Malignant Tumors in Vagal-innervated Organs: Exploring Its Homeostatic Role

Cancer Lett. 2025 Feb 13:217539. doi: 10.1016/j.canlet.2025.217539. Online ahead of print.

ABSTRACT

Cancer remains a significant global health challenge, with its progression shaped by complex and multifactorial mechanisms. Recent research suggests that the vagus nerve could play a critical role in mediating communication between the tumor microenvironment and the central nervous system (CNS). This review highlights the diversity of vagal afferent receptors, which could position the vagus nerve as a unique pathway for transmitting immune, metabolic, mechanical, and chemical signals from tumors to the CNS. Such signaling could influence systemic disease progression and tumor-related responses. Additionally, the vagus nerve’s interactions with the microbiome and the renin-angiotensin system (RAS)-both implicated in cancer biology-further underscore its potential central role in modulating tumor-related processes. Contradictions in the literature, particularly concerning vagal fibers, illustrate the complexity of its involvement in tumor progression, with both tumor-promoting and tumor-suppressive effects reported depending on cancer type and context. These contradictions often overlook certain experimental biases, such as the failure to distinguish between vagal afferent and efferent fibers during vagotomies or the localized parasympathetic effects that cannot always be extrapolated to the systemic level. By focusing on the homeostatic role of the vagus nerve, understanding these mechanisms could open the door to new perspectives in cancer research related to the vagus nerve and lead to potential therapeutic innovations.

PMID:39954934 | DOI:10.1016/j.canlet.2025.217539

Update on Neuromodulation for Migraine and Other Primary Headache Disorders: Recent Advances and New Indications

Curr Pain Headache Rep. 2025 Feb 15;29(1):47. doi: 10.1007/s11916-024-01314-7.

ABSTRACT

PURPOSE OF REVIEW: Neuromodulation techniques currently available for headache management are reviewed in this article, with a focus on recent advances in non-invasive devices for migraine and trigeminal autonomic cephalalgias.

RECENT FINDINGS: The currently available FDA-cleared non-invasive devices for migraine include transcutaneous supraorbital and supratrochlear nerve stimulation, single-pulse transcranial magnetic stimulation (sTMS), external concurrent occipital and trigeminal neurostimulation (eCOT-NS), remote electrical neuromodulation (REN), and non-invasive vagal nerve stimulation (nVNS) with indications for migraine and trigeminal autonomic cephalalgias. Emerging non-invasive techniques being explored for use in migraine include transcranial direct current stimulation (tDCS), kinetic oscillation stimulation (KOS), and auricular transcutaneous vagal nerve stimulation (at-VNS). In addition to primary headache, non-invasive neuromodulation is being investigated for comorbid conditions such as depression. Non-invasive neuromodulation devices remain a safe, well-tolerated, and effective therapy for patients with primarily migraine and trigeminal autonomic cephalalgias. Ongoing research is needed to determine efficacy in other headache disorders and comorbid conditions.

PMID:39954214 | DOI:10.1007/s11916-024-01314-7

Enterococcus faecalis Exerts Neuroprotective Effects via the Vagus Nerve in a Mouse Model of Parkinson’s Disease

Mol Neurobiol. 2025 Feb 15. doi: 10.1007/s12035-025-04741-8. Online ahead of print.

ABSTRACT

Parkinson’s disease (PD) is a common neurodegenerative disease worldwide. Current treatment methods for PD are unable to halt disease progression. The gut microbiota contributes to the neurodevelopment of PD; however, the gut-brain connections and underlying neural bases that regulate this complex behavior are not yet clear. Enterococcus faecalis (EF) is a common commensal bacterium of the gut and a common pathogen associated with hospital-acquired infections. Here, we demonstrated the significant therapeutic effects of a non-pathogenic strain of EF (EF ATCC19433) on PD. In this study, we established a mouse model of PD by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We found that EF treatment alleviated behavioral impairment, dopaminergic neuronal loss, blood-brain barrier damage, and neuroinflammation induced by MPTP in the mice. Additionally, 16S rRNA sequencing revealed that dysbiosis of PD-related microbial communities induced by MPTP was reversed by EF treatment. Moreover, EF treatment relieved gastrointestinal dysfunction in the mice. The therapeutic efficacy of EF in MPTP-induced PD mice is markedly diminished when the activity of EF is lost. Further mechanistic studies indicated that the neuroprotective effects of EF in PD were associated with the vagus nerve pathway. Following the surgical severance of the vagus nerve through subdiaphragmatic vagotomy, the protective effects of EF on PD were markedly diminished. Our study suggests that EF can alleviate neurofunctional impairments and gastrointestinal disorders associated with PD, indicating that gut-derived microbes influence brain function through the vagus nerve pathway.

PMID:39954164 | DOI:10.1007/s12035-025-04741-8

Long-Term Outcome of Vagus Nerve Stimulation for Drug-Resistant Epilepsy

Ann Indian Acad Neurol. 2025 Feb 14. doi: 10.4103/aian.aian_389_24. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: In this study, we aimed to assess the long-term outcome of vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE).

METHODS: A retrospective analysis of outcome data of 24 patients with DRE, who had been implanted with VNS and had at least 5 years of post-surgery follow-up was performed. The seizure outcome at the latest follow-up was classified as class I-V as proposed by John C. McHugh. The cognitive, psychiatric, and behavioral outcomes were recorded using standardized tests.

RESULTS: Mean age at the time of VNS implantation was 18.7 (6-38) years; nine (37.5%) of the patients were females. Mean duration of epilepsy was 13.6 years (range: 2.5-35 years); 18 (75%) patients had multiple (≥2) seizure types and 15 (62.5%) had daily seizures. The most common etiology was perinatal hypoxic injury (15, 62.5%). More than 50% seizure reduction (class 1 and 2) was noted in 54.2% of patients at 1 year, which increased to 75% at ≥5 years follow-up. A significantly higher number of patients with other etiologies had >50% reduction in seizures at the latest follow-up, when compared to those with hypoxic-ischemic encephalopathy (53.3% vs. 100%, P = 0.0024). The average intelligence quotient (IQ; 71.17 ± 28.92 vs. 64.65 ± 29.61, P = 0.014) and quality of life (66.64 ± 14.63 vs. 64.65 ± 29.61, P < 0.001) scores were significantly higher in patients post-VNS implantation, when compared to their baseline scores. Furthermore, significant number of patients had improvement in psychiatric diagnosis (29.2% vs. 4.2%, P = 0.047) and behavioral problems (50% vs. 4.2%, P < 0.001) post-VNS implantation.

CONCLUSIONS: The present study shows >50% seizure reduction in 75% of patients after VNS implantation at long-term follow-up, with improvement in IQ, quality of life, psychiatric and behavioral problems.

PMID:39951020 | DOI:10.4103/aian.aian_389_24

Unusual Surgical Resection of Asymptomatic Schwannoma of the Cervical Vagus Nerve With Risk of Stroke: Case Report

Case Rep Surg. 2025 Jan 23;2025:9443139. doi: 10.1155/cris/9443139. eCollection 2025.

ABSTRACT

Schwannomas are the most common tumors of the peripheral nerves, originating from their support cells, the Schwann cells. The location of the tumor in the vagus nerve is rare. Vagus schwannomas usually present as a solitary, slow-growing, asymptomatic mass that rarely causes neurological alterations. The differential diagnosis of vagus nerve schwannomas includes other tumors of the parapharyngeal space or neoplasms of the jugular foramen. We report the case of a patient with an asymptomatic schwannoma of the vagus nerve involving important neck structures, with radiological compression of the carotid artery with a high risk of stroke; because of this, we underwent surgery using a transcervical approach with intracapsular excision of the tumor. The patient has a good outcome. In asymptomatic patients’ surgical indication is not an easy decision; in this case, the main reason for surgical indication was the risk of stroke with potential neurological sequels.

PMID:39949900 | PMC:PMC11824593 | DOI:10.1155/cris/9443139

Paradigms of intraoperative neuromonitoring in paediatric thyroid surgery

Front Endocrinol (Lausanne). 2025 Jan 30;15:1455217. doi: 10.3389/fendo.2024.1455217. eCollection 2024.

ABSTRACT

The larynx of children and adolescents is still in the developmental phase and the anatomical structure is still very small and sensitive. The higher malignancy and faster progression of some paediatric thyroid cancers make surgery more difficult. Intraoperative neuromonitoring (IONM) is frequently used in thyroid surgery as an effective means of securing the recurrent laryngeal nerve (RLN). Little information is available on the clinical efficacy of IONM in paediatric surgery. In addition, classic IONM techniques such as reinforced tracheal tube models with integrated surface electrodes are not standardised for children and adolescents. The use of innovative devices such as laryngeal masks with surface electrodes and thyroid cartilage receiving electrodes could replace monitoring tubes as a new form of IONM. Tracheal intubation in children needs to be performed by a highly experienced anaesthetist. The continued maturation of AI technology could be attempted in the future in conjunction with IONM to further reduce RLN injuries in children and adolescents. This article describes the anatomical features of the paediatric larynx, which differ from those of adults, and the advantages and shortcomings of IONM techniques for thyroid surgery in this population. The use of IONM in paediatric surgery is a complex technique and should be performed by experienced thyroid surgeons with in-depth IONM training. The use of IONM should be standardised within the clinical parameters of children.

PMID:39950168 | PMC:PMC11821486 | DOI:10.3389/fendo.2024.1455217

Auricular nerve block for otitis externa: A case series

Am J Emerg Med. 2025 Feb 5:S0735-6757(25)00096-8. doi: 10.1016/j.ajem.2025.01.081. Online ahead of print.

ABSTRACT

INTRODUCTION: Acute otitis externa (OE) is a prevalent infectious condition of the external ear canal, often presenting with painful inflammation and purulent drainage. Sensory innervation of the external ear and canal involves several nerves, including the auriculotemporal, lesser occipital, great auricular, and auricular branch of the vagus nerve. This case series explores the efficacy of the auricular nerve block as a targeted pain management technique in patients presenting with OE in the emergency department (ED).

CASE REPORTS: Three patients with AOE underwent auricular nerve blocks with bupivacaine 0.5 %. All three patients reported immediate pain relief from nerve block. Two out of the three patients were lost to follow up.

DISCUSSION: The auricular nerve block is safe and involves injection sites distant from major vascular structures, utilizes a small amount of anesthetic, is easy to perform by a landmark-based technique, and does not require the use of ultrasound.

CONCLUSION: Auricular nerve blocks may provide a safe, efficient, and localized alternative for OE pain relief. Further research, including larger case series or randomized trials, is recommended to establish its efficacy and refine its application.

PMID:39952849 | DOI:10.1016/j.ajem.2025.01.081

Early detection of cranial nerve dysfunction during carotid endarterectomy through intraoperative neurophysiological monitoring

Clin Neurophysiol. 2025 Feb 1;172:10-16. doi: 10.1016/j.clinph.2025.01.013. Online ahead of print.

ABSTRACT

OBJECTIVE: Intraoperative neurophysiological monitoring (IONM) is used to detect cerebral ischemia during carotid endarterectomy (CEA). IONM of cranial nerves during CEA has been reported anecdotally. The aim of this study was to assess the use of IONM in identifying and preventing cranial nerve damage during CEA.

METHODS: Prospective and observational study from a cohort of 81 patients undergoing CEA. Cranial nerve IONM was performed using electromyography (EMG), corticobulbar motor evoked potentials (CoMEP) and mapping techniques. Responses from spinal accessory, vagus, hypoglossal and facial nerves were recorded.

RESULTS: CoMEP changes were detected in 49 patients (60.4 %). Most were related to indirect retraction and normalized at the end of the procedure. In 11 (13.5 %) cases, CoMEP changes persisted at the conclusion of the surgery, and 9 (11.1 %) of them showed a postoperative paresis. All patients normalized the neurological examination within a year. Cranial nerve mapping identified functional atypical nerve branches anterior to the carotid axis.

CONCLUSION: IONM is a safe and reliable tool for detecting cranial nerve injuries during CEA and may allow to assess the functionality of surgically inconvenient nerve branches.

SIGNIFICANCE: IONM plays a critical role in detecting and potentially preventing cranial nerve damage during CEA leading to better surgical practices.

PMID:39952002 | DOI:10.1016/j.clinph.2025.01.013

A biodegradable capacitive-coupling neurostimulator for wireless electroceutical treatment of inflammatory bowel diseases

Sci Adv. 2025 Feb 14;11(7):eadu5887. doi: 10.1126/sciadv.adu5887. Epub 2025 Feb 14.

ABSTRACT

Electroceuticals based on peripheral nerve stimulation offer promising treatment for refractory inflammatory diseases such as inflammatory bowel diseases (IBDs). For pediatric IBD (PIBD) patients, wireless, biodegradable miniaturized bioelectronic devices are crucial to prevent neural damage and support neural development during and after therapy. Here we demonstrate a battery-free, miniaturized neurostimulator based on biodegradable materials and capacitive-coupling wireless power transfer. The biodegradable capacitive-coupling (BCC) neurostimulator consists of molybdenum (Mo) electronic components and self-healing biodegradable polyurethane elastomer (SBPUE) encapsulations. The self-healing property of SBPUE enables a stable neural interface. Capacitive coupling wirelessly transfers high-frequency electric fields through a single capacitor between wearable transmitters and implanted BCC neurostimulators. Programmed electrical stimulation of the vagus nerve alleviates PIBD symptoms by restoring CD4+ T cell balance, enhancing anti-inflammatory effects and suppressing pro-inflammatory effects in the intestines.

PMID:39951521 | DOI:10.1126/sciadv.adu5887

Vagus nerve stimulation in Lennox-Gastaut syndrome: Twenty-four-month data and experience from the CORE-VNS study

Epilepsia. 2025 Feb 8. doi: 10.1111/epi.18289. Online ahead of print.

ABSTRACT

OBJECTIVE: The drug-resistant epilepsy associated with Lennox-Gastaut syndrome (LGS) has a long-term effect on patients and is difficult to treat with conventional pharmacological and nonpharmacological therapies. Our objective is to demonstrate that adjunctive vagus nerve stimulation (VNS) can help manage the seizures associated with LGS.

METHODS: CORE-VNS (NCT03529045) is a prospective, multicenter, multinational observational study to collect data on seizure and nonseizure outcomes following treatment with VNS. Participants were identified as having a documented LGS diagnosis and received initial VNS implants. Baseline seizure frequency data and patient-reported outcome measures were collected at 3, 6, 12, 24, and 36 months. This interim analysis compared baseline data to VNS therapy outcomes at 24 months, and the results are presented here.

RESULTS: Sixty participants in the CORE-VNS study had a diagnosis of LGS and received an initial implant of VNS. The population was geographically diverse: 31.7% European, 26.7% from the Americas, and 26.7% from the Western Pacific. The median age at implant was 11.8 years (range = 2.2-47.6), and only 26.7% of those diagnosed with LGS were >18 years of age. Most (70%) of the participants had severe cognitive impairment. The LGS participants failed a median of 6 antiseizure medications, and 83.3% had not undergone epilepsy surgery. The LGS responder rate (≥50% reduction in seizure frequency) at 24 months for focal and generalized seizures was 66.7% and 47.4%, respectively. Some participants (20%, 12/60) experienced a ≥80% reduction in total seizure frequency. VNS was well tolerated, with only 15% (9/60) reporting at least one treatment-emergent adverse event, primarily cough, dysphonia, and oropharyngeal pain.

SIGNIFICANCE: LGS participants who received adjunctive VNS therapy to manage seizures were predominantly severely cognitively impaired children. Reductions in seizure frequency, including those with drops, and the sustained nature of the response support VNS as a promising therapy in LGS.

PMID:39921595 | DOI:10.1111/epi.18289