Integrative effects of transcutaneous auricular vagus nerve stimulation on esophageal motility and pharyngeal symptoms via vagal mechanisms in patients with laryngopharyngeal reflux disease

Front Neurosci. 2024 Mar 7;18:1287809. doi: 10.3389/fnins.2024.1287809. eCollection 2024.

ABSTRACT

BACKGROUND AND AIM: Laryngopharyngeal reflux disease (LPRD) is primarily characterized by discomfort in the pharynx and has limited treatment options. This research aimed to assess the efficacy of transcutaneous auricular vagus nerve stimulation (tVNS) in patients with LPRD and delve into the potential underlying mechanisms.

METHODS: A total of 44 participants, diagnosed with LPRD were divided into two groups randomly. Twice-daily stimulation was delivered for 2 weeks for patients in experimental group, with stimulation ranging from 1.0 mA to 1.5 mA (n = 22), while the control group underwent sham tVNS (n = 22) with the same stimulation parameters and different anatomical location. The severity of symptoms and levels of anxiety and depression were monitored using questionnaires. High-resolution esophageal manometry data were collected, and the patients’ autonomic function was assessed through heart rate variability analysis.

RESULTS: There was a positive correlation between reflux symptom index (RSI) scores and low frequency/high frequency (LF/HF) ratio (r = 0.619; p < 0.001), Hamilton anxiety scale (HAMA) scores (r = 0.623; p < 0.001), and Hamilton depression scale (HAMD) scores (r = 0.593; p < 0.001). Compared to the pre-tVNS phase, RSI (p < 0.001), HAMA (p < 0.001), and HAMD (p < 0.001) scores were significantly reduced after 2 weeks of treatment. Additionally, the resting pressure of the upper esophageal sphincter (UESP; p < 0.05) and lower esophageal sphincter (LESP; p < 0.05) showed significant enhancement. Notably, tVNS led to an increase in root mean square of successive differences (RMSSD; p < 0.05) and high frequency (HF; p < 0.05) within heart rate variability compared to the pre-treatment baseline. Compared to the control group, RSI (p < 0.001), HAMA (p < 0.001), and HAMD (p < 0.001) scores in tVNS group were significantly lower at the end of treatment. Similarly, the resting pressure of UESP (p < 0.05) and LESP (p < 0.05) in tVNS group were significantly higher than that of control group. Notably, RMSSD (p < 0.05) and HF (p < 0.05) in tVNS group were significantly higher than that of control group.

CONCLUSION: This study demonstrated that tVNS as a therapeutic approach is effective in alleviating LPRD symptoms. Furthermore, it suggests that improvements in esophageal motility could be associated with vagus nerve-dependent mechanisms.

PMID:38516311 | PMC:PMC10954818 | DOI:10.3389/fnins.2024.1287809

The changing landscape of palliative epilepsy surgery for Lennox Gastaut Syndrome

Front Neurol. 2024 Mar 7;15:1380423. doi: 10.3389/fneur.2024.1380423. eCollection 2024.

ABSTRACT

Lennox Gastaut Syndrome (LGS) is characterized by drug-resistant epilepsy that typically leads to decreased quality of life and deleterious neurodevelopmental comorbidities from medically refractory seizures. In recent years there has been a dramatic increase in the development and availability of novel treatment strategies for Lennox Gastaut Syndrome patient to improve seizure. Recent advances in neuromodulation and minimally invasive magnetic resonance guided laser interstitial thermal therapy (MRgLITT) have paved the way for new treatments strategies including deep brain stimulation (DBS), responsive neurostimulation (RNS), and MRgLITT corpus callosum ablation. These new strategies offer hope for children with drug-resistant generalized epilepsies, but important questions remain about the safety and effectiveness of these new approaches. In this review, we describe the opportunities presented by these new strategies and how each treatment strategy is currently being employed. Next, we will critically assess available evidence for these new approaches compared to traditional palliative epilepsy surgery approaches, such as vagus nerve stimulation (VNS) and open microsurgical corpus callosotomy (CC). Finally, we will describe future directions that would help define which of the available strategies should be employed and when.

PMID:38515452 | PMC:PMC10954786 | DOI:10.3389/fneur.2024.1380423

Neurostimulation After Stroke

Phys Med Rehabil Clin N Am. 2024 May;35(2):369-382. doi: 10.1016/j.pmr.2023.06.008. Epub 2023 Aug 21.

ABSTRACT

Neural stimulation technology aids stroke survivors in regaining lost motor functions. This article explores its applications in upper and lower limb stroke rehabilitation. The authors review various methods to target the corticomotor system, including transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and vagus nerve stimulation. In addition, the authors review the use of peripheral neuromuscular electrical stimulation for therapeutic and assistive purposes, including transcutaneous electrical nerve stimulation, neuromuscular electrical stimulation, and functional electrical stimulation. For each, the authors examine the potential benefits, limitations, safety considerations, and FDA status.

PMID:38514224 | DOI:10.1016/j.pmr.2023.06.008

The predictive potential of Heart Rate Variability for Depression

Neuroscience. 2024 Mar 19:S0306-4522(24)00126-X. doi: 10.1016/j.neuroscience.2024.03.013. Online ahead of print.

ABSTRACT

Heart rate variability (HRV),a measure of the fluctuations in the intervals between consecutive heartbeats, is an indicator of changes in the autonomic nervous system. A chronic reduction in HRV has been repeatedly linked to clinical depression. However, the chronological and mechanistic aspects of this relationship, between the neural, physiological, and psychopathological levels, remain unclear. In this review we present evidence by which changes in HRV might precede the onset of depression. We describe several pathways that can facilitate this relationship. First, we examine a theoretical model of the impact of autonomic imbalance on HRV and its role in contributing to mood dysregulation and depression. We then highlight brain regions that are regulating both HRV and emotion, suggesting these neural regions as potential mediators of this relationship, and the Insula in particular. We also present additional possible mediating mechanisms involving the immune system and inflammation processes. Lastly, we support this model by showing evidence that modification of HRV with biofeedback leads to an improvement in some depression symptoms. The possibility that changes in HRV precede the onset of depression is a critical possibility to put to the test, not only because it will provide insights into the mechanisms of the illness but also because it may offer a predictive anddiagnosticphysiological marker for depression. Importantly, it may then also help develop new effective clinical interventions for the treatment of depression.

PMID:38513761 | DOI:10.1016/j.neuroscience.2024.03.013

Vagus nerve stimulation alleviates cardiac dysfunction and inflammatory markers during heart failure in rats

Auton Neurosci. 2024 Mar 4;253:103162. doi: 10.1016/j.autneu.2024.103162. Online ahead of print.

ABSTRACT

Vagus nerve stimulation (VNS) is under clinical investigation as a therapy for heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate its therapeutic effects on three main components of heart failure: cardiac function, cardiac remodeling and central neuroinflammation using a pressure overload (PO) rat model. Male Sprague-Dawley rats were divided into four groups: PO, PO + VNS, PO + VNS sham, and controls. All rats, except controls, underwent a PO surgery to constrict the thoracic aorta (~50 %) to induce HFrEF. Open loop VNS therapy was continuously administered to PO + VNS rats at 20 Hz, 1.0 mA for 60 days. Evaluation of cardiac function and structure via echocardiograms showed decreases in stroke volume and relative ejection fraction and increases in the internal diameter of the left ventricle during systole and diastole in PO rats (p < 0.05). However, these PO-induced adverse changes were alleviated with VNS therapy. Additionally, PO rats exhibited significant increases in myocyte cross sectional areas indicating hypertrophy, along with significant increases in myocardial fibrosis and apoptosis, all of which were reversed by VNS therapy (p < 0.05). Furthermore, VNS mitigated microglial activation in two central autonomic nuclei: the paraventricular nucleus of the hypothalamus and locus coeruleus. These findings demonstrate that when VNS therapy is initiated at an early stage of HFrEF progression (<10 % reduction in relative ejection fraction), the supplementation of vagal activity is effective in restoring multi organ homeostasis in a PO model.

PMID:38513382 | DOI:10.1016/j.autneu.2024.103162

Unmet needs of drugs for irritable bowel syndrome and inflammatory bowel diseases: interest of vagus nerve stimulation and hypnosis

Inflammopharmacology. 2024 Mar 21. doi: 10.1007/s10787-024-01446-7. Online ahead of print.

ABSTRACT

The gut and the brain communicate bidirectionally through the autonomic nervous system. The vagus nerve is a key component of this gut-brain axis, and has numerous properties such as anti-inflammatory, antinociceptive, anti-depressive effects. A perturbation of this gut-brain communication is involved in the pathogeny of functional digestive disorders, such as irritable bowel syndrome, and inflammatory bowel diseases. Stress plays a role in the pathogeny of these diseases, which are biopsychosocial models. There are presently unmet needs of pharmacological treatments of these chronic debilitating diseases. Treatments are not devoid of side effects, cost-effective, do not cure the diseases, can lose effects over time, thus explaining the poor satisfaction of patients, their lack of compliance, and their interest for non-drug therapies. The gut-brain axis can be targeted for therapeutic purposes in irritable bowel syndrome and inflammatory bowel disease through non-drug therapies, such as hypnosis and vagus nerve stimulation, opening up possibilities for responding to patient expectations.

PMID:38512653 | DOI:10.1007/s10787-024-01446-7

Surgical complications of vagus nerve stimulation surgery: A 14-years single-center experience

Brain Spine. 2023 Dec 14;4:102733. doi: 10.1016/j.bas.2023.102733. eCollection 2024.

ABSTRACT

INTRODUCTION: Vagus nerve stimulation (VNS) is the most frequently used neuromodulation treatment for Drug-Resistant Epilepsy (DRE) patients. Complications of VNS surgery include surgical site infection and unilateral vocal cord paresis. Complication rates vary across studies.

RESEARCH QUESTION: What is the safety profile of VNS related surgeries?

MATERIALS AND METHODS: Retrospective cohort study using patient files of DRE-patients who had undergone primary implantation of a VNS-system, replacement of the VNS pulse generator, replacement of the lead, replacement of both pulse generator and lead, or VNS removal surgery in the Maastricht UMC+. Multiple Imputation was used for missing data. Univariable and multivariable logistic regression analysis were performed to analyze possible risk factors, in case of a small sample size, an independent-samples t-test and Fisher’s exact test or Pearson’s X2-test were used. The complication rate was calculated as percentage.

RESULTS: This study included a total of 606 VNS surgical procedures, leading to 67 complications of which 3 permanent complications. Complication rate after primary implantation was 13.4%; 2,5% for pulse generator replacement; 21.4% for lead revision and 27.3% for complete VNS removal. No statistically significant results were found when analyzing the results of adults and children <18 years separately.

DISCUSSION AND CONCLUSION: Complication rates of VNS-related surgeries in our own institutional series are low and comparable to previously reported series. VNS surgery is a relatively safe procedure. The complication rate differs per type of surgery and mean surgery duration was longer for patients with complications after lead revision surgery compared to patients without complications.

PMID:38510607 | PMC:PMC10951712 | DOI:10.1016/j.bas.2023.102733

A framework for the interpretation of heart rate variability applied to transcutaneous auricular vagus nerve stimulation and osteopathic manipulation

Physiol Rep. 2024 Mar;12(6):e15981. doi: 10.14814/phy2.15981.

ABSTRACT

Reports on autonomic responses to transcutaneous auricular vagus nerve stimulation (taVNS) and osteopathic manipulative techniques have been equivocal, partly due to inconsistent interpretation of heart rate variability (HRV). We developed a mechanistic framework for the interpretation of HRV based on a model of sinus node automaticity that considers autonomic effects on Phase 3 repolarization and Phase 4 depolarization of the sinoatrial action potential. The model was applied to HRV parameters calculated from ECG recordings (healthy adult humans, both genders) before (30 min), during (15 min), and after (30 min) a time control intervention (rest, n = 23), taVNS (10 Hz, 300 μs, 1-2 mA, cymba concha, left ear, n = 12), or occipitoatlantal decompression (OA-D, n = 14). The experimental protocol was repeated on 3 consecutive days. The model simulation revealed that low frequency (LF) HRV best predicts sympathetic tone when calculated from heart rate time series, while high frequency (HF) HRV best predicts parasympathetic tone when calculated from heart period time series. Applying our model to the HRV responses to taVNS and OA-D, revealed that taVNS increases cardiac parasympathetic tone, while OA-D elicits a mild decrease in cardiac sympathetic tone.

PMID:38508860 | PMC:PMC10954510 | DOI:10.14814/phy2.15981

Racial disparities in the utilization of invasive neuromodulation devices for the treatment of drug-resistant focal epilepsy

Epilepsia. 2024 Mar 20. doi: 10.1111/epi.17961. Online ahead of print.

ABSTRACT

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for patients reporting more than one race. Of 154 patients enrolled in HEP2, 55 (36%) underwent invasive neuromodulation for DRE management at some point in the course of their epilepsy. Of those, 36 (71%) were patients who identified as White. Patients were significantly less likely to have a device if they identified solely as Black/African American than if they did not (odds ratio = .21, 95% confidence interval = .05-.96, p = .03). Invasive neuromodulation for management of DRE is underutilized in the Black/African American population, indicating a new facet of racial disparities in epilepsy care.

PMID:38506370 | DOI:10.1111/epi.17961

Right upper lobectomy with mediastinal dissection under uniportal video-assisted thoracoscopic surgery for lung cancer in a patient with a right-sided aortic arch: a case report

J Cardiothorac Surg. 2024 Mar 19;19(1):136. doi: 10.1186/s13019-024-02627-9.

ABSTRACT

BACKGROUND: A right-sided aortic arch is a rare congenital vascular structure variation. Right lobectomy is not commonly performed on patients with such a condition. Further, there are no reports on lobectomy under uniportal video-assisted thoracoscopic surgery (VATS) in this patient group.

CASE PRESENTATION: A 67-year-old man with a right-sided aortic arch and Kommerell diverticulum underwent right upper lobectomy with mediastinal lymph node dissection under uniportal VATS for primary lung cancer. Due to the right descending aorta, which narrows the space of the dorsal hilum, handling of the stapler for stapling the right upper lobe bronchus from the uniport in the 6th intercostal space at the medial axillary line can be challenging. This issue was resolved by manipulating the staple over the azygos vein toward the inferior margin of the aortic arch. Via mediastinal lymphadenectomy, we found that the right recurrent laryngeal nerve branched from the right vagus nerve and hooked around the right-sided aortic arch.

CONCLUSIONS: Right lobectomy with mediastinal lymph node dissection under uniportal VATS can be performed for lung cancer in patients with a right-sided aortic arch.

PMID:38504342 | DOI:10.1186/s13019-024-02627-9