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Earn CME/CE credit for reading medical news Use this code to embed video on your website or blog: HINES, Ill., Jan. 6 -- Deep brain stimulation was more effective in improving Parkinson's disease symptoms than "best medical therapy" in a large randomized trial, but was also associated with more adverse effects, said researchers here. After six months, patients receiving deep brain stimulation had a mean of 4.6 more hours a day without troubling dyskinesia, while medically treated patients saw no improvement (P<0.001), reported Frances Weaver, Ph.D., of the VA Medical Center here, and colleagues in the Jan. 7 issue of the Journal of the American Medical Association. Deep brain stimulation was also superior to medical treatment in other outcomes of the 255-person study, including motor function and quality of life, and the benefits did not seem to vary with age. But, 49 patients who had deep brain stimulation suffered adverse effects -- including one death from cerebral hemorrhage. Only 15 medically treated patients suffered adverse effects. (P<0.001) Older patients were more likely to experience adverse effects overall, the researchers said, although serious events occurred at similar rates in younger and older patients. The researchers said the clinical significance of the adverse events, and whether patients view the benefits as offsetting them, remain uncertain. In an accompanying editorial, Guenther Deuschl, M.D., Ph.D., of the University Hospital of Schleswig-Holstein in Kiel, Germany, said the findings "have convincingly confirmed the six-month efficacy of deep brain stimulation for advanced Parkinson's disease." However, he added, the study "shows that such progress cannot be made without costs in terms of adverse effects." In the study, Dr. Weaver and colleagues enrolled patients at 13 hospitals from 2002 to 2005, of whom 25% were at least 70 years old -- earlier research had excluded older patients. Hoehn and Yahr scores of at least 2 for disease severity while unmedicated were required for inclusion. Patients with atypical syndromes, surgical contraindications or past surgery for the disease, or other potential confounding factors were excluded. Deep brain stimulation was delivered to the subthalamic nucleus in 60 patients and to the globus pallidus in 61 patients. The remaining 134 patients received medical therapy as determined by neurologists specializing in movement disorders. Drugs as well as non- pharmacologic therapies were provided and adjusted as necessary to optimize outcomes. The primary study endpoint was "on" time, defined as the hours per day during which patients were free of troubling dyskinesias and had good motor control as recorded in patient-kept diaries. Additional outcomes included "off" time, disease symptoms as measured by the Unified Parkinson's Disease Rating Scale, neurocognitive abilities evaluated with the Wechsler Adult Intelligence Scales and other tests, and quality of life as assessed with the Parkinson's Disease Questionnaire. These were evaluated periodically through the six-month study. Key efficacy findings at six months, given as changes from baseline, included: Motor function "on" time: 0 hrs/day medical therapy, 4.6 hrs/day deep brain stimulation (P<0.001) Motor function "off" time: 0 hrs/day medical therapy, -2.4 hrs/day deep brain stimulation (P<0.001) UPDRS Activities of Daily Living scores: 0 medical therapy, -4.6 deep brain stimulation (P<0.001) Quality of life, single index: 0.4 medical therapy, -7.7 deep brain stimulation (P<0.001) Wechsler working memory index: 1.0 medical therapy, -1.6 deep brain stimulation (P=0.005) Wechsler processing speed index: 0.7 medical therapy, -2.1 deep brain stimulation (P=0.006) The latter two findings reflect decreases in neurocognitive function with deep brain stimulation, suggesting an adverse effect for the procedure, although it was not counted as such in the JAMA report. In 10 other tests of cognitive ability, significant decreases among those in the deep brain stimulation group were seen in two -- phonemic fluency and delayed recall in the Brief Visuospatial Memory Test -- and trends were noted in several others. On the other hand, neither group showed significant changes in depression or dementia scores on standard instruments. Totals of 659 adverse effects were reported in the deep brain stimulation group and 236 in the medical-therapy group. These included falls, gait disturbance, dyskinesia, motor dysfunction, balance disorder, depression, and dystonia. Falls, gait disturbance, depression and dystonia were significantly more common with deep brain stimulation. Effects related to implantation of the neurostimulation device, such as surgical site infections and pain, were seen in about 10% of the deep brain stimulation patients. In addition to 16 cases of surgical site infections, serious adverse events in the deep brain stimulation group included nervous system disorders in 15 patients, psychiatric disorders in 11, and device-related complications in eight. Falls resulting in injury occurred in six patients. In his editorial, Dr. Deuschl said the efficacy findings were greatly encouraging, with the between-group differences clinically as well as statistically significant. He said they confirmed and extended results found in a smaller randomized study he and other researchers had reported in 2006. (See: Deep Brain Stimulation Improves Parkinson's Symptoms) Dr. Deuschl characterized deep brain stimulation as "the most important innovation for treatment of advanced Parkinson's disease since the discovery of levodopa," but cautioned that the new study as well as others left important questions unanswered. In particular, he said, the findings of similar efficacy and safety in older and younger patients need to be confirmed, because earlier research had suggested lower complication rates in younger individuals. Dr. Deuschl added that possible differences in outcomes according to whether stimulation was delivered to the globus pallidus versus subthalamic nucleus -- which were not reported in the current study -- deserved examination. Longer-term outcomes also need to be assessed, he said. Dr. Weaver and colleagues said they were following their study participants for up to two years after randomization, with data stratified by stimulation site to be included in their final report. They said data collection should be completed this April. The study was funded by the Department of Veterans Affairs, the National Institute of Neurological Disorders and Stroke, and Medtronic Neuromodulation. Study authors reported relationships with Medtronic, Advanced Neuromodulation Systems, and Boehringer Ingelheim. Dr. Deuschl reported relationships with Medtronic, TEVA, Lundbeck, and Boehringer Ingelheim, and is currently co-directing a clinical study funded by Medtronic and government sources. Primary source: Journal of the American Medical Association Source reference: Weaver F, et al, "Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial" JAMA 2009; 301: 63-73. Additional source: Journal of the American Medical Association Source reference: Deuschl G, "Neurostimulation for Parkinson disease" JAMA 2009; 301: 104-105. Related Article(s): Deep Brain Stimulation Improves Parkinson's Symptoms ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn