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Deep Brain Stimulation Improves Parkinson's Symptoms

   Portland, Ore.

OHSU study shows surgery may be better than medication in later stages

Like a malevolent curse, Parkinson's disease hit Mary Ann Fanyak-Mendenhall of Salem, Ore., and Steven D. Smith of Salt Lake City where it hurt.

For Fanyak-Mendenhall, a former promotion director for a Denver-based radio broadcast corporation, it meant losing her ability to speak as the disease twisted and pulled her tongue during uncontrollable convulsions.

"My speech was almost unintelligible because my tongue curled on both sides, and it would have a thrust to it, so it would thrust itself forward, almost out of my mouth when I was trying to speak," said Fanyak-Mendenhall, 60. "Not only was it difficult to speak, I had to almost go to my brain like it was a word salad and select the words I could pronounce. It took a tremendous amount of energy."

For Smith, a gifted podiatrist who performed delicate foot surgeries, the disease took the form of severe tremors that seized his hands and toyed with his dexterity.

"I had difficulty suturing at the end of a long surgery," recalled Smith, 60. After being diagnosed with Parkinson's, "I continued to practice for about a year, but it was getting to the point where it was possible to compromise my surgery. So I stopped practicing."

But Fanyak-Mendenhall and Smith have high hopes for a new surgical procedure that's showing promise as a possible primary form of therapy for later-stage symptoms of the disease. Both are Oregon Health & Science University patients participating in a national study launched in part by the results of a series of OHSU studies showing deep brain stimulation improves many features of advanced Parkinson's disease.

According to the most recent study, published this week in the American Medical Association journal Archives of Neurology, stimulation of two different areas of the brain - the globus pallidus interna, or GPi, and the subthalamic nucleus, or STN - appears to improve motor function of Parkinson disease patients. The study found that the results of stimulating the STN, thought by many to be the preferred target for stimulation, and the GPi are generally comparable.

The differences between the two sites in their responsiveness to stimulation have largely stemmed from "the views of a few people who decided, based on their experience, that STN is a better site," said Kim Burchiel, M.D., professor and chairman of neurological surgery, OHSU School of Medicine, and a study co-author. "One of the points we make in this article is that GPi, the other site, can work as well."

During stimulation therapy, a pacemaker-like device implanted under the skin near the collarbone sends electrical impulses through an insulated wire to two electrodes surgically implanted in the brain from the top of the skull. Stimulation blocks the signals that cause the disabling motor symptoms of Parkinson's. The technology, manufactured by Medtronic Inc., was approved by the U.S. Food and Drug Administration in 2002.

The study's lead author, Valerie Anderson, Ph.D., OHSU associate professor of neurological surgery said deep brain stimulation has been studied as a Parkinson's therapy for 10 to 15 years. Initial trials focused on its effectiveness in reducing rest tremor, the disease's most common symptom, and they showed that stimulating an area of the brain called the motor thalamus is effective in reducing tremor in the long term.

 "In this study, we have focused on the ability of stimulation to modulate symptoms associated with more advanced stages of the disease, including rigidity, slowness, and problems with balance and walking," Anderson said. "In addition, we were interested in looking at whether it can reduce the movement problems that many of these patients experience due to chronic dosing with L-dopa." L-dopa, or levodopa, is a natural substance, taken as a pill, that stimulates the production of dopamine in the brain and treats such Parkinson's symptoms as tremors, stiffness and slow movement.

The OHSU study examined two groups of 10 Parkinson's disease patients, each randomly assigned to GPi or STN therapy. Motor skills improved 39 percent among the GPi group and 48 percent among the STN group. Bradykinesia, or slow movement, improved more with STN than GPi stimulation, and L-dopa doses were reduced 38 percent among STN stimulation patients compared with 3 percent in GPi stimulation patients. However, dyskinesia, or involuntary movement, was similarly reduced by GPi and STN stimulation.

Anderson said the differences between the STN and the GPi in their ability to reduce the need for L-dopa therapy was one reason some experts abandoned GPi stimulation. "Our results suggest that despite the medication reduction, the benefits of STN stimulation over GPi are not clear-cut, and we know too little about how stimulation at either site really works to exclude GPi as a target for stimulation."

The OHSU study helped spur a similar national study, sponsored by the U.S. Department of Veterans Affairs and the National Institutes of Health, that is expected to be completed this summer. OHSU patients Fanyak-Mendenhall and Smith are both participants.

"It's a multi-center trial that basically does the same thing we did, but on a much larger scale," Burchiel said. "You need to have large numbers of people to be able to make a statement, and the two statements we're trying to make with the larger study is whether surgery is superior to best medical management in somebody who's in the later stages of Parkinson's disease, and question No. 2 is which site (STN or GPi) is better."

Fanyak-Mendenhall said she hopes deep brain stimulation allows her to help other people overcome the disabling symptoms of Parkinson's disease. "This whole thing, for me, has been a very spiritual journey and healing is very spiritual to me, and I really want to write the story of my life in a way that will be, hopefully, helpful to people," she said.

Smith hopes the therapy helps him regain his independence so he doesn't have to rely so much on others for basic needs. "I can do without somebody having to feed me, or without shaking the food off my fork," he said.

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