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March 12, 2000

New treatments to control Parkinson's disease

By Karen Goldberg Goff THE WASHINGTON TIMES

Jeana Bartlett first noticed her right hand trembling while she sat in the bleachers watching her sons play football. She attributed the shaking to nerves.

The shaking kept occurring though, and neurological tests proved inconclusive. The tremors got worse, and Mrs. Bartlett, then in her mid-30s, became more scared. She was downright terrified when she was driving and could not take her foot off the accelerator.

Further tests showed the Augusta, Ga., woman had Parkinson's disease, a neurological condition doctors initially dismissed because of her young age. "Parkinson's was considered 'an old person's disease,' " she says.

"But I was actually relieved to find out that is what I had. I thought I was a hypochondriac or psychotic or had a brain tumor."

About 1 million people in the United States suffer from Parkinson's disease. About 20 percent of that number are younger than 40, according to data from the National Parkinson's Foundation. Though the disease is not fatal, it gets progressively worse.

To a younger person, that can mean decades of adjusting medication, undergoing surgery and dealing with sometimes debilitating physical symptoms.

"The issues for young people with Parkinson's are very different," says Hilary Blue, a 51-year-old Annandale woman who has had Parkinson's for 27 years.

"Older people are expected to get all sorts of conditions as they age. The acceptance is very difficult when you are young. You have to think about issues like will you be able to work or take care of your children."

An increasing number of people younger than 40 are being diagnosed with Parkinson's, says Dr. Tom Chase, chief of experimental therapeutics at the National Institute of Neurological Disorder and Stroke, part of the National Institutes of Health. However, it is unknown whether more people than ever have the disease or doctors are just diagnosing it more accurately.

Young Parkinson's sufferers also have received newfound attention through the work of actor Michael J. Fox, who announced in 1998 that he had been living with the disease for seven years. Mr. Fox, now 39, recently said he will not continue with his role on ABC's "Spin City" so he can devote more time to raising awareness — and finding a cure.

"For many people with Parkinson's, managing their disease is a full-time job," Mr. Fox said in congressional testimony last September.

"It is a constant balancing act. While I am able, for the time being, to do what I love best, others are not so fortunate. There are doctors, teachers, policemen and parents who are no longer able to work to provide for their families and live out their dreams."

A neurological mystery

Parkinson's disease is a progressive disorder caused by the degeneration of nerve cells in the part of the brain that controls movement. This degeneration creates a shortage of a neurotransmitter called dopamine.

The first sign of Parkinson's usually is a tremor (trembling or shaking) of a limb, especially when the body is at rest. The tremor often begins on one side of the body, frequently in one hand.

Other common symptoms include slow movement (called bradykinesia), an inability to move (akinesia), im-paired balance and coordination, and trouble talking or completing other simple tasks.

What causes Parkinson's has been a subject of great debate and research for decades. Some scientists have suggested that Parkinson's is a result of toxins selectively destroying dopamine-containing neurons. Exposure to pesticides in the air or in food, for instance, hypothetically could be the trigger for the disease.

Parkinson's also can occur as a result of illness, such as encephalitis or other serious viruses, injury or some medications used to treat psychiatric disorders and high blood pressure.

More recently, NIH scientists have identified a gene abnormality that causes some cases of Parkinson's. That discovery doesn't explain all cases, but it is a step toward a breakthrough, Dr. Chase says.

"Parkinson's disease is probably due to a multiplicity of factors," he says. "In the past, we were looking for the cause. Now that we know it is likely a combination of environmental and genetic factors . . . our chances of stopping the disease improve."

In search of the right dosage

The most common treatment for the early stages of Parkinson's is the drug levodopa, which replaces the lost dopamine in the brain. Many patients control tremors for years by taking it.

"I took [levodopa] for eight or 10 years, and it really helped," Mrs. Bartlett says. "No one knew I had Parkinson's. I was able to keep up with my sons, who were 8 and 9 years old at the time I was diagnosed. I didn't tell most people I had the disease, not even my sons."

As the disease progressed, however, the drug began to lose its effectiveness, and Mrs. Bartlett began having severe side effects. That is an unfortunate common scenario with patients who rely on levodopa, Dr. Chase says.

Dyskinesia — involuntary movements such as twitching, nodding and jerking — commonly develops in people who take the drug over a long period. The period of effectiveness of each dose gets shorter and shorter over time, and doctors and patients have to work hard to readjust the medication or add other drugs.

"After I turned 40, it got to the point where the tremors were much more severe," Mrs. Bartlett says.

"I couldn't walk well. It was like my feet were stuck to the floor. The dyskinesia can be worse than the disease. If I were sitting at a restaurant, I would weave all over the place. People thought I was tipsy."

Other drugs are being studied. Doctors sometimes give the drugs bromocriptine and pergolide, which mimic dopamine and can boost levodopa's length of effectiveness.

The drug selegiline, which delays the breakdown of dopamine, can be given to early-stage sufferers to delay their having to take levodopa.

Other drugs commonly prescribed include anticholinergics and the anti-viral drug amantadine, both of which help control tremors and rigidity.

A promising class of drugs, called dopamine antagonists, eventually might replace levodopa. A five-year study in France showed using dopamine antagonists at the outset and using levodopa later resulted in less dyskinesia. In the study, 85 people took the new drug and 45 took levodopa. Five percent of those who took dopamine antagonists had dyskinesia, compared to 36 percent who were on levodopa.

Surgery: probing the brain

When Parkinson's patients reach an impasse with medication, there are three surgical choices available to them.

The most common, a pallidotomy, has been around in several forms for decades. Refinements of the procedure in the early 1990s showed it to be a promising treatment for Parkinson's patients, and its popularity has seen a resurgence.

In a pallidotomy, doctors insert a probe into the portion of the brain called the globus pallidus, creating a lesion in a precise area. The lesion interrupts neural pathways and reduces tremors and rigidity.

In a thalamotomy, a similar lesion is made in the thalamus, which contains two walnut-size bundles of nerves located near the core of the brain. A thalomotomy, which Mr. Fox underwent, also controls tremors in a majority of patients whose disease originates from the thalamus.

A third type of surgery, called deep brain stimulation (DBS), is considered the new frontier of Parkinson's surgery.

In that treatment, which the U.S. Food and Drug Administration approved in 1997, high-frequency electrical stimulation is delivered to the brain via an electrode. The electrode is powered by a battery pack to which it is connected under the skin, below the patient's collarbone. The mechanism is controlled by a magnet to increase the frequency as the disease progresses or to turn off the device at night, when symptoms tend to decrease.

"It seems more people prefer DBS," says Dr. Joseph Smith, a neurosurgeon who has implanted many devices at the Medical College of Georgia. "It is reversible, and it does not destroy tissue.

"You still have to take medication, and it does not destroy the disease process," Dr. Smith cautions. "What people have found, however, is that after a year or so, it appears the disease has stopped progressing. And when the disease does progress, rather than re-operate, we turn up the amplitude of stimulation."

Mrs. Bartlett has undergone two surgeries. She underwent a pallidotomy in 1996. The operation was on the left side of her brain to control tremors, rigidity and dyskinesia on the right side.

"The operation was marvelous," Mrs. Bartlett says. "It was like I had been wrapped up in wires, and somebody set me free."

However, the Parkinson's continued to progress on her left side, and the dyskinesia worsened. In a 20-hour operation last June, she underwent DBS. The results of that operation are more subtle, she says.

"I don't have the dyskinesia or tremors," she says. "It got rid of a condition I had where my foot curled in. Having [the pack placed under your skin] takes some getting used to. I always feel like something is there. I still have balance trouble. My speech is affected; when I am tired or hungry, my volume and pronunciation are low.

"I do not feel I am cured," Mrs. Bartlett says. "I did feel like I was after the pallidotomy. But I am better."

Living and coping

In the past 13 years, depression has been a side effect for Mrs. Bartlett, as it is for many Parkinson's sufferers. She had to make lifestyle changes, including quitting her job at a bookstore, where counting change and standing on her feet were almost impossible.

Mrs. Bartlett has found that exercise helps, as does a good support group. She does water aerobics and lifts weights.

"I really believe that moving water does not freeze," she says. "We need to get our muscles moving. It has made me so much stronger. I don't think I could have made it through 20 hours of surgery if I wasn't strong."

Mrs. Blue, who had to give up driving a car a few years ago, says she is considering having DBS. She belongs to a support group in Annandale and takes part in a Parkinson's exercise class.

"I definitely find it helps," she says of the class. "It keeps my muscles working and helps me to cope. I dream of being alive when the cure comes, so I need to keep my muscles moving."

janet paterson
53 now / 41 dx / 37 onset
a new voice: http://www.geocities.com/janet313/
613 256 8340 PO Box 171 Almonte Ontario Canada K0A 1A0