Researchers Focus On Deep-Brain Stimulation for Parkinson's

Two areas of brain appear equally useful targets, new study suggests

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By
HealthDay Reporter

FRIDAY, April 15, 2005 (HealthDayNews) -- A treatment called deep brain stimulation has proven effective in controlling Parkinson's disease symptoms, but doctors have long debated which areas of the brain should be stimulated to produce the best results.

Now a small study suggests the stimulation of two distinct brain regions can each bring about good outcomes, with the best choice varying patient to patient.

Parkinson's disease falls into the category of diseases known as motor system disorders. The main symptoms are trembling and stiffness in extremities and face; slowness of movement; and impaired balance and coordination. As these symptoms worsen, patients experience difficulty walking, talking, or other simple tasks. Parkinson's is chronic and progressive, but is not contagious and usually not inherited.

Treatment consists of controlling symptoms with the drug levodopa, which replaces depleted levels of the brain chemical dopamine. As the disease progresses, levodopa can lose its effectiveness, however. When this happens, deep brain stimulation (DBS) can be brought in to help maintain motor function.

DBS consists of a multi-electrode lead implanted into the brain. The lead is connected to a pulse generator implanted under the skin in the chest. The pulse generator produces a high-frequency, pulsed electric current, conducted by the electrode to the brain. This electrical stimulation appears to block tremors.

"The whole idea of DBS therapy for Parkinson's is a bit toward the cutting edge," explained lead researcher Valerie C. Anderson, an associate professor and director of clinical research at Oregon Health and Science University. "One of the issues is where should we implant stimulators to get the best response."

Earlier studies have shown that stimulation of two brain centers -- the globus pallidus interna (GPi) or the subthalamic nucleus (STN) -- can be done safely with effective results. While both sites have been approved for electrode implantation by the U.S. Food and Drug Administration (FDA), STN has been the preferred target among neurosurgeons.

However, "we really don't know which one of these sites produces what spectrum of symptom response," Anderson said, "so we don't know which site might be best for an individual patient with advanced Parkinson's disease."

To help find out, the Oregon team randomly selected 23 patients with advanced Parkinson's disease to receive stimulation in either the GPi or the STN areas of the brain. They monitored patient symptoms with and without medication at three, six and 12 months after implanting the stimulators, according to the report in the April issue of the Archives of Neurology.

According to Anderson, both sites produced similar results.

Her team found that DBS doesn't help improve symptoms when they are already being suppressed with medication. What it can do is improve patient's functional ability when they are no longer taking drugs, Anderson said. "Implantation in either site produces very good long-term response when patients' medications are not working," she said.

Compared with GPi stimulation, STN stimulation was associated with more mood disorders and cognitive problems lasting for about a month after surgery, the researchers found. This may be a result of lower doses of levodopa given during STN-based therapy, she suggested.

"There is a period when you are trying to add stimulation and adjust the medications at the same time," Anderson said. "So it is possible that these side effects are due to a dose of levodopa that is not yet optimized for the stimulation that has been added on."

Anderson thinks that there may be differences in particular symptom response based on where these devices are implanted. "We really need to know where the best site might be for certain symptoms of the disease," she said.

She also pointed out that many doctors have traditionally preferred the STN site. This preference seems to be based on habit, she said, as well as an increased ability on the part of doctors to reduce patient medications.

According to the researchers, stimulation at both the STN and GPi sites can be effective in controlling Parkinson's symptoms. "We really need to look at this more carefully," Anderson said. "GPi has some advantages that we need to understand, and we shouldn't just ignore the benefits of implanting in both localities."

One expert noted that earlier studies had claimed that STN was better than GPi. "But that may have not been the right decision for the patients," said Dr. Michael S. Okun, an assistant professor of neurology and co-director of the Movement Disorders Center at the University of Florida.

"It appears that the targets for DBS may be more equal than thought before," Okun said. "And there may be individual reasons to choose one target over another."

Okun and his colleague Dr. Kelly D. Foote, the authors of an accompanying editorial, note that since the GPi is a larger target than STN, GPi maybe a better target because there appear to be fewer cognitive side effects. "These are things that need to be explored with a larger study," Okun said. He noted that three large trials are currently underway studying exactly these types of issues.

"DBS is great for a lot of the symptoms of Parkinson's disease," Okun said. "We have two targets that are approved by the FDA. They both work well, but there may be specific reasons to use one target over the other target for specific patient populations." However, right now there isn't a definitive answer, he said.

Although STN is the preferred site today, Okun believes that eventually there will be reasons to use both sites based on individual patient symptoms. "This is a beginning of a rematch between the targets," Okun said. "I think we are going to find out that there are reasons to use the GTi target, and patients to use it in, and it's going to affect the way we treat patients."

Another expert agrees that both sites are viable for DBS. But knowing when the leads are in the right place can be problematic. "These two targets are different in size and in how easy they are to locate and put a lead in," noted Dr. Jerrold L. Vitek, co-director of the Center for Neurological Restoration at the Cleveland Clinic.

Vitek believes many of the problems with DBS result from faulty placement of electrodes. "STN is real small, and if you put a lead in that's off target, you are more likely to see side effects." On the other hand, STN stimulation gives surgeons immediate feedback in the operating room, he added, allowing them to spot immediate symptom relief. That lets surgeons know the lead is in the right place, he explained.

"With GPi, there is often a delay in the benefit, so you don't see it right away," Vitek said. "You turn on your stimulator and don't see a benefit, but you may be right where you want to be and not know it."

He believes the primary limitation of Anderson's study is its size. There were too few patients to really prove which site is best. To try to answer that question, Vitek is conducting his own study, involving 130 patients.

More information

The National Institute of Neurological Disorders and Stroke can tell you more about deep brain stimulation.

SOURCES: Valerie C. Anderson, Ph.D., associate professor and director, clinical research, Oregon Health and Science University, Portland; Michael S. Okun, M.D., assistant professor, neurology, and co-director, Movement Disorders Center, University of Florida, Gainesville; Jerrold L. Vitek, M.D., Ph.D., co-director, Center for Neurological Restoration, Cleveland Clinic, Ohio; April 2005 Archives of Neurology

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