Correspondence
Deep-Brain Stimulation in Parkinson's Disease
N Engl J Med 2002; 346:452-453February 7, 2002
- Article
To the Editor:
The Deep-Brain Stimulation for Parkinson's Disease Study Group (Sept. 27 issue)1 reported the results of a prospective, double-blind, crossover study in patients with advanced Parkinson's disease, in whom electrodes were implanted in the subthalamic nucleus or pars interna of the globus pallidus and who then underwent bilateral high-frequency deep-brain stimulation. In the Discussion section, the authors wrote: “Although initiation of stimulation was associated with transient symptoms in some patients, we do not believe that this influenced the blinded assessment, since neither the patients nor the investigators were certain of whether stimulation was being given at the time.” In 1998, some of the same authors reported, with respect to a double-blind evaluation of deep-brain stimulation of the subthalamic nucleus in eight of the same patients, that “all patients were able to guess which assessments were performed with the stimulators on.”2 Everyone with some experience of deep-brain stimulation of the subthalamic nucleus knows that neither the patient nor the evaluator can be blinded to the status of a patient with advanced Parkinson's disease who has resumed stimulation of the subthalamic nucleus after having been without stimulation and medication for 12 hours. Since the authors themselves have admitted this fact in a previous publication,2 one cannot help but wonder about the validity of this double-blind evaluation.
2 ReferencesPatric Blomstedt, M.D.
University Hospital, 901 85 Umeå, Sweden
patric_blomstedt@hotmail.com 1
The Deep-Brain Stimulation for Parkinson's Disease Study Group
Full Text | Web of Science | Medline2
Kumar R ,Lozano AM ,Kim YJ , et al. Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease. Neurology 1998;51:850-855
Web of Science | Medline
To the Editor:
The article on deep-brain stimulation for Parkinson's disease included a comprehensive listing of adverse events associated with subthalamic and pallidal stimulation. Preliminary results of the same study were presented at the Movement Disorder Society meeting in New York in October 1998. Obeso reported on the adverse events associated with deep-brain stimulation of the subthalamic nucleus in 36 patients, 33 of whom had bilateral implants, and concluded that the risk cannot be minimized but that the benefit is substantial.1 Lang presented the adverse events associated with deep-brain stimulation of the pallidum in 36 patients, 25 of whom had bilateral implants, and concluded that complications were not uncommon but that the risk–benefit ratio was quite acceptable.2 We are concerned about apparent major inconsistencies in the reported number of side effects in the 1998 report and the current report. In 1998 eight centers were involved in the study of deep-brain stimulation of the subthalamic nucleus, and six centers were involved in the pallidal deep-brain stimulation study.1,2 The current report lists 18 centers. Nonetheless, the number of some of the listed complications decreased between 1998 and 2001. To cite but one example, 4 of 36 patients who received deep-brain stimulation of the subthalamic nucleus had dysarthria in 1998, whereas none of 102 such patients had dysarthria as reported in 2001. Hypophonia is not even mentioned. Deep-brain stimulation of the basal ganglia is an efficient treatment for Parkinson's disease, but this method may lose credibility if its side effects are not properly accounted for.
2 ReferencesMarwan I. Hariz, M.D., Ph.D.
University Hospital, 901 85 Umeå, Sweden
marwan.hariz@neuro. umu. se Harald Fodstad, M.D., Ph.D.
New York Methodist Hospital, Brooklyn, NY 112151
Obeso JA . Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD). Mov Disord 1998;13:Suppl 2:303-303 abstract.
CrossRef | Web of Science | Medline2
Lang A . Deep brain stimulation (DBS) of the globus pallidus internus (Gpi) in advanced Parkinson's disease (PD). Mov Disord 1998;13:Suppl 2:264-264 abstract.
To the Editor:
Although the study of deep-brain stimulation for Parkinson's disease was described as a double-blind, crossover, randomized study, this design pertains only to the three-month evaluation. Blinding patient and investigator to stimulation status is difficult, however, especially if the patient has tremor or if the evaluations are performed by the same investigator who programs the patient's stimulator settings. The key indications for deep-brain stimulation in current practice are motor fluctuations and dyskinesias (“off” periods), variables not measured with the use of a blinded evaluation.
Will deep-brain stimulation help the average patient with Parkinson's disease, and if so, for how long? The 143 patients in the study were in their early 40s at the onset of disease — considerably younger than most patients with Parkinson's disease. The analysis should have included all patients who underwent surgery, even those who had complications, reflecting the intention-to-treat principle inherent in actual practice. To be able to generalize the results, readers need to know whether the study group included all eligible patients and patients who underwent the procedure at each center during the enrollment period.
All who care for patients with Parkinson's disease recognize the potential of deep-brain stimulation and hope that its good effects will prove to be long lasting. But a true test of this method requires a much longer follow-up than three or six months.
Blair Ford, M.D.
Columbia University, New York, NY 10032-3784Author/Editor Response
The authors reply:
To the Editor: Blomstedt and Ford raise issues related to blinding. We agree that when an intervention provides a dramatic benefit, it has the potential to alert the patient or evaluator to the treatment assignment. In the article quoted by Blomstedt,1 patients were able to guess when their stimulators were on almost entirely as a result of the profound benefit associated with stimulation. Surely, when efficacy leads to the unblinding of a study, this outcome supports the extent of efficacy, rather than raises questions about the validity of the observation. Stimulation can also be associated with transient symptoms such as paresthesias or motor twitch. However, neither the patients nor the evaluators in our study were informed about or could be certain of the patients' stimulation status — hence, the advantage of double-blind trials.
We agree that the effect of the intervention on “off” time and dyskinesia are important variables. These are better assessed in long-term, parallel-group, double-blind studies, which are presently under way. Nonetheless, patients in our study who were markedly disabled and whose condition could not be further improved by medical therapy obtained substantial benefits from deep-brain stimulation with regard to off time and dyskinesia. It is hard to imagine that this benefit was entirely due to a placebo effect.
We included all patients who underwent or who were intended to undergo bilateral procedures. We analyzed data from all patients who participated in the crossover study and from all visits completed. We enrolled patients who were relatively young when they became ill, because these patients have the most profound disability from motor complications and are the most likely to benefit from this surgery.
Hariz and Fodstad fear that we did not account for all adverse events. During the study, patients and physicians were asked to record all adverse events in an open-ended fashion. This information was duly collected and reported to regulatory agencies. As stated in our article, we reported only adverse events that were serious, that were severe and were attributed to the intervention, or that affected more than one patient. Because of space limitations, we did not report mild, transient, and clinically insignificant adverse events, such as those associated with the initiation of stimulation. Our preliminary reports were presented in non–peer-reviewed abstract form2,3 and included some patients from the current study as well as patients who underwent unilateral procedures and who were not included in the study. In these reports, we used different criteria for reporting adverse events, and the adverse events were reported before we had thoroughly reviewed the data base and uniformly classified and confirmed adverse events. We agree that the side effects of a new procedure must be carefully documented, and we took great pains to ensure that this was done.
3 ReferencesJose A. Obeso, M.D.
University of Navarra, Pamplona 31008, SpainC. Warren Olanow, M.D.
Mount Sinai School of Medicine, New York, NY 10029
warren.olanow@mssm. edu Anthony Lang, M.D.
University of Toronto, Toronto, ON M5T 2S8, Canada1
Kumar R ,Lozano AM ,Kim YJ , et al. Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease. Neurology 1998;51:850-855
Web of Science | Medline2
Obeso JA . Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD). Mov Disord 1998;13:Suppl 2:303-303 abstract.
CrossRef | Web of Science | Medline3
Lang A . Deep brain stimulation (DBS) of the globus pallidus internus (Gpi) in advanced Parkinson's disease (PD). Mov Disord 1998;13:Suppl 2:264-264 abstract.
- Citing Articles (2)
Citing Articles
1
Stanley Fahn, Joseph Jankovic, Mark Hallett. 2011. Surgical treatment of Parkinson disease and other movement disorders. , 157-182.
CrossRef2
Elina Tripoliti, Ludvic Zrinzo, Irene Martinez-Torres, Stephen Tisch, Eleanor Frost, Ellie Borrell, Marwan I. Hariz, Patricia Limousin. (2008) Effects of contact location and voltage amplitude on speech and movement in bilateral subthalamic nucleus deep brain stimulation. Movement Disorders 23:16, 2377-2383
CrossRef
