Responsive Neurostimulation RNS for the treatment of epilepsy

Responsive Neurostimulation (RNS) for the treatment of epilepsy Daniel Friedman, MD Assistant Professor NYU Comprehensive Epilepsy Center April 27, 2014

The RNS™ System • Cranially implanted battery powered responsive neurostimulator • Connected to 2 leads (depth and/or subdural) with 4 electrode contacts each

Figure 3 The Neuro. Pace Responsive Neurostimulator (RNS®) System (Mountain View, CA) Stacey WC and Litt B (2008) Technology Insight: neuroengineering and epilepsy—designing devices for seizure control Nat Clin Pract Neurol 10. 1038/ncpneuro 0750

The RNS® System: Responsive Stimulation Neurostimulator and Leads Remote Monitor Programmer Patient Data Management System (PDMS)

RNS® System Indication The RNS® System is an adjunctive therapy for: • >18 years of age • partial onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci • refractory to two or more antiepileptic medications • have frequent and disabling seizures (motor partial seizures, complex partial seizures and/or secondarily generalized seizures)

The RNS™ System Neurostimulator detects and stimulates abnormal brain electrical activity with implanted electrodes Programmer sets detection and stimulation parameters Programmer and Patient Data Transmitter send ECo. G data to web-based repository for review

RNS® System: Responsive Stimulation • Physician identifies electrocortico-graphic activity to be detected • Detection and stimulation settings programmed, then adjusted as needed • Varied seizure patterns require individualized settings

Patient Data Management System Caution: Investigational. Device. Limited by US Law to Investigational Use Only. Caution: investigational device. Limited by US law to investigational use only.

Single Patient Seizure Plot: 20092014 Red: disabling seizures, Green: auras; Black: total seizures

The Neuro. Pace Responsive Neurostimulator (RNS®) System Trial • 191 patients; 32 centers • Randomized to Treatment vs. Sham group for 3 months • Need to know localization of epileptic brain tissue 1 - 2 foci • 3 or more disabling seizures per month

Study Design Morrell M J Neurology 2011; 77: 1295 -1304

The Neuro. Pace Responsive Neurostimulator (RNS®) System TRIAL RESULTS Overall: • 38% Seizure Reduction in Active Treatment • 17% Seizure Reduction in Sham Treatment

Other outcomes • Improved quality of life in treated group • No difference in memory function between treated and sham groups

Safety • Bleeding in the brain in 2. 3% • Infection of scalp/soft tissue in 5. 3% (4 pts had to have device removed); no brain infection • Other rarer side effects included pain, abnormal sensations related to stimulation and worsening seizures

Two‐year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial At the end of 2 years of treatment, 9% were seizure free during the last 3 mo - Those with 1 focus were more likely to be seizure-free ~7% had worsening of seizures Epilepsia Volume 55, Issue 3, pages 432 -441, 22 FEB 2014 DOI: 10. 1111/epi. 12534 http: //onlinelibrary. wiley. com/doi/10. 1111/epi. 12534/full#epi 12534 -fig-0005 Many had improvement in cognitive functioning

Treatment with RNS – Patient perspective • Localize seizure onset regions using EEG, MRI, PET, MEG, SPECT and/or intracranial EEG • RNS leads and stimulator implanted & recording activated – Patient uploads data daily • Post-op visit 10 -14 days – Data reviewed, detectors adjusted if necessary, stimulation activated • Follow up visits ~ 1 -3 months – Data reviewed, detectors and stimulation parameters adjusted – Patient continues to upload data every 1 -7 days • Long term follow-up, every 3 months – Continue to upload data – Monitor battery/device function – Adjust parameters as necessary • Battery change about every 2 years, may be longer/shorter