Long-term treatment with responsive brain stimulation in adults with refractory partial seizures

Abstract

Objective:The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures.Methods:All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy.Results:The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%).Conclusions:The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures.Classification of evidence:This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

Not all that glitters is gold: A guide to surgical trials in epilepsy

“…Its benefits are similar to the VNS results reported earlier, with a 37.9% reduction in seizure frequency in the treatment arm versus 17.3% reduction in the sham group at the end of the blinded phase 18. No difference in responder rates was seen between the treatment and sham groups during the blinded phase of the study; additional reductions in seizure frequency to 44% at 1 year and 53% at 2 years were reported during the open‐label extension 10, 16. Complications of RNS included a 4.7% rate of intracerebral hemorrhage and a 9% rate of infection after a mean of 5.4 years of follow‐up, requiring neurostimulator explantation in 4.7% of the cases 10, 16…”

“…Statistically significant improvements in QOL scores were also seen with RNS 10, 16. Treatment with the RNS system was not associated with cognitive decline when tested through 2 years.…”

“…Several RCTs (5/12) evaluated VNS (whether implanted9, 14, 17, 31, 32 or transcutaneous6). Two evaluated HS (implanted34 or transcranial12), and the rest individually evaluated CS,35 TNS,11 rTMS,13 thalamic stimulation,33 and RNS 10, 16, 18. All pivotal RCTs were followed by open‐label extensions that allowed long‐term data collection 7, 8, 10, 16, 36…”

“…Resective epilepsy surgery, in appropriately selected patients, is the accepted treatment of choice for DRE as supported by two randomized clinical trials,3, 4 multiple retrospective cohort series, and a practice parameter issued by the American Academy of Neurology recommending a surgical evaluation for any patient with uncontrolled disabling complex partial seizures 5. Similarly, a plethora of nonresective yet surgical DRE treatments have flourished recently, including various neuromodulation procedures6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 and thermal‐based19 and radiation‐based neurosurgeries 20. A position statement by the Practice Management Committee Health Care Reform Workgroup of the American Epilepsy Society called for access and insurance coverage for all patients with epilepsy for more aggressive therapeutic strategies, including neurosurgery and implanted electronic devices, when medications fail to yield optimal seizure control 21.…”

Making sense: Determining the parameter space of electrical brain stimulation

“…In some clinical situations, however, it is undesirable to produce readily detectable (illusory) stimulation of cortical neurons. For instance, in closed-loop "responsive neurostimulation" in cortex and deeper structures in medically refractory epilepsy, electrical stimulation is used to abort intractable seizures (8), and is ideally imperceptible to the patient. It is absolutely essential to establish the most safe and effective electrical stimulation protocols in nonhuman primates that can be applied to both cortical devices that can reproduce sensory experiences and devices that can activate neurons indiscernibly.…”