An Epileptic-Network Closed-loop Stimulation Device (enCLS) Designed to Target and Arrest Ictogenesis

Rutgers Biomedical And Health Sciences, Newark NJ

Investigators

Abstract

PROJECT SUMMARY Epilepsy, occurring in 1 percent of the world’s population, is associated with disability, injury, cognitive and neurological dysfunction, depression, loss of productivity, socioeconomic decline and even death. Of this population, 30 percent of epilepsy cases are medically intractable, leaving surgical interventions as the only option for treatment. Whereas open resection, the current surgical standard of treatment, can yield seizure freedom rates as high as 60-80 percent, these are often associated with cognitive dysfunction and focal neurological deficits. Particularly, patients with dominant hemisphere mesial temporal lobe epilepsy (MTLE), the target population for this proposal, are at risk for significant decline in memory and associated disability. It was estimated that there are nearly 200,000 patients with drug-resistant MTLE waiting for treatment. The only option for these patients at present is electrical neuromodulation, which, although effective at reducing seizures, only achieves seizure freedom in ~10% of patients. Patients and their caregivers, however, generally need a 100% decrease in seizures to safely drive a vehicle, hold down a job, enroll in education programs, or live independently. This represents a sizeable treatment gap. To answer this unmet need, we identified gaps in the technology implemented in the current responsive neurostimulation (RNS) device that we aim to address with this proposal. One, the intended design of RNS is to terminate seizures in response to seizure onset, similar to a cardiac pacemaker, which senses and responds to maintain regular cardiac rhythm. In practice, however, RNS does not function this way. Patients with MTLE, on average, have approximately 8 seizures a month. RNS, however, deploys more than 1000 stimulations a day. Two, the FDA-approved use of RNS is to implant the recording and stimulation electrodes in one or two areas of the seizure onset zone (SOZ). This seizure control strategy approaches focal epilepsy as a focus-based disorder, which is outdated. In this proposed study, we plan to design and implement a proof-of-concept epileptic-network closed-loop stimulation (enCLS) device to address the two technology gaps of RNS. This device will adopt a new set of pattern detectors to improve the specificity and timing of ictogenesis detection, coupled with a neurostimulation protocol to stop ictogenesis in the larger epileptic network beyond SOZ. The enCLS device otherwise assumes the same overall physical design, functional usage, intended users, use environment, operating principles, and the safety limits of the current state- of-the-art RNS system. We shall construct a proof-of-concept laboratory enCLS prototype and conduct experiments to inform the design requirements associated with a minimum viable product (MVP) at the end of the funding period. The efficacy of enCLS in seizure prevention, hence meeting the need for seizure freedom, will be compared with RNS. We will leverage the multi-institutional research efforts in partnership with the medical device industry to bring this technology to human use within five years.