Parkinson's Disease
Parkinson's disease is a slowly progressive degenerative disorder of the nervous system characterized by tremor when muscles are at rest (resting tremor), slowness of voluntary movements, and increased muscle tone (rigidity).
Parkinson's disease affects about 1 of 250 people older than 40 and about 1 of 100 people older than 65. It commonly begins between the ages of 50 and 79. It is twice as common among whites as among blacks.
When the brain initiates an impulse to move a muscle (for example, to lift an arm), the impulse passes through the basal ganglia (collections of nerve cells located at the base of the cerebrum, deep within the brain). The basal ganglia help smooth out muscle movements and coordinate changes in posture. Like all nerve cells, those in the basal ganglia release chemical messengers (neurotransmitters) that trigger the next nerve cell in the pathway to send an impulse. The main neurotransmitter in the basal ganglia is dopamine. Its overall effect is to increase nerve signals to muscles. In Parkinson's disease, nerve cells in part of the basal ganglia (called the substantia nigra) degenerate, reducing the production of dopamine and the number of connections between nerve cells in the basal ganglia. As a result, the basal ganglia cannot smooth out movements as they normally do, leading to tremor, incoordination, and slowed, reduced movement (bradykinesia).
The cause of nerve cell degeneration in Parkinson's disease is unknown. Genetics does not appear to play a large role, although the disease tends to occur in some families.
Parkinsonism is a disorder with many or all of the symptoms of Parkinson's disease. Various conditions can cause parkinsonism. It may be a complication of viral encephalitis, a rare disorder that follows a flu-like infection. Parkinsonism may also result when other degenerative diseases, drugs, or toxins interfere with or block the action of dopamine and other neurotransmitters. For example, antipsychotic drugs, used to treat paranoia and schizophrenia, block dopamine's action. Use of the substance MPTP (which was produced accidentally when illicit drugs users tried to synthesize the opioid meperidine) can cause sudden, severe, and irreversible parkinsonism in young people. Other causes include structural brain disorders (such as brain tumors and strokes) and head injury, particularly the repeated injury that occurs in boxing.
Corticobasal ganglionic degeneration is a rare cause of parkinsonism. It results from degeneration of brain tissue in the cerebral cortex and the basal ganglia. Corticobasal ganglionic degeneration is distinguished from other forms of parkinsonism by abnormalities in the cortex causing, for example, the inability to express or understand spoken or written language (aphasia), the inability to perform simple skilled tasks (apraxia), and the inability to associate objects with their usual role or function (agnosia). Symptoms begin after age 60, causing immobility after about 5 years and death after about 10 years.
Symptoms
Usually, Parkinson's disease begins subtly and progresses gradually. In many people, it begins with a coarse, rhythmic tremor in the hand while the hand is at rest. The tremor decreases when the hand is moving purposefully and disappears completely during sleep. Emotional stress or fatigue may increase the tremor. The tremor may eventually progress to the other hand, the arms, and the legs. A tremor may also affect the jaws, tongue, forehead, and eyelids. Tremor may become less obvious as the disease progresses. In about one third of people with Parkinson's disease, a tremor is not the first symptom. In some people, a tremor never develops. Other early symptoms may include a reduced sense of smell, a tendency to reduce body movements, difficulty walking, and lack of facial expression with infrequent blinking.
The sense of smell appears to be reduced partly because people with Parkinson's disease have difficulty sniffing--deliberately breathing in a large amount of air. (Degeneration of brain cells in the areas involved in smell may also contribute.) Although a reduced sense of smell may seem a minor problem, it can dampen the appetite, contributing to malnutrition.
Muscles become rigid, impairing movement. When the forearm is bent back or straightened out by another person, the movement may feel stiff and ratchet-like. Movements become slow and difficult to initiate, and mobility is decreased. Stiffness and decreased mobility can contribute to muscle ache and fatigue. Because the small muscles of the hands are often impaired, daily tasks, such as buttoning a shirt and tying shoelaces, become increasingly harder. Most people with Parkinson's disease have shaky, tiny handwriting (micrographia) because initiating and sustaining each stroke of the pen is difficult.
People with Parkinson's disease have difficulty walking, especially taking the first step. Once started, they often shuffle, taking short steps without swinging their arms as they walk. While walking, some people have difficulty stopping or turning. When the disease is advanced, some people suddenly stop walking because they feel as if their feet are glued to the ground. Other people unintentionally quicken their steps, breaking into a short stumbling run to avoid falling. Posture becomes stooped, and balance is difficult to maintain, leading to a tendency to fall forward. Because movements are slow, people often cannot move their hands quickly enough to break a fall.
The face becomes less expressive because the facial muscles that control expression do not move. This lack of expression may be mistaken for depression, or it may cause depression to be overlooked. (Depression is common among people with Parkinson's disease.) Eventually, the face can take on a blank stare with the mouth open, and the eyes may not blink often. Often, people drool or choke because muscle rigidity in the face and throat makes swallowing difficult. Malnutrition and dehydration can result. People with Parkinson's disease often speak softly in a monotone and may stutter because they have difficulty articulating words.
Constipation may develop. In many people with Parkinson's disease, intellect remains normal, but about half of the people develop dementia.
Diagnosis
Diagnosis is based on symptoms. Mild, early disease may be difficult for doctors to diagnose because it usually begins subtly. Diagnosis is especially difficult in older people, because aging can cause some of the same problems as Parkinson's disease, such as loss of balance, slow movements, muscle stiffness, and stooped posture. No tests or imaging procedures can directly confirm the diagnosis. However, computed tomography (CT) and magnetic resonance imaging (MRI) may be performed to look for a structural disorder that may be the cause of the symptoms. The diagnosis of Parkinson's disease is likely if drug treatment for the disease results in improvement.
Treatment
The physical measures used to treat Parkinson's disease and parkinsonism are the same. However, the drugs used to treat Parkinson's disease are often not effective in people with parkinsonism. Treating the underlying disorder or discontinuing the drug causing parkinsonism is more effective and may result in a cure.
Physical Measures: Continuing to perform as many daily activities as possible and following a program of regular exercise can help people with Parkinson's disease maintain mobility. Physical and occupational therapy can help them maintain or regain muscle tone, maintain range of motion, and learn adaptive strategies (see Section 1, Chapter 7). Mechanical aids, such as wheeled walkers, can help them maintain independence.
A high-fiber diet can help counteract constipation, which may be worsened by the use of levodopa. Certain foods, such as prune juice and other juices, and stool softeners, such as senna concentrate, can help keep bowel movements regular. Difficulty swallowing can result in malnutrition, so doctors must ensure that the diet is nutritious. Learning to sniff more deeply may improve the ability to smell, enhancing the appetite.
Simple changes around the home can make the home safer for people with Parkinson's disease. For example, removing throw rugs can prevent tripping, and installing railings in bathrooms, hallways, and other locations reduces the risk of falling. Daily tasks can be simplified, for example by having buttons on clothing replaced with Velcro fasteners or buying shoes with such fasteners.
Drugs: No drug can cure Parkinson's disease or stop its progression, but many drugs can make movement easier and enable people to function effectively for many years. Two or more drugs may be needed.
Levodopa is most effective in reducing tremor and muscle rigidity and in improving movement. Treatment with levodopa can produce dramatic improvement in people with Parkinson's disease, but people with parkinsonism due to another disorder usually do not improve. Levodopa, taken by mouth, is converted to dopamine in the basal ganglia, thus compensating for the decrease in dopamine production. Taking levodopa enables many people with mild Parkinson's disease to return to a nearly normal level of activity and enables some people who are bedridden to walk again.
Levodopa is given with carbidopa. Carbidopa prevents levodopa from being converted to dopamine before it reaches the brain. When the two drugs are given together, a lower dose of levodopa can be used, and the side effects of levodopa (nausea and flushing) are reduced. Levodopa-carbidopa is the mainstay of treatment for Parkinson's disease.
To determine the best dose of levodopa for a particular person, doctors must balance control of the disease with the development of certain side effects, which may limit the amount of levodopa the person can tolerate. These side effects include involuntary movements of the mouth, face, and limbs; nightmares; hallucinations; and changes in blood pressure. Many experts believe that the development of involuntary movements can be delayed by using a drug that mimics the action of dopamine (a dopamine agonist) with or instead of levodopa during the early years of treatment.
After taking levodopa for 5 or more years, more than half of the people begin to alternate rapidly between a good response to the drug and no response--an effect called the on-off phenomenon. Within seconds, they may change from being fairly mobile to being severely impaired. The period of relief after each dose becomes shorter, and periods of immobility alternate with periods of improved mobility. However, improved mobility may be accompanied by writhing or hyperactivity--when the involuntary movements due to levodopa use are greatly increased. Taking lower, more frequent doses controls these effects at first, but after 15 to 20 years, these effects become hard to suppress. Surgery is then considered.
Other drugs are generally less effective than levodopa, but they may benefit some people, particularly if levodopa is not tolerated or is insufficient. Dopamine agonists (such as pramipexole and ropinirole), which mimic the action of dopamine, may be useful at any stage of the disease. Selegiline, a type of antidepressant called a monoamine oxidase inhibitor (MAOI) (see Section 7, Chapter 101), prevents the breakdown of dopamine, thereby prolonging dopamine's action in the body. Tolcapone and entacapone also prevent the breakdown of dopamine and appear to be useful supplements to levodopa.
Anticholinergic drugs (see Section 2, Chapter 14), such as benztropine and trihexyphenidyl, are effective in reducing the severity of a tremor and can be used in the early stages of Parkinson's disease. They can also be used in the later stages to supplement levodopa. Anticholinergic drugs may reduce tremor because they block the action of acetylcholine, and tremor is thought to be caused by an imbalance of acetylcholine (too much) and dopamine (too little). Other anticholinergic drugs, including some antihistamines and tricyclic antidepressants, are mildly effective and are used to supplement levodopa.
Amantadine, a drug sometimes used to treat influenza, may be used alone to treat mild disease or as a supplement to levodopa. Propranolol, a beta-blocker, may be prescribed to reduce the severity of a tremor.
 See the drug table Drugs Used to Treat Parkinson's Disease.
Surgery: In a pallidotomy, a tiny area in one of the basal ganglia is surgically destroyed. This procedure can greatly reduce the "off" part--the difficulty initiating movements--of the on-off phenomenon and the involuntary movements that occur after years of levodopa therapy. Alternatively, tiny electrodes can be implanted in the same area. They provide high-frequency electrical stimulation to this area, often producing similar improvements.
Nerve cells that produce dopamine may be taken from human fetal tissue and implanted in the brain of a person with Parkinson's disease. These cells form connections with other nerve cells and produce dopamine, thus supplying the missing neurotransmitter. However, this procedure is still experimental and requires further study.
Caregiver and End-of-Life Issues: Because Parkinson's disease is progressive, people eventually need help performing normal daily activities, such as eating, bathing, dressing, and toileting. Caregivers can benefit from learning about the physical and psychologic effects of Parkinson's disease and about ways to enable people to function as well as possible. Because such care is tiring and stressful, caregivers may benefit from support groups.
Eventually, people with Parkinson's disease usually become severely disabled and immobile. They may be unable to eat, even with assistance. Dementia develops in about half of the people. Because swallowing becomes increasingly difficult, death due to aspiration pneumonia is a risk. For some people, depending on many factors, a nursing home may be the best place for care. Before people with this disease are incapacitated, they should establish advance directives, indicating what kind of medical care they want at the end of life (see Section 1, Chapter 9).
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