Effects of multisession prefrontal cortex tDCS or taVNS on stress, perceived stress and sleep quality: a double-blind, randomized controlled study.

Introduction: Chronic stress is a condition characterized by prolonged stimulation, leading to mental and physical weakness. It can have detrimental effects on individuals' mental health and cognitive function, potentially causing various health issues. This article explores the potential of non-invasive neuromodulation techniques, specifically transcranial direct current stimulation (tDCS) and transcutaneous auricular vagus nerve stimulation (taVNS), in managing chronic stress and improving sleep quality. Methods: The study conducted a randomized, double-blinded, controlled trial with participants experiencing chronic stress. In total, 100 participants were randomly assigned to one of four conditions: the anodal tDCS group (n = 50), the sham tDCS group (n = 50), the taVNS group (n = 50), or the sham taVNS group (n = 50). Within each condition, participants received five sessions of either active treatment or sham treatment, with 20 min of tDCS over the dorsolateral prefrontal cortex (2 mA) for the tDCS groups, or taVNS on the left ear (20 Hz) for the taVNS groups. At baseline, post-intervention, and 4 weeks thereafter, we evaluated stress using the Lipp's Inventory of Stress Symptoms for Adults (LSSI), perceived stress through the Perceived Stress Scale (PSS-10), and sleep quality via the Pittsburgh Sleep Quality Index (PSQI). Results: The tDCS and taVNS interventions resulted in reduced stress levels, improved sleep quality, and enhanced perception of stress. Discussion: These findings suggest that tDCS and taVNS hold promise as effective treatments for chronic stress, offering a safe and accessible approach to improving individuals' wellbeing and overall quality of life. Clinical trial registration: https://ensaiosclinicos.gov.br/rg/RBR-2ww2ts8, identifier UTN: U1111-1296-1810; Brazilian Registry of Clinical Trials (REBEC) RBR-2ww2ts8.

Transcutaneous vagus nerve stimulation effects on chronic pain: systematic review and meta-analysis.

Chronic pain is one of the major causes of disability with a tremendous impact on an individual's quality of life and on public health. Transcutaneous vagus nerve stimulation (tVNS) is a safe therapeutic for this condition. We aimed to evaluate its effects in adults with chronic pain. A comprehensive search was performed, including randomized controlled trials published until October 2023, which assessed the effects of noninvasive tVNS. Cohen's d effect size and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were performed. Fifteen studies were included. The results revealed a mean effect size of 0.41 (95% CI 0.17-0.66) in favor of tVNS as compared with control, although a significant heterogeneity was observed (χ2 = 21.7, df = 10, P = 0.02, I 2 = 53.9%). However, when compared with nonactive controls, tVNS shows a larger effect size (0.79, 95% CI 0.25-1.33), although the number of studies was small (n = 3). When analyzed separately, auricular tVNS and cervical tVNS against control, it shows a significant small to moderate effect size, similar to that of the main analysis, respectively, 0.42 (95% CI 0.08-0.76, 8 studies) and 0.36 (95% CI 0.01-0.70, 3 studies). No differences were observed in the number of migraine days for the trials on migraine. This meta-analysis indicates that tVNS shows promise as an effective intervention for managing pain intensity in chronic pain conditions. We discuss the design of future trials to confirm these preliminary results, including sample size and parameters of stimulation.

Brain Perception of Different Oils on Appetite Regulation: An Anorectic Gene Expression Pattern in the Hypothalamus Dependent on the Vagus Nerve.

(1) Background: We examined the effect of the acute administration of olive oil (EVOO), linseed oil (GLO), soybean oil (SO), and palm oil (PO) on gastric motility and appetite in rats. (2) Methods: We assessed food intake, gastric retention (GR), and gene expression in all groups. (3) Results: Both EVOO and GLO were found to enhance the rate of stomach retention, leading to a decrease in hunger. On the other hand, the reduction in food intake caused by SO was accompanied by delayed effects on stomach retention. PO caused an alteration in the mRNA expression of NPY, POMC, and CART. Although PO increased stomach retention after 180 min, it did not affect food intake. It was subsequently verified that the absence of an autonomic reaction did not nullify the influence of EVOO in reducing food consumption. Moreover, in the absence of parasympathetic responses, animals that received PO exhibited a significant decrease in food consumption, probably mediated by lower NPY expression. (4) Conclusions: This study discovered that different oils induce various effects on parameters related to food consumption. Specifically, EVOO reduces food consumption primarily through its impact on the gastrointestinal tract, making it a recommended adjunct for weight loss. Conversely, the intake of PO limits food consumption in the absence of an autonomic reaction, but it is not advised due to its contribution to the development of cardiometabolic disorders.

Age as an Effect Modifier of the Effects of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Heart Rate Variability in Healthy Subjects.

Background: Evidence suggests that vagus nerve stimulation can modulate heart rate variability (HRV). However, there is a lack of mechanistic studies in healthy subjects assessing the effects of bilateral transcutaneous auricular vagus nerve stimulation (taVNS) on HRV. Our study aims to investigate how taVNS can influence the HRV response, including the influence of demographic variables in this response. Methods: Therefore, we conducted a randomized controlled study with 44 subjects, 22 allocated to active and 22 to sham taVNS. Results: Our results showed a significant difference between groups in the high-frequency (HF) metric. Active taVNS increased the HF metric significantly as compared to sham taVNS. Also, we found that age was a significant effect modifier of the relationship between taVNS and HF-HRV, as a larger increase in HF-HRV was seen in the older subjects. Importantly, there was a decrease in HF-HRV in the sham group. Conclusions: These findings suggest that younger subjects can adapt and maintain a constant level of HF-HRV regardless of the type of stimulation, but in the older subjects, only the active taVNS recipients were able to maintain and increase their HF-HRV. These results are important because they indicate that taVNS can enhance physiological regulation processes in response to external events.

Manejo quirúrgico en el estado epiléptico superrefractario / Surgical management in Super-refractory epilepticus status

Resumen Introducción: El estado epiléptico refractario (EER) constituye una emergencia médica grave, donde la crisis no cede a pesar del tratamiento farmacológico convencional. Se describe como estado epiléptico superrefractario (EESR) la continua presencia de episodios con una duración de 24 horas o más. Este reporte de caso detalla la complejidad en el manejo y explora un enfoque multidisciplinario. Presentación del caso: Paciente masculino de 32 años con antecedente de epilepsia focal secundaria a traumatismo craneoencefálico en la niñez, quien ingresó en contexto de EESR, el cual recibió coma barbitúrico, plasmaféresis y dieta cetogénica. En los exámenes, la resonancia magnética reveló una lesión en la región frontotemporal insular derecha; en la tomografía por emisión de positrones se observaron zonas de hipermetabolismo y en el videoelectroencefalograma una continua actividad epileptiforme. Se optó por la cirugía paliativa, logrando la resolución exitosa del EESR y una clasificación Engels IA a los 14 meses. Discusión: El EESR es un evento neurológico crítico con pronóstico reservado y opciones terapéuticas desafiantes. Se describen opciones terapéuticas desde anticonvulsivantes, inmunoterapia y cirugía, donde el abordaje quirúrgico emerge como una opción eficaz, especialmente en casos con lesiones estructurales. La identificación temprana y la terapia adecuada son vitales para prevenir complicaciones. Conclusiones: El EESR representa un desafío crítico con alta carga de morbimortalidad, sin embargo, la cirugía de epilepsia muestra promisorios resultados en el contexto de causa cerebral estructural, responsable de la actividad epileptiforme. Se destaca la importancia de la identificación temprana y el manejo quirúrgico paliativo como opción viable, mejorando la calidad de vida de los pacientes.

Abstract Introduction: Refractory Status Epilepticus (RSE) is a serious medical emergency where the seizure does not subside despite conventional pharmacological treatment. The continuous presence of episodes lasting 24 hours or more is described as super-refractory status epilepticus (SRSE). This case report details the complex in teraphy management and explores a multidisciplinary approach. Case presentation: A 32-year-old male with a history of focal epilepsy secondary to head trauma in childhood. Enters emergency with a RSE episode. Barbiturate coma, plasmapheresis and ketogenic diet were administered. The Magnetic Resonance Imaging revealed a lesion in the right fronto-temporo-insular cortex, areas of hypermetabolism on Positron Emission Tomography and continuous epileptiform activity on video-electroencephalogram. Palliative surgery was chosen, achieving successful resolution of the SRSE and Engel Scale IA classification at 14 months of follow up. Discussion: The SRSE is a critical neurological event with a guarded prognosis and complex therapeutic options. Therapeutic options are described from anticonvulsants, immunotherapy and surgery. The surgical approach emerges as an effective option, especially in cases with structural injuries. Early identification and appropriate therapy are vital to prevent complications. Conclusions: SRSE represents a critical challenge with a high burden of morbidity and mortality. However, epilepsy surgery shows promising results in the context of the structural brain cause responsible for epileptiform activity. The importance of early identification and palliative surgical management as a viable option is highlighted, improving the quality of life of patients.

Cholinergic Stimulation Exerts Cardioprotective Effects and Alleviates Renal Inflammatory Responses after Acute Myocardial Infarction in Spontaneous Hypertensive Rats (SHRs).

BACKGROUND: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). METHODS: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)-40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. RESULTS: Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury. CONCLUSIONS: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

Replacement of traditional vagus nerve stimulation with cardiac-based device and seizure reduction: A systematic review and meta-analysis.

INTRODUCTION: For patients with drug-resistant epilepsy (DRE) who are not suitable for surgical resection, neuromodulation with vagus nerve stimulation (VNS) is an established approach. However, there is limited evidence of seizure reduction when replacing traditional VNS (tVNS) device with a cardiac-based one (cbVNS). This meta-analysis compares the seizure reduction achieved by replacing tVNS with cbVNS in a population with DRE. METHODS: We systematically searched PubMed, Embase, and Cochrane Central following PRISMA guidelines. The main outcomes were number of patients experiencing a ≥ 50 % and ≥80 % reduction in seizures, as defined by the McHugh scale. Additionally, we assessed the number of patients achieving freedom from seizures. RESULTS: We included 178 patients with DRE from 7 studies who were initially treated with tVNS and subsequently had it replaced by cbVNS. The follow-up for cbVNS ranged from 6 to 37.5 months. There was a statistically significant reduction in seizure frequency with the replacement of tVNS by cbVNS, using a ≥ 50 % (OR 1.79; 95 % CI 1.07 to 2.97; I²=0 %; p = 0.03) and a ≥ 80 % (OR 2.06; 95 % CI 1.17 to 3.62; I²=0 %; p = 0.01) reduction threshold. Nineteen (13 %) participants achieved freedom from seizures after switching to cbVNS. There was no difference in the rate of freedom from seizures between groups (OR 1.85; 95 % CI 0.81 to 4.21; I²=0 %; p = 0.14). CONCLUSION: In patients with DRE undergoing battery replacement, cbVNS might be associated with seizure reduction (≥50 % and ≥80 % threshold) after switching from tVNS. Randomised controlled trials are necessary to validate these findings.

Transcutaneous Auricular Vagus Nerve Stimulation in Adolescent Treatment Resistant Depression-A Case Report.

Adolescence is a critical time period for the onset of depression, and many patients do not respond to treatment. Transcutaneous auricular vagus nerve stimulation may be a promising alternative. Here, we present the case of an adolescent girl with treatment-resistant depression who received transcutaneous auricular vagus nerve stimulation over the course of 7.5 months.

Anatomical variations of recurrent laryngeal nerve: a systematic review and meta-analyses.

PURPOSE: The aim of this systematic review and meta-analysis was to systematically review and perform a meta-analysis on the anatomical variations of the RLN. METHODS: We performed online research for studies that addressed anatomical variations of the RLN and laterality, published between 2015 and 2021. We found 230 articles, and nine were included. RESULTS: Eight variations were found, with Type I prevailing (41.17%; 95% CI 19.44-64.88), extra laryngeal divergence of the RLN. The other types were: II-fan shape; III-distance greater than 5 mm to the cricothyroid joint; IV-thickening and adipopexy in the elderly; V-non-recurrent laryngeal nerve; VI-intracranial branch; VII-tortuous ascending RLN; and VIII-combination between the inferior branch of the NV and the ascending trunk of the RLN. Types I (p = 0) and III (p < 0.01) prevailed on the left and types II (p < 0.01) and V (p < 0.01) on the right. CONCLUSIONS: It was observed that variations occurred due to the path of the RLN to the entrance to the larynx, its shape, and the age of the evaluated individual. The most frequent variation and side were, respectively, Type I, extra laryngeal divergence and left.

Making Sense of Vagus Nerve Stimulation for Stroke.

Implantable vagus nerve stimulation, paired with high-dose occupational therapy, has been shown to be effective in improving upper limb function among patients with stroke and received regulatory approval from the US Food and Drug Administration and the Centers for Medicare & Medicaid Services. Combining nonsurgical and surgical approaches of vagus nerve stimulation in recent meta-analyses has resulted in misleading reports on the efficacy of each type of stimulation among patients with stroke. This article aims to clarify the confusion surrounding implantable vagus nerve stimulation as a poststroke treatment option, highlighting the importance of distinguishing between transcutaneous auricular vagus nerve stimulation and implantable vagus nerve stimulation. Recent meta-analyses on vagus nerve stimulation have inappropriately combined studies of fundamentally different interventions, outcome measures, and participant selection, which do not conform to methodological best practices and, hence, cannot be used to deduce the relative efficacy of the different types of vagus nerve stimulation for stroke rehabilitation. Health care providers, patients, and insurers should rely on appropriately designed research to guide well-informed decisions.

Modulation of vagal activity may help reduce neurodevelopmental damage in the offspring of mothers with pre-eclampsia.

Maternal Immune Activation (MIA) has been linked to the pathogenesis of pre-eclampsia and adverse neurodevelopmental outcomes in the offspring, such as cognitive deficits, behavioral abnormalities, and mental disorders. Pre-eclampsia is associated with an activation of the immune system characterized by persistently elevated levels of proinflammatory cytokines, as well as a decrease in immunoregulatory factors. The Cholinergic Anti-inflammatory Pathway (CAP) may play a relevant role in regulating the maternal inflammatory response during pre-eclampsia and protecting the developing fetus from inflammation-induced damage. Dysregulation in the CAP has been associated with the clinical evolution of pre-eclampsia. Some studies suggest that therapeutic stimulation of this pathway may improve maternal and fetal outcomes in preclinical models of pre-eclampsia. Modulation of vagal activity influences the CAP, improving maternal hemodynamics, limiting the inflammatory response, and promoting the growth of new neurons, which enhances synaptic plasticity and improves fetal neurodevelopment. Therefore, we postulate that modulation of vagal activity may improve maternal and fetal outcomes in pre-eclampsia by targeting underlying immune dysregulation and promoting better fetal neurodevelopment. In this perspective, we explore the clinical and experimental evidence of electrical, pharmacological, physical, and biological stimulation mechanisms capable of inducing therapeutical CAP, which may be applied in pre-eclampsia to improve the mother's and offspring's quality of life.

Neuroestimulación del nervio vago, hipocampal y de núcleos anteriores y centromedianos del tálamo en epilepsia temporal: revisión de la literatura / Neurostimulation of the vagus nerve, hippocampal and anterior and centromedian nuclei of the thalamus in temporal epilepsy: literature review

Introducción: En pacientes con epilepsia del lóbulo temporal refractarios que no son candidatos a cirugía, se debe considerar la estimulación eléctrica cerebral como una opción. Contenido: La estimulación eléctrica cerebral es la administración directa de pulsos eléctricos al tejido nervioso que permite modular un sustrato patológico, interrumpir la manifestación clínica de las crisis y reducir la gravedad de estas. Así, dada la importancia de estos tratamientos para los pacientes con epilepsia del lóbulo temporal refractaria, se hace una revisión de cuatro tipos de estimulación eléctrica. La primera, la del nervio vago, es una buena opción en crisis focales y crisis generalizadas o multifocales. La segunda, la del hipocampo, es más útil en pacientes no candidatos a lobectomía por riesgo de pérdida de memoria, con resonancia magnética normal o sin esclerosis mesial temporal. La tercera, la del núcleo anterior, es pertinente principalmente en pacientes con crisis focales, pero debe realizarse con precaución en pacientes con alto riesgo de cambios cognitivos, como los ancianos, o en los que presentan alteración del estado de ánimo basal, y, por último, la del núcleo centromediano se recomienda para el tratamiento crisis focales en el síndrome de Rasmussen y crisis tónico-clónicas en el síndrome de Lennox-Gastaut. Conclusiones: El interés por la estimulación eléctrica cerebral ha venido aumentando, al igual que las estructuras diana en las cuales se puede aplicar, debido a que es un tratamiento seguro y eficaz en pacientes con epilepsia del lóbulo temporal para controlar las crisis, pues disminuye la morbimortalidad y aumenta la calidad de vida.

Introduction: In patients with refractory temporal lobe epilepsy who are not candidates for surgery, electrical brain stimulation should be considered as another option. Contents: Electrical brain stimulation is the direct administration of electrical pulses to nerve tissue that modulates a pathological substrate, interrupts the clinical manifestation of seizures, and reduces their severity. Thus, given the importance of these treatments for patients with refractory temporal lobe epilepsy, four types of electrical stimulation are reviewed. The first, vagus nerve stimulation, is a good option in focal seizures and generalized or multifocal seizures. The second, hippocampal stimulation, is more useful in patients who are not candidates for lobectomy due to the risk of memory loss, with normal MRI or without mesial temporal sclerosis. The third, the anterior nucleus, is mainly in patients with focal seizures, but with caution in patients at high risk of cognitive changes such as the elderly, or in those with baseline mood disturbance and, finally, the centromedian nucleus is recommended for the treatment of focal seizures in Rasmussen's syndrome and tonic-clonic seizures in Lennox-Gastaut syndrome. Conclusions: the interest in brain electrical stimulation has been increasing as well as the target structures in which it can be applied because it is a safe and effective treatment in patients with temporal lobe epilepsy to control seizures, decreasing morbidity and mortality and increasing quality of life

Predictive factors for successful vagus nerve stimulation in patients with refractory epilepsy: real-life insights from a multicenter study.

Introduction: Vagus nerve stimulation (VNS) therapy is an established treatment for patients with drug-resistant epilepsy that reduces seizure frequency by at least 50% in approximately half of patients; however, the characteristics of the patients with the best response have not yet been identified. Thus, it is important to identify the profile of patients who would have the best response to guide early indications and better patient selection. Methods: This retrospective study evaluated vagus nerve stimulation (VNS) as an adjuvant therapy for patients with drug-resistant epilepsy from six epilepsy centers in Brazil. Data from 192 patients aged 2-66 years were analyzed, and all patients received at least 6 months of therapy to be included. Results: Included patients were aged 2-66 years (25.6 ± 14.3), 105 (54.7%) males and 87 (45.8%) females. Median follow-up interval was 5 years (range, 2005-2018). Overall, the response rate (≥50% seizure reduction) after VNS implantation was 65.6% (126/192 patients). Most patients had 50-90% seizure reduction (60.9%) and nine patients became seizure-free. There were no serious complications associated with VNS implantation. The rate of a ≥ 50% seizure reduction response was significantly higher in patients with no history of neurosurgery. The presence of focal without generalized seizures and focal discharges on interictal EEG was associated with better response. Overall, etiological predictors of a better VNS response profile were tumors while a worse response to VNS was related to the presence of vascular malformations and Lennox-Gastaut Syndrome. Discussion: We observed an association between a better response to VNS therapy no history of neurosurgery, focal interictal epileptiform activity, and focal seizure pattern. Additionally, it is important to highlight that age was not a determinant factor of the response, as children and adults had similar response rates. Thus, VNS therapy should be considered in both adults and children with DRE.

Gut-microbiome-brain axis: the crosstalk between the vagus nerve, alpha-synuclein and the brain in Parkinson's disease.

This critical review of the literature shows that there is a close link between the microbiome, the gut, and the brain in Parkinson's disease. The vagus nerve, the main component of the parasympathetic nervous system, is involved in the regulation of immune response, digestion, heart rate, and control of mood. It can detect microbiota metabolites through its afferents, transferring this gut information to the central nervous system. Preclinical and clinical studies have shown the important role played by the gut microbiome and gut-related factors in disease development and progression, as well as treatment responses. These findings suggest that the gut microbiome may be a valuable target for new therapeutic strategies for Parkinson's disease. More studies are needed to better understand the underlying biology and how this axis can be modulated for the patient's benefit.

Organization of the Subdiaphragmatic Vagus Nerve and Its Connection with the Celiac Plexus and the Ovaries in the Female Rat.

Communication between the ovaries and the central nervous system occurs by peripheral innervation through the celiac plexus, superior ovarian nerve, and ovarian plexus nerve. The vagus nerve is involved in regulating the ovaries, but the neuroanatomical pathway that links them is not clear. Adult female rats were used for gross anatomy, acetylcholinesterase histochemistry, and the immunofluorescence analysis of tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), and tryptophan hydroxylase 2 (TPH). The results obtained indicate that the right vagus nerve (RVN) travels parallel and caudal to the esophagus, where three nerve branches were identified. Also, a right vagal plexus (RVP) formed by microganglia was described, establishing communication with the celiac plexus, and was mainly reactive to tyrosine hydroxylase (TH); some serotoninergic and cholinergic neurons were also found. The left vagus nerve (LVN) travels over the esophagus, bifurcates before its insertion into the stomach and enters the RCG. This neuroanatomical and biochemical description of the RVN and LVN in the rat suggests the RVP is formed by presynaptic catecholaminergic terminals and cholinergic neurons. This information could support detailed studies of communication between the vagus nerve and the ovaries and identify the type of neural signaling involved in abdominal control of the vagus nerve.

Neurophysiology of Brain Networks Underlies Symptoms of Parkinson's Disease: A Basis for Diagnosis and Management.

Parkinson's disease (PD) is one of the leading neurodegenerative disorders. It is considered a movement disorder, although it is accepted that many nonmotor symptoms accompany the classic motor symptoms. PD exhibits heterogeneous and overlaying clinical symptoms, and the overlap of motor and nonmotor symptoms complicates the clinical diagnosis and management. Loss of modulation secondary to the absence of dopamine due to degeneration of the substantia nigra compacta produces changes in firing rates and patterns, oscillatory activity, and higher interneuronal synchronization in the basal ganglia-thalamus-cortex and nigrovagal network involvement in motor and nonmotor symptoms. These neurophysiological changes can be monitored by electrophysiological assessment. The purpose of this review was to summarize the results of neurophysiological changes, especially in the network oscillation in the beta-band level associated with parkinsonism, and to discuss the use of these methods to optimize the diagnosis and management of PD.

Higher Dose Noninvasive Transcutaneous Auricular Vagus Nerve Stimulation Increases Feeding Volumes and White Matter Microstructural Complexity in Open-Label Study of Infants Slated for Gastrostomy Tube.

OBJECTIVE: To determine whether transcutaneous auricular vagus nerve stimulation (taVNS) paired with twice daily bottle feeding increases the volume of oral feeds and white matter neuroplasticity in term-age-equivalent infants failing oral feeds and determined to need a gastrostomy tube. STUDY DESIGN: In this prospective, open-label study, 21 infants received taVNS paired with 2 bottle feeds for 2 - 3 weeks (2x). We compared 1) increase oral feeding volumes with 2x taVNS and previously reported once daily taVNS (1x) to determine a dose response, 2) number of infants who attained full oral feeding volumes, and 3) diffusional kurtosis imaging and magnetic resonance spectroscopy before and after treatment by paired t tests. RESULTS: All 2x taVNS treated infants significantly increased their feeding volumes compared with 10 days before treatment. Over 50% of 2x taVNS infants achieved full oral feeds but in a shorter time than 1x cohort (median 7 days [2x], 12.5 days [1x], P < .05). Infants attaining full oral feeds showed greater increase in radial kurtosis in the right corticospinal tract at the cerebellar peduncle and external capsule. Notably, 75% of infants of diabetic mothers failed full oral feeds, and their glutathione concentrations in the basal ganglia, a measure of central nervous system oxidative stress, were significantly associated with feeding outcome. CONCLUSIONS: In infants with feeding difficulty, increasing the number of daily taVNS-paired feeding sessions to twice-daily significantly accelerates response time but not the overall response rate of treatment. taVNS was associated with white matter motor tract plasticity in infants able to attain full oral feeds. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04643808).

Estimulación de nervio vago en epilepsia refractaria y callosotomía previa sin mejoría. Reporte de caso / Vagus nerve stimulation in refractory epilepsy and previous callosotomy without vimprovement. Case report / Estimulação do nervo vago em epilepsia refratária e calosotomia prévia sem melhora. Relato de caso

La epilepsia refractaria tanto generalizada como focal, es una patología sumamente incapacitante, para el tratamiento de la misma se ha establecido a la callosotomía desde hace décadas como primera línea quirúrgica para su control, la cual puede presentar efectos secundarios importantes como síndrome de desconexión y pérdida de memoria, sin embargo, existen pacientes que no responden a la callosotomía y necesitan nuevas líneas de tratamiento, buscando en la estimulación de nervio vago una respuesta a su condición. Descripción del caso de estudio. Se presenta el caso de paciente masculino de 24 años de edad con antecedente patológico de convulsiones tipo tónico clónicas generalizadas confirmadas por video electroencefalograma de 24 horas, de predominio nocturno de 13 años de evolución, es sometido a 2 regímenes farmacológicos antiepilépticos diferentes en un período de 7 años de duración, posteriormente diagnosticado con epilepsia refractaria, por lo que se realiza callosotomía sin control de su cuadro clínico, el mismo año se realiza estimulación de nervio vago, presentando resultados favorables en su evolución. Conclusión. Luego de evidenciar el presente caso de estudio se concluye que el tratamiento de epilepsia refractaria con la colocación de un estimulador de nervio vago izquierdo asociado a un correcto régimen FAE es una alternativa muy eficaz para considerar en estos pacientes.

Refractory epilepsy, both generalized and focal, is an extremely disabling pathology. For its treatment, callosotomy has been established for decades as the first surgical line for its control, which can present important side effects such as disconnection and loss syndrome. by heart, however, there are patients who do not respond to callosotomy and need new lines of treatment, looking for an answer to their condition in vagus nerve stimulation. Description of the case study. We present the case of a 24-year-old male patient with a pathological history of generalized tonic-clonic seizures confirmed by a 24-hour video electroencephalogram, predominantly nocturnal for 13 years, undergoing 2 different antiepileptic pharmacological mechanisms over a period of 7 years in duration, later diagnosed with refractory epilepsy, for which callosotomy was performed without control of its clinical picture, the same year vagus nerve stimulation was performed, presenting favorable results in its evolution. Conclution. After evidencing the present case study, it is concluded that the treatment of refractory epilepsy with the placement of a left vagus nerve stimulator associated with a correct AED regimen is a very effective alternative to consider in these patients.

A epilepsia refratária, tanto generalizada quanto focal, é uma patologia extremamente incapacitante. Para seu tratamento, a calosotomia se estabeleceu há décadas como a primeira linha cirúrgica para seu controle, que pode apresentar importantes efeitos colaterais como desconexão e síndrome de perda., há pacientes que não respondem à calosotomia e precisam de novas linhas de tratamento, buscando resposta para sua condição na estimulação do nervo vago. Descrição do estudo de caso. Apresentamos o caso de um doente do sexo masculino, 24 anos, com antecedentes patológicos de crises tónico-clónicas generalizadas confirmadas por videoeletroencefalograma de 24 horas, predominantemente nocturnas há 13 anos, submetido a 2 mecanismos farmacológicos antiepilépticos diferentes ao longo de 7 anos de duração, posteriormente diagnosticada com epilepsia refratária, para a qual foi realizada calosotomia sem controle de seu quadro clínico, no mesmo ano foi realizada estimulação do nervo vago, apresentando resultados favoráveis em sua evolução. Conclusão. Depois de evidenciar o presente estudo de caso, conclui-se que o tratamento da epilepsia refratária com a colocação de um estimulador de nervo vago esquerdo associado a um esquema correto de DEA é uma alternativa muito eficaz a ser considerada nesses pacientes.

Brief periods of transcutaneous auricular vagus nerve stimulation improve autonomic balance and alter circulating monocytes and endothelial cells in patients with metabolic syndrome: a pilot study.

BACKGROUND: There is emerging evidence that the nervous system regulates immune and metabolic alterations mediating Metabolic syndrome (MetS) pathogenesis via the vagus nerve. This study evaluated the effects of transcutaneous auricular vagus nerve stimulation (TAVNS) on key cardiovascular and inflammatory components of MetS. METHODS: We conducted an open label, randomized (2:1), two-arm, parallel-group controlled trial in MetS patients. Subjects in the treatment group (n = 20) received 30 min of TAVNS with a NEMOS® device placed on the cymba conchae of the left ear, once weekly. Patients in the control group (n = 10) received no stimulation. Hemodynamic, heart rate variability (HRV), biochemical parameters, and monocytes, progenitor endothelial cells, circulating endothelial cells, and endothelial micro particles were evaluated at randomization, after the first TAVNS treatment, and again after 8 weeks of follow-up. RESULTS: An improvement in sympathovagal balance (HRV analysis) was observed after the first TAVNS session. Only patients treated with TAVNS for 8 weeks had a significant decrease in office BP and HR, a further improvement in sympathovagal balance, with a shift of circulating monocytes towards an anti-inflammatory phenotype and endothelial cells to a reparative vascular profile. CONCLUSION: These results are of interest for further study of TAVNS as treatment of MetS.