Feasibility study of microburst VNS therapy in drug-resistant focal and generalized epilepsy.
Drug resistant epilepsy
Feasibility study
Generalized seizures
Titration
Vagus nerve stimulation
Journal
Brain stimulation
ISSN: 1876-4754
Titre abrégé: Brain Stimul
Pays: United States
ID NLM: 101465726
Informations de publication
Date de publication:
16 Mar 2024
16 Mar 2024
Historique:
received:
20
09
2023
revised:
31
01
2024
accepted:
12
03
2024
medline:
19
3
2024
pubmed:
19
3
2024
entrez:
18
3
2024
Statut:
aheadofprint
Résumé
Vagus nerve stimulation (VNS) at low frequencies (≤30 Hz) has been an established treatment for drug-resistant epilepsy (DRE) for over 25 years. To examine the initial safety and efficacy performance of an investigational, high-frequency (≥250 Hz) VNS paradigm herein called "Microburst VNS" (μVNS). μVNS consists of short, high-frequency bursts of electrical pulses believed to preferentially modulate certain brain regions. Thirty-three (33) participants were enrolled into an exploratory feasibility study, 21 with focal-onset seizures and 12 with generalized-onset seizures. Participants were titrated to a personalized target dose of μVNS using an investigational fMRI protocol. Participants were then followed for up to 12 months, with visits every 3 months, and monitored for side-effects at all time points. This study was registered as NCT03446664 on February 27th, 2018. The device was well-tolerated. Reported adverse events were consistent with typical low frequency VNS outcomes and tended to diminish in severity over time, including dysphonia, cough, dyspnea, and implant site pain. After 12 months of μVNS, the mean seizure frequency reduction for all seizures was 61.3% (median reduction: 70.4%; 90% CI of median: 48.9%-83.3%). The 12-month responder rate (≥50% reduction) was 63.3% (90% CI: 46.7%-77.9%) and the super-responder rate (≥80% reduction) was 40% (90% CI: 25.0%-56.6%). Participants with focal-onset seizures appeared to benefit similarly to participants with generalized-onset seizures (mean reduction in seizures at 12 months: 62.6% focal [n = 19], versus 59.0% generalized [n = 11]). Overall, μVNS appears to be safe and potentially a promising therapeutic alternative to traditional VNS. It merits further investigation in randomized controlled trials which will help determine the impact of investigational variables and which patients are most suitable for this novel therapy.
Sections du résumé
BACKGROUND
BACKGROUND
Vagus nerve stimulation (VNS) at low frequencies (≤30 Hz) has been an established treatment for drug-resistant epilepsy (DRE) for over 25 years.
OBJECTIVE
OBJECTIVE
To examine the initial safety and efficacy performance of an investigational, high-frequency (≥250 Hz) VNS paradigm herein called "Microburst VNS" (μVNS). μVNS consists of short, high-frequency bursts of electrical pulses believed to preferentially modulate certain brain regions.
METHODS
METHODS
Thirty-three (33) participants were enrolled into an exploratory feasibility study, 21 with focal-onset seizures and 12 with generalized-onset seizures. Participants were titrated to a personalized target dose of μVNS using an investigational fMRI protocol. Participants were then followed for up to 12 months, with visits every 3 months, and monitored for side-effects at all time points. This study was registered as NCT03446664 on February 27th, 2018.
RESULTS
RESULTS
The device was well-tolerated. Reported adverse events were consistent with typical low frequency VNS outcomes and tended to diminish in severity over time, including dysphonia, cough, dyspnea, and implant site pain. After 12 months of μVNS, the mean seizure frequency reduction for all seizures was 61.3% (median reduction: 70.4%; 90% CI of median: 48.9%-83.3%). The 12-month responder rate (≥50% reduction) was 63.3% (90% CI: 46.7%-77.9%) and the super-responder rate (≥80% reduction) was 40% (90% CI: 25.0%-56.6%). Participants with focal-onset seizures appeared to benefit similarly to participants with generalized-onset seizures (mean reduction in seizures at 12 months: 62.6% focal [n = 19], versus 59.0% generalized [n = 11]).
CONCLUSION
CONCLUSIONS
Overall, μVNS appears to be safe and potentially a promising therapeutic alternative to traditional VNS. It merits further investigation in randomized controlled trials which will help determine the impact of investigational variables and which patients are most suitable for this novel therapy.
Identifiants
pubmed: 38499287
pii: S1935-861X(24)00046-9
doi: 10.1016/j.brs.2024.03.010
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT03446664']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Danielle McDermott
(D)
Mesha Gay Brown
(MG)
Michael Macken
(M)
Irena Bellinski
(I)
Elizabeth Cunningham
(E)
Rebecca O'Dwyer
(R)
Fiona Lynn
(F)
William O Tatum
(WO)
Selim R Benbadis
(SR)
Zeenat Jaisani
(Z)
Muhammad Zafar
(M)
Blake Newman
(B)
Seyhmus Aydemir
(S)
Kristl Vonck
(K)
Ann Mertens
(A)
Jane Allendorfer
(J)
Charles Gordon
(C)
Jason Begnaud
(J)
Elhum Shamshiri
(E)
Steffen Fetzer
(S)
Giovanni Ranuzzi
(G)
Gaia Giannicola
(G)
Wim Van Grunderbeek
(W)
Informations de copyright
Copyright © 2024. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CD, PA, LK, and The Microburst Study Group were investigators for the Microburst Feasibility Study, and they or their institutions received funding from LivaNova PLC or its subsidiaries to conduct the research. JS received compensation from LivaNova USA Inc to design the fMRI titration protocol for the study. RV, AK, MJ, and KN are employees of LivaNova USA Inc and hold stock or stock options with the company. No authors were compensated for time spent writing this manuscript.