Dr Modur is Director of Seton Comprehensive Epilepsy Program and Associate Professor of Neurology, Dell Medical School, The University of Texas at Austin.
Responsive neurostimulation (RNS) refers to a novel method of controlling seizures by delivering electrical stimulations to the seizure focus from an implanted device. The RNS device (NeuroPace Inc., Mountain View, CA) received FDA approval in 2013. It is indicated as an adjunctive therapy for seizure control in adults aged 18 years or older with frequent (≥ 3/mos) or disabling partial seizures (focal motor, complex partial and/or secondarily generalized seizures) arising from 1 or 2 foci that are refractory to 2 or more antiepileptic medications.
RNS is a closed-loop device, designed to be triggered to deliver therapy only when the desired, abnormal electrocorticographic (ECoG) pattern of interest (eg, seizure) occurs, which is accomplished in 3 main steps:
1. The ECoG activity is continuously monitored and recorded by the implanted depth or subdural electrodes near the seizure focus.
2. The device detects abnormal seizure-like patterns from these recordings using algorithms based on programmable parameters.
3. The device delivers electrical stimulations to the seizure focus in response to the detected abnormal pattern at preset current and charge density with the goal of terminating the pattern (Figure).
A battery-operated, microprocessor-enabled neurostimulator device, placed under the skull, performs these tasks. Using a remote (hand-held wand connected to a laptop) and network connection, the patient can periodically upload the ECoG data to a cloud-based server, which is accessible to the physician. During subsequent follow-up visits, the physician analyzes the ECoG data and reprograms the device with appropriate detection and treatment parameters that are tailored to the specific seizure signatures of the patient. The overall goal is to terminate the seizure as soon as it begins, thereby offering palliative therapy for seizures.
Efficacy and safety
RNS has shown incremental efficacy in controlling seizures. In the pivotal trial (n = 191), the mean seizure reduction over a 3-month period was 38% in the RNS treatment group and 17% in the sham group compared with baseline (ie, preimplant).1 In the open-label extension phase (n = 175), the median seizure reduction over 2 years increased to 53% compared with baseline.2
More recent data on long-term efficacy show that the median seizure reduction increased to 66% by 6 years.3 Over the 6 years of follow-up, no one was seizure-free for the entire period, but 13% experienced at least one period of seizure freedom lasting 1 year or longer. Quality of life improved at 1 year and the improvement was maintained at 5 years.
Over the short-term, implant site infection (5%) and hemorrhage (5%) were the most common device-related adverse effects.1 Over the long-term, implant site infection involving soft tissue (9%) and neurostimulator explantation (5%) were the most common device-related adverse effects.3
Comparing RNS to other types of brain stimulation
RNS is an alternative to vagus nerve stimulation (VNS) and deep brain stimulation (DBS) to control seizures. Unlike RNS, both VNS and DBS are open-loop devices that are programmed to deliver electrical therapy at preset intervals that are not necessarily timed to the occurrence of abnormal EEG activity. VNS (Cyberonics/LivaNova, Houston TX), which involves stimulation of the left vagus nerve in the neck, received FDA approval over 20 years ago for the treatment of drug-resistant focal epilepsy in persons aged over 12 years. In the pivotal trials, the mean seizure reduction with VNS was 25% to 28% (compared with baseline), but it increased to 44% at 2 years.4-6
Subsequent clinical experience suggests that the VNS is also beneficial for treating intractable seizures in children and in Lennox-Gastaut syndrome as noted in a recent practice parameter.7
More recently, a large clinical trial of a DBS device (Medtronic, Minneapolis, MN), involving the stimulation of the anterior nucleus of thalamus, was completed. The device is not approved by the FDA although it is approved in Europe. Data from the DBS pivotal trial showed a 29% greater seizure reduction in the stimulated group compared with controls.8 Long-term data from the trial showed improved efficacy over time with a 41% median seizure reduction at 1 year and 69% at 5 years.9
Ideal candidates for RNS are patients with intractable epilepsy with a seizure focus that cannot be safely resected or those with 2 independent seizure foci. Examples of such cases include those with neocortical seizure foci close to eloquent cortex (such as speech or somatosensory areas), temporal lobe epilepsy with memory dominance in the surgical side, bilateral temporal lobe epilepsy, and neocortical epilepsy with a widespread seizure onset zone spanning more than one lobe.
1. Morrell MJ. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology. 2011;77:1295-1304.
2. Heck CN, King-Stephens D, Massey AD, et al. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS system pivotal trial. Epilepsia. 2014;55:432-441.
3. Bergey GK, Morrell MJ, Mizrahi EM, et al. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology. 2015;84:810-817.
4. The Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology. 1995;45:224-230.
5. Handforth A, DeGiorgio CM, Schachter SC, et al. Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology. 1998;51:48-55.
6. Morris GL III, Mueller WM, for the Vagus Nerve Stimulation Study Group E01-E05. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. Neurology. 1999;53:1731-1735.
7. Morris GL III, Gloss D, Buchhalter J, et al. Evidence-based guideline update: Vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;81;1453-1459.
8. Fisher R, Salanova V, Witt T, et al, for the SANTE Study Group. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010;51:899-908.
9. Salanova V, Witt T, Worth R, et al, for the SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015;84:1017-1025.