Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters.

BACKGROUND: Noninvasive transcutaneous vagus nerve stimulation (tVNS) has promising therapeutic potential in a wide range of applications across somatic and psychiatric conditions. Compared with invasive vagus nerve stimulation, good safety and tolerability profiles also support the use of tVNS in pediatric patients. Potential neurodevelopment-specific needs, however, raise concerns regarding the age-appropriate adjustment of treatment protocols and applied stimulation parameters. OBJECTIVE: In this study, we aimed to review registered trials and published studies to synthesize existing tVNS treatment protocols and stimulation parameters applied in pediatric patients. MATERIALS AND METHODS: A systematic search of electronic data bases (PubMed, Scopus, MEDLINE, Cochrane Library, and PsycINFO) and ClinicalTrials was conducted. Information on patient and study-level characteristics (eg, clinical condition, sample size), the tVNS device (eg, brand name, manufacturer), stimulation settings (eg, pulse width, stimulation intensity), and stimulation protocol (eg, duration, dosage of stimulation) was extracted. RESULTS: We identified a total of 15 publications (four study protocols) and 15 registered trials applying tVNS in pediatric patients (<18 years of age). Most of these studies did not exclusively address pediatric patients. None of the studies elaborated on neurodevelopmental aspects or justified the applied protocol or stimulation parameters for use in pediatric patients. CONCLUSIONS: No dedicated pediatric tVNS devices exist. Neither stimulation parameters nor stimulation protocols for tVNS are properly justified in pediatric patients. Evidence on age-dependent stimulation effects of tVNS under a neurodevelopment framework is warranted. We discuss the potential implications of these findings with clinical relevance, address some of the challenges of tVNS research in pediatric populations, and point out key aspects in future device development and research in addition to clinical studies on pediatric populations.

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas.

Vagus nerve stimulation (VNS) is an established treatment option for patients with treatment resistant epilepsy and depression. However, the procedure is invasive and has side-effects. Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive alternative. Particularly transcutaneous stimulation at the outer ear is gaining increasing interest. While the scope of therapeutic tVNS applications is expanding, there are still questions regarding the optimal stimulation parameters and site as well as the physiology and pathways of auricular tVNS. This Special Issue of Autonomic Neuroscience: Basic & Clinical provides an introduction and overview on basic aspects as well as special topics of tVNS.

Technical aspects and future approaches in transcutaneous vagus nerve stimulation (tVNS).

With the emergence of transcutaneous vagus nerve stimulation (tVNS) as a therapy option for a multitude of clinical indications, the development and improvement of the stimulators becomes an increasingly important point of focus. This paper aims to discuss electrotechnical and software-based improvements to the state-of-the-art stimulators, in order to reduce the experienced side effects of the subjects as well as to increase the efficacy of the stimulation. It was found that side effects such as erythema and pain at the stimulation site are caused by electrolysis at the site of stimulation, which can be reduced by maintaining a voltage below the decomposition voltage. This can be achieved by using electroactive materials and rare-earth fractal metal coatings on the electrode, or by stimulating at the chronaxie with a biphasic rectangular waveform and an in-built short circuit to avoid an after-potential. It is furthermore discussed how the currently most promising stimulation site, the cymba conchae, can technically be stimulated in a feasible and tolerable way for the subject. Utilizing the subjects individual pain threshold is also demonstrated as a good indicator for optimal stimulation, as stimulation just below the pain threshold activates Aα and Aß-fibers, while being unable to polarize the smaller diameter Aδ and C-fibers responsible for pain signaling. Finally, an outlook to individualized tVNS therapy is given, by using evolution algorithms that utilize device and subject data to optimize stimulation parameters.