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

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

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

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

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

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

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

Neurobiol Dis. 2024 Jun 18:106573. doi: 10.1016/j.nbd.2024.106573. Online ahead of print.

ABSTRACT

Arketamine, the (R)-enantiomer of ketamine, exhibits antidepressant-like effects in mice, though the precise molecular mechanisms remain elusive. It has been shown to reduce splenomegaly and depression-like behaviors in the chronic social defeat stress (CSDS) model of depression. This study investigated whether the spleen contributes to the antidepressant-like effects of arketamine in the CSDS model. We found that splenectomy significantly inhibited arketamine’s antidepressant-like effects in CSDS-susceptible mice. RNA-sequencing analysis identified the oxidative phosphorylation (OXPHOS) pathway in the prefrontal cortex (PFC) as a key mediator of splenectomy’s impact on arketamine’s effects. Furthermore, oligomycin A, an inhibitor of the OXPHOS pathway, reversed the suppressive effects of splenectomy on arketamine’s antidepressant-like effects. Specific genes within the OCPHOS pathways, such as COX11, UQCR11 and ATP5e, may contribute to these inhibitory effects. Notably, transforming growth factor (TGF)-β1, along with COX11, appears to modulate the suppressive effects of splenectomy and contribute to arketamine’s antidepressant-like effects. Additionally, SRI-01138, an agonist of the TGF-β1 receptor, alleviated the inhibitory effects of splenectomy on arketamine’s antidepressant-like effects. Subdiaphragmatic vagotomy also counteracted the inhibitory effects of splenectomy on arketamine’s antidepressant-like effects in CSDS-susceptible mice. These findings suggest that the OXPHOS pathway and TGF-β1 in the PFC play significant roles in the antidepressant-like effects of arketamine, mediated through the spleen-brain axis via the vagus nerve.

PMID:38901783 | DOI:10.1016/j.nbd.2024.106573

Trials. 2024 Jun 19;25(1):397. doi: 10.1186/s13063-024-08230-6.

ABSTRACT

BACKGROUND: Borderline personality disorder (BPD) is considered a disorder of emotion regulation resulting from the expression of a biologically determined emotional vulnerability (that is, heightened sensitivity to emotion, increased emotional intensity/reactivity, and a slow return to emotional baseline) combined with exposure to invalidating environments. Vagal tone has been associated with activity in cortical regions involved in emotion regulation and a lower resting state of vagal tone has been observed in BPD patients relative to healthy controls. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to reduce temper outbursts in adults with Prader-Willi Syndrome, to enhance recognition of emotions in healthy students, and to improve depressive and anxiety symptoms. Furthermore, a single session of taVNS has been shown to acutely alter the recognition of facial expressions of negative valence in adolescents with MDD and increase emotion recognition in controls. However, the effect of taVNS on emotional vulnerability and regulation in individuals diagnosed with BPD has not been investigated. Our aims are to determine if taVNS is effective in acutely reducing emotional vulnerability and improve emotional regulation in BPD patients.

METHODS: Forty-two patients will be randomized to a single session of taVNS or sham-taVNS while going through an affect induction procedure. It will consist of the presentation of one neutral and three negative affect-evoking 4-min-long videos in sequence, each of which is followed by a 4-min post-induction period during which participants will rate the quality and intensity of their current self-reported emotions (post-induction ratings) and the perceived effectiveness in managing their emotions during the video presentation. The rating of the current self-reported emotions will be repeated after every post-induction period (recovery ratings). Mixed models with individuals as random effect will be used to investigate the ratings at each stage of the study, taking into account the repeated measures of the same individuals at baseline, pre-induction, post-induction, and recovery.

DISCUSSION: The study has potential to yield new insights into the role of vagal tone in emotion dysregulation in BPD and offer preliminary data on the effectiveness of taVNS as a possible non-invasive brain stimulation to treat a core symptom of BPD.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05892900. Retrospectively registered on Jun 07, 2023.

PMID:38898522 | PMC:PMC11186228 | DOI:10.1186/s13063-024-08230-6

Auton Neurosci. 2024 Jun 2;254:103192. doi: 10.1016/j.autneu.2024.103192. Online ahead of print.

ABSTRACT

BACKGROUND: Para-sympathetic vagal activation has profound influence on heart rate and other cardiovascular parameters. We tested the hypothesis that transcutaneous Vagal Nerve Stimulation (tVNS) through the auricular branch of the vagus nerve would attenuate the normal sympathetic response to central blood volume reduction by lower body negative pressure (LBNP).

METHOD: 10 healthy volunteers (6 female; age 21 ± 2 years; weight 62 ± 13 kg; height 167 ± 12 cm) were included in this cross-over design trial. After 15 min rest in supine position, subjects underwent three 15-min periods of 30 mmHg LBNP intervention with and without cyclic tVNS stimulation. Continuous cardiovascular parameters (Nexfin) were recorded.

RESULTS: Overall tVNS did not convincingly attenuate sympathetic response to central hypovolemia. Deactivation of the tVNS during LBNP resulted in increased MAP at 2.3 ± 0.5 mmHg (P < 0.001). Comparing the cyclic actual active stimulation periods to periods with pause during tVNS intervention showed a decrease in HR by 72.9 ± 11.2 to 70.2 ± 11.6 bpm (mean ± SD; P < 0.05), and concomitant increases in SV (86.0 ± 12.1 to 87.2 ± 12.6 mL; P < 0.05), MAP (82.9 ± 6.3 to 84.0 ± 6.2 mmHg; P < 0.05) and TPR (1116.0 ± 111.1 to 1153 ± 104.8 dyn*s/cm5; P < 0.05).

CONCLUSION: tVNS in 30 s cycles during LBNP can selectively attenuate HR, prompting a compensatory augmented sympathetic response. It would appear the method used in this study at least, has an isolated cardiac inhibitory effect probably mediated by augmented vagal activity on the sinoatrial or atrio-ventricular node, possibly in combination with reduced activity in the sympathetic cardiac nerve.

PMID:38896931 | DOI:10.1016/j.autneu.2024.103192