Effects of vagal nerve stimulation parameters on heart rate variability in epilepsy patients.

Introduction: Vagal nerve stimulation (VNS) is used as an alternative treatment in drug-resistant epilepsy patients. Effects of VNS on the cardiac autonomic system are controversial. In this study, we aimed to investigate the relationship between VNS parameters and heart rate variability (HRV) in epilepsy patients who underwent VNS treatment. Methods: Our study included 31 patients who underwent VNS for drug-resistant epilepsy. Patients were divided into groups according to response to VNS and VNS parameters. All patients underwent 24-h Holter ECG. Results: The mean age of 31 VNS-treated epilepsy patients included in the study was 33.87 ± 7.6 years. When patients were grouped according to VNS response, 25 patients were in the VNS responder group and six patients were in the VNS-nonresponder group. When comparing Holter parameters in the VNS responder and non-responder groups, the median HF was significantly lower in the VNS responder group. VNS duration and signal frequency had a positive effect on LF/HF, while output and off time had a negative effect on LF/HF. When ROC analysis was performed to determine the cut-off values of the parameters for the VNS-responsive state, the AUC value of the HF parameter was 0.780, which was statistically significant. The cut-off value to distinguish response to VNS was 156.9. Conclusion: In conclusion, the effects of VNS parameters on HRV parameters are quite complex. However, the conclusion is that VNS is a neuromodulation method that affects the autonomic system in a complex way. Different levels of VNS parameters may also contribute to this effect. Furthermore, HRV parameters can be used as biomarkers to predict the patient population that may benefit from VNS.

Polygenic risk for psychotic disorders in relation to cardiac autonomic dysfunction in unmedicated patients with schizophrenia.

Cardiac autonomic dysfunction (CADF), mainly characterized by increased heart rate, decreased heart rate variability, and loss of vagal modulation, has been extensively described in patients with schizophrenia (SCZ) and their healthy first-degree relatives. As such, it represents an apparent physiological link that contributes to the increased cardiovascular mortality in these patients. Common genetic variation is a putative underlying mechanism, along with lifestyle factors and antipsychotic medications. However, the extent to which CADF is associated with genetic factors for SCZ is unknown. A sample of 83 drug-naive SCZ patients and 96 healthy controls, all of European origin, underwent a 30-minute autonomic assessment under resting conditions. We incorporated parameters from several domains into our model, including time and frequency domains (mean heart rate, low/high frequency ratio) and compression entropy, each of which provides different insights into the dynamics of cardiac autonomic function. These parameters were used as outcome variables in linear regression models with polygenic risk scores (PRS) for SCZ as predictors and age, sex, BMI, smoking status, principal components of ancestry and diagnosis as covariates. Of the three CADF parameters, SCZ PRS was significantly associated with mean heart rate in the combined case/control sample. However, this association was was no longer significant after including diagnosis as a covariate (p = 0.29). In contrast, diagnostic status is statistically significant for all three CADF parameters, accounting for a significantly greater proportion of the variance in mean heart rate compared to SCZ PRS (approximately 16% vs. 4%). Despite evidence for a common genetic basis of CADF and SCZ, we were unable to provide further support for an association between the polygenic burden of SCZ and cardiac autonomic function beyond the diagnostic state. This suggests that there are other important characteristics associated with SCZ that lead to CADF that are not captured by SCZ PRS.

Variability of the PR intervals in Wenckebach atrioventricular block.

The duration of the PR intervals in atypical Wenckebach atrioventricular block before and after a non-conducted P wave can exhibit a wide range of values and patterns. Understanding the different or at times puzzling manifestations of Wenckebach atrioventricular block in terms of its PR intervals can avoid diagnostic errors, especially the erroneous more serious diagnosis of Mobitz type II atrioventricular block.

Examining the acute cardiovagal consequences of supine recovery during high-intensity interval exercise.

PURPOSE: Exercise training requires the careful application of training dose to maximize adaptation while minimizing the risk of illness and injury. High-intensity interval training (HIIT) is a potent method for improving health and fitness but generates substantial autonomic imbalance. Assuming a supine posture between intervals is a novel strategy that could enhance physiological readiness and training adaptations. This study aimed to establish the safety and feasibility of supine recovery within a HIIT session and explore its acute effects. METHODS: Fifteen healthy, active males (18-34 years) underwent assessment of cardiopulmonary fitness. Participants completed two identical HIIT treadmill sessions (4 x [3 min at 95% VO2max, 3 min recovery]) employing passive recovery in standing (STANDard) or supine (SUPER) posture between intervals. Heart rate variability (HRV), HRV recovery (HRVrec; lnRMSSD) and heart rate recovery at 1 min (HRrec) were assessed using submaximal constant speed running tests (CST) completed prior to, immediately after and 24 h following HIIT. RESULTS: No severe adverse events occurred with SUPER, and compliance was similar between conditions (100 ± 0%). The change in HRVrec from the CST pre-to-post-HIIT was not different between conditions (p = 0.38); however, HRrec was faster following SUPER (39 ± 7 bpm) vs. STANDard (36 ± 5 bpm). HRV 24 h post-SUPER was also greater (3.56 ± 0.57 ms) compared to STANDard (3.37 ± 0.42 ms). Despite no differences in perceived exertion (p = 0.23) and blood lactate levels (p = 0.35) between SUPER and STANDard, average running HRs were lower (p = 0.04) with SUPER (174 ± 7 bpm) vs. STANDard (176 ± 7 bpm). CONCLUSIONS: Supine recovery within HIIT attenuates acute cardioautonomic perturbation and accelerates post-exercise vagal reactivation. SUPER enhances recovery of vagal modulation, potentially improving physiological preparedness 24 h post-HIIT. Further research exploring the chronic effects of SUPER are now warranted.

Valsalva Maneuver Versus Carotid Sinus Massage for Supraventricular Tachycardia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Supraventricular tachycardia (SVT) is one of the most common cardiac arrhythmias, characterized by a sudden increase in heart rate. Initial management often involves vagal maneuvers, including the Valsalva maneuver (VM) and carotid sinus massage (CSM). VM can be categorized into standard VM (sVM) and modified VM (mVM). This study aimed to synthesize the first evidence from published randomized controlled trials (RCTs) comparing the efficacy of VM versus CSM. A comprehensive search across databases, including PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar, was conducted up to July 29, 2024. The primary endpoint was the success rate of converting SVT to sinus rhythm. The dichotomous outcome was analyzed using a fixed-effect model to calculate the risk ratio (RR) and 95% confidence intervals (CI). The Risk of Bias (RoB) tool, version 2, was employed to assess bias in the included RCTs. In total, three RCTs with 346 cases were analyzed. Concerns were noted regarding potential bias related to the randomization process in all three studies. The meta-analysis of these RCTs (comprising four arms) revealed that VM had a higher success rate than CSM for treating SVT, with an RR of 1.82 (95% CI: 1.29-2.57, p<0.001). Subgroup analysis showed that the rate of conversion to sinus rhythm was significantly higher in the sVM compared to CSM (RR=1.61, 95% CI (1.13-2.29), p=0.01). Additionally, subgroup analysis of one study indicated that mVM was associated with a higher rate of SVT conversion to sinus rhythm compared to CSM (RR=9.28, 95% CI (1.25-69.13), p=0.03). In conclusion, VM demonstrated a higher success rate compared to CSM in treating SVT. Specifically, mVM was more effective than CSM in both terminating SVT and restoring sinus rhythm, though this evidence was based on a single RCT; hence, the related conclusion should be interpreted with caution and requires validation using additional RCTs. Further research in diverse patient populations and clinical settings is necessary to validate these findings and potentially support the broader use of mVM in practice. Additional well-designed, multi-center studies with diverse populations are needed to confirm these observations and provide more comprehensive guidance on SVT management. This is important to enhance the generalizability of results across different demographics and clinical settings. This approach helps ensure that treatment effectiveness is applicable to a broader range of patients, accounting for variations in age, gender, comorbidities, and regional practices.

Intravenous Bolus Injection of Fentanyl Triggers an Immediate Central and Upper Airway Obstructive Apnea via Activating Vagal Sensory Afferents.

Intravenous bolus (IVb) injection of fentanyl induces an immediate apnea, but the characteristics of the apnea and relevant mechanism remain unclear. Here, we tested whether IVb injection of fentanyl induced an immediate central and upper airway obstructive apnea associated with chest wall rigidity via activating vagal C-fibers (VCFs) and vagal afferent opioid receptors (ORs). Cardiorespiratory and electromyography of external and internal intercostal, thyroarytenoid and superior pharyngeal constrictor muscles (EMGEI, EMGII, EMGTA and EMGSPC) responses to IVb injection of fentanyl were recorded in anesthetized and spontaneously breathing rats with or without bilateral peri-vagal capsaicin treatment or intra-vagal microinjection of naloxone. Immunohistochemical approach was employed to define the presence of opioid mu-receptor (MOR) expression in vagal C-neurons and a patch clamp technique utilized to determine the evoked current responses of vagal C-neurons to fentanyl in vitro. Fentanyl induced an immediate apnea and subsequent respiratory depression. The apnea was characterized by cessation of EMGEI activity and augmentation of tonic discharges of EMGII, EMGTA, and EMGSPC, i.e., central expiratory apnea, laryngeal closure and pharyngeal constriction/collapse accompanied with chest wall rigidity. The apneic response was abolished by blockade of VCF signal conduction and largely attenuated by antagonism of vagal afferent ORs. The latter significantly alleviated the initial (within 5 min post injection), but not the later, respiratory depression. Vagal C-neurons expressed MORs and were activated by fentanyl. We conclude that IVb injection of fentanyl causes a VCF- and vagal afferent OR-mediated immediate central apnea, upper airway obstruction and chest wall rigidity.

Vagal sensory neuron-derived FGF3 controls insulin secretion.

Vagal nerve stimulation has emerged as a promising modality for treating a wide range of chronic conditions, including metabolic disorders. However, the cellular and molecular pathways driving these clinical benefits remain largely obscure. Here, we demonstrate that fibroblast growth factor 3 (Fgf3) mRNA is upregulated in the mouse vagal ganglia under acute metabolic stress. Systemic and vagal sensory overexpression of Fgf3 enhanced glucose-stimulated insulin secretion (GSIS), improved glucose excursion, and increased energy expenditure and physical activity. Fgf3-elicited insulinotropic and glucose-lowering responses were recapitulated when overexpression of Fgf3 was restricted to the pancreas-projecting vagal sensory neurons. Genetic ablation of Fgf3 in pancreatic vagal afferents exacerbated high-fat diet-induced glucose intolerance and blunted GSIS. Finally, electrostimulation of the vagal afferents enhanced GSIS and glucose clearance independently of efferent outputs. Collectively, we demonstrate a direct role for the vagal afferent signaling in GSIS and identify Fgf3 as a vagal sensory-derived metabolic factor that controls pancreatic ß-cell activity.

Effect of Neurostimulation on Chronic Pancreatic Pain: A Systematic Review.

BACKGROUND: Chronic pancreatic pain is one of the most severe causes of visceral pain, and treatment response is often limited. Neurostimulation techniques have been investigated for chronic pain syndromes once there are pathophysiological reasons to believe that these methods activate descending pain inhibitory systems. Considering this, we designed this systematic literature review to investigate the evidence on neuromodulation techniques as a treatment for chronic pancreatic pain. MATERIALS AND METHODS: We performed a literature search using the databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase until April 2024. The included studies used neurostimulation techniques in participants with chronic pancreatic pain and reported pain-related outcomes, with a focus on pain scales and opioid intake. Two reviewers screened and extracted data, and a third reviewer resolved discrepancies. We assessed the risk of bias using the Jadad scale. The authors then grouped the findings by the target of the neurostimulation, cortex, spinal cord, or peripheral nerves; described the findings qualitatively in the results section, including qualitative data reported by the articles; and calculated effect sizes of pain-related outcomes. RESULTS: A total of 22 studies were included (7 randomized clinical trials [RCTs], 14 case series, and 1 survey), including a total of 257 clinical trial participants. The two outcomes most commonly reported were pain, measured by the visual analogue scale (VAS), numeric rating scale (NRS), and pressure pain threshold scores, and opioid intake. Two RCTs investigated repetitive transcranial magnetic stimulation (rTMS), showing a reduction of 36% (±16) (d = 2.25; 95% CI, 0.66-3.83) and 27.2% (±24.5%) (d = 2.594; 95% CI, 1.303-3.885) in VAS pain scale. In another clinical trial, transcranial direct-current stimulation (tDCS) and transcranial pulsed current stimulation were not observed to effect a significant reduction in VAS pain (χ2 = 5.87; p = 0.12). However, a complete remission was reported in one tDCS case. Spinal cord stimulation (SCS) and dorsal root ganglion stimulation were performed in a survey and 11 case series, showing major pain decrease and diminished opioid use in 90% of participants after successful implantation; most studies had follow-up periods of months to years. Two noninvasive vagal nerve stimulation (VNS) RCTs showed no significant pain reduction in pain thresholds or VAS (d = 0.916; 95% CI, -0.005 to 1.838; and d = 0.17; -0.86 to 1.20; p = 0.72; respectively). Splanchnic nerve stimulation in one case report showed complete pain reduction accompanied by discontinuation of oral morphine and fentanyl lozenges and a 95% decrease in fentanyl patch use. Two RCTs investigated transcutaneous electrical nerve stimulation (TENS). One found a significant pain reduction effect with the NRS (d = 1.481; 95% CI, 1.82-1.143), and decreased opioid use, while the other RCT did not show significant benefit. Additionally, one case report with TENS showed pain improvement that was not quantitatively measured. DISCUSSION: The neuromodulation techniques of rTMS and SCS showed the most consistent potential as a treatment method for chronic pancreatic pain. However, the studies have notable limitations, and SCS has had no clinical trials. For VNS, we have two RCTs that showed a non-statistically significant improvement; we believe that both studies had a lack of power issue and suggest a gap in the literature for new RCTs exploring this modality. Additionally, tDCS and TENS showed mixed results. Another important insight was that opioid intake decrease is a common trend among most studies included and that adverse effects were rarely reported. To further elucidate the potential of these neurostimulation techniques, we suggest the development of new clinical trials with larger samples and adequate sham controls.

Atypical Presentation and Postoperative Management of Vagal Nerve Tumors.

OBJECTIVES: Tumors involving the vagus nerve are often clinically silent. We offer a case series with different clinical presentations and distinctive post-surgical sequelae that highlight some of the challenges associated with managing cervical vagal nerve tumors. METHODS: Single-institution, retrospective review of patients with tumors involving the vagus nerve. We describe clinical presentations and postoperative sequelae of five patients who underwent surgical management of vagal nerve pathology with atypical presentation or subsequent clinical course. RESULTS: Here, we present five patients treated at our institution for vagal tumors. In four of the five patients, the presenting symptoms resolved after surgery. Two patients presented with intractable neurogenic cough, and another two presented with autonomic symptoms, one with syncope/palpitations and the other with intractable sweating. The final patient presented with a rapidly enlarging vagal paraganglioma and developed intractable cough after resection. We present two patients with novel approach to vagal paragangliomas that underwent ligation of feeding blood supply without removing the tumor, resulting in resolution of an intractable cough in one patient and resolution of severe nighttime sweating in the other. CONCLUSION: Management of tumors associated with the cervical vagus nerve that present with symptoms or rapid growth poses a clinical dilemma. Consideration of the tumor origin with either enucleation of schwannomas or ligation of feeding vessels may preserve function while addressing the presenting symptoms.

Robust and time-resolved estimation of cardiac sympathetic and parasympathetic indices.

The time-resolved analysis of heart rate (HR) and heart rate variability (HRV) is crucial for the evaluation of the dynamic changes of autonomic activity under different clinical and behavioral conditions. Standard HRV analysis is performed in the frequency domain because the sympathetic activations tend to increase low-frequency HRV oscillations, while the parasympathetic ones increase high-frequency HRV oscillations. However, a strict separation of HRV in frequency bands may cause biased estimations, especially in the low frequency range. To overcome this limitation, we propose a robust estimator that combines HR and HRV dynamics, based on the correlation of the Poincaré plot descriptors of interbeat intervals from the electrocardiogram. To validate our method, we used electrocardiograms gathered from open databases where standardized paradigms were applied to elicit changes in autonomic activity. Our proposal outperforms the standard spectral approach for the estimation of low- and high-frequency fluctuations in HRV, and its performance is comparable to newer methods. Our method constitutes a valuable, robust, time-resolved, and cost-effective tool for a better understanding of autonomic activity through HR and HRV in healthy state and potentially for pathological conditions.

tVNS alters inflammatory response in adult VPA-induced mouse model of autism: evidence for sexual dimorphism.

Autism is a neurodevelopmental disorder with limited treatment alternatives and which incidence is increasing. Some research suggests that vagus nerve simulation might lead to the reduction of certain symptom. Therefore, we aimed to examine the effect of bilateral transcutaneous auricular vagus nerve stimulation (tVNS) on the inflammatory response in an adult valproic acid (VPA) induced mouse (C57BL6) model of autism for the first time. The autism model was induced by oral VPA administration (600 mg·kg-1) to C57BL/6 pregnant mice on E12.5 days. The study included three groups: the VPA Transcutaneous Auricular Stimulation Group (VPA + tVNS), the VPA Control Group (VPA + sham), and the Healthy Control Group (Control + sham). Each group included 16 mice (8 M/8 F). Our results show that serum IL-1ß and IL-6 levels were significantly higher in male VPA-exposed mice than controls. However, IL-1ß was significantly lower, and IL-6, TNF- α, and IL-22 were not different in female VPA-exposed mice compared to the control group. Brain NLRP3 levels were significantly higher in both sexes in the VPA autism model (P < 0.05). tVNS application increased brain NLRP3 levels in both sexes and reduced serum IL-1ß levels in male mice. We conclude that cytokine dysregulation is associated with the VPA-induced adult autism model, and the inflammatory response is more pronounced in male mice. tVNS application altered the inflammatory response and increased brain NLPR3 levels in both sexes. Further studies are needed to understand the beneficial or detrimental role of the inflammatory response in autism and its sexual dimorphism.

MrgprC11+ Jugular Neurons Control Airway Hyperresponsiveness in Allergic Airway Inflammation.

The lung is densely innervated by sensory nerves, the majority of which are derived from the vagal sensory neurons. Vagal ganglia consist of two different ganglia, termed nodose and jugular ganglia, with distinct embryonic origins, innervation patterns, and physiological functions in the periphery. Since nodose neurons constitute the majority of the vagal ganglia, our understanding of the function of jugular nerves in the lung is very limited. This study aims to investigate the role of MrgprC11+ jugular sensory neurons in a mouse allergic asthma model. Our previous study has shown that MrgprC11+ jugular neurons mediate cholinergic bronchoconstriction. In this study, we found that in addition to MrgprC11, several other Mrgpr family members including MrgprA3, MrgprB4, and MrgprD are also specifically expressed in the jugular sensory neurons. MrgprC11+ jugular neurons exhibit dense innervation in the respiratory tract including the larynx, trachea, proximal, and distal bronchus. We also found that receptors for IL-4 and oncostatin M, two critical cytokines promoting allergic airway inflammation, are mainly expressed in jugular sensory neurons. Both IL-4 and oncostatin M can sensitize the neuronal responses of MrgprC11+ jugular neurons. Moreover, ablation of MrgprC11+ neurons significantly inhibited airway hyperresponsiveness in the asthmatic lung, demonstrating the critical role of MrgprC11+ neurons in controlling airway constriction. Our results emphasize the critical role of jugular sensory neurons in respiratory diseases.

Mixing transcutaneous vagal nerve stimulation and galvanic cutaneous stimulation to decrease simulator adaptation syndrome.

Purpose: Simulator Adaptation Syndrome arises from a perceptual discordance between expected and actual motion, giving rise to symptoms such as nausea and disorientation. This research focused on determining the benefit of Transcutaneous Vagal Nerve Stimulation (tVNS) and Galvanic Cutaneous Stimulation (GCS), where both were applied in conjunction, as compared to their administration in isolation, to decrease Simulator Adaptation Syndrome (SAS). Method: A driving simulation study was proposed where SAS, body balance, and driving performance were measured. These measurements were taken during seven different stimulation scenarios with a baseline condition without stimulation compared against tVNS and GCS conditions. Results: The main result showed that the combination of tVNS and GCS reduced SAS and improved body balance and driving performance more successfully than their administration in isolation. Conclusion: Similar neuromodulation in the temporoparietal junction is proposed to mitigate SAS for GCS and tVNS (although additional explanations are discussed). Applying both techniques simultaneously is encouraged to decrease SAS in future interventions.

Comparison of Heart Rate Variability Psychological Responses and Performance in Virtual and Real Archery.

BACKGROUND: This study examines the psychophysiological differences between virtual reality (VR) and real archery. It explores whether VR archery induces heart rate (HR), heart rate variability (HRV), and breathing rates similar to those experienced in real archery. Additionally, the study assesses differences in perceived anxiety, difficulty, confidence, rate of perceived exertion (RPE), and shooting performance between the two modalities, providing insights into the efficacy of VR as a training tool for archery. METHODS: Twenty-two (women: 8) individuals aged 20-24 participated in the study. We first recorded individuals' resting HR, HRV, and breathing rates during baseline. Afterward, participants shot 10 real and virtual arrows from 18 m, whereas their HR, HRV, and breathing rate were measured, each lasting 4 min. Performance in VR and real archery was determined separately as the sum of the shots. We performed paired sample t-tests to compare individuals' performance, psychological, and psychophysiological responses recorded during VR and real arrow shooting. Afterward, we compared percentage changes between VR and real archery. RESULTS: Results showed that HR and root mean square of successive differences (RMMSD) were significantly higher during real archery compared to virtual archery. In addition, VR archery led to a greater percentage change in RMSSD compared to real archery. Participants reported greater RPE and perceived difficulty after real archery. Performance was also higher during VR archery than real archery. CONCLUSIONS: Consequently, the results of the present study illustrated that VR, and real archery might lead to different autonomic response patterns in terms of vagal activity.

Refractory Obstructive Sleep Apnea Secondary to Vagal Nerve Stimulation.

Vagal nerve stimulator (VNS) devices are commonly used as a non-pharmacologic option for improved seizure control in patients with refractory epilepsy. However, a side effect associated with VNS device placement includes sleep-disordered breathing, which is complicated by the fact that a significant minority of patients with epilepsy have sleep-disordered breathing. We describe a patient with iatrogenically worsened refractory obstructive sleep apnea (OSA) secondary to VNS device placement, which resolved upon turning off the VNS device. This case highlights the need to screen for OSA in patients who are candidates for VNS device placement, as iatrogenic sleep-disordered breathing could place the patient at risk for adverse clinical outcomes, as well as paradoxically worsen seizure control due to poor quality sleep.

Inter-Organ Communication Involved in Brown Adipose Tissue Thermogenesis.

Brown and beige adipocytes produce heat from substrates such as fatty acids and glucose. Such heat productions occur in response to various stimuli and are called adaptive non-shivering thermogenesis. This review introduces mechanisms known to regulate brown and beige adipocyte thermogenesis. Leptin and fibroblast growth factor 21 (FGF21) are examples of periphery-derived humoral factors that act on the central nervous system (CNS) and increase brown adipose tissue (BAT) thermogenesis. Additionally, neuronal signals such as those induced by intestinal cholecystokinin and hepatic peroxisome proliferator-activated receptor γ travel through vagal afferent-CNS-sympathetic efferent-BAT pathways and increase BAT thermogenesis. By contrast, some periphery-derived humoral factors (ghrelin, adiponectin, plasminogen activator inhibitor-1, and soluble leptin receptor) act also on CNS but inhibit BAT thermogenesis. Neuronal signals also reduce BAT sympathetic activities and BAT thermogenesis, one such example being signals derived by hepatic glucokinase activation. Beige adipocytes can be induced by myokines (interleukin 6, irisin, and ß-aminoisobutyric acid), hepatokines (FGF21), and cardiac-secreted factors (brain natriuretic peptide). Cold temperature and leptin also stimulate beige adipocytes via sympathetic activation. Further investigation on inter-organ communication involving adipocyte thermogenesis may lead to the elucidation of how body temperature is regulated and, moreover, to the development of novel strategies to treat metabolic disorders.

Heart Rate and Its Variability Are Associated With Resting Metabolic Rate and Substrate Oxidation in Young Women but Not in Men.

BACKGROUND: This study aims to examine the relationship between resting vagal-related heart rate variability (HRV) parameters and heart rate (HR) with resting metabolic rate (RMR) and respiratory exchange ratio (RER) in young adults. METHODS: A total of 74 young adults (22 ± 2 years old, 51 women) were included in this cross-sectional study. HRV was assessed using a HR monitor, whereas RMR and RER were determined by indirect calorimetry. RESULTS: Linear regression analyses showed a positive association between HR and RER in women (standardized ß = 0.384, p = 0.008), while negative associations were observed between vagal-related HRV parameters and RER in women (ß ranged from -0.262 to -0.254, all p ≤ 0.042). No significant association was found between the abovementioned physiological parameters in men. CONCLUSION: Here, we show that HR is positively associated with RER in young women but not in men, while vagal-related HRV parameters are inversely related to RMR, therefore suggesting a potential sexual dimorphism between cardiac rhythm and its relationship with markers of cardiometabolic health status. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02365129.

A single-session stereotactic radiosurgery for vagal paraganglioma: Effective tumor reduction and innovative treatment option.

Background: Vagal paragangliomas (VPs) are rare tumors in the upper cervical region. Although surgical resection is the standard treatment for these tumors, it carries significant risks due to the tumor's high vascularity and proximity to vital structures. Stereotactic radiosurgery (SRS) for skull base paraganglioma could be a minimally invasive alternative. Case Description: We report the case of a 47-year-old man with a large, asymptomatic VP who was successfully treated with SRS with Gamma Knife Icon, which was performed in the parapharyngeal space (volume: 25.7 mL) using a marginal dose of 14 Gy to the 45% isodose line. This case illustrates the successful treatment of a lesion near the conventional limits (lower limit of C2 vertebral body) using noninvasive mask fixation. Excellent tumor control without neurological deficits was achieved for 25 months after SRS. The tumor volume decreased by 70% (final volume: 7.6 mL). Conclusion: This study demonstrates the utility of Gamma Knife Icon, which facilitates optimal SRS for upper cervical lesions, including VPs.

An Unusual and Discrepant Presentation of a Skull Base Paraganglioma.

Paragangliomas are rare tumors of neuroendocrine origin. Within the head and neck, these tumors are slow-growing and locally destructive, with a small malignant potential. Vagal paragangliomas (VPs) originate from paraganglia around the vagus nerve, typically at the level of the skull base. Cranial nerve deficits are common at presentation, with the vagus nerve and hypoglossal nerves being most affected. Similarly, hypoglossal paragangliomas (HPs) originate from around the hypoglossal nerve but are extremely rare and less documented. We describe the case of a patient presenting with an isolated hypoglossal nerve palsy in the setting of a tumor that radiologically represents a VP. A descriptive literature review was conducted to highlight presentation, management, and outcomes related to this pathology. A 65-year-old male presented to the clinic with tongue fasciculations and several years of dysarthria. Physical examination showed intermittent right tongue fasciculations in addition to ipsilateral hemi-atrophy. A computed tomography scan with contrast revealed an enhancing skull base mass inferior to the right carotid space. Subsequently, magnetic resonance imaging with contrast further delineated its anatomic involvement and site of origin, allowing for the diagnosis of a VP. After further discussion with the patient about his clinical findings, the decision was made to proceed with observation and serial imaging. Skull base paragangliomas are a rare pathologic entity that may pose a challenging multidisciplinary approach to optimize management strategies. Treatment may vary on a case-by-case basis and is dependent on patient and tumor characteristics.

Head and neck paragangliomas: Recent advances in translational and clinical research and guidelines for patient care.

Head and neck paragangliomas (HNPGLs), rare neuroendocrine tumors that mainly arise from parasympathetic ganglia along the cranial nerves, are challenging due to anatomic origin, tendency to aggressive neurovascular and skull base infiltration, unpredictable metastatic potential, radio-chemoresistance, and risk of multiplicity. Symptoms range from mild to life threatening depending on location/size, but rarely relate to catecholamine excess. Risk factors include female sex and pathogenic germline variants in genes affecting hypoxia signaling (foremost succinate dehydrogenase genes). Diagnostic work-up relies on imaging, measurements of plasma free metanephrines/methoxytyramine, genetic testing, and pathology/immunohistochemistry. Management is tailored to patient/tumor characteristics and encompasses wait-scan, upfront surgery, debulking surgery, and radiotherapy. Presurgical embolization is recommended, except for small tympanic and tympanomasoid tumors. Presurgical stenting is required for internal carotid artery involvement, and two-stage surgery for intradural extension. Current treatments for metastatic/inoperable HNPGL are non-curative, and long-term follow-up should be recommended for all patients to monitor local recurrence and new tumors.