More Information on Parkinson's Disease
Parkinsons Disease, Parkinson Disease
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.
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.
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). Several causative genes have
been identified, usually causing young onset parkinsonism. Mutations in
the gene for the protein alpha-synuclein, located on chromosome 4 results
in autosomal dominant parkinsonism. The function of this protein is not
known. The most commonly occurring genetic defect affects the gene for the
protein called parkin on chromosome 6. Mutations in this gene result in
autosomal recessive parkinsonism that is slowly progressive with onset
before the age of 40. 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, and families with maternal inheritance
of parkinsonism, suggesting mitochondrial DNA defects, are being actively
investigated. 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.
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.
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.
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.
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.
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.
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.
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.
Prolonging Levodopa Action
Recent studies revealed that when the drug tolcapone is added to the
standard drug treatment for Parkinson's disease, levodopa-carbidopa,
symptom relief is prolonged greatly. 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.
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.
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, pergolide, pramipexole and ropinirole. These four
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. Studies supported by the NINDS have shown that the drug
(also known as deprenyl) delays the need for levodopa therapy by an
average of nine months. When selegiline is given with levodopa, it
appears to enhance and prolong the response to levodopa and thus may
reduce wearing-off fluctuations. 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 and also provides mild symptomatic
relief from parkinsonism in-and-of itself. 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).
- 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.
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. Currently, surgery is reserved for patients who have failed to
respond satisfactorily to drugs. 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, such as thalamic stimulation, 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. Restorative
surgery, using nerve cell transplants to supplement the patient's own
dopamine-producing nerve cells, is also under investigation.
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.
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.
As yet, there is no way to predict or prevent the disease; however
more information on Parkinson's Disease continues to emerge.
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, along with other information on
Parkinson's Disease, could help scientists
better understand the disease process and may potentially lead to improved
treatments.
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 how defective
genes play a role. Although Parkinson's disease is rarely 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.
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.
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.
Keeping on Top of Your Condition
Keeping in tune with your disease or condition not only makes treatment less intimidating but also increases its chance of success, and has been shown to lower a patients risk of complications. As well, as an informed patient, you are better able to discuss your condition and treatment options with your physician.
A new service available to patients provides a convenient means of staying informed, and ensures that the information is both reliable and accurate. If you wish to find out more about HealthNewsflash's innovative service, take the tour.
BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov/
American Parkinson Disease Association
1250 Hylan Boulevard, Suite
4B
Staten Island, NY 10305-1946
(718)981-8001
800-223-APDA
(2732)
http://www.apdaparkinson.com/
Michael J. Fox Foundation for Parkinson's Research
840 Third
Street
Santa Rosa, CA 95404
Tel: 800-708-7644
http://www.michaeljfox.com/
National Parkinson Foundation, Inc.
1501 N.W. 9th Avenue
Bob
Hope Research Center
Miami, FL 33136-1494
(305)547-6666
800-327-4545 (in Florida 1-800-433-7022)
http://www.parkinson.org/
or
1500 San Pablo Street
Los Angeles, CA 90033
800-522-8855 (in
California 1-800-400-8448)
or
10 Union Square East
Suite 5L
New York, NY 10003
(212)844-6050
Parkinson's Action Network
840 3rd Street
Santa Rosa, CA
95404
(800) 850-4726
California: (707) 544-1994
http://www.parkinsonaction.org/
Parkinson's Disease Foundation, Inc.
710 West 168th Street
New
York, NY 10032-9982
(212)923-4700
800-457-6676
http://www.parkinsons-foundation.org/
The Parkinson's Institute
1170 Morse Avenue
Sunnyvale, CA
94089-1605
(408)734-2800
(800) 786-2958
http://www.parkinsonsinstitute.org/
Parkinson's Support Groups of America (PSGA)
11376 Cherry Hill
Road, # 204
Beltsville, MD 20705
(301) 937-1545
Worldwide Education and Awareness for Movement Disorders (WE
MOVE)
204 W. 84th Street
New York, NY 10024
(212)
875-8312
(800) 437-MOV2 (6682)
http://www.wemove.org/
