Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy

Abstract

Objective: To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localizationrelated epilepsy.Methods: This long-term follow-up is a continuation of a previously reported trial of 5-vs 0-V ANT stimulation. Long-term follow-up began 13 months after device implantation with stimulation parameters adjusted at the investigators' discretion. Seizure frequency was determined using daily seizure diaries.Results: The median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate ($50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years (p , 0.001).Conclusion: Long-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population. Classification of evidence:This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years. Approximately 3 million people in the United States have epilepsy and approximately 30% remain resistant to medical treatment. Some of these patients are candidates for resective surgery.1,2 For those who are not surgical candidates, or who continue to have seizures after surgery, neuromodulation may offer a viable therapeutic option. Several pilot studies, [3][4][5][6] and recent trials including the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) trial 7 and a trial of responsive cortical stimulation, 8 have demonstrated reduction in seizures. The SANTE trial in 110 subjects with localization-related epilepsy found that seizures were significantly reduced by stimulation. 7 We now report the 5-year efficacy and safety outcomes of this trial.METHODS The SANTE trial 7 utilized a design with a 3-month baseline, 1-month postoperative recovery, followed by 3 months of double-blind treatment randomized to 5 V or 0 V of stimulation, then an open-label conversion of all subjects to 5-V stimulation for 9

Infection and Erosion Rates in Trials of a Cranially Implanted Neurostimulator Do Not Increase with Subsequent Neurostimulator Placements

“…Anticipated advantages over a pectoral implant are a lower risk for lead or device migration [8]. Considerable prospective data from clinical trials of the RNS System indicate that the risk of infection or erosion with the cranial implant compares favorably with other neurostimulation systems that utilize a pectorally implanted pulse generator, such as vagal nerve stimulation [1] and deep brain stimulation for Parkinson disease [9] or epilepsy [8], and that this risk does not increase with subsequent routine neurostimulator replacements. These data support the hypothesis that a cranially implanted stimulator may offer several technical advantages over one placed pectorally without increasing the risk of infection or erosion.…”

Network effects of deep brain stimulation

“…More recently, the use of DBS has expanded into the field of neuropsychiatry, with investigators exploring the potential of DBS to produce clinical improvement for patients with major depressive disorder (MDD) , obsessive-compulsive disorder (OCD) (Mallet et al 2008), Tourette syndrome (Ackermans et al 2011), neuropathic pain (Pereira and Aziz 2014), and addiction (Alba-Ferrara et al 2014). Epilepsy also is an important emerging indication for DBS (Bergey et al 2015;Salanova et al 2015). In parallel, the technology itself is improving, with closed-loop systems and novel electrode arrays currently under development that are expected to improve the efficacy of DBS (McIntyre et al 2015).…”

Neuromodulation in refractory epilepsy: Brazilian specialists consensus

“…The Sante study showed many interesting results during their long-term follow-up after DBS implantation, like: a reduction of 40% seizure from baseline at one year and 69% at five years; The responder rate (≥ 50% reduction in seizure frequency) at one year was 43%, and 68% at five years; At the five-year follow-up, 16% of subjects had been seizure-free for at least six months; There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages; And the Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy scores showed statistically significant improvement over baseline, both at one year and at five years follow-up (p < 0.001) 15 . The most serious potential side effects of DBS for epilepsy are death, infection, hemorrhage, and status epilepticus.…”