FDA Panel Backs Approval of Neurostimulator.
At a meeting of the Food and Drug Administration's neurological devices panel, the expert panel agreed unanimously that the device, the Activa Parkinson's Disease Control System, was "approvable" for controlling symptoms in patients with advanced Parkinson's disease who are not adequately controlled on medications but are still responsive to levodopa.
The panel outlined several conditions for approval, including a requirement that the manufacturer conduct a 3-year follow-up study of patients, including neurocognitive and neuropsychiatric assessments. One panelist also recommended that labeling state that this is not a treatment for everyone with Parkinson's.
The FDA usually follows the advice of its panels, which are not binding.
The device was approved in 1997 for treatment of unilateral essential or Parkinson's tremor via stimulation of the thalamus. That approval was for implantation in one side of the brain.
Manufactured by Medtronic, Minneapolis, the device consists of a programmable, battery-operated neurostimulator that is about the size of a cardiac pacemarker, Implanted under the skin near the clavicle, it sends mild electrical pulses through a thin, insulated wire that is implanted under the skin of the shoulder, neck, and head.
The pulses are delivered to the subthalamic nucleus (STN) or the global pallidus, structures that are involved in motor control and are overactive in Parkinson's. Electrodes are implanted into each side of the brain by a neurosurgeon experienced in the required stereotactic technique.
Patients activate the device using a hand-held magnet; physicians can adjust the amount of stimulation noninvasively.
The treatment is targeted at controlling the four cardinal symptoms: rigidity, bradykinesia and akinesia, tremor, and postural instability in patients whose responses to medical therapy have started to fail, according to Medtronic.
This treatment "represents an advance in science comparable with when 1evodopa was first used in Parkinson's," said Dr. C. Warren Olanow, professor and chair of the department of neurology; Mount Sinai School of Medicine, New York. He presented the results of a 12-month, international, multicenter prospective study of bilateral stimulation in people with advanced idiopathic Parkinson's, aged 30-75 years, who were not adequately controlled with medications. Nearly 70% were men and more than 90% had dyskinesia.
Of the 95 patients whose leads were implanted in the subthalamic nucleus, motor scores that measured the cardinal Parkinson's symptoms improved by 48% when the neurostimulator was activated.
Daily "on" time (defined as good motor function and relief from parkinsonian symptoms) without dyskinesia increased from about 5 hours to 11-12 hours a day during follow-up, according to patient diaries. Treatment also made it possible to reduce the dose of levodopa equivalent by 25%-37% during follow-up The proportion of patients rated as severely or markedly disabled by patients and physicians dropped from 74% to 23% by the end of the study, Dr. Olanow said.
Of the 54 patients whose leads were implanted into the global pallidus, motor scores improved by 38% when the stimulator was turned on. The study was not designed to answer which target was more effective, but ongoing studies are directly comparing the two.
Dr. Olanow showed videos of patients with severe symptoms, showing dramatic improvements in their ability to walk down a corridor when the device was activated.
Nearly 90% of the patients in the study had at least one adverse event, related to the implantation procedure, the device, and/or electrical stimulation. The most serious event was intracranial hemorrhage, which occurred in 11 patients. Other side effects included lead migration and infection.
The most frequent adverse effects due to stimulation were dysarthria, dyskinesia, dystonia, and paresthesias in 8%-12% of patients. These side effects were "typically mild and well-tolerated," said Dr. Olanow, who described the overall safety profile as "acceptable," considering that it involves an intracranial procedure and is reversible.
In addition to being relatively safe, the use of deep brain stimulation in this population avoids the need for destructive surgery such as a pallidotomy, and the electrical stimulation can be adjusted at any time to "maximize clinical benefit and minimize adverse events," he said.
Panelist Dr. Lucia J. Zamorano, professor of neurosurgery at Wayne State University, Detroit, said that the device may be an important advance in treating Parkinson's disease. But she speculated that the complication rate could be 5-10 times higher once the procedure is available to the general community of neurosurgeons. Among the panel's concerns were how the company could ensure that the device would be implanted by neurosurgeons with adequate stereotactic experience.
Panelist Dr. Mark Hallett, clinical director of the National Institute of Neurological Diseases and Stroke, Bethesda, Md., said that although he and others considered the study poorly designed, "the benefit seems to be so dramatic in many circumstances, and the benefit is clear." In his view, the increase in the length of daily "on" time was the most convincing outcome.
Dr. Olanow said that he has no financial interests in Medtronic but has served as a consultant to the company, which paid for his trip to the hearing.
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|Comment:||FDA Panel Backs Approval of Neurostimulator.|
|Publication:||Family Practice News|
|Article Type:||Brief Article|
|Date:||Jun 15, 2000|
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