In a surprising finding, researchers have discovered that deep brain stimulation for Parkinson's disease is equally effective at either of the two most commonly used sites. Parkinson experts had believed that stimulation of the subthalamic nucleus was more effective than stimulation of the globus pallidus interna for controlling movement symptoms, but that it was more likely to aggravate other symptoms of the disease. But a new study of 299 patients randomized to receive one or the other of the techniques concluded that there were only very minor differences between the approaches. The study was reported Wednesday in the New England Journal of Medicine.
Parkinson's, which strikes as many as 100,000 Americans each year, is characterized by muscle control problems that produce shaking, rigidity, slowed movement and poor balance. Patients also tend to develop mental problems, including depression, apathy, slowed thinking, confusion, impaired memory and trouble sleeping. The disorder is caused by the loss of brain cells that produce the neurotransmitter dopamine, which plays a key role in transmitting commands from the brain to muscles. Its cause is unknown, but is at least partially genetic.
Medications such as L-dopa can control motor symptoms initially, but over time, they can worsen some symptoms. Researchers have also attempted to implant fetal brain cells to replace the dopamine-producing cells and have attempted gene therapy for the same purpose, but the results of such tests remain problematic. Perhaps the best intervention when medications begin to fail is deep brain stimulation, in which a surgeon threads a fine electrode through the brain to either the subthalamic nucleus or the globus pallidus, both of which are involved in motor control. The electrodes, one on each side of the head, are connected to a battery implanted in the chest that produces a minute electrical stimulation of the brain cells. Surgeons often see an improvement in patients while they are still on the operating table.
The new study is actually the second phase of a major clinical trial. In the first phase, deep brain stimulation in the patients at 13 U.S. centers was compared with the best treatment with medications and physical therapy. Researchers reported last year that stimulation was more effective at controlling all the symptoms. At the end of that stage, the patients who had been receiving drugs were randomized to receive deep brain stimulation.
"We found that motor outcomes between the two groups were not significantly different," Dr. Kenneth Follett of the University of Nebraska Medical Center, one of the lead authors, said in a statement. "Meanwhile there were very modest differences in mood and cognitive function between the two groups. Patients and physicians can have confidence in both types of [deep brain stimulation], and can make their choice based on the constellation of motor and nonmotor symptoms that determine the quality of life in Parkinson's disease."
On possible difference between the two approaches is that targeting the subthalamic nucleus allowed doctors to reduce the patient's dose of L-dopa by a larger amount. For patients who need higher levels of L-dopa to control nonmotor symptoms, targeting the globus pallidus might be a better choice, they said.
The study was funded primarily by the Department of Veterans Affairs and the National Institute of Neurological Diseases and Stroke. Some funding was provided by Medtronic Inc. of Minneapolis, which manufactures the equipment used.
-- Thomas H. Maugh II
Illustration: In deep brain stimulation, a battery and electronics implanted in the chest provide a minute electrical stimulus to the brain through implanted electrodes. Credit: Medtronic