SAN DIEGO – Bilateral stimulation of the anterior nuclei of the thalamus led to a median reduction in partial-onset seizure frequency of 69% after a follow-up period of 5 years in the ongoing multicenter, double-blind, randomized SANTE trial.
"We were surprised that these patients still showed improvement, despite the fact that they had failed so many other treatments, including surgery," Dr. Vicenta Salanova said during a press briefing at the annual meeting of the American Epilepsy Society. "We were happy to see that."
Based on SANTE (Stimulation of the Anterior Nucleus of Thalamus for Epilepsy) trial results to date, deep brain stimulation (DBS) therapy for medically refractory partial and secondarily generalized seizures has been approved in Europe and in Canada, but it remains investigational in the United States. In 2010, the SANTE trial’s sponsor, Medtronic, submitted a premarket approval application for DBS therapy in epilepsy with the Food and Drug Administration, but both parties "are still in discussions," said Dr. Salanova, professor of neurology and director of the Indiana University School of Medicine Comprehensive Epilepsy Program in Indianapolis. "We hope that, based on the results we have shown, this will eventually be approved in the United States."
The researchers reported on 110 participants aged 18-65 years with at least six partial or secondarily generalized seizures per month who had failed treatment with at least three antiepileptic drugs. Patients with an IQ of less than 70 and those who were unable to complete neuropsychological testing or had progressive neurologic lesions were excluded from the analysis. After a baseline period of 3 months, the researchers used a stereotactic technique to implant DBS electrodes in the anterior nuclei of the thalamus bilaterally. One month after implantation, study participants were randomized to stimulation at 5 V or to no stimulation. After 3 months of blinded treatment, all patients received stimulation. Long-term follow-up began at 13 months with stimulation parameters adjusted at the investigators’ discretion. Primary analysis was performed on patients with at least 70 days of seizure diary data.
Dr. Salanova reported that by the end of the blinded treatment phase, the median seizure frequency reduction was 40% in patients who underwent DBS, compared with 14.5% in controls. Over time, patients in the DBS group demonstrated stepwise improvements in the median percent reduction of seizures from baseline, to 41% at 1 year, 56% at 2 years, and 69% at 5 years. Responder rates, defined as a 50% or greater reduction in seizure frequency, also progressively improved over time to 43% at 1 year, 54% at 2 years, and 69% at 5 years.
The researchers also found that over the entire study period 16% of patients were seizure-free for at least 6 months. They observed no unanticipated adverse device effects or symptomatic intracranial hemorrhages. Both the Liverpool Seizure Severity Scale and Quality of Life in Epilepsy-31 inventory also showed statistically significant improvement over baseline by 1 year, which continued to be significant at 5 years (P less than .001).
Medtronic sponsored the study. Dr. Salanova said that she had no relevant financial conflicts to disclose.