LONG TERM EFFICACY OF THE SANTE TRIAL (STIMULATION OF THE ANTERIOR NUCLEUS OF THALAMUS FOR EPILEPSY)

Authors: V. Salanova, R. Fisher, G. Sante
Instit: indiana university

Content:
RATIONALE:
Fisher et al. (Epilepsia, 51:899,2010), reported the results of 110 patients who participated in a multicenter, double blind, randomized controlled trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy, and found benefit that persisted through 2 years. This is a report of the efficacy for patients with at least 5 years stimulation.
METHODS:
Subjects were 18-65 yrs old with at least 6 partial or secondarily generalized seizures per month, who had failed at least 3 AEDs due to lack of efficacy. Patients with IQ < 70,inability to complete neuropsychological testing or progressive neurological lesions were excluded. The trial utilized a prospective, randomized, double-blind, parallel group design. After a 3-month baseline, deep brain stimulation (DBS) electrodes were implanted in the ANT bilaterally using a stereotactic technique. One month after implantation,subjects were randomized to stimulation at 5 V or no stimulation. After 3 months of blinded treatment, all received stimulation;limited stimulation changes were allowed.Long term follow-up began at 13 months with stimulation parameters adjusted at the investigators 'discretion. Primary analysis was performed on subjects with at least 70 days of seizure diary data.
RESULTS:
DBS therapy reduced the number of seizures in a very refractory patient population, with a median seizure frequency reduction of 40% by the end of the blinded phase (vs.14.5%for control). There was continuous efficacy improvement; the median percent reduction from baseline at one year was 41%, at 2 years was 56% and at 5 years was 69%. The responder rates (>= 50% reduction in seizure frequency) also improved over time; at one year the responder rate was 43%, 54% at 2 yrs and 69% at 5 years . Over the entire study 16% of patients were seizure free for at least 6 months. There were no unanticipated adverse device effects, and no symptomatic intracranial hemorrhages. The Liverpool seizure severity scale and quality of life measures (QOLIE-31) also showed statistically significant improvement over baseline by 1 year, which continued to be significant at 5 years (p<0.001).
CONCLUSIONS:
Long term follow-up of bilateral stimulation of the anterior nuclei of the thalamus showed sustained efficacy and continuous improvement, with a median percent reduction in seizure frequency of 69% at 5years. Based on the results of the SANTE trial deep brain stimulation of the thalamus for medically refractory partial and secondarily generalized seizures has been approved in Europe and Canada but remains investigational in the USA