Abstracts

Rationale: Many patients treated with VNS Therapy find that using the magnet to activate stimulation near the beginning of a seizure terminates or decreases severity of the seizure (Boon 2001, Morris 2003, Wang 2009, Majkowska-Zwolinska 2012). However, it is not always possible for patients to use the magnet due to multiple reasons including cognitive impairment, sleep, lack of an aura or the disabling effects of the seizure itself. To address this unmet need, a novel implantable pulse generator (AspireSR ) was developed with an automatic magnet mode feature triggered by a patented cardiac-based seizure detection algorithm. This algorithm detects heart rate increases that may be indicative of a seizure (Leutmezer 2003) and delivers stimulation in the same manner in which patients can currently activate the device using the magnet. Six thresholds that correspond to different heart rate increases allow physicians to adjust to patient needs. Methods: A prospective, unblinded, multi-site study (NCT01325623) was designed to enroll up to 35 patients with refractory epilepsy to confirm device performance. Patients were implanted with the AspireSR investigational device and, after a recovery period, stimulation parameters were titrated for up to four weeks. Patients devices were set to one of three thresholds and patients were then followed during an Epilepsy Monitoring Unit (EMU) stay of up to 5 days. Continuous observational video electroencephalogram (vEEG) and electrocardiogram (ECG) monitoring was employed to identify seizures and collect heart rate data. Device performance was measured by sensitivity, potential false positive rate and latency from detection to seizure onset by comparing detections to confirmed seizures. These performance measures were calculated based upon actual detections experienced during the EMU stay. In addition, in-silico modeling of the device performance using the patient s ECG signal was performed for all six thresholds in order to evaluate other configurations not tested during the patient s EMU stay. Results: At the time of abstract submission, 27 patients are enrolled in this study, with a mean age of 39.9 years (10 M, 17 F). The average age at onset of epilepsy was 17.4 years old, 92.3% had failed 4 or more AEDs, and 22.2% had prior epilepsy surgery. To date, over 50 focal seizures with or without impairment of consciousness were experienced during the patients EMU stays and more than 30 demonstrated heart rate increases in excess of 20%. The remaining seizures had a slight heart rate decrease, no change or an increase below the lowest detection threshold of the device. Conclusions: Preliminary in-silico analysis of seizures with significant heart rate changes demonstrated reliable performance as the sensitivity was generally in excess of 80% when evaluated against the appropriate threshold. Final device performance results will be available for the full study population at the time of the conference.