Abstracts

Rationale: The AspireSR® generator for VNS Therapy®, recently approved by the FDA, offers a new feature called Automatic Stimulation Mode (AutoStim) that provides responsive stimulation to heart rate increases that are often associated with seizures in people with epilepsy. Physicians can adjust the threshold of detection within a range of 20% to 70% increase in heart rate compared to baseline, providing flexibility to customize the feature for individual patients. The AutoStim feature was evaluated in an epilepsy monitoring unit (EMU) setting during two clinical trials (E-36 and E-37).Methods: The AspireSR VNS Therapy System was evaluated in two clinical trials with similar enrollment criteria and design (E-36: CT.gov NCT01325623 and E-37: CT.gov NCT01846741). A total of 51 patients with drug-resistant epilepsy underwent implantation and participated in a 3-5 day EMU stay where only the AutoStim Mode was activated (i.e., Normal Mode stimulation was inactive). During the EMU, clinical investigators annotated seizure onset and offset times. Detections by the AutoStim feature were compared to seizure annotations. The percentage of seizures that ended during AutoStim was calculated. In addition, physician reported seizure severity outcome data (National Hospital Seizure Severity Scale (NHS3)) at EMU discharge was collected and compared to baseline.Results: Based on pooled data from both trials during the EMU evaluation, clinical investigators annotated a total of 170 seizures with concurrent ECG (E-36=86 seizures, E-37=84 seizures) from 34 of the 51 patients. Of these, 73.5% (n=25/34) of patients and 48.2% (n=82/170) of seizures had ≥20% increase in heart rate representing the lowest threshold for detection by the AutoStim feature. Of 82 seizures with ≥20% increase in heart rate, 46 (56.1%) were treated with AutoStim. 60.9% (28/46) of all treated seizures ended during AutoStim, including 14/16 (87.5%) simple partial seizures, and 11/23 (47.8%) complex partial seizures. For seizures that ended during AutoStim (n=28), stimulation that occurred closer to seizure onset was associated with shorter seizure duration (R2=0.69). At EMU discharge, NHS3 showed that for complex partial seizures without secondarily generalization, 64.3% (n=18/28) of patients experienced severity reduction and a statistically significant (p<0.001) mean score reduction of -2.2 (SD 3.1, n=28) from baseline. Similar reductions were not seen in simple partial seizures; the severity rating for simple partial seizures on the NHS3 scale is sufficiently low that the scale is relatively insensitive to improvements for simple partial seizures.Conclusions: The data collected during the EMU evaluation of the AutoStim feature during the E-36 and E-37 clinical studies support improvement in several clinical outcomes including seizure cessation and reduction in both seizure duration and severity. Improvement was seen during the EMU when only the Automatic Stimulation Mode was being used. The AutoStim feature offers a potential solution to automatically deliver VNS Therapy stimulation near seizure onset.