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. 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). 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.
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:
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.
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.
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.
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.
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.
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.
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.