The RNS System: brain-responsive neurostimulation for the treatment of epilepsy

ABSTRACT

Introduction: Epilepsy affects more than 1% of the US population, and over 30% of adults with epilepsy do not respond to antiseizure medications without life-impacting medication-related side effects. Resection of the seizure focus is not an option for many patients because it would cause unacceptable neurological or cognitive harm. For these patients, neuromodulation has emerged as a nondestructive, effective, and safe alternative. The NeuroPace® RNS® System, the only brain-responsive neurostimulation device, records neural activity from leads placed at one or two seizure foci. When the neurostimulator detects epileptiform activity, as defined for each patient by his or her physician, brief pulses of electrical stimulation are delivered to normalize the activity.

Areas covered: This review describes the RNS System, the results of multi-year clinical trials, and the research discoveries enabled by the chronic ambulatory brain data collected by the RNS System.

Expert commentary: Brain-responsive neurostimulation could potentially be used to treat any episodic neurological disorder that’s accompanied by a neurophysiological biomarker of severity. Combining advanced machine learning approaches with the chronic ambulatory brain data collected by the RNS System could eventually enable automatic fine-tuning of detection and stimulation for each patient, creating a general-purpose neurotechnological platform for precision medicine.

KEYWORDS:

• Epilepsy
• seizures
• neurostimulation
• neuromodulation
• RNS System
• brain stimulation
• closed-loop
• patients
• neurotechnology

Acknowledgements

The authors would like to thank Tara Skarpaas, Cairn Seale, Wade Barry, Emily Mirro, and Michelle Rodgers for their contributions to this manuscript.

Article Highlights

• The RNS System, the first device to provide closed-loop brain-responsive neurostimulation, was approved in 2013 by the US Food and Drug Administration (FDA) as an adjunctive therapy for adults with medically refractory focal-onset epilepsy with 1–2 seizure foci.

• The neurostimulator continually monitors brain activity at or near the seizure foci and delivers brief pulses of electrical stimulation when abnormal activity is detected.

• Class 1 evidence from a randomized controlled trial and Class IV evidence from prospective open-label follow-up for a median of 8.97 years show that brain-responsive neurostimulation is acceptably safe, reduces seizure frequency, and improves quality of life in adults with medically refractory partial onset epilepsy arising from 1–2 seizure foci.

• At the end of the blinded period in the randomized controlled trial (5^th month post-implant), the treatment group had a 41.5% mean reduction in seizures, compared to 9.4% in the Sham stimulated group. At 9 years in the open-label study, the median percent reduction in seizures was 75% (responder rate 73%); 35% of patients had a ≥ 90% median seizure reduction; and 28% had at least one seizure free period of ≥ 6 months.

• In addition to the therapeutic benefits of brain-responsive neurostimulation, the data recorded by the RNS system has the potential to further advance scientific understanding and patient care.

Declaration of interest

B Jarosiewicz and M Morrell are both employees of, and hold stock options at, NeuroPace, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer has equity in Soterix Medical Inc. and serves as an advisor of Boston Scientific Inc. and GlaxoSmithKline. Another peer reviewer has acted as a consultant for NeuroPace. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was funded by NeuroPace.