I found this review from NINDS informative.  It may be helpful for those
members of the list who are new or who don't have access to the Net.
                                                                        Peace, John
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Parkinson's Disease: Hope Through Research

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This pamphlet was written and published by the National Institute of
Neurological Disorders and Stroke (NINDS), the United States' leading
supporter of research on disorders of the brain and nervous system,
including Parkinson's disease. NINDS, one of the U.S. Government's 17
National Institutes of Health in Bethesda, Maryland, is part of the Public
Health Service within the U.S. Department of Health and Human Services.


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Table of Contents:
Introduction
What is Parkinson's Disease?
What Causes the Disease?
Who Gets Parkinson's Disease?
What are the Early Symptoms?
What are the Major Symptoms of the Disease?
Are There Other Symptoms?
What are the Other Forms of Parkinsonism?
How do Doctors Diagnose Parkinson's Disease?
How is the Disease Treated?
Are There Other Medications Available for Managing Disease Symptoms?
Is Surgery Ever Used to Treat Parkinson's Disease?
Can Diet or Exercise Programs Help Relieve Symptoms?
What are the Benefits of Support Groups?
Can Scientists Predict or Prevent Parkinson's Disease?
What Research is Being Done?
What is the Role of the NINDS?
What Can I Do to Help?
Glossary
Information Resources
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Introduction
Parkinson's disease may be one of the most baffling and complex of the
neurological disorders. Its cause remains a mystery but research in this
area is active, with new and intriguing findings constantly being reported.

Parkinson's disease was first described in 1817 by James Parkinson, a
British physician who published a paper on what he called "the shaking
palsy." In this paper, he set forth the major symptoms of the disease that
would later bear his name. For the next century and a half, scientists
pursued the causes and treatment of the disease. They defined its range of
symptoms, distribution among the population, and prospects for cure.

In the early 1960s, researchers identified a fundamental brain defect that
is a hallmark of the disease: the loss of brain cells that produce a
chemical -- dopamine -- that helps direct muscle activity. This discovery
pointed to the first successful treatment for Parkinson's disease and
suggested ways of devising new and even more effective therapies.

Society pays an enormous price for Parkinson's disease. According to the
National Parkinson Foundation, each patient spends an average of $2,500 a
year for medications. After factoring in office visits, Social Security
payments, nursing home expenditures, and lost income, the total cost to the
Nation is estimated to exceed $5.6 billion annually.
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What is Parkinson's Disease?
Parkinson's disease belongs to a group of conditions called motor system
disorders. The four primary symptoms are tremor or trembling in hands,
arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk;
bradykinesia or slowness of movement; and postural instability or impaired
balance and coordination. As these symptoms become more pronounced,
patients may have difficulty walking, talking, or completing other simple
tasks.

The disease is both chronic, meaning it persists over a long period of
time, and progressive, meaning its symptoms grow worse over time. It is not
contagious nor is it usually inherited -- that is, it does not pass
directly from one family member or generation to the next.

Parkinson's disease is the most common form of parkinsonism, the name for a
group of disorders with similar features (see section entitled "What are
the Other Forms of Parkinsonism?"). These disorders share the four primary
symptoms described above, and all are the result of the loss of
dopamine-producing brain cells. Parkinson's disease is also called primary
parkinsonism or idiopathic Parkinson's disease; idiopathic is a term
describing a disorder for which no cause has yet been found. In the other
forms of parkinsonism either the cause is known or suspected or the
disorder occurs as a secondary effect of another, primary neurological
disorder.
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What Causes the Disease?
Parkinson's disease occurs when certain nerve cells, or neurons, in an area
of the brain known as the substantia nigra die or become impaired.
Normally, these neurons produce an important brain chemical known as
dopamine. Dopamine is a chemical messenger responsible for transmitting
signals between the substantia nigra and the next "relay station" of the
brain, the corpus striatum, to produce smooth, purposeful muscle activity.
Loss of dopamine causes the nerve cells of the striatum to fire out of
control, leaving patients unable to direct or control their movements in a
normal manner. Studies have shown that Parkinson's patients have a loss of
80 percent or more of dopamine-producing cells in the substantia nigra. The
cause of this cell death or impairment is not known but significant
findings by research scientists continue to yield fascinating new clues to
the disease.

One theory holds that free radicals -- unstable and potentially damaging
molecules generated by normal chemical reactions in the body -- may
contribute to nerve cell death thereby leading to Parkinson's disease. Free
radicals are unstable because they lack one electron; in an attempt to
replace this missing electron, free radicals react with neighboring
molecules (especially metals such as iron), in a process called oxidation.
Oxidation is thought to cause damage to tissues, including neurons.
Normally, free radical damage is kept under control by antioxidants,
chemicals that protect cells from this damage. Evidence that oxidative
mechanisms may cause or contribute to Parkinson's disease includes the
finding that patients with the disease have increased brain levels of iron,
especially in the substantia nigra, and decreased levels of ferritin, which
serves as a protective mechanism by chelating or forming a ring around the
iron, and isolating it.

Some scientists have suggested that Parkinson's disease may occur when
either an external or an internal toxin selectively destroys dopaminergic
neurons. An environmental risk factor such as exposure to pesticides or a
toxin in the food supply is an example of the kind of external trigger that
could hypothetically cause Parkinson's disease. The theory is based on the
fact that there are a number of toxins, such as
1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) and neuroleptic drugs,
known to induce parkinsonian symptoms in humans. So far, however, no
research has provided conclusive proof that a toxin is the cause of the
disease.

A relatively new theory explores the role of genetic factors in the
development of Parkinson's disease. Fifteen to twenty percent of
Parkinson's patients have a close relative who has experienced parkinsonian
symptoms (such as a tremor). After studies in animals showed that MPTP
interferes with the function of mitochondria within nerve cells,
investigators became interested in the possibility that impairment in
mitochondrial DNA may be the cause of Parkinson's disease. Mitochondria are
essential organelles found in all animal cells that convert the energy in
food into fuel for the cells.

Yet another theory proposes that Parkinson's disease occurs when, for
unknown reasons, the normal, age-related wearing away of dopamine-producing
neurons accelerates in certain individuals. This theory is supported by the
knowledge that loss of antioxidative protective mechanisms is associated
with both Parkinson's disease and increasing age.

Many researchers believe that a combination of these four mechanisms --
oxidative damage, environmental toxins, genetic predisposition, and
accelerated aging -- may ultimately be shown to cause the disease.
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Who Gets Parkinson's Disease?
About 50,000 Americans are diagnosed with Parkinson's disease each year,
with more than half a million Americans affected at any one time. Getting
an accurate count of the number of cases may be impossible however, because
many people in the early stages of the disease assume their symptoms are
the result of normal aging and do not seek help from a physician. Also,
diagnosis is sometimes difficult and uncertain because other conditions may
produce some of the symptoms of Parkinson's disease. People with
Parkinson's disease may be told by their doctors that they have other
disorders or, conversely, people with similar diseases may be initially
diagnosed as having Parkinson's disease.

Parkinson's disease strikes men and women in almost equal numbers and it
knows no social, economic, or geographic boundaries. Some studies show that
African-Americans and Asians are less likely than whites to develop
Parkinson's disease. Scientists have not been able to explain this apparent
lower incidence in certain populations. It is reasonable to assume,
however, that all people have a similar probability of developing the
disease.

Age, however, clearly correlates with the onset of symptoms. Parkinson's
disease is a disease of late middle age, usually affecting people over the
age of 50. The average age of onset is 60 years. However, some physicians
have reportedly noticed more cases of "early-onset" Parkinson's disease in
the past several years, and some have estimated that 5 to 10 percent of
patients are under the age of 40.
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What are the Early Symptoms?
Early symptoms of Parkinson's disease are subtle and occur gradually.
Patients may be tired or notice a general malaise. Some may feel a little
shaky or have difficulty getting out of a chair. They may notice that they
speak too softly or that their handwriting looks cramped and spidery. They
may lose track of a word or thought, or they may feel irritable or
depressed for no apparent reason. This very early period may last a long
time before the more classic and obvious symptoms appear.

Friends or family members may be the first to notice changes. They may see
that the person's face lacks expression and animation (known as "masked
face") or that the person remains in a certain position for a long time or
does not move an arm or leg normally. Perhaps they see that the person
seems stiff, unsteady, and unusually slow.

As the disease progresses, the shaking, or tremor, that affects the
majority of Parkinson's patients may begin to interfere with daily
activities. Patients may not be able to hold utensils steady or may find
that the shaking makes reading a newspaper difficult. Parkinson's tremor
may become worse when the patient is relaxed. A few seconds after the hands
are rested on a table, for instance, the shaking is most pronounced. For
most patients, tremor is usually the symptom that causes them to seek
medical help.
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What are the Major Symptoms of the Disease?
Parkinson's disease does not affect everyone the same way. In some people
the disease progresses quickly, in others it does not. Although some people
become severely disabled, others experience only minor motor disruptions.
Tremor is the major symptom for some patients, while for others tremor is
only a minor complaint and different symptoms are more troublesome.

Tremor. The tremor associated with Parkinson's disease has a characteristic
appearance. Typically, the tremor takes the form of a rhythmic
back-and-forth motion of the thumb and forefinger at three beats per
second. This is sometimes called "pill rolling." Tremor usually begins in a
hand, although sometimes a foot or the jaw is affected first. It is most
obvious when the hand is at rest or when a person is under stress. In three
out of four patients, the tremor may affect only one part or side of the
body, especially during the early stages of the disease. Later it may
become more general. Tremor is rarely disabling and it usually disappears
during sleep or improves with intentional movement.
Rigidity. Rigidity, or a resistance to movement, affects most parkinsonian
patients. A major principle of body movement is that all muscles have an
opposing muscle. Movement is possible not just because one muscle becomes
more active, but because the opposing muscle relaxes. In Parkinson's
disease, rigidity comes about when, in response to signals from the brain,
the delicate balance of opposing muscles is disturbed. The muscles remain
constantly tensed and contracted so that the person aches or feels stiff or
weak. The rigidity becomes obvious when another person tries to move the
patient's arm, which will move only in ratchet-like or short, jerky
movements known as "cogwheel" rigidity.
Bradykinesia. Bradykinesia, or the slowing down and loss of spontaneous and
automatic movement, is particularly frustrating because it is
unpredictable. One moment the patient can move easily. The next moment he
or she may need help. This may well be the most disabling and distressing
symptom of the disease because the patient cannot rapidly perform routine
movements. Activities once performed quickly and easily -- such as washing
or dressing -- may take several hours.
Postural instability. Postural instability, or impaired balance and
coordination, causes patients to develop a forward or backward lean and to
fall easily. When bumped from the front or when starting to walk, patients
with a backward lean have a tendency to step backwards, which is known as
retropulsion. Postural instability can cause patients to have a stooped
posture in which the head is bowed and the shoulders are drooped.
As the disease progresses, walking may be affected. Patients may halt in
mid-stride and "freeze" in place, possibly even toppling over. Or patients
may walk with a series of quick, small steps as if hurrying forward to keep
balance. This is known as festination.
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Are There Other Symptoms?
Various other symptoms accompany Parkinson's disease; some are minor,
others are more bothersome. Many can be treated with appropriate medication
or physical therapy. No one can predict which symptoms will affect an
individual patient, and the intensity of the symptoms also varies from
person to person. None of these symptoms is fatal, although swallowing
problems can cause choking.

Depression. This is a common problem and may appear early in the course of
the disease, even before other symptoms are noticed. Depression may not be
severe, but it may be intensified by the drugs used to treat other symptoms
of Parkinson's disease. Fortunately, depression can be successfully treated
with antidepressant medications.
Emotional changes. Some people with Parkinson's disease become fearful and
insecure. Perhaps they fear they cannot cope with new situations. They may
not want to travel, go to parties, or socialize with friends. Some lose
their motivation and become dependent on family members. Others may become
irritable or uncharacteristically pessimistic.
Memory loss and slow thinking may occur, although the ability to reason
remains intact. Whether people actually suffer intellectual loss (also
known as dementia) from Parkinson's disease is a controversial area still
being studied.

Difficulty in swallowing and chewing. Muscles used in swallowing may work
less efficiently in later stages of the disease. In these cases, food and
saliva may collect in the mouth and back of the throat, which can result in
choking or drooling. Medications can often alleviate these problems.
Speech changes. About half of all parkinsonian patients have problems with
speech. They may speak too softly or in a monotone, hesitate before
speaking, slur or repeat their words, or speak too fast. A speech therapist
may be able to help patients reduce some of these problems.
Urinary problems or constipation. In some patients bladder and bowel
problems can occur due to the improper functioning of the autonomic nervous
system, which is responsible for regulating smooth muscle activity. Some
people may become incontinent while others have trouble urinating. In
others, constipation may occur because the intestinal tract operates more
slowly. Constipation can also be caused by inactivity, eating a poor diet,
or drinking too little fluid. It can be a persistent problem and, in rare
cases, can be serious enough to require hospitalization. Patients should
not let constipation last for more than several days before taking steps to
alleviate it.
Skin problems. In Parkinson's disease, it is common for the skin on the
face to become very oily, particularly on the forehead and at the sides of
the nose. The scalp may become oily too, resulting in dandruff. In other
cases, the skin can become very dry. These problems are also the result of
an improperly functioning autonomic nervous system. Standard treatments for
skin problems help. Excessive sweating, another common symptom, is usually
controllable with medications used for Parkinson's disease.
Sleep problems. These include difficulty staying asleep at night, restless
sleep, nightmares and emotional dreams, and drowsiness during the day. It
is unclear if these symptoms are related to the disease or to the
medications used to treat Parkinson's disease. Patients should never take
over-the-counter sleep aids without consulting their physicians.
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What are the Other Forms of Parkinsonism?
Other forms of parkinsonism include the following:

Postencephalitic parkinsonism. Just after the first World War, a viral
disease, encephalitis lethargica, attacked almost 5 million people
throughout the world, and then suddenly disappeared in the 1920s. Known as
sleeping sickness in the United States, this disease killed one third of
its victims and in many others led to post-encephalitic parkinsonism, a
particularly severe form of movement disorder in which some patients
developed, often years after the acute phase of the illness, disabling
neurological disorders, including various forms of catatonia. (In 1973,
neurologist Oliver Sacks published Awakenings, an account of his work in
the late 1960's with surviving post-encephalitic patients in a New York
hospital. Using the then-experimental drug levodopa, Dr. Sacks was able to
temporarily "awaken" these patients from their statue-like state. A film by
the same name was released in 1990.) In rare cases, other viral infections,
including western equine encephalomyelitis, eastern equine
encephalomyelitis, and Japanese B encephalitis, can leave patients with
parkinsonian symptoms.
Drug-induced parkinsonism. A reversible form of parkinsonism sometimes
results from use of certain drugs -- chlorpromazine and haloperidol, for
example -- prescribed for patients with psychiatric disorders. Some drugs
used for stomach disorders (metoclopramide) and high blood pressure
(reserpine) may also produce parkinsonian symptoms. Stopping the medication
or lowering the dosage causes the symptoms to abate.
Striatonigral degeneration. In this form of parkinsonism, the substantia
nigra is only mildly affected, while other brain areas show more severe
damage than occurs in patients with primary Parkinson's disease. People
with this type of parkinsonism tend to show more rigidity and the disease
progresses more rapidly.
Arteriosclerotic parkinsonism. Sometimes known as pseudoparkinsonism,
arteriosclerotic parkinsonism involves damage to brain vessels due to
multiple small strokes. Tremor is rare in this type of parkinsonism, while
dementia -- the loss of mental skills and abilities -- is common.
Antiparkinsonian drugs are of little help to patients with this form of
parkinsonism.
Toxin-induced parkinsonism. Some toxins -- such as manganese dust, carbon
disulfide, and carbon monoxide -- can also cause parkinsonism. A chemical
known as MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) causes a
permanent form of parkinsonism that closely resembles Parkinson's disease.
Investigators discovered this reaction in the 1980s when heroin addicts in
California who had taken an illicit street drug contaminated with MPTP
began to develop severe parkinsonism. This discovery, which demonstrated
that a toxic substance could damage the brain and produce parkinsonian
symptoms, caused a dramatic breakthrough in Parkinson's research: for the
first time scientists were able to simulate Parkinson's disease in animals
and conduct studies to increase understanding of the disease.
Parkinsonism-dementia complex of Guam. This form occurs among the Chamorro
populations of Guam and the Mariana Islands and may be accompanied by a
disease resembling amyotrophic lateral sclerosis (Lou Gehrig's disease).
The course of the disease is rapid, with death typically occurring within 5
years. Some investigators suspect an environmental cause, perhaps the use
of flour from the highly toxic seed of the cycad plant. This flour was a
dietary staple for many years when rice and other food supplies were
unavailable in this region, particularly during World War II. Other
studies, however, refute this link.
Parkinsonism accompanying other conditions. Parkinsonian symptoms may also
appear in patients with other, clearly distinct neurological disorders such
as Shy-Drager syndrome (sometimes called multiple system atrophy),
progressive supranuclear palsy, Wilson's disease, Huntington's disease,
Hallervorden-Spatz syndrome, Alzheimer's disease, Creutzfeldt-Jakob
disease, olivopontocerebellar atrophy, and post-traumatic encephalopathy.
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How do Doctors Diagnose Parkinson's Disease?
Even for an experienced neurologist, making an accurate diagnosis in the
early stages of Parkinson's disease can be difficult. There are, as yet, no
sophisticated blood or laboratory tests available to diagnose the disease.
The physician may need to observe the patient for some time until it is
apparent that the tremor is consistently present and is joined by one or
more of the other classic symptoms. Since other forms of parkinsonism have
similar features but require different treatments, making a precise
diagnosis as soon as possible is essential for starting a patient on proper
medication.
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How is the Disease Treated?
At present, there is no cure for Parkinson's disease. But a variety of
medications provide dramatic relief from the symptoms.

When recommending a course of treatment, the physician determines how much
the symptoms disrupt the patient's life and then tailors therapy to the
person's particular condition. Since no two patients will react the same
way to a given drug, it may take time and patience to get the dose just
right. Even then, symptoms may not be completely alleviated. In the early
stages of Parkinson's disease, physicians often begin treatment with one or
a combination of the less powerful drugs -- such as the anticholinergics or
amantadine (see section entitled "Are There Other Medications Available for
Managing Disease Symptoms?"), saving the most powerful treatment,
specifically levodopa, for the time when patients need it most.

Levodopa

Without doubt, the gold standard of present therapy is the drug levodopa
(also called L-dopa). L- Dopa (from the full name
L-3,4-dihydroxyphenylalanine) is a simple chemical found naturally in
plants and animals. Levodopa is the generic name used for this chemical
when it is formulated for drug use in patients. Nerve cells can use
levodopa to make dopamine and replenish the brain's dwindling supply.
Dopamine itself cannot be given because it doesn't cross the blood-brain
barrier, the elaborate meshwork of fine blood vessels and cells that
filters blood reaching the brain. Usually, patients are given levodopa
combined with carbidopa. When added to levodopa, carbidopa delays the
conversion of levodopa into dopamine until it reaches the brain, preventing
or diminishing some of the side effects that often accompany levodopa
therapy. Carbidopa also reduces the amount of levodopa needed.

Levodopa's success in treating the major symptoms of Parkinson's disease is
a triumph of modern medicine. First introduced in the 1960s, it delays the
onset of debilitating symptoms and allows the majority of parkinsonian
patients -- who would otherwise be very disabled -- to extend the period of
time in which they can lead relatively normal, productive lives.

Although levodopa helps at least three-quarters of parkinsonian cases, not
all symptoms respond equally to the drug. Bradykinesia and rigidity respond
best, while tremor may be only marginally reduced. Problems with balance
and other symptoms may not be alleviated at all.

People who have taken other medications before starting levodopa therapy
may have to cut back or eliminate these drugs in order to feel the full
benefit of levodopa. Once levodopa therapy starts people often respond
dramatically, but they may need to increase the dose gradually for maximum
benefit.

Because a high-protein diet can interfere with the absorption of levodopa,
some physicians recommend that patients taking the drug restrict protein
consumption to the evening meal.

Levodopa is so effective that some people may forget they have Parkinson's
disease. But levodopa is not a cure. Although it can diminish the symptoms,
it does not replace lost nerve cells and it does not stop the progression
of the disease.

Side Effects of Levodopa

Although beneficial for thousands of patients, levodopa is not without its
limitations and side effects. The most common side effects are nausea,
vomiting, low blood pressure, involuntary movements, and restlessness. In
rare cases patients may become confused. The nausea and vomiting caused by
levodopa are greatly reduced by the combination of levodopa and carbidopa
which enhances the effectiveness of a lower dose. A slow-release
formulation of this product, which gives patients a longer lasting effect,
is also available.

Dyskinesias, or involuntary movements such as twitching, nodding, and
jerking, most commonly develop in people who are taking large doses of
levodopa over an extended period. These movements may be either mild or
severe and either very rapid or very slow. The only effective way to
control these drug-induced movements is to lower the dose of levodopa or to
use drugs that block dopamine, but these remedies usually cause the disease
symptoms to reappear. Doctors and patients must work together closely to
find a tolerable balance between the drug's benefits and side effects.

Other more troubling and distressing problems may occur with long-term
levodopa use. Patients may begin to notice more pronounced symptoms before
their first dose of medication in the morning, and they can feel when each
dose begins to wear off (muscle spasms are a common effect). Symptoms
gradually begin to return. The period of effectiveness from each dose may
begin to shorten, called the wearing-off effect. Another potential problem
is referred to as the on-off effect -- sudden, unpredictable changes in
movement, from normal to parkinsonian movement and back again, possibly
occurring several times during the day. These effects probably indicate
that the patient's response to the drug is changing or that the disease is
progressing.

One approach to alleviating these side effects is to take levodopa more
often and in smaller amounts. Sometimes, physicians instruct patients to
stop levodopa for several days in an effort to improve the response to the
drug and to manage the complications of long-term levodopa therapy. This
controversial technique is known as a "drug holiday." Because of the
possibility of serious complications, drug holidays should be attempted
only under a physician's direct supervision, preferably in a hospital.
Parkinson's disease patients should never stop taking levodopa without
their physician's knowledge or consent because of the potentially serious
side effects of rapidly withdrawing the drug.

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Are There Other Medications Available for Managing Disease Symptoms?
Levodopa is not a perfect drug. Fortunately, physicians have other
treatment choices for particular symptoms or stages of the disease. Other
therapies include the following:

Bromocriptine and pergolide. These two drugs mimic the role of dopamine in
the brain, causing the neurons to react as they would to dopamine. They can
be given alone or with levodopa and may be used in the early stages of the
disease or started later to lengthen the duration of response to levodopa
in patients experiencing wearing off or on-off effects. They are generally
less effective than levodopa in controlling rigidity and bradykinesia. Side
effects may include paranoia, hallucinations, confusion, dyskinesias,
nightmares, nausea, and vomiting.
Selegiline. Also known as deprenyl, selegiline has become a commonly used
drug for Parkinson's disease. Recent studies supported by the NINDS have
shown that the drug delays 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
fluctuations. In studies with animals, selegiline has been shown to protect
the dopamine-producing neurons from the toxic effects of MPTP. Selegiline
inhibits the activity of the enzyme monoamine oxidase B (MAO-B), the enzyme
that metabolizes dopamine in the brain, delaying the breakdown of naturally
occurring dopamine and of dopamine formed from levodopa. Dopamine then
accumulates in the surviving nerve cells. Some physicians, but not all,
favor starting all parkinsonian patients on selegiline because of its
possible protective effect. Selegiline is an easy drug to take, although
side effects may include nausea, orthostatic hypotension, or insomnia (when
taken late in the day). Also, toxic reactions have occurred in some
patients who took selegiline with fluoxetine (an antidepressant) and
meperidine (used as a sedative and an analgesic).
Research scientists are still trying to answer questions about selegiline
use: How long does the drug remain effective? Does long-term use have any
adverse effects? Evaluation of the long-term effects will help determine
its value for all stages of the disease.

Anticholinergics. These drugs were the main treatment for Parkinson's
disease until the introduction of levodopa. Their benefit is limited, but
they may help control tremor and rigidity. They are particularly helpful in
reducing drug-induced parkinsonism. Anticholinergics appear to act by
blocking the action of another brain chemical, acetylcholine, whose effects
become more pronounced when dopamine levels drop. Only about half the
patients who receive anticholinergics respond, usually for a brief period
and with only a 30 percent improvement. Although not as effective as
levodopa or bromocriptine, anticholinergics may have a therapeutic effect
at any stage of the disease when taken with either of these drugs. Common
side effects include dry mouth, constipation, urinary retention,
hallucinations, memory loss, blurred vision, changes in mental activity,
and confusion.
Amantadine. An antiviral drug, amantadine, helps reduce symptoms of
Parkinson's disease. It is often used alone in the early stages of the
disease or with an anticholinergic drug or levodopa. After several months
amantadine's effectiveness wears off in a third to a half of the patients
taking it, although effectiveness may return after a brief withdrawal from
the drug. Amantadine has several side effects, including mottled skin,
edema, confusion, blurred vision, and depression.
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Is Surgery Ever Used to Treat Parkinson's Disease?
Treating Parkinson's disease with surgery was once a common practice. But
after the discovery of levodopa, surgery was restricted to only a few
cases. One of the procedures used, called cryothalamotomy, requires the
surgical insertion of a supercooled metal tip of a probe into the thalamus
(a "relay station" deep in the brain) to destroy the brain area that
produces tremors. This and related procedures are coming back into favor
for patients who have severe tremor or have the disease only on one side of
the body. Investigators have also revived interest in a surgical procedure
called pallidotomy in which a portion of the brain called the globus
pallidus is lesioned. Some studies indicate that pallidotomy may improve
symptoms of tremor, rigidity, and bradykinesia, possibly by interrupting
the neural pathway between the globus pallidus and the striatum or
thalamus. Further research on the value of surgically destroying these
brain areas is currently being conducted.
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Can Diet or Exercise Programs Help Relieve Symptoms?
Diet. Eating a well-balanced, nutritious diet can be beneficial for
anybody. But for preventing or curing Parkinson's disease, there does not
seem to be any specific vitamin, mineral, or other nutrient that has any
therapeutic value. A high protein diet, however, may limit levodopa's
effectiveness.

Despite some early optimism, recent studies have shown that tocopherol (a
form of vitamin E) does not delay Parkinson's disease. This conclusion came
from a carefully conducted study supported by the NINDS called DATATOP
(Deprenyl and Tocopherol Antioxidative Therapy for Parkinson's Disease)
that examined, over 5 years, the effects of both deprenyl and vitamin E on
early Parkinson's disease. While deprenyl was found to slow the early
symptomatic progression of the disease and delay the need for levodopa,
there was no evidence of therapeutic benefit from vitamin E.

Exercise. Because movements are affected in Parkinson's disease, exercising
may help people improve their mobility. Some doctors prescribe physical
therapy or muscle-strengthening exercises to tone muscles and to put
underused and rigid muscles through a full range of motion. Exercises will
not stop disease progression, but they may improve body strength so that
the person is less disabled. Exercises also improve balance, helping people
overcome gait problems, and can strengthen certain muscles so that people
can speak and swallow better. Exercises can also improve the emotional
well-being of parkinsonian patients by giving them a feeling of
accomplishment. Although structured exercise programs help many patients,
more general physical activity, such as walking, gardening, swimming,
calisthenics, and using exercise machines, is also beneficial.
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What are the Benefits of Support Groups?
One of the most demoralizing aspects of the disease is how completely the
patient's world changes. The most basic daily routines may be affected --
from socializing with friends and enjoying normal and congenial
relationships with family members to earning a living and taking care of a
home. Faced with a very different life, people need encouragement to remain
as active and involved as possible. That's when support groups can be of
particular value to parkinsonian patients, their families, and their
caregivers.

A list of national volunteer organizations that can help patients locate
support groups in their communities appears at the end of this brochure.


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Can Scientists Predict or Prevent Parkinson's Disease?
As yet, there is no way to predict or prevent the disease. However,
researchers are now looking for a biomarker -- a biochemical abnormality
that all patients with Parkinson's disease might share -- that could be
picked up by screening techniques or by a simple chemical test given to
people who do not have any parkinsonian symptoms.

Positron emission tomography (PET) scanning may lead to important advances
in our knowledge about Parkinson's disease. PET scans of the brain produce
pictures of chemical changes as they occur in the living brain. Using PET,
research scientists can study the brain's dopamine receptors (the sites on
nerve cells that bind with dopamine) to determine if the loss of dopamine
activity follows or precedes degeneration of the neurons that make this
chemical. This information could help scientists better understand the
disease process and may potentially lead to improved treatments.
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What Research is Being Done?
In the last decade research has laid the groundwork for many of today's
promising new clinical trials, technologies, and drug treatments.
Scientists, physicians, and patients hope that today's progress means
tomorrow's cure and prevention.

Parkinson's disease research focuses on many areas. Some investigators are
studying the functions and anatomy of the motor system and how it regulates
movement and relates to major command centers in the brain. Scientists
looking for the cause of Parkinson's disease will continue to search for
possible environmental factors, such as toxins that may trigger the
disorder, and to study genetic factors to determine if one or many
defective genes play a role. Although Parkinson's disease is not directly
inherited, it is possible that some people are genetically more or less
susceptible to developing it. Other scientists are working to develop new
protective drugs that can delay, prevent, or reverse the disease.

Since the accidental discovery that MPTP causes parkinsonian symptoms in
humans, scientists have found that by injecting MPTP into laboratory
animals, they can reproduce the brain lesions that cause these symptoms.
This allows them to study the mechanisms of the disease and helps in the
development of new treatments. For instance, it was from animal studies
that researchers discovered that the drug selegiline can prevent the toxic
effects of MPTP. This discovery helped spark interest in studying
selegiline as a preventive treatment in humans.

Scientists are also investigating the role of mitochondria, structures in
cells that provide the energy for cellular activity, in Parkinson's
disease. Because MPTP interferes with the function of mitochondria within
nerve cells, some scientists suspect that similar abnormalities may be
involved in Parkinson's disease.

Today, an array of promising research involves studying brain areas other
than the substantia nigra that may be involved in the disease. One group of
NINDS-supported scientists is studying the consequences of dopamine cell
degeneration in the basal ganglia -- brain structures located deep in the
forebrain that help control voluntary movement. In laboratory animals,
MPTP-induced reduction of dopamine results in overactivity of nerve cells
in a region of the brain called the subthalamic nucleus, producing tremors
and rigidity and suggesting that these symptoms may be related to excessive
activity in this region. Destroying the subthalamic nucleus results in a
reversal of parkinsonian symptoms in the animal models.

Scientists supported by the NINDS are also looking for clues to the cause
of Parkinson's disease by studying malfunctions in the structures called
"dopamine transporters" that carry dopamine in and out of the synapse, or
narrow gap between nerve cells. For example, one research group recently
found an age-related decrease in the concentration of dopamine transporters
in healthy human nerve cells taken from areas of the brain damaged by
Parkinson's. This decline in transporter concentration means that any
further threat to the remaining dopamine transporters could result in
Parkinson's disease.

The search for more effective medications for Parkinson's disease is likely
to be aided by the recent isolation of at least five individual brain
receptors for dopamine. New information about the unique effects of each
individual dopamine receptor on different brain areas has led to new
treatment theories and clinical trials.

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Scientists are also studying new methods for delivering dopamine to
critical areas in the brain. NINDS-supported investigators, using an animal
model of the disease, implanted tiny dopamine-containing particles into
brain regions affected by the disease. They found that such implants can
partially ameliorate the movement problems exhibited by these animals. The
results suggest that similar techniques may one day work for people with
Parkinson's disease.

A recent study revealed that when the experimental drug Ro 40-7592 is added
to the standard drug treatment for Parkinson's disease, levodopa-carbidopa,
symptom relief is prolonged by more than 60 percent. Although
levodopa-carbidopa restores normal movement early in the disease's course,
the treatment loses effectiveness as the disease progresses (wearing-off
effect). NINDS scientists found, however, that patients treated with both
levodopa-carbidopa and Ro 40-7592 experienced longer periods of improved
movement. This promising new drug that blocks the breakdown of dopamine and
levodopa would allow patients to take fewer doses and smaller amounts of
levodopa-carbidopa and to decrease the problems of the wearing-off effect.
At the present time, Ro 40-7592 is still in the experimental stage.
Scientists are continuing to study the drug to learn whether it can be
given in multiple daily doses to provide even further improvement.

Also under investigation are additional controlled-release formulas of
Parkinson's disease drugs and implantable pumps that give a continuous
supply of levodopa to help patients who have problems with fluctuating
levels of response. Another promising treatment method involves implanting
capsules containing dopamine-producing cells into the brain. The capsules
are surrounded by a biologically inert membrane that lets the drug pass
through at a timed rate.

Neural grafting, or transplantation of nerve cells, is an experimental
technique proposed for treating the disease. NINDS-supported investigators
have shown in animal models that implanting fetal brain tissue from the
substantia nigra into a parkinsonian brain causes damaged nerve cells to
regenerate. In January 1994, the NINDS awarded a research grant to a group
of scientists from three institutions to conduct a controlled clinical
trial of fetal tissue implants in humans. The treatment attempts to replace
the lost or damaged dopamine-producing neurons with healthy, fetal neurons,
and thereby improve movement and response to medications. A new and
promising approach may be the use of genetically engineered cells -- that
is, cells such as modified skin cells that do not come from the nervous
system but are grown in tissue culture -- that could have the same
beneficial effects. Skin cells would be much easier to harvest and patients
could serve as their own donors.
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What is the Role of the NINDS?
As a world leader in research on neurological disorders, including
Parkinson's disease, the NINDS supports a wide range of basic laboratory
studies and clinical trials at its Bethesda, Maryland, location and at
grantee institutions around the world. Current research programs funded by
the NINDS include using animal models to study how the disease progresses,
developing new drug therapies, and implanting tissue in animals and humans.
Through these and other research projects, scientists are moving ever
closer to unraveling the mysteries of Parkinson's disease. For patients and
families of patients, this research should offer encouragement and hope for
the future.

The Institute also sponsors an active information program that provides
patients and the general public with educational materials and research
highlights. Among the NINDS publications that may be of interest to those
concerned about Parkinson's disease is "Know Your Brain," an 8-page fact
sheet that explains how the healthy brain works and what happens when the
brain is diseased or dysfunctional. The Institute's address and phone
number, as well as information on other organizations that offer various
services to those affected by Parkinson's disease, are provided on the
information resources card enclosed in the back pocket of this brochure.
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What Can I Do to Help?
The NINDS and the National Institute of Mental Health jointly support two
national brain specimen banks. These banks supply research scientists
around the world with nervous system tissue from patients with neurological
and psychiatric disorders. They need tissue from patients with Parkinson's
disease so that scientists can study and understand the disorder. Those who
may be interested in donating should write to:

Dr. Wallace W. Tourtellotte, Director
National Neurological Research Specimen Bank
VAMC-West Los Angeles
11301 Wilshire Boulevard
Los Angeles, CA 90073
(310) 824-4307

Dr. Edward D. Bird, Director
Brain Tissue Resource Center
McLean Hospital
115 Mill Street
Belmont, MA 02178
(617)855-2400
1-800-BRAIN-BANK (1-800-272-4622)

Two organizations, not funded by the NINDS, also provide research
scientists with nervous system tissue from patients with neurological
disorders. Interested donors should write or call:

National Disease Research Interchange (NDRI)
1880 JFK Boulevard
6th Floor
Philadelphia, PA 19103
(215) 557-7361
1-800-222-NDRI (1-800-222-6374)

University of Miami Brain Endowment Bank
Department of Neurology (D4-5)
1501 NW 9th Avenue
Miami, FL 33101
(305) 547-6219
1-800-UM-BRAIN (1-800-86-27246)
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Glossary
bradykinesia: gradual loss of spontaneous movement.
corpus striatum: a part of the brain that helps regulate motor activities.
cryothalamotomy: a surgical procedure in which a supercooled probe is
inserted into a         part of the brain called the thalamus in order to stop
tremors.
dementia: loss of intellectual abilities.
dopamine: a chemical messenger, deficient in the brains of Parkinson's
disease         patients, that transmits impulses from one nerve cell to another.
dyskinesias: abnormal involuntary movements that can result from long-term
use of high     doses of levodopa.
festination: a symptom characterized by small, quick forward steps.
on-off effect: a change in the patient's condition, with sometimes rapid
fluctuations    between uncontrolled movements and normal movement, usually
occurring after         long-term use of levodopa and probably caused by changes
in the ability to       respond to this drug.
pallidotomy: a surgical procedure in which a part of the brain called the
globus  pallidus is lesioned in order to improve symptoms of tremor,
rigidity, and   radykinesia.
parkinsonism: a term referring to a group of conditions that are
characterized by four   typical symptoms--tremor, rigidity, postural
instability, and bradykinesia.
postural instability: impaired balance and coordination, often causing
patients to lean        forward or backward and to fall easily.
retropulsion: the tendency to step backwards if bumped from the front or
upon    initiating walking, usually seen in patients who tend to lean
backwards because       of problems with balance.
rigidity: a symptom of the disease in which muscles feel stiff and display
resistance      to movement even when another person tries to move the affected
part of the     body, such as an arm.
substantia nigra: movement-control center in the brain where loss of
dopamine-producing      nerve cells triggers the symptoms of Parkinson's
disease; substantia nigra means         "black substance," so called because the
cells in this area are dark.
tremor: shakiness or trembling, often in a hand, which in Parkinson's
disease is      usually most apparent when the affected part is at rest.
wearing-off effect: the tendency, following long-term levodopa treatment,
for each dose   of the drug to be effective for shorter and shorter periods.
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Information Resources

NIH Neurological Institute
P.O. Box 5801
Bethesda, MD 20824
(301)496-5924
1-800-352-9424

The National Institute of Neurological Disorders and Stroke, a component of
the National Institutes of Health, is the leading Federal supporter of
research on disorders of the brain and nervous system. The Institute also
sponsors an active public information program and can answer questions
about diagnosis, treatment, and research related to Parkinson's disease.
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Private voluntary organizations that provide the public with information on
treatment, diagnosis, and services include the following:

American Parkinson Disease Association
250 Hylan Boulevard
Staten Island, NY 10305
(718)981-8001
1-800-223-APDA (2732)

This association funds research; sponsors support groups, symposia, and
information and referral centers; and publishes a newsletter and other
educational manuals.
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National Parkinson Foundation, Inc.
1501 N.W. 9th Avenue
Bob Hope Road
Miami, FL 33136-1494
(305)547-6666
1-800-327-4545 (in Florida 1-800-433-7022)

or

4929 Wilshire Boulevard
Suite 945
Los Angeles, CA 90010
1-800-522-8855 (in California 1-800-400-8448)
or

122 East 42nd Street
Suite 2806
New York, NY 10168
(212)374-1741

This foundation supports research, clinical services, and physical,
occupational, speech, and psychological therapies. It also offers public
education, disseminates information by means of its brochures, and raises
public awareness of Parkinson's disease.
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Parkinson's Disease Foundation, Inc.
650 West 168th Street
New York, NY 10032-9982
(212)923-4700
1-800-457-6676

This foundation supports research; promotes the formation of support
groups; and offers professional training fellowships and symposia, patient
and professional information, counseling, advocacy, and referral.
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The Parkinson's Institute
1170 Morse Avenue
Sunnyvale, CA 94089-1605
(408)734-2800

This foundation operates a clinic and research facility, publishes a
newsletter, and offers many services for patients and their families.
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Parkinson's Support Groups of America (PSGA)
11376 Cherry Hill Road, # 204
Beltsville, MD 20705
(301)937-1545

This organization promotes research; maintains a library; and sponsors a
speakers' bureau, support groups, and an annual convention. The
organization also offers a variety of services and programs for the public.
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United Parkinson Foundation
833 West Washington Blvd.
Chicago, IL 60607
(312)733-1893

This foundation funds research; offers information for patients, families,
and professionals; and publishes a newsletter, brochures, and fact sheets.