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Parkinson's Disease

Parkinson's disease (PD) is one of the most common progressive neurological diseases; second only to Alzheimer's disease. It is a chronic and progressive disorder that results from the death of nerve cells in the area of the brain called the substantia niagra. The cause of these changes is unknown. PD affects between 500,000 and one million Americans and these numbers will increase significantly as the elderly population increases. The prevalence of PD increases sharply with age, it affects 1 to 2 percent of older adults. The average age of onset is 60 years, however, about 10 percent of patients are under the age of 40. Parkinson's disease affects men and women equally. Some studies show that African-Americans and Asians are less likely to get Parkinson's disease. Age is the most strongly correlated factor.

The nerve cells affected by PD normally produce dopamine which is an essential chemical transmitter for muscle function. The resulting depletion in dopamine results in an impaired ability to control motor movements.

Parkinson's patients have lost 80 percent or more of dopamine-producing cells. The dopamine deficit causes the classic symptoms of Parkinson's disease:

Resting tremor: a rhythmic "pill rolling" type motion of the hands
Bradykinesia: a slowing down and loss of spontaneous and automatic movement. It is unpredictable and one moment the person can move easily while the next moment they are "stuck" and need help.
Muscle rigidity: a resistance to movement because the muscles are constantly tensed and contracted. When you try to move the arm, it will only move in short jerky movements known as "cogwheel" rigidity
Impaired balance and coordination (postural instability): causes a forward or backward lean that places individuals at greater risk for falling. Persons with PD also have a stooped posture with head and shoulders bowed forward

PD is associated with the co-occurrence of several other disorders and problems. As many as 40 percent of people with PD have depression which may be the result of the neurological changes taking place as well as an emotional response to the disabling aspects of the disease. Similarly, one-third to one-half of persons with PD have dementia. The need to treat depression and dementia with drugs can produce further problems associated with drug interactions and side effects. In addition, the presence of these conditions can place an additional strain on the caregiver.

Common problems include constipation, urinary symptoms, choking/drooling, weight loss and difficulty with speech. Constipation is one of the most frequent symptoms. The causes are probably related to inactivity, the effects of drugs, and disease-related changes in GI functioning. Up to 70% of patients with PD have urinary symptoms including nocturia, frequency, and urge incontinence. Difficulties in swallowing and chewing can result in choking or drooling. Weight loss may not be due to changes in appetite so much as increasing difficulties in eating. About half of people with PD have problems with speech-- talking too softly, monotonic voice, hesitating before speaking, slurring or repeating words, or speaking too fast.

Treatment of Parkinson's Disease

Although there is no cure for Parkinson's disease, many of the symptoms can be controlled with drug therapy. Since the early 1960s, the most widely prescribed and effective drug for PD has been levodopa/carbidopa. However, several new drugs have become available in the past 6 months which produce less debilitating side effects. Two new and promising drugs are Requip (a dopamine agonist) and Comtam (a COMT inhibitor). Each of these drugs will be described in the following section.

Levodopa-Carbidopa (e.g., sinemet) is the most commonly prescribed treatment for Parkinson's disease. Levodopa is a short-acting drug that can be converted by nerve cells into dopamine, the neurotransmitter that is deficient in this conditions. When levodopa is given alone is converted to dopamine elsewhere in the body before it reaches the brain. Carbidopa allows more levodopa to get to the brain by preventing it from being metabolized elsewhere in the body.

Initially, levodopa is very effective in treating the symptoms of bradykinesia and rigidity. It is less successful in alleviating tremor and problems with balance. Unfortunately, it does not prevent progression of the disease. As Parkinson's Disease progresses or response to the medication decreases, the benefits received from levodopa tend to shorten. After two to 5 years, more than 50 percent of individuals with PD find they experience an unpredictable phenomenon referred to as an "on-off" effect which affects ability to move. Increasing the dosage generally helps but increases the risk of major side effects that include involuntary movements (called dyskinesias) such as twitching, nodding and jerking. Other adverse side effects such as sudden psychosis and hallucinations are more rare but also problematic.

Other drug therapies used to treat Parkinson's disease include:

Selegiline (e.g. deprenyl, eldepryl) which can delay the need for levodopa therapy for a year or more. When selegiline is given with levodopa it enhances and prolongs the response.
Amantadine (Symmetrel) is an anti-viral drug that also reduces the symptoms of Parkinson's. It is often used in combination with levodopa or anti-cholinergics. After several months, its effectiveness wears off in one-third to one-half of the patients taking it.
Anti-cholinergics (e.g., Benadryl, Artane, and Cogentine) may help control tremor and rigidity. While effective, these drugs can have side effects such as dry mouth, burred vision, urinary retention and constipation which limits their use in older adults.
Dopamine agonists (e.g., Bromocriptine, Pergolide) enter the brain directly at the dopamine receptor sites. They are less effective than levodopa and so they are often prescribed in conjunction with Sinemet to prolong the duration of action of each dose of levodopa. They may also reduce the involuntary movements associated with levodopa.
COMT (catechol-0-methyl-transterase) inhibitors: Comtan is a new COMT medication which received FDA approval in October, 1999. This new class of medications offers totally new way of treating Parkinson's disease. COMT inhibitors block the COMT enzyme which results in greater and more sustained availability of the prescribed levodopa/carbidopa.

For those who are no longer responsive to medications, neurosurgery and transplants may be an option. Surgical procedures for Parkinson's disease were developed in the 1950s but after the discovery of levodopa they were abandoned. Recently, there have been renewed interest in developing procedures. Adrenal medulla transplants and fetal tissue implantation have led to the development of procedures such as thalamotomy for tremor, and pallidotomy to relieve bradykinesia, rigidity, and tremor. One of the latest advances in neurosurgery are controlled trials involving brain stimulation in which an electrode is implanted within the brain and controlled by the patient with an on/off magnetic device.