Deep-Brain Stimulation for Dystonia: Stimulation is Superior to Simulation
Abstract & Commentary
By Melissa J. Nirenberg, MD, PhD, Assistant Professor, Neurology and Neuroscience, Weill Cornell Medical College. Dr. Nirenberg reports no financial relationship relevant to this field of study.
Synopsis: Deep-brain stimulation of the globus pallidus interna improves symptoms, reduces disability, and improves quality of life in primary segmental and generalized dystonia.
Source: Kupsch, A et al. Pallidal deep-brain stimulation in primary generalized or segmental dystonia, N Engl J Med. 2006;355(19):1978-1990.
Deep-brain stimulation (DBS) of the globus pallidus interna (GPi) is an FDA-approved treatment for certain types of dystonia, but previous studies have been limited by a small sample size and/or a lack of adequate controls. There are no prior large-scale, randomized controlled trials examining the safety and efficacy of DBS in the treatment of segmental dystonia.
This study examined the safety and efficacy of GPi DBS in the treatment of primary segmental or generalized dystonia. A total of 40 subjects between the ages of 14 and 75 were enrolled at 10 academic centers in Germany, Norway, and Austria. All subjects had a 5-year history of severe, medically refractory, primary segmental (n = 16) or generalized (n = 24) dystonia. Exclusion criteria included cognitive impairment, moderate-to-severe depression, marked brain atrophy, prior brain surgery, or surgical contraindications. All subjects were treated with bilateral DBS of the GPi. Half of the subjects were randomized to active neurostimulation and half to sham stimulation for the blinded portion of the study.
The initial phase of the study was a 3-month double-blind, randomized comparison of active vs sham stimulation. This was followed by an open-label extension during which all subjects received active stimulation. The primary endpoint was the change in the movement score on the Burke-Fahn-Marsden Dystonia Rating Scale at the end of the first phase of the study, as evaluated by blinded raters through review of standardized videotaped examinations. Secondary endpoints included changes in the disability score on the Burke-Fahn-Marsden scale and in the physical and mental quality-of-life scores on the Medical Outcomes Study 36-Item Short Form General Health Survey (SF-36).
At the end of the 3-month, randomized, blinded portion of the study, there was a significantly greater improvement in the mean movement score on the Burke-Fahn-Marsden Dystonia Rating Scale in the neurostimulation group (-15.8 ± 14.1) than in the sham-stimulation group (-1.4 ± 3.8, p < 0.001). The neurostimulation group also had a significantly greater improvement in the mean disability score on the Burke-Fahn-Marsden Dystonia Rating Scale, and in the mean quality-of-life score on the SF-36. After 6 months of open-label neurostimulation, comparable benefits occurred in the sham-stimulation group, with improvement in all motor symptoms other than speech and swallowing. After 6 months of neurostimulation (open-label portion of the study), the study population as a whole showed a significant improvement in the mean disability score on the Burke-Fahn-Marsden Dystonia Scale and in the mean quality-of-life score on the SF-36. Adverse events (n = 22) occurred in 19 (48%) of the study subjects, the most common of which was dysarthria (in 5 subjects). Serious adverse events included hardware infection in 4 subjects and lead dislodgement in one subject.
Commentary
Primary segmental and generalized dystonia are disabling conditions that are often refractory to medical treatment. Oral medications have limited efficacy and considerable side-effects, and botulinum toxin therapy is implausible given the wide distribution of affected muscles. In this setting, DBS has emerged as a promising treatment option.
This well-designed study provides further evidence that GPi DBS is an effective treatment for medically refractory, primary segmental and generalized dystonia. Compared with many prior DBS studies, it has a number of strengths, including the use of sham stimulation and blinded raters. Limitations include the short duration of the blinded portion of the study, relatively short follow-up time, and absence of additional control groups (eg, sham surgery or medical management) to allow for risk-benefit assessment; the latter is important given the high rate of complications in trial as compared with prior studies of DBS. The study was partially funded by, and some of the authors have received, compensation from Medtronic, which markets the DBS hardware. Nonetheless, the results of the study are convincing, and provide welcome news for dystonia patients and the physicians who treat them.
Deep-brain stimulation (DBS) of the globus pallidus interna (GPi) is an FDA-approved treatment for certain types of dystonia, but previous studies have been limited by a small sample size and/or a lack of adequate controls.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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