Transcutaneous Auricular Vagus Nerve Stimulation Research Articles

Effect of Vagal Nerve Stimulation on Swallowing in Subjects with Post Stroke Dysphagia

Background: The study was developed to find the effect of auricular transcutaneous vagal nerve stimulation ondifficulty in swallowing in post stroke dysphagia.Purpose: The purpose of this research is to extensively investigate and analyse how VNS impacts swallowing inpeople with post-stroke dysphagia.Materials and Methods: A total, 30 individuals have been selected mainly according to the criteria of both theinclusion and exclusion, from the above-mentioned study setting. The study was explained to subjects and writtenconsent was collected from all subjects prior to the initiation of procedure. The subjects included the study wasrandomly allocated into 2 groups The participants in group A will receive Transcutaneous auricular vagal nervestimulation, which is given for 20 min with the frequency of about 25 Hz, amplitude: 1 mA, pulse width: 360μs using clip electrode being placed in Cymba Concha, along with the conventional exercises and Group B willreceive Neuromuscular electrical stimulation will be given as Interrupted direct current at 30 Hz for 100ms, andthe intensity was increased until perceptible visible contraction.Results: Auricular transcutaneous vagal nerve stimulation showed a significant effect in improving swallowingfunctions at 4 weeks, with a p value which is < 0.001.Conclusion: This study showed that the transcutaneous auricular vagal nerve stimulation showed a positive effectin improving swallowing functions in patients with dysphagia.

Effect of non-invasive transcutaneous auricular vagus nerve stimulation on cerebral motor excitability-Study protocol for a randomized, sham controlled trial.

www.drks.de, number: DRKS00029937.

Current status and prospect of transcutaneous auricular vagus nerve stimulation for disorders of consciousness.

Disordered Consciousness (DOC) is among neurological disorders for which there is currently no admitted treatment. The pathogenesis of DOC is still unclear, covering a variety of indistinguishable types of diseases, high misdiagnosis rate and poor prognosis. Most treatments remain to be clarified in the future to provide adequate evidence for clinical guidance. Neuromodulation technology aims to regulate neural circuits to promote awakening more directly. At present, it is confirmed that the potential of transcutaneous auricular vagus nerve stimulation (taVNS) as a therapeutic tool is worth exploring in the context of consciousness disorders, as previously proposed for invasive forms of VNS, in which the means of stimulating the vagus nerve to change the brain areas related to cosciousness have also received widespread attention. In this paper, we review the literature on taVNS and DOC to better understand the current status and development prospect of taVNS treament as a non-invasive neuromodulation method with sensitivity and/or specificity at the single subject.

Primer Dismenore’li Bir Genç Yetişkinde Transkütanöz Auriküler Vagus Sinir Stimülasyonunun Etkileri: Bir Olgu Sunumu

Amaç: Bu olgu sunumunun amacı Primer Dismenore’li bir genç yetişkinde transkütanöz auriküler vagus sinir stimülasyonunun ağrı, menstrüal semptomlar, depresyon ve anksiyete üzerine etkisinin araştırılmasıdır. Yöntem: Olgunun, ilk menstrüal siklusunun 1. gününde, ağrı şiddeti “Visüel Analog Skala (VAS)”, ağrı eşiği “basınç algometresi”, depresyon düzeyi “Beck Depresyon Envanteri”, anksiyete düzeyi “Beck Anksiyete Envanteri”, menstrüal semptomları da “Menstrüal Belirti Ölçeği” ile değerlendirildi. Olguya menstrüal siklusun 14. gününden ikinci menstrüal siklusa kadar 10 seans vagus sinir stimülasyonu uygulandı. Uygulamalardan sonra ikinci menstrüal siklusun en ağrılı gününde olgu tekrar değerlendirildi. Bulgular: Müdahale sonrası olgunun menstrüal ağrı şiddetinde azalma, ağrı eşiği değerlerinde artma, depresyon ve anksiyete düzeylerinde azalma ve menstrüal belirtilerinin şiddetinde azalma görüldü. Sonuç: Primer Dismenore’li bireylerde vagal sinir stimülasyonu ağrı ve ilişkili belirtileri iyileştirmede etkili olabilir.

Short-term effects of transcutaneous auricular vagus nerve stimulation on T-wave alternans in people with focal epilepsy – An exploratory pilot study

High levels of T-wave alternans (TWA) are linked to an increased risk of sudden cardiac death. People with epilepsy display elevated TWA levels that are decreased by chronic vagus nerve stimulation via implanted devices after 2–4 weeks or later. Our objective was to explore short-term effects of transcutaneous auricular vagus nerve stimulation (tVNS) on TWA. Five patients (3 female) with focal epilepsy undergoing video-EEG monitoring were included. TWA levels were determined using a one-channel modified lead I ECG via an open-source TWA-algorithm on two consecutive days, 1 h before, during and after tVNS via the left auricle. Data are given as mean ± SE. Mean TWA at baseline was 3.8 ± 0.4 µV and 3.0 ± 0.6 µV during stimulation on day 2. Stimulations on the second day were associated with TWA reductions by 22 ± 13 % that exceeded stimulation effects on the first day relative to baseline (p < 0.05). Linear mixed-models revealed effects of both stimulation (p < 0.05) and stimulation number (p < 0.005). Normalized TWA showed reproducible peak reductions at both days within 35 min after the initiation of tVNS (p < 0.05). Our observations suggest that tVNS has short-term effects on TWA, supporting the notion that vagus nerve stimulation has a beneficial impact on electrical cardiac properties.

The efficacy and safety of bilateral synchronous transcutaneous auricular vagus nerve stimulation for prolonged disorders of consciousness: a multicenter, double-blind, stratified, randomized controlled trial protocol.

Treatment of disorders of consciousness (DOC) poses a huge challenge for clinical medicine. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation method, which shows potential in improving recovery of DOC. However, the evidence came from single-center, small-sample randomized controlled trial, which is insufficient to form a conclusion. Thereby, we propose a prospective, multicenter, double-blind, stratified, two-arm randomized controlled trial protocol to investigate the efficacy and safety of bilateral synchronous taVNS for treatment of DOC. We aim to recruit 382 patients with prolonged DOC, and divide them into an active stimulation group and a sham stimulation group. The patients in the active stimulation group will receive bilateral synchronous taVNS with a 200 μs pulse width, 20 Hz frequency, and personal adjusted intensity. The sham stimulation group will wear the same stimulator but without current output. Both groups will receive treatment for 30 min per session, twice per day, 6 days per week lasting for 4 weeks. The clinical assessment including Coma Recovery Scale-Revised (CRS-R), Full Outline of Unresponsiveness (FOUR), Glasgow Coma Scale (GCS), and Extended Glasgow Outcome Scale (GOS-E) will be conducted to evaluate its efficacy. Heart rate variability (HRV), blood pressure, and adverse events will be recorded to evaluate its safety. These results will enable us to investigate the efficacy and safety of taVNS for DOC. This protocol will provide multicenter, large-sample, high-quality Class II evidence to support bilateral synchronous taVNS for DOC, and will advance the field of treatment options for DOC.Clinical trial registration:https://www.chictr.org.cn/showproj.html?proj=221851, ChiCTR2400081978.

Transcutaneous auricular vagus nerve stimulation improves social deficits through the inhibition of IL-17a signaling in a mouse model of autism.

Maternal exposure to inflammation is one of the causes of autism spectrum disorder (ASD). Electrical stimulation of the vagus nerve exerts a neuroprotective effect via its anti-inflammatory action. We thus investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) can enhance social abilities in a mouse model of ASD induced by maternal immune activation (MIA). ASD mouse model were constructed by intraperitoneal injection of polyinosinic:polycytidylic acid (poly (I:C)). TaVNS with different parameters were tested in ASD mouse model and in C57BL/6 mice, then various behavioral tests and biochemical analyses related to autism were conducted. ASD model mice were injected with an interleukin (IL)-17a antibody into the brain, followed by behavioral testing and biochemical analyses. TaVNS reduced anxiety, improved social function, decreased the number of microglia, and inhibited M1 polarization of microglia. Additionally, taVNS attenuated the expression of the IL-17a protein in the prefrontal cortex and blood of ASD model mice. To examine the possible involvement of IL-17a in taVNS-induced neuroprotection, we injected an IL-17a antibody into the prefrontal cortex of ASD model mice and found that neutralizing IL-17a decreased the number of microglia and inhibited M1 polarization. Furthermore, neutralizing IL-17a improved social function in autism model mice. Our study revealed that reduced neuroinflammation is an important mechanism of taVNS-mediated social improvement and neuroprotection against autism. This effect of taVNS could be attributed to the inhibition of the IL-17a pathway.

The Neural Basis of the Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Emotion Regulation Related Brain Regions: An rs-fMRI Study

The Neural Basis of the Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Emotion Regulation Related Brain Regions: An rs-fMRI Study

Current status of transcutaneous auricular vagus nerve stimulation for tinnitus: a narrative review of modern research.

Tinnitus, characterized by phantom sound perception, is a highly disruptive disorder lacking definitive and effective treatments. Its intricate neural mechanisms are not fully understood. Transcutaneous auricular vagus nerve stimulation (taVNS) has demonstrated potential as a substitute or supplementary treatment by activating central vagal pathways. However, standardized therapeutic protocols and objective tests to assess efficacy are lacking. Therefore, taVNS shows promise as a therapy for tinnitus, and treatment protocols should be optimized in future clinical trials.

Effectiveness of Rehabilitative Interventions Beginning within the First Month of Stroke Onset in Improving Lower Extremity-related Outcomes: A Systematic Review and Network Meta-Analysis

Reviews about early interventions, which are important in stroke rehabilitation due to significant neural plasticity, are relatively less. This study objective was to investigate the effectiveness of different interventions started within one-month post-stroke in improving lower extremity-related outcomes as compared to conventional rehabilitation and the corresponding effectiveness ranking. Cochrane Library, Ovid, PubMed, and Scopus were searched for articles dated up to 18 March 2022. Randomised controlled trials were included if they evaluated the effectiveness of two or more different non-drug, non-invasive, and non-surgical interventions which were started within one-month post-stroke on lower extremity-related outcomes. Network meta-analysis revealed that transcranial direct current stimulation, repetitive transcranial magnetic stimulation, mirror therapy, cycling, transcutaneous auricular vagus nerve stimulation, neuromuscular electrical stimulation (NMES), combination of robot and NMES, and thermal stimulation were significantly more effective in improving lower extremity motor function than conventional rehabilitation. In improving mobility, mirror therapy, cycling, and thermal stimulation were significantly more effective. In enhancing balance, physio ball, transcutaneous electrical nerve stimulation, cycling, thermal stimulation, and robot showed significantly higher effectiveness. Thermal stimulation scored the highest effectiveness ranking in improving lower extremity motor function and mobility whereas robot and backward walking achieved the highest effectiveness ranking in improving balance and gait speed respectively.

Locus coeruleus tyrosine hydroxylase positive neurons mediated the peripheral and central therapeutic effects of transcutaneous auricular vagus nerve stimulation (taVNS) in MRL/lpr mice

ObjectiveThis study aims to investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on the development of systemic lupus erythematosus (SLE) in MRL/lpr mice. MethodsMRL/lpr mice were treated with taVNS for ten weeks. Locus coeruleus (LC) tyrosine hydroxylase positive (TH+) neurons were selectively lesioned by stereotactic injection of 6-hydroxydopamine (6-OHDA) or selectively activated by chemogenetic methods. Sympathetic denervation was conducted by intraperitoneal injection of 6-OHDA. ResultsTaVNS activated the TH + neurons in LC. TaVNS produced central therapeutic effects by reducing the number of hippocampal microglia, and increasing the number of surviving LC TH+ neurons in MRL/lpr mice. TaVNS also retarded the development of lymphadenectasis and splenomegaly, decreased the proportion of double-negative T (DNT) cells, and alleviated nephritis in MRL/lpr mice. The lesion of LC TH+ neurons eliminated both these central and peripheral therapeutic effects of taVNS, while chemogenetic activation of LC TH+ neurons mimicked most central and peripheral protective effects of taVNS in MRL/lpr mice. Furthermore, taVNS regulated the autonomic nervous system in MRL/lpr mice. ConclusionThis study provides direct evidence that taVNS can retard the development of peripheral and central symptoms of SLE, which is mediated by the LC TH+ neurons.

Advances in Non-Invasive Neuromodulation: Designing Closed-Loop Devices for Respiratory-Controlled Transcutaneous Vagus Nerve Stimulation.

Studies suggest non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) as a potential therapeutic option for various pathological conditions, such as epilepsy and depression. Exhalation-controlled taVNS, which synchronizes stimulation with internal body rhythms, holds promise for enhanced neuromodulation, but there is no closed-loop system in the literature capable of performing such integration in real time. In this context, the objective was to develop real-time signal processing techniques and an integrated closed-loop device with sensors to acquire physiological data. After a conditioning stage, the signal is processed and delivers synchronized electrical stimulation during the patient's expiratory phase. Additional modules were designed for processing, software-controlled selectors, remote and autonomous operation, improved analysis, and graphical visualization. The signal processing method effectively extracted respiratory cycles and successfully attenuated signal noise. Heart rate variability was assessed in real time, using linear statistical evaluation. The prototype feedback stimulator device was physically constructed. Respiratory peak detection achieved an accuracy of 90%, and the real-time processing resulted in a small delay of up to 150 ms in the detection of the expiratory phase. Thus, preliminary results show promising accuracy, indicating the need for additional tests to optimize real-time processing and the application of the prototype in clinical studies.

The efficacy and safety of transcutaneous auricular vagus nerve stimulation for patients with minimally conscious state: a sham-controlled randomized double-blind clinical trial.

Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potentially effective neuromodulation technique for addressing neurological disorders, including disorders of consciousness. Expanding upon our prior clinical study, which demonstrated the superior effectiveness of a 4-week taVNS treatment in patients with minimally conscious state (MCS) compared to those in a vegetative state/unresponsive wakefulness state, the aim of this investigation was to evaluate the safety and therapeutic efficacy of taVNS in individuals with MCS through a sham-controlled randomized double-blind clinical trial. A cohort of 50 adult patients (male = 33, female = 17) diagnosed with a MCS were randomly assigned to either the active taVNS (N = 25) or sham taVNS (N = 25) groups. The treatment period lasted for 4 weeks, followed by an 8-week follow-up period. The Coma Recovery Scale-Revised (CRS-R) and Glasgow Coma Scale (GCS) were administered at baseline and weekly during the initial 4 weeks. Additionally, the Disability Rating Scale (DRS) was used to assess the patients' functional abilities via telephone at week 12. Furthermore, various neurophysiological measures, including electroencephalogram (EEG), upper-limb somatosensory evoked potentials (USEP), brainstem auditory evoked potentials (BAEP), and P300 event-related potentials (P300), were employed to monitor changes in brain activity and neural conduction pathways. The scores for the active taVNS group in the CRS-R and GCS showed greater improvement over time compared to the sham taVNS group (CRS-R: 1-week, Z = -1.248, p = 0.212; 2-week, Z = -1.090, p = 0.276; 3-week, Z = -2.017, p = 0.044; 4-week, Z = -2.267, p = 0.023. GCS: 1-week, Z = -1.325, p = 0.185; 2-week, Z = -1.245, p = 0.213; 3-week, Z = -1.848, p = 0.065; 4-week, Z = -1.990, p = 0.047). Additionally, the EEG, USEP, BAEP, and P300 also demonstrated significant improvement in the active taVNS group compared to the sham taVNS group at week 4 (EEG, Z = -2.086, p = 0.037; USEP, Z = -2.014, p = 0.044; BAEP, Z = -2.298, p = 0.022; P300 amplitude, Z = -1.974, p = 0.049; P300 latency, t = 2.275, p = 0.027). Subgroup analysis revealed that patients with MCS derived greater benefits from receiving taVNS treatment earlier (CRS-R, Disease duration ≤ 1-month, mean difference = 8.50, 95% CI = [2.22, 14.78], p = 0.027; GCS, Disease duration ≤ 1-month, mean difference = 3.58, 95% CI = [0.14, 7.03], p = 0.044). By week 12, the active taVNS group exhibited lower Disability Rating Scale (DRS) scores compared to the sham taVNS group (Z = -2.105, p = 0.035), indicating a more favorable prognosis for MCS patients who underwent taVNS. Furthermore, no significant adverse events related to taVNS were observed during treatment. The findings of this study suggest that taVNS may serve as a potentially effective and safe intervention for facilitating the restoration of consciousness in individuals diagnosed with MCS. This therapeutic approach appears to enhance cerebral functioning and optimize neural conduction pathways. http://www.chictr.org.cn, Identifier ChiCTR2200066629.

Making Sense of Vagus Nerve Stimulation for Stroke.

Implantable vagus nerve stimulation, paired with high-dose occupational therapy, has been shown to be effective in improving upper limb function among patients with stroke and received regulatory approval from the US Food and Drug Administration and the Centers for Medicare & Medicaid Services. Combining nonsurgical and surgical approaches of vagus nerve stimulation in recent meta-analyses has resulted in misleading reports on the efficacy of each type of stimulation among patients with stroke. This article aims to clarify the confusion surrounding implantable vagus nerve stimulation as a poststroke treatment option, highlighting the importance of distinguishing between transcutaneous auricular vagus nerve stimulation and implantable vagus nerve stimulation. Recent meta-analyses on vagus nerve stimulation have inappropriately combined studies of fundamentally different interventions, outcome measures, and participant selection, which do not conform to methodological best practices and, hence, cannot be used to deduce the relative efficacy of the different types of vagus nerve stimulation for stroke rehabilitation. Health care providers, patients, and insurers should rely on appropriately designed research to guide well-informed decisions.

Effect of Transcutaneous Auricular Vagus Nerve Stimulation Addition on Disability in Chronic Low Back Pain Patients: A Randomized Controlled Study

Background &amp; objective: Low back pain is a common problem, especially in the young and middle-aged working people, and is often very resistant to the conventional management. We evaluated the impact of transcutaneous auricular vagus nerve stimulation (tVNS), applied in conjunction with an exercise treatment program, on disability in chronic low back pain patients.&#x0D; Methodology: The study was conducted from June to October 2022. Twenty-two patients aged 42.18 ± 9.91 y, with Numerical Pain Rating Scale (NPRS) score 5.64 ± 1.09 and Roland Morris Disability Questionnaire (RMDQ) score 10 ± 4.670, were randomly assigned to two groups. The control group received only exercise therapy (EXC group, n = 11), and the intervention group received exercise and tVNS therapy (EXC + tVNS group, n = 11). The primary outcome was RMDQ, measured before and after the intervention.&#x0D; Result: The mean RMDQ was significantly improved in both groups. In the intervention group the improvement was from 9.45 ± 4.44 to 2.18 ± 2.71 (P = 0.000), in the control group it was from 10.55 ± 5.05 to 2.36 ± 2.06 (P = 0.001). Inter-group comparison showed no significant difference. The effect size of the control group (2.12) was similar with the intervention group (1.98).&#x0D; Conclusion: Addition of 2-weeks tVNS to exercise therapy did not show superior effect on disability improvement compared to exercise only in chronic low back pain. Exercise alone was sufficient to improve the mean RMDQ.&#x0D; Abbreviations: CLBP: Chronic low back pain; EXC: Exercise; tVNS: Transcutaneous auricular vagus nerve stimulation; NPRS: Numerical pain rating scale; RMDQ: Roland Morris disability questionnaire&#x0D; Key words: Chronic low back pain; Disability; Exercise; Transcutaneous Auricular Vagus Nerve Stimulation&#x0D; Citation: Uzlifatin Y, Arfianti L, Wardhani IL, Hidayati HB, Melaniani S. Effect of transcutaneous auricular vagus nerve stimulation in addition to exercise on disability in chronic low back pain patients: a randomized controlled study. Anaesth. pain intensive care 2022;27(1):73−81; DOI: 10.35975/apic.v27i1.2084&#x0D; Received: December 07, 2022; Reviewed: December 28, 2022; Accepted: January 11, 2022

Modulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on attentional processes

BackgroundThe modulatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) on attention has varied in previous studies. This inconsistency might be attributed to the combined influence of the modulation effect...

An international survey of experiences and attitudes towards transcutaneous auricular vagus nerve stimulation for people with Myalgic Encephalomyelitis/chronic fatigue syndrome

ABSTRACT Background and objectives: Myalgic encephalomyelitis (ME) is a complex, multi-system neurological condition. Dysfunction of the autonomic nervous system is a primary feature in diagnostic criteria, and management may include attempts to stimulate the parasympathetic nervous system. Transcutaneous auricular vagus nerve stimulation is an intervention that has been researched in neurological disorders, e.g. epilepsy, depression. While little evidence exists for its use in ME, this survey aims to explore the experiences and attitudes of people with ME to this intervention. Methods A 31-question online survey was devised and released on ME websites, Twitter and Facebook pages. People with ME read the information sheet and followed an online link to the survey. The survey was open for four weeks and all answers were anonymous. Results 116 responses were received. 56% of respondents reported favourable effects. Benefits of transcutaneous auricular vagus nerve stimulation were identified in relation to post exertional malaise, pain, gut problems, urinary problems, mental health, and the ability to leave the house. 67.2% of respondents would recommend the intervention to other people with ME. However, 4.3% would not recommend it and 6% reported it made them worse. 8.6% received support in setting up the device from healthcare workers. Conclusion The survey highlights that many people with ME experience significant benefits from using transcutaneous auricular vagus nerve stimulation; however due to potential negative effects there is the need for formal intervention studies to clearly identify safe parameters.

Transcutaneous auricular vagus nerve stimulation on upper limb motor function with stroke: a functional near-infrared spectroscopy pilot study

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) emerges as a promising neuromodulatory technique. However, taVNS uses left ear stimulation in stroke survivors with either left or right hemiparesis. Understanding its influence on the cortical responses is pivotal for optimizing post-stroke rehabilitation protocols.ObjectiveThe primary objective of this study was to elucidate the influence of taVNS on cortical responses in stroke patients presenting with either left or right hemiparesis and to discern its potential ramifications for upper limb rehabilitative processes.MethodsWe employed functional near-infrared spectroscopy (fNIRS) to ascertain patterns of cerebral activation in stroke patients as they engaged in a “block transfer” task. Additionally, the Lateralization Index (LI) was utilized to quantify the lateralization dynamics of cerebral functions.ResultsIn patients exhibiting left-side hemiplegia, there was a notable increase in activation within the pre-motor and supplementary motor cortex (PMC-SMC) of the unaffected hemisphere as well as in the left Broca area. Conversely, those with right-side hemiplegia displayed heightened activation in the affected primary somatosensory cortex (PSC) region following treatment.Significantly, taVNS markedly amplified cerebral activation, with a pronounced impact on the left motor cortical network across both cohorts. Intriguingly, the LI showcased consistency, suggesting a harmonized enhancement across both compromised and uncompromised cerebral regions.ConclusionTaVNS can significantly bolster the activation within compromised cerebral territories, particularly within the left motor cortical domain, without destabilizing cerebral lateralization. TaVNS could play a pivotal role in enhancing upper limb functional restoration post-stroke through precise neuromodulatory and neuroplastic interventions.

The effect of transcutaneous auricular vagus nerve stimulation on cycling ergometry and recovery in healthy young individuals.

It is aimed to examine the potential benefits and effects of the use of transcutaneous auricular vagus nerve stimulation (VNS) for sporting purposes on recovery, fatigue, and sportive performance level. In this study, 90 people between the ages of 18-23 were participated. They were randomly divided into three groups as bilateral sham, unilateral left, and bilateral VNS. A 4-day protocol was applied to the participants. Cycling exercise was performed with maximum performance for 30min under the same watt load. Pulse, systolic and diastolic blood pressure, distance, pain, fatigue, lactic acid level, and autonomic nervous system were evaluated. Within the groups, there was a statistically significant difference between the data (p<.05) except for the distance covered parameter. When we compare the groups, in addition to the distance traveled in all groups, there is no statistically significant difference in the 1st day 1st measurement and 2nd measurement data of all parameters (p>.05 When we compared the data according to days, there was a statistically significant difference between bilateral stimulation (BS) and unilateral stimulation, only pain and fatigue levels (p<.05). In our study, we saw that BS application gave positive results in reducing pain and fatigue due to cycling exercise compared to other applications. Similar results were obtained when we evaluated the data on a daily basis. We believe that VNS will be beneficial in reducing pain and fatigue, especially during and after the competition halftime.

Efficacy and safety of vagus nerve stimulation on upper extremity motor function in patients with stroke: A meta-analysis of randomized controlled trials.

In 2021, the U.S. Food and Drug Administration (FDA) approved paired vagus nerve stimulation (VNS) for patients with moderate-to-severe upper extremity motor impairments following chronic ischemic stroke. Previous meta-analyses have shown that VNS may impact stroke rehabilitation, but each has some limitations. PubMed, Ovid, Cochrane Library, ScienceDirect, Web of Science and WHO ICTRP databases were searched until July 14, 2022 for randomized controlled trials (RCTs). We defined primary outcomes as Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT). Subgroup analyses included types of VNS, time since onset and long-term effects. Secondary outcomes included adverse events of VNS. Eight RCTs involving 266 patients were analyzed, of which five used direct VNS and three transcutaneous auricular VNS. The results revealed that VNS enhanced upper extremity function via FMA-UE (SMD = 0.73; 95% CI: 0.48 to 0.99; P < 0.00001) and WMFT (SMD = 0.82; 95% CI:0.52 to 1.13; P < 0.00001) in comparison to the control group, but showed no significant change on long-term effects of FMA-UE (SMD = 0.69; 95% CI: - 0.06 to 1.44; P = 0.07). There was no difference in adverse events between the VNS and control groups (RR = 1.16; 95% CI: 0.46 to 2.92; P = 0.74). For stroke victims with upper limb disabilities, VNS paired with rehabilitation was significantly safe and effective. More high-quality multicentric RCTs are needed to validate this conclusion.