Abstracts

Rationale: A new VNS Therapy® pulse generator, AspireSR^TM, was developed with a cardiac-based seizure detection algorithm (CBSDA) to automatically trigger vagus nerve stimulation in response to seizure activity associated with ictal tachycardia. Previously it was demonstrated in the E-36 trial that AspireSR successfully and reliably detected seizure activity, since multiple configuration settings achieved a sensitivity of at least 80%. The purpose of the long term E-36 patient follow-up was to assess safety and clinical benefit of the automatic stimulation feature. AspireSR has received CE mark approval, and in the US it is approved for investigational use only. Methods: The E-36 multi-site study (NCT01325623) enrolled 31 patients with drug resistant epilepsy who underwent video electroencephalogram and electrocardiogram during an Epilepsy Monitoring Unit (EMU) admission of up to 5 days. After discharge from the EMU, patients were followed for two years to evaluate device safety and efficacy. Clinical benefit was assessed based on 1) the proportion of seizures which terminated during automatic stimulation, and 2) the seizure severity scoring by patients (Seizure Severity Questionnaire, Cramer 2002) and physicians (National Hospital Seizure Severity Scale, O'Donoghue 1996) using validated scales. The physician scored NHS3 can detect improvement mediated solely by the autostimulation feature, since it was completed at EMU discharge, and during that study period autostimulation was activated in isolation of other VNS modes. Results: Safety profiles were comparable to prior VNS Therapy trials (Handforth 1998). During the EMU phase of the study 82 focal seizures were recorded by investigators. Forty demonstrated heart rate increases in excess of 20% relative to baseline rate, and 28 were stimulated within 2 minutes of onset allowing evaluation of potential clinical benefit. Based on the stimulated EMU seizures, 46% of debilitating focal seizures (6/13) terminated during automatic stimulation. These debilitating focal seizures were 61% shorter in duration compared to historical controls (pooled debilitating focal seizures collected from prior EMU admissions). NHS3 seizure severity scores for debilitating focal seizures showed statistically significant improvement (p<0.05) at EMU discharge, and at 3 and 6 month follow-up compared to baseline. Patients reported clinically significant reduction in overall severity, movements that could result in patient harm, and various aspects of post-ictal recovery at the 3 and 6 month follow-up compared to baseline. Conclusions: Acute therapy appears to have similar clinical benefit to manual magnet-activated stimulation (on-demand), with added convenience to the patient and caregiver. In about half of the debilitating focal seizures where stimulation was automatically triggered by the device, seizures terminated prior to conclusion of the 60 second automatic stimulation. Seizure severity as reported by physicians was significantly lower due to this acute VNS treatment. Combined automatic and duty cycle VNS appears to reduce seizure severity after 6 months of treatment.