Left Vagus Research Articles

Asymmetric Control of Food Intake by Left and Right Vagal Sensory Neurons

Gut‐innervating vagal sensory neurons residing in the nodose ganglia (NG) conveys meal‐borne signals and control food intake, however, the underlying gut‐brain neurocircuit is unclear. The neuropeptide cocaine‐ and amphetamine‐regulated transcript (CART) is expressed in a subpopulation of vagal sensory neurons (~40%) that innervate the whole length of the gut and its release in the NTS is sufficient for meal termination. Thus, it can be an excellent target to understand the role of sensory neurons in feeding. Emerging evidence suggests that right or left NG (LNG or RNG) neurons recruit different downstream central circuits to control feeding, but the mechanisms remain poorly understood. Our hypothesis is that LNGCART and RNGCART neurons sense different meal‐related signals and are necessary and sufficient to modulate feeding.MethodsIn vivo calcium imaging, viral neuronal tracing, and feeding behaviors were assessed in response to chemo‐ and opto‐genetic stimulation of gut‐innervating vagal sensory neurons using CARTcre mice.ResultsAnatomical tracing revealed that LNGCART and RNGCART neurons innervate different regions of the duodenum (n=3). LNGCART innervate the muscular layer, while RNGCART innervate the villi. Importantly, 2‐photon calcium imaging highlighted real time increased activity in LNGCART in response to stretch, while intraduodenal fat infusions preferentially increased RNGCART neuron activity (n=7/group). Mice with LNGCART neurons ablation consumed higher volumes of liquid meal indicative of attenuated response to gastric and intestinal distension (n=6‐7/group). Furthermore, chemogenetic stimulation of LNGCART, but not RNGCART, caused pronounced and sustained hypophagia (n=7/group). Interestingly, mice with chemogenetic activation of RNGCART, but not LNGCART, increased flavor conditioning (n=7/group), while ablation of RNGCART neurons abolished the conditioned flavor preference that was paired with intragastric fat infusion (n=7/group) supporting their role in reward. In addition, optogenetic stimulation of RNGCART promoted self‐stimulation in a nose poke task (n=4). Lastly, dopaminergic neurons of the substantia nigra increased their firing rate in response to intraduodenal fat infusion, but not duodenal distension (n=2/group).ConclusionLeft and right vagus nerves provide different sensory information about a meal to the brain. Both anatomical and behavioral feeding studies support the necessity and sufficiency LNGCART neurons as food quantity detectors and RNGCART neurons as food reward mediators ‐ which has less influence on how much is consumed but rather plays a role in the decision‐making process about which foods to consume. Our findings on asymmetrical vagal innervation of the gut provides new mechanistic insight for how feeding decisions are made in response to vast and complex meal‐related signals.

Ultraflexible and Stretchable Intrafascicular Peripheral Nerve Recording Device with Axon-Dimension, Cuff-Less Microneedle Electrode Array.

Peripheral nerve mapping tools with higher spatial resolution are needed to advance systems neuroscience, and potentially provide a closed-loop biomarker in neuromodulation applications. Two critical challenges of microscale neural interfaces are 1) how to apply them to small peripheral nerves, and 2) how to minimize chronic reactivity. A flexible microneedle nerve array (MINA) is developed, which is the first high-density penetrating electrode array made with axon-sized silicon microneedles embedded in low-modulus thin silicone. The design, fabrication, acute recording, and chronic reactivity to an implanted MINA, are presented. Distinctive units are identified in the rat peroneal nerve. The authors also demonstrate a long-term, cuff-free, and suture-free fixation manner using rose bengal as a light-activated adhesive for two time-points. The tissue response is investigated at 1-week and 6-week time-points, including two sham groups and two MINA-implanted groups. These conditions are quantified in the left vagus nerve of rats using histomorphometry. Micro computed tomography (micro-CT) is added to visualize and quantify tissue encapsulation around the implant. MINA demonstrates a reduction in encapsulation thickness over previously quantified interfascicular methods. Future challenges include techniques for precise insertion of the microneedle electrodes and demonstrating long-term recording.

Vagus Nerve Stimulation Reduces Neuroinflammation Through Microglia Polarization Regulation to Improve Functional Recovery After Spinal Cord Injury.

BackgroundSpinal cord injury (SCI) is a devastating disease that lacks effective treatment. Interestingly, recent studies indicated that vagus nerve stimulation (VNS), neuromodulation that is widely used in a variety of central nervous system (CNS) diseases, improved motor function recovery after SCI. But the exact underlying mechanism of how VNS ameliorates SCI is unclear. This study aimed to confirm the efficacy and further explore the potential therapeutic mechanism of VNS in SCI.MethodA T10 spinal cord compression model was established in adult female Sprague-Dawley rats. Then the stimulation electrode was placed in the left cervical vagus nerve (forming Sham-VNS, VNS, and VNS-MLA groups). Basso-Beattie-Bresnahan (BBB) behavioral scores and Motor evoked potentials (MEPs) analysis were used to detect motor function. A combination of histological and molecular methods was used to clarify the relevant mechanism.ResultsCompared with the Sham-VNS group, the VNS group exhibited better functional recovery, reduced scar formation (both glial and fibrotic scars), tissue damage, and dark neurons, but these beneficial effects of VNS were diminished after alpha 7 nicotinic acetylcholine receptor (α7nAchR) blockade. Specifically, VNS inhibited the pro-inflammatory factors TNF-α, IL-1β, and IL-6 and increased the expression of the anti-inflammatory factors IL-10. Furthermore, we found that VNS promotes the shift of M1-polarized Iba-1+/CD86+ microglia to M2-polarized Iba-1+/CD206+ microglia via upregulating α7nAchR to alleviate neuroinflammation after SCI.ConclusionOur results demonstrated that VNS promotes microglial M2 polarization through upregulating α7nAChR to reduce neuroinflammation, thus improving motor function recovery after SCI. These findings indicate VNS might be a promising neuromodulation strategy for SCI.

Zone 2 hybrid thoracic endovascular aortic repair: Is it a good option for all types of thoracic aortic disease?

BackgroundZone 2 thoracic endovascular aortic repair (TEVAR) is performed for the treatment of various thoracic aortic diseases involving the left subclavian artery. This study aimed to analyze the late clinical outcomes of zone 2 hybrid TEVAR according to the various indications.MethodsA total of 48 patients who underwent zone 2 TEVAR at our institution between December, 2010 and July, 2020 were enrolled. The indications were aortic aneurysm (AA, n = 15), acute type B aortic dissection (AD, n = 14), penetrating aortic ulcer (PAU, n = 8), traumatic aortic injury (TAI, n = 8), and others (n = 3). The clinical outcomes including early complications and mid-term aortic measurements were retrospectively reviewed.ResultsThe technical success rate was 100% and in-hospital mortality occurred in one patient. The early postoperative complications included stroke (n = 1), transient spinal cord ischemia (n = 1), neck wound hematoma (n = 1), and left phrenic or vagus nerve injury (n = 9). In patients with AD, positive remodeling was observed in ten patients (76.9%) (false lumen regression in the entire or thoracic aorta [n = 9], false lumen thrombosis in the thoracic aorta [n = 1]). However, in patients with AA, increased aneurysm was found in six patients (40%). Persistent aneurysmal growth was found in patients with a maximal aortic diameter of > 60 mm on initial imaging (4/6, 50%). No aortic expansion was observed in those with TAI or PAU. Endoleak was noted in five patients (10.4%), and among them, aortic reintervention was required only in patients with large AAs.ConclusionsZone 2 hybrid TEVAR was associated with an acceptable early complication rate and provided acceptable mid-term aortic results for patients with AD, PAU, and TAI. However, patients with large AAs were at increased risk of aortic reintervention. In cases of large AA, clinicians should carefully consider whether zone 2 hybrid TEVAR or open surgical repair will be more effective for the patient.

Preoperative ultrasound mapping of the vagus nerve in thyroid surgery.

Intraoperative neuromonitoring (IONM) in thyroid surgery requires electric stimulation of the vagus nerve to verify correct electrode placement. Classically the nerve is found deep to or in-between the common carotid artery and internal jugular vein, but previous studies have shown that the nerve can sometimes be found superficial to the vessels. Our aim was to determine the incidence of a superficial vagus nerve using ultrasound (US) and study possible clinical factors associated with an anteriorly-located vagus nerve. Retrospective study of patients undergoing thyroid surgery (lobectomy or total thyroidectomy) with intermittent IONM. Substernal goiters, locally invasive tumors or bulky lymph nodes were excluded. The vagus nerve was identified at the level of the mid-thyroid lobe on each side on preoperative US performed by two specialized radiologists, and its location according to 6 possible positions in relationship to the common carotid artery was recorded. The anatomic variability of the vagus nerve was analyzed in relationship to patient demographics and thyroid pathology. Five-hundred twenty-seven patients were included. The right vagus nerve (n=522) was in-between, superficial or deep to the vessels in 92.3%, 6.1% and 1.5% and of cases, respectively, and the left vagus (n=517) in 80.2%, 18.6% and 1.2% of cases, respectively, with a statistically significant difference between right and left vagus nerves (P<0.001). The type of pathology, size of the dominant nodule or the volume of the thyroid lobe were not correlated to finding a superficial vagus nerve. The vagus nerve was identified in all cases on US and found to be anterior to common carotid artery at the level of the thyroid lobe in 18.6% of cases on the left and 6.1% of cases on the right. Identifying this anatomic variant preoperatively may facilitate IONM and avoid inadvertent trauma to the vagus nerve during thyroid surgery.

Vagus nerve ultrasound in transthyretin familial amyloid polyneuropathy: A pilot study.

Background and PurposeAutonomic dysfunction is common in transthyretin familial amyloid polyneuropathy (TTR‐FAP). Because ultrasonography is a powerful tool to study peripheral neuropathy, vagus nerve (VN) ultrasonography was used in our study to investigate the possible changes of the dimension of VN in TTR‐FAP.MethodsEighteen patients with TTR‐FAP and 17 age‐ and gender‐matched individuals without any neuropathies were enrolled in a pilot study. The cross‐sectional areas (CSAs) were measured bilaterally on transverse scans of vagus, median, and ulnar nerves. Clinical data were collected to explore the correlations with CSAs of VN.ResultsThe median CSAs of VN in TTR‐FAP were 3.5 (2.0‐6.0) mm2 on the right side and 2.5 (1.0‐6.0) mm2 on the left side, compared with 2.0 (1.0‐3.0) mm2 and 1.0 (1.0‐2.0) mm2 for healthy controls (HCs). There was a significant difference between the two groups on both sides (p < .001). The mean VN CSAs were correlated positively with the course of disease (r = .7203, p = .0016)（not including the patient with the longest disease course), the Composite Autonomic Symptom Score 31 (r = .5252, p = .0252), the left ventricular posterior wall thickness (r = .5426, p = .0200), and the interventricular septum thickness (r = .5103, p = .0305). The cutoff values of right and left VN CSAs to identify TTR‐FAP from HCs were 2.5 and 1.5 mm2 and the areas under the curve were .9395 and .8856, with a high sensitivity (.889 and .889) and specificity (.941 and .765), respectively.ConclusionVN enlargement is prevalent among TTR‐FAP patients. VN ultrasonography may be an important clinical tool for assessing the severity of autonomic dysfunction in TTR‐FAP.

Self-Administration of Right Vagus Nerve Stimulation Activates Midbrain Dopaminergic Nuclei.

Background: Left cervical vagus nerve stimulation (l-VNS) is an FDA-approved treatment for neurological disorders including epilepsy, major depressive disorder, and stroke, and l-VNS is increasingly under investigation for a range of other neurological indications. Traditional l-VNS is thought to induce therapeutic neuroplasticity in part through the coordinated activation of multiple broadly projecting neuromodulatory systems in the brain. Recently, it has been reported that striking lateralization exists in the anatomical and functional connectivity between the vagus nerves and the dopaminergic midbrain. These emerging findings suggest that VNS-driven activation of this important plasticity-promoting neuromodulatory system may be preferentially driven by targeting the right, rather than the left, cervical nerve.Objective: To compare the effects of right cervical VNS (r-VNS) vs. traditional l-VNS on self-administration behavior and midbrain dopaminergic activation in rats.Methods: Rats were implanted with a stimulating cuff electrode targeting either the right or left cervical vagus nerve. After surgical recovery, rats underwent a VNS self-administration assay in which lever pressing was paired with r-VNS or l-VNS delivery. Self-administration was followed by extinction, cue-only reinstatement, and stimulation reinstatement sessions. Rats were sacrificed 90 min after completion of behavioral training, and brains were removed for immunohistochemical analysis of c-Fos expression in the dopaminergic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), as well as in the noradrenergic locus coeruleus (LC).Results: Rats in the r-VNS cohort performed significantly more lever presses throughout self-administration and reinstatement sessions than did rats in the l-VNS cohort. Moreover, this appetitive behavioral responding was associated with significantly greater c-Fos expression among neuronal populations within the VTA, SNc, and LC. Differential c-Fos expression following r-VNS vs. l-VNS was particularly prominent within dopaminergic midbrain neurons.Conclusion: Our results support the existence of strong lateralization within vagal-mesencephalic signaling pathways, and suggest that VNS targeted to the right, rather than left, cervical nerve preferentially activates the midbrain dopaminergic system. These findings raise the possibility that r-VNS could provide a promising strategy for enhancing dopamine-dependent neuroplasticity, opening broad avenues for future research into the efficacy and safety of r-VNS in the treatment of neurological disease.

Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals

BackgroundAlthough electrical stimulation of the peripheral and central nervous systems has attracted much attention owing to its potential therapeutic effects on neuropsychiatric diseases, its non-cell-type-specific activation characteristics may hinder its wide clinical application. Unlike electrical methodologies, optogenetics has more recently been applied as a cell-specific approach for precise modulation of neural functions in vivo, for instance on the vagus nerve. The commonly used implantable optical waveguides are silica optical fibers, which for brain optogenetic stimulation (BOS) are usually fixed on the skull bone. However, due to the huge mismatch of mechanical properties between the stiff optical implants and deformable vagal tissues, vagus nerve optogenetic stimulation (VNOS) in free-behaving animals continues to be a great challenge.ResultsTo resolve this issue, we developed a simplified method for the fabrication of flexible and stretchable polymer optical fibers (POFs), which show significantly improved characteristics for in vivo optogenetic applications, specifically a low Young’s modulus, high stretchability, improved biocompatibility, and long-term stability. We implanted the POFs into the primary motor cortex of C57 mice after the expression of CaMKIIα-ChR2-mCherry detected frequency-dependent neuronal activity and the behavioral changes during light delivery. The viability of POFs as implantable waveguides for VNOS was verified by the increased firing rate of the fast-spiking GABAergic interneurons recorded in the left vagus nerve of VGAT-ChR2 transgenic mice. Furthermore, VNOS was carried out in free-moving rodents via chronically implanted POFs, and an inhibitory influence on the cardiac system and an anxiolytic effect on behaviors was shown.ConclusionOur results demonstrate the feasibility and advantages of the use of POFs in chronic optogenetic modulations in both of the central and peripheral nervous systems, providing new information for the development of novel therapeutic strategies for the treatment of neuropsychiatric disorders.

Acute vagus nerve stimulation does not affect liking or wanting ratings of food in healthy participants

The vagus nerve plays a vital role in the regulation of food intake and vagal afferent signals may help regulate food cue reactivity by providing negative homeostatic feedback. Despite strong evidence from preclinical studies on vagal afferent “satiety” signals in guiding food intake, evidence from human studies is largely inconclusive to date. Here, we investigated the acute effects of left or right transcutaneous auricular vagus nerve stimulation (taVNS) on subjective ratings of wanting and liking of various food and non-food items in 82 healthy participants (46 women, MBMI = 23.1 kg/m2). In contrast to previous reports in patients with depression, we found moderate to anecdotal evidence supporting the absence of taVNS-induced changes in food ratings. To test whether the absence of taVNS effects on food ratings is due to heterogeneity in the sample, we conducted post hoc subgroup analyses by splitting the data according to stimulation side and sex (between-subject factors) as well as caloric density, perceived healthiness, and flavor (sweet vs. savory) of the food (within-subject factors). This multiverse analysis largely supported the absence of taVNS-induced changes since the strongest subgroup effects provided only anecdotal evidence in favor of taVNS-induced changes. We conclude that acute taVNS only has a marginal effect on subjective ratings of food, suggesting that it is an unlikely mechanism for the reported long-term effects of VNS on body weight. In light of an absence of acute taVNS effects on conscious food liking and wanting, our results call for future research on the correspondence between acute and chronic effects of vagal afferent stimulation.

Vagus nerve stimulation activates nucleus of solitary tract neurons via supramedullary pathways.

Vagus nerve stimulation (VNS) treats patients with drug-resistant epilepsy, depression and heart failure, but the mechanisms responsible are uncertain. The mild stimulus intensities used in chronic VNS suggest activation of myelinated primary visceral afferents projecting to the nucleus of the solitary tract (NTS). Here, we monitored the activity of second and higher order NTS neurons in response to peripheral vagal activation using therapeutic VNS criteria. A bipolar stimulating electrode activated the left cervical vagus nerve, and stereotaxically placed single tungsten electrodes recorded unit activity from the left caudomedial NTS of chloralose-anaesthetized rats. High-intensity single electrical stimuli established vagal afferent conduction velocity (myelinated A-type or unmyelinated C-type) as well as synaptic order (second vs. higher order using paired electrical stimuli) for inputs to single NTS neurons. Then, VNS treatment was applied. A mid-collicular knife cut (KC) divided the brainstem from all supramedullary regions to determine their contribution to NTS activity. Our chief findings indicate that the KC reduced basal spontaneous activity of second-order NTS neurons receiving myelinated vagal input by 85%. In these neurons, acute VNS increased activity similarly in Control and KC animals. Interestingly, the KC interrupted VNS activation of higher order NTS neurons and second-order NTS neurons receiving unmyelinated vagal input, indicating that supramedullary descending projections to NTS are needed to amplify the peripheral neuronal signal from VNS. The present study begins to define the pathways activated during VNS and will help to better identify the central nervous system contributions to the therapeutic benefits of VNS therapy. KEY POINTS: Vagus nerve stimulation is routinely used in the clinic to treat epilepsy and depression, despite our uncertainty about how this treatment works. For this study, the connections between the nucleus of the solitary tract (NTS) and the higher brain regions were severed to learn more about their contribution to activity of these neurons during stimulation. Severing these brain connections reduced baseline activity as well as reducing stimulation-induced activation for NTS neurons receiving myelinated vagal input. Higher brain regions play a significant role in maintaining both normal activity in NTS and indirect mechanisms of enhancing NTS neuronal activity during vagus nerve stimulation.

Abstract 14090: Myocardial Infarction Selectively Decreases Cardiac Vagal Afferent Neurotransmission: Implications for Mechanisms Behind Cardiac Parasympathetic Dysfunction

Introduction: Parasympathetic dysfunction after myocardial infarction (MI) predisposes to arrhythmias and heart failure. Mechanisms behind this dysfunction are unclear. It is known that cardiac sensory afferent neurons in the vagal ganglia sense beat-to-beat changes at the level of the heart. This vagal afferent signaling/activation then increases central cardiac vagal efferent drive. Hypothesis: We hypothesized that MI causes a functional reduction in vagal afferent signaling that subsequently decreases efferent vagal tone, resulting in parasympathetic dysfunction. Methods: A transgenic mouse line was created by crossing mice expressing excitatory vesicular glutamate transporter 2, VGlut-ires-cre, with those expressing channel rhodopsin 2 EYFP (ChR2), resulting in mice with VGlut and ChR2 expression in afferent-specific vagal neurons and fibers. MI was created by left anterior descending artery ligation. Sham animals underwent thoracotomy only. Control animals did not undergo a thoracotomy. Two weeks post-MI or sham, the left cervical vagus nerve was isolated and optically stimulated in vivo using blue light laser (473 nm, 20 Hz, 10 &amp; 20 msec). Heart rate (HR), respiratory rate (RR), and time to activation of efferent vagal effects (time to nadir HR/RR) were assessed. Results: In response to optical stimulation, MI animals (n=5) demonstrated significantly reduced HR responses vs. sham (n=4) and control (n=7) animals at both 10 ms and 20 ms, figure. Time to nadir HR was also increased in MI animals (P&lt;0.05 vs. sham/control). RR decreased in all animals, without significant differences between groups. Conclusions: MI is associated with decreased efferent vagal responses to similar levels of parasympathetic afferent activation. These results suggests that mechanisms behind decreased vagal tone post-MI may be due altered vagal afferent neurotransmission and signaling capabilities. MI selectively affects cardiac, not respiratory, neural responses.

Cross-sectional area of the vagus nerve on carotid duplex ultrasound and atrial fibrillation in acute stroke: A retrospective analysis.

IntroductionThe autonomic nervous system, including the vagus nerve, is associated with the development of atrial fibrillation (AF). However, the association between the cross-sectional area (CSA) of the vagus nerve on ultrasound and the presence of AF has not been fully clarified. This study investigated the association between vagus nerve CSA and the presence of AF in patients with acute stroke.MethodsWe retrospectively reviewed 150 consecutive patients with ischemic stroke or transient ischemic attack. Vagus nerve CSA was evaluated by carotid ultrasonography on the axial view at the thyroid gland level. Univariate and multivariable analyses were performed to examine the association between vagus nerve CSA and AF.ResultsOf 133 patients included in the analysis, 31 (23.3%) were diagnosed with AF before hospital discharge. The median right vagus nerve CSA was significantly smaller in patients with AF than in patients without AF (p = 0.03). However, there was no significant difference in median left vagus nerve CSA. Multivariable logistic regression analysis revealed that log transformed and quintiled brain natriuretic peptide level (odds ratio [OR], 5.03; 95% confidence interval [CI], 2.43–10.40) and right vagus nerve CSA (OR, 0.33; 95% CI, 0.12–0.91) were independent predictors of AF.Discussion/conclusionSmaller right vagus nerve CSA in carotid ultrasonography was an independent predictor of AF in patients with ischemic stroke or transient ischemic attack, suggesting that patients with small right vagus nerve CSA should be closely monitored for development of AF.

Ультразвуковое исследование блуждающих нервов у пациентов с болезнью Паркинсона

Parkinson’s disease (PD) is a neurodegenerative multisystem disorder characterized by pathologic α-synuclein aggregation affecting, among other things, vagal fibers. The aim of this study was to investigate the cross-sectional area (CSA) of the vagus nerve (VN) in patients with PD using ultrasound imaging. The study was conducted in 32 patients with PD (15 men and 17 women; mean age 58 ± 10 years) and 32 healthy controls comparable with the main group in terms of sex and age. All study participants underwent ultrasound examination of the VN using a high-resolution transducer. Left VN CSA was significantly smaller in patients with PD than in the control group (1.78 ± 0.52 mm2 vs 2.11 ± 0.41 mm2; р = 0.007). A similar result was obtained for right VN CSA at the trend level. ROC analysis demonstrated that the threshold CSA value of &lt; 2.10 mm2 for the left VN has low diagnostic sensivity (59%) for VN atrophy in patients with PD. Right VN CSA was significantly larger than left VN CSA in both groups (p &lt; 0.001). The analysis of the PD group did not reveal any associations between VN CSA and age, duration and stage of the disease, motor (UPDRS III) and non-motor (NMSQ) scores. Patients with akinetic-rigid form of PD had smaller left VN CSA than patients with the mixed form of the disease (р &lt; 0.05). A moderate inverse correlation was established between left VN CSA and the area of substantia nigra hyperechogenicity on both sides (р &lt; 0.04); for the right VN a similar correlation was established at the trend level. High-resolution ultrasound of patients with PD demonstrated atrophy of the VN and the association of VN CSA with the clinical form of the disease and the ultrasound features of the substantia nigra.

A Pilot Study of Thermal Effect of Low-intensity Focused Ultrasound on Blood Pressure Modulation.

Our recent study showed that low-intensity focused ultrasound stimulation (FUS) of the vagus nerve is capable of lowering blood pressure (BP). However, it remains unknown that what is the underlying mechanisms of BP modulation with FUS. In our preliminary experiments, we noticed that there was temperature elevation accompanied the FUS. Thus, to verify whether the thermal effect of ultrasound contributes in the BP-lowering effect, this study compared the BP response under the FUS (with thermal effect and mechanical effect) and the alternative heating source treatment (AHST) (with thermal effect only) of left vagus nerve. Six Sprague Dawley rats were randomly divided into two groups (FUS, n=3 and AHST, n=3). In vivo temperature measurements were conducted to evaluate the heating performance of the FUS and the AHST. Blood pressure (BP) waveform was continuously recorded from the right common artery and was used for analyzing systolic BP (SBP), diastolic BP (DBP), mean BP (MBP), and heart rate (HR). The results showed that the SBP, DBP, MBP and HR decreased during the 15-min FUS. However, most of the SBP, DBP, MBP and HR increased during the 15-min AHST, which had the approximate temperature elevation of the FUS. Thus, the thermal effect of ultrasound probably does not contribute in the BP-lowering effect induced by low-intensity FUS of the vagus nerve.

477 MINIMALLY INVASIVE MEDIASTINOSCOPIC IVOR-LEWIS ESOPHAGECTOMY WITH CERVICAL ANASTOMOSIS FOR ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA PATIENT UNDER INTRAOPERATIVE RECURRENT LARYNGEAL NERVE MONITORING

Abstract In early 2000s, cervical anastomosis after esophagectomy was associated with a higher rate of recurrent nerve trauma than thoracic anastomosis. Recently, new technologies have been developed that reduce surgical complications. Mediastinoscopic esophagectomy is reportedly less invasive and allows faster recovery than thoracoscopic esophagectomy. Intraoperative nerve monitoring (IONM) prevents recurrent laryngeal nerve (RNL) palsy. We present the case of minimally invasive mediastinoscopic Ivor-Lewis Esophagectomy (MMIE) under IONM performed on an elderly esophagogastric junction (EGJ) adenocarcinoma patient. Methods An 84-year old man was consulted for adenocarcinoma of GEJ without lymphnode metastasis. Despite his advanced age, he had no comorbidities. We planned to perform MMIE under IONM. The procedure started with a patient lithotomy, and three trocars plus small incision were made in the upper abdomen. Celiac lymphadenectomy was performed. Subsequently, a 35 mm incision was made in the left side of the neck and a monitor was attached to left vagus nerve. Three trocars were placed with single incision surgical devices and pneumomediastinum was noticed. Mediastinoscopic esophagectomy was performed. Gastric tube reconstruction via mediastinum with cervical anastomosis was performed. Results The operation was successful. Total operation time was 393 minutes, with an estimated blood loss of 5 mL. There were no intraoperative and postoperative complications, and no RLN palsy occurred. Conclusion MMIE with cervical anastomosis under IONM is safe and less invasive especially for the respiratory system as a thoracotomy is unnecessary. Video https://www.dropbox.com/s/9yqkzg3pm619pf6/%E7%B8%A6%E9%9A%94%E9%8F%A12%E5%88%8656%E7%A7%92.mp4?dl=0.

Vagus nerve ultrasonography in Parkinson's disease: A systematic review and meta-analysis.

Vagus nerve (VN) has been suggested as one of the major routes of Parkinson's disease (PD) progression from enteric nervous system to brain. Therefore, the recent studies have investigated the VN structurally, with a focus on the changes in its size in PD patients using high-frequency ultrasonography. This systematic review and meta-analysis aims to evaluate VN size via ultrasound in PD compared to controls. Totally, five studies were included with a total of 238 participants (128 PD patients and 111 controls). The estimate mean difference in four studies showed that the VN CSA was smaller in PD patients with 0.29mm2 (95% CI, -0.52 to -0.06) and 0.23mm2 (95% CI, -0.42 to -0.05) for right and left VNs respectively. The test for overall effect was significant for both measurements (p=0.01). This review reveals that there is a degree of vagus nerve atrophy in PD which could be detected sonographically with high confidence, thus can be used as a marker for vagus neuronal lesion or neuropathy. Further studies are needed to examine its clinical correlation thoroughly.

Neurovascular Compression in Arterial Hypertension: Correlation of Clinical Data to 3D-Visualizations of MRI-Findings

Aims: In this study, we attempted to identify clinical parameters predicting the absence or presence of Neurovascular Compression (NVC) at the Ventrolateral Medulla (VLM) in arterial hypertension (HTN) in MRI findings. Background: Cardiovascular and pulmonary afferences are transmitted through the left vagus and glossopharyngeal nerve to the brain stem and vasoactive centers. Evidence supports the association between HTN and NVC at the left VLM. Several independent studies indicate a reduction of HTN after Microvascular Decompression (MVD) of the left. Several independent studies indicate a reduction of HTN after Microvascular Decompression (MVD) of the left VLM. Image processing of MRI provides comprehensible detection of NVC. HTN affects hemodynamic parameters and organs. Objective: This study analyzes and correlates clinical data and MRI findings in patients with and without NVC at the VLM in treatment resistant HTN to obtain possible selection criteria for neurogenic hypertension. Methods: In 44 patients with treatment resistant HTN, we compared MRI findings of neurovascular imaging to demographic, clinical and lifestyle data, office and 24-hour ambulatory Blood Pressure (BP), and cardiovascular imaging and parameters. Results: Twenty-nine (66%) patients had evidence of NVC at the VLM in MRI. Sixteen patients (36%) had unilateral NVC on the left side, 7 (16%) unilateral right and 6 (14%) bilateral NVC. Fifteen (34%) had no evidence of NVC at the VLM. Patients with left sided NVC were significantly younger, than those without NVC (p=0.034). They showed a statistically significant variance in daytime (p=0.020) and nighttime diastolic BP (p&lt;0.001) as the mean arterial pressure (p=0.020). Other measured parameters did not show significant differences between the two groups. Conclusion: We suggest to examine young adults with treatment resistant HTN for the presence of NVC at VLM, before signs of permanent organ damage appear. Clinical and hemodynamic parameters did not emerge as selection criteria to predict NVC. MVD as a surgical treatment of NVC in HTN is not routine yet as a surgical treatment of NVC in HTN is not routine yet. Detection of NVC by imaging and image processing remains the only criteria to suggest MVD, which should be indicated on an individual decision.

Comparison of Monopolar and Bipolar Stimulator Probes for Intraoperative Nerve Mapping During Thyroidectomy: A Prospective Study.

During intraoperative neuromonitoring in thyroid surgery, two different kinds of stimulator probes, monopolar and bipolar, are commonly used to stimulate the laryngeal nerves. We explore the unique characteristics of both of these probes as they relate to intraoperative laryngeal nerve mapping. Twenty-one patients undergoing neuromonitored thyroidectomy by a single surgeon were enrolled. Electromyography (EMG) amplitude and latency measurements were prospectively recorded concurrently from 1 mA stimulation of vagus nerve (VN) and inferior/superior recurrent laryngeal nerve before (with and without fascia) and after thyroid resection using bipolar and monopolar stimulator probes. Significantly higher amplitudes were obtained with monopolar stimulator probes as compared to bipolar probes, in several stimulation scenarios such as at right VN pre-resection (carotid sheath intact), right VN pre-resection (carotid sheath dissected), right VN post-resection and left VN (carotid sheath dissected). No significant differences were found between amplitudes and latency values in all other stimulation scenarios. According to this study, both probes are reliable and safe for neural mapping. The kind of probe used during neural monitoring is based on surgical situations and surgeon preference. 3 (According to Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence) Laryngoscope, 131:E2718-E2726, 2021.

FV 7. Cross-sectional area of the vagus nerve correlates with parasympathetic dysfunction in Parkinson's Disease

Introduction . In this study we evaluated the autonomic neural function in Parkinson's disease (PD) by combining the use of clinical scoring, functional evaluation with head-up tilt test (HUTT) and morphological studies of the vagus nerve (VN) with nerve ultrasound (NU). This allowed us to correlate morphological changes of the VN with markers of parasympathetic dysfunction from HUTT. Patients/Methods. In our study we used NU to compare the mean values of the cross-sectional area (CSA) of the VNs of 80 PD patients with those of controls (n=40) and patients with chronic inflammatory demyelinating polyneuropathy (CIDP) (n=76). In 69 cases HUTT data was analyzed concerning the presence of orthostatic hypotension (OH), postural orthostatic tachycardia syndrome (POTS) and chronotropic incompetence (CI). Functional haemodynamic parameters in HUTT were used to evaluate parasympathetic functions and correlate them with VN CSA (n=65). Results . In PD, the CSA of right / left VN was significantly smaller compared to the right/left VN of the control and CIDP patients (Table 1). Based on HUTT, 60.5 % of the patients were diagnosed with autonomic dysfunction (OH n=11, CI n=31, POTS n=1). Patients with OH showed significantly higher UPDRS-III values than those with CI (p=0.025). The CSA of the VN correlated inversely with heart rate and positively with parameters representing parasympathetic modulation through vagal activity (Fig. 1). Conclusion . By using NU significant morphological differences of the CSA of the VN were detected in CIDP, PD and a healthy control group. Furthermore, we demonstrated for the first time that anatomical characteristics of the VN correlate with parameters of parasympathetic function from the spectral analysis of cardiovascular parameters in HUTT for PD. This finding enables a new interpretation of the anatomical characteristics of the VN for PD patients and diagnosis of autonomic dysfunction. Fig. 1. Schematic presentation of the inverse correlation of the cross-sectional area of the right vagus nerve with the heart rate. Positive correlation with markers of parasympathetic activity HFnu-RRI. (Spearman Correlation). Abbreviations: HR=heart rate, HFnuRRI = high frequency power of the RR-Interval, bpm= beats per minute, CSA= cross-sectional area Table 1. Demographical and epidemiological characteristics as well as the cross-sectional area (CSA) of the vagus nerve. All values are provided as mean ± standard deviation. Abbreviations: INCAT/ODSS = inflammatory neuropathy cause and treatment/overall disability sum score, MDS-UPDRS III= MDS-Unified Parkinson's Disease Rating Scale, SCOPA-AUT= Scales for Outcomes in Parkinson's Disease- Autonomic Dysfunction, PDQ39 = Parkinson's Disease Questionnaire, CSA = cross sectional area.

In-vivo application of low frequency alternating currents on porcine cervical vagus nerve evokes reversible nerve conduction block

BackgroundThis paper describes a method to reversibly block nerve conduction through direct application of a 1 Hz sinusoidal current waveform delivered through a bipolar nerve cuff electrode. This low frequency alternating current (LFAC) waveform was previously shown to reversibly block the effects of vagal pulse stimulation evoked bradycardia in-vivo in the anaesthetised rat model (Mintch et al. 2019). The present work measured the effectiveness of LFAC block on larger caliber myelinated vagal afferent fibers in human sized nerve bundles projecting to changes in breathing rate mediated by the Hering-Breuer (HB) reflex in anaesthetized domestic swine (n=5).MethodsTwo bipolar cuff electrodes were implanted unilaterally to the left cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar recording cuff electrode was placed rostral to the bipolar stimulating electrodes on the same nerve to measure changes in the compound nerve action potentials (CNAP) elicited by the vagal pulse stimulation and conditioned by the LFAC waveform. Standard pulse stimulation was applied at a sufficient level to induce a reduction in breathing rate through the HB reflex. If unblocked, the HB reflex would cause breathing to slow down and potentially halt completely. Block was quantified by the ability of LFAC to reduce the effect of the HB reflex by monitoring the respiration rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone.ResultsLFAC achieved 87.2 ±8.8% block (n=5) at current levels of 1.1 ±0.3 mAp (current to peak), which was well within the water window of the working electrode. CNAP showed changes that directly correlated to the effectiveness of LFAC block, which manifested itself as the slowing and amplitude reduction of components of the CNAP.ConclusionThese novel findings suggest that LFAC is a potential alternative or complementary method to other electrical blocking techniques in clinical applications.