We assessed the clinical impact of Microburst-VNS in an early feasibility study.

This prospective, unblinded multicenter study aimed to recruit 2 cohorts of 20 VNS-naïve patients each, age ≥12 years, with either refractory focal (FE) or generalized epilepsy with tonic-clonic convulsions (GE). Enrolled subjects underwent 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 included demographics, seizure frequency, antiseizure medications (ASMs), quality of life in epilepsy questionnaires (QOLIE-31-P/QOLIE-AD-48), seizure severity questionnaire (SSQ), VNS parameters/malfunction and adverse events (AE). Primary endpoints were safety and efficacy, secondary endpoints changes in QOLIE and SSQ scores.

A total of 32 subjects were implanted with µVNS, 20 FE and 12 GE patients. At baseline, patients had failed 4-6 ASMs (FE 4.5 vs GE 6.6). 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). At 12-months, overall seizure severity decreased in 70% of subjects (21/30), QOLIE total scores improved, and median ASM drug load decreased by 10%. Stimulation/device-related AE from 6 to 12 months were reported in one FE patient (cough, battery replacement), and 5 GE patients (dysphonia, device removal, implant site pain, seizure, agitation).

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.