Cornelia Drees, MD – Mayo Clinic Arizona; Mesha-Gay Brown, MD – CenturaHealthPG Neuroscience & Spine; Danielle McDermott, MD – Colorado University; Lesley Kaye, MD – Colorado University; Rebecca O'Dwyer, MD – Rush University; Micheal Macken, MD – Northwestern Medical Group; Muhammad Zafar, MD – Duke University; William Tatum, MD – Mayo Clinic; Zeenat Jaisani, MD – University of Alabama; Kristl Vonck, MD – University of Gent; Pegah Afra, MD – Cornell University; Blake Newman, MD – University of Utah; Ryan Verner, PhD – LivaNova; Amy Keith, BS/BA – LivaNova; Mei Jiang, PhD – LivaNova; Selim Benbadis, MD – University of South Florida
Vagus nerve stimulation therapy is an established treatment for drug-resistant epilepsy. New settings called “microburst stimulation” (µVNS) with high-frequency bursts of 100-350 Hz have been investigated in humans hypothesizing that µVNS may be more tolerable and efficacious than standard VNS (VNS) therapy. Methods:
This prospective, unblinded multicenter study aimed to recruit 2 cohorts of 20 patients each, age ≥12 years, with either refractory focal- (FOS) or generalized-onset seizures with tonic-clonic convulsions (PGTC). Inclusion criteria were ≥3 countable seizures per month for FOS or a total of
≥3 for PGTC during a 3-month baseline period. Patients with VNS or history thereof were excluded. Enrolled subjects underwent implantation of the investigational VNS device and 4 functional MRIs to titrate settings to µVNS parameters with the most robust thalamic blood-oxygen-level-dependent signal response. Data collected at baseline and during 12-months follow-up (FU) included demographics, seizure frequency (diary), antiseizure medications (ASMs), quality of life in epilepsy questionnaires (QOLIE-31-P/QOLIE-AD-48), seizure severity questionnaire (SSQ), Columbia suicide severity rating scale (SSRS), VNS parameters/malfunction and adverse events (AE). Primary endpoints were safety (AE and treatment-emergent AE (TEAE)) and efficacy (change in seizure frequency/month), and secondary endpoints changes in QOLIE and SSQ scores. Enrollment started in 2018 and was halted in late 2020 due to the COVID-19 pandemic.Results:
A total of 32 subjects were implanted with µVNS, 20 FOS and 12 PGTC patients. Demographics were comparable between the two groups. Epilepsy history revealed that FOS patients compared to PGTC trended toward longer mean time from diagnosis to µVNS and were more likely to have had brain surgery; of note, the percentage of those with “aura” feelings was similar in both cohorts. At baseline, patients in both groups were on average on 3.0 ASMs (FOS 2.8 vs. PGTC 3.0) and had failed 4-6 ASMs (FOS 4.5 vs. PGTC 6.6). Table 1 depicts VNS settings for all patients during FU. After implantation, 1 FOS patient was lost to FU and 1 PGTC patient had device explantation due to high lead impedance. For the total population, responder rates (≥50% seizure reduction) at 6- and 12-months were 41.9% and 63.3%, respectively, with 63.2% of responders experiencing ≥80% reduction (12/19) (Figure 1). At 12-months FU, overall seizure severity was decreased in 70% (21/30), QOLIE total scores were improved, and median ASM drug load decreased by 10%. Stimulation/device related TEAE from 6 to 12 months were reported in 1 FOS patient (cough, battery replacement) and 5 PGTC patients (dysphonia, device removal, implant site pain, seizure, agitation). Conclusions:
Despite limitations of design, sampling, and premature termination, µVNS therapy seems safe and potentially more efficacious than VNS, as responders appeared more likely to have ≥80% seizure reduction within the first 12 months. Seizure severity, QOL, and ASM load improved. Rate of AEs were similar to VNS. Further prospective study is warranted.Funding:
LivaNova USA Inc.