Medical Device Daily Associate Managing Editor

According to the results of a major randomized, controlled, multicenter study published in the Aug. 31 issue of The New England Journal of Medicine (NEJM), a treatment from Medtronic (Minneapolis), called the Activa Deep Brain Stimulation (DBS) therapy, combined with medication, is significantly more effective than medication alone in treating motor symptoms of advanced Parkinson's disease.

Conducted at 10 academic medical centers in Germany and Austria, the study included 156 patients with severe motor symptoms of Parkinson's disease and rated improvements in motor function (among other outcomes) after six months of treatment.

Patients were randomly assigned to one of two treatment groups: half were selected to receive medication plus bilateral DBS of the subthalamic nucleus (STN), a brain structure involved in regulating movement, using Medtronic's Kinetra neurostimulation system; and the other half were selected to receive medication alone.

At the time of enrollment in the trial, all patients were under 75 years old, had been diagnosed with Parkinson's disease at least five years previously, and suffered from impaired mobility despite optimal drug treatment.

Compared to medication alone, DBS of the STN caused significantly greater improvements in motor function after six months. On average, patients who received DBS plus medication showed a 41% improvement in motor function (as measured by the motor examination component of the Unified Parkinson's Disease Rating Scale (UPDRS-III). Medication-only patients showed no change on the same measure.

“In conclusion,” the authors wrote, “this six-month study demonstrated that subthalamic neurostimulation resulted in a significantly and clinically meaningful improvement in . . . patients under 75 years of age who had advanced Parkinson's disease with severe fluctuations in mobility and dyskinesia (involuntary movements caused by medication). The patients who received neurostimulation had longer periods and better quality of mobility with less dyskinesia.”

Lead author Gunther Deuschl, MD, professor of neurology and chairman of the Department of Neurology at the University of Kiel (Kiel, Germany), explained the significance of the study's results: “DBS clearly provides important benefits to Parkinson's patients who suffer troubling motor symptoms despite optimal treatment with medication. It should therefore be offered to this group of patients as soon as mobility problems can no longer be managed sufficiently with medication.”

Joe McGrath, a company spokesman, told Medical Device Daily that while serious adverse events were more common with neurostimulation than with medication alone – and included a fatal intracerebral hematoma – the total number of adverse events was higher among medication-only patients.

“There were three deaths in the neurostimulation group,” said McGrath, including the intracerebral hematoma, directly caused by the implantation procedure, he said. “That's a known risk of undergoing brain surgery.”

The authors stated that all of the non-fatal adverse events “resolved without permanent complications” and that “most adverse events were well-known medical problems associated with advanced Parkinson's disease.”

While the initial patient population are those patients for which medication alone is not working anymore and causing “intolerable side effects,” he said the question that needs to be answered is whether offering deep brain stimulation earlier in their disease progression will hold any benefit.”

Adjustable to best meet the needs of each patient and reversible if necessary, Activa therapy stimulates structures deep within the brain that influence motor control and appears to block brain signals that cause the stiffness, slowness of movement and/or shaking that characterize the disease.

The Activa Soletra, often called a “brain pacemaker,” was first cleared for the treatment of advanced-stage Parkinson's disease in January 2002 (MDD, Jan 16, 2002) and is the only brain stimulation therapy currently commercially available in the U.S. That original system used two pacemaker-like devices implanted on each side of the chest with leads implanted in the brain.

The new Kinetra neurostimulator, cleared by the FDA in January 2004 (MDD, Jan. 23, 2004), is a single device that accommodates two Medtronic DBS leads carrying precisely controlled, electrical impulses to both the left and right sides of the brain, thus reducing surgical incisions. Before the Kinetra device, treatment of bilateral symptoms caused by Parkinson's disease required separate implants of two neurostimulators to control some of the disabling symptoms of Parkinson's on both sides of the patient's body

“We welcome the results of this latest study, which represent an excellent addition to the clinical evidence for Activa DBS Therapy as a treatment for Parkinson's disease,” said Dr. Richard Kuntz, president of Medtronic's Neurological division and senior vice president of Medtronic. As the pioneer and leader of this therapeutic technology, Medtronic is committed to studying DBS for a variety of clinical applications. We are also committed to advancing the technology itself.”

The study was supported by a grant from the German Federal Ministry of Education and Research. Medtronic coordinated several investigator meetings and covered the cost of supplemental patient insurance for study participants.

McGrath said the implant procedure, which was used in the trial, is typically done in two parts. In the first step, he said, the leads are implanted in the brain with the aid of an image-guided navigation system pinpointing the precise location in the brain for producing maximum benefit. Patients must remain conscious during the procedure to test out therapeutic effectiveness.

In a second phase, the patient comes in to have the pacemaker-like device implanted in the shoulder area and to have that device attached to the leads that were implanted during the first part of the procedure.

“A couple of days later,” said McGrath, “the device is actually turned on.” After that, he noted, it can take from one month up to six months for fine-tuning to the individual patient's need.

McGrath said that while the heart pacemaker comparison is valid one – and the DBS device evolved out of that technology pioneered by Medtronic – there is a great deal of difference in the frequency that therapy is delivered. “A heart pacemaker delivers about 60 electrical pulses per minute compared to a neurostimulation system, which is delivering somewhere between 130 and 180 pulses per second, so it's a lot faster in terms of frequency.”

He estimated that the cost of the device, including the device, physician and hospital fees at from $50,000 to $60,000. While the up-front costs are significant “over time, the costs are recouped,” he said.

The Centers for Medicare & Medicaid Services (Baltimore) in early 2003 approved Medicare reimbursement for the Activa Soletra system for the treatment of Parkinson's disease and essential tremor. The Kinetra is also reimbursable, the company said, but under a different set of codes.

The company reports that more than 30,000 people worldwide have received Activa DBS Therapy, approved for the treatment of the three most common movement disorders, Parkinson's disease, essential tremor, and dystonia.