On January 14 the Food and Drug Administration (FDA) approved the first device for deep brain electrostimulation to relieve the symptoms of Parkinson’s disease. The pivotal study on which the approval was based was published in the September 27, 2001, New England Journal of Medicine. It showed that the device, which provides bilateral stimulation of the subthalamic nucleus or of the pars interna of the globus pallidus, dramatically improved motor function, increased mobility, and reduced levodopa requirements in patients with advanced Parkinson’s disease

C. Warren Olanow, MD, told NEUROLOGY REVIEWS, “This represents a dramatic advance in Parkinson’s disease treatment. This procedure offers us the opportunity to improve function in advanced Parkinson’s disease patients who cannot be satisfactorily controlled with medical therapy.” Dr. Olanow, who is Professor and Chair of the Neurology Department at Mount Sinai School of Medicine in New York City, was a principal investigator in the Deep-Brain Stimulation for Parkinson’s Disease Study Group, which included researchers in 18 medical centers in Europe, the United States, Canada, and Australia.

The investigators tested Medtronic’s Activa® Tremor Control Therapy device in a controlled, double-blind study in 134 patients (ages 30 to 75) who had at least two cardinal features of parkinsonism (tremor, rigidity, or bradykinesia), a good response to levodopa, a minimal off-medication score of 30 on the motor portion of the Unified Parkinson’s Disease Rating Scale, and motor complications that could not be controlled with medical therapy. Patients with dementia, cognitive impairment, and major psychiatric illness were excluded.

SELECTING A SITE FOR STIMULATION

In Parkinson’s disease there appear to be changes such that abnormal information is conveyed from the basal ganglia to the motor system, Dr. Olanow said. Subthalamic nucleus or globus pallidus lesions eradicate that abnormal signaling, and deep brain stimulation apparently accomplishes the same thing without tissue destruction. “In terms of Parkinson’s disease symptoms, it appears to be better for the motor system to receive no information than to receive wrong information.” It is not yet known if the subthalamic nucleus or the globus pallidus is the most effective site for deep brain stimulation in Parkinson’s disease, he noted. “In this study both sites provided benefit and the choice of target site was up to each investigator.”

The double-blind crossover study, performed three months after surgery, included 91 patients with implants in the subthalamic nucleus and 36 with implants in the globus pallidus. Both sites were effective, but according to Dr. Olanow, subthalamic nucleus stimulation was somewhat more effective. Percent “off” time decreased from 49% to 19% in subthalamic nucleus stimulation patients and from 37% to 24% in globus pallidus patients. Percent “on” time without dyskinesia increased from 27% to 74% in subthalamic nucleus patients and from 28% to 64% in globus pallidus patients. Daily levodopa dose equivalents were reduced from 1,218 to 764 mg in the subthalamic nucleus group but were unchanged in the globus pallidus group. Hemiballismus was not seen in any patient.

POTENTIAL DRAWBACKS

Beyond this risk of hemorrhage, two barriers are likely to prevent quick adoption of this new treatment. The first is that installation requires a fairly sophisticated clinical team. “You need a Parkinson’s disease expert, a surgeon skilled in stereotactic functional neurosurgery, a radiologist to help locate the target, and a physiologist for microelectrode placement and reading,” Dr. Olanow allowed. “Setting the stimulation parameters can take several hours, and more time is required for repeat evaluations to make certain the settings are correct.”

The second barrier is the cost of the procedure and the device, currently estimated at $50,000 to $60,000 per patient. However, this potentially prohibitive price tag notwithstanding, the Activa system is currently being studied in a randomized clinical trial meant to determine whether the subthalamic nucleus or the globus pallidus is the better site for microelectrode placement, Dr. Olanow said.

NR