Deep-brain stimulation with a constant-current implant significantly boosted "on" time in patients with Parkinson’s disease, with an increase of almost 3 hours more than a group of control patients who had inactive brain implants.

The control group experienced a small improvement immediately after device implantation but a significantly greater one by 3 months after activation – a sign that stimulation, not microlesional effects, mostly likely caused the biggest benefit, according to Dr. Michael S. Okun and his colleagues (Lancet Neurol. 2012;11:140-9).

Most often, deep brain stimulation is administered with a voltage-controlled device with variable current.

"Constant-current devices, such as the one used in this study, have theoretical advantages over voltage-driven devices in that the field of stimulation within brain tissue should be stable in size, whereas stimulation fields produced by voltage-driven devices are susceptible to changes in size caused by changing tissue impedance," wrote Dr. Okun, codirector of the University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, and his associates.

The study randomized 101 patients to immediate activation of a constant-current deep brain stimulation device and 35 to delayed activation. The patients were a mean of 60 years old; mean disease duration was 12 years. They had a mean of 7 hours of good-quality on-medication time at baseline.

All received the Libra DBS device, a constant-current subthalamic nucleus stimulator. The study was not blinded – both patients and physicians knew who would receive immediate and delayed stimulation.

The primary endpoint was the change in good-quality "on" time – that is, free from bothersome dyskinesias. Secondary endpoints included changes in Unified Parkinson’s Disease Rating Scale (UPDRS) scores, quality of life and sleep, medication dosage, and depression.

Patients who underwent active stimulation at the beginning of the trial were assessed at 3, 6, and 12 months. Control patients were assessed at 3 months, after which their stimulation was switched on and they were also assessed at 6 and 12 months. Thus, the active group had 12 months of stimulation time and the control group had 9 months.

At 3 months, both groups reported an increase in good-quality on time. The active group’s response was significantly better, however, increasing by a mean of 4.27 hours (from 7 to 11 hours), compared with 1.77 hours in the control group (from 7 to 9 hours), Dr. Okun and his colleagues reported.

The responder rate (at least a 2-hour improvement from baseline) was 72% in the active group and 38% in the control group – a significant difference. The active group also experienced a significant improvement in the UPDRS motor subscore, compared with the control group. At 3 months, however, there were no significant between-group differences in the UPDRS scores on mentation and activities of daily living.

Verbal fluency scores worsened similarly in both groups 3 months after device activation. "These results indicate that verbal fluency deficits, the most frequent cognitive side-effect after DBS of the subthalamic nucleus, are probably secondary to surgical implantation," the authors wrote.

Both groups experienced a significant decrease in the scale’s L-dopa therapy complications subscore, but the active group had a significantly better score than the control group. The same decline was seen in L-dopa equivalent dosing in both groups. Although both groups had significant declines in L-dopa equivalent dosing compared with baseline, the active group fared significantly better than the control group.

The investigators assessed the groups separately after the control group’s stimulation began at 3 months. By the 6-month visit, the active group’s good-quality on time remained stable. After 3 months of active treatment, the control group’s on time had increased to a extent similar to the treatment group.

At 12 months after the start of the trial, the on time remained steady in the active group and was matched by the control group. The L-dopa equivalent dose also declined similarly in both groups, Dr. Okun and his associates said.

Both groups showed significant improvements in depression over the year. A recent study found the same device to be an effective therapy for treatment-resistant major depression.

Verbal fluency stabilized in both groups after 3 months of treatment but did not improve.

In the active group, there were 20 adverse events among 14 patients. In the control group, there were seven among four patients. The events correlated with the timing of stimulation. Dysarthria, fatigue, falls, postoperative pain and discomfort, and edema were significantly more common in the active group than in the control group.

"These findings have great clinical relevance to clinicians and to patients, who should be aware that programming the DBS device might have unanticipated effects, despite substantial improvement of other motor symptoms and overall increases in on time and quality of life," the investigators wrote.

The study was sponsored by the neuromodulation division of St. Jude Medical Inc. All of the authors reported numerous financial disclosures, including six who are paid consultants for St. Jude Medical.

Constant-Current Stimulation Boosts 'On' Time in Parkinson's