 |
 |
New Surgical Approaches to Parkinson Disease Vancouver, BC — Deep brain stimulation and cell transplantation have fired interest in the surgical treatment of patients with Parkinson disease (PD), particularly those with more advanced, severe disease. One factor pushing the resurgence of surgical treatment is the limited success of medical therapy with levodopa, said C. Warren Olanow, MD, chair of neurology at Mount Sinai School of Medicine in New York City, who spoke on "surgery from a physician's point of view" at the 13th International Congress on Parkinson Disease here in July. Other factors are safer and more accurate surgical techniques, improvements in intraoperative microrecordings, and advances in neuroimaging, all of which combine to allow surgeons to reach their targets with greater accuracy and less likelihood of adverse effects. DEEP BRAIN STIMULATION At specialized centers in Europe and North America, high-frequency deep brain stimulation of three different targets in the brain has been the focus of a promising surgical approach. The targets are the subthalamic nucleus (STN)—the stimulation of which, in the opinion of many at the meeting, appears to offer the greatest clinical benefit—globus pallidus internus (GPI), and ventral intermediate nucleus (VIM) of the thalamus. The procedure involves implanting an electrode deep into one of the three target areas using a stereotactic technique and microelectrode guidance. The microelectrodes provide microrecordings of neurons that enable the neurosurgeon to discern typical patterns of cell targets or of adjacent structures to be avoided. Microstimulation mimics the therapeutic effects of the final implant and helps identify the target location. Intraoperative mapping and confirmation of the electrode placement may involve the use of magnetic resonance imaging and ventriculography, as well as electrophysiological measurements. After placement, the electrode is tunneled under the skin to a reversible external electrical stimulator that can be switched on or off by the patient and adjusted for intensity and frequency. The procedure usually is performed bilaterally. Alim L. Benabid, MD, of Grenoble University Hospital in France, presented data on 248 patients who have received 418 implants (some on both sides of the brain, others on one). Of this total, 99 received STN stimulation, usually on both sides of the brain; 12, GPI stimulation; and 137, VIM stimulation. These patients have been evaluated at 3, 6, and 12 months after surgery, then once each year. The longest follow-up of STN-treated patients is 6˝ years. Benabid said that the result of evaluation of symptoms at 3-year follow-up and beyond has been comparable to the result at 1 year, suggesting that the beneficial effects of the procedure are stable. At 1-year follow-up, Benabid said he found a striking reduction in the signs and symptoms of PD. "Tremor was abolished by 80%, akinesia and rigidity were diminished by 65%, and levodopa dosage was reduced by 50%, thus reducing levodopa-induced dyskinesias," he said. "About 10% of patients became drug-free." These effects remained constant at 3 years or more of follow-up. "STN stimulation is extremely efficient in reducing the triad of PD symptoms," Benabid said. He suggested that the STN may be the unique target for controlling the disease and that stimulating that area may become the surgical treatment of choice for advanced disease. Benabid said the results in these older and seriously ill patients suggest that STN stimulation may achieve more than symptomatic improvement; it may also have a neuroprotective effect, interfering with the degenerative process and slowing the progression of disease. The most serious surgical complication, hematoma, occurred in two patients, he said, and in one was fatal. Equipment-related infections occurred in three patients. The two most common adverse effects were hypophonia and eyelid apraxia; each occurred in about 25% of the patients. The degree of defective speech varied in different patients, said the surgeon, but sometimes the voice level was so diminished that it became difficult to understand the patient. Based on his long-term follow-up of patients who have undergone STN stimulation, Benabid said, "High-frequency stimulation is reversible, adaptable, and safe. Bilateral surgery is safe." Comparing the results of surgery on two of the three target areas, Benabid has found that the main effect of GPI stimulation is to reduce and control levodopa-induced dyskinesias. However, it reduces other PD symptoms only moderately: "In general, STN stimulation improves all the signs and symptoms by more than 60%, while GPI stimulation improves [them] by less than 60%," Benabid said. VIM stimulation has been used to treat essential tremor as well as PD tremor. Although the technique has a major salutary effect on tremor, it does not affect rigidity and akinesias, said Benabid. Donald Calne, MD, director of the Neurodegenerative Centre at the University of British Columbia, said Benabid's findings are "significant," adding, "STN stimulation may become an important surgical approach." Olanow, commenting on the US experience, cited data showing that STN stimulation significantly improved patients' motor scores on the Unified Parkinson Disease Rating Scale by 65%, while GPI stimulation improved the scores by 35%. STN stimulation reduced the use of levodopa by 25%, while GPI stimulation increased its use by 24%. "STN stimulation has the potential to offer dramatic benefit to patients whose disease cannot be satisfactorily controlled with medical therapy," Olanow said. However, he pointed out various disadvantages of deep brain stimulation, which in addition to being a relatively expensive procedure can be performed now at only a limited number of centers. "There is a whole new group of adverse effects that are related to the equipment," he said, "including lead breaks, infections, and ulcerations of the skin. And there is the need to replace the battery, which must be done under general anesthesia." In an interview, neurosurgeon Andres Lozano, MD, of the University of Toronto, Ontario, said, "Deep brain stimulation has the advantage of being adjustable and the electric current can be titrated to match the signs and symptoms of the disorder, but the technique has the disadvantage of higher medical cost to program the device to get the optimal effect. Also, the procedure carries with it the risk of implanting a foreign body into the brain." The main alternative to deep brain stimulation is pallidotomy, said Lozano. This procedure has similar efficacy, he said, but involves creating an irreversible lesion in the brain and is too "risky" to do bilaterally. CELL TRANSPLANTATION Worldwide, fetal cell transplantation has been performed on about 360 patients in 17 centers, and preliminary evidence shows that the procedure can be done safely, reliably, and reproducibly, said neurosurgeon Thomas Freeman, MD, of the University of South Florida, Tampa. "There is evolving evidence that these transplants are efficacious and that graft survival correlates with clinical improvement and radiologic improvement on [positron emission tomographic] PET scans," he said. However, he noted, the approach has been limited because of societal concern about the use of fetal tissue and because of technical surgical issues, including identification of the best target area for transplantation. "It is unlikely that fetal tissue transplantation ever will be performed outside of a small number of centers," Freeman said. "Instead, fetal tissue transplantation is likely to serve as the gold standard for future transplant protocols using cell lines." The largest experience with fetal cell transplantation is in Sweden, where patients have received transplants (on only one side of the brain rather than both) since 1989 and showed improvement lasting about 5 years before deterioration began. Freeman suggested that the single-side approach was responsible for the deterioration. He said he is optimistic that bilateral transplantation will result in superior clinical improvement, because the disorder affects both sides of the brain, but long-term data are not yet available on such patients. Of the global total of 360 patients with fetal cell transplantation for PD, approximately 150 are in the United States, University of Colorado neurosurgeon Curt Freed, MD, said in an interview. Since 1988, 60 have been done at his institution, 50 in Los Angeles, 30 at the University of South Florida, and four at Yale University. Researchers currently are experimenting with as many as 18 ways of providing cells other than fetal cells that can be used for transplantation. "Two methods involve cells derived from stem cells," Freeman said. "Another involves retinal cells, which secrete dopamine and neurotrophic factors. Evidence is evolving quite rapidly that one or more of these different strategies may be useful clinically." by Pat Phillips 1999 American Medical Association. All rights reserved. <http://jama.ama-assn.org/issues/v282n12/full/jmn0922-1.html> janet paterson 52 now / 41 dx / 37 onset 613 256 8340 po box 171 almonte ontario canada K0A 1A0 a new voice: <http://www.geocities.com/SoHo/Village/6263/> <[log in to unmask]>