Constant-current deep brain stimulation (DBS) can significantly increase the amount of “on time” per day in patients with Parkinson’s disease, according to research published in the January 11 online issue of Lancet Neurology.
Patients who received constant-current DBS for three months reported a mean increase of 4.27 hours of on time per day, compared with a mean increase of 1.77 hours for the control group. Patients who received stimulation when they were off their medication reported a 39% increase in Unified Parkinson’s Disease Rating Scale motor scores compared with their off-medication baseline state.
Testing the Safety and Efficacy of DBS
DBS of the subthalamic nucleus improves the primary motor symptoms and overall quality of life in patients with Parkinson’s disease, but a constant-current approach had not been studied in controlled trials, according to Michael S. Okun, MD, Administrative Director and Codirector of the Center for Movement Disorders and Neurorestoration at the University of Florida in Gainesville. Dr. Okun’s study was conducted at 15 clinical sites to assess the technique’s safety and efficacy.
He and his colleagues selected 136 patients between the ages of 18 and 80 who had had Parkinson’s disease for at least five years and experienced at least six hours of “off time” per day. The patients’ mean age was 60, and about 62% were men.
Between September 26, 2005, and August 13, 2010, a constant-current DBS device was implanted bilaterally in the subthalamic nucleus of each patient. Patients were randomly assigned to the control group, which received no stimulation for three months, or the stimulation group, which received immediate stimulation. The primary outcome variable was the change in good quality on time after three months, as recorded in patients’ diaries. The study was not blinded, and patients were followed up for one year.
After the DBS devices were implanted, five patients developed infections and four had intracranial hemorrhages. During the follow-up period, dysarthria, fatigue, falls, and edema were more common in patients who had stimulation than in patients in the control group.
Promising Grounds for Further Research
“The results of this study show that a constant-current DBS device was relatively safe and efficacious for the treatment of advanced Parkinson’s disease,” stated Dr. Okun’s group. Patient diaries enabled the researchers to estimate the quantity and quality of study participants’ on time accurately, they added.
Unlike voltage-driven hardware, constant-current DBS devices are not susceptible to changes in the size of the field of stimulation. “This study did not offer a comparison with a voltage-driven device, and future studies should further explore the relative values of these different approaches,” the study authors wrote.
Diversification in Neurostimulation?
The use of a control group by Dr. Okun and colleagues sets their study apart from previous investigations of DBS of the subthalamic nucleus, wrote Jens Volkmann, MD, Director and Chairman of the Department of Neurology at the University Hospital of Würzburg, in an accompanying editorial. The study design allows researchers to distinguish the effects of neurostimulation from those of the implantation of the device, he added.
The control group’s improvement in motor symptoms was smaller than that of the stimulation group, but still clinically relevant. “Unfortunately, because of the absence of masking, the cause and the magnitude of this benefit in the control group are difficult to interpret,” wrote Dr. Volkmann. The absence of masking “was a flaw in the study design and a lost opportunity,” although maintaining masking could have been difficult, he added.
The mild adverse effects on brain function observed in the control group indicated that “the surgical procedure, rather than neurostimulation of the subthalamic nucleus, was responsible for this type of cognitive decline,” wrote Dr. Volkmann. Neurosurgeons might be able to avoid these harmful effects through improved surgical technique, he added.
—Erik Greb