Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance—The U.S. E-37 Trial

Abstract

ObjectivesThe Automatic Stimulation Mode (AutoStim) feature of the Model 106 Vagus Nerve Stimulation (VNS) Therapy System stimulates the left vagus nerve on detecting tachycardia. This study evaluates performance, safety of the AutoStim feature during a 3‐5‐day Epilepsy Monitoring Unit (EMU) stay and long‐ term clinical outcomes of the device stimulating in all modes.Materials and MethodsThe E‐37 protocol (NCT01846741) was a prospective, unblinded, U.S. multisite study of the AspireSR® in subjects with drug‐resistant partial onset seizures and history of ictal tachycardia. VNS Normal and Magnet Modes stimulation were present at all times except during the EMU stay. Outpatient visits at 3, 6, and 12 months tracked seizure frequency, severity, quality of life, and adverse events.ResultsTwenty implanted subjects (ages 21–69) experienced 89 seizures in the EMU. 28/38 (73.7%) of complex partial and secondarily generalized seizures exhibited ≥20% increase in heart rate change. 31/89 (34.8%) of seizures were treated by Automatic Stimulation on detection; 19/31 (61.3%) seizures ended during the stimulation with a median time from stimulation onset to seizure end of 35 sec. Mean duty cycle at six‐months increased from 11% to 16%. At 12 months, quality of life and seizure severity scores improved, and responder rate was 50%. Common adverse events were dysphonia (n = 7), convulsion (n = 6), and oropharyngeal pain (n = 3).ConclusionsThe Model 106 performed as intended in the study population, was well tolerated and associated with clinical improvement from baseline. The study design did not allow determination of which factors were responsible for improvements.

The role of vagus nerve stimulation in refractory epilepsy

“…Short-term evaluation of 20 patients in the epilepsy monitoring unit after implantation showed that almost 35% of 89 seizures were treated by the responsive stimulation and 61% of them terminated. In the long term, the responder rate after 12 months was 50% and the adverse effects were similar to the previous VNS devices 16 . In another published prospective and multicenter study, short-term evaluation demonstrated that 40% of seizures were treated by closed-loop stimulation and 58% of them ended.…”

Autostimulation in Vagus Nerve Stimulator Treatment: Modulating Neuromodulation

“…Due to the autostimulation and better seizure control, it is possible to prolong the OFF‐time, which leads to significantly reduced power usage. The initiation of AutoStim itself does not seem to increase power usage prominently . The normal mode stimulation cycle was prolonged in ten patients, only one of them being a responder; in three out of four (75%) responders, the duty cycle remained unaltered.…”

“…At present, there is a lack of data concerning the long‐term effect of VNS with AutoStim features. In one study with 20 VNS patients with a one‐year follow‐up, AutoStim and the extra stimulations did not significantly affect power usage, since the measured duty cycles increased from a baseline of 11% with stimulation to about 16% when Normal Mode, AutoStim, and Magned Mode were combined, all on at six months . The majority, 74%, of focal impaired awareness seizures (FIAS) and focal to bilateral tonic clonic seizures (FBTCS) evoked at least a 20% increase in the heart rate.…”

Vagus Nerve Stimulation: Rapid versus Slow Cycling in a Laboratory Model

“…Therefore, the evidence for benefit of rapid cycling of VNS is limited. The latest generation of stimulator can deliver stimulation in response to a preprogrammed degree of ictal tachycardia, thereby providing a type of responsive rapid cycling [11,12].When optimal stimulation parameters and the mechanisms underlying them are unknown, controlled experiments in a laboratory can be useful, and such an experiment is provided by the article by Larsen et al [13] in this issue, entitled BVagus nerve stimulation applied with a rapid cycle has more profound influence on hippocampal electrophysiology than standard cycle.T he investigators implanted stimulating electrodes in rat perforant path (PP), which is afferent to dentate gyrus of hippocampus, and recording field [electroencephalography (EEG)] electrodes in dentate gyrus. Spontaneous dentate EEG and EEG evoked by PP stimulation were studied under different conditions of vagus nerve activation.…”

“…Therefore, the evidence for benefit of rapid cycling of VNS is limited. The latest generation of stimulator can deliver stimulation in response to a preprogrammed degree of ictal tachycardia, thereby providing a type of responsive rapid cycling [11,12].…”