in older patients. Another study found that while patients under 60 improved, patients older than 60 did not. In fact, some of the older patients got worse, and at this time there is no way to predict who will benefit from tissue transplants. Some experts consider fetal tissue transplant an exciting and promising horizon of treatment, as the fetal cells survive and manufacture dopamine in the brain. The use of fetal tissue is extremely controversial, however, and research is ongoing for alternatives, including the use of cells from other mammals or human placentas and the use of synthetic microspheres to deliver dopamine directly to the brain. Some researchers hope to use cloning techniques on animal fetuses as a source for dopamine-producing nerve cells. Animal and laboratory studies are also using gene therapies and other advanced treatments for transplanting dopamine-producing cells or nerve-protecting cells into the brain. An exciting experimental technique involves replacing damaged cells in the brain with dopamine-producing nerve cells grown under laboratory conditions.


Radiosurgery
Radiosurgery is a non-invasive surgical technique typically used for brain cancer that is now being investigated for both thalamotomy and pallidotomy in patients who are not candidates for standard surgery. It employs a so-called gamma knife, which is not a knife at all, but 300 intersecting radiation beams that are directed through holes in a helmet to target precisely affected sites in the brain. Early studies are showing that it improves symptoms after about six to eight weeks. The only side effect reported so far has been swelling in the brain in a few patients, which appears to resolve over time. 

Transcranial Magnetic Stimulation
Transcranial magnetic stimulation (TMS) employs high frequency magnetic pulses that target affected areas of the brain. It is noninvasive and is being investigated for Parkinson's disease, and one 1999 study reported symptom improvement in patients treated twice a day. It should be pointed out that comparable successes were being reported in patients with depression who were given TMS, but well-controlled studies found TMS no more effective than placebo (a "dummy" treatment). And it should be noted that Parkinson's patients often respond very well to placebo treatments.




What Lifestyle Changes Can Help Parkinson's Disease 
Diet
No special diets or natural foods have been shown to slow down the progression of Parkinson's disease. High levels of proteins, however, compete with levodopa for transport to the brain and reduce its effectiveness. Some experts advise a low 
protein diet during the day with almost all protein eaten in the evening meal. Loading proteins at night, however, can produce a severe "off" period during sleep, causing some people to awaken unable to move. Avoiding protein altogether is not the solution, since malnutrition can result. Most experts now recommend trying to 
maintain a carbohydrate-to-protein ratio of 7:1 throughout the day. This may be difficult to calculate and some physicians recommend simply keeping proteins to 12% of total daily calories. As an aid in calculation, it may be helpful to note that food labels indicate proteins in grams and that one gram of protein equals four calories. Good control of protein intake may help minimize fluctuations and wearing-off and may allow some patients to reduce their daily levodopa dosage. Animal studies indicate that restricting the intake of total calories increases resistance to toxic 
effects on nerve cells.

Eating whole grains and fresh fruits and vegetables is the best approach for any healthy life. A diet rich in fruits and vegetables may help protect nerve cell function. Many of these foods are also often rich in fiber, which is particularly important for helping to prevent constipation. People whose diets have been low in fiber should increase it gradually. It is best to obtain dietary fiber, soluble or insoluble, in the natural form of whole grains, nuts, legumes, fruits and vegetables; if it proves difficult to do so, psyllium, a grain naturally found in India, is an excellent soluble fiber supplement (Metamucil, Fiberall, Perdiem Fiber). Non-caffeinated beverages are particularly important in preventing constipation. Coffee and tea can actually reduce fluids, however, by increasing urination.


Rehabilitation, Exercise, and Other Helpful Therapies
Exercise Programs. Physical therapy is extremely important for the Parkinson's patient and usually follows an approach that uses active and passive exercise, gait training, practice in normal activities, and if needed, hot or cold treatments, water therapy, and electrical stimulation. Passive exercise, mostly stretching and manipulation of muscles by a physical therapist, is aimed at preventing muscles 
from shortening. An active exercise program that begins with slow and gentle exercises and becomes progressively more intense may improve mobility in patients with early and mid-stage Parkinson's disease. Active exercises are used to help range-of-motion, coordination, and speed. Exercise is also essential for well-being; it is a common denominator in patients who are able to maintain productive years. Patients should continually make efforts to practice movement, even simple ones, such as marching in place, making circular arm movements, and raising the legs up and down while sitting. Patients who enjoy sports or the use of exercise equipment should continue with these activities even if their skills diminish, assuming there are no other medical conditions that would prevent them.

Gait Training. Practicing new methods for standing, walking, and turning are 
important for retaining balance. Experts recommend taking large steps when walking, raising the toes at the forward step, and hitting the ground with the heel. Small steps should be taken while turning. When walking or turning, the legs should be 12 to 15 inches apart to provide a wide base. Patients should not wear rubber or 
crepe-soled shoes because they grip the floor and may cause the patient to fall forward. The use of rhythmic stimulation, such as the use of a metronome (a simple device used by musicians to keep time), may be even more effective than music in enabling some patients to walk faster and take longer steps. One study found that setting a metronome rhythm to about 10% faster than the patient's fastest gait offers significant improvement over walking to no rhythm at all or to a rhythm that matches the gait.

Reducing Muscle Freezing. The patient should practice regular daily activities that simplify actions and reduce the incidence of muscle freezing. Most often, freezing occurs when a patient begins to move or is presented with an obstacle. Sometimes, simply being touched by another person can release the patient (although a Parkinson's patient should never be pulled or pushed). If the legs feel frozen, sometimes simply lifting the toes frees the spasm. Rocking from side to side is 
useful, and some people have found that humming a marching tune helps. Because trying to coordinate a number of physical operations at the same time can cause freezing, the patient might find it helpful to divide actions into separate events. For instance, when going through a doorway, a patient should approach the door, stop, open the door, stop, then walk through the doorway. Music has been shown to help people move and to get out of bed in the morning. Some report that wearing a Walkman and turning music on in situations associated with freezing, such as crossing a street, is helpful.

Sleep Deprivation Therapy. Sleep deprivation therapy may have a role in treating some cases of depression and some studies are finding some benefits on the depression, tremor, and rigidity experienced by Parkinson's patients. Scientists believe that sleep deprivation produces certain anticholinergic effects, which may ameliorate both depression and Parkinson's symptoms.

Mental Therapies. Some studies indicate that being mentally fit may be as important for Parkinson's patients as being physically fit. Mental training may actually increase dopamine in the brain. Some experts recommend selecting or learning new hobbies that require finger and hand mobility, such as sewing, carpentry, fishing, or playing cards. Deep breathing and relaxation exercises are important; they may help maintain proper speech control, control tremor, and reduce anxiety. Psychologic therapy and support is important for the depression and loss of motivation that often accompany this difficult condition. One study suggests that marital stress can even encourage loss of mobility. Although psychological and behavioral therapies can 
be expensive, a number of support programs and groups that can be invaluable for the patient and the family are available at little or no cost.

Speech Therapy. Speech therapy may be required for those who develop a monotone voice and lose volume. A technique called the Lee Silverman Voice Treatment may be particularly effective. It has five major components: 1. Focus on 
the voice ("think loud/think shout"). 2. High effort (pushes patients to overcome limitations). 3. Intensive treatment (16 session in one month). 4 Calibration (learning 
to know and accept the amount effort needed to produce normal sound so it becomes automatic. 5. Quantification (continuous feedback to objectively document success).

Equipment and Devices. A number of devices can be helpful. Rails can be installed where the patient needs support in getting up or down, such as along the bed and in the bathroom. Walkers with locking wheels are helpful. Chairs should have straight backs, with firm seats and arm rests. Firm mattresses and satin sheets or less expensive sheets with high thread counts are useful for helping patients slide out of bed.


Vitamin Supplements and Alternative Therapies
No evidence exists that vitamins improve the outlook of Parkinson's disease. However, some people believe that vitamin B6 (pyridoxine) is beneficial because it is necessary in the production and metabolism of dopamine. Most B vitamins play important roles in the brain and central nervous system. Although the major food sources of B vitamins are meats and dairy products, which are high in protein, these vitamins are also found in whole grains and are added as supplements to commercial cereals. Co-enzyme Q10, a vitamin-like antioxidant substance may 
have protective benefits for Parkinson's patients and is available in natural product stores. Some people think certain antioxidant vitamins, such as C and E, may be helpful. High doses (2000 IU per day) of vitamin E have shown no benefit in Parkinson's disease, however, and research is now suggesting that some antioxidant vitamins may even become harmful in high doses. People have found that herb tea made from Senna is helpful.


Board of Editors
Harvey Simon, MD, Editor-in-Chief, Massachusetts Institute of Technology; Physician, Massachusetts General Hospital

Stephen A. Cannistra, MD, Oncology, Associate Professor of Medicine, Harvard Medical School; 
Director, Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center

Masha J. Etkin, MD, PhD, Gynecology, Harvard Medical School; Physician, Massachusetts General Hospital

John E. Godine, MD, PhD, Metabolism, Harvard Medical School; Associate Physician, Massachusetts General Hospital

Daniel Heller, MD, Pediatrics, Harvard Medical School; Associate Pediatrician, Massachusetts General Hospital; Active Staff, Children's Hospital

Paul C. Shellito, MD, Surgery, Harvard Medical School; Associate Visiting Surgeon, Massachusetts General Hospital

Theodore A. Stern, MD, Psychiatry, Harvard Medical School; Psychiatrist and Chief, Psychiatric Consultation Service, Massachusetts General Hospital

Carol Peckham, Editorial Director

Cynthia Chevins, Publisher

Sherry Knecht, Update Editor




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Source: Well-Connected
Copyright: ? 2000 Nidus Information Services, Inc. 
Posted On Site: May 2000
Publication Date: Mar. 2000