Effects of transcutaneous vagus nerve stimulation on chronic low back pain: a systematic review

BMC Musculoskelet Disord. 2024 Jun 26;25(1):498. doi: 10.1186/s12891-024-07569-w.

ABSTRACT

BACKGROUND: Chronic low back pain (CLBP) is a frequent disease. It is a critical health concern that can influence functional capacity by restricting living activities.

OBJECTIVES: The current study is to investigate the effects of transcutaneous vagus nerve stimulation (TVNs) in the management of CLBP.

METHODS: We searched the databases on Google Scholar, PubMed, Web of Science, Cochrane, and Pedro for randomized clinical trial (RCT) studies published in any language that looked at the effectiveness of TVNs in people with chronic LBP. The inclusion criteria were PICO. Participants in the research were people (≥ 18 years) diagnosed with persistent low back pain for more than 3 months. Study quality was assessed using Cochrane ROB 2.

RESULTS: Our database search found 1084 RCT. A number of studies that were not necessary for the issue were removed, and the overall outcome was six trials. Risk of bias (ROB) evaluations at the study level (derived from outcomes) are reported. In the six studies, two (33.3%) had an overall uncertain ROB (i.e., some concerns), whereas one (16.7%) had a high overall ROB. Three trials (50%) had a low overall RoB.

CONCLUSION: There is still no evidence to support the use of transcutaneous vagus nerve stimulation as a viable therapeutic rehabilitation strategy. Therefore, we recommend high-quality trials and long-term follow-up to evaluate disability, quality of life, and pain outcomes in these patients.

PMID:38926726 | DOI:10.1186/s12891-024-07569-w

Neuroimmune recognition and regulation in the respiratory system

Eur Respir Rev. 2024 Jun 26;33(172):240008. doi: 10.1183/16000617.0008-2024. Print 2024 Apr.

ABSTRACT

Neuroimmune recognition and regulation in the respiratory system is a complex and highly coordinated process involving interactions between the nervous and immune systems to detect and respond to pathogens, pollutants and other potential hazards in the respiratory tract. This interaction helps maintain the health and integrity of the respiratory system. Therefore, understanding the complex interactions between the respiratory nervous system and immune system is critical to maintaining lung health and developing treatments for respiratory diseases. In this review, we summarise the projection distribution of different types of neurons (trigeminal nerve, glossopharyngeal nerve, vagus nerve, spinal dorsal root nerve, sympathetic nerve) in the respiratory tract. We also introduce several types of cells in the respiratory epithelium that closely interact with nerves (pulmonary neuroendocrine cells, brush cells, solitary chemosensory cells and tastebuds). These cells are primarily located at key positions in the respiratory tract, where nerves project to them, forming neuroepithelial recognition units, thus enhancing the ability of neural recognition. Furthermore, we summarise the roles played by these different neurons in sensing or responding to specific pathogens (influenza, severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, human metapneumovirus, herpes viruses, Sendai parainfluenza virus, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, amoebae), allergens, atmospheric pollutants (smoking, exhaust pollution), and their potential roles in regulating interactions among different pathogens. We also summarise the prospects of bioelectronic medicine as a third therapeutic approach following drugs and surgery, as well as the potential mechanisms of meditation breathing as an adjunct therapy.

PMID:38925790 | DOI:10.1183/16000617.0008-2024

Transcutaneous auricular vagus nerve stimulation improves anxiety symptoms and cortical activity during verbal fluency task in Parkinson’s disease with anxiety

J Affect Disord. 2024 Jun 24;361:556-563. doi: 10.1016/j.jad.2024.06.083. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the effect of 20/4Hz transcutaneous auricular vagus nerve stimulation (taVNS) on anxiety symptoms in Parkinson’s disease (PD) and the potential neural mechanism.

METHODS: In the current randomized, double-blind, sham-controlled trial, 30 PD patients with anxiety (PD-A), 30 PD patients without anxiety (PD-nA), and 30 healthy controls (HCs) were enrolled. PD-A patients were randomly (1:1) allotted to real taVNS stimulation group (RS) or sham stimulation group (SS) to explore the efficacy of a two-week treatment of taVNS to promote anxiety recovery. Simultaneously, all participants were measured activation in the bilateral prefrontal cortex during verbal fluency task (VFT) using functional near-infrared spectroscopy.

RESULTS: PD-A patients showed significantly decreased oxyhemoglobin in the left triangle part of the inferior frontal gyrus (IFG) during VFT, which was negatively related to the severity of anxiety symptoms. After two-week treatment of taVNS, the interaction of group and time had significant effect on HAMA scores (F = 18.476, p < 0.001, η2 = 0.398). In RS group, compared with baseline, HAMA scores decreased significantly in the post-treatment and follow-up condition (both p < 0.001). Meanwhile, in RS group, HAMA scores were lower than those in SS group in the post-treatment and follow-up condition (p = 0.006, <0.001, respectively). Furthermore, the 20/4Hz taVNS remarkably ameliorated anxiety symptoms in PD patients, directly correlated with the increased activation of the left triangle part of the IFG during VFT in RS group.

CONCLUSION: Our results depicted that taVNS could ameliorate the anxiety symptoms of PD-A patients and regulated the function of the left triangle part of the IFG.

PMID:38925314 | DOI:10.1016/j.jad.2024.06.083

Electroacupuncture Promotes Liver Regeneration by Activating DMV Acetylcholinergic Neurons-Vagus-Macrophage Axis in 70% Partial Hepatectomy of Mice

Adv Sci (Weinh). 2024 Jun 25:e2402856. doi: 10.1002/advs.202402856. Online ahead of print.

ABSTRACT

Lack of liver regenerative capacity is the primary cause of hepatic failure and even mortality in patients undergoing hepatectomy, with no effective intervention strategies currently available. Therefore, identifying efficacious interventions to enhance liver regeneration is pivotal for optimizing clinical outcomes. Recent studies have demonstrated that vagotomy exerts an inhibitory effect on liver regeneration following partial hepatectomy, thereby substantiating the pivotal role played by the vagus nerve in the process of liver regeneration. In recent years, electroacupuncture (EA) has emerged as a non-invasive technique for stimulating the vagus nerve. However, EA on hepatic regeneration remains uncertain. In this study, a 70% partial hepatectomy (PH) mouse model is utilized to investigate the effects of EA on acute liver regeneration and elucidate its underlying molecular mechanisms. It is observed that EA at ST36 acutely activated cholinergic neurons in the dorsal motor nucleus of the vagus nerve (DMV), resulting in increased release of acetylcholine from hepatic vagal nerve endings and subsequent activation of IL-6 signaling in liver macrophages. Ultimately, these events promoted hepatocyte proliferation and facilitated liver regeneration. These findings provide insights into the fundamental brain-liver axis mechanism through which EA promotes liver regeneration, offering a novel therapeutic approach for post-hepatectomy liver regeneration disorders.

PMID:38923873 | DOI:10.1002/advs.202402856

The Effect of Hemithyroidectomy in Papillary Thyroid Carcinoma with an Exclusive Involvement of the Recurrent Laryngeal Nerve: A Retrospective Study with a Propensity Score-Matched Analysis

Curr Oncol. 2024 Jun 20;31(6):3603-3614. doi: 10.3390/curroncol31060265.

ABSTRACT

BACKGROUND: Involvement of the recurrent laryngeal nerve (RLN) in papillary thyroid carcinoma (PTC) is an important prognostic factor and is associated with a higher risk of recurrence. This study aimed to retrospectively analyze the outcomes of patients treated with hemithyroidectomy (HT) in PTC patients with an exclusive RLN invasion who could not tolerate staged surgery, did not wish to undergo another operation, or had other reasons.

METHODS: A retrospective review was conducted on 163 patients with PTC and exclusive RLN involvement at our institution between 2013 and 2019. Patients were divided into a total thyroidectomy (TT) group and HT group. The clinicopathologic factors and prognostic outcomes were compared between the two groups. A propensity score-matched analysis was carried out to reduce selection bias, with the following covariates: gender, age, tumor size, multifocality, central lymph node metastasis (CLNM), and RLN resection. The Kaplan-Meier method was used for a comparison of recurrence outcomes.

RESULTS: In the baseline data of the 163 PTC patients, tumor size (p < 0.001), multifocality (p = 0.011), CLNM (p < 0.001), and RLN resection (p < 0.008) in the TT and HT groups differed significantly, whereas age and gender did not differ between the two groups. The TT group reported significantly higher temporary and permanent hypoparathyroidism than the HT group (p < 0.001 and p = 0.042, respectively). With 72-month median follow-up, 11 (6.7%) patients developed recurrence. After propensity score matching, 24 patients with HT and 43 patients with TT were included. Recurrence-free survival (RFS) in the matched samples showed no difference between the TT and HT groups (p = 0.092).

CONCLUSION: Our results indicate that HT may be a feasible treatment for PTC patients with exclusive RLN involvement in specific circumstances without significantly increasing the risk of recurrence. Performing a thorough preoperative examination is crucial to exclude multifocal tumors and lymph node metastasis before undergoing HT.

PMID:38920748 | PMC:PMC11203164 | DOI:10.3390/curroncol31060265

Clinical Characteristics and Prognosis of Herpes Zoster Laryngitis With Vocal Fold Immobility

J Voice. 2024 Jun 20:S0892-1997(24)00172-3. doi: 10.1016/j.jvoice.2024.05.020. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics and prognosis of herpes zoster laryngitis with vocal fold immobility.

STUDY DESIGN: Retrospective study.

METHODS: Clinical characteristics, laryngeal signs on strobolaryngoscopy, imaging examination findings, and outcomes of patients were analyzed retrospectively.

RESULTS: This study included 17 patients (11 males [64.7%] and six females [35.3%]), with a mean age of 63.3 ± 6.7 years. The primary symptoms were hoarseness (94.1%), dysphagia (76.5%), pharyngalgia on one side (76.5%), and aspiration (70.6%). No patient had skin herpes of the head and neck. The duration of symptoms was 5-30 days (median: 10 days). Twelve patients (70.6%) were in an immunocompromised state before the disease. Strobolaryngoscopy showed congestion and swelling of the mucosa on one side of the larynx, with whitish eruptions on the supraglottic mucosa and ipsilateral vocal fold immobility. Five patients (29.4%) exhibited signs of ipsilateral accessory nerve injury. The imaging examination showed supraglottic inflammatory changes in 12 patients (70.6%). Among the 14 patients whose treatment could be clearly described, only one patient received antiviral treatment, whereas others received neurotrophic and symptomatic treatment. Notably, all patients demonstrated good outcomes because their symptoms eventually returned to normal.

CONCLUSION: Herpes zoster laryngitis is caused by varicella-zoster virus infection of the vagus nerve. It is characterized by laryngeal herpetic changes on one side and unilateral vocal fold immobility. The inducement of the disease tends to be associated with the abnormal immune state of patients. It can be easily misdiagnosed because of the absence of skin herpetic changes. Regardless of antiviral therapy, patients generally exhibit a favorable outcome.

PMID:38906743 | DOI:10.1016/j.jvoice.2024.05.020

Effect of vagus nerve stimulation on emergency department utilization in children with drug-resistant epilepsy: a retrospective cohort study

J Neurosurg Pediatr. 2024 Jun 21:1-8. doi: 10.3171/2024.4.PEDS23310. Online ahead of print.

ABSTRACT

OBJECTIVE: Epilepsy affects approximately 470,000 children in the United States. The estimated median incidence is 50.4 cases per 100,000 persons per year. There are approximately 3.1 million seizure-related emergency department (ED) visits per year among children. Vagus nerve stimulation (VNS) is a treatment option for drug-resistant epilepsy (DRE). While its primary goal is to decrease seizure burden, VNS may decrease seizure intensity and improve quality of life. The authors assessed whether VNS decreased the number of seizure-related ED visits in a cohort of children with DRE.

METHODS: The authors performed a retrospective chart review of pediatric patients (aged 0-21 years) who underwent implantation of a vagus nerve stimulator between January 2009 and January 2020 at the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh. They used paired t-tests to assess differences in the number of ED visits 2 years before versus 2 years after VNS device implantation. Univariable linear regression analyses were used to test associations of preoperative characteristics with change in the number of ED visits following vagus nerve stimulator insertion.

RESULTS: This study included 240 patients. Compared with patients without seizure-related ED visits before VNS, patients with ≥ 1 ED visits were younger in age at first VNS surgery (9.5 vs 10.8 years), had a shorter epilepsy duration before VNS surgery (5.8 vs 7.4 years), had a later year of device implantation (2014 vs 2012), and on average took more antiseizure medications (ASMs; 2.4 vs 2.1). There was no significant difference between the total number of seizure-related ED visits pre- versus post-VNS surgery (1.72 vs 1.59, p = 0.50), and no difference in status epilepticus-related visits (0.59 vs 0.46, p = 0.17). Univariable linear regression analyses revealed a mean change in ED visits of +0.3 for each year prior to 2022 and -0.5 for each additional ASM that patients took before vagus nerve stimulator insertion.

CONCLUSIONS: This single-institution analysis demonstrated no significant change in the number of seizure-related ED visits within 2 years following VNS device implantation. Earlier VNS surgery was associated with more seizure-related ED visits after device insertion, suggesting that medical management and center experience may play a role in decreasing seizure-related ED visits. A greater number of ASMs was associated with fewer seizure-related ED visits after VNS device insertion, suggesting the role of medical management, patient baseline seizure threshold, and caregiver comfort with at-home seizure management.

PMID:38905712 | DOI:10.3171/2024.4.PEDS23310

A Critical Review of Noninvasive Brain Stimulation Technologies in Alzheimer’s Dementia and Primary Progressive Aphasia

J Alzheimers Dis. 2024 Jun 20. doi: 10.3233/JAD-240230. Online ahead of print.

ABSTRACT

Multiple pharmacologic agents now have been approved in the United States and other countries as treatment to slow disease and clinical progression for Alzheimer’s disease. Given these treatments have not been proven to lessen the cognitive deficits already manifested in the Alzheimer’s Clinical Syndrome (ACS), and none are aimed for another debilitating dementia syndrome identified as primary progressive aphasia (PPA), there is an urgent need for new, safe, tolerable, and efficacious treatments to mitigate the cognitive deficits experienced in ACS and PPA. Noninvasive brain stimulation has shown promise for enhancing cognitive functioning, and there has been interest in its potential therapeutic value in ACS and PPA. This review critically examines the evidence of five technologies in ACS and PPA: transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), repetitive transcranial magnetic stimulation (rTMS), and noninvasive vagus nerve stimulation (nVNS). Many randomized controlled trials of tDCS and rTMS report positive treatment effects on cognition in ACS and PPA that persist out to at least 8 weeks, whereas there are few trials for tACS and none for tRNS and nVNS. However, most positive trials did not identify clinically meaningful changes, underscoring that clinical efficacy has yet to be established in ACS and PPA. Much is still to be learned about noninvasive brain stimulation in ACS and PPA, and shifting the focus to prioritize clinical significance in addition to statistical significance in trials could yield greater success in understanding its potential cognitive effects and optimal parameters.

PMID:38905047 | DOI:10.3233/JAD-240230

Closed-loop transcutaneous auricular vagus nerve stimulation for the improvement of upper extremity motor function in stroke patients: a study protocol

Front Neurol. 2024 Jun 5;15:1379451. doi: 10.3389/fneur.2024.1379451. eCollection 2024.

ABSTRACT

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) has garnered attention for stroke rehabilitation, with studies demonstrating its benefits when combined with motor rehabilitative training or delivered before motor training. The necessity of concurrently applying taVNS with motor training for post-stroke motor rehabilitation remains unclear. We aimed to investigate the necessity and advantages of applying the taVNS concurrently with motor training by an electromyography (EMG)-triggered closed-loop system for post-stroke rehabilitation.

METHODS: We propose a double-blinded, randomized clinical trial involving 150 stroke patients assigned to one of three groups: concurrent taVNS, sequential taVNS, or sham control condition. In the concurrent group, taVNS bursts will synchronize with upper extremity motor movements with EMG-triggered closed-loop system during the rehabilitative training, while in the sequential group, a taVNS session will precede the motor rehabilitative training. TaVNS intensity will be set below the pain threshold for both concurrent and sequential conditions and at zero for the control condition. The primary outcome measure is the Fugl-Meyer Assessment of Upper Extremity (FMA-UE). Secondary measures include standard upper limb function assessments, as well as EMG and electrocardiogram (ECG) features.

ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee, affiliated with Zhujiang Hospital of Southern Medical University for Clinical Studies (2023-QX-012-01). This study has been registered on ClinicalTrials (NCT05943431). Signed informed consent will be obtained from all included participants. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings.

DISCUSSION: This study represents a pioneering effort in directly comparing the impact of concurrent taVNS with motor training to that of sequential taVNS with motor training on stroke rehabilitation. Secondly, the incorporation of an EMG-triggered closed-loop taVNS system has enabled the automation and individualization of both taVNS and diverse motor training tasks-a novel approach not explored in previous research. This technological advancement holds promise for delivering more precise and tailored training interventions for stroke patients. However, it is essential to acknowledge a limitation of this study, as it does not delve into examining the neural mechanisms underlying taVNS in the context of post-stroke rehabilitation.

PMID:38903173 | PMC:PMC11188480 | DOI:10.3389/fneur.2024.1379451

Vagus nerve stimulation for the treatment of treatment-refractory epilepsy

Ugeskr Laeger. 2024 Jun 3;186(23):V10230638. doi: 10.61409/V10230638.

ABSTRACT

About 40 % of new-onset epilepsy is drug refractory. If epilepsy surgery is not an option or fails, vagal nerve stimulation (VNS) can be considered. VNS efficacy is reported as more than 50 % seizure frequency reduction in 50-56 % of patients. Features in the newer models offer additional treatment optimization possibilities. Side effects include hoarseness, cough, and dyspnoea. Caution is advised for patients with sleep apnoea or lung disease. VNS has specific limitations concerning MRI. This review presents an overview of VNS treatment in Denmark and discusses future challenges.

PMID:38903031 | DOI:10.61409/V10230638