Abstracts

Rationale: The AspireSR® generator for VNS Therapy®, recently approved by the FDA, was developed with the capability to monitor heart rate and automatically trigger vagus nerve stimulation (VNS) in response to rapid increases in heart rate. Heart rate changes are associated with seizures for a large proportion of epilepsy patients (82%). The epilepsy monitoring unit (EMU) phase of the trial previously demonstrated reliable performance of the automatic stimulation feature (AutoStim Mode), with a sensitivity of at least 80% for multiple detection thresholds. The long term patient follow-up assessed safety and clinical benefit over a two year period.Methods: The E-36 study (NCT01325623) enrolled 31 patients with drug resistant epilepsy who underwent video electroencephalography during an EMU admission of up to 5 days. Through use of downloaded device detection logs, seizures treated by automatic stimulation were identified for analysis. After EMU discharge, patients were treated using both the Normal Mode (duty cycle) and AutoStim Mode (responsive stimulation). Throughout the follow-up phase clinical benefit was assessed based on 1) seizure severity scoring by patients (Seizure Severity Questionnaire; SSQ), 2) seizure severity scoring by physicians (National Hospital Seizure Severity Scale; NHS3), and 3) patient-rated Quality of Life (QOLIE-31-P).Results: Based on seizures receiving stimulation during the EMU, 59% (10 of 17) ended during automatic stimulation. Among seizures that ended during automatic stimulation, those stimulated nearer to annotated onset were shorter in duration (p<0.001). NHS3 scores for complex partial seizures showed significant improvement (p<0.05) at EMU discharge, and at 3, 6, and 12 month follow-up. During 3, 6, and 12 month follow-up, patients reported clinical improvement in key components of seizure severity (SSQ), including: movements that could result in harm, overall recovery, and aspects of post-ictal recovery. Nearly all categories (6 of 8) within the patient-rated quality of life scale (QOLIE-31-P) showed significant improvement at the 12 month follow-up. Safety profiles were comparable to prior VNS Therapy trials, with dysphonia (voice alteration) being the most frequently reported adverse event. Additional results through 24-months will be available at the meeting.Conclusions: Acute delivery of therapy via AutoStim Mode was studied in isolation of other VNS Modes within the EMU. During this period, use of the feature was associated with a high percentage of seizures that ended during the 60 second automatic stimulation (59%) and reduced physician-rated seizure severity (NHS3 scale). AutoStim Mode is intended to supplement VNS Therapy from scheduled (Normal Mode) and on-demand (Magnet Mode) stimulation. When studied in this configuration, through two years of long-term follow-up, the total therapy delivered by AspireSR: reduced physician-scored seizure severity, improved several aspects of patient-rated seizure severity including cognitive/physical post-ictal recovery, and improved the patients’ quality of life.