Vagus Nerve Stimulation in Neurology and Beyond: A Comprehensive Review of Clinical Use, Mechanisms, Innovations and Future Directions

Michał Janiszewski; Marcin Komorowski; Joanna Piecek; Marta Omiecińska; Natalia Surosz; Aleksandra Graczyk; Michał Grochowalski; Jakub Szydło; Dominika Ziętara; Kacper Kmieć

doi:10.12775/QS.2026.49.67248

Authors

Michał Janiszewski Mazovian "Bródnowski" Hospital, Ludwika Kondratowicza 8, 03-242 Warsaw, Poland https://orcid.org/0009-0007-8932-3808
Marcin Komorowski Międzylesie Specialist Hospital, Bursztynowa 2, 04-749 Warsaw, Poland https://orcid.org/0009-0009-1423-7176
Joanna Piecek Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland https://orcid.org/0009-0003-6729-2386
Marta Omiecińska Międzylesie Specialist Hospital, Bursztynowa 2, 04-749 Warsaw, Poland https://orcid.org/0009-0002-3134-8141
Natalia Surosz Międzylesie Specialist Hospital, Bursztynowa 2, 04-749 Warsaw, Poland https://orcid.org/0009-0005-1939-151X
Aleksandra Graczyk Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland https://orcid.org/0009-0006-3505-1416
Michał Grochowalski Nicolaus Copernicus Memorial Hospital, 93-513 Lodz, Poland https://orcid.org/0009-0005-0293-9411
Jakub Szydło Independent Public Complex of Outpatient Health Care Centers Warsaw Żoliborz-Bielany, Karola Szajnochy 8, 01-637 Warsaw, Poland https://orcid.org/0009-0009-1092-2571
Dominika Ziętara Międzylesie Specialist Hospital, Bursztynowa 2, 04-749 Warsaw, Poland https://orcid.org/0009-0000-2535-7995
Kacper Kmieć Międzylesie Specialist Hospital, Bursztynowa 2, 04-749 Warsaw, Poland https://orcid.org/0009-0000-8076-2387

DOI:

https://doi.org/10.12775/QS.2026.49.67248

Keywords

Vagus Nerve Stimulation, Biomarkers, Drug-Resistant Epilepsy, Neuroimmunomodulation, Closed-Loop Neuromodulation, Bioelectronic Medicine

Abstract

Background:

Vagus nerve stimulation (VNS) has evolved from a treatment for drug-resistant epilepsy (DRE) into a broader neuromodulatory platform with expanding applications in neurology, psychiatry, immunology, and cardiology. Technological advances, particularly in non-invasive and adaptive modalities, have renewed interest in its therapeutic potential.

Aim:

To provide a comprehensive review of the clinical applications, mechanisms of action, safety profile, and emerging technological innovations in VNS, with emphasis on non-invasive techniques, adaptive stimulation, candidate biomarkers, and associated ethical considerations.

Material and Methods:

This narrative review synthesizes findings from peer-reviewed studies, clinical trials, and experimental reports identified through targeted searches in PubMed, Google Scholar, and related databases.

Results:

VNS demonstrates consistent efficacy in reducing seizure frequency in epilepsy and improving outcomes in treatment-resistant depression (TRD), inflammatory conditions, and cardiovascular disorders. Mechanistically, it modulates brainstem–cortical circuits, autonomic tone, and neuroimmune signaling pathways. Side effects are typically mild and transient. Non-invasive and closed-loop systems show promise in enhancing individualization and tolerability, although challenges remain in terms of standardization, long-term data, and equitable access.

Conclusions:

VNS represents a safe, increasingly personalized intervention with broad therapeutic scope. Future research should prioritize biomarker validation, optimization of stimulation paradigms, and integration with artificial intelligence (AI) and digital health tools, ensuring ethical and scalable implementation across diverse clinical populations.

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Vagus Nerve Stimulation in Neurology and Beyond: A Comprehensive Review of Clinical Use, Mechanisms, Innovations and Future Directions

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Vagus Nerve Stimulation in Neurology and Beyond: A Comprehensive Review of Clinical Use, Mechanisms, Innovations and Future Directions

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