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Medical Therapy Alone vs Addition of Deep Brain Stimulation in Advanced PD
Abstract & Commentary
By Panida Piboolnurak, MD and Michael G. Kaplitt, MD, PhD. Dr. Piboolnurak is Assistant Professor, Department of Neurology and Neuroscience, Weill Medical College, Cornell University. Dr. Kaplitt is Associate Professor and Vice-Chairman for Research, Department of Neurological Surgery, Weill Medical College, Cornell University. Neither Dr. Piboolnurak nor Dr. Kaplitt reports any financial relationship relevant to this field of study.
Synopsis: Deep brain stimulation (DBS) is an effective treatment in Parkinson's disease with motor fluctuations and dyskinesias. However, given the potential adverse events, proper patient selection is vital.
Source: Williams A, et al. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): Randomized, open-label trial. Lancet Neurology 2010;9:581-591.
In this randomized, open-label trial, the investigators recruited 366 patients with Parkinson's disease (PD) who did not have an adequate benefit from medications. Patients were randomly assigned to a group treated with medication and surgery, or medical therapy alone. Of the total, 178 patients had surgery (174 had subthalamic nucleus DBS, and four had globus pallidus interna DBS), and 171 patients had only medical therapy (12 patients switched over to DBS after the assignment). Dyskinesia and severe "off" periods were the most common reasons for considering surgery.
Patients' self-evaluating, 39-item, PD questionnaire summary index improved by 5 points in the surgical group and by 0.3 point in the medical group. There was no evidence that the degree of improvement in favor of surgery varied with age, disease duration, Hoehn & Yahr stage, reason for surgery, or whether apomorphine treatment was planned. Total Unified Parkinson's Disease Rating Scale (UPDRS) score in the "on-medication" state improved by 6.6 points in the surgical group, but worsened by 1.6 points in the medical group. Total UPDRS score in the "off-med" state improved by 27.4 points in the surgical group and by 0.9 points in the medical group. Of note, patients in the surgical group were evaluated while DBS was on in either the "on-med" or "off-med" state. At one year, 75 patients in the surgical group had no dyskinesia and 45 reported no "off" time. On the contrary, 21 patients in the medical group had no dyskinesia, and five reported no "off" time.
Dementia Rating Scale Score decreased by 0.4 points in both groups. Only a subset of patients had detailed neuropsychological evaluation. Utilizing the Delis-Kaplan executive function system, phonemic mean score and verbal fluency decreased by 6.5 and 4.5 points in the surgical group, and by 0.6 and 0.2 point in the medical group. Wechsler abbreviated scale of intelligence vocabulary reduced by 1.5 point in the surgical group, but improved by 0.6 point in the medical group. Patients in the surgical group required 34% less medication compared to the patients in medical group. At baseline, 45 patients in each group were on apomorphine. By one year, this had decreased to 13 (six with continuous infusion) in the surgical group, but had increased to 63 (48 with continuous infusion) in the medical group. Thirty-six patients in the surgical group had 43 surgery-related serious adverse events, of which infections were the most common. There were 25 PD-related or drug-related serious adverse events in 20 patients in the surgical group and 14 events in 13 patients in the medical group. One patient who had previously attempted suicide before the study had an unsuccessful suicide attempt after the surgery. Two patients in the surgical group died (intraoperative hemorrhage and preoperative pneumonia). One patient in the medical group died from stroke.
In keeping with previous studies, this study showed that DBS can reduce dyskinesia, "off" duration, and medication requirement. A combination of DBS and best medical therapy was more effective than best medical therapy alone. However, this study was not designed to compare the benefit of DBS to medical therapy, because they did not compare the UPDRS scores in the "on-med" state in the medical group to the scores in the "off-med/on-stim" state in the surgical group. This is an academic consideration, however, since the goal of therapy is to optimize patient quality of life and the combination of DBS and best medical therapy was clearly superior in this particular patient population. Given the well-documented potential for adverse events from surgery, proper patient selection remains very important. In general, DBS is recommended in a patient with motor fluctuation, increasing "off-times" and/or disabling tremors, with or without dyskinesias, who is no longer adequately responding to previously effective medical treatment and who has no significant cognitive deficit or uncontrollable psychiatric disorders that are unrelated to their PD medications. Limitations of this study include an open-label design, limited number of patients with a detailed neuropsychological evaluation, and lack of data on adverse events that were not serious enough to require or prolong hospitalization.