Methods Mol Biol. 2025;2868:285-301. doi: 10.1007/978-1-0716-4200-9_15.

ABSTRACT

An intricate relationship exists between the vagus nerve and systemic immune cell regulation, specifically during fetal development. Little is known about the connection between the vagus nerve and the brain’s regional circulatory control. In this chapter, we present a methodology for studying the impact of vagus nerve signaling on these connections in the developing fetus using the sheep model for human fetal physiology. First, we present the protocol to study the connection between the vagus nerve physiology and the regional cerebral blood flow (rCBF). Next, we detail the protocol for measuring how vagal signaling alters microglial cell plasticity in gut and brain. In previous work, our team showed that vagotomy results in amplified redistribution of rCBF toward subcortical structures in the fetal brain. Conversely, efferent VNS reduces rCBF to cortical structures while afferent VNS diminishes the rise of rCBF to subcortical structures (independent of cortical rCBF) when compared to controls in the fetal brain. Additionally, our team showed that Iba-1 expression, a marker for microglial cellular signaling activation, rises in a dose-dependent relationship with systemic inflammatory activation in the setting of vagotomy. The findings support existing preclinical and clinical evidence in adult human physiology that vagotomy is neuroprotective for neurodegenerative diseases such as Parkinson’s likely via a glial cell-mediated mechanism. Vagus nerve stimulation (VNS) has also been shown to alter rCBF patterns in adults with treatment-resistant depression, underscoring the importance of further investigation of the relationship between the vagus nerve and rCBF as early as in utero. Together, the body of evidence emphasizes that the vagal pathway is an important player in the programming of microglial cell phenotypes within the developing brain. Further study is needed to better understand the significance of these relationships for the development and treatment of early susceptibility to neuroinflammatory and neurodegenerative disorders in later life. Therefore, we present a methodology for assessing rCBF and morphometric features of microglial and macrophage cell activation to allow future teams to expand on the existing body of work and further examine these relationships at a cellular and systems’ levels.

PMID:39546236 | DOI:10.1007/978-1-0716-4200-9_15

Psychoradiology. 2024 Nov 4;4:kkae016. doi: 10.1093/psyrad/kkae016. eCollection 2024.

ABSTRACT

BACKGROUND: We reported a case of cervical invasive vagus nerve stimulation (iVNS) treatment for avoidant/restrictive food intake disorder (ARFID) in a patient with severe anxiety and depression. This patient was even given a critical illness notice during his hospitalization and all treatment efforts were failed.

OBJECTIVE: We aimed to verfiy the effectiveness of iVNS in a patient with ARFID.

METHODS: We first attempted to perform cervical iVNS in this case and then observed the changes in clinical scores. We also analyzed the alterations in brain magnetic resonance imaging characteristics before and after iVNS using multi-modal neuroimagings.

RESULTS: After 18 days of iVNS (from 1 to 19 July 2023), the patient’s clinical symptoms improved significantly and he rapidly gained 5 kg in weight. The brain functional characteristics of this patient tended toward those of the normal group. Functional connectivities of the medial of orbitalis prefrontal cortex returned to the normal range after iVNS.

CONCLUSION: This is a precedent for performing cervical iVNS in an ARFID patient. Brain neural activity can be modulated through iVNS. The observed improvements in clinical scores and positive changes in brain function validated the effectiveness of iVNS. This case study provides evidence that this intervention technique could be used to reduce the burden on more similar ARFID patients.

PMID:39539529 | PMC:PMC11560375 | DOI:10.1093/psyrad/kkae016

West Afr J Med. 2024 Nov 10;41(11 Suppl 1):S21.

ABSTRACT

SUMMARY/INTRODUCTION: Velopharyngeal incompetence(VPI) is the failure of closure of the velopharyngeal sphincter, which consists of the muscles of the soft palate and the superior pharyngeal constrictor, and functions to separate the nasopharynx and oropharynx during phonation and swallowing. VPI is most frequently congenital/syndromic (with structural deficit) but can be acquired. A subset of acquired VPI, occurring in structurally intact velopharynx, has been described in children, and these are isolated and acute-onset, with a substantial proportion thought to have an infectious origin. So far measles was identified to be the aetiology in one reported case. This report aims to create awareness that VPI could be a rare post-measles complication.

CASE REPORT: A two-year-old female who, two weeks after a measles episode, developed sudden-onset nasal regurgitation, rhinolalia, and dysphagia. She had never experienced these symptoms before and has not had any recent throat surgeries. The review of systems was not contributory. On examination, she was ill-looking with no dysmorphic features; was not febrile or pale, and had generalized brownish-scaly, desquamating skin lesions. Nasal regurgitation of liquids was observed when she drank. Oral/oropharyngeal examination revealed no structural defects but she had absent gag reflex with bilateral palatal paralysis (indicating Glossopharyngeal and Vagus nerve palsies). All other neurological and systemic findings were normal. Management was conservative with a Nasogastric tube for feeding. She made a complete recovery with total restoration of neurologic functions after 21 days. Six-month follow-up revealed no recurrence or signs of progression.

CONCLUSION: This report adds to the evidence that measles is one of the infectious causes of acute-onset isolated VPI. The proposed mechanisms underlying this unusual manifestation of measles are direct viral neuronal injury given its neurotropic nature; and autoimmune neuronal injury. The reason for the rarity of this post-measles complication despite the high incidence of measles remains to be elucidated.

PMID:39535764

Seizure. 2024 Oct 28;123:97-103. doi: 10.1016/j.seizure.2024.10.013. Online ahead of print.

ABSTRACT

PURPOSE: To provide consensus-based recommendations for use of vagus nerve stimulation (VNS) therapy in the management of pediatric epilepsy.

METHODS: Delphi methodology with two rounds of online survey was used to build consensus. A steering committee developed 43 statements related to pediatric epilepsy and the use of VNS therapy, which were evaluated by a panel of 12 neurologists/neurosurgeons with expertise in pediatric epilepsy, who graded their agreement with each statement on a scale of 1 (“I do not agree at all”) to 5 (“I strongly agree”). For each statement, consensus was established if ≥70% of the agreement scores were 4 or 5 and <30% were 1 or 2 in the final survey.

RESULTS: Twenty-four statements regarding the need for seizure reduction in pediatric epilepsy, the recommended treatment algorithm, the benefits and safety of VNS therapy, management of side effects of VNS therapy, patient selection for VNS therapy, and the use, dosing, and titration of VNS therapy achieved consensus. VNS and other neuromodulation therapies should be considered for pediatric patients with drug-resistant epilepsy who are not candidates for resective surgery, or who do not remain seizure free after resective surgery. When VNS therapy is initiated, the target dose range should be achieved via the fastest and safest titration schedule for each patient. Scheduled programming can be helpful in dose titration.

CONCLUSION: The expert consensus statements represent the panelists’ collective opinion on the best practice use of VNS therapy to optimize outcomes in the management of pediatric epilepsy.

PMID:39536380 | DOI:10.1016/j.seizure.2024.10.013

Nat Commun. 2024 Nov 13;15(1):9824. doi: 10.1038/s41467-024-54056-w.

ABSTRACT

Gastric pain has limited treatment options and the mechanisms within the central circuitry remain largely unclear. This study investigates the central circuitry in gastric pain induced by noxious gastric distension (GD) in mice. Here, we identified that the nucleus tractus solitarius (NTS) serves as the first-level center of gastric pain, primarily via the vagus nerve. The prelimbic cortex (PL) is engaged in the perception of gastric pain. The lateral parabrachial nucleus (LPB) and the paraventricular thalamic nucleus (PVT) are crucial regions for synaptic transmission from the NTS to the PL. The glutamatergic tetra-synaptic NTS-LPB-PVT-PL circuitry is necessary and sufficient for the processing of gastric pain. Overall, our finding reveals a glutamatergic tetra-synaptic NTS-LPB-PVT-PL circuitry that transmits gastric nociceptive signaling by the vagus nerve in mice. It provides an insight into the gastric pain ascending pathway and offers potential therapeutic targets for relieving visceral pain.

PMID:39537596 | PMC:PMC11561356 | DOI:10.1038/s41467-024-54056-w

West Afr J Med. 2024 Nov 10;41(11 Suppl 1):S20-S21.

ABSTRACT

SUMMARY/INTRODUCTION: Cephalic tetanus (CT) constitutes only 1-3% of total reported tetanus cases. It is marked by flaccid paralysis of one or more cranial nerves (CN) with or without spasticity, typically following craniofacial injuries. The facial nerve is the most frequently paralyzed. Other CNs are rarely involved but mostly alongside facial nerve palsy. Broomstick injury as a portal of entry has been reported in generalized tetanus but not in CT to the best of our knowledge. Here is presented a case of CT with two peculiarities: broomstick penetrating ear trauma as a portal of entry, and an unusual onset with features of isolated glossopharyngeal and/or vagus nerve palsy.

CASE REPORT: A 30-month-old unimmunized male who one week before presentation developed sudden-onset dysphagia, drooling, nasal regurgitation, and rhinolalia. Two days later, he developed trismus and left-sided rd torticollis; on the 3 day, provoked spasms, initially of the face and neck muscles, and later including the limbs. Three weeks earlier he had accidentally injured his left ear while poking it with a broomstick. This was poorly managed at home without anti-tetanus prophylaxis. Examination revealed a conscious acutely ill child with risus sardonicus and episodic generalized spasms, more intense in the face and neck regions. Trismus/provoked spasms did not permit an objective assessment of glossopharyngeal, vagus, and hypoglossal nerves but other CNs were normal. Managed in a quiet, dark isolation room where he received IM anti-tetanus serum, staggered doses of chlorpromazine, phenobarbitone, diazepam; and metronidazole, his condition gradually improved, and was discharged after 21 days of hospitalization.

CONCLUSION: The rarity and sometimes unusual presentation of CT delays prompt diagnosis and early treatment leading to secondary generalization with its attendant poor outcomes. A careful history, examination, and heightened suspicion are needed. Furthermore, this report highlights ear poking, particularly with broomsticks, as a risk for CT and should be strongly discouraged.

PMID:39535734

JAMA Surg. 2024 Nov 13:e245077. doi: 10.1001/jamasurg.2024.5077. Online ahead of print.

ABSTRACT

IMPORTANCE: Radical gastric cancer surgery can cause functional and physiological disorders due to the resection of perigastric vagus nerves. Few studies have used intraoperative neurophysiological monitoring and indocyanine green (ICG) labeling to preserve the perigastric vagus nerve and to evaluate the corresponding effects.

OBJECTIVE: To assess the feasibility and effects of vagus nerve preservation using neurophysiologic monitoring and ICG labeling during laparoscopic distal gastrectomy in patients with early distal gastric cancer.

DESIGN, SETTING, AND PARTICIPANTS: This open-label, prospective randomized clinical trial initially enrolled 285 patients with clinical stage cT1N0M0 distal gastric cancer from May 2022 to May 2023. This trial was conducted at Qilu Hospital of Shandong University in Jinan, China, and enrolled patients aged 18 to 80 years with histologically proven gastric adenocarcinoma scheduled for distal gastrectomy. The final follow-up examination was performed May 1, 2024.

INTERVENTIONS: Eligible participants were randomly assigned 1:1 to vagus nerve preservation distal gastrectomy (VPG) or vagus nerve resection distal gastrectomy (VRG).

MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of postsurgical gastroparesis. Secondary outcomes included postoperative gallstone formation, quality of life, morbidity, mortality, overall survival, and disease-free survival up to 12 months postoperatively. All analyses were based on both intention-to-treat and per-protocol analyses.

RESULTS: Of 264 patients included in the intention-to-treat analysis, the median (IQR) patient age was 58.0 (52.0-67.0) years, and 67 patients (25.4%) were female. Both the VPG and VRG groups included 132 patients. Postoperative gastroparesis occurred in 1 patient (0.8%) in the VPG group and in 10 patients (7.6%) in the VRG group. Gallstones developed in 0 patients in the VPG group and in 9 patients (6.8%) in the VRG group. As assessed by mean (SD) score on the 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, the VRG group experienced more nausea and vomiting at 6 months postsurgery (19.38 [7.62]) than the VPG group (17.15 [9.21]) (P = .03) and had significantly higher rates of persistent appetite loss, reflux symptoms, and eating difficulties at both 6 months and 12 months than the VPG group. Differences in postoperative complications and metastasis were not significant.

CONCLUSIONS AND RELEVANCE: Neurophysiologic monitoring and ICG labeling during distal laparoscopic gastrectomy for vagus nerve preservation in patients with early distal gastric cancer are safe and feasible. Preserving the perigastric vagus nerve may retain the function of the remnant stomach and improve quality of life.

TRIAL REGISTRATION: Chictr.org.cn Identifier: ChiCTR2200059489.

PMID:39535740 | PMC:PMC11561724 | DOI:10.1001/jamasurg.2024.5077

Epilepsy Behav. 2024 Nov 12;161:110138. doi: 10.1016/j.yebeh.2024.110138. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the effects of vagus nerve stimulation (VNS) on the seizure frequency in patients with drug-resistant epilepsy (DRE) and bilateral temporal lobe epilepsy (bi-TLE). Additionally, we aimed to determine the safety of VNS and its side effects.

METHODS: Our retrospective study included 17 patients with bi-TLE who underwent VNS-device implantation at our center from 1997 to 2019. The main outcome was a reduction in seizure frequency. Bitemporal cases were confirmed using scalp electroencephalography (EEG) or invasive electroencephalography (iEEG).

RESULTS: The median age at seizure onset was 18 years. Bi-TLE was confirmed by scalp EEG in 47 % and by iEEG in 53 % of the patients. The median follow-up period was 36 months. The median seizure frequency per month before and after VNS was 9.5 (IQR = 4.3-35.3) and 2 (IQR = 0.8-4.2), respectively. Compared to baseline, 70.5 % of the patients achieved ≥ 50 % reduction in seizure frequency, whereas 35.3 % experienced either no or minimal reduction in seizure frequency. The response rate (>50 % reduction in seizure frequency) was 87.5 % in patients who underwent scalp EEG and 55.5 % in those who underwent iEEG. For VNS treatment, the median follow-up was at 36 months (IQR = 17-46.5). Adverse effects were observed in 59 % of the patients, including cough and hoarseness.

DISCUSSION: Therapeutic choices are limited in cases of drug-resistant bi-TLE. Our study on VNS-device implantation in bi-TLE suggests a positive outcome.

PMID:39536365 | DOI:10.1016/j.yebeh.2024.110138

Innovation (Camb). 2024 Oct 21;5(6):100721. doi: 10.1016/j.xinn.2024.100721. eCollection 2024 Nov 4.

ABSTRACT

Cough is a vital defensive reflex for expelling harmful substances from the airway. The sensory afferents for the cough reflex have been intensively studied. However, the brain mechanisms underlying the cough reflex remain poorly understood. Here, we developed a paradigm to quantitatively measure cough-like reflexes in mice. Using this paradigm, we found that prodynorphin-expressing (Pdyn+) neurons in the nucleus of the solitary tract (NTS) are critical for capsaicin-induced cough-like reflexes. These neurons receive cough-related neural signals from Trpv1+ vagal sensory neurons. The activation of Pdyn+ NTS neurons triggered respiratory responses resembling cough-like reflexes. Among the divergent projections of Pdyn+ NTS neurons, a glutamatergic pathway projecting to the caudal ventral respiratory group (cVRG), the canonical cough center, was necessary and sufficient for capsaicin-induced cough-like reflexes. These results reveal that Pdyn+ NTS neurons, as a key neuronal population at the entry point of the vagus nerve to the brainstem, initiate cough-like reflexes in mice.

PMID:39529953 | PMC:PMC11551472 | DOI:10.1016/j.xinn.2024.100721

Ann Surg Oncol. 2024 Nov 11. doi: 10.1245/s10434-024-16426-y. Online ahead of print.

ABSTRACT

BACKGROUND: Leiomyomas are benign smooth muscle tumors found at the gastroesophageal junction (GEJ) ( Mathew G, Osueni A, Carter YM. Esophageal Leiomyoma. StatPearls. StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC; 2024.). Traditional management often involves total gastrectomy with esophagojejunostomy, a highly morbid procedure that impacts quality of life ( Teh JL, Shabbir A. Resection of Gastroesophageal Junction Submucosal Tumors (SMTs). In: Lomanto D, Chen WT-L, Fuentes MB (eds). Mastering Endo-Laparoscopic and Thoracoscopic Surgery: ELSA Manual. Springer Nature Singapore; 2023. pp. 207-211.). We present a case of a large endophytic GEJ leiomyoma managed with robotic-assisted endoluminal mass resection and transoral specimen extraction.

METHODS: A 46-year-old female with upper abdominal pain was diagnosed with a 9×3 cm lobular leiomyoma at the GEJ via computed tomography and endoscopic biopsy. The tumor was excised using the da Vinci Xi system, with transgastric endoluminal trocar placement. The GEJ defect was closed over a gastroscope, allowing visualization and continuous insufflation.

RESULTS: Complete resection was achieved without creating a full-thickness defect. The mass was retrieved transorally with an endoscope, and the defect was repaired to minimize the risk of stenosis. The procedure lasted 236 min with minimal blood loss (150 mL) and with no complications. Pathology confirmed leiomyoma with negative margins. The patient was discharged on postoperative day 4 on a full liquid diet, requiring no narcotics, and was later advanced to a regular diet. No complications, readmissions, or mortality were reported at the 7-month follow-up.

CONCLUSIONS: Robotic-assisted endoluminal GEJ mass resection is a feasible, safe technique for large benign tumors, preserving the stomach and GEJ, and thereby obviating lifestyle changes from total gastrectomy. It minimizes the risk of anastomotic leak, stricture, vagus nerve injury, gastroparesis, and reflux (Levine et al. AJR Am J Roentgenol. 157:1189-1194). Closure of the GEJ defect using an endoscope allows for adequate insufflation of the proximal stomach. When feasible, combining transoral specimen extraction enhances the benefits of this minimally invasive approach (Yin et al. Chin Clin Oncol. 13:6).

PMID:39527157 | DOI:10.1245/s10434-024-16426-y