BACKGROUND: According to the current Parkinson\'s Disease (PD) pathogenesis hypotheses, the vagus nerve (VN) is essential for disease development. It has been identified as a main entry point for misfolded α-synuclein to the central nervous system, and surgical vagotomy appears to limit disease progress both in animal models and in humans. A recent approach tried to assess VN size in PD patients via neck ultrasonography, but the clinical value of this method is yet to be established.
BACKGROUND: A systematic search of the MEDLINE, Scopus, and Web of Science databases was conducted, and 12 case- -control studies were included. Meta-analysis revealed a modest reduction in VN size in PD (effect size - 0.79 SD (95%CI [-1.34, -0.25] p = 0.004)). The atrophy was more pronounced on the right side, and the nerve was smaller in females. In PD patients, VN reduction correlated with cardiac parasympathetic function decline and with advances in motor ratings. The discrimination potential for PD diagnosis, and any association with other non-motor domains, remains unclear.
CONCLUSIONS: VN atrophy in PD could be detected by ultrasound imaging. However, the clinical significance of this phenomenon has yet to be clarified. Size reduction is not readily apparent and is individually variable. However, it may be considered a promising means to improve early PD diagnosis and the recognition of autonomic dysfunction.
CONCLUSIONS: With more extensive research, VN sonography could provide useful evidence regarding disease origins. Imaging should be performed together with a profound clinical assessment and biomarker testing to establish the role to be played by this method in future practice.

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.

Currently, clinical practice and scientific research mostly revolve around a single disease or system, but the single disease-oriented diagnostic and therapeutic paradigm needs to be revised. This review describes how transcutaneous auricular vagus nerve stimulation (taVNS), a novel non-invasive neuromodulation approach, connects the central and peripheral systems of the body. Through stimulation of the widely distributed vagus nerve from the head to the abdominal cavity, this therapy can improve and treat central system disorders, peripheral system disorders, and central-peripheral comorbidities caused by autonomic dysfunction. In the past, research on taVNS has focused on the treatment of central system disorders by modulating this brain nerve. As the vagus nerve innervates the heart, lungs, liver, pancreas, gastrointestinal tract, spleen and other peripheral organs, taVNS could have an overall modulatory effect on the region of the body where the vagus nerve is widespread. Based on this physiological basis, the authors summarize the existing evidence of the taVNS ability to regulate cardiac function, adiposity, glucose levels, gastrointestinal function, and immune function, among others, to treat peripheral system diseases, and complex diseases with central and peripheral comorbidities. This review shows the successful examples and research progress of taVNS using peripheral neuromodulation mechanisms from more perspectives, demonstrating the expanded scope and value of taVNS to provide new ideas and approaches for holistic therapy from both central and peripheral perspectives.

Roemheld syndrome (RS) is a condition that triggers cardiac symptoms due to gastrointestinal compression of the heart. It is often misdiagnosed as other types of cardiac or digestive disorders, leading to unnecessary treatments and reduced quality of life. Here, we provide a thorough review of RS, covering its pathogenesis, etiology, diagnosis, treatment, and outcome. We found that a number of conditions, including gallstones, hiatal hernia, excessive gas, and gastroesophageal reflux syndrome, can cause RS. The symptoms of RS can include chest pain, palpitations, shortness of breath, nausea, vomiting, bloating, and abdominal pain. Clinical history, physical examination, electrocardiograms, and improvement in symptoms following gastrointestinal therapy can all be used to identify RS. We also propose a set of criteria, the IKMAIR criteria, to improve the diagnostic approach for this condition. Dietary changes, lifestyle adjustments, pharmaceutical therapies, and surgical procedures can all be used to control RS. Depending on the underlying etiology and the outcome of treatment, RS has a varying prognosis. We conclude that RS is a complicated and understudied disorder that needs more attention from researchers and patients as well as from medical professionals. We recommend the inclusion of RS in the differential diagnosis for individuals with gastrointestinal problems and unexplained cardiac symptoms. Additionally, we advise treating RS holistically by attending to its cardiac and gastrointestinal components.
UNASSIGNED: Das Roemheld-Syndrom (RS) ist eine Erkrankung, die kardiale Symptome durch eine gastrointestinale Kompression des Herzens auslöst. Häufig wird es als andere Arten von Erkrankungen des Herzens oder des Verdauungstrakts verkannt, was zu unnötigen Behandlungen und einer verminderten Lebensqualität führt. Im vorliegenden Beitrag wird eine umfassende Übersicht über das RS gegeben, einschließlich Pathogenese, Ätiologie, Diagnose, Therapie und Verlauf. Die Autoren stellten fest, dass eine Reihe von Erkrankungen, wie Gallensteine, Hiatushernie, ausgeprägte Blähungen und gastroösophageales Refluxsyndrom, ein RS verursachen können. Zu den Symptomen des RS können Schmerzen in der Brust, Palpitationen, Kurzatmigkeit, Übelkeit, Erbrechen, Blähungen und Bauchschmerzen gehören. Zur Feststellung eines RS eignen sich die klinische Anamnese, körperliche Untersuchung, EKG und eine Symptomlinderung nach gastrointestinaler Therapie. Die Autoren schlagen auch eine Reihe von Kriterien vor, die IKMAIR-Kriterien, um den diagnostischen Ansatz bei dieser Erkrankung zu verbessern. Veränderungen bei der Ernährung, in der Lebensweise, medikamentöse Therapien und chirurgische Eingriffe können zur Beherrschung des RS eingesetzt werden. Je nach zugrunde liegender Ätiologie und Ergebnis der Behandlung weist das RS eine unterschiedlich Prognose auf. Die Autoren kommen zu dem Schluss, dass RS eine komplizierte und zu wenig erforschte Erkrankung ist, die mehr Aufmerksamkeit von Wissenschaftlern und Patienten sowie von Ärzten benötigt. Sie empfehlen bei Personen mit gastrointestinalen Beschwerden und unerklärlichen kardialen Symptomen die Einbeziehung von RS in die Differenzialdiagnose. Darüber hinaus raten sie dazu, das RS ganzheitlich zu behandeln, indem auch die kardialen gastrointestinalen Komponenten berücksichtigt werden.

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The goal of this review is to synthesize the literature on vagus nerve stimulator (VNS)-related changes in heart rate variability (HRV) in patients with drug-resistant epilepsy (DRE) and assess the role of these changes in seizure relief. A scoping literature review was performed with the following inclusion criteria: primary articles written in English, involved implantable VNS in humans, and had HRV as a primary outcome. Twenty-nine studies were retrieved, however with considerable heterogeneity in study methods. The overall depression in HRV seen in DRE patients compared to healthy controls persisted even after VNS implant, indicating that achieving \"healthy\" HRV is not necessary for VNS therapeutic success. Within DRE patients, changes in frequency domain parameters six months after VNS implant returned to baseline after a year. The mechanism of how VNS reduces seizure burden does not appear to be significantly related to alterations in baseline HRV. However, the subtlety of sympathetic/parasympathetic signaling likely requires a more structured approach to experimental and analytic techniques than currently found in the literature.

OBJECTIVE: The aim of this systematic review and meta-analysis was to systematically review and perform a meta-analysis on the anatomical variations of the RLN.
METHODS: We performed online research for studies that addressed anatomical variations of the RLN and laterality, published between 2015 and 2021. We found 230 articles, and nine were included.
RESULTS: Eight variations were found, with Type I prevailing (41.17%; 95% CI 19.44-64.88), extra laryngeal divergence of the RLN. The other types were: II-fan shape; III-distance greater than 5 mm to the cricothyroid joint; IV-thickening and adipopexy in the elderly; V-non-recurrent laryngeal nerve; VI-intracranial branch; VII-tortuous ascending RLN; and VIII-combination between the inferior branch of the NV and the ascending trunk of the RLN. Types I (p = 0) and III (p < 0.01) prevailed on the left and types II (p < 0.01) and V (p < 0.01) on the right.
CONCLUSIONS: It was observed that variations occurred due to the path of the RLN to the entrance to the larynx, its shape, and the age of the evaluated individual. The most frequent variation and side were, respectively, Type I, extra laryngeal divergence and left.

Vagus nerve stimulation (VNS) has been identified as an innovative immunosuppressive treatment strategy in rodent studies. However, its\' clinical potential is still unclear. Therefore, we aimed to assess whether VNS can reduce inflammatory proteins and/or immune cells in humans, through a pre-registered systematic review and meta-analysis according to PRISMA guidelines. The databases Cochrane, Pubmed and World of Knowledge were searched in duplicate up to the 3rd of March 2022 and publications from identified clinical trial registrations were identified until 20th of August 2023. Studies were included if they provided peer-reviewed data for humans who received VNS as short-term (<=1 day) or long-term (>=2 days-365 days) stimulation and reported at least one cytokine or immune cell after treatment.Screening of title, abstract, full text, and data extraction was performed in duplicate by two independent reviewers. Data were pooled using a random-effects model and meta-regression was performed for moderating factors. Reporting bias was assessed. The standardized mean difference (Hedge\'s g) was used to indicate overall differences of cytokine data (mean and standard deviation or median and interquartile range at the study level) to test our a-priori hypothesis. The systematic review of 36 studies with 1135 participants (355 receiving a control/sham condition and 780 receiving VNS) revealed anti-inflammatory effects of VNS for cytokines in several reports, albeit often in subgroup analyses, but our meta-analyses of 26 studies did not confirm these findings. Although most cytokines were numerically reduced, the reduction did not reach statistical significance after VNS: not in the between-group comparisons (short-term: TNF-α: g = -0.21, p = 0.359; IL-6: g = -0.94, p = 0.112; long-term: TNF-α: g = -0.13, p = 0.196; IL-6: g = -0.67, p = 0.306); nor in the within-study designs (short-term: TNF-α: g = -0.45, p = 0.630; IL-6: g = 0.28, p = 0.840; TNF-α: g = -0.53, p = 0.297; IL-6:g = -0.02, p = 0.954). Only the subgroup analysis of 4 long-term studies with acute inflammation was significant: VNS decreased CRP significantly more than sham stimulation. Additional subgroup analyses including stimulation duration, stimulation method (invasive/non-invasive), immune stimulation, and study quality did not alter results. However, heterogeneity was high, and most studies had poor to fair quality. Given the low number of studies for each disease, a disease-specific analysis was not possible. In conclusion, while numeric effects were reported in individual studies, the current evidence does not substantiate the claim that VNS impacts inflammatory cytokines in humans. However, it may be beneficial during acute inflammatory events. To assess its full potential, high-quality studies and technological advances are required.

Stroke is a devastating cerebrovascular pathology with high morbidity and mortality. Inflammation plays a central role in the pathophysiology of stroke. Vagus nerve stimulation (VNS) is a promising immunomodulatory method that has shown positive effects in stroke treatment, including neuroprotection, anti-apoptosis, anti-inflammation, antioxidation, reduced infarct volume, improved neurological scores, and promotion of M2 microglial polarization. In this review, we summarize the current knowledge about the vagus nerve\'s immunomodulatory effects through the cholinergic anti-inflammatory pathway (CAP) and provide a comprehensive assessment of the available experimental literature focusing on the use of VNS in stroke treatment.