Effect of vagus nerve stimulation on emergency department utilization in children with drug-resistant epilepsy: a retrospective cohort study

J Neurosurg Pediatr. 2024 Jun 21:1-8. doi: 10.3171/2024.4.PEDS23310. Online ahead of print.

ABSTRACT

OBJECTIVE: Epilepsy affects approximately 470,000 children in the United States. The estimated median incidence is 50.4 cases per 100,000 persons per year. There are approximately 3.1 million seizure-related emergency department (ED) visits per year among children. Vagus nerve stimulation (VNS) is a treatment option for drug-resistant epilepsy (DRE). While its primary goal is to decrease seizure burden, VNS may decrease seizure intensity and improve quality of life. The authors assessed whether VNS decreased the number of seizure-related ED visits in a cohort of children with DRE.

METHODS: The authors performed a retrospective chart review of pediatric patients (aged 0-21 years) who underwent implantation of a vagus nerve stimulator between January 2009 and January 2020 at the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh. They used paired t-tests to assess differences in the number of ED visits 2 years before versus 2 years after VNS device implantation. Univariable linear regression analyses were used to test associations of preoperative characteristics with change in the number of ED visits following vagus nerve stimulator insertion.

RESULTS: This study included 240 patients. Compared with patients without seizure-related ED visits before VNS, patients with ≥ 1 ED visits were younger in age at first VNS surgery (9.5 vs 10.8 years), had a shorter epilepsy duration before VNS surgery (5.8 vs 7.4 years), had a later year of device implantation (2014 vs 2012), and on average took more antiseizure medications (ASMs; 2.4 vs 2.1). There was no significant difference between the total number of seizure-related ED visits pre- versus post-VNS surgery (1.72 vs 1.59, p = 0.50), and no difference in status epilepticus-related visits (0.59 vs 0.46, p = 0.17). Univariable linear regression analyses revealed a mean change in ED visits of +0.3 for each year prior to 2022 and -0.5 for each additional ASM that patients took before vagus nerve stimulator insertion.

CONCLUSIONS: This single-institution analysis demonstrated no significant change in the number of seizure-related ED visits within 2 years following VNS device implantation. Earlier VNS surgery was associated with more seizure-related ED visits after device insertion, suggesting that medical management and center experience may play a role in decreasing seizure-related ED visits. A greater number of ASMs was associated with fewer seizure-related ED visits after VNS device insertion, suggesting the role of medical management, patient baseline seizure threshold, and caregiver comfort with at-home seizure management.

PMID:38905712 | DOI:10.3171/2024.4.PEDS23310

Clinical Characteristics and Prognosis of Herpes Zoster Laryngitis With Vocal Fold Immobility

J Voice. 2024 Jun 20:S0892-1997(24)00172-3. doi: 10.1016/j.jvoice.2024.05.020. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics and prognosis of herpes zoster laryngitis with vocal fold immobility.

STUDY DESIGN: Retrospective study.

METHODS: Clinical characteristics, laryngeal signs on strobolaryngoscopy, imaging examination findings, and outcomes of patients were analyzed retrospectively.

RESULTS: This study included 17 patients (11 males [64.7%] and six females [35.3%]), with a mean age of 63.3 ± 6.7 years. The primary symptoms were hoarseness (94.1%), dysphagia (76.5%), pharyngalgia on one side (76.5%), and aspiration (70.6%). No patient had skin herpes of the head and neck. The duration of symptoms was 5-30 days (median: 10 days). Twelve patients (70.6%) were in an immunocompromised state before the disease. Strobolaryngoscopy showed congestion and swelling of the mucosa on one side of the larynx, with whitish eruptions on the supraglottic mucosa and ipsilateral vocal fold immobility. Five patients (29.4%) exhibited signs of ipsilateral accessory nerve injury. The imaging examination showed supraglottic inflammatory changes in 12 patients (70.6%). Among the 14 patients whose treatment could be clearly described, only one patient received antiviral treatment, whereas others received neurotrophic and symptomatic treatment. Notably, all patients demonstrated good outcomes because their symptoms eventually returned to normal.

CONCLUSION: Herpes zoster laryngitis is caused by varicella-zoster virus infection of the vagus nerve. It is characterized by laryngeal herpetic changes on one side and unilateral vocal fold immobility. The inducement of the disease tends to be associated with the abnormal immune state of patients. It can be easily misdiagnosed because of the absence of skin herpetic changes. Regardless of antiviral therapy, patients generally exhibit a favorable outcome.

PMID:38906743 | DOI:10.1016/j.jvoice.2024.05.020

Role of oxidative phosphorylation in the antidepressant effects of arketamine via the vagus nerve-dependent spleen-brain axis

Neurobiol Dis. 2024 Jun 18:106573. doi: 10.1016/j.nbd.2024.106573. Online ahead of print.

ABSTRACT

Arketamine, the (R)-enantiomer of ketamine, exhibits antidepressant-like effects in mice, though the precise molecular mechanisms remain elusive. It has been shown to reduce splenomegaly and depression-like behaviors in the chronic social defeat stress (CSDS) model of depression. This study investigated whether the spleen contributes to the antidepressant-like effects of arketamine in the CSDS model. We found that splenectomy significantly inhibited arketamine’s antidepressant-like effects in CSDS-susceptible mice. RNA-sequencing analysis identified the oxidative phosphorylation (OXPHOS) pathway in the prefrontal cortex (PFC) as a key mediator of splenectomy’s impact on arketamine’s effects. Furthermore, oligomycin A, an inhibitor of the OXPHOS pathway, reversed the suppressive effects of splenectomy on arketamine’s antidepressant-like effects. Specific genes within the OCPHOS pathways, such as COX11, UQCR11 and ATP5e, may contribute to these inhibitory effects. Notably, transforming growth factor (TGF)-β1, along with COX11, appears to modulate the suppressive effects of splenectomy and contribute to arketamine’s antidepressant-like effects. Additionally, SRI-01138, an agonist of the TGF-β1 receptor, alleviated the inhibitory effects of splenectomy on arketamine’s antidepressant-like effects. Subdiaphragmatic vagotomy also counteracted the inhibitory effects of splenectomy on arketamine’s antidepressant-like effects in CSDS-susceptible mice. These findings suggest that the OXPHOS pathway and TGF-β1 in the PFC play significant roles in the antidepressant-like effects of arketamine, mediated through the spleen-brain axis via the vagus nerve.

PMID:38901783 | DOI:10.1016/j.nbd.2024.106573

Transcutaneous vagal nerve stimulation during lower body negative pressure

Auton Neurosci. 2024 Jun 2;254:103192. doi: 10.1016/j.autneu.2024.103192. Online ahead of print.

ABSTRACT

BACKGROUND: Para-sympathetic vagal activation has profound influence on heart rate and other cardiovascular parameters. We tested the hypothesis that transcutaneous Vagal Nerve Stimulation (tVNS) through the auricular branch of the vagus nerve would attenuate the normal sympathetic response to central blood volume reduction by lower body negative pressure (LBNP).

METHOD: 10 healthy volunteers (6 female; age 21 ± 2 years; weight 62 ± 13 kg; height 167 ± 12 cm) were included in this cross-over design trial. After 15 min rest in supine position, subjects underwent three 15-min periods of 30 mmHg LBNP intervention with and without cyclic tVNS stimulation. Continuous cardiovascular parameters (Nexfin) were recorded.

RESULTS: Overall tVNS did not convincingly attenuate sympathetic response to central hypovolemia. Deactivation of the tVNS during LBNP resulted in increased MAP at 2.3 ± 0.5 mmHg (P < 0.001). Comparing the cyclic actual active stimulation periods to periods with pause during tVNS intervention showed a decrease in HR by 72.9 ± 11.2 to 70.2 ± 11.6 bpm (mean ± SD; P < 0.05), and concomitant increases in SV (86.0 ± 12.1 to 87.2 ± 12.6 mL; P < 0.05), MAP (82.9 ± 6.3 to 84.0 ± 6.2 mmHg; P < 0.05) and TPR (1116.0 ± 111.1 to 1153 ± 104.8 dyn*s/cm5; P < 0.05).

CONCLUSION: tVNS in 30 s cycles during LBNP can selectively attenuate HR, prompting a compensatory augmented sympathetic response. It would appear the method used in this study at least, has an isolated cardiac inhibitory effect probably mediated by augmented vagal activity on the sinoatrial or atrio-ventricular node, possibly in combination with reduced activity in the sympathetic cardiac nerve.

PMID:38896931 | DOI:10.1016/j.autneu.2024.103192

Transcutaneous auricular vagus nerve stimulation to acutely reduce emotional vulnerability and improve emotional regulation in borderline personality disorder (tVNS-BPD): study protocol for a randomized, single-blind, sham-controlled trial

Trials. 2024 Jun 19;25(1):397. doi: 10.1186/s13063-024-08230-6.

ABSTRACT

BACKGROUND: Borderline personality disorder (BPD) is considered a disorder of emotion regulation resulting from the expression of a biologically determined emotional vulnerability (that is, heightened sensitivity to emotion, increased emotional intensity/reactivity, and a slow return to emotional baseline) combined with exposure to invalidating environments. Vagal tone has been associated with activity in cortical regions involved in emotion regulation and a lower resting state of vagal tone has been observed in BPD patients relative to healthy controls. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to reduce temper outbursts in adults with Prader-Willi Syndrome, to enhance recognition of emotions in healthy students, and to improve depressive and anxiety symptoms. Furthermore, a single session of taVNS has been shown to acutely alter the recognition of facial expressions of negative valence in adolescents with MDD and increase emotion recognition in controls. However, the effect of taVNS on emotional vulnerability and regulation in individuals diagnosed with BPD has not been investigated. Our aims are to determine if taVNS is effective in acutely reducing emotional vulnerability and improve emotional regulation in BPD patients.

METHODS: Forty-two patients will be randomized to a single session of taVNS or sham-taVNS while going through an affect induction procedure. It will consist of the presentation of one neutral and three negative affect-evoking 4-min-long videos in sequence, each of which is followed by a 4-min post-induction period during which participants will rate the quality and intensity of their current self-reported emotions (post-induction ratings) and the perceived effectiveness in managing their emotions during the video presentation. The rating of the current self-reported emotions will be repeated after every post-induction period (recovery ratings). Mixed models with individuals as random effect will be used to investigate the ratings at each stage of the study, taking into account the repeated measures of the same individuals at baseline, pre-induction, post-induction, and recovery.

DISCUSSION: The study has potential to yield new insights into the role of vagal tone in emotion dysregulation in BPD and offer preliminary data on the effectiveness of taVNS as a possible non-invasive brain stimulation to treat a core symptom of BPD.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05892900. Retrospectively registered on Jun 07, 2023.

PMID:38898522 | PMC:PMC11186228 | DOI:10.1186/s13063-024-08230-6

Nonpharmacological Approaches to Managing Heart Failure With Preserved Ejection Fraction

Circ Heart Fail. 2024 Jun 18:e011269. doi: 10.1161/CIRCHEARTFAILURE.123.011269. Online ahead of print.

ABSTRACT

Heart failure with preserved ejection fraction (HFpEF) is a common subtype of heart failure marked by impaired left ventricular diastolic function and decreased myocardial compliance. Given the limited availability of evidence-based pharmacological treatments for HFpEF, there is a growing interest in nonpharmacological interventions as viable therapeutic alternatives. This review aims to explore the pathophysiology of HFpEF and present recent advancements in nonpharmacological management approaches, encompassing noninvasive therapies, invasive procedures and targeted treatments for comorbidities. An extensive literature review was undertaken to identify and synthesize emerging nonpharmacological treatment options for HFpEF, assessing their potential to enhance patient outcomes. Nonpharmacological strategies, such as vagus nerve stimulation, percutaneous pulmonary artery denervation, renal denervation, transcatheter insertion of atrial shunts and pericardial resection, demonstrate promising potential for alleviating HFpEF symptoms and improving patient prognosis. Moreover, addressing comorbidities, such as hypertension and diabetes, may offer additional therapeutic benefits. These cutting-edge techniques, in conjunction with well-established exercise therapies, pave the way for future research and clinical applications in the field. Nonpharmacological interventions hold promise for advancing HFpEF patient care and fostering a deeper understanding of these treatment approaches, which will facilitate new clinical applications and contribute to the development of more targeted therapies.

PMID:38887946 | DOI:10.1161/CIRCHEARTFAILURE.123.011269

Proof of mechanism investigation of Transcutaneous auricular vagus nerve stimulation through simultaneous measurement of autonomic functions: a randomized controlled trial protocol

Biopsychosoc Med. 2024 Jun 18;18(1):15. doi: 10.1186/s13030-024-00311-x.

ABSTRACT

BACKGROUND: The autonomic nervous system plays a vital role in regulating physiological functions. Transcutaneous auricular vagus nerve stimulation (taVNS) is a method that provides insights into autonomic nerve modulation. This paper presents a research protocol investigating proof of mechanism for the impact of taVNS on autonomic functions and aims to both deepen theoretical understanding and pave the way for clinically relevant applications.

METHODS: This protocol employs a single-blind, randomized cross-over design involving 10 healthy male participants. Simultaneous assessment of both the afferent and efferent aspects of the vagus nerve will be performed by integrating physiological measures, magnetic resonance imaging, and a questionnaire survey. Electrocardiogram will be measured to assess changes in heart rate, as a primary outcome, and heart rate variability. Active taVNS and sham stimulation will be compared, which ensures precision and blinding. Electrical stimulation will be applied to the left concha cymba and the left lobule for the active and sham conditions, respectively. The specific parameters of taVNS involve a pulse width of 250 µs, a frequency of 25 Hz, and a current adjusted to the perception threshold (0.1 mA ≤ 5 mA), delivered in cycles of 32 s on and 28 s off.

CONCLUSIONS: This research investigates proof of mechanism for taVNS to elucidate its modulatory effects on the central and peripheral components of the autonomic nervous system. Beyond theoretical insights, the findings will provide a foundation for designing targeted neuromodulation strategies, potentially benefiting diverse patient populations experiencing autonomic dysregulation. By elucidating the neural mechanisms, this study contributes to the evolution of personalized and effective clinical interventions in the field of neuromodulation.

TRIAL REGISTRATION: JRCT, jRCTs032220332, Registered 13 September 2022; https://jrct.niph.go.jp/latest-detail/jRCTs032220332 .

PMID:38890677 | PMC:PMC11184723 | DOI:10.1186/s13030-024-00311-x

Sinus Node Dysfunction Triggered by Tonsillar Abscess: Effects of Vagal Nerve Compression

Am J Case Rep. 2024 Jun 16;25:e943944. doi: 10.12659/AJCR.943944.

ABSTRACT

BACKGROUND Compression of the vagus nerve by a pharyngeal mass is a well-documented condition that can result in sinus node dysfunction (SND). However, there is scarce literature on extrinsic vagal nerve compression from a tonsillar abscess. CASE REPORT A 59-year-old woman with a history of asthma and chronic throat discomfort presented to the Emergency Department with bradycardia, palpitations, and voice changes. Following a shellfish allergy hospitalization, an otolaryngology evaluation revealed an enlarged right tonsil, recommending tonsillectomy, but scheduling challenges persisted. The patient reported mild throat pain, dysphagia, hoarseness, rhinorrhea, and exertional dyspnea and was admitted for the evaluation of peritonsillar mass. She was found to be bradycardic with a heart rate of 47, with an electrocardiogram revealing SND. Albuterol and ipratropium nebulizers, as well as dexamethasone and pantoprazole, were initiated. With this treatment, the patient symptomatically improved with a new heart rate of 68. She was discharged with outpatient appointments, but was unfortunately lost to follow-up. CONCLUSIONS This case reveals sinus node dysfunction resulting from extrinsic vagal nerve compression by a tonsillar abscess. Pressure on the vagus nerve can trigger bradycardia and low blood pressure, possibly due to compensatory overfiring of afferent vagal nerve signals from local mass effect. Early recognition and antibiotic treatment are essential to prevent cardiac complications. Clinicians must remain vigilant for such extrinsic causes, particularly in patients with chronic sore throat and cardiac symptoms. Further research and case reports are needed to deepen our understanding of this rare yet significant association.

PMID:38879750 | DOI:10.12659/AJCR.943944

Management of Parapharyngeal Metastatic Medullary Thyroid Carcinoma Via a Combined Trans-Cervical and Trans-Oral Robotic Approach

Ann Otol Rhinol Laryngol. 2024 Jun 14:34894241261630. doi: 10.1177/00034894241261630. Online ahead of print.

ABSTRACT

INTRODUCTION: Medullary thyroid carcinoma constitutes 5% to 10% of all thyroid cancers. Metastatic adenopathies may pose challenges in intricate anatomical locations, such as the parapharyngeal space. A rare case of metastatic medullary thyroid carcinoma in the parapharyngeal space has been treated in our unit using combined trans-cervical trans-oral robotic surgery. Our objective was to provide a detailed description of the surgery performed on this patient.

METHOD: We reported a singular case report worth of interest.

RESULT: A 42-year-old woman was addressed in our unit for the management of a medullary thyroid carcinoma adenopathy located in the right parapharyngeal space. A parapharyngeal 40.0 mm × 25.0 mm × 12.0 mm adenopathy was removed using a combined trans-cervical and trans-oral robotic approach without sacrifice or injury of vascular or nervous structure. Neither the tracheostomy nor the feeding tube was implemented. Feeding was resumed on postoperative day 1 and hospitalization spanned 7 days.

CONCLUSION: An innovative combined trans-cervical and trans-oral robotic surgery approach was conducted to address a metastatic medullary thyroid carcinoma in the parapharyngeal space. This surgical technique allowed us to circumvent the need for a trans-mandibular approach, tracheostomy, and feeding tube and enabling successful tumor removal without fragmentation. Postoperative care was significantly eased. The sole complication observed was dysphonia, likely resulting from intra-operative stretching of the vagus nerve during the dissection of the carotid artery.

PMID:38877727 | DOI:10.1177/00034894241261630

Feasibility of the enhanced neuromuscular blockade recovery protocol with selective use of sugammadex in thyroid surgery with intraoperative neuromonitoring

Head Neck. 2024 Jun 15. doi: 10.1002/hed.27826. Online ahead of print.

ABSTRACT

BACKGROUND: To investigate feasibility of utilizing enhanced neuromuscular blocking agents with selective recovery protocol during thyroid surgery with intraoperative neuromonitoring (IONM).

METHODS: Two-hundred and ninety patients were randomized into two groups: group A 0.3 mg/kg rocuronium and group B 0.6 mg/kg. Sugammadex 2 mg/kg was injected if needed followed initial vagal stimulation (V0). Electromyography signals from vagus and recurrent laryngeal nerves before and after resection were recorded as V1, V2, R1, and R2.

RESULTS: In group B, 30 patients (20.7%) had V0 signals <100 μV, compared to 9 (6.2%) in group A. After sugammadex administration, 144 patients (99.3%) in both groups achieved positive V1 signals. Group B demonstrated a shorter surgical time from rocuronium injection to V2 stimulation compared to group A, accompanied by a significantly lower incidence of intraoperative body movement (0 vs. 16 patients).

CONCLUSIONS: 0.6 mg/kg rocuronium with selective use 2 mg/kg sugammadex for IONM in thyroid surgery can meet both anesthesia and surgery demands.

PMID:38877778 | DOI:10.1002/hed.27826