Vagus Nerve Stimulation for Electrographic Status Epilepticus in Slow-Wave Sleep.

PubMed

Carosella, Christopher M; Greiner, Hansel M; Byars, Anna W; Arthur, Todd M; Leach, James L; Turner, Michele; Holland, Katherine D; Mangano, Francesco T; Arya, Ravindra

2016-07-01

Electrographic status epilepticus in slow sleep or continuous spike and waves during slow-wave sleep is an epileptic encephalopathy characterized by seizures, neurocognitive regression, and significant activation of epileptiform discharges during nonrapid eye movement sleep. There is no consensus on the diagnostic criteria and evidence-based optimal treatment algorithm for children with electrographic status epilepticus in slow sleep. We describe a 12-year-old girl with drug-resistant electrographic status epilepticus in slow wave sleep that was successfully treated with vagus nerve stimulation. Her clinical presentation, presurgical evaluation, decision-making, and course after vagus nerve stimulator implantation are described in detail. After vagus nerve stimulator implantation, the girl remained seizure free for more than a year, resolved the electrographic status epilepticus in slow sleep pattern on electroencephalography, and exhibited significant cognitive improvement. Vagus nerve stimulation may be considered for electrographic status epilepticus in slow sleep. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve

NASA Astrophysics Data System (ADS)

Caravaca, A. S.; Tsaava, T.; Goldman, L.; Silverman, H.; Riggott, G.; Chavan, S. S.; Bouton, C.; Tracey, K. J.; Desimone, R.; Boyden, E. S.; Sohal, H. S.; Olofsson, P. S.

2017-12-01

Objective. Neural reflexes regulate immune responses and homeostasis. Advances in bioelectronic medicine indicate that electrical stimulation of the vagus nerve can be used to treat inflammatory disease, yet the understanding of neural signals that regulate inflammation is incomplete. Current interfaces with the vagus nerve do not permit effective chronic stimulation or recording in mouse models, which is vital to studying the molecular and neurophysiological mechanisms that control inflammation homeostasis in health and disease. We developed an implantable, dual purpose, multi-channel, flexible ‘microelectrode’ array, for recording and stimulation of the mouse vagus nerve. Approach. The array was microfabricated on an 8 µm layer of highly biocompatible parylene configured with 16 sites. The microelectrode was evaluated by studying the recording and stimulation performance. Mice were chronically implanted with devices for up to 12 weeks. Main results. Using the microelectrode in vivo, high fidelity signals were recorded during physiological challenges (e.g potassium chloride and interleukin-1β), and electrical stimulation of the vagus nerve produced the expected significant reduction of blood levels of tumor necrosis factor (TNF) in endotoxemia. Inflammatory cell infiltration at the microelectrode 12 weeks of implantation was limited according to radial distribution analysis of inflammatory cells. Significance. This novel device provides an important step towards a viable chronic interface for cervical vagus nerve stimulation and recording in mice.

Flexible multichannel vagus nerve electrode for stimulation and recording for heart failure treatment.

PubMed

Xue, Ning; Martinez, Ignacio Delgado; Sun, Jianhai; Cheng, Yuhua; Liu, Chunxiu

2018-07-30

Vagus nerve stimulation is an emerging bioelectronic medicine to modulate cardiac function, as the nerve provides parasympathetic innervation to the heart. In this study, we developed a polyimide based 2D cuff electrode to wrap around on the vagus nerve. Thanks to the tiny size and bendable protruding structure of the contact tips of the device, the electrode sites are able to flexibly bend to touch the nerve, selectively record and stimulate the vagus nerve. Gold, platinum and platinum black materials were chosen to compose the electrodes for nerve stimulation and recording, respectively. Since the platinum black has ~30 times larger charge delivery capacity (CDC) than gold, Pt black electrode is used for nerve stimulation. The electrochemical impedance spectroscopy and cyclic voltammetry measurement of the three materials were conducted in vitro, revealing the results of 405 kΩ, 41 kΩ, 10.5 kΩ, @1 kHz and 0.81 mC/cm 2 , 4.26 mC/cm 2 , 25.5 mC/cm 2 , respectively (n = 3). The cuff electrodes were implanted into the right-sided vagus nerve of rats for in vivo experiment. Biphasic current configuration was implemented for nerve stimulation with frequency of 10 Hz, pulse during of 300 μs and various currents stimulus. The result shows the heart beat frequency drops up to 36% during the stimulation and was able to return the regular frequency as stimulation was removed. Subsequently, the vagus nerve signals were recorded with the four channel cuff electrodes. The magnitude of the compound nerve action potentials (CNAPs) is ~10 μV and the signal to noise ratio (SNR) is ~20. Copyright © 2018 Elsevier B.V. All rights reserved.

The vagus and recurrent laryngeal nerves in the rodent experimental model of esophageal atresia.

PubMed

Qi, B Q; Merei, J; Farmer, P; Hasthorpe, S; Myers, N A; Beasley, S W; Hutson, J M

1997-11-01

After surgical correction of their esophageal atresia and tracheoesophageal fistula (EA-TEF), many patients exhibit evidence of esophageal dysmotility. Controversy exists as to whether the esophageal motility disorders result from denervation caused by surgery or from an inherent abnormal innervation of the esophagus. The present study used an Adriamycin-induced EA-TEF fetal rat model to trace the course and branching of both the vagus and recurrent laryngeal nerves. Abnormalities observed in EA-TEF rat fetuses include: (1) fewer branches from both recurrent laryngeal nerves; (2) deviation of the left vagus from its normal course below the aorta, passing behind the fistula to approach and join with the right vagus to form a single nerve trunk on the right side of the esophagus; (3) relatively few branches from the single vagal nerve trunk (composed of fibers of the left and the right vagus) on the surface of the lower esophagus. Fetuses affected by EA-TEF have inherent abnormalities in the course and branching pattern of the vagus nerves as they descend through the thorax, culminating in a deficient extrinsic nerve fiber plexus in the lower esophagus. These observations may account for the esophageal motility disorders seen in patients who have EA-TEF even before surgical intervention.

Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity.

PubMed

Zanos, Theodoros P; Silverman, Harold A; Levy, Todd; Tsaava, Tea; Battinelli, Emily; Lorraine, Peter W; Ashe, Jeffrey M; Chavan, Sangeeta S; Tracey, Kevin J; Bouton, Chad E

2018-05-22

The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g., blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brainstem. IL-1β and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific neural signals to discriminate between two different cytokines. Nerve impulses recorded from the vagus nerve of mice exposed to IL-1β and TNF were sorted into groups based on their shape and amplitude, and their respective firing rates were computed. This revealed sensory neural groups responding specifically to TNF and IL-1β in a dose-dependent manner. These cytokine-mediated responses were subsequently decoded using a Naive Bayes algorithm that discriminated between no exposure and exposures to IL-1β and TNF (mean successful identification rate 82.9 ± 17.8%, chance level 33%). Recordings obtained in IL-1 receptor-KO mice were devoid of IL-1β-related signals but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1β, and distal lidocaine nerve block attenuated all vagus neural signals recorded. The results obtained in this study using the methodological framework suggest that cytokine-specific information is present in sensory neural signals within the vagus nerve. Copyright © 2018 the Author(s). Published by PNAS.

Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation.

PubMed

Andrews, Russell J

2003-05-01

Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation

NASA Technical Reports Server (NTRS)

Andrews, Russell J.

2003-01-01

Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

Transcutaneous vagus nerve stimulation (tVNS) enhances recognition of emotions in faces but not bodies.

PubMed

Sellaro, Roberta; de Gelder, Beatrice; Finisguerra, Alessandra; Colzato, Lorenza S

2018-02-01

The polyvagal theory suggests that the vagus nerve is the key phylogenetic substrate enabling optimal social interactions, a crucial aspect of which is emotion recognition. A previous study showed that the vagus nerve plays a causal role in mediating people's ability to recognize emotions based on images of the eye region. The aim of this study is to verify whether the previously reported causal link between vagal activity and emotion recognition can be generalized to situations in which emotions must be inferred from images of whole faces and bodies. To this end, we employed transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique that causes the vagus nerve to fire by the application of a mild electrical stimulation to the auricular branch of the vagus nerve, located in the anterior protuberance of the outer ear. In two separate sessions, participants received active or sham tVNS before and while performing two emotion recognition tasks, aimed at indexing their ability to recognize emotions from facial and bodily expressions. Active tVNS, compared to sham stimulation, enhanced emotion recognition for whole faces but not for bodies. Our results confirm and further extend recent observations supporting a causal relationship between vagus nerve activity and the ability to infer others' emotional state, but restrict this association to situations in which the emotional state is conveyed by the whole face and/or by salient facial cues, such as eyes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic cuffing of cervical vagus nerve inhibits efferent fiber integrity in rat model

NASA Astrophysics Data System (ADS)

Somann, Jesse P.; Albors, Gabriel O.; Neihouser, Kaitlyn V.; Lu, Kun-Han; Liu, Zhongming; Ward, Matthew P.; Durkes, Abigail; Robinson, J. Paul; Powley, Terry L.; Irazoqui, Pedro P.

2018-06-01

Objective. Numerous studies of vagal nerve stimulation (VNS) have been published showing it to be a potential treatment for chronic inflammation and other related diseases and disorders. Studies in recent years have shown that electrical stimulation of the vagal efferent fibers can artificially modulate cytokine levels and reduce systematic inflammation. Most VNS research in the treatment of inflammation have been acute studies on rodent subjects. Our study tested VNS on freely moving animals by stimulating and recording from the cervical vagus with nerve cuff electrodes over an extended period of time. Approach. We used methods of electrical stimulation, retrograde tracing (using Fluorogold) and post necropsy histological analysis of nerve tissue, flow cytometry to measure plasma cytokine levels, and MRI scanning of gastric emptying. This novel combination of methods allowed examination of physiological aspects of VNS previously unexplored. Main results. Through our study of 53 rat subjects, we found that chronically cuffing the left cervical vagus nerve suppressed efferent Fluorogold transport in 43 of 44 animals (36 showed complete suppression). Measured cytokine levels and gastric emptying rates concurrently showed nominal differences between chronically cuffed rats and those tested with similar acute methods. Meanwhile, results of electrophysiological and histological tests of the cuffed nerves revealed them to be otherwise healthy, consistent with previous literature. Significance. We hypothesize that due to these unforeseen and unexplored physiological consequences of the chronically cuffed vagus nerve in a rat, that inflammatory modulation and other vagal effects by VNS may become unreliable in chronic studies. Given our findings, we submit that it would benefit the VNS community to re-examine methods used in previous literature to verify the efficacy of the rat model for chronic VNS studies.

Vagus-brain communication in atherosclerosis-related inflammation: a neuroimmunomodulation perspective of CAD.

PubMed

Gidron, Yori; Kupper, Nina; Kwaijtaal, Martijn; Winter, Jobst; Denollet, Johan

2007-12-01

The current understanding of the pathophysiology of atherosclerosis leading to coronary artery disease (CAD) emphasizes the role of inflammatory mediators. Given the bidirectional communication between the immune and central nervous systems, an important question is whether the brain can be "informed" about and modulate CAD-related inflammation. A candidate communicator and modulator is the vagus nerve. Until now, the vagus nerve has received attention in cardiology mainly due to its role in the parasympathetic cardiovascular response. However, the vagus nerve can also "inform" the brain about peripheral inflammation since its paraganglia have receptors for interleukin-1. Furthermore, its efferent branch has a local anti-inflammatory effect. These effects have not been considered in research on the vagus nerve in CAD or in vagus nerve stimulation trials in CAD. In addition, various behavioural interventions, including relaxation, may influence CAD prognosis by affecting vagal activity. Based on this converging evidence, we propose a neuroimmunomodulation approach to atherogenesis. In this model, the vagus nerve "informs" the brain about CAD-related cytokines; in turn, activation of the vagus (via vagus nerve stimulation, vagomimetic drugs or relaxation) induces an anti-inflammatory response that can slow down the chronic process of atherogenesis.

Vagus nerve stimulation therapy in partial epilepsy: a review.

PubMed

Panebianco, Mariangela; Zavanone, Chiara; Dupont, Sophie; Restivo, Domenico A; Pavone, Antonino

2016-09-01

Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked epileptic seizures. The majority of people given a diagnosis of epilepsy have a good prognosis, but 20-30 % will develop drug-resistant epilepsy. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with medically refractory epilepsy. It consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator (Neuro-Cybernetic Prosthesis). In 1997, the Food and Drug Administration approved VNS as adjunctive treatment for medically refractory partial-onset seizures in adults and adolescents. This article reviews the literature from 1988 to nowadays. We discuss thoroughly the anatomy and physiology of vagus nerve and the potential mechanisms of actions and clinical applications involved in VNS therapy, as well as the management, safety, tolerability and effectiveness of VNS therapy. VNS for partial seizures appears to be an effective and well tolerated treatment in adult and pediatric patients. People noted improvements in feelings of well-being, alertness, memory and thinking skills, as well as mood. The adverse effect profile is substantially different from the adverse effect profile associated with antiepileptic drugs, making VNS a potential alternative for patients with difficulty tolerating antiepileptic drug adverse effects. Despite the passing years and the advent of promising neuromodulation technologies, VNS remains an efficacy treatment for people with medically refractory epilepsy. Past and ongoing investigations in other indications have provided signals of the therapeutic potential in a wide variety of conditions.

Mechanical ventilation increases substance P concentration in the vagus, sympathetic, and phrenic nerves.

PubMed

Balzamo, E; Joanny, P; Steinberg, J G; Oliver, C; Jammes, Y

1996-01-01

Substance P (SP), a neurotransmitter localized to primary sensory neurons, is found in the vagus nerve, nodose ganglion, sympathetic chain, and phrenic nerve in various animal species. However, the changes in endogeneous SP concentration under various circumstances that involve the participation of cardiorespiratory afferent nerves are still unexplored. In the present study, attention was focused on the variations in SP content measured by radioimmunoassay (RIA) in respiratory afferent nerves (vagus nerve, cervical sympathetic chain, phrenic nerve) and respiratory muscles (diaphragm, intercostal muscles) during positive inspiratory pressure (PIP) breathing alone or PIP with an expiratory threshold load (ETL) in rabbits. SP was found in all sampled structures in spontaneously breathing control animals, prevailing in the nodose ganglion. Left-versus right-sided differences were noticed in nerves. As compared with that in control animals, the SP concentration was markedly higher in vagal and sympathetic nervous structures during PIP or PIP with ETL, and also in the phrenic nerve during ETL breathing. The SP content did not vary in respiratory muscles. These observations suggest that two very common circumstances of mechanical ventilation are associated with an increased SP concentration in nervous structures participating in the control of breathing.

Effects of short and prolonged transcutaneous vagus nerve stimulation on heart rate variability in healthy subjects.

PubMed

De Couck, M; Cserjesi, R; Caers, R; Zijlstra, W P; Widjaja, D; Wolf, N; Luminet, O; Ellrich, J; Gidron, Y

2017-03-01

The vagus nerve is strategically located in the body, and has multiple homeostatic and health-promoting effects. Low vagal activity predicts onset and progression of diseases. These are the reasons to activate this nerve. This study examined the effects of transcutaneous vagus nerve stimulation (t-VNS) on a main index of vagal activity, namely heart rate variability (HRV). In Study 1, we compared short (10min) left versus right ear t-VNS versus sham (no stimulation) in a within-subjects experimental design. Results revealed significant increases in only one HRV parameter (standard deviation of the RR intervals (SDNN)) following right-ear t-VNS. Study 2 examined the prolonged effects of t-VNS (1h) in the right ear. Compared to baseline, right-t-VNS significantly increased the LF and LF/HF components of HRV, and SDNN in women, but not in men. These results show limited effects of t-VNS on HRV, and are discussed in light of neuroanatomical and statistical considerations and future directions are proposed. Copyright © 2016 Elsevier B.V. All rights reserved.

Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease.

PubMed

Farrand, Ariana Q; Helke, Kristi L; Gregory, Rebecca A; Gooz, Monika; Hinson, Vanessa K; Boger, Heather A

Parkinson's disease (PD) is a progressive, neurodegenerative disorder with no disease-modifying therapies, and symptomatic treatments are often limited by debilitating side effects. In PD, locus coeruleus noradrenergic (LC-NE) neurons degenerate prior to substantia nigra dopaminergic (SN-DA) neurons. Vagus nerve stimulation (VNS) activates LC neurons, and decreases pro-inflammatory markers, allowing improvement of LC targets, making it a potential PD therapeutic. To assess therapeutic potential of VNS in a PD model. To mimic the progression of PD degeneration, rats received a systemic injection of noradrenergic neurotoxin DSP-4, followed one week later by bilateral intrastriatal injection of dopaminergic neurotoxin 6-hydroxydopamine. At this time, a subset of rats also had vagus cuffs implanted. After eleven days, rats received a precise VNS regimen twice a day for ten days, and locomotion was measured during each afternoon session. Immediately following final stimulation, rats were euthanized, and left dorsal striatum, bilateral SN and LC were sectioned for immunohistochemical detection of monoaminergic neurons (tyrosine hydroxylase, TH), α-synuclein, astrocytes (GFAP) and microglia (Iba-1). VNS significantly increased locomotion of lesioned rats. VNS also resulted in increased expression of TH in striatum, SN, and LC; decreased SN α-synuclein expression; and decreased expression of glial markers in the SN and LC of lesioned rats. Additionally, saline-treated rats after VNS, had higher LC TH and lower SN Iba-1. Our findings of increased locomotion, beneficial effects on LC-NE and SN-DA neurons, decreased α-synuclein density in SN TH-positive neurons, and neuroinflammation suggest VNS has potential as a novel PD therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship of vocal cord paralysis to the coil diameter of vagus nerve stimulator leads.

PubMed

Robinson, Leslie C; Winston, Ken R

2015-03-01

This investigation was done to examine, following implantation of vagus nerve stimulators, the relationship of vocal cord paralysis to the inner diameter of the coils used to attach the stimulator lead to the nerve. All data in this investigation were collected, as mandated by the FDA, by the manufacturer of vagus nerve stimulators and were made available without restrictions for analysis by the authors. The data reflect all initial device implantations in the United States for the period from 1997 through 2012. Vocal cord paralysis was reported in 193 of 51,882 implantations. In patients aged 18 years and older, the incidence of paralysis was 0.26% when the stimulator leads had coil diameters of 3 mm and 0.51% when the leads had 2-mm-diameter coils (p < 0.05). Across all age groups, the incidence of vocal cord paralysis increased with age at implantation for leads having 2-mm-diameter coils. In patients aged 18 years and older, vocal cord paralysis occurred at almost twice the rate with the implantation of vagus nerve stimulator leads having 2-mm-diameter coils than with leads having 3-mm-diameter coils. The incidence of vocal cord paralysis increases with patient age at implantation.

Mechanisms underpinning sympathetic nervous activity and its modulation using transcutaneous vagus nerve stimulation.

PubMed

Deuchars, Susan A; Lall, Varinder K; Clancy, Jennifer; Mahadi, Mohd; Murray, Aaron; Peers, Lucy; Deuchars, Jim

2018-03-01

What is the topic of this review? This review briefly considers what modulates sympathetic nerve activity and how it may change as we age or in pathological conditions. It then focuses on transcutaneous vagus nerve stimulation, a method of neuromodulation in autonomic cardiovascular control. What advances does it highlight? The review considers the pathways involved in eliciting the changes in autonomic balance seen with transcutaneous vagus nerve stimulation in relationship to other neuromodulatory techniques. The autonomic nervous system, consisting of the sympathetic and parasympathetic branches, is a major contributor to the maintenance of cardiovascular variables within homeostatic limits. As we age or in certain pathological conditions, the balance between the two branches changes such that sympathetic activity is more dominant, and this change in dominance is negatively correlated with prognosis in conditions such as heart failure. We have shown that non-invasive stimulation of the tragus of the ear increases parasympathetic activity and reduces sympathetic activity and that the extent of this effect is correlated with the baseline cardiovascular parameters of different subjects. The effects could be attributable to activation of the afferent branch of the vagus and, potentially, other sensory nerves in that region. This indicates that tragus stimulation may be a viable treatment in disorders where autonomic activity to the heart is compromised. © 2017 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Application of Rubber Band with Hooks on Both Ends for Vagus Nerve Stimulator Implantation.

PubMed

Hosoyama, Hiroshi; Hanaya, Ryosuke; Otsubo, Toshiaki; Sato, Masanori; Kashida, Yumi; Sugata, Sei; Katagiri, Masaya; Iida, Koji; Arita, Kazunori

2018-03-01

Vagus nerve stimulation (VNS) is a valuable therapeutic option for many types of drug-resistant epilepsy. Muscle hooks and carotid endarterectomy rings have been used for cervical delamination preceding the implantation of stimulation electrodes. The attachment on both sides of a rubber band of Kamiyama-style hanging needles, as are used for scalp and dural retraction during craniotomy, yields a useful tool for VNS implantation. Here we report our experience with this method. We present our method using a rubber band plus hooks and a review of 21 consecutive patients who underwent VNS implantation using our rubber band-plus-hooks method. None of the 21 patients experienced intraoperative or perioperative complications. Hooks placed in connective tissue around the common carotid artery and jugular vein raised the vagus nerve by elevating the carotid sheath. A single surgeon was able to perform all cervical manipulations under a surgical microscope. The average operation time in this series of 21 patients was 137 minutes. The use of hooks attached to both sides of a rubber band rendered VNS implantation safer by lifting the vagus nerve and standardizing the procedure. Copyright © 2017 Elsevier Inc. All rights reserved.

Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis.

PubMed

Erin, Nuray; Duymuş, Ozlem; Oztürk, Saffet; Demir, Necdet

2012-11-10

Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod. Copyright © 2012 Elsevier B.V. All rights reserved.

Transcutaneous Vagus Nerve Stimulation: A Promising Method for Treatment of Autism Spectrum Disorders

PubMed Central

Jin, Yu; Kong, Jian

2017-01-01

Transcutaneous Vagus Nerve Stimulation (tVNS) on the auricular branch of the vagus nerve has been receiving attention due to its therapeutic potential for neuropsychiatric disorders. Although the mechanism of tVNS is not yet completely understood, studies have demonstrated the potential role of vagal afferent nerve stimulation in the regulation of mood and visceral state associated with social communication. In addition, a growing body of evidence shows that tVNS can activate the brain regions associated with Autism Spectrum Disorder (ASD), trigger neuroimmune modulation and produce treatment effects for comorbid disorders of ASD such as epilepsy and depression. We thus hypothesize that tVNS may be a promising treatment for ASD, not only for comorbid epilepsy and depression, but also for the core symptoms of ASD. The goal of this manuscript is to summarize the findings and rationales for applying tVNS to treat ASD and propose potential parameters for tVNS treatment of ASD. PMID:28163670

Vagus nerve contributes to the development of steatohepatitis and obesity in phosphatidylethanolamine N-methyltransferase deficient mice.

PubMed

Gao, Xia; van der Veen, Jelske N; Zhu, Linfu; Chaba, Todd; Ordoñez, Marta; Lingrell, Susanne; Koonen, Debby P Y; Dyck, Jason R B; Gomez-Muñoz, Antonio; Vance, Dennis E; Jacobs, René L

2015-04-01

Phosphatidylethanolamine N-methyltransferase (PEMT), a liver enriched enzyme, is responsible for approximately one third of hepatic phosphatidylcholine biosynthesis. When fed a high-fat diet (HFD), Pemt(-/-) mice are protected from HF-induced obesity; however, they develop steatohepatitis. The vagus nerve relays signals between liver and brain that regulate peripheral adiposity and pancreas function. Here we explore a possible role of the hepatic branch of the vagus nerve in the development of diet induced obesity and steatohepatitis in Pemt(-/-) mice. 8-week old Pemt(-/-) and Pemt(+/+) mice were subjected to hepatic vagotomy (HV) or capsaicin treatment, which selectively disrupts afferent nerves, and were compared to sham-operated or vehicle-treatment, respectively. After surgery, mice were fed a HFD for 10 weeks. HV abolished the protection against the HFD-induced obesity and glucose intolerance in Pemt(-/-) mice. HV normalized phospholipid content and prevented steatohepatitis in Pemt(-/-) mice. Moreover, HV increased the hepatic anti-inflammatory cytokine interleukin-10, reduced chemokine monocyte chemotactic protein-1 and the ER stress marker C/EBP homologous protein. Furthermore, HV normalized the expression of mitochondrial electron transport chain proteins and of proteins involved in fatty acid synthesis, acetyl-CoA carboxylase and fatty acid synthase in Pemt(-/-) mice. However, disruption of the hepatic afferent vagus nerve by capsaicin failed to reverse either the protection against the HFD-induced obesity or the development of HF-induced steatohepatitis in Pemt(-/-) mice. Neuronal signals via the hepatic vagus nerve contribute to the development of steatohepatitis and protection against obesity in HFD fed Pemt(-/-) mice. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The pig as preclinical model for laparoscopic vagus nerve stimulation.

PubMed

Wolthuis, A M; Stakenborg, N; D'Hoore, A; Boeckxstaens, G E

2016-02-01

Cervical vagus nerve stimulation (VNS) prevents manipulation-induced intestinal inflammation and improves intestinal transit in a mouse model of postoperative ileus (POI). Cervical VNS, however, is accompanied by cardiovascular and respiratory side effects. In view of potential clinical application, we therefore evaluated the safety and feasibility of abdominal VNS via laparoscopic approach in a porcine model. Six pigs were used in a non-survival study for both cervical and abdominal VNS. Two cardiac pacing electrodes were positioned around the right cervical and posterior abdominal vagus nerve and connected to an external stimulator. VNS was performed using four different settings (5 and 20 Hz, 0.5 and 1 ms pulse width) during 2 min with ECG recording. Laparoscopic VNS was timed and videotaped, and technical difficulties were noted. A validated National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire was used to evaluate the task and workload. The procedure was completed in all pigs with 4-port laparoscopic technique. Cervical and abdominal VNS were performed after correct identification and isolation of the nerve, and positioning of the electrodes around the nerve. Median laparoscopic operating time was 16 min (range 8-33 min), and median NASA-TLX was 31 (range 11-74). No major complications were encountered. Reduction of heart rate was between 5.5 and 14% for cervical VNS and undetectable for abdominal VNS. In a porcine model, laparoscopic VNS is feasible and safe with cardiac pacing electrodes and may lead to a similar novel approach in humans in the near future.

Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes.

PubMed

Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-Sang J; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Rosin, Diane L; Guyenet, Patrice G; Okusa, Mark D

2016-05-02

The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes.

[A Case of Left Vertebral Artery Aneurysm Showing Evoked Potentials on Bilateral Electrode by the Left Vagus Nerve Stimulation to Electromyographic Tracheal Tube].

PubMed

Kadoya, Tatsuo; Uehara, Hirofumi; Yamamoto, Toshinori; Shiraishi, Munehiro; Kinoshita, Yuki; Joyashiki, Takeshi; Enokida, Kengo

2016-02-01

Previously, we reported a case of brainstem cavernous hemangioma showing false positive responses to electromyographic tracheal tube (EMG tube). We concluded that the cause was spontaneous respiration accompanied by vocal cord movement. We report a case of left vertebral artery aneurysm showing evoked potentials on bilateral electrodes by the left vagus nerve stimulation to EMG tube. An 82-year-old woman underwent clipping of a left unruptured vertebral artery-posterior inferior cerebellar artery aneurysm. General anesthesia was induced with remifentanil, propofol and suxamethonium, and was maintained with oxygen, air, remifentanil and propofol. We monitored somatosensory evoked potentials, motor evoked potentials, and electromyogram of the vocal cord. When the manipulation reached brainstem and the instrument touched the left vagus nerve, evoked potentials appeared on bilateral electrodes. EMG tube is equipped with two electrodes on both sides. We concluded that the left vagus nerve stimulation generated evoked potentials of the left laryngeal muscles, and they were simultaneously detected as potential difference between two electrodes on both sides. EMG tube is used to identify the vagus nerve. However, it is necessary to bear in mind that each vagus nerve stimulation inevitably generates evoked potentials on bilateral electrodes.

The effect of vagus nerve stimulation on response inhibition.

PubMed

Schevernels, Hanne; van Bochove, Marlies E; De Taeye, Leen; Bombeke, Klaas; Vonck, Kristl; Van Roost, Dirk; De Herdt, Veerle; Santens, Patrick; Raedt, Robrecht; Boehler, C Nico

2016-11-01

In the current study, we explored whether vagus nerve stimulation (VNS) in patients with epilepsy, which is believed to increase norepinephrine (NE) levels via activation of the locus coeruleus, would positively affect response inhibition. Moreover, we tried to identify the dynamics of the underlying neural processes by investigating event-related potentials (ERPs) and pupil size. Patients performed a stop-signal task once when stimulation was switched on and once when it was switched off. We found a correlational pattern suggesting that patients who clinically benefit more from VNS treatment also show a larger behavioral advantage, in terms of faster response inhibition, when the vagus nerve is being stimulated. Event-related potential (ERP) results suggested more pronounced reactive inhibition when stimulation was switched on, independent of the individual amount of seizure reduction. Transient go-locked pupil size was increased from go trials to successful stop trials to unsuccessful stop trials but without displaying a clear VNS effect, which however, might relate to limited sensitivity. We conclude that VNS likely has a positive effect on response inhibition, at least in patients with epilepsy that benefit clinically from the treatment, presumably relating to enhancements of response-inhibition mechanisms and, therefore, identify enhanced response inhibition as a possible cognitive benefit of VNS. Copyright © 2016 Elsevier Inc. All rights reserved.

STUDIES WITH THE ELECTROCARDIOGRAPH ON THE ACTION OF THE VAGUS NERVE ON THE HUMAN HEART

PubMed Central

Robinson, G. Canby; Draper, George

1911-01-01

In hearts showing auricular fibrillation mechanical stimulation of the right vagus nerve causes, as a rule, marked slowing or stoppage of ventricular rhythm, without producing any appreciable effect in the electrocardiographic record of the auricular fibrillation. The ventricular pauses are apparently due to the blocking of stimuli from the auricles. The force of ventricular systole is distinctly weakened for several beats after vagus stimulation, and ectopic ventricular systoles have been seen in several instances, apparently the result of the vagus action. There may, in some cases, be lowered excitability of the ventricles, while no constant change is seen in the size of the electrical complexes representing ventricular systole. PMID:19867466

Rapid Remission of Conditioned Fear Expression with Extinction Training Paired with Vagus Nerve Stimulation

PubMed Central

Peña, David F.; Engineer, Navzer D.; McIntyre, Christa K.

2012-01-01

Background Fearful experiences can produce long-lasting and debilitating memories. Extinction of conditioned fear requires consolidation of new memories that compete with fearful associations. In human subjects, as well as rats, posttraining stimulation of the vagus nerve enhances memory consolidation. Subjects with posttraumatic stress disorder (PTSD) show impaired extinction of conditioned fear. The objective of this study was to determine whether vagus nerve stimulation (VNS) can enhance the consolidation of extinction of conditioned fear. Methods Male Sprague-Dawley rats were trained on an auditory fear conditioning task followed by 1–10 days of extinction training. Treatment with vagus nerve or sham stimulation was administered concurrently with exposure to the fear conditioned stimulus. Another group was given VNS and extinction training but the VNS was not paired with exposure to conditioned cues. Retention of fear conditioning was tested 24 hours after each treatment. Results VNS paired with exposure to conditioned cues enhanced the extinction of conditioned fear. After a single extinction trial, rats given VNS stimulation demonstrated a significantly lower level of freezing, compared to that of sham controls. When extinction trials were extended to 10 days, paired VNS accelerated extinction of the conditioned response. Conclusions Extinction paired with VNS is more rapid than extinction paired with sham stimulation. As it is currently approved by the Federal Food and Drug Administration for depression and seizure prevention, VNS is a readily-available and promising adjunct to exposure therapy for the treatment of severe anxiety disorders. PMID:23245749

Vagus Nerve Stimulation Reduces Cocaine Seeking and Alters Plasticity in the Extinction Network

ERIC Educational Resources Information Center

Childs, Jessica E.; DeLeon, Jaime; Nickel, Emily; Kroener, Sven

2017-01-01

Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces rates of relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic…

Non-neuronal cardiac cholinergic system influences CNS via the vagus nerve to acquire a stress-refractory propensity.

PubMed

Oikawa, Shino; Kai, Yuko; Tsuda, Masayuki; Ohata, Hisayuki; Mano, Asuka; Mizoguchi, Naoko; Sugama, Shuei; Nemoto, Takahiro; Suzuki, Kenji; Kurabayashi, Atsushi; Muramoto, Kazuyo; Kaneda, Makoto; Kakinuma, Yoshihiko

2016-11-01

We previously developed cardiac ventricle-specific choline acetyltransferase (ChAT) gene-overexpressing transgenic mice (ChAT tgm), i.e. an in vivo model of the cardiac non-neuronal acetylcholine (NNA) system or non-neuronal cardiac cholinergic system (NNCCS). By using this murine model, we determined that this system was responsible for characteristics of resistance to ischaemia, or hypoxia, via the modulation of cellular energy metabolism and angiogenesis. In line with our previous study, neuronal ChAT-immunoreactivity in the ChAT tgm brains was not altered from that in the wild-type (WT) mice brains; in contrast, the ChAT tgm hearts were the organs with the highest expression of the ChAT transgene. ChAT tgm showed specific traits in a central nervous system (CNS) phenotype, including decreased response to restraint stress, less depressive-like and anxiety-like behaviours and anti-convulsive effects, all of which may benefit the heart. These phenotypes, induced by the activation of cardiac NNCCS, were dependent on the vagus nerve, because vagus nerve stimulation (VS) in WT mice also evoked phenotypes similar to those of ChAT tgm, which display higher vagus nerve discharge frequency; in contrast, lateral vagotomy attenuated these traits in ChAT tgm to levels observed in WT mice. Furthermore, ChAT tgm induced several biomarkers of VS responsible for anti-convulsive and anti-depressive-like effects. These results suggest that the augmentation of the NNCCS transduces an effective and beneficial signal to the afferent pathway, which mimics VS. Therefore, the present study supports our hypothesis that activation of the NNCCS modifies CNS to a more stress-resistant state through vagus nerve activity. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Ablation of the sphenopalatine ganglion does not attenuate the infarct reducing effect of vagus nerve stimulation

PubMed Central

Ay, Ilknur; Ay, Hakan

2013-01-01

Electrical stimulation of the cervical vagus nerve reduces infarct size by approximately 50% after cerebral ischemia in rats. The mechanism of ischemic protection by vagus nerve stimulation (VNS) is not known. In this study, we investigated whether the infarct reducing effect of VNS was mediated by activation of the parasympathetic vasodilator fibers that originate from the sphenopalatine ganglion (SPG) and innervate the anterior cerebral circulation. We examined the effects of electrical stimulation of the cervical vagus nerve in two groups of rats: one with and one without SPG ablation. Electrical stimulation was initiated 30 min after induction of ischemia, and lasted for 1h. Measurement of infarct size 24h later revealed that the volume of ischemic damage was smaller in those animals that received VNS treatment (41.32 ± 2.07% vs. 24.19 ± 2.62% of the contralateral hemispheric volume, n=6 in both; p<0.05). SPG ablation did not abolish this effect; the reduction in infarct volume following VNS was 58% in SPG-damaged animals, 41% in SPG-intact animals (p>0.05). In both SPG-intact and SPG-damaged animals VNS treatment resulted in better motor outcome (p<0.05 vs. corresponding controls for both). Our findings show that VNS can protect the brain against acute ischemic injury, and that this effect is not mediated by SPG projections. PMID:23273773

Combustion-derived nanoparticles, the neuroenteric system, cervical vagus, hyperphosphorylated alpha synuclein and tau in young Mexico City residents.

PubMed

Calderón-Garcidueñas, Lilian; Reynoso-Robles, Rafael; Pérez-Guillé, Beatriz; Mukherjee, Partha S; Gónzalez-Maciel, Angélica

2017-11-01

Mexico City (MC) young residents are exposed to high levels of fine particulate matter (PM 2.5 ), have high frontal concentrations of combustion-derived nanoparticles (CDNPs), accumulation of hyperphosphorylated aggregated α-synuclein (α-Syn) and early Parkinson's disease (PD). Swallowed CDNPs have easy access to epithelium and submucosa, damaging gastrointestinal (GI) barrier integrity and accessing the enteric nervous system (ENS). This study is focused on the ENS, vagus nerves and GI barrier in young MC v clean air controls. Electron microscopy of epithelial, endothelial and neural cells and immunoreactivity of stomach and vagus to phosphorylated ɑ-synuclein Ser129 and Hyperphosphorylated-Tau (Htau) were evaluated and CDNPs measured in ENS. CDNPs were abundant in erythrocytes, unmyelinated submucosal, perivascular and intramuscular nerve fibers, ganglionic neurons and vagus nerves and associated with organelle pathology. ɑSyn and Htau were present in 25/27 MC gastric,15/26 vagus and 18/27 gastric and 2/26 vagus samples respectively. We strongly suggest CDNPs are penetrating and damaging the GI barrier and reaching preganglionic parasympathetic fibers and the vagus nerve. This work highlights the potential role of CDNPs in the neuroenteric hyperphosphorylated ɑ-Syn and tau pathology as seen in Parkinson and Alzheimer's diseases. Highly oxidative, ubiquitous CDNPs constitute a biologically plausible path into Parkinson's and Alzheimer's pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety and efficacy of vagus nerve stimulation paired with tones for the treatment of tinnitus: a case series.

PubMed

De Ridder, Dirk; Vanneste, Sven; Engineer, Navzer D; Kilgard, Michael P

2014-02-01

Classical neuromodulation applies current to the nervous system in an attempt to alter ongoing activity. However, classical neuromodulation interferes with activity but does not drive it in a controlled way. Recently, an animal study demonstrated it is possible to drive plasticity in a controlled way by using stimulation of the vagus nerve paired with tones. This reversed the tinnitus percept and pathological neural plasticity in noise-exposed rats with behavioral characteristics of tinnitus. The aim of the current study was to translate this innovative neuromodulation method to humans suffering from tinnitus. Ten patients with severe chronic tinnitus were implanted with electrodes on their left vagus nerve. Two and a half hours each day for 20 days, the patients heard tones, excluding the tinnitus-matched frequency, paired with brief electrical stimulation of the vagus nerve. The therapy was well tolerated, and no patient withdrew from the study due to complications or side-effects. Four of the ten patients exhibited clinically meaningful improvements in their tinnitus, both for the affective component, as quantified by the Tinnitus Handicap Inventory, and for the sound percept, as quantified by the minimum masking level. These improvements were stable for more than two months after the end of therapy. Of the ten patients, five were on medications that included muscarinic antagonists, norepinephrine agonists, and γ-amino butyric acid agonists, thereby possibly interfering with acetylcholine and norepinephrine release induced by vagus nerve stimulation (VNS) and essential for inducing plasticity. These patients had no improvement in contrast to medication-free patients. VNS paired with tones excluding the tinnitus-matched frequency is safe and feasible. It seems to exert a beneficial effect in nonmedication-taking patients, both with regard to the perceived sound and the distress. Further studies are therefore mandated. © 2013 International Neuromodulation

An alternative therapy for drug-resistant epilepsy: transcutaneous auricular vagus nerve stimulation.

PubMed

Rong, Peijing; Liu, Aihua; Zhang, Jianguo; Wang, Yuping; Yang, Anchao; Li, Liang; Ben, Hui; Li, Liping; Liu, Rupeng; He, Wei; Liu, Huanguang; Huang, Feng; Li, Xia; Wu, Peng; Zhu, Bing

2014-01-01

Previous studies demonstrated that vagus nerve stimulation (VNS) is an effective therapy for drug-resistant epilepsy. Acupuncture is also used to treat epilepsy. This study was designed to examine the safety and effectiveness of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with drug-resistant epilepsy. A total of 50 volunteer patients with drug-resistant epilepsy were selected for a random clinical trial to observe the therapeutic effect of ta-VNS. The seizure frequency, quality of life, and severity were assessed in weeks 8, 16, and 24 of the treatment according to the percentage of seizure frequency reduction. In the pilot study, 47 of the 50 epilepsy patients completed the 24-week treatment; three dropped off. After 8-week treatment, six of the 47 patients (12%) were seizure free and 12 (24%) had a reduction in seizure frequency. In week 16 of the continuous treatment, six of the 47 patients (12%) were seizure free; 17 (34%) had a reduction in seizure frequency. After 24 weeks' treatment, eight patients (16%) were seizure free; 19 (38%) had reduced seizure frequency. Similar to the therapeutic effect of VNS, ta-VNS can suppress epileptic seizures and is a safe, effective, economical, and widely applicable treatment option for drug-resistant epilepsy. (ChiCTR-TRC-10001023).

Origin of 5-hydroxytryptamine-induced hyperpolarization of the rat superior cervical ganglion and vagus nerve.

PubMed Central

Ireland, S. J.

1987-01-01

1 5-Hydroxytryptamine (5-HT)-induced membrane potential changes were recorded extracellularly from rat superior cervical ganglia (SCG) and cervical vagus nerves in vitro. 2 On the SCG, low concentrations of 5-HT (1 X 10(-8)-3 X 10(-7) M) induced concentration-related hyperpolarization responses. Higher concentrations of 5-HT (1 X 10(-6) 1 X 10(-4) M) induced complex responses which typically consisted of an initial hyperpolarization, followed by a depolarization and subsequent after-hyperpolarization. The depolarization, but not the initial hyperpolarization, was blocked by metoclopramide (3 X 10(-5) M), quipazine (1 X 10(-6) M) or MDL 72222 (1 X 10(-5) M). 3 5-HT-induced hyperpolarization of the SCG was potentiated when the amount of calcium chloride added to the superfusion medium was reduced from 2.5 to 0.15 mmol l-1. Hyperpolarization responses recorded from SCG preparations superfused with this low-calcium medium were unaffected by the substitution of lithium chloride for sodium chloride and were potentiated by the omission of potassium ions. Ouabain (1 X 10(-3) M) abolished both the hyperpolarization and the depolarization induced by 5-HT. 4 On the vagus nerve, 5-HT (1 X 10(-7) - 3 X 10(-5)M) did not induce initial hyperpolarization in either normal or low-calcium Krebs-Henseleit medium. However, in the latter solution only, depolarization responses induced by 5-HT at concentrations of 1 X 10(-6)M or greater were followed by hyperpolarization. Both the depolarization and the post-5-HT hyperpolarization were blocked by metoclopramide (3 X 10(-5)M) but were unaffected by spiperone (1 X 10(-7)M). 5 On the vagus nerve, post-5-HT hyperpolarization responses were selectively and reversibly inhibited by ouabain, and by superfusion with Krebs-Henseleit medium that was either potassium-free or contained lithium chloride in place of sodium chloride. 7 These results demonstrate the generation in the rat SCG of a 5-HT-induced hyperpolarization response that is not

Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS)

PubMed Central

George, Mark S; Aston-Jones, Gary

2010-01-01

Although the preceding chapters discuss much of the new knowledge of neurocircuitry of neuropsychiatric diseases, and an invasive approach to treatment, this chapter describes and reviews the noninvasive methods of testing circuit-based theories and treating neuropsychiatric diseases that do not involve implanting electrodes into the brain or on its surface. These techniques are transcranial magnetic stimulation, vagus nerve stimulation, and transcranial direct current stimulation. Two of these approaches have FDA approval as therapies. PMID:19693003

The role of the vagus nerve in the generation of cardiorespiratory interactions in a neotropical fish, the pacu, Piaractus mesopotamicus.

PubMed

Leite, Cleo Alcantara Costa; Taylor, E W; Guerra, C D R; Florindo, L H; Belão, T; Rantin, F T

2009-08-01

The role of the vagus nerve in determining heart rate (f(H)) and cardiorespiratory interactions was investigated in a neotropical fish, Piaractus mesopotamicus. During progressive hypoxia f(H) initially increased, establishing a 1:1 ratio with ventilation rate (f(R)). Subsequently there was a hypoxic bradycardia. Injection of atropine abolished a normoxic inhibitory tonus on the heart and the f(H) adjustments during progressive hypoxia, confirming that they are imposed by efferent parasympathetic inputs via the vagus nerve. Efferent activity recorded from the cardiac vagus in lightly anesthetized normoxic fish included occasional bursts of activity related to spontaneous changes in ventilation amplitude, which increased the cardiac interval. Restricting the flow of aerated water irrigating the gills resulted in increased respiratory effort and bursts of respiration-related activity in the cardiac vagus that seemed to cause f(H) to couple with f(R). Cell bodies of cardiac vagal pre-ganglionic neurons were located in two distinct groups within the dorsal vagal motor column having an overlapping distribution with respiratory motor-neurons. A small proportion of cardiac vagal pre-ganglionic neurons (2%) was in scattered positions in the ventrolateral medulla. This division of cardiac vagal pre-ganglionic neurons into distinct motor groups may relate to their functional roles in determining cardiorespiratory interactions.

Failure of a vagus nerve stimulator following a nearby lightning strike.

PubMed

Terry, Garth E; Conry, Joan A; Taranto, Eleanor; Yaun, Amanda

2011-01-01

We recently reported our experience with implanted vagus nerve stimulators (VNS) in 62 children over a 7-year period. Here, we present a case of a VNS that successfully reduced the number and severity of seizures in a patient with an unusual seizure pattern, and failed to function shortly after a lightning storm. To our knowledge, the failure of VNS or any implantable electrical devices by lightning has not been reported in the literature. This mechanism of electrical interference, while unusual, may require more attention as these devices are expected to be used more frequently. Copyright © 2011 S. Karger AG, Basel.

Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis.

PubMed

Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

2018-01-01

Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types A α and A β fibers) with a large conduction velocity (70-120 m/s), and the second component originated from fibers (Type A γ ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders.

Association of vagus nerve severance and decreased risk of subsequent type 2 diabetes in peptic ulcer patients

PubMed Central

Wu, Shih-Chi; Chen, William Tzu-Liang; Fang, Chu-Wen; Muo, Chih-Hsin; Sung, Fung-Chang; Hsu, Chung Y.

2016-01-01

Abstract Vagus nerve may play a role in serum glucose modulation. The complicated peptic ulcer patients (with perforation or/and bleeding) who received surgical procedures with or without vagotomy provided 2 patient populations for studying the impact of vagus nerve integrity. We assessed the risk of developing type 2 diabetes in peptic ulcer patients without and with complications by surgical treatment received in a retrospective population study using the National Health Insurance database in Taiwan. A cohort of 163,385 patients with peptic ulcer and without Helicobacter pylori infection in 2000 to 2003 was established. A randomly selected cohort of 163,385 persons without peptic ulcer matched by age, sex, hypertension, hyperlipidemia, Charlson comorbidity index score, and index year was utilized for comparison. The risks of developing diabetes in both cohorts and in the complicated peptic ulcer patients who received truncal vagotomy or simple suture/hemostasis (SSH) were assessed at the end of 2011. The overall diabetes incidence was higher in patients with peptic ulcer than those without peptic ulcer (15.87 vs 12.60 per 1000 person-years) by an adjusted hazard ratio (aHR) of 1.43 (95% confidence interval [CI] = 1.40–1.47) based on the multivariable Cox proportional hazards regression analysis (competing risk). Comparing ulcer patients with truncal vagotomy and SSH or those without surgical treatment, the aHR was the lowest in the vagotomy group (0.48, 95% CI = 0.41–0.56). Peptic ulcer patients have an elevated risk of developing type 2 diabetes. Moreover, there were associations of vagus nerve severance and decreased risk of subsequent type 2 diabetes in complicated peptic ulcer patients. PMID:27930533

Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis

PubMed Central

Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

2018-01-01

Background Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Materials and methods Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types Aα and Aβ fibers) with a large conduction velocity (70–120 m/s), and the second component originated from fibers (Type Aγ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. Results We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Conclusion Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders. PMID:29731661

α-Synuclein pathology in the cranial and spinal nerves in Lewy body disease.

PubMed

Nakamura, Keiko; Mori, Fumiaki; Tanji, Kunikazu; Miki, Yasuo; Toyoshima, Yasuko; Kakita, Akiyoshi; Takahashi, Hitoshi; Yamada, Masahito; Wakabayashi, Koichi

2016-06-01

Accumulation of phosphorylated α-synuclein in neurons and glial cells is a histological hallmark of Lewy body disease (LBD) and multiple system atrophy (MSA). Recently, filamentous aggregations of phosphorylated α-synuclein have been reported in the cytoplasm of Schwann cells, but not in axons, in the peripheral nervous system in MSA, mainly in the cranial and spinal nerve roots. Here we conducted an immunohistochemical investigation of the cranial and spinal nerves and dorsal root ganglia of patients with LBD. Lewy axons were found in the oculomotor, trigeminal and glossopharyngeal-vagus nerves, but not in the hypoglossal nerve. The glossopharyngeal-vagus nerves were most frequently affected, with involvement in all of 20 subjects. In the spinal nerve roots, Lewy axons were found in all of the cases examined. Lewy axons in the anterior nerves were more frequent and numerous in the thoracic and sacral segments than in the cervical and lumbar segments. On the other hand, axonal lesions in the posterior spinal nerve roots appeared to increase along a cervical-to-sacral gradient. Although Schwann cell cytoplasmic inclusions were found in the spinal nerves, they were only minimal. In the dorsal root ganglia, axonal lesions were seldom evident. These findings indicate that α-synuclein pathology in the peripheral nerves is axonal-predominant in LBD, whereas it is restricted to glial cells in MSA. © 2015 Japanese Society of Neuropathology.

TRANSCUTANEOUS CERVICAL VAGUS NERVE STIMULATION AMELIORATES ACUTE ISCHEMIC INJURY IN RATS

PubMed Central

Ay, Ilknur; Nasser, Rena; Simon, Bruce; Ay, Hakan

2016-01-01

Background Direct stimulation of the vagus nerve in the neck via surgically implanted electrodes is protective in animal models of stroke. We sought to determine the safety and efficacy of a non-invasive cervical VNS (nVNS) method using surface electrodes applied to the skin overlying the vagus nerve in the neck in a model of middle cerebral artery occlusion (MCAO). Methods nVNS was initiated variable times after MCAO hour in rats (n=33). Control animals received sham stimulation (n=33). Infarct volume and functional outcome were assessed on day 7. Brains were processed by immunohistochemistry for microglial activation and cytokine levels. The ability of nVNS to activate the nucleus tractus solitarius (NTS) was assessed using c-Fos immunohistochemistry. Results Infarct volume was 43.15±3.36 percent of the contralateral hemisphere (PCH) in control and 28.75±4.22 PCH in nVNS-treated animals (p<0.05). The effect of nVNS on infarct size was consistent when stimulation was initiated up to 4 hours after MCAO. There was no difference in heart rate and blood pressure between control and nVNS-treated animals. The number of c-Fos positive cells was 32.4±10.6 and 6.2±6.3 in the ipsilateral NTS (p<0.05) and 30.4±11.2 and 5.8±4.3 in the contralateral NTS (p<0.05) in nVNS-treated and control animals, respectively. nVNS reduced the number of Iba-1, CD68, and TNF-α positive cells and increased the number of HMGB1 positive cells. Conclusions nVNS inhibits ischemia-induced immune activation and reduces the extent of tissue injury and functional deficit in rats without causing cardiac or hemodynamic adverse effects when initiated up to 4 hours after MCAO. PMID:26723020

Vagus nerve contributes to metabolic syndrome in high-fat diet-fed young and adult rats.

PubMed

Barella, Luiz F; Miranda, Rosiane A; Franco, Claudinéia C S; Alves, Vander S; Malta, Ananda; Ribeiro, Tatiane A S; Gravena, Clarice; Mathias, Paulo C F; de Oliveira, Júlio C

2015-01-01

What is the central question of this study? Different nerve contributes periods of life are known for their differential sensitivity to interventions, and increased parasympathetic activity affects the development and maintenance of obesity. Thus, we evaluated the involvement of the vagus nerve by performing a vagotomy in young or adult rats that were offered an obesogenic high-fat diet. What is the main finding and its importance? Although the accumulation of adipose tissue decreased in both younger and older groups, the younger rats showed a greater response to the effects of vagotomy in general. In addition to the important role of the parasympathetic activity, we suggest that the vagus nerve contributes to the condition of obesity. Obesity has become a global problem, and this condition develops primarily because of an imbalance between energy intake and expenditure. The high complexity involved in the regulation of energy metabolism results from several factors besides endocrine factors. It has been suggested that obesity could be caused by an imbalance in the autonomous nervous system, which could lead to a condition of high parasympathetic activity in counterpart to low sympathetic tonus. High-fat (HF) diets have been used to induce obesity in experimental animals, and their use in animals leads to insulin resistance, hyperinsulinaemia and high parasympathetic activity, among other disorders. The aim of this work was to evaluate the effects of a vagotomy performed at the initiation of a HF diet at two different stages of life, weaning and adulthood. The vagotomy reduced parasympathetic activity (-32 and -51% in normal fat-fed rats and -43 and -55% in HF diet-fed rats; P < 0.05) and fat depots (-17 and -33%, only in HF diet-fed rats; P < 0.05). High-fat diet-fed rats exhibited fasting hyperinsulinaemia (fivefold higher in young rats and threefold higher in older rats; P < 0.05); however, vagotomy corrected it in younger rats only, and a similar effect was

Extracellular pH monitoring for use in closed-loop vagus nerve stimulation

NASA Astrophysics Data System (ADS)

Cork, Simon C.; Eftekhar, Amir; Mirza, Khalid B.; Zuliani, Claudio; Nikolic, Konstantin; Gardiner, James V.; Bloom, Stephen R.; Toumazou, Christofer

2018-02-01

Objective. Vagal nerve stimulation (VNS) has shown potential benefits for obesity treatment; however, current devices lack physiological feedback, which limit their efficacy. Changes in extracellular pH (pHe) have shown to be correlated with neural activity, but have traditionally been measured with glass microelectrodes, which limit their in vivo applicability. Approach. Iridium oxide has previously been shown to be sensitive to fluctuations in pH and is biocompatible. Iridium oxide microelectrodes were inserted into the subdiaphragmatic vagus nerve of anaesthetised rats. Introduction of the gut hormone cholecystokinin (CCK) or distension of the stomach was used to elicit vagal nerve activity. Main results. Iridium oxide microelectrodes have sufficient pH sensitivity to readily detect changes in pHe associated with both CCK and gastric distension. Furthermore, a custom-made Matlab script was able to use these changes in pHe to automatically trigger an implanted VNS device. Significance. This is the first study to show pHe changes in peripheral nerves in vivo. In addition, the demonstration that iridium oxide microelectrodes are sufficiently pH sensitive as to measure changes in pHe associated with physiological stimuli means they have the potential to be integrated into closed-loop neurostimulating devices.

The electrophysiology of thyroid surgery: electrophysiologic and muscular responses with stimulation of the vagus nerve, recurrent laryngeal nerve, and external branch of the superior laryngeal nerve.

PubMed

Liddy, Whitney; Barber, Samuel R; Cinquepalmi, Matteo; Lin, Brian M; Patricio, Stephanie; Kyriazidis, Natalia; Bellotti, Carlo; Kamani, Dipti; Mahamad, Sadhana; Dralle, Henning; Schneider, Rick; Dionigi, Gianlorenzo; Barczynski, Marcin; Wu, Che-Wei; Chiang, Feng Yu; Randolph, Gregory

2017-03-01

Correlation of physiologically important electromyographic (EMG) waveforms with demonstrable muscle activation is important for the reliable interpretation of evoked waveforms during intraoperative neural monitoring (IONM) of the vagus nerve, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve (EBSLN) in thyroid surgery. Retrospective chart review. Data were reviewed retrospectively for thyroid surgery patients with laryngeal nerve IONM from January to December, 2015. EMG responses to monopolar stimulation of the vagus/RLN and EBSLN were recorded in bilateral vocalis, cricothyroid (CTM), and strap muscles using endotracheal tube-based surface and intramuscular hook electrodes, respectively. Target muscles for vagal/RLN and EBSLN stimulation were the ipsilateral vocalis and CTM, respectively. All other recording channels were nontarget muscles. Fifty surgical sides were identified in 37 subjects. All target muscle mean amplitudes were significantly higher than in nontarget muscles. With vagal/RLN stimulation, target ipsilateral vocalis mean amplitude was 1,095.7 μV (mean difference range = -814.1 to -1,078 μV, P < .0001). For EBSLN stimulation, target ipsilateral CTM mean amplitude was 6,379.3 μV (mean difference range = -6,222.6 to -6,362.3 μV, P < .0001). Target muscle large-amplitude EMG responses correlated with meaningful visual or palpable muscular responses, whereas nontarget EMG responses showed no meaningful muscle activation. Target and nontarget laryngeal muscles are differentiated based on divergence of EMG response directly correlating with presence or absence of visual and palpable muscle activation. Low-amplitude EMG waveforms in nontarget muscles with neural stimulation can be explained by the concept of far-field artifactual waveforms and do not correspond to a true muscular response. The surgeon should be aware of these nonphysiologic waveforms when interpreting and applying IONM during thyroid surgery. 4

Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial.

PubMed

Antonino, Diego; Teixeira, André L; Maia-Lopes, Paulo M; Souza, Mayara C; Sabino-Carvalho, Jeann L; Murray, Aaron R; Deuchars, Jim; Vianna, Lauro C

Despite positive outcomes of transcutaneous vagus nerve stimulation (tVNS) via the auricular branch of the vagus nerve (ABVN), the mechanisms underlying these outcomes remain unclear. Additionally, previous studies have not been controlled the possible placebo effects of tVNS. To test the hypothesis that tVNS acutely improves spontaneous cardiac baroreflex sensitivity (cBRS) and autonomic modulation, and that these effects are specific to stimulation of ABVN. Thirteen healthy men (23±1yrs) were randomized across three experimental visits. In active tVNS, electrodes were placed on the tragus of the ear and electrical current was applied by using a Transcutaneous Electrical Nerve Stimulation device. A time-control visit was performed with the electrodes placed on tragus, but no current was applied (sham-T). Additionally, to avoid a placebo effect, another sham protocol was performed with same electrical current of the active visit, but the electrodes were placed on the ear lobe (an area without cutaneous nerve endings from the vagus - tLS). Beat-to-beat heart rate (HR) and blood pressure (BP) were monitored at rest, during stimulation (active, sham-T and tLS) and recovery. cBRS was measured via sequence technique. Both HR (HRV) and BP variability (BPV) were also measured. Arterial BP and BPV were not affected by any active or sham protocols (P > 0.05). Resting HR and LF/HF ratio of HRV decreased (Δ-3.4 ± 1% and Δ-15 ± 12%, P < 0.05, respectively) and cBRS increased (Δ24 ± 8%, P < 0.05) during active tVNS, but were unchanged during both sham protocols. tVNS acutely improves cBRS and autonomic modulation in healthy young men. Copyright © 2017 Elsevier Inc. All rights reserved.

Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning and stimulated hippocampal neurogenesis in bulbectomized rats.

PubMed

Gebhardt, Nils; Bär, Karl-Jürgen; Boettger, Michael K; Grecksch, Gisela; Keilhoff, Gerburg; Reichart, Rupert; Becker, Axel

2013-01-01

Vagus nerve stimulation (VNS) has been introduced as a therapeutic option for treatment-resistant depression. The neural and chemical mechanisms responsible for the effects of VNS are largely unclear. Bilateral removal of the olfactory bulbs (OBX) is a validated animal model in depression research. We studied the effects of vagus nerve stimulation (VNS) on disturbed one-way active avoidance learning and neurogenesis in the hippocampal dentate gyrus of rats. After a stimulation period of 3 weeks, OBX rats acquired the learning task as controls. In addition, the OBX-related decrease of neuronal differentiated BrdU positive cells in the dentate gyrus was prevented by VNS. This suggests that chronic VNS and changes in hippocampal neurogenesis induced by VNS may also account for the amelioration of behavioral deficits in OBX rats. To the best of our knowledge, this is the first report on the restorative effects of VNS on behavioral function in an animal model of depression that can be compared with the effects of antidepressants. Copyright © 2013 Elsevier Inc. All rights reserved.

Placebo-controlled vagus nerve stimulation paired with tones in a patient with refractory tinnitus: a case report.

PubMed

De Ridder, Dirk; Kilgard, Michael; Engineer, Navzer; Vanneste, Sven

2015-04-01

Classical neuromodulation consists of applying electrical or magnetic stimuli to the nervous system to modulate ongoing activity and connectivity. However, recently, an exciting novel neuromodulation technique was developed in which stimulation of the vagal nerve was paired with simultaneous presentation of tones, demonstrating that it reverses a tinnitus percept in noise-exposed rats. To determine whether this therapy could also be effective in humans, we delivered a similar therapy in a patient with chronic tinnitus unresponsive to previous therapies. In this report, we describe the case of a 59-year-old man who suffered from bilateral tinnitus for 14 years that arose after a cervical fusion operation. Pharmacotherapy, transcranial magnetic stimulation, transcranial direct current stimulation, neurofeedback, and bilateral auditory cortex stimulation via implanted electrodes did not improve the tinnitus. After implanting the vagal nerve stimulator, the patient received daily vagus nerve stimulation tone pairings for 4 weeks in a non-placebo-controlled way. At the end of therapy, the patient experienced a significant reduction in tinnitus symptoms that lasted for 2 months after treatment. Tinnitus Handicap Inventory and Tinnitus Reaction Questionnaire were reduced by 48% and 68%, respectively. Symptoms of depression were also improved by 40%, as quantified by the Beck Depression Inventory. Three months after ending therapy, placebo stimulation was performed consisting of only tone presentation without the simultaneous electrical stimuli. This resulted in further continuation of the gradual relapse to the baseline state, without renewed improvement. Our results suggest that vagus nerve stimulation paired with tones could become an effective therapy for the treatment of tinnitus.

The role of laryngeal electromyography in vagus nerve stimulation-related vocal fold dysmotility.

PubMed

Saibene, Alberto M; Zambrelli, Elena; Pipolo, Carlotta; Maccari, Alberto; Felisati, Giovanni; Felisati, Elena; Furia, Francesca; Vignoli, Aglaia; Canevini, Maria Paola; Alfonsi, Enrico

2017-03-01

Vagus nerve stimulation (VNS) is a useful tool for drug-resistant epilepsy, but it induces known laryngeal side effects, with a significant role on patients' quality of life. VNS patients may show persistent left vocal fold (LVF) palsy at rest and/or recurrent LVF adduction during stimulation. This study aims at electromyographically evaluating laryngeal muscles abnormalities in VNS patients. We compared endoscopic laryngeal evaluation data in six VNS patients with laryngeal muscle electromyography (LMEMG) carried out on the thyroarytenoid, cricothyroid, posterior cricoarytenoid, and cricopharyngeal muscles. Endoscopy showed LVF palsy at rest in 3/6 patients in whom LMEMG documented a tonic spastic activity with reduced phasic modulation. In four out of six patients with recurrent LVF adduction during VNS activation, LMEMG showed a compound muscle action potential persisting for the whole stimulation. This is the first LMEMG report of VNS-induced motor unit activation via recurrent laryngeal nerve and upper laryngeal nerve stimulation. LMEMG data were could, therefore, be considered consistent with the endoscopic laryngeal examination in all patient.

Impact of Anesthetics on Immune Functions in a Rat Model of Vagus Nerve Stimulation

PubMed Central

Picq, Chloé A.; Clarençon, Didier; Sinniger, Valérie E.; Bonaz, Bruno L.; Mayol, Jean-François S.

2013-01-01

Vagus nerve stimulation (VNS) has been successfully performed in animals for the treatment of different experimental models of inflammation. The anti-inflammatory effect of VNS involves the release of acetylcholine by vagus nerve efferent fibers inhibiting pro-inflammatory cytokines (e.g. TNF-α) produced by macrophages. Moreover, it has recently been demonstrated that splenic lymphocytic populations may also be involved. As anesthetics can modulate the inflammatory response, the current study evaluated the effect of two different anesthetics, isoflurane and pentobarbital, on splenic cellular and molecular parameters in a VNS rat model. Spleens were collected for the characterization of lymphocytes sub-populations by flow cytometry and quantification of cytokines secretion after in vitro activation. Different results were observed depending on the anesthetic used. The use of isoflurane displayed a non-specific effect of VNS characterized by a decrease of most splenic lymphocytes sub-populations studied, and also led to a significantly lower TNF-α secretion by splenocytes. However, the use of pentobarbital brought to light immune modifications in non-stimulated animals that were not observed with isoflurane, and also revealed a specific effect of VNS, notably at the level of T lymphocytes’ activation. These differences between the two anesthetics could be related to the anti-inflammatory properties of isoflurane. In conclusion, pentobarbital is more adapted than isoflurane in the study of the anti-inflammatory effect of VNS on an anesthetized rat model in that it allows more accurate monitoring of subtle immunomodulatory processes. PMID:23840592

Vagus Nerve Stimulation: A Non-Invasive Treatment to Improve the Health of Gulf Veterans with Gulf War Illness

DTIC Science & Technology

2017-05-01

Gulf War Illness (GWI) is a condition occurring in some veterans who served in the 1990-91 Gulf War. To date there is no specific treatment for it. A...device (which does not stimulate the vagus nerve). We will also test to see if the active device improves migraine which commonly occurs with widespread pain in GWI.

Effect of copper sulphate on the rate of afferent discharge in the gastric branch of the vagus nerve in the rat

NASA Technical Reports Server (NTRS)

Niijima, Akira; Jiang, Zheng-Yao; Daunton, Nancy G.; Fox, Robert A.

1991-01-01

The afferent nerve activity was recorded from a nerve filament isolated from the peripheral cut end of the gastric branch of the vagus nerve. The gastric perfusion of 4 ml of two different concentrations (0.04 percent and 0.08 percent) of CuSO4 solution provoked an increase in afferent activity. The stimulating effect of the 0.08 percent solution was stronger than that of the 0.04 percent solution, and lasted for a longer period of time. The observations suggest a possible mechanism by which CuSO4 elicits emesis.

Malignant nerve sheath tumor involving glossopharyngeal, vagus and spinal nerve with intracranial-extracranial extension and systemic metastases in a patient with type 1 neurofibromatosis: A case report.

PubMed

Guerra-Mora, José Raúl; Del Castillo-Calcáneo, Juan D; Córdoba-Mosqueda, María Elena; Yáñez-Castro, Jorge; García-González, Ulises; Soriano-Navarro, Eduardo; Llamas-Ceras, Leticia; Vicuña-González, Rosa María

2016-01-01

Intracranial malignant peripheral nerve sheath tumors are an extremely rare pathology with a high morbidity and mortality. Epidemiological, clinical and prognostic data are scarce and with little certainty in the literature. The aim of this paper is to report for first time in English literature, the case of a patient with type 1 neurofibromatosis, who presented a malignant peripheral nerve sheath tumor that involved the left glossopharyngeal, vagus and spinal nerves with intracranial and extracranial extension through jugular foramen and systemic metastases. A 37 years-old female patient with malnutrition and Villaret́s syndrome. It was confirmed by brain magnetic resonance imaging and PET-CT the presence of a neoplasic lesion which was radiologically compatible with malignant peripheral nerve sheath tumor with systemic metastases. Partial surgical resection was performed; the patient postoperative course was without significant clinical improvement but with added peripheral facial palsy. The patient did not accept adjuvant management because of personal reasons. Behavior therapy is unclear due to the low frequency of the disease and the lack of case series, representing a challenge for the physician in its approach and a poor prognosis for the patient. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Auricular Neuromodulation: The Emerging Concept beyond the Stimulation of Vagus and Trigeminal Nerves

PubMed Central

Mercante, Beniamina; Rangon, Claire-Marie

2018-01-01

Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops, seems to be the best way to exploit brain plasticity for therapeutic purposes. In the past years, there has been tremendous advances in the field of non-pharmacological modulation of brain activity. This review of different neurostimulation techniques will focus on sites and mechanisms of both transcutaneous vagus and trigeminal nerve stimulation. These methods are scientifically validated non-invasive bottom-up brain modulation techniques, easily implemented from the outer ear. In the light of this, auricles could transpire to be the most affordable target for non-invasive manipulation of central nervous system functions. PMID:29361732

Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

PubMed Central

Corsi-Zuelli, Fabiana Maria das Graças; Brognara, Fernanda; Quirino, Gustavo Fernando da Silva; Hiroki, Carlos Hiroji; Fais, Rafael Sobrano; Del-Ben, Cristina Marta; Ulloa, Luis; Salgado, Helio Cesar; Kanashiro, Alexandre; Loureiro, Camila Marcelino

2017-01-01

Schizophrenia is one of the most debilitating mental disorders and is aggravated by the lack of efficacious treatment. Although its etiology is unclear, epidemiological studies indicate that infection and inflammation during development induces behavioral, morphological, neurochemical, and cognitive impairments, increasing the risk of developing schizophrenia. The inflammatory hypothesis of schizophrenia is also supported by clinical studies demonstrating systemic inflammation and microglia activation in schizophrenic patients. Although elucidating the mechanism that induces this inflammatory profile remains a challenge, mounting evidence suggests that neuroimmune interactions may provide therapeutic advantages to control inflammation and hence schizophrenia. Recent studies have indicated that vagus nerve stimulation controls both peripheral and central inflammation via alpha-7 nicotinic acetylcholine receptor (α7nAChR). Other findings have indicated that vagal stimulation and α7nAChR-agonists can provide therapeutic advantages for neuropsychiatric disorders, such as depression and epilepsy. This review analyzes the latest results regarding: (I) the immune-to-brain pathogenesis of schizophrenia; (II) the regulation of inflammation by the autonomic nervous system in psychiatric disorders; and (III) the role of the vagus nerve and α7nAChR in schizophrenia. PMID:28620379

Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

PubMed

Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

2015-11-15

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. Copyright © 2015 the American Physiological Society.

Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function

PubMed Central

Rajendran, Pradeep S.; Nier, Heath A.; KenKnight, Bruce H.; Armour, J. Andrew

2015-01-01

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. PMID:26371171

A review of vagus nerve stimulation as a therapeutic intervention

PubMed Central

Johnson, Rhaya L; Wilson, Christopher G

2018-01-01

In this review, we provide an overview of the US Food and Drug Administration (FDA)-approved clinical uses of vagus nerve stimulation (VNS) as well as information about the ongoing studies and preclinical research to expand the use of VNS to additional applications. VNS is currently FDA approved for therapeutic use in patients aged >12 years with drug-resistant epilepsy and depression. Recent studies of VNS in in vivo systems have shown that it has anti-inflammatory properties which has led to more preclinical research aimed at expanding VNS treatment across a wider range of inflammatory disorders. Although the signaling pathway and mechanism by which VNS affects inflammation remain unknown, VNS has shown promising results in treating chronic inflammatory disorders such as sepsis, lung injury, rheumatoid arthritis (RA), and diabetes. It is also being used to control pain in fibromyalgia and migraines. This new preclinical research shows that VNS bears the promise of being applied to a wider range of therapeutic applications. PMID:29844694

Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy

PubMed Central

Rolston, John D.; Wright, Clinton W.; Hassnain, Kevin H.; Chang, Edward F.

2015-01-01

BACKGROUND: Neuromodulation-based treatments have become increasingly important in epilepsy treatment. Most patients with epilepsy treated with neuromodulation do not achieve complete seizure freedom, and, therefore, previous studies of vagus nerve stimulation (VNS) therapy have focused instead on reduction of seizure frequency as a measure of treatment response. OBJECTIVE: To elucidate rates and predictors of seizure freedom with VNS. METHODS: We examined 5554 patients from the VNS therapy Patient Outcome Registry, and also performed a systematic review of the literature including 2869 patients across 78 studies. RESULTS: Registry data revealed a progressive increase over time in seizure freedom after VNS therapy. Overall, 49% of patients responded to VNS therapy 0 to 4 months after implantation (≥50% reduction seizure frequency), with 5.1% of patients becoming seizure-free, while 63% of patients were responders at 24 to 48 months, with 8.2% achieving seizure freedom. On multivariate analysis, seizure freedom was predicted by age of epilepsy onset >12 years (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.38-2.58), and predominantly generalized seizure type (OR, 1.36; 95% CI, 1.01-1.82), while overall response to VNS was predicted by nonlesional epilepsy (OR, 1.38; 95% CI, 1.06-1.81). Systematic literature review results were consistent with the registry analysis: At 0 to 4 months, 40.0% of patients had responded to VNS, with 2.6% becoming seizure-free, while at last follow-up, 60.1% of individuals were responders, with 8.0% achieving seizure freedom. CONCLUSION: Response and seizure freedom rates increase over time with VNS therapy, although complete seizure freedom is achieved in a small percentage of patients. ABBREVIATIONS: AED, antiepileptic drug VNS, vagus nerve stimulation PMID:26645965

A comprehensive review with potential significance during skull base and neck operations, Part II: glossopharyngeal, vagus, accessory, and hypoglossal nerves and cervical spinal nerves 1-4.

PubMed

Shoja, Mohammadali M; Oyesiku, Nelson M; Shokouhi, Ghaffar; Griessenauer, Christoph J; Chern, Joshua J; Rizk, Elias B; Loukas, Marios; Miller, Joseph H; Tubbs, R Shane

2014-01-01

Knowledge of the possible neural interconnections found between the lower cranial and upper cervical nerves may prove useful to surgeons who operate on the skull base and upper neck regions in order to avoid inadvertent traction or transection. We review the literature regarding the anatomy, function, and clinical implications of the complex neural networks formed by interconnections between the lower cranial and upper cervical nerves. A review of germane anatomic and clinical literature was performed. The review is organized into two parts. Part I discusses the anastomoses between the trigeminal, facial, and vestibulocochlear nerves or their branches and other nerve trunks or branches in the vicinity. Part II deals with the anastomoses between the glossopharyngeal, vagus, accessory and hypoglossal nerves and their branches or between these nerves and the first four cervical spinal nerves; the contribution of the autonomic nervous system to these neural plexuses is also briefly reviewed. Part II is presented in this article. Extensive and variable neural anastomoses exist between the lower cranial nerves and between the upper cervical nerves in such a way that these nerves with their extra-axial communications can be collectively considered a plexus. Copyright © 2013 Wiley Periodicals, Inc.

Parkinson disease affects peripheral sensory nerves in the pharynx.

PubMed

Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Nyirenda, Themba; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Sue, Lucia I; Beach, Thomas G

2013-07-01

Dysphagia is very common in patients with Parkinson disease (PD) and often leads to aspiration pneumonia, the most common cause of death in PD. Current therapies are largely ineffective for dysphagia. Because pharyngeal sensation normally triggers the swallowing reflex, we examined pharyngeal sensory nerves in PD patients for Lewy pathology.Sensory nerves supplying the pharynx were excised from autopsied pharynges obtained from patients with clinically diagnosed and neuropathologically confirmed PD (n = 10) and healthy age-matched controls (n = 4). We examined the glossopharyngeal nerve (cranial nerve IX), the pharyngeal sensory branch of the vagus nerve (PSB-X), and the internal superior laryngeal nerve (ISLN) innervating the laryngopharynx. Immunohistochemistry for phosphorylated α-synuclein was used to detect Lewy pathology. Axonal α-synuclein aggregates in the pharyngeal sensory nerves were identified in all of the PD subjects but not in the controls. The density of α-synuclein-positive lesions was greater in PD patients with dysphagia versus those without dysphagia. In addition, α-synuclein-immunoreactive nerve fibers in the ISLN were much more abundant than those in cranial nerve IX and PSB-X. These findings suggest that pharyngeal sensory nerves are directly affected by pathologic processes in PD. These abnormalities may decrease pharyngeal sensation, thereby impairing swallowing and airway protective reflexes and contributing to dysphagia and aspiration.

Association of vagus nerve severance and decreased risk of subsequent type 2 diabetes in peptic ulcer patients: An Asian population cohort study.

PubMed

Wu, Shih-Chi; Chen, William Tzu-Liang; Fang, Chu-Wen; Muo, Chih-Hsin; Sung, Fung-Chang; Hsu, Chung Y

2016-12-01

Vagus nerve may play a role in serum glucose modulation. The complicated peptic ulcer patients (with perforation or/and bleeding) who received surgical procedures with or without vagotomy provided 2 patient populations for studying the impact of vagus nerve integrity. We assessed the risk of developing type 2 diabetes in peptic ulcer patients without and with complications by surgical treatment received in a retrospective population study using the National Health Insurance database in Taiwan.A cohort of 163,385 patients with peptic ulcer and without Helicobacter pylori infection in 2000 to 2003 was established. A randomly selected cohort of 163,385 persons without peptic ulcer matched by age, sex, hypertension, hyperlipidemia, Charlson comorbidity index score, and index year was utilized for comparison. The risks of developing diabetes in both cohorts and in the complicated peptic ulcer patients who received truncal vagotomy or simple suture/hemostasis (SSH) were assessed at the end of 2011.The overall diabetes incidence was higher in patients with peptic ulcer than those without peptic ulcer (15.87 vs 12.60 per 1000 person-years) by an adjusted hazard ratio (aHR) of 1.43 (95% confidence interval [CI] = 1.40-1.47) based on the multivariable Cox proportional hazards regression analysis (competing risk). Comparing ulcer patients with truncal vagotomy and SSH or those without surgical treatment, the aHR was the lowest in the vagotomy group (0.48, 95% CI = 0.41-0.56).Peptic ulcer patients have an elevated risk of developing type 2 diabetes. Moreover, there were associations of vagus nerve severance and decreased risk of subsequent type 2 diabetes in complicated peptic ulcer patients.

On-off closed-loop control of vagus nerve stimulation for the adaptation of heart rate.

PubMed

Ugalde, Hector Romero; Le Rolle, Virginie; Bel, Alain; Bonnet, Jean-Luc; Andreu, David; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I

2014-01-01

Vagus nerve stimulation (VNS) is a potential therapeutic approach in a number of clinical applications. Although VNS is commonly delivered in an open-loop approach, it is now recognized that closed-loop approaches may be necessary to optimize the therapy and minimize side effects of neuro-stimulation devices. In this paper, we describe a prototype system for real-time control of the instantaneous heart rate, working synchronously with the heart period. As a first step, an on-off control method has been integrated. The system is evaluated on one sheep with induced heart failure, showing the interest of the proposed approach.

Microsurgical endoscopy-assisted anterior corpus callosotomy for drug-resistant epilepsy in an adult unresponsive to vagus nerve stimulation.

PubMed

Nasi, Davide; Iacoangeli, Maurizio; Di Somma, Lucia; Dobran, Mauro; Di Rienzo, Alessandro; Gladi, Maurizio; Benigni, Roberta; Passamonti, Claudia; Zamponi, Nelia; Scerrati, Massimo

2016-01-01

Because most of the corpus callosotomy (CC) series available in literature were published before the advent of vagus nerve stimulation (VNS), the efficacy of CC in patients with inadequate response to VNS remains unclear, especially in adult patients. We present the case of a 21-year-old female with medically refractory drop attacks that began at the age of 8 years, which resulted in the patient being progressively unresponsive to vagus nerve stimulation implanted at the age of 14 years. Corpus callosotomy was recommended to reduce the number of drop attacks. However, the patient had only mild cognitive impairments and no neurological deficits. For this reason, we were forced to plan a surgical approach able to maximize the disconnection for good seizure control while, at the same time, minimizing sequelae from disconnection syndromes and neurosurgical complications because in such cases of long-lasting epilepsy the gyri cinguli and the arteries can be tenaciously adherent and dislocated with all the normal anatomy altered. In this scenario, we opted for a microsurgical endoscopy-assisted anterior two-thirds corpus callosotomy. The endoscopic minimally invasive approach proved to be quite adequate in this technically demanding case and confirmed that CC may offer advantages, with good results, even in adult patients with drop attacks who have had inadequate response to VNS.

Cranial nerve vascular compression syndromes of the trigeminal, facial and vago-glossopharyngeal nerves: comparative anatomical study of the central myelin portion and transitional zone; correlations with incidences of corresponding hyperactive dysfunctional syndromes.

PubMed

Guclu, Bulent; Sindou, Marc; Meyronet, David; Streichenberger, Nathalie; Simon, Emile; Mertens, Patrick

2011-12-01

The aim of this study was to evaluate the anatomy of the central myelin portion and the central myelin-peripheral myelin transitional zone of the trigeminal, facial, glossopharyngeal and vagus nerves from fresh cadavers. The aim was also to investigate the relationship between the length and volume of the central myelin portion of these nerves with the incidences of the corresponding cranial dysfunctional syndromes caused by their compression to provide some more insights for a better understanding of mechanisms. The trigeminal, facial, glossopharyngeal and vagus nerves from six fresh cadavers were examined. The length of these nerves from the brainstem to the foramen that they exit were measured. Longitudinal sections were stained and photographed to make measurements. The diameters of the nerves where they exit/enter from/to brainstem, the diameters where the transitional zone begins, the distances to the most distal part of transitional zone from brainstem and depths of the transitional zones were measured. Most importantly, the volume of the central myelin portion of the nerves was calculated. Correlation between length and volume of the central myelin portion of these nerves and the incidences of the corresponding hyperactive dysfunctional syndromes as reported in the literature were studied. The distance of the most distal part of the transitional zone from the brainstem was 4.19  ±  0.81 mm for the trigeminal nerve, 2.86  ±  1.19 mm for the facial nerve, 1.51  ±  0.39 mm for the glossopharyngeal nerve, and 1.63  ±  1.15 mm for the vagus nerve. The volume of central myelin portion was 24.54  ±  9.82 mm(3) in trigeminal nerve; 4.43  ±  2.55 mm(3) in facial nerve; 1.55  ±  1.08 mm(3) in glossopharyngeal nerve; 2.56  ±  1.32 mm(3) in vagus nerve. Correlations (p  < 0.001) have been found between the length or volume of central myelin portions of the trigeminal, facial, glossopharyngeal and vagus nerves and incidences

Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke.

PubMed

Khodaparast, N; Hays, S A; Sloan, A M; Hulsey, D R; Ruiz, A; Pantoja, M; Rennaker, R L; Kilgard, M P

2013-12-01

Upper limb impairment is a common debilitating consequence of ischemic stroke. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement. We have recently developed a novel method that uses vagus nerve stimulation (VNS) paired with forelimb movements to drive specific, long-lasting map plasticity in rat primary motor cortex. Here we report that VNS paired with rehabilitative training can enhance recovery of forelimb force generation following infarction of primary motor cortex in rats. Quantitative measures of forelimb function returned to pre-lesion levels when VNS was delivered during rehab training. Intensive rehab training without VNS failed to restore function back to pre-lesion levels. Animals that received VNS during rehab improved twice as much as rats that received the same rehabilitation without VNS. VNS delivered during physical rehabilitation represents a novel method that may provide long-lasting benefits towards stroke recovery. © 2013.

Parkinson Disease Affects Peripheral Sensory Nerves in the Pharynx

PubMed Central

Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Nyirenda, Themba; Adler, Charles H.; Shill, Holly A.; Caviness, John N.; Samanta, Johan E.; Sue, Lucia I.; Beach, Thomas G.

2013-01-01

Dysphagia is very common in patients with Parkinson’s disease (PD) and often leads to aspiration pneumonia, the most common cause of death in PD. Unfortunately, current therapies are largely ineffective for dysphagia. As pharyngeal sensation normally triggers the swallowing reflex, we examined pharyngeal sensory nerves in PD for Lewy pathology. Sensory nerves supplying the pharynx were excised from autopsied pharynges obtained from patients with clinically diagnosed and neuropathologically confirmed PD (n = 10) and healthy age-matched controls (n = 4). We examined: the glossopharyngeal nerve (IX); the pharyngeal sensory branch of the vagus nerve (PSB-X); and the internal superior laryngeal nerve (ISLN) innervating the laryngopharynx. Immunohistochemistry for phosphorylated α-synuclein was used to detect potential Lewy pathology. Axonal α-synuclein aggregates in the pharyngeal sensory nerves were identified in all of the PD subjects but not in the controls. The density of α-synuclein-positive lesions was significantly greater in PD subjects with documented dysphagia compared to those without dysphagia. In addition, α-synuclein-immunoreactive nerve fibers in the ISLN were much more abundant than those in the IX and PSBX. These findings suggest that pharyngeal sensory nerves are directly affected by the pathologic process of PD. This anatomic pathology may decrease pharyngeal sensation impairing swallowing and airway protective reflexes, thereby contributing to dysphagia and aspiration. PMID:23771215

Online patient information on Vagus Nerve Stimulation: How reliable is it for facilitating shared decision making?

PubMed

Ved, Ronak; Cobbold, Naomi; Igbagiri, Kueni; Willis, Mark; Leach, Paul; Zaben, Malik

2017-08-01

This study evaluates the quality of information available on the internet for carers of children with epilepsy considering treatment with Vagus Nerve Stimulation (VNS). Selected key phrases were entered into two popular search engines (Google™, Yahoo™). These phrases were: "Vagus nerve stimulator", alone and in combination with "childhood epilepsy", "paediatric epilepsy" and "epilepsy in childhood"; "VNS", and "VNS epilepsy". The first 50 hits per search were then screened. Of 600 identified sites, duplicated (262), irrelevant (230) and inaccessible (15) results were excluded. 93 websites were identified for evaluation using the DISCERN instrument, an online validation tool for patient information websites. The mean DISCERN score of all analysed websites was 39/80 (49%; SD 13.5). This equates to Fair to borderline Poor global quality, (Excellent=80-63; Good=62-51; Fair=50-39; Poor=38-27; Very poor=26-15). None of the analysed sites obtained an Excellent quality rating. 13% (12) obtained a Good score, 40% (37) obtained an Average score, 35% (33) obtained a Poor score, and 12% (11) obtained a Very poor score. The cohort of websites scored particularly poorly on assessment of whether reliable, holistic information was presented, for instance provision of reliable sources, (28%, SD 18) and discussion of alternative treatments, (30%, SD 14). To facilitate patient-centred shared decision-making, high quality information needs to be available for patients and families considering VNS. This study identifies that such information is difficult to locate on the internet. There is a need to develop focussed and reliable online patient resources for VNS. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Vagus nerve stimulation: state of the art of stimulation and recording strategies to address autonomic function neuromodulation

NASA Astrophysics Data System (ADS)

Guiraud, David; Andreu, David; Bonnet, Stéphane; Carrault, Guy; Couderc, Pascal; Hagège, Albert; Henry, Christine; Hernandez, Alfredo; Karam, Nicole; Le Rolle, Virginie; Mabo, Philippe; Maciejasz, Paweł; Malbert, Charles-Henri; Marijon, Eloi; Maubert, Sandrine; Picq, Chloé; Rossel, Olivier; Bonnet, Jean-Luc

2016-08-01

Objective. Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. Approach. This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. Main results. We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans.

Ablation of the Right Cardiac Vagus Nerve Reduces Acetylcholine Content without Changing the Inflammatory Response during Endotoxemia.

PubMed

Plaschke, Konstanze; Do, Thuc Quyen Monica; Uhle, Florian; Brenner, Thorsten; Weigand, Markus A; Kopitz, Jürgen

2018-02-01

Acetylcholine is the main transmitter of the parasympathetic vagus nerve. According to the cholinergic anti-inflammatory pathway (CAP) concept, acetylcholine has been shown to be important for signal transmission within the immune system and also for a variety of other functions throughout the organism. The spleen is thought to play an important role in regulating the CAP. In contrast, the existence of a "non-neuronal cardiac cholinergic system" that influences cardiac innervation during inflammation has been hypothesized, with recent publications introducing the heart instead of the spleen as a possible interface between the immune and nervous systems. To prove this hypothesis, we investigated whether selectively disrupting vagal stimulation of the right ventricle plays an important role in rat CAP regulation during endotoxemia. We performed a selective resection of the right cardiac branch of the Nervus vagus (VGX) with a corresponding sham resection in vehicle-injected and endotoxemic rats. Rats were injected with lipopolysaccharide (LPS, 1 mg/kg body weight, intravenously) and observed for 4 h. Intraoperative blood gas analysis was performed, and hemodynamic parameters were assessed using a left ventricular pressure-volume catheter. Rat hearts and blood were collected, and the expression and concentration of proinflammatory cytokines using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were measured, respectively. Four hours after injection, LPS induced a marked deterioration in rat blood gas parameters such as pH value, potassium, base excess, glucose, and lactate. The mean arterial blood pressure and the end-diastolic volume had decreased significantly. Further, significant increases in blood cholinesterases and in proinflammatory (IL-1β, IL-6, TNF-α) cytokine concentration and gene expression were obtained. Right cardiac vagus nerve resection (VGX) led to a marked decrease in heart acetylcholine

Ablation of the Right Cardiac Vagus Nerve Reduces Acetylcholine Content without Changing the Inflammatory Response during Endotoxemia

PubMed Central

Plaschke, Konstanze; Do, Thuc Quyen Monica; Brenner, Thorsten; Weigand, Markus A.; Kopitz, Jürgen

2018-01-01

Acetylcholine is the main transmitter of the parasympathetic vagus nerve. According to the cholinergic anti-inflammatory pathway (CAP) concept, acetylcholine has been shown to be important for signal transmission within the immune system and also for a variety of other functions throughout the organism. The spleen is thought to play an important role in regulating the CAP. In contrast, the existence of a “non-neuronal cardiac cholinergic system” that influences cardiac innervation during inflammation has been hypothesized, with recent publications introducing the heart instead of the spleen as a possible interface between the immune and nervous systems. To prove this hypothesis, we investigated whether selectively disrupting vagal stimulation of the right ventricle plays an important role in rat CAP regulation during endotoxemia. We performed a selective resection of the right cardiac branch of the Nervus vagus (VGX) with a corresponding sham resection in vehicle-injected and endotoxemic rats. Rats were injected with lipopolysaccharide (LPS, 1 mg/kg body weight, intravenously) and observed for 4 h. Intraoperative blood gas analysis was performed, and hemodynamic parameters were assessed using a left ventricular pressure-volume catheter. Rat hearts and blood were collected, and the expression and concentration of proinflammatory cytokines using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were measured, respectively. Four hours after injection, LPS induced a marked deterioration in rat blood gas parameters such as pH value, potassium, base excess, glucose, and lactate. The mean arterial blood pressure and the end-diastolic volume had decreased significantly. Further, significant increases in blood cholinesterases and in proinflammatory (IL-1β, IL-6, TNF-α) cytokine concentration and gene expression were obtained. Right cardiac vagus nerve resection (VGX) led to a marked decrease in heart acetylcholine

Dietary 2’-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication through the Vagus Nerve in Rodents

PubMed Central

Vazquez, Enrique; Barranco, Alejandro; Ramirez, Maria; Gruart, Agnes; Delgado-Garcia, Jose M.; Jimenez, Maria L.; Buck, Rachael; Rueda, Ricardo

2016-01-01

2´-fucosyllactose (2´-FL) is an abundant human milk oligosaccharide (HMO) in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS) function, such as hippocampal long term potentiation (LTP) and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA), specifically the vagus nerve, and L-fucose (Fuc) may play a role. This study had two aims: (1) determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2) confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits. PMID:27851789

Cervical Sympathetic Chain Schwannoma Masquerading as a Vagus Nerve Schwannoma Complicated by Postoperative Horner's Syndrome and Facial Pain: A Case Report.

PubMed

Baker, Austin T; Homewood, Tyler J; Baker, Terry R

2018-06-09

Cervical Sympathetic Chain Schwannomas (CSCS) of the carotid sheath are rare neoplasms that can be misdiagnosed on imaging. The following case documents a rare incident of a misdiagnosed CSCS with unusual outcomes of permanent Horner's syndrome and facial pain. A 36-year-old female presented with a slow-growing neck mass. CT and MRI led to a preoperative diagnosis of vagus nerve schwannoma (VNS). However, surgical treatment revealed the mass to be involved with the cervical sympathetic chain rather than the vagus nerve. The diagnosis was corrected to CSCS and the nerve was resected with the mass. The patient presented postoperatively with Horner's syndrome and severe facial pain. These symptoms persisted despite two years of medical management. Studies indicate that imaging trends used for distinction between VNS and CSCS show inconsistencies in making preoperative diagnoses. Recent literature reveals helpful criteria for improving diagnostic standards that assist with preoperative patient counseling. In addition, postoperative outcomes, such as temporary, asymptomatic Horner's syndrome are common in CSCS. The following case report exemplifies the difficulties in diagnosis and addresses the unique complications of facial pain and permanent Horner's syndrome. This case report examines postoperative outcomes and improves clinician awareness of the potential for misdiagnosis of a rare neoplasm and the recently improved diagnostic measures, providing for higher quality preoperative counseling. Future research is recommended to confirm and improve diagnostic guidelines and accuracy. Additional studies may focus on evaluating the effects of incorrect preoperative diagnosis on postoperative complication rates. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Defining the neural fulcrum for chronic vagus nerve stimulation: implications for integrated cardiac control.

PubMed

Ardell, Jeffrey L; Nier, Heath; Hammer, Matthew; Southerland, E Marie; Ardell, Christopher L; Beaumont, Eric; KenKnight, Bruce H; Armour, J Andrew

2017-11-15

The evoked cardiac response to bipolar cervical vagus nerve stimulation (VNS) reflects a dynamic interaction between afferent mediated decreases in central parasympathetic drive and suppressive effects evoked by direct stimulation of parasympathetic efferent axons to the heart. The neural fulcrum is defined as the operating point, based on frequency-amplitude-pulse width, where a null heart rate response is reproducibly evoked during the on-phase of VNS. Cardiac control, based on the principal of the neural fulcrum, can be elicited from either vagus. Beta-receptor blockade does not alter the tachycardia phase to low intensity VNS, but can increase the bradycardia to higher intensity VNS. While muscarinic cholinergic blockade prevented the VNS-induced bradycardia, clinically relevant doses of ACE inhibitors, beta-blockade and the funny channel blocker ivabradine did not alter the VNS chronotropic response. While there are qualitative differences in VNS heart control between awake and anaesthetized states, the physiological expression of the neural fulcrum is maintained. Vagus nerve stimulation (VNS) is an emerging therapy for treatment of chronic heart failure and remains a standard of therapy in patients with treatment-resistant epilepsy. The objective of this work was to characterize heart rate (HR) responses (HRRs) during the active phase of chronic VNS over a wide range of stimulation parameters in order to define optimal protocols for bidirectional bioelectronic control of the heart. In normal canines, bipolar electrodes were chronically implanted on the cervical vagosympathetic trunk bilaterally with anode cephalad to cathode (n = 8, 'cardiac' configuration) or with electrode positions reversed (n = 8, 'epilepsy' configuration). In awake state, HRRs were determined for each combination of pulse frequency (2-20 Hz), intensity (0-3.5 mA) and pulse widths (130-750 μs) over 14 months. At low intensities and higher frequency VNS, HR increased during the

Vagus nerve stimulation as a potential adjuvant to behavioral therapy for autism and other neurodevelopmental disorders.

PubMed

Engineer, Crystal T; Hays, Seth A; Kilgard, Michael P

2017-01-01

Many children with autism and other neurodevelopmental disorders undergo expensive, time-consuming behavioral interventions that often yield only modest improvements. The development of adjunctive interventions that can increase the benefit of rehabilitation therapies is essential in order to improve the lives of individuals with neurodevelopmental disorders. Vagus nerve stimulation (VNS) is an FDA approved therapy that is safe and effective in reducing seizure frequency and duration in individuals with epilepsy. Individuals with neurodevelopmental disorders often exhibit decreased vagal tone, and studies indicate that VNS can be used to overcome an insufficient vagal response. Multiple studies have also documented significant improvements in quality of life after VNS therapy in individuals with neurodevelopmental disorders. Moreover, recent findings indicate that VNS significantly enhances the benefits of rehabilitative training in animal models and patients, leading to greater recovery in a variety of neurological diseases. Here, we review these findings and provide a discussion of how VNS paired with rehabilitation may yield benefits in the context of neurodevelopmental disorders. VNS paired with behavioral therapy may represent a potential new approach to enhance rehabilitation that could significantly improve the outcomes of individuals with neurodevelopmental disorders.

Inoculation of α-synuclein preformed fibrils into the mouse gastrointestinal tract induces Lewy body-like aggregates in the brainstem via the vagus nerve.

PubMed

Uemura, Norihito; Yagi, Hisashi; Uemura, Maiko T; Hatanaka, Yusuke; Yamakado, Hodaka; Takahashi, Ryosuke

2018-05-11

Intraneuronal α-synuclein (α-Syn) aggregates known as Lewy bodies (LBs) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the pathological hallmarks of Parkinson's disease (PD). Braak's hypothesis based on autopsy studies suggests that Lewy pathology initially occurs in the enteric nervous system (ENS) and then travels retrogradely to the dorsal motor nucleus of the vagus nerve (dmX), proceeding from there in a caudo-rostral direction. Recent evidence that α-Syn aggregates propagate between interconnected neurons supports this hypothesis. However, there is no direct evidence demonstrating this transmission from the ENS to the dmX and then to the SNpc. We inoculated α-Syn preformed fibrils (PFFs) or phosphate-buffered saline (PBS) into the mouse gastric wall and analyzed the progression of the pathology. The mice inoculated with α-Syn PFFs, but not with PBS, developed phosphorylated α-Syn (p-α-Syn)-positive LB-like aggregates in the dmX at 45 days postinoculation. This aggregate formation was completely abolished when vagotomy was performed prior to inoculation of α-Syn PFFs, suggesting that the aggregates in the dmX were retrogradely induced via the vagus nerve. Unexpectedly, the number of neurons containing p-α-Syn-positive aggregates in the dmX decreased over time, and no further caudo-rostral propagation beyond the dmX was observed up to 12 months postinoculation. P-α-Syn-positive aggregates were also present in the myenteric plexus at 12 months postinoculation. However, unlike in patients with PD, there was no cell-type specificity in neurons containing those aggregates in this model. These results indicate that α-Syn PFF inoculation into the mouse gastrointestinal tract can induce α-Syn pathology resembling that of very early PD, but other factors are apparently required if further progression of PD pathology is to be replicated in this animal model.

The novel orally active guanylhydrazone CPSI-2364 prevents postoperative ileus in mice independently of anti-inflammatory vagus nerve signaling.

PubMed

Wehner, S; Vilz, T O; Sommer, N; Sielecki, T; Hong, G S; Lysson, M; Stoffels, B; Pantelis, D; Kalff, J C

2012-10-01

Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). Previously, we demonstrated that intravenous application of the tetravalent guanylhydrazone semapimod (CNI-1493) prevents POI, but the underlying mode of action could not definitively be confirmed. Herein, we investigated the effect of a novel orally active salt of semapimod (CPSI-2364) on POI in rodents and distinguished between its inhibitory peripheral and stimulatory central nervous effects on anti-inflammatory vagus nerve signaling. Distribution of radiolabeled orally administered CPSI-2364 was analyzed by whole body autoradiography and liquid scintillation counting. POI was induced by intestinal manipulation with or without preoperative vagotomy. CPSI-2364 was administered preoperatively via gavage in a dose- and time-dependent manner. ME specimens were assessed for p38-MAP kinase activity by immunoblotting, neutrophil extravasation, and nitric oxide production. Furthermore, in vivo gastrointestinal (GIT) and colonic transit were measured. Autoradiography demonstrated a near-exclusive detection of CPSI-2364 within the gastrointestinal wall and contents. Preoperative CPSI-2364 application significantly reduced postoperative neutrophil counts, nitric oxide release, GIT deceleration, and delay of colonic transit time, while intraoperatively administered CPSI-2364 failed to improve POI. CPSI-2364 also prevents postoperative neutrophil increase and GIT deceleration in vagotomized mice. Orally administered CPSI-2364 shows a near-exclusive dispersal in the gastrointestinal tract and effectively reduces POI independently of central vagus nerve stimulation. Its efficacy after single oral dosage affirms CPSI-2364 treatment as a promising strategy for prophylaxis of POI.

Hemicrania Continua: Beneficial Effect of Non-Invasive Vagus Nerve Stimulation in a Patient With a Contraindication for Indomethacin.

PubMed

Eren, Ozan; Straube, Andreas; Schöberl, Florian; Schankin, Christoph

2017-02-01

Hemicrania continua (HC) is a primary chronic headache disorder, characterized by a continuous and strictly unilateral headache, with possible cranial autonomic symptoms during episodes of pain exacerbation. The unilateral headache generally responds well to indomethacin; however, continuous indomethacin intake is often not tolerated due to severe adverse effects, like hypertension, gastrointestinal discomfort (especially if combined with aspirin), slightly increased risk of vascular events, and bronchial spasms. Therefore, alternative treatment options are desperately needed. Non-invasive vagus nerve stimulation (nVNS) has been shown to be effective in patients with cluster headache, another trigeminal autonomic cephalalgia (TAC), with cranial parasympathetic autonomic activation during the attacks. © 2016 American Headache Society.

Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction

PubMed Central

Beaumont, Eric; Southerland, Elizabeth M.; Hardwick, Jean C.; Wright, Gary L.; Ryan, Shannon; Li, Ying; KenKnight, Bruce H.; Armour, J. Andrew

2015-01-01

This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. PMID:26276818

Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction.

PubMed

Beaumont, Eric; Southerland, Elizabeth M; Hardwick, Jean C; Wright, Gary L; Ryan, Shannon; Li, Ying; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

2015-10-01

This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. Copyright © 2015 the American Physiological Society.

Attempt of peripheral nerve reconstruction during lung cancer surgery.

PubMed

Li, Hanyue; Hu, Yingjie; Huang, Jia; Yang, Yunhai; Xing, Kaichen; Luo, Qingquan

2018-05-01

Vagus nerve and recurrent laryngeal nerve (RLN) injury are not rare complications of lung cancer surgery and can cause lethal consequences. Until now, no optimal method other than paying greater attention during surgery has been available. Four patients underwent lung surgery that involved RLN or vagus nerve injury. The left RLN or vagus nerve was cut off and then reconstructed immediately during surgery. Two patients underwent direct anastomosis, while the remaining two underwent phrenic nerve replacing tension-relieving anastomosis. All patients were able to speak immediately after recovery. No or minimal glottal gap was observed during laryngoscopy conducted on the second day after surgery. Most patients achieved full recovery of voice quality. Immediate reconstruction of RLN is technically feasible and can be carried out with satisfying short-term and long-term outcomes. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Vagus Nerve Stimulation in Intractable Childhood Epilepsy: a Korean Multicenter Experience

PubMed Central

You, Su Jeong; Kang, Hoon-Chul; Kim, Heung Dong; Kim, Deok-Soo; Hwang, Yong Soon; Kim, Dong Suk; Lee, Jung-Kyo; Park, Sang Keun

2007-01-01

We evaluated the long-term outcome of vagus nerve stimulation (VNS) in 28 children with refractory epilepsy. Of these 28 children, 15 (53.6%) showed a >50% reduction in seizure frequency and 9 (32.1%) had a >75% reduction. When we compared seizure reduction rates according to seizure types (generalized vs. partial) and etiologies (symptomatic vs. cryptogenic), we found no significant differences. In addition, there was no correlation between the length of the stimulation period and treatment effect. The seizure reduction rate, however, tended to be inversely related to the seizure duration before VNS implantation and age at the time of VNS therapy. VNS also improved quality of life in this group of patients, including improved memory in 9 (32.1%), improved mood in 12 (42.9%), improved behavior in 11 (39.3%), improved altertness in 12 (42.9%), improved achievement in 6 (21.4%), and improved verbal skills in 8 (28.6%). Adverse events included hoarseness in 7 patients, dyspnea at sleep in 2 patients, and wound infection in 1 patient, but all were transient and successfully managed by careful follow-up and adjustment of parameters. These results indicate that VNS is a safe and effective alternative therapy for pediatric refractory epilepsy, without significant adverse events. PMID:17596651

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

PubMed

Goadsby, P J; Grosberg, B M; Mauskop, A; Cady, R; Simmons, K A

2014-10-01

We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Fasting is a physiological stimulus of vagus-mediated enhancement of nociception in the female rat.

PubMed

Khasar, S G; Reichling, D B; Green, P G; Isenberg, W M; Levine, J D

2003-01-01

The vagus nerve modulates nociception by a mechanism dependent upon gonadal hormones and the adrenal medulla. In the present study we tested the hypothesis that this modulation is dynamically controlled by physiological stimulation of structures innervated by the subdiaphragmatic vagus. Specifically, food deprivation (fasting) was employed to increase activity in the subdiaphragmatic vagus, and the experiments were performed mainly in female rats because our previous observations suggested that baseline activity in the pathway is lower in females than in males. Consistent with the hypothesis, after a 48-h fast, female rats exhibited increased nociceptive behavior in the formalin test. In contrast, fasting had no effect on formalin-evoked nociceptive behavior in male rats. The fasting-induced effect on nociception appears to be mediated by the vagus nerve since it is prevented by subdiaphragmatic vagotomy. Also similar to the previously characterized vagus-mediated modulation, the effect of fasting in the female is blocked by gonadectomy or adrenal medullectomy, and hormone replacement with 17beta-estradiol in gonadectomized female rats restored the effect of fasting. Decreased glucose metabolism apparently does not play a significant role in the effect of fasting on nociception, since the effect was unchanged when 5% glucose was provided in the drinking water throughout the fasting period. On the other hand, increasing the bulk content of the stomach (without providing nutrients) by infusion of petrolatum significantly attenuated the effect of fasting during the interphase period of the formalin response, suggesting that decreased gut distention, and possibly motility, are important in fasting-induced enhancement of nociception. These results indicate that fasting is a physiological activator of the vagus-mediated pain modulation pathway. This suggests the possibility that, especially in females, natural periodic changes in gut distention and motility may control

Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance--The U.S. E-37 Trial.

PubMed

Fisher, Robert S; Afra, Pegah; Macken, Micheal; Minecan, Daniela N; Bagić, Anto; Benbadis, Selim R; Helmers, Sandra L; Sinha, Saurabh R; Slater, Jeremy; Treiman, David; Begnaud, Jason; Raman, Pradheep; Najimipour, Bita

2016-02-01

The Automatic Stimulation Mode (AutoStim) feature of the Model 106 Vagus Nerve Stimulation (VNS) Therapy System stimulates the left vagus nerve on detecting tachycardia. This study evaluates performance, safety of the AutoStim feature during a 3-5-day Epilepsy Monitoring Unit (EMU) stay and long- term clinical outcomes of the device stimulating in all modes. The E-37 protocol (NCT01846741) was a prospective, unblinded, U.S. multisite study of the AspireSR(®) in subjects with drug-resistant partial onset seizures and history of ictal tachycardia. VNS Normal and Magnet Modes stimulation were present at all times except during the EMU stay. Outpatient visits at 3, 6, and 12 months tracked seizure frequency, severity, quality of life, and adverse events. Twenty implanted subjects (ages 21-69) experienced 89 seizures in the EMU. 28/38 (73.7%) of complex partial and secondarily generalized seizures exhibited ≥20% increase in heart rate change. 31/89 (34.8%) of seizures were treated by Automatic Stimulation on detection; 19/31 (61.3%) seizures ended during the stimulation with a median time from stimulation onset to seizure end of 35 sec. Mean duty cycle at six-months increased from 11% to 16%. At 12 months, quality of life and seizure severity scores improved, and responder rate was 50%. Common adverse events were dysphonia (n = 7), convulsion (n = 6), and oropharyngeal pain (n = 3). The Model 106 performed as intended in the study population, was well tolerated and associated with clinical improvement from baseline. The study design did not allow determination of which factors were responsible for improvements. © 2015 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study.

PubMed

Huang, Feng; Dong, Jianxun; Kong, Jian; Wang, Hongcai; Meng, Hong; Spaeth, Rosa B; Camhi, Stephanie; Liao, Xing; Li, Xia; Zhai, Xu; Li, Shaoyuan; Zhu, Bing; Rong, Peijing

2014-06-26

Impaired glucose tolerance (IGT) is a pre-diabetic state of hyperglycemia that is associated with insulin resistance, increased risk of type II diabetes, and cardiovascular pathology. Recently, investigators hypothesized that decreased vagus nerve activity may be the underlying mechanism of metabolic syndrome including obesity, elevated glucose levels, and high blood pressure. In this pilot randomized clinical trial, we compared the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS on patients with IGT. 72 participants with IGT were single-blinded and were randomly allocated by computer-generated envelope to either taVNS or sham taVNS treatment groups. In addition, 30 IGT adults were recruited as a control population and not assigned treatment so as to monitor the natural fluctuation of glucose tolerance in IGT patients. All treatments were self-administered by the patients at home after training at the hospital. Patients were instructed to fill in a patient diary booklet each day to describe any side effects after each treatment. The treatment period was 12 weeks in duration. Baseline comparison between treatment and control group showed no difference in weight, BMI, or measures of systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), or glycosylated hemoglobin (HbAlc). 100 participants completed the study and were included in data analysis. Two female patients (one in the taVNS group, one in the sham taVNS group) dropped out of the study due to stimulation-evoked dizziness. The symptoms were relieved after stopping treatment. Compared with sham taVNS, taVNS significantly reduced the two-hour glucose tolerance (F(2) = 5.79, p = 0.004). In addition, we found that taVNS significantly decreased (F(1) = 4.21, p = 0.044) systolic blood pressure over time compared with sham taVNS. Compared with the no-treatment control group, patients receiving taVNS significantly

Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation.

PubMed

Hulsey, Daniel R; Hays, Seth A; Khodaparast, Navid; Ruiz, Andrea; Das, Priyanka; Rennaker, Robert L; Kilgard, Michael P

2016-01-01

Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry. We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex. Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192-IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex. VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation. Together, these findings indicate that the NB is required for VNS-dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Endogenous angiotensin affects responses to stimulation of baroreceptor afferent nerves.

PubMed

DiBona, Gerald F; Jones, Susan Y

2003-08-01

To study effects of endogenous angiotensin II on responses to standardized stimulation of afferent neural input into the central portion of the arterial and cardiac baroreflexes. Different dietary sodium intakes were used to physiologically alter endogenous angiotensin II activity. Candesartan, an angiotensin II type 1 receptor antagonist, was used to assess dependency of observed effects on angiotensin II stimulation of angiotensin II type 1 receptors. Electrical stimulation of arterial and cardiac baroreflex afferent nerves was used to provide a standardized input to the central portion of the arterial and cardiac baroreflexes. In anesthetized rats in balance on low, normal and high dietary sodium intake, arterial pressure, heart rate and renal sympathetic nerve activity responses to electrical stimulation of vagus and aortic depressor nerves were determined. Compared with plasma renin activity values in normal dietary sodium intake rats, those from low dietary sodium intake rats were higher and those from high dietary sodium intake rats were lower. During vagus nerve stimulation, the heart rate, arterial pressure and renal sympathetic nerve activity responses were similar in all three dietary sodium intake groups. During aortic depressor nerve stimulation, the heart rate and arterial pressure responses were similar in all three dietary sodium intake groups. However, the renal sympathetic nerve activity response was significantly greater in the low sodium group than in the normal and high sodium group at 4, 8 and 16 Hz. Candesartan administered to low dietary sodium intake rats had no effect on the heart rate and arterial pressure responses to either vagus or aortic depressor nerve stimulation but increased the magnitude of the renal sympathoinhibitory responses. Increased endogenous angiotensin II in rats on a low dietary sodium intake attenuates the renal sympathoinhibitory response to activation of the cardiac and sinoaortic baroreflexes by standardized vagus

Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex.

PubMed

Porter, Benjamin A; Khodaparast, Navid; Fayyaz, Tabbassum; Cheung, Ryan J; Ahmed, Syed S; Vrana, William A; Rennaker, Robert L; Kilgard, Michael P

2012-10-01

Although sensory and motor systems support different functions, both systems exhibit experience-dependent cortical plasticity under similar conditions. If mechanisms regulating cortical plasticity are common to sensory and motor cortices, then methods generating plasticity in sensory cortex should be effective in motor cortex. Repeatedly pairing a tone with a brief period of vagus nerve stimulation (VNS) increases the proportion of primary auditory cortex responding to the paired tone (Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake J, Sudanagunta SP, Borland MS, Kilgard MP. 2011. Reversing pathological neural activity using targeted plasticity. Nature. 470:101-104). In this study, we predicted that repeatedly pairing VNS with a specific movement would result in an increased representation of that movement in primary motor cortex. To test this hypothesis, we paired VNS with movements of the distal or proximal forelimb in 2 groups of rats. After 5 days of VNS movement pairing, intracranial microstimulation was used to quantify the organization of primary motor cortex. Larger cortical areas were associated with movements paired with VNS. Rats receiving identical motor training without VNS pairing did not exhibit motor cortex map plasticity. These results suggest that pairing VNS with specific events may act as a general method for increasing cortical representations of those events. VNS movement pairing could provide a new approach for treating disorders associated with abnormal movement representations.

Acute effect of Vagus nerve stimulation parameters on cardiac chronotropic, inotropic, and dromotropic responses

NASA Astrophysics Data System (ADS)

Ojeda, David; Le Rolle, Virginie; Romero-Ugalde, Hector M.; Gallet, Clément; Bonnet, Jean-Luc; Henry, Christine; Bel, Alain; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I.

2017-11-01

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy and depression, and is considered as a potential therapy for other pathologies, including Heart Failure (HF) or inflammatory diseases. In the case of HF, several experimental studies on animals have shown an improvement in the cardiac function and a reverse remodeling of the cardiac cavity when VNS is applied. However, recent clinical trials have not been able to reproduce the same response in humans. One of the hypothesis to explain this lack of response is related to the way in which stimulation parameters are defined. The combined effect of VNS parameters is still poorly-known, especially in the case of VNS synchronously delivered with cardiac activity. In this paper, we propose a methodology to analyze the acute cardiovascular effects of VNS parameters individually, as well as their interactive effects. A Latin hypercube sampling method was applied to design a uniform experimental plan. Data gathered from this experimental plan was used to produce a Gaussian process regression (GPR) model in order to estimate unobserved VNS sequences. Finally, a Morris screening sensitivity analysis method was applied to each obtained GPR model. Results highlight dominant effects of pulse current, pulse width and number of pulses over frequency and delay and, more importantly, the degree of interactions between these parameters on the most important acute cardiovascular responses. In particular, high interacting effects between current and pulse width were found. Similar sensitivity profiles were observed for chronotropic, dromotropic and inotropic effects. These findings are of primary importance for the future development of closed-loop, personalized neuromodulator technologies.

Vagus nerve stimulation blocks vascular permeability following burn injury in both local and distal sites

PubMed Central

Ortiz-Pomales, Yan T; Krzyzaniak, Michael; Coimbra, Raul; Baird, Andrew; Eliceiri, Brian P.

2012-01-01

Recent studies have shown that vagus nerve stimulation (VNS) can block the burn injury-induced systemic inflammatory response (SIRS). In this study we examined the potential for VNS to modulate vascular permeability (VP) in local sites (i.e. skin) and in secondary sites (i.e. lung) following burn injury. In a 30% total body surface area burn injury model, VP was measured using intravascular fluorescent dextran for quantification of the VP response in skin and lung. A peak in VP of the skin was observed 24 hours post-burn injury, that was blocked by VNS. Moreover, in the lung, VNS led to a reduction in burn-induced VP compared to sham-treated animals subjected to burn injury alone. The protective effects of VNS in this model were independent of the spleen, suggesting that the spleen was not a direct mediator of VNS. These studies identify a role for VNS in the regulation of VP in burns, with the translational potential of attenuating lung complications following burn injury. PMID:22694873

Transcutaneous vagus nerve stimulation (tVNS) enhances conflict-triggered adjustment of cognitive control.

PubMed

Fischer, Rico; Ventura-Bort, Carlos; Hamm, Alfons; Weymar, Mathias

2018-04-24

Response conflicts play a prominent role in the flexible adaptation of behavior as they represent context-signals that indicate the necessity for the recruitment of cognitive control. Previous studies have highlighted the functional roles of the affectively aversive and arousing quality of the conflict signal in triggering the adaptation process. To further test this potential link with arousal, participants performed a response conflict task in two separate sessions with either transcutaneous vagus nerve stimulation (tVNS), which is assumed to activate the locus coeruleus-noradrenaline (LC-NE) system, or with neutral sham stimulation. In both sessions the N2 and P3 event-related potentials (ERP) were assessed. In line with previous findings, conflict interference, the N2 and P3 amplitude were reduced after conflict. Most importantly, this adaptation to conflict was enhanced under tVNS compared to sham stimulation for conflict interference and the N2 amplitude. No effect of tVNS on the P3 component was found. These findings suggest that tVNS increases behavioral and electrophysiological markers of adaptation to conflict. Results are discussed in the context of the potentially underlying LC-NE and other neuromodulatory (e.g., GABA) systems. The present findings add important pieces to the understanding of the neurophysiological mechanisms of conflict-triggered adjustment of cognitive control.

Neuroendocrine responses to stimulation of the vagus nerves in bursts in conscious calves.

PubMed

Adrian, T E; Bloom, S R; Edwards, A V

1983-11-01

Effects of stimulation of the peripheral ends of the vagus nerves below the heart at 4 Hz continuously, and at 40 Hz for 1 s at 10 s intervals, have been compared in conscious calves below behavioural threshold. Neither pattern of stimulation caused any significant change in mean aortic blood pressure or heart rate but both invariably produced a substantial increase in the flow of intestinal lymph. Each form of stimulation provoked release of glucagon, insulin and pancreatic polypeptide from the pancreas and produced a small but significant rise in mean arterial plasma glucose concentration. The release of gastric inhibitory peptide- and bombesin-like molecules from the gastrointestinal tract was not affected by vagal stimulation whereas release of vasoactive intestinal peptide was observed in response to both patterns of vagal stimulation. Evidence was obtained to suggest that gastrin-like peptides are preferentially released into the bloodstream whereas cholecystokinin-like peptides are not. Vagal stimulation releases somatostatin from the gastrointestinal tract but discontinuous stimulation seems to inhibit the release of somatostatin into the general circulation. The results that have been obtained, employing this particular protocol, suggest that the pattern of the stimulus that is applied to the vagal splanchnic innervation has relatively little effect on neuroendocrine response in this species.

Neuroendocrine responses to stimulation of the vagus nerves in bursts in conscious calves.

PubMed Central

Adrian, T E; Bloom, S R; Edwards, A V

1983-01-01

Effects of stimulation of the peripheral ends of the vagus nerves below the heart at 4 Hz continuously, and at 40 Hz for 1 s at 10 s intervals, have been compared in conscious calves below behavioural threshold. Neither pattern of stimulation caused any significant change in mean aortic blood pressure or heart rate but both invariably produced a substantial increase in the flow of intestinal lymph. Each form of stimulation provoked release of glucagon, insulin and pancreatic polypeptide from the pancreas and produced a small but significant rise in mean arterial plasma glucose concentration. The release of gastric inhibitory peptide- and bombesin-like molecules from the gastrointestinal tract was not affected by vagal stimulation whereas release of vasoactive intestinal peptide was observed in response to both patterns of vagal stimulation. Evidence was obtained to suggest that gastrin-like peptides are preferentially released into the bloodstream whereas cholecystokinin-like peptides are not. Vagal stimulation releases somatostatin from the gastrointestinal tract but discontinuous stimulation seems to inhibit the release of somatostatin into the general circulation. The results that have been obtained, employing this particular protocol, suggest that the pattern of the stimulus that is applied to the vagal splanchnic innervation has relatively little effect on neuroendocrine response in this species. PMID:6361233

Optimization of epilepsy treatment with vagus nerve stimulation

NASA Astrophysics Data System (ADS)

Uthman, Basim; Bewernitz, Michael; Liu, Chang-Chia; Ghacibeh, Georges

2007-11-01

Epilepsy is one of the most common chronic neurological disorders that affects close to 50 million people worldwide. Antiepilepsy drugs (AEDs), the main stay of epilepsy treatment, control seizures in two thirds of patients only. Other therapies include the ketogenic diet, ablative surgery, hormonal treatments and neurostimulation. While other approaches to stimulation of the brain are currently in the experimental phase vagus nerve stimulation (VNS) has been approved by the FDA since July 1997 for the adjunctive treatment of intractable partial onset epilepsy with and without secondary generalization in patients twelve years of age or older. The safety and efficacy of VNS have been proven and duplicated in two subsequent double-blinded controlled studies after two pilot studies demonstrated the feasibility of VNS in man. Long term observational studies confirmed the safety of VNS and that its effectiveness is sustained over time. While AEDs influence seizure thresholds via blockade or modulation of ionic channels, inhibit excitatory neurotransmitters or enhance inhibitory neurotransmitters the exact mechanism of action of VNS is not known. Neuroimaging studies revealed that VNS increases blood flow in certain regions of the brain such as the thalamus. Chemical lesions in the rat brains showed that norepinephrine is an important link in the anticonvulsant effect of VNS. Analysis of cerebrospinal fluid obtained from patients before and after treatment with VNS showed modest decreases in excitatory neurotransmitters. Although Hammond et al. reported no effect of VNS on scalp EEG by visual analysis and Salinsky et al. found no effect of VNS on scalp EEG by spectral analysis, Kuba et al. suggested that VNS reduces interictal epileptiform activity. Further, nonlinear dynamical analysis of the electroencephalogram in the rat and man have reportedly shown predictable changes (decrease in the short term Lyapunov exponent STLmax and T-index) more than an hour prior to the

Vagus Nerve Stimulation in children: A focus on intellectual disability.

PubMed

Sourbron, Jo; Klinkenberg, Sylvia; Kessels, Alfons; Schelhaas, Helenius Jurgen; Lagae, Lieven; Majoie, Marian

2017-05-01

Vagus Nerve Stimulation (VNS) can be an efficacious add-on treatment in patients with drug-resistant epilepsy, who are not eligible for surgery. Evidence of VNS efficacy in children with intellectual disability (ID) is scarce. The purpose of this study was to review all available VNS data in the pediatric population (≤18 years old) and focus on the subpopulation with ID since appropriate treatment of these children is often challenging and complex. Cochrane, EMBASE, PubMed and MEDLINE were used to collect all research associated to VNS and ID (or synonyms) leading to a total of 37 studies. Seven studies showed the results of patients with ID and those without separately; thereby only these studies were included in the VNS meta-analysis. Our meta-analysis showed that VNS was less effective in pediatric epilepsy patients with ID compared to those without ID (Mantel-Haenszel meta-analysis; p = 0.028, OR 0.18 (CI 95% 0.039-0.84)). However, there were no prospective controlled studies. Numerous studies reported quality of life (QoL) improvements in this subpopulation. The most common adverse events were transient and well tolerated. Side effects on cognition and behavior were not reported. These results might be a reason to consider VNS early on in the treatment of this subgroup. The significantly greater amount of retrospective studies, differences in follow-up (FU), lack of control data, heterogeneous series and limited number of patients could have biased the outcome measurements. Hence, current data do not exclude VNS for children with drug-resistant epilepsy and ID but should be interpreted with caution. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Vagus nerve stimulation enhances perforant path-CA3 synaptic transmission via the activation of β-adrenergic receptors and the locus coeruleus.

PubMed

Shen, Huilian; Fuchino, Yuta; Miyamoto, Daisuke; Nomura, Hiroshi; Matsuki, Norio

2012-05-01

Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and depression and has cognition-enhancing effects in patients with Alzheimer's disease. The hippocampus is widely recognized to be related to epilepsy, depression, and Alzheimer's disease. One possible mechanism of VNS involves its effect on the hippocampus; i.e. it increases the release of noradrenaline in the hippocampus. However, the effect of VNS on synaptic transmission in the hippocampus is unknown. To determine whether VNS modulates neurotransmission in the hippocampus, we examined the effects of VNS on perforant path (PP)-CA3 synaptic transmission electrophysiologically in anaesthetized rats. VNS induces a persistent enhancement of PP-CA3 field excitatory post-synaptic potentials (fEPSPs). Arc, an immediate early gene, was used to identify active brain regions after VNS. The locus coeruleus (LC), which contains the perikarya of noradrenergic projections, harboured more Arc-positive cells, as measured by in-situ hybridization, after 10-min VNS. In addition, electrical lesions of LC neurons or intraventricular administration of the β-adrenergic receptor antagonist timolol prevented the enhancement of PP-CA3 responses by VNS. In conclusion, the protracted increase in PP-CA3 synaptic transmission that is induced by VNS entails activation of the LC and β-adrenergic receptors. Our novel findings suggest that information from the periphery modulates synaptic transmission in the CA3 region of the hippocampus.

Role of the vegus nerve in epilepsy (image)

MedlinePlus

The vagus nerves branch off the brain on either side of the head and travel down the neck, along the esophagus to the intestinal tract. They are the longest nerves in the body, and affect swallowing and speech. ...

Feasibility, safety and efficacy of transcutaneous vagus nerve stimulation in chronic tinnitus: an open pilot study.

PubMed

Kreuzer, Peter M; Landgrebe, Michael; Resch, Markus; Husser, Oliver; Schecklmann, Martin; Geisreiter, Florian; Poeppl, Timm B; Prasser, Sarah J; Hajak, Goeran; Rupprecht, Rainer; Langguth, Berthold

2014-01-01

Vagus nerve stimulation represents an established treatment strategy for epilepsy and affective disorders. Recently, positive effects were also shown in animals and humans with tinnitus. Here we report the results of an open pilot study exploring feasibility, safety and efficacy of tVNS in the treatment of chronic tinnitus. Fifty patients with chronic tinnitus underwent tVNS in an open single-armed pilot study which was conducted in two phases applying two different stimulating devices (Cerbomed CM02 and NEMOS). Clinical assessment was based on Tinnitus Questionnaire (TQ), Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), WHO Quality of Life, and various numeric rating scales. Primary outcome was defined as change in TQ (baseline vs. final visit in week 24). The study has been registered with clinicaltrials.gov (NCT01176734). Primary analysis indicated mean TQ reductions of 3.7 points (phase 1) and 2.8 points (phase 2) significant for the first study phase. Secondary analyses indicated a significant BDI reduction for phase 1 (uncorrected for multiple testing), but no further systematic or significant effects. Adverse events included twitching and pressure at electrode placement site. The occurrence of one hospitalization because of palpations and the development of a left bundle branch block were considered as unrelated to the intervention. Cognitive testing revealed no significant changes. Our data demonstrate the feasibility of tVNS over a period of 6 months. There was no clinically relevant improvement of tinnitus complaints. Our data suggest tVNS to be considered safe in patients without a history of cardiac disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Vagus nerve stimulation reduces cocaine seeking and alters plasticity in the extinction network

PubMed Central

Childs, Jessica E.; DeLeon, Jaime; Nickel, Emily

2017-01-01

Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces rates of relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic plasticity to facilitate extinction of appetitive behaviors and to reduce relapse. Rats self-administered cocaine and were given VNS during extinction. Relapse to drug-seeking was assessed in a cued reinstatement session. We used immunohistochemistry to measure changes in the expression of the phosphorylated transcription factor cAMP response-element binding protein (pCREB) in the PFC and the basolateral amygdala (BLA), which regulate cue learning and extinction. In vivo recordings of evoked field potentials measured drug- and VNS-induced changes in metaplasticity in the pathway from the PFC to the BLA. VNS-treated rats showed improved rates of extinction and reduced reinstatement. Following reinstatement, pCREB levels were reduced in the IL and BLA of VNS-treated rats. Evoked responses in the BLA were greatly reduced in VNS-treated rats, and these rats were also resistant to the induction of LTD. Taken together, these results show that VNS facilitates extinction and reduces reinstatement. Changes in the pathway between the PFC and the amygdala may contribute to these beneficial effects. PMID:27980074

Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals.

PubMed

Pelot, N A; Behrend, C E; Grill, W M

2017-08-01

There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics' vBloc ® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed 're-excitation', arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our results indicate that compound neural or downstream muscle

Tumors Presenting as Multiple Cranial Nerve Palsies

PubMed Central

Kumar, Kishore; Ahmed, Rafeeq; Bajantri, Bharat; Singh, Amandeep; Abbas, Hafsa; Dejesus, Eddy; Khan, Rana Raheel; Niazi, Masooma; Chilimuri, Sridhar

2017-01-01

Cranial nerve palsy could be one of the presenting features of underlying benign or malignant tumors of the head and neck. The tumor can involve the cranial nerves by local compression, direct infiltration or by paraneoplastic process. Cranial nerve involvement depends on the anatomical course of the cranial nerve and the site of the tumor. Patients may present with single or multiple cranial nerve palsies. Multiple cranial nerve involvement could be sequential or discrete, unilateral or bilateral, painless or painful. The presentation could be acute, subacute or recurrent. Anatomic localization is the first step in the evaluation of these patients. The lesion could be in the brain stem, meninges, base of skull, extracranial or systemic disease itself. We present 3 cases of underlying neoplasms presenting as cranial nerve palsies: a case of glomus tumor presenting as cochlear, glossopharyngeal, vagus and hypoglossal nerve palsies, clivus tumor presenting as abducens nerve palsy, and diffuse large B-cell lymphoma presenting as oculomotor, trochlear, trigeminal and abducens nerve palsies due to paraneoplastic involvement. History and physical examination, imaging, autoantibodies and biopsy if feasible are useful for the diagnosis. Management outcomes depend on the treatment of the underlying tumor. PMID:28553221

Vagus nerve stimulation reduces cocaine seeking and alters plasticity in the extinction network.

PubMed

Childs, Jessica E; DeLeon, Jaime; Nickel, Emily; Kroener, Sven

2017-01-01

Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces rates of relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic plasticity to facilitate extinction of appetitive behaviors and to reduce relapse. Rats self-administered cocaine and were given VNS during extinction. Relapse to drug-seeking was assessed in a cued reinstatement session. We used immunohistochemistry to measure changes in the expression of the phosphorylated transcription factor cAMP response-element binding protein (pCREB) in the PFC and the basolateral amygdala (BLA), which regulate cue learning and extinction. In vivo recordings of evoked field potentials measured drug- and VNS-induced changes in metaplasticity in the pathway from the PFC to the BLA. VNS-treated rats showed improved rates of extinction and reduced reinstatement. Following reinstatement, pCREB levels were reduced in the IL and BLA of VNS-treated rats. Evoked responses in the BLA were greatly reduced in VNS-treated rats, and these rats were also resistant to the induction of LTD. Taken together, these results show that VNS facilitates extinction and reduces reinstatement. Changes in the pathway between the PFC and the amygdala may contribute to these beneficial effects. © 2016 Childs et al.; Published by Cold Spring Harbor Laboratory Press.

Pairing tone trains with vagus nerve stimulation induces temporal plasticity in auditory cortex.

PubMed

Shetake, Jai A; Engineer, Navzer D; Vrana, Will A; Wolf, Jordan T; Kilgard, Michael P

2012-01-01

The selectivity of neurons in sensory cortex can be modified by pairing neuromodulator release with sensory stimulation. Repeated pairing of electrical stimulation of the cholinergic nucleus basalis, for example, induces input specific plasticity in primary auditory cortex (A1). Pairing nucleus basalis stimulation (NBS) with a tone increases the number of A1 neurons that respond to the paired tone frequency. Pairing NBS with fast or slow tone trains can respectively increase or decrease the ability of A1 neurons to respond to rapidly presented tones. Pairing vagus nerve stimulation (VNS) with a single tone alters spectral tuning in the same way as NBS-tone pairing without the need for brain surgery. In this study, we tested whether pairing VNS with tone trains can change the temporal response properties of A1 neurons. In naïve rats, A1 neurons respond strongly to tones repeated at rates up to 10 pulses per second (pps). Repeatedly pairing VNS with 15 pps tone trains increased the temporal following capacity of A1 neurons and repeatedly pairing VNS with 5 pps tone trains decreased the temporal following capacity of A1 neurons. Pairing VNS with tone trains did not alter the frequency selectivity or tonotopic organization of auditory cortex neurons. Since VNS is well tolerated by patients, VNS-tone train pairing represents a viable method to direct temporal plasticity in a variety of human conditions associated with temporal processing deficits. Copyright © 2011 Elsevier Inc. All rights reserved.

Muscarinic contribution to the acute cortical effects of vagus nerve stimulation

NASA Astrophysics Data System (ADS)

Nichols, Justin A.

2011-12-01

Electrical stimulation of the vagus nerve (VNS) has been used to treat more than 60,000 patients with drug-resistant epilepsy and is under investigation as a treatment for several other neurological disorders and conditions. Among these, VNS increases memory performance and enhances recovery of motor and cognitive function in animal models of traumatic brain injury. Recent research indicates that pairing brief VNS with tones multiple-times a day for several weeks induces long-term, input specific cortical plasticity, which can be used to re-normalize the pathological cortical reorganization and eliminate a behavioral correlate of chronic tinnitus in noise exposed rats. Despite the therapeutic potential, the mechanisms of action of VNS remain speculative. In chapter 2 of this dissertation, the acute effects of VNS on cortical synchrony, excitability, and temporal processing are examined. In anesthetized rats implanted with multi-electrode arrays, VNS increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6 to 8 Hz, but not after systemic administration of the muscarinic antagonist scopolamine. Chapter 3 focuses on VNS-tone pairing induced cortical plasticity. Pairing VNS with a tone one hundred times in anesthetized rats resulted in frequency specific plasticity in 31% of the auditory cortex sites. Half of these sites exhibited a frequency specific increase in firing rate and half exhibited a frequency specific decrease. Muscarinic receptor blockade with scopolamine almost entirely prevented the frequency specific increases, but not decreases. Collectively, these experiments demonstrate the capacity for VNS to not only acutely influence cortical synchrony, and excitability, but to also influence temporal and spectral tuning via muscarinic receptor activation. These results strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in the mechanisms of action of VNS and

Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig

PubMed Central

Beaumont, Eric; Wright, Gary L.; Southerland, Elizabeth M.; Li, Ying; Chui, Ray; KenKnight, Bruce H.; Armour, J. Andrew

2016-01-01

Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15–20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID:26993230

Evidence-Based Guideline Update: Vagus Nerve Stimulation for the Treatment of Epilepsy

PubMed Central

Morris, George L.; Gloss, David; Buchhalter, Jeffrey; Mack, Kenneth J.; Nickels, Katherine; Harden, Cynthia

2013-01-01

OBJECTIVE: To evaluate the evidence since the 1999 assessment regarding efficacy and safety of vagus nerve stimulation (VNS) for epilepsy, currently approved as adjunctive therapy for partial-onset seizures in patients >12 years. METHODS: We reviewed the literature and identified relevant published studies. We classified these studies according to the American Academy of Neurology evidence-based methodology. RESULTS: VNS is associated with a >50% seizure reduction in 55% (95% confidence interval [CI] 50%–59%) of 470 children with partial or generalized epilepsy (13 Class III studies). VNS is associated with a >50% seizure reduction in 55% (95% CI 46%–64%) of 113 patients with Lennox-Gastaut syndrome (LGS) (4 Class III studies). VNS is associated with an increase in ≥50% seizure frequency reduction rates of ~7% from 1 to 5 years postim-plantation (2 Class III studies). VNS is associated with a significant improvement in standard mood scales in 31 adults with epilepsy (2 Class III studies). Infection risk at the VNS implantation site in children is increased relative to that in adults (odds ratio 3.4, 95% CI 1.0–11.2). VNS is possibly effective for seizures (both partial and generalized) in children, for LGS-associated seizures, and for mood problems in adults with epilepsy. VNS may have improved efficacy over time. RECOMMENDATIONS: VNS may be considered for seizures in children, for LGS-associated seizures, and for improving mood in adults with epilepsy (Level C). VNS may be considered to have improved efficacy over time (Level C). Children should be carefully monitored for site infection after VNS implantation. Neurology® 2013;81:1–7 PMID:24348133

Evidence-based guideline update: Vagus nerve stimulation for the treatment of epilepsy

PubMed Central

Morris, George L.; Gloss, David; Buchhalter, Jeffrey; Mack, Kenneth J.; Nickels, Katherine; Harden, Cynthia

2013-01-01

Objective: To evaluate the evidence since the 1999 assessment regarding efficacy and safety of vagus nerve stimulation (VNS) for epilepsy, currently approved as adjunctive therapy for partial-onset seizures in patients >12 years. Methods: We reviewed the literature and identified relevant published studies. We classified these studies according to the American Academy of Neurology evidence-based methodology. Results: VNS is associated with a >50% seizure reduction in 55% (95% confidence interval [CI] 50%–59%) of 470 children with partial or generalized epilepsy (13 Class III studies). VNS is associated with a >50% seizure reduction in 55% (95% CI 46%–64%) of 113 patients with Lennox-Gastaut syndrome (LGS) (4 Class III studies). VNS is associated with an increase in ≥50% seizure frequency reduction rates of ∼7% from 1 to 5 years postimplantation (2 Class III studies). VNS is associated with a significant improvement in standard mood scales in 31 adults with epilepsy (2 Class III studies). Infection risk at the VNS implantation site in children is increased relative to that in adults (odds ratio 3.4, 95% CI 1.0–11.2). VNS is possibly effective for seizures (both partial and generalized) in children, for LGS-associated seizures, and for mood problems in adults with epilepsy. VNS may have improved efficacy over time. Recommendations: VNS may be considered for seizures in children, for LGS-associated seizures, and for improving mood in adults with epilepsy (Level C). VNS may be considered to have improved efficacy over time (Level C). Children should be carefully monitored for site infection after VNS implantation. PMID:23986299

Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals

NASA Astrophysics Data System (ADS)

Pelot, N. A.; Behrend, C. E.; Grill, W. M.

2017-08-01

Objective. There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics’ vBloc® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. Approach. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. Main results. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed ‘re-excitation’, arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Significance. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our

Neuromuscular ultrasound of cranial nerves.

PubMed

Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

2015-04-01

Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

Amelioration of intractable epilepsy by adjunct vagus nerve stimulation therapy in a girl with a CDKL5 mutation.

PubMed

Baba, Shimpei; Sugawara, Yuji; Moriyama, Kengo; Inaji, Motoki; Maehara, Taketoshi; Yamamoto, Toshiyuki; Morio, Tomohiro

2017-04-01

We report the case of on an 8-year-old girl with a cyclin-dependent kinase-like 5 mutation and who underwent vagus nerve stimulation (VNS) therapy for 2years. She had developed epilepsy at the age of 6months and had severe developmental delays. Initially, she had tonic and tonic-clonic seizures; however, around the age of 5years, she also developed epileptic spasms. These seizures were never completely controlled by conventional medical treatments. At the age of 7, after VNS initiation, her seizure frequency markedly reduced, and abnormal electrical activities on her electroencephalography tests strikingly decreased. Moreover, using questionnaires, we confirmed an improvement in her quality of life in the fields of alertness and activity. Although the efficacy of VNS therapy for patients with intractable epilepsy associated with a genetic anomaly has not been fully established, adjunctive VNS therapy may widen the scope of treatment choices available to these patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig.

PubMed

Beaumont, Eric; Wright, Gary L; Southerland, Elizabeth M; Li, Ying; Chui, Ray; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

2016-05-15

Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15-20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. Copyright © 2016 the American Physiological Society.

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats.

PubMed

Miranda, Rosiane A; Torrezan, Rosana; de Oliveira, Júlio C; Barella, Luiz F; da Silva Franco, Claudinéia C; Lisboa, Patrícia C; Moura, Egberto G; Mathias, Paulo C F

2016-07-01

Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus-pituitary-adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodium l-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX-VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3 muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX-VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity. © 2016 Society for Endocrinology.

Time perception in patients with major depressive disorder during vagus nerve stimulation.

PubMed

Biermann, T; Kreil, S; Groemer, T W; Maihöfner, C; Richter-Schmiedinger, T; Kornhuber, J; Sperling, W

2011-07-01

Affective disorders may affect patients' time perception. Several studies have described time as a function of the frontal lobe. The activating eff ects of vagus nerve stimulation on the frontal lobe might also modulate time perception in patients with major depressive disorder (MDD). Time perception was investigated in 30 patients with MDD and in 7 patients with therapy-resistant MDD. In these 7 patients, a VNS system was implanted and time perception was assessed before and during stimulation. A time estimation task in which patients were asked "How many seconds have passed?" tested time perception at 4 defined time points (34 s, 77 s, 192 s and 230 s). The differences between the estimated and actual durations were calculated and used for subsequent analysis. Patients with MDD and healthy controls estimated the set time points relatively accurately. A general linear model revealed a significant main eff ect of group but not of age or sex. The passing of time was perceived as significantly slower in patients undergoing VNS compared to patients with MDD at all time points (T34: t = − 4.2; df = 35; p < 0.001; T77: t = − 4.8; df = 35; p < 0.001; T192: t = − 2.0; df = 35; p = 0.059; T230 t = −2.2; df = 35; p = 0.039) as well as compared to healthy controls (at only T77: t = 4.1; df = 35; p < 0.001). There were no differences in time perception with regard to age, sex or polarity of depression (uni- or bipolar). VNS is capable of changing the perception of time. This discovery furthers the basic research on circadian rhythms in patients with psychiatric disorders.

Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study.

PubMed

Silberstein, Stephen D; Calhoun, Anne H; Lipton, Richard B; Grosberg, Brian M; Cady, Roger K; Dorlas, Stefanie; Simmons, Kristy A; Mullin, Chris; Liebler, Eric J; Goadsby, Peter J; Saper, Joel R

2016-08-02

To evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks. In this first prospective, multicenter, double-blind, sham-controlled pilot study of nVNS in CM prophylaxis, adults with CM (≥15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months). The primary endpoints were safety and tolerability. Efficacy endpoints in the intent-to-treat population included change in the number of headache days per 28 days and acute medication use. Fifty-nine participants (mean age, 39.2 years; mean headache frequency, 21.5 d/mo) were enrolled. During the randomized phase, tolerability was similar for nVNS (n = 30) and sham treatment (n = 29). Most adverse events were mild/moderate and transient. Mean changes in the number of headache days were -1.4 (nVNS) and -0.2 (sham) (Δ = 1.2; p = 0.56). Twenty-seven participants completed the open-label phase. For the 15 completers initially assigned to nVNS, the mean change from baseline in headache days after 8 months of treatment was -7.9 (95% confidence interval -11.9 to -3.8; p < 0.01). Therapy with nVNS was well-tolerated with no safety issues. Persistent prophylactic use may reduce the number of headache days in CM; larger sham-controlled studies are needed. NCT01667250. This study provides Class II evidence that for patients with CM, nVNS is safe, is well-tolerated, and did not significantly change the number of headache days. This pilot study lacked the precision to exclude important safety issues or benefits of nVNS. © 2016 American Academy of Neurology.

Long term effects on epileptiform activity with vagus nerve stimulation in children.

PubMed

Hallböök, Tove; Lundgren, Johan; Blennow, Gösta; Strömblad, Lars-Göran; Rosén, Ingmar

2005-12-01

We report long-term effects of vagus nerve stimulation (VNS) on epileptiform activity in 15 children, and how these changes are related to activity stage and to clinical effects on seizure reduction, seizure severity (NHS3) and quality of life (QOL). Initially, and after 3 and 9 months of VNS-treatment, 15 children were investigated with 24 h ambulatory EEG monitoring for spike detection. The number of interictal epileptiform discharges (IEDs) and the inter spike intervals (ISIs) were analysed during 2 h in the awake state, and 1h of rapid eye movement (REM)-, spindle- and delta-sleep, respectively. Total number and duration of electrographic seizure episodes were also analysed. At 9 months the total number of IEDs was significantly reduced (p=0.04). There was a tendency of reduction in all activity stages, and significantly so in delta-sleep (p=0.008). Total electrographic seizure number was significantly reduced in the 24 h EEG at 3 and 9 months (p=0.03, 0.05). There was a significant concordance in direction of changes in epileptiform activity and electrographic seizures at 9 months (p=0.04). Concordance in direction of changes was seen in 9 of 15 children between clinical seizures and IED (p>0.3), in 10 of 15 children between QOL and IED (p=0.3) and in 8 of 15 children between NHS3 and IED (p>0.3). There was no direct correlation between the extent of improvement in these clinical data and the degree of spike reduction. This study shows that VNS reduces IEDs especially in REM and delta sleep, as well as the number of electrographic seizures. It also shows a concordance between reduction in IEDs and electrographic seizures.

Innervation of the cricothyroid muscle by the recurrent laryngeal nerve.

PubMed

Masuoka, Hiroo; Miyauchi, Akira; Yabuta, Tomonori; Fukushima, Mitsuhiro; Miya, Akihiro

2016-04-01

The recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve (SLN) are generally thought to innervate the endolaryngeal muscles and the cricothyroid muscle (CTM), respectively. Meticulous anatomic studies found communication between these nerves (ie, the human communicating nerve). In this study, we report the innervation of the CTM by the RLN. We performed electromyographic studies of 50 patients during thyroidectomy (20 total and 30 hemithyroidectomies). During surgery, the external branch of the SLN, RLN, and vagus nerve were stimulated. Responses were evaluated by visual observation of the CTM and by electromyographies through needle electrodes inserted into the CTM. Seventy CTMs were evaluated. The RLN stimulation yielded both visible contractions and clear electromyographic responses (>300 µV) in 27 (39%), either response in 24 (34%), and neither response in 19 (27%) of the CTMs. The vagus stimulation gave similar results. The RLN innervated the CTM at least in 39% cases. © 2015 Wiley Periodicals, Inc. Head Neck 38: E441-E445, 2016. © 2015 Wiley Periodicals, Inc.

Morphological relationship between the superior cervical ganglion and cervical nerves in Japanese cadaver donors.

PubMed

Mitsuoka, Kazuyuki; Kikutani, Takeshi; Sato, Iwao

2017-02-01

There are various communications between the superior cervical ganglion (SCG) and the vagus and glossopharyngeal nerves. However, little information exists concerning the origin of these sympathetic ganglion branches at the superior, middle, and inferior regions of the human SCG. The aim of this study was to describe the human SCG in a morphometric manner with the communication with cranial and cervical nerves and supply. This study characterized 72 SCG samples from 54 elderly Japanese human cadavers (30 males, 24 females; 65-100 years old). The SCG size (length, width, and thickness) and location were measured from the jugular foramen. We also defined the communication branches of the SCG to the vagus, glossopharyngeal, cervical, and accessory nerves at three regions (superior, middle, and inferior regions) of the SCG. Finally, we examined the arrangement and origin of the branch communications in detail and confirmed our observations, using histological sections of the SCG. The SCG in all cadaver donors was detected at the C2 and C3 vertebra levels. The number of SCG branches supplied the communicating branches, such as the carotid branch, communicating branch of the vagus nerve, and glossopharyngeal nerve, were frequently detected in the superior region of the SCG (χ 2  = 587.72, df = 26, p  <   .001). The number of ganglion cells with a large number of neurons per unit area (1 mm 2 ) was most often found in the middle region with shrunken neurons of the SCG compared with other regions. The communication branches of the SCG are mainly connected to the vagus and glossopharyngeal nerves. Characterizing these branches can provide useful data for head and neck ganglion block and surgical treatments.

Degenerative Nerve Diseases

MedlinePlus

... may include toxins, chemicals, and viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ataxia Huntington's disease ...

Measurement of wavefront aberrations in cortex and peripheral nerve using a two-photon excitation guidestar

NASA Astrophysics Data System (ADS)

Futia, Gregory L.; Fontaine, Arjun; McCullough, Connor; Ozbay, Baris N.; George, Nickolas M.; Caldwell, John; Restrepo, Diego; Weir, Richard; Gibson, Emily A.

2018-02-01

Neural-machine interfaces using optogenetics are of interest due to their minimal invasiveness and potential for parallel read in and read out of activity. One possible biological target for such an interface is the peripheral nerve, where axonlevel imaging or stimulation could greatly improve interfacing with artificial limbs or enable neuron/fascicle level neuromodulation in the vagus nerve. Two-photon imaging has been successful in imaging brain activity using genetically encoded calcium or voltage indicators, but in the peripheral nerve, this is severely limited by scattering and aberrations from myelin. We employ a Shack-Hartman wavefront sensor and two-photon excitation guidestar to quantify optical scattering and aberrations in peripheral nerves and cortex. The sciatic and vagus nerves, and cortex from a ChAT-Cre ChR-eYFP transgenic mouse were excised and imaged directly. In peripheral nerves, defocus was the strongest aberration followed by astigmatism and coma. Peripheral nerve had orders of magnitude higher aberration compared with cortex. These results point to the potential of adaptive optics for increasing the depth of two-photon access into peripheral nerves.

Long-term Expectations of Vagus Nerve Stimulation: A Look at Battery Replacement and Revision Surgery.

PubMed

Couch, Jonathan D; Gilman, Arthur M; Doyle, Werner K

2016-01-01

Vagus nerve stimulation (VNS) is an established surgical treatment for medically intractable epilepsy with more than 75 000 devices implanted worldwide. While there are many reports documenting efficacy, complications, and clinical use, there are very few reports concerning VNS battery replacement and revision surgeries. To review our experience with VNS battery replacement and revision surgery. We retrospectively reviewed 1144 consecutive VNS procedures performed by a single surgeon between 1998 and 2012. Six hundred forty-four of those procedures were the initial placement of the VNS device. These patients were then followed to determine when a battery change occurred and what type of revision or removal was necessary. In the study, 46% of patients required at least 1 or more type of battery replacement or revision surgery. The most common types of surgery were for generator battery depletion (27%), poor efficacy (9%), and lead malfunction (8%). Only 2% of patients were noted to have an infection. VNS battery replacement, revisions, and removals account for almost one-half of all VNS procedures. Our findings suggest important long-term expectations for VNS including expected complications, battery life, and other surgical issues. Review of the literature suggests that this is the first large review of VNS revisions by a single center. Our findings are important to better characterize long-term surgical expectations of VNS therapy. A significant portion of patients undergoing VNS therapy will eventually require revision.

Schwannoma originating from lower cranial nerves: report of 4 cases.

PubMed

Oyama, Hirofumi; Kito, Akira; Maki, Hideki; Hattori, Kenichi; Noda, Tomoyuki; Wada, Kentaro

2012-02-01

Four cases of schwannoma originating from the lower cranial nerves are presented. Case 1 is a schwannoma of the vagus nerve in the parapharyngeal space. The operation was performed by the transcervical approach. Although the tumor capsule was not dissected from the vagus nerve, hoarseness and dysphagia happened transiently after the operation. Case 2 is a schwannoma in the jugular foramen. The operation was performed by the infralabyrinthine approach. Although only the intracapsular tumor was enucleated, facial palsy, hoarseness, dysphagia and paresis of the deltoid muscle occurred transiently after the operation. The patient's hearing had also slightly deteriorated. Case 3 is a dumbbell-typed schwannoma originating from the hypoglossal nerve. The hypoglossal canal was markedly enlarged by the tumor. As the hypoglossal nerves were embedded in the tumor, the tumor around the hypoglossal nerves was not resected. The tumor was significantly enlarged for a while after stereotactic irradiation. Case 4 is an intracranial cystic schwannoma originating from the IXth or Xth cranial nerves. The tumor was resected through the cerebello-medullary fissure. The tumor capsule attached to the brain stem was not removed. Hoarseness and dysphagia happened transiently after the operation. Cranial nerve palsy readily occurs after the removal of the schwannoma originating from the lower cranial nerves. Mechanical injury caused by retraction, extension and compression of the nerve and heat injury during the drilling of the petrous bone should be cautiously avoided.

Effect of low-level laser therapy (LLLT) on peripheral nerve regeneration using fibrin glue derived from snake venom.

PubMed

Buchaim, Rogerio Leone; Andreo, Jesus Carlos; Barraviera, Benedito; Ferreira Junior, Rui Seabra; Buchaim, Daniela Vieira; Rosa Junior, Geraldo Marco; de Oliveira, Alexandre Leite Rodrigues; de Castro Rodrigues, Antonio

2015-04-01

The purpose of this study was to assess whether the adhesive permits the collateral repair of axons originating from a vagus nerve to the interior of a sural nerve graft, and whether low-level laser therapy (LLLT) assists in the regeneration process. Study sample consisted of 32 rats randomly separated into three groups: Control Group (CG; n=8), from which the intact sural nerve was collected; Experimental Group (EG; n=12), in which one of the ends of the sural nerve graft was coapted to the vagus nerve using the fibrin glue; and Experimental Group Laser (EGL; n=12), in which the animals underwent the same procedures as those in EG with the addition of LLLT. Ten weeks after surgery, the animals were euthanized. Morphological analysis by means of optical and electron microscopy, and morphometry of the regenerated fibers were employed to evaluate the results. Collateral regeneration of axons was observed from the vagus nerve to the interior of the autologous graft in EG and EGL, and in CG all dimensions measured were greater and presented a significant difference in relation to EG and EGL, except for the area and thickness of the myelin sheath, that showed significant difference only in relation to the EG. The present study demonstrated that the fibrin glue makes axonal regeneration feasible and is an efficient method to recover injured peripheral nerves, and the use of low-level laser therapy enhances nerve regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Motor evoked potential monitoring of the vagus nerve with transcranial electrical stimulation during skull base surgeries.

PubMed

Ito, Eiji; Ichikawa, Masahiro; Itakura, Takeshi; Ando, Hitoshi; Matsumoto, Yuka; Oda, Keiko; Sato, Taku; Watanabe, Tadashi; Sakuma, Jun; Saito, Kiyoshi

2013-01-01

Dysphasia is one of the most serious complications of skull base surgeries and results from damage to the brainstem and/or cranial nerves involved in swallowing. Here, the authors propose a method to monitor the function of the vagus nerve using endotracheal tube surface electrodes and transcranial electrical stimulation during skull base surgeries. Fifteen patients with skull base or brainstem tumors were enrolled. The authors used surface electrodes of an endotracheal tube to record compound electromyographic responses from the vocalis muscle. Motor neurons were stimulated using corkscrew electrodes placed subdermally on the scalp at C3 and C4. During surgery, the operator received a warning when the amplitude of the vagal motor evoked potential (MEP) decreased to less than 50% of the control level. After surgery, swallowing function was assessed clinically using grading criteria. In 5 patients, vagal MEP amplitude permanently deteriorated to less than 50% of the control level on the right side when meningiomas were dissected from the pons or basilar artery, or when a schwannoma was dissected from the vagal rootlets. These 5 patients had postoperative dysphagia. At 4 weeks after surgery, 2 patients still had dysphagia. In 2 patients, vagal MEPs of one side transiently disappeared when the tumors were dissected from the brainstem or the vagal rootlets. After surgery, both patients had dysphagia, which recovered in 4 weeks. In 7 patients, MEP amplitude was consistent, maintaining more than 50% of the control level throughout the operative procedures. After surgery all 7 patients were neurologically intact with normal swallowing function. Vagal MEP monitoring with transcranial electrical stimulation and endotracheal tube electrode recording was a safe and effective method to provide continuous real-time information on the integrity of both the supranuclear and infranuclear vagal pathway. This method is useful to prevent intraoperative injury of the brainstem

Bladder Control and Nerve Disease

MedlinePlus

... VUR) The Urinary Tract & How It Works Bladder Control Problems & Nerve Disease For the urinary system to ... the bladder do not work properly. What bladder control problems does nerve damage cause? Nerves that work ...

Reinstatement of contextual conditioned anxiety in virtual reality and the effects of transcutaneous vagus nerve stimulation in humans.

PubMed

Genheimer, Hannah; Andreatta, Marta; Asan, Esther; Pauli, Paul

2017-12-20

Since exposure therapy for anxiety disorders incorporates extinction of contextual anxiety, relapses may be due to reinstatement processes. Animal research demonstrated more stable extinction memory and less anxiety relapse due to vagus nerve stimulation (VNS). We report a valid human three-day context conditioning, extinction and return of anxiety protocol, which we used to examine effects of transcutaneous VNS (tVNS). Seventy-five healthy participants received electric stimuli (unconditioned stimuli, US) during acquisition (Day1) when guided through one virtual office (anxiety context, CTX+) but never in another (safety context, CTX-). During extinction (Day2), participants received tVNS, sham, or no stimulation and revisited both contexts without US delivery. On Day3, participants received three USs for reinstatement followed by a test phase. Successful acquisition, i.e. startle potentiation, lower valence, higher arousal, anxiety and contingency ratings in CTX+ versus CTX-, the disappearance of these effects during extinction, and successful reinstatement indicate validity of this paradigm. Interestingly, we found generalized reinstatement in startle responses and differential reinstatement in valence ratings. Altogether, our protocol serves as valid conditioning paradigm. Reinstatement effects indicate different anxiety networks underlying physiological versus verbal responses. However, tVNS did neither affect extinction nor reinstatement, which asks for validation and improvement of the stimulation protocol.

A distinct biomarker of continuous transcutaneous vagus nerve stimulation treatment in major depressive disorder.

PubMed

Tu, Yiheng; Fang, Jiliang; Cao, Jin; Wang, Zengjian; Park, Joel; Jorgenson, Kristen; Lang, Courtney; Liu, Jun; Zhang, Guolei; Zhao, Yanping; Zhu, Bing; Rong, Peijing; Kong, Jian

Major depression is the fourth leading cause of disability worldwide and poses a socioeconomic burden worldwide. Transcutaneous vagus nerve stimulation (tVNS) is a promising noninvasive clinical device that may reduce the severity of major depression. However, the neural mechanism underlying continuous tVNS has not yet been elucidated. We aimed to explore the effect of hypothalamic subregion functional connectivity (FC) changes during continuous tVNS treatment on major depressive disorder (MDD) patients and to identify the potential biomarkers for treatment outcomes. Forty-one mild to moderate MDD patients were recruited and received either real or sham tVNS treatment for 4 weeks. We used a seed-to-whole brain approach to estimate the FC changes of hypothalamic subregions and their surrounding control areas during continuous tVNS treatment and explored their association with clinical outcome changes after 4 weeks of treatment. Of the thirty-six patients that completed the study, those in the tVNS group had significantly lower scores on the 24-item Hamilton Depression (HAM-D) Rating Scale compared to the sham tVNS group after 4 weeks of treatment. The FC between the bilateral medial hypothalamus (MH) and rostral anterior cingulate cortex (rACC) was significantly decreased during tVNS but not during sham tVNS. The strength of this FC was significantly correlated with HAM-D improvements after 4 weeks of tVNS. The FC between the bilateral MH and rACC may serve as a potential biomarker for the tVNS state and predict treatment responses. Our results provide insights into the neural modulation mechanisms of continuous tVNS and reveal a potential therapeutic target for MDD patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Arterial supply of the lower cranial nerves: a comprehensive review.

PubMed

Hendrix, Philipp; Griessenauer, Christoph J; Foreman, Paul; Loukas, Marios; Fisher, Winfield S; Rizk, Elias; Shoja, Mohammadali M; Tubbs, R Shane

2014-01-01

The lower cranial nerves receive their arterial supply from an intricate network of tributaries derived from the external carotid, internal carotid, and vertebrobasilar territories. A contemporary, comprehensive literature review of the vascular supply of the lower cranial nerves was performed. The vascular supply to the trigeminal, facial, vestibulocochlear, glossopharyngeal, vagus, spinal accessory, and hypoglossal nerves are illustrated with a special emphasis on clinical issues. Frequently the external carotid, internal carotid, and vertebrobasilar territories all contribute to the vascular supply of an individual cranial nerve along its course. Understanding of the vasculature of the lower cranial nerves is of great relevance for skull base surgery. Copyright © 2013 Wiley Periodicals, Inc.

Vagus Nerve Stimulation Applied with a Rapid Cycle Has More Profound Influence on Hippocampal Electrophysiology Than a Standard Cycle.

PubMed

Larsen, Lars E; Wadman, Wytse J; Marinazzo, Daniele; van Mierlo, Pieter; Delbeke, Jean; Daelemans, Sofie; Sprengers, Mathieu; Thyrion, Lisa; Van Lysebettens, Wouter; Carrette, Evelien; Boon, Paul; Vonck, Kristl; Raedt, Robrecht

2016-07-01

Although vagus nerve stimulation (VNS) is widely used, therapeutic mechanisms and optimal stimulation parameters remain elusive. In the present study, we investigated the effect of VNS on hippocampal field activity and compared the efficiency of different VNS paradigms. Hippocampal electroencephalography (EEG) and perforant path dentate field-evoked potentials were acquired before and during VNS in freely moving rats, using 2 VNS duty cycles: a rapid cycle (7 s on, 18 s off) and standard cycle (30 s on, 300 s off) and various output currents. VNS modulated the evoked potentials, reduced total power of the hippocampal EEG, and slowed the theta rhythm. In the hippocampal EEG, theta (4-8 Hz) and high gamma (75-150 Hz) activity displayed strong phase amplitude coupling that was reduced by VNS. Rapid-cycle VNS had a greater effect than standard-cycle VNS on all outcome measures. Using rapid cycle VNS, a maximal effect on EEG parameters was found at 300 μA, beyond which effects saturated. The findings suggest that rapid-cycle VNS produces a more robust outcome than standard cycle VNS and support already existing preclinical evidence that relatively low output currents are sufficient to produce changes in brain physiology and thus likely also therapeutic efficacy.

Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen.

PubMed

Braak, H; Rüb, U; Gai, W P; Del Tredici, K

2003-05-01

The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially upwards through susceptible regions of the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain until it reaches the cerebral cortex. With time, multiple components of the autonomic, limbic, and motor systems become severely impaired. All of the vulnerable subcortical grays and cortical areas are closely interconnected. Incidental cases of idiopathic Parkinson's disease may show involvement of both the enteric nervous system and the dorsal motor nucleus of the vagus nerve. This observation, combined with the working hypothesis that the stereotypic topographic expansion pattern of the lesions may resemble that of a falling row of dominos, prompts the question whether the disorder might originate outside of the central nervous system, caused by a yet unidentified pathogen that is capable of passing the mucosal barrier of the gastrointestinal tract and, via postganglionic enteric neurons, entering the central nervous system along unmyelinated praeganglionic fibers generated from the visceromotor projection cells of the vagus nerve. By way of retrograde axonal and transneuronal transport, such a causative pathogen could reach selectively vulnerable subcortical nuclei and, unimpeded, gain access to the cerebral cortex. The here hypothesized mechanism offers one possible explanation for the sequential and apparently uninterrupted manner in which vulnerable brain regions, subcortical grays and cortical areas become involved in idiopathic Parkinson's disease.

Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation.

PubMed

Napadow, Vitaly; Edwards, Robert R; Cahalan, Christine M; Mensing, George; Greenbaum, Seth; Valovska, Assia; Li, Ang; Kim, Jieun; Maeda, Yumi; Park, Kyungmo; Wasan, Ajay D

2012-06-01

Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Counterbalanced, crossover study. Patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. INTERVENTIONS/OUTCOMES: We evaluated evoked pain analgesia for respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) compared with nonvagal auricular stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least 1 week apart. Outcome measures included deep-tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N = 15 CPP patients, compared with NVAS, with moderate to large effect sizes (η(2) > 0.2). Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. Wiley Periodicals, Inc.

Transmission failure in sympathetic nerves produced by hemicholinium

PubMed Central

Chang, V.; Rand, M. J.

1960-01-01

It has been shown by others that hemicholinium (α,α'-dimethylethanolamino-4,4'-biacetophenone) inhibits the synthesis of acetylcholine, an effect which is reversed by choline. Hemicholinium produces a failure of response to nerve stimulation in the following sympathetically innervated preparations: guinea-pig isolated vas deferens, rabbit isolated uterus, rabbit isolated colon, perfused rabbit ear, cat isolated atria and the piloerector muscles in the cat's tail. The blocking action of hemicholinium on the responses to postganglionic sympathetic stimulation resembles its blocking action against cholinergic nerve stimulation observed on rabbit isolated atria with vagus nerves, rabbit isolated vagina with pelvic nerves, and guinea-pig isolated diaphragm with phrenic nerve. The failure of transmission produced by hemicholinium in sympathetic nerves and in cholinergic nerves can be reversed by choline. It is suggested that if there were a cholinergic junction at sympathetic nerve endings the mechanism of the blocking action of hemicholinium at these endings could be explained by inhibition of acetylcholine synthesis. ImagesFIG. 13FIG. 14 PMID:13692344

Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke.

PubMed

Dawson, Jesse; Pierce, David; Dixit, Anand; Kimberley, Teresa J; Robertson, Michele; Tarver, Brent; Hilmi, Omar; McLean, John; Forbes, Kirsten; Kilgard, Michael P; Rennaker, Robert L; Cramer, Steven C; Walters, Matthew; Engineer, Navzer

2016-01-01

Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke. Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl-Meyer Assessment-Upper Extremity). Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, -0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6). This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01669161. © 2015 The Authors.

A Respiratory Marker Derived From Left Vagus Nerve Signals Recorded With Implantable Cuff Electrodes.

PubMed

Sevcencu, Cristian; Nielsen, Thomas N; Kjaergaard, Benedict; Struijk, Johannes J

2018-04-01

Left vagus nerve (LVN) stimulation (LVNS) has been tested for lowering the blood pressure (BP) in patients with resistant hypertension (RH). Whereas, closed-loop LVNS (CL-LVNS) driven by a BP marker may be superior to open-loop LVNS, there are situations (e.g., exercising) when hypertension is normal. Therefore, an ideal anti-RH CL-LVNS system requires a variable to avoid stimulation in such conditions, for example, a respiratory marker ideally extracted from the LVN. As the LVN conducts respiratory signals, this study aimed to investigate if such signals can be recorded using implantable means and if a marker to monitor respiration could be derived from such recordings. The experiments were performed in 14 anesthetized pigs. Five pigs were subjected to changes of the respiratory frequency and nine to changes of the respiratory volume. The LVN electroneurogram (VENG) was recorded using two cuff electrodes and the respiratory cycles (RC) using a pressure transducer. To separate the afferent and efferent VENGs, vagotomy was performed between the cuffs in the first group of pigs. The VENG was squared to derive respiration-related neural profiles (RnPs) and their correlation with the RCs was investigated in regard to timing and magnitude parameters derived from the two waveforms. The RnPs were morphologically similar with the RCs and the average RnPs represented accurate copies of the average RCs. Consequently, the lung inflation/deflation RC and RnP components had the same duration, the respiratory frequency changes affected in the same way both waveforms and the RnP amplitude increased linearly with the lung inflation in all tested pigs (R 2 values between 0.85 and 0.99). The RnPs comprise information regarding the timing and magnitude of the respiratory parameters. As those LVN profiles were derived using implantable means, this study indicates that the RnPs could serve as respiratory markers in implantable systems. © 2017 International Neuromodulation Society.

Corneal Nerves in Health and Disease

PubMed Central

Shaheen, Brittany; Bakir, May; Jain, Sandeep

2013-01-01

Corneal nerves are responsible for the sensations of touch, pain, and temperature and play an important role in the blink reflex, wound healing, and tear production and secretion. Corneal nerve dysfunction is a frequent feature of diseases that cause opacities and result in corneal blindness. Corneal opacities rank as the second most frequent cause of blindness. Technological advances in in vivo corneal nerve imaging, such as optical coherence tomography and confocal scanning, have generated new knowledge regarding the phenomenological events that occur during reinnervation of the cornea following disease, injury, or surgery. The recent availability of transgenic neurofluorescent murine models has stimulated the search for molecular modulators of corneal nerve regeneration. New evidence suggests that neuro-regenerative and inflammatory pathways in the cornea are intertwined. Evidence-based treatment of neurotrophic corneal diseases includes using neuro-regenerative (blood component-based and neurotrophic factors), neuroprotective, and ensconcing (bandage contact lens and amniotic membrane) strategies and avoiding anti-inflammatory therapies, such as cyclosporine and corticosteroids. PMID:24461367

A clear map of the lower cranial nerves at the superior carotid triangle.

PubMed

Cavalcanti, Daniel D; Garcia-Gonzalez, Ulises; Agrawal, Abhishek; Tavares, Paulo L M S; Spetzler, Robert F; Preul, Mark C

2010-07-01

The lower cranial nerves must be identified to avoid iatrogenic injury during skull base and high cervical approaches. Prompt recognition of these structures using basic landmarks could reduce surgical time and morbidity. The anterior triangle of the neck was dissected in 30 cadaveric head sides. The most superficial segments of the glossopharyngeal, vagus and its superior laryngeal nerves, accessory, and hypoglossal nerves were exposed and designated into smaller anatomic triangles. The midpoint of each nerve segment inside the triangles was correlated to the angle of the mandible (AM), mastoid tip (MT), and bifurcation of the common carotid artery. A triangle bounded by the styloglossus muscle, external carotid artery, and facial artery housed the glossopharyngeal nerve. This nerve segment was 0.06 ± 0.71 cm posterior to the AM and 2.50 ± 0.59 cm inferior to the MT. The vagus nerve ran inside the carotid sheath posterior to internal carotid artery and common carotid artery bifurcation in 48.3% of specimens. A triangle formed by the posterior belly of digastric muscle, sternocleidomastoid muscle, and internal jugular vein housed the accessory nerve, 1.90 ± 0.60 cm posterior to the AM and 2.30 ± 0.57 cm inferior to the MT. A triangle outlined by the posterior belly of digastric muscle, internal jugular vein, and common facial vein housed the hypoglossal nerve, which was 0.82 ± 0.84 cm posterior to the AM and 3.64 ± 0.70 cm inferior to the MT. Comprehensible landmarks can be defined to help expose the lower cranial nerves to avoid injury to this complex region. Copyright © 2010 Elsevier Inc. All rights reserved.

[Effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking method on auditory brainstem response and neurotransmitters of inferior colliculus in rats of tinnitus].

PubMed

Yang, Songbai; Mei, Zhigang; Tan, Lingjing; Ma, Wenhan; Zhang, Dingqi; Wang, Zhaojun; Li, Tiantian; Huang, Kunyan; Cai, Sanjin

2016-05-01

To explore the effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking on auditory brainstem response (ABR) and contents of neurotransmitters of γ-aminobutyric acid (γ-GABA), 5-hydroxytryptamine (5-HT) and acetyl choline (Ach) in inferior colliculus of tinnitus rats. Twenty-four male adult SD rats were randomized into a control group, a model group, a 7-d treatment group and a 15-d treatment group. Except the control group, rats in the remaining groups were treated with intraperitoneal injection of 10% salicylate sodium at a dose of 350 mg/kg to establish tinnitus model. Rats in the control group were treated with injection of 0.9% NaCl. Rats in the 7-d treatment group and 15-d treatment group were treated with electrical stimulation at "Shenmen (TF₄)" and "Yidan (CO₁₁)" in the distribution area of auricular vagus nerve combined with sound masking, once a day, for 7 days and 15 days. The SigGenRP software of TDT system was applied to provide voice for single ear and collect the signal, and the voice threshold of ABR was tested. The levels of γ-GABA, 5-HT and Ach in inferior colliculus of rats were detected by enzyme linked immunosorbent assay (ELISA) and compared. Compared with the model group, the threshold values of ABR in 12 kHz and 16 kHz voice stimulation in the 7-d treatment group were significantly lower all P < 0.05); the threshold values of ABR from 4 kHz to 28 kHz voice stimulation in the 15-d treatment group were signally reduced (P < 0.05, P < 0.01), which was more significant than those in the 7-d treatment group. The level of γ-GABA in the model group was significantly lower than that in the control group (P < 0.05), and that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of 5-HT in the model group was markedly higher than that in the control group (P < 0.05), and that in the 7-d treatment group was lower than that in

Vagus nerve stimulation for 6- to 12-year-old children with refractory epilepsy: Impact on seizure frequency and parenting stress index.

PubMed

Fan, Hueng-Chuen; Hsu, Ting-Rong; Chang, Kai-Ping; Chen, Shyi-Jou; Tsai, Jeng-Dau

2018-06-01

Refractory epilepsy (RE) is frequently associated with neuropsychological impairment in children and may disrupt their social development. Vagus nerve stimulation (VNS) had been reported to have beneficial effects on behavioral outcomes. The aim of this study was to compare Parenting Stress Index (PSI) scores before and after VNS device implantation in children with RE, especially those who experienced seizure frequency reduction. We conducted a one-group pretest-posttest study in school age children with RE. Seizure frequency and PSI were recorded at 12months after VNS device implantation. Treatment with VNS was significantly associated with reduced seizure frequency and parental stress as measured by PSI. Factors contributing to seizure frequency included idiopathic/cryptogenic etiology and neurobehavioral comorbidities. In children with reduced seizure frequency, statistically significant improvements in the child domain of the PSI on the subscales of mood and reinforces parent were found. In the parent domain, the scores for social isolation were reduced. Treatment with VNS was significantly associated with reduced seizure frequency and improved PSI scores, especially within the child domain on the mood and reinforces parent subscales. These findings suggest that VNS reduced not only seizure frequency but also the psychological burden on children with RE. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke

PubMed Central

Pierce, David; Dixit, Anand; Kimberley, Teresa J.; Robertson, Michele; Tarver, Brent; Hilmi, Omar; McLean, John; Forbes, Kirsten; Kilgard, Michael P.; Rennaker, Robert L.; Cramer, Steven C.; Walters, Matthew; Engineer, Navzer

2016-01-01

Background and Purpose— Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke. Methods— Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl–Meyer Assessment-Upper Extremity). Results— Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl–Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, −0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl–Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6). Conclusions— This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01669161. PMID:26645257

Parenting stress in parents of children with refractory epilepsy before and after vagus nerve stimulation implantation.

PubMed

Li, Sung-Tse; Chiu, Nan-Chang; Kuo, Yung-Ting; Shen, Ein-Yiao; Tsai, Pei-Chieh; Ho, Che-Sheng; Wu, Wen-Hsiang; Chen, Juei-Chao

2017-12-01

The purpose of this study was to evaluate parenting stress in parents of children with refractory epilepsy before and after their children received vagus nerve stimulation (VNS) implantation. Parents of children with refractory epilepsy completed the Parenting Stress Index (PSI) under a psychologist's assessment before and at least 12 months after their children received VNS implantation. The PSI questionnaire measures parenting stress in two domains; a parent domain with seven subscales, and a child domain with six. Age, gender, epilepsy comorbidity, VNS implantation date, seizure frequency, and anticonvulsant history before and after VNS implantation were obtained from reviews of medical charts. In total, 30 parents completed the first and follow-up PSI questionnaires. Seventeen of their children (56.7%) were boys. The children aged from 1 to 12 years (7.43 ± 3.59 years, mean ± SD). After VNS implantation, the mean total parenting stress scores decreased from 282.1 ± 38.0 to 272.4 ± 42.9. A significant decrease was found on the spouse subscale of the parent domain. For the parents of boys, the mean total parenting stress scores decreased significantly. The mean total parenting stress scores also decreased significantly for parents of epileptic children without autism and who did not taper off the number of different anticonvulsants used after VNS. VNS is an advisable choice to treat refractory epilepsy. Our study showed that 12 months or more after VNS implantation, seizure frequency and parenting stress typically decreased. However, in some special cases the parenting stress may increase, and external help may be required to support these patients and their parents. Copyright © 2017. Published by Elsevier B.V.

Low-Level Vagus Nerve Stimulation Attenuates Myocardial Ischemic Reperfusion Injury by Antioxidative Stress and Antiapoptosis Reactions in Canines.

PubMed

Chen, Mingxian; Zhou, Xiaoya; Yu, Lilei; Liu, Qiming; Sheng, Xia; Wang, Zhuo; Wang, Songyun; Jiang, Hong; Zhou, Shenghua

2016-02-01

Low-level vagus nerve stimulation (LL-VNS) has been demonstrated to protect myocardium against acute ischemia/reperfusion (I/R) injury. However, the underlying mechanism of this protective effect remains unknown. This study aimed to test the hypothesis that LL-VNS exerts cardioprotective effect on acute I/R injury in canines via antioxidative stress and antiapoptosis reactions. Thirty anesthetized mongrel dogs were randomly divided into three groups: I/R group (N = 12, the left anterior descending coronary artery was occluded for 1 hour following by 1 hour reperfusion), LL-VNS group (N = 9, I/R plus LL-VNS), and sham group (N = 9, sham surgery without LL-VNS). The voltage threshold was set at 80% of the voltage required to slow the sinus rate. Infarct size was assessed with Evans Blue and triphenyltetrazolium chloride. Activity assays, TUNEL staining, and western blotting were performed to determine markers of oxidative stress and apoptosis. LL-VNS significantly decreased the incidence of ventricular arrhythmias, increased vagal tone, as confirmed by heart rate viability, and reduced infarct size compared with the I/R group. This improvement was associated with a reduction in myocardial neutrophil infiltration, the inhibition of oxidative stress, and the suppression in cardiomyocyte apoptosis. In contrast, the lack of LL-VNS in the I/R group induced the opposite effect compared with the sham group. LL-VNS exerts protective effects on myocardial I/R injury. Its potential mechanisms involve the suppression of oxidative stress and cellular apoptosis. © 2015 Wiley Periodicals, Inc.

Vagal nerve stimulator: Evolving trends

PubMed Central

Ogbonnaya, Sunny; Kaliaperumal, Chandrasekaran

2013-01-01

Over three decades ago, it was found that intermittent electrical stimulation from the vagus nerve produces inhibition of neural processes, which can alter brain activity and terminate seizures. This paved way for the concept of vagal nerve stimulator (VNS). We describe the evolution of the VNS and its use in different fields of medicine. We also review the literature focusing on the mechanism of action of VNS producing desired effects in different conditions. PUBMED and EMBASE search was performed for ‘VNS’ and its use in refractory seizure management, depression, obesity, memory, and neurogenesis. VNS has been in vogue over for the past three decades and has proven to reduce the intensity and frequency of seizure by 50% in the management of refractory seizures. Apart from this, VNS has been shown to promote neurogenesis in the dentate gyrus of rat hippocampus after 48 hours of stimulation of the vagus nerve. Improvement has also been observed in non-psychotic major depression from a randomized trial conducted 7 years ago. The same concept has been utilized to alter behavior and cognition in rodents, and good improvement has been observed. Recent studies have proven that VNS is effective in obesity management in patients with depression. Several hypotheses have been postulated for the mechanism of action of VNS contributing to its success. VNS has gained significant popularity with promising results in epilepsy surgery and treatment-resistant depression. The spectrum of its use has also extended to other fields of medicine including obesity, memory, and neurogenesis, and there is still a viable scope for its utility in the future. PMID:23633829

Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data.

PubMed

Englot, Dario J; Hassnain, Kevin H; Rolston, John D; Harward, Stephen C; Sinha, Saurabh R; Haglund, Michael M

2017-01-01

Drug-resistant epilepsy is a devastating disorder associated with diminished quality of life (QOL). Surgical resection leads to seizure freedom and improved QOL in many epilepsy patients, but not all individuals are candidates for resection. In these cases, neuromodulation-based therapies such as vagus nerve stimulation (VNS) are often used, but most VNS studies focus exclusively on reduction of seizure frequency. QOL changes and predictors with VNS remain poorly understood. Using the VNS Therapy Patient Outcome Registry, we examined 7 metrics related to QOL after VNS for epilepsy in over 5000 patients (including over 3000 with ≥12months follow-up), as subjectively assessed by treating physicians. Trends and predictors of QOL changes were examined and related to post-operative seizure outcome and likelihood of VNS generator replacement. After VNS therapy, physicians reported patient improvement in alertness (58-63%, range over follow-up period), post-ictal state (55-62%), cluster seizures (48-56%), mood change (43-49%), verbal communication (38-45%), school/professional achievements (29-39%), and memory (29-38%). Predictors of net QOL improvement included shorter time to implant (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.6), generalized seizure type (OR, 1.2; 95% CI, 1.0-1.4), female gender (OR, 1.2; 95% CI, 1.0-1.4), and Caucasian ethnicity (OR, 1.3; 95% CI, 1.0-1.5). No significant trends were observed over time. Patients with net QOL improvement were more likely to have favorable seizure outcomes (chi square [χ 2 ]=148.1, p<0.001) and more likely to undergo VNS generator replacement (χ 2 =68.9, p<0.001) than those with worsened/unchanged QOL. VNS for drug-resistant epilepsy is associated with improvement on various QOL metrics subjectively rated by physicians. QOL improvement is associated with favorable seizure outcome and a higher likelihood of generator replacement, suggesting satisfaction with therapy. It is important to consider QOL

Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats.

PubMed

Noble, L J; Gonzalez, I J; Meruva, V B; Callahan, K A; Belfort, B D; Ramanathan, K R; Meyers, E; Kilgard, M P; Rennaker, R L; McIntyre, C K

2017-08-22

Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.

Vagus nerve stimulation inhibits seizure activity and protects blood-brain barrier integrity in kindled rats with cortical dysplasia.

PubMed

Kaya, Mehmet; Orhan, Nurcan; Karabacak, Emrah; Bahceci, Metin Berkant; Arican, Nadir; Ahishali, Bulent; Kemikler, Gonul; Uslu, Atilla; Cevik, Aydin; Yilmaz, Canan Ugur; Kucuk, Mutlu; Gürses, Candan

2013-03-12

This study investigates the effects of vagus nerve stimulation (VNS) on seizure severity and blood-brain barrier (BBB) integrity in kindled rats with cortical dysplasia (CD). Pregnant rats were exposed to 145 cGy of gamma-irradiation on day 17 of pregnancy. In offsprings, kindling was induced by giving subconvulsive doses of pentylenetetrazole. Left VNS was performed for 48 h at output currents of 0.5 or 1 mA. Horseradish peroxidase (HRP) was used to study the BBB permeability. Immunohistochemistry for occludin and P-glycoprotein (P-gp) was also performed. Kindled rats with CD exhibited seizures with mean Racine's scores of 3.57 ± 1.2 during video EEG recording. Kindled animals with CD receiving VNS at 0.5 and 1.0 mA did not exhibit either clinical or electrophysiological signs of seizure. Immunostaining for occludin, a tight junction protein, in hippocampus remained relatively intact in all groups. VNS-treated and -untreated kindled animals with CD revealed intense immunostaining for P-gp in hippocampal formation (P<0.01). Electron microscopic observations revealed frequent transport vesicles containing electron-dense HRP reaction products in the cytoplasm of brain capillary endothelial cells in both cerebral cortex and hippocampus of kindled animals with CD. Those which were exposed to 1 mA VNS were observed to have brain capillary endothelial cells largely devoid of HRP reaction products in both cerebral cortex and hippocampus. The results of this study suggest that VNS therapy at 1 mA inhibits seizure activity and protects BBB integrity by limiting the enhancement of transcellular pathway in kindled animals with CD. Copyright © 2013 Elsevier Inc. All rights reserved.

Non-recurrent inferior laryngeal nerve identification during robotic thyroidectomy.

PubMed

Wang, C-C; Wu, C-H

2014-02-01

A non-recurrent inferior laryngeal nerve is a rare anomaly in which the nerve enters the larynx directly off the cervical vagus nerve, without descending to the thoracic level. It is very susceptible to damage during surgery. This report describes the important pre-operative radiological evaluations and surgical landmarks in a case of a non-recurrent inferior laryngeal nerve, identified during the recently developed technique of robotic thyroidectomy. A 38-year-old woman presented with suspected papillary microcarcinoma, as indicated by aspiration cytology. Pre-operative computed tomography showed a right aberrant subclavian artery that indicated a possible right non-recurrent inferior laryngeal nerve. Using robotic thyroidectomy methods, it was possible to carefully dissect along the thyroid capsule. The laryngeal entrance point of the right non-recurrent inferior laryngeal nerve (a constant anatomical landmark) was successfully identified via the three-dimensional, high-magnification views provided by the robotic endoscope. With proper knowledge of radiological and surgical anatomy, and the benefits of high-magnification endoscopic views, a non-recurrent inferior laryngeal nerve can be safely preserved during robotic surgery.

An analysis of quality of life (QOL) in patients with epilepsy and comorbid psychogenic nonepileptic seizures (PNES) after vagus nerve stimulation (VNS).

PubMed

Vivas, Andrew C; Reitano, Christian J; Waseem, Hena; Benbadis, Selim R; Vale, Fernando L

2017-08-01

Patients with epilepsy (PWE) may suffer from comorbid psychogenic nonepileptic seizures (PNES). The efficacy of vagus nerve stimulation (VNS) in the treatment of epilepsy and depression is established, however the impact on PNES is unknown. Since many patients with PNES have comorbid depression, we explored the impact on quality of life (QOL) that VNS has on PWE and PNES. The video electroencephalogram (vEEG) of all patients who underwent VNS at our institution was reviewed. Patients diagnosed with both psychogenic seizures and epileptic seizures on their vEEG were included in this study. These patients were contacted, and given a QOLIE-31 survey to assess their quality of life after VNS. Patients also completed a separate survey created by our group to categorize the quartile of their improvement. Pre-operative psychiatric disease was retrospectively reviewed. From a period of 2001 to 2016, 518 patients underwent placement of VNS for drug resistant epilepsy (DRE) at our institution. In total, 16 patients were diagnosed with both epilepsy and PNES. 11/16 patients responded to our questionnaire and survey. 9 out of 11 patients felt that their epileptic seizures had improved after VNS, while 7 of the 11 patients felt that their psychogenic episodes had improved. 2(28.6%), 1 (14.3%), and 4 (57.1%) of participants said their PNES improved by 25-50%, 50-75%, and 75-100%, respectively. 3(27.3%), 3 (27.3%), 1 (9.1%), and 4 (36.4%) of the participants said their epileptic seizures improved by 0-25%, 25-50%, 50-75%, and 75-100%, respectively. The average overall score for quality of life for the study participants was found to be 51 (±8) out of 100. Patients with epilepsy and comorbid PNES may benefit from VNS. It is unclear whether the benefit is conferred strictly from decreased epileptic seizure burden. The possible effect on PNES may be related to the known effect of VNS on depression. Further studies are necessary to elucidate the role of VNS in the treatment of PNES

Evaluation of the Predictive Value of Intraoperative Changes in Motor-Evoked Potentials of Caudal Cranial Nerves for the Postoperative Functional Outcome.

PubMed

Kullmann, Marcel; Tatagiba, Marcos; Liebsch, Marina; Feigl, Guenther C

2016-11-01

The predictive value of changes in intraoperatively acquired motor-evoked potentials (MEPs) of the lower cranial nerves (LCN) IX-X (glossopharyngeal-vagus nerve) and CN XII (hypoglossal nerve) on operative outcomes was investigated. MEPs of CN IX-X and CN XII were recorded intraoperatively in 63 patients undergoing surgery of the posterior cranial fossa. We correlated the changes of the MEPs with postoperative nerve function. For CN IX-X, we found a correlation between the amplitude of the MEP ratio and uvula deviation (P = 0.028) and the amplitude duration of the MEP and gag reflex function (P = 0.027). Patients with an MEP ratio of the glossopharyngeal-vagus amplitude ≤1.47 μV had a 3.4 times increased risk of developing a uvula deviation. Patients with a final MEP duration of the CN IX-X ≤11.6 milliseconds had a 3.6 times increased risk for their gag reflex to become extinct. Our study greatly contributes to the current knowledge of intraoperative MEPs as a predictor for postoperative cranial nerve function. We were able to extent previous findings on MEP values of the facial nerve on postoperative nerve function to 3 additional cranial nerves. Finding reliable predictors for postoperative nerve function is of great importance to the overall quality of life for a patient undergoing surgery of the posterior cranial fossa. Copyright © 2016 Elsevier Inc. All rights reserved.

[Pay attention on optical coherence tomography evaluation for optic nerve diseases].

PubMed

Wang, M

2016-12-11

Optical coherence tomography(OCT) had become the most important imaging technique in ophthalmology. OCT is able to segment the retinal nerve fiber layer and retinal ganglion cell layer accurately. Quantitative analysis can be performed for both layers. OCT is very important to evaluate the neuron and axon loss in optic nerve diseases diagnosis. Meanwhile, OCT has great value for differentiating glaucoma and macular diseases from optic nerve diseases. This review presented OCT application in optic nerve diseases diagnosis, differentiation diagnosis, the key points in use and the features of en face OCT and OCT angiography. It gave us suggestions that it should be pay more attention to OCT examination in diagnosis and treatment of optic nerve diseases. (Chin J Ophthalmol, 2016, 52: 885 - 888) .

Physiology and immunology of the cholinergic antiinflammatory pathway

PubMed Central

Tracey, Kevin J.

2007-01-01

Cytokine production by the immune system contributes importantly to both health and disease. The nervous system, via an inflammatory reflex of the vagus nerve, can inhibit cytokine release and thereby prevent tissue injury and death. The efferent neural signaling pathway is termed the cholinergic antiinflammatory pathway. Cholinergic agonists inhibit cytokine synthesis and protect against cytokine-mediated diseases. Stimulation of the vagus nerve prevents the damaging effects of cytokine release in experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, arthritis, and other inflammatory syndromes. Herein is a review of this physiological, functional anatomical mechanism for neurological regulation of cytokine-dependent disease that begins to define an immunological homunculus. PMID:17273548

Cross-cultural psychometric assessment of the VAGUS insight into psychosis scale - Spanish version.

PubMed

de León, Patricia Ponce; Gerretsen, Philip; Shah, Parita; Saracco-Alvarez, Ricardo; Graff-Guerrero, Ariel; Fresán, Ana

2018-01-01

Impaired insight into illness, a core feature of schizophrenia with negative clinical implications, is a multidimensional phenomenon existing on a continuum. However, the degree to which illness perception in distinct cultures influences the appraisal of insight into illness in schizophrenia remains unclear. As such, we aimed to determine if the psychometric properties of the VAGUS insight into psychosis scale (www.vagusonline.com), which was originally assessed in English speaking Canadians, were similar in a sample of Latino Mexican Spanish speaking patients with schizophrenia. To accomplish this, the VAGUS - Self-Report (SR) version was translated from English to Spanish and psychometrically evaluated in 95 participants. The Spanish version of the VAGUS-SR was internally consistent (ᾳ = 0.713), and demonstrated good convergent and discriminant validity with the subscales of the Positive and Negative Syndrome Scale. Factor analysis identified two components of insight, congruent with two of the components of the English version of the VAGUS-SR. In conclusion, the VAGUS-SR is a brief, novel, and valid measure of insight into illness in schizophrenia, which demonstrated similar psychometric properties in two culturally and linguistically distinct samples with schizophrenia. Future studies should assess whether the VAGUS demonstrates similar psychometric properties in non-Western cultures. Copyright © 2017 Elsevier B.V. All rights reserved.

Anastomoses between lower cranial and upper cervical nerves: a comprehensive review with potential significance during skull base and neck operations, part I: trigeminal, facial, and vestibulocochlear nerves.

PubMed

Shoja, Mohammadali M; Oyesiku, Nelson M; Griessenauer, Christoph J; Radcliff, Virginia; Loukas, Marios; Chern, Joshua J; Benninger, Brion; Rozzelle, Curtis J; Shokouhi, Ghaffar; Tubbs, R Shane

2014-01-01

Descriptions of the anatomy of the neural communications among the cranial nerves and their branches is lacking in the literature. Knowledge of the possible neural interconnections found among these nerves may prove useful to surgeons who operate in these regions to avoid inadvertent traction or transection. We review the literature regarding the anatomy, function, and clinical implications of the complex neural networks formed by interconnections among the lower cranial and upper cervical nerves. A review of germane anatomic and clinical literature was performed. The review is organized in two parts. Part I concerns the anastomoses between the trigeminal, facial, and vestibulocochlear nerves or their branches with any other nerve trunk or branch in the vicinity. Part II concerns the anastomoses among the glossopharyngeal, vagus, accessory and hypoglossal nerves and their branches or among these nerves and the first four cervical spinal nerves; the contribution of the autonomic nervous system to these neural plexuses is also briefly reviewed. Part I is presented in this article. An extensive anastomotic network exists among the lower cranial nerves. Knowledge of such neural intercommunications is important in diagnosing and treating patients with pathology of the skull base. Copyright © 2013 Wiley Periodicals, Inc.

Transcutaneous Auricular Vagus Nerve Stimulation with Concurrent Upper Limb Repetitive Task Practice for Poststroke Motor Recovery: A Pilot Study.

PubMed

Redgrave, Jessica N; Moore, Lucy; Oyekunle, Tosin; Ebrahim, Maryam; Falidas, Konstantinos; Snowdon, Nicola; Ali, Ali; Majid, Arshad

2018-03-23

Invasive vagus nerve stimulation (VNS) has the potential to enhance the effects of physiotherapy for upper limb motor recovery after stroke. Noninvasive, transcutaneous auricular branch VNS (taVNS) may have similar benefits, but this has not been evaluated in stroke recovery. We sought to determine the feasibility of taVNS delivered alongside upper limb repetitive task-specific practice after stroke and its effects on a range of outcome measures evaluating limb function. Thirteen participants at more than 3 months postischemic stroke with residual upper limb dysfunction were recruited from the community of Sheffield, United Kingdom (October-December 2016). Participants underwent 18 × 1-hour sessions over 6 weeks in which they made 30-50 repetitions of 8-10 arm movements concurrently with taVNS (NEMOS; Cerbomed, Erlangen, Germany, 25 Hz, .1-millisecond pulse width) at maximum tolerated intensity (mA). An electrocardiogram and rehabilitation outcome scores were obtained at each visit. Qualitative interviews determined the acceptability of taVNS to participants. Median time after stroke was 1.16 years, and baseline median/interquartile range upper limb Fugl-Meyer (UFM) score was 63 (54.5-99.5). Participants attended 92% of the planned treatment sessions. Three participants reported side effects, mainly fatigue, but all performed mean of more than 300 arm repetitions per session with no serious adverse events. There was a significant change in the UFM score with a mean increase per participant of 17.1 points (standard deviation 7.8). taVNS is feasible and well-tolerated alongside upper limb repetitive movements in poststroke rehabilitation. The motor improvements observed justify a phase 2 trial in patients with residual arm weakness. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Superiority of resection over enucleation for schwannomas of the cervical vagus nerve: A retrospective cohort study of 22 consecutive patients.

PubMed

Illuminati, Giulio; Pizzardi, Giulia; Minni, Antonio; Masci, Federica; Ciamberlano, Bernardo; Pasqua, Rocco; Calio, Francesco G; Vietri, Francesco

2016-05-01

Schwannoma of the cervical vagus nerve is rare. Treatment options include intracapsular enucleation and en bloc resection. The purpose of this study was to compare the outcomes of enucleation and resection in terms of postoperative mortality and morbidity, freedom from vocal cord palsy, freedom from local recurrence, quality-adjusted life-year (QALY) and vocal handicap index (VHI). Twentytwo consecutive patients were divided into two groups. Patients in group A (n = 9) underwent intracapsular enucleation, whereas patients in Group B (n = 13) underwent en bloc resection. Main endpoints of the study were postoperative mortality and morbidity, freedom from vocal cord palsy, freedom from local recurrence and quality of life. The quality of life after surgery was assessed according to the quality-adjusted life-year (QALY) EQ-5D-5L methodology, and calculation of the voice handicap index (VHI). Postoperative mortality was nil. Morbidity included 1 wound dehiscence in group A and 2 transitory dysphagias in group B. Freedom from vocal cord palsy was 22% in group A and zero in group B (p = 0.15). Operation-specific local recurrence rate was 33% (3/9 patients) in group A and nil in group B (0/23 patients) (p = 0.05). QALYs was 0.55 in group A and 0.54 in group B (p = 1.0). VHI was 23.77 in group A and 26.15 in group B (p = 1.00). Resection is superior to enucleation in terms of freedom from local recurrence. Functional results are comparable for both techniques. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Extracranial schwannoma in the carotid space: A retrospective review of 91 cases.

PubMed

Zheng, Xiaoke; Guo, Kai; Wang, Hongshi; Li, Duanshu; Wu, Yi; Ji, Qinghai; Shen, Qiang; Sun, Tuanqi; Xiang, Jun; Zeng, Wei; Chen, Yaling; Wang, Zhuoying

2017-01-01

Schwannomas of the vagus nerve and cervical sympathetic nerve are rare; hence, only limited information exists regarding their diagnosis and clinical management. We conducted a retrospective review of the clinical features, imaging studies, and treatment results of patients with schwannoma of the vagus nerve and schwannoma of the sympathetic nerve. Of 91 patients, 91% (n = 83) were preoperatively diagnosed with schwannoma tumors. Using the hyoid bone as an anatomic landmark, the location of the schwannoma of the vagus nerve in the carotid space was significantly different to the location of schwannoma of the sympathetic nerve (p = .003). Although 52 of the 76 patients followed up (68%) had postoperative nerve weaknesses, 13 patients (50%) and 14 patients (53.8%), respectively, fully recovered from schwannoma of the vagus nerve and schwannoma of the sympathetic nerve. In the carotid space, schwannomas of the vagus nerve are usually located below the hyoid bone, whereas schwannomas of the sympathetic nerve more commonly arise from the suprahyoid compartment. Accurate preoperative diagnosis and the intracapsular enucleation surgical approach decreased the incidence of postoperative morbidity. © 2016 Wiley Periodicals, Head Neck 39: 42-47, 2017. © 2016 Wiley Periodicals, Inc.

A history of the optic nerve and its diseases.

PubMed

Reeves, C; Taylor, D

2004-11-01

We will trace the history of ideas about optic nerve anatomy and function in the Western world from the ancient Greeks to the early 20th century and show how these influenced causal theories of optic nerve diseases. Greek and Roman humoral physiology needed a hollow optic nerve, the obstruction of which prevented the flow of visual spirit to and from the brain and resulted in blindness. Medieval physicians understood that the presence of a fixed dilated pupil indicated optic nerve obstruction, preventing the passage of visual spirit, and that cataract surgery in such cases would not restore sight. During the Renaissance, the organ of vision was transferred from the lens to the optic nerve, which was generally believed to be on the axis of the eye. The acuity of central vision (at the optic disc) was explained by the concentration of visual spirit where the optic nerve met the retina. The growth of anatomy and influence of mechanical philosophy from the 17th century led to visual spirit being replaced with the concept of nerve force, which later became associated with electricity travelling along nerve fibres. This coincided with discourse about the nature of the nervous system and a shift in orientation from understanding illness holistically in terms of an individual's humoral imbalance to the concept of organ-based diseases. Both the microscope and the ophthalmoscope allowed visualisation of the optic nerve, but problems of interpretation persisted until conceptual transformations in medical science were made.

High-performance wireless powering for peripheral nerve neuromodulation systems

PubMed Central

Liu, Jiayin; Liao, Song-Yan; Zhen, Zhe; Hsu, Stephanie; Shuto, Chika; Zhu, Zi-Yi; Ma, Andrew; Vassos, Christopher; Chen, Peter; Tse, Hung Fat; Poon, Ada S. Y.

2017-01-01

Neuromodulation of peripheral nerves with bioelectronic devices is a promising approach for treating a wide range of disorders. Wireless powering could enable long-term operation of these devices, but achieving high performance for miniaturized and deeply placed devices remains a technological challenge. We report the miniaturized integration of a wireless powering system in soft neuromodulation device (15 mm length, 2.7 mm diameter) and demonstrate high performance (about 10%) during in vivo wireless stimulation of the vagus nerve in a porcine animal model. The increased performance is enabled by the generation of a focused and circularly polarized field that enhances efficiency and provides immunity to polarization misalignment. These performance characteristics establish the clinical potential of wireless powering for emerging therapies based on neuromodulation. PMID:29065141

High-performance wireless powering for peripheral nerve neuromodulation systems.

PubMed

Tanabe, Yuji; Ho, John S; Liu, Jiayin; Liao, Song-Yan; Zhen, Zhe; Hsu, Stephanie; Shuto, Chika; Zhu, Zi-Yi; Ma, Andrew; Vassos, Christopher; Chen, Peter; Tse, Hung Fat; Poon, Ada S Y

2017-01-01

Neuromodulation of peripheral nerves with bioelectronic devices is a promising approach for treating a wide range of disorders. Wireless powering could enable long-term operation of these devices, but achieving high performance for miniaturized and deeply placed devices remains a technological challenge. We report the miniaturized integration of a wireless powering system in soft neuromodulation device (15 mm length, 2.7 mm diameter) and demonstrate high performance (about 10%) during in vivo wireless stimulation of the vagus nerve in a porcine animal model. The increased performance is enabled by the generation of a focused and circularly polarized field that enhances efficiency and provides immunity to polarization misalignment. These performance characteristics establish the clinical potential of wireless powering for emerging therapies based on neuromodulation.

Severe localised granulomatosis with polyangiitis (Wegener's granulomatosis) manifesting with extensive cranial nerve palsies and cranial diabetes insipidus: a case report and literature review.

PubMed

Peters, James E; Gupta, Vivek; Saeed, Ibtisam T; Offiah, Curtis; Jawad, Ali S M

2018-05-01

Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a multisystem vasculitis of small- to medium-sized blood vessels. Cranial involvement can result in cranial nerve palsies and, rarely, pituitary infiltration. We describe the case of a 32 year-old woman with limited but severe GPA manifesting as progressive cranial nerve palsies and pituitary dysfunction. Our patient initially presented with localised ENT involvement, but despite treatment with methotrexate, she deteriorated. Granulomatous inflammatory tissue around the skull base resulted in cavernous sinus syndrome, facial nerve palsy, palsies of cranial nerves IX-XII (Collet-Sicard syndrome), and the rare complication of cranial diabetes insipidus due to pituitary infiltration. The glossopharyngeal, vagus and accessory nerve palsies resulted in severe dysphagia and she required nasogastric tube feeding. Her neurological deficits substantially improved with treatment including high dose corticosteroid, cyclophosphamide and rituximab. This case emphasises that serious morbidity can arise from localised cranial Wegener's granulomatosis in the absence of systemic disease. In such cases intensive induction immunosuppression is required. Analysis of previously reported cases of pituitary involvement in GPA reveals that this rare complication predominantly affects female patients.

Paraganglioma of the hypoglossal nerve.

PubMed

Fink, Daniel S; Benoit, Margo McKenna; Lamuraglia, Glenn M; Deschler, Daniel G

2010-01-01

To report a case of paraganglioma arising from the hypoglossal nerve and review the anatomy, clinical features, and literature to date. Case report and review of the literature. Case records including paper and electronic chart and imaging reports were reviewed and summarized for the index case. A literature search was performed using pubmed keywords paraganglioma, hypoglossal, chemodactoma, carotid body, and glomus tumor. The available literature on the topic was reviewed and summarized. Paragangliomas associated with the hypoglossal nerve were reported in 4 cases over the past 47 years. Our index case presented with similar clinical features compared to those reported in the literature. Imaging with computed tomography and angiography showed a hypervascular mass at the carotid bifurcation, splaying the internal and external carotid arteries. As in previously reported cases, the source of the paraganglioma was only identified intraoperatively. The current case differs from prior reported literature in that the tumor was dissected from the associated hypoglossal nerve which was preserved. The patient clinically had no deficits in articulation or deglutination following excision of the lesion and was able to return to a normal diet within 24 hours of surgery. Hypoglossal paraganglioma is a neck mass that may not be distinguishable from more common carotid body or vagus tumors despite the use of multiple imaging modalities. Although XIIth nerve sacrifice may be requires in some instances, nerve preserving surgery, when possible, allows for complete recovery without functional deficits.

Coincidental Optic Nerve Meningioma and Thyroid Eye Disease.

PubMed

Garg, Aakriti; Patel, Payal; Lignelli, Angela; Baron, Edward; Kazim, Michael

2015-01-01

A 57-year-old woman with diabetes mellitus, hypertension, obesity, and Graves disease presented with clinical evidence of thyroid eye disease (TED) and optic neuropathy. She was referred when a tapered dose of steroids prompted worsening of her TED. CT and MRI were consistent with TED and bilateral optic nerve meningioma. To the authors' knowledge, this is the first reported case of concurrent TED and unsuspected bilateral optic nerve meningioma. When investigating the etiology of TED-associated optic neuropathy, careful attention to orbital imaging is required because coexisting pathology may exist.

The distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the medulla oblongata, spinal cord, cranial and spinal nerves of frog, Microhyla ornata.

PubMed

Jadhao, Arun G; Biswas, Saikat P; Bhoyar, Rahul C; Pinelli, Claudia

2017-04-01

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) enzymatic activity has been reported in few amphibian species. In this study, we report its unusual localization in the medulla oblongata, spinal cord, cranial nerves, spinal nerves, and ganglions of the frog, Microhyla ornata. In the rhombencephalon, at the level of facial and vagus nerves, the NADPH-d labeling was noted in the nucleus of the abducent and facial nerves, dorsal nucleus of the vestibulocochlear nerve, the nucleus of hypoglossus nerve, dorsal and lateral column nucleus, the nucleus of the solitary tract, the dorsal field of spinal grey, the lateral and medial motor fields of spinal grey and radix ventralis and dorsalis (2-10). Many ependymal cells around the lining of the fourth ventricle, both facial and vagus nerves and dorsal root ganglion, were intensely labeled with NADPH-d. Most strikingly the NADPH-d activity was seen in small and large sized motoneurons in both medial and lateral motor neuron columns on the right and left sides of the brain. This is the largest stained group observed from the caudal rhombencephalon up to the level of radix dorsalis 10 in the spinal cord. The neurons were either oval or elongated in shape with long processes and showed significant variation in the nuclear and cellular diameter. A massive NADPH-d activity in the medulla oblongata, spinal cord, and spinal nerves implied an important role of this enzyme in the neuronal signaling as well as in the modulation of motor functions in the peripheral nervous systems of the amphibians. Copyright © 2017 Elsevier B.V. All rights reserved.

3 Tesla MRI of patients with a vagus nerve stimulator: initial experience using a T/R head coil under controlled conditions.

PubMed

Gorny, Krzysztof R; Bernstein, Matt A; Watson, Robert E

2010-02-01

To assess safety of clinical MRI of the head in patients with implanted model 100, 102, and 103 vagus nerve stimulation (VNS) Therapy Systems (Cyberonics, Inc., Houston, TX) in 3.0 Tesla MRI (GE Healthcare, Milwaukee, WI). The distributions of the radiofrequency B(1) (+)-field produced by the clinically used transmit/receive (T/R) head coil (Advanced Imaging Research Incorporated, Cleveland, OH) and body coil were measured in a head and shoulders phantom. These measurements were supplemented by temperature measurements on the lead tips and the implantable pulse generator (IPG) of the VNS devices in a head and torso phantom with the same two coils. Clinical 3T MRI head scans were then acquired under highly controlled conditions in a series of 17 patients implanted with VNS. Phantom studies showed only weak B(1) (+) fields at the location of the VNS IPG and leads for MRI scans using the T/R head coil. The MRI-related heating on a VNS scanned in vitro at 3T was also found to be minimal (0.4-0.8 degrees C at the leads, negligible at the IPG). The patient MRI examinations were completed successfully without any adverse incidents. No patient reported any heating, discomfort, or any other unusual sensation. Safe clinical MRI head scanning of patients with implanted VNS is shown to be feasible on a GE Signa Excite 3T MRI system using one specific T/R head coil. These results apply to this particular MRI system configuration. Extrapolation or generalization of these results to more general or less controlled imaging situations without supporting data of safety is highly discouraged.

Vagus nerve stimulation in 15 children with therapy resistant epilepsy; its impact on cognition, quality of life, behaviour and mood.

PubMed

Hallböök, Tove; Lundgren, Johan; Stjernqvist, Karin; Blennow, Gösta; Strömblad, Lars-Göran; Rosén, Ingmar

2005-10-01

Vagus nerve stimulation (VNS) is a neurophysiologic treatment for patients with refractory epilepsy. There is growing evidence of additional quality of life (QOL) benefits of VNS. We report the effects of VNS on seizure frequency and severity and how these changes are related to cognitive abilities, QOL, behaviour and mood in 15 children with medically refractory and for surgery not eligible epilepsy. Initially, and after 3 and 9 months of VNS-treatment, 15 children were investigated with Bayley Scales of Infant Development (BSID), Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R), Wechlser Intelligence Scales for Children (WISC-III) depending on the child's level of functioning, a Visual Analogue Scale for validating QOL, Child Behaviour Checklist (CBCL) for quantifying behaviour problems, Dodrill Mood Analogue Scale and Birleson Depression Self-Rating Scale, and the National Hospital Seizure Severity Scale (NHS3). A diary of seizure frequency was collected. Six of 15 children showed a 50% or more reduction in seizure frequency; one of these became seizure-free. Two children had a 25-50% seizure reduction. Two children showed increased seizure frequency. In 13 of 15 children there was an improvement in NHS3. The parents reported shorter duration of seizure and recovery phase. There were no changes in cognitive functioning. Twelve children showed an improvement in QOL. Eleven of these also improved in seizure severity and mood and five also in depressive parameters. This study has shown a good anti-seizure effect of VNS, an improvement in seizure severity and in QOL and a tendency to improvement over time regarding behaviour, mood and depressive parameters. The improvement in seizure severity, QOL, behaviour, mood and depressive parameters was not related to the anti-seizure effect.

Fetal facial nerve course in the ear region revisited.

PubMed

Jin, Zhe Wu; Cho, Kwang Ho; Abe, Hiroshi; Katori, Yukio; Murakami, Gen; Rodríguez-Vázquez, Jose Francisco

2017-08-01

The aim of this study was to re-examine the structures that determine course of the facial nerve (FN) in the fetal ear region. We used sagittal or horizontal sections of 28 human fetuses at 7-8, 12-16, and 25-37 weeks. The FN and the chorda tympani nerve ran almost parallel until 7 weeks. The greater petrosal nerve (GPN) ran vertical to the distal FN course due to the trigeminal nerve ganglion being medial to the geniculate ganglion at 7 weeks. Afterwards, due to the radical growth of the former ganglion, the GPN became an anterior continuation of the FN. The lesser petrosal nerve ran straight, parallel to the FN at 7 weeks, but later, it started to wind along the otic capsule, possibly due to the upward invasion of the tympanic cavity epithelium. Notably, the chorda tympanic nerve origin from the FN, and the crossing between the vagus nerve branch and the FN, was located outside of the temporal bone even at 37 weeks. The second knee of the FN was not evident, in contrast to the acute anterior turn below the chorda tympanic nerve origin. In all examined fetuses, the apex of the cochlea did not face the middle cranial fossa, but the tympanic cavity. Topographical relation among the FN and related nerves in the ear region seemed not to be established in the fetal age but after birth depending on growth of the cranial fossa.

Pattern analysis of nerve enlargement using ultrasonography in chronic inflammatory demyelinating polyneuropathy.

PubMed

Jang, Jae Hong; Cho, Charles S; Yang, Kyung-Sook; Seok, Hung Youl; Kim, Byung-Jo

2014-09-01

Focal nerve enlargement is a characteristic finding in chronic inflammatory demyelinating polyneuropathy (CIDP). We performed this study to assess the distribution of nerve enlargement through ultrasonographic examination of peripheral nerves and to correlate the ultrasonographic findings with clinical features. To compare the ultrasonographic features of 10 subjects with CIDP with those of 18 healthy controls, we bilaterally measured the cross-sectional areas (CSA) of the vagus, brachial plexus, musculocutaneous, median, ulnar, radial, sciatic, tibial, common peroneal, and sural nerves. We also analyzed correlations between CSAs and various clinical and electrophysiological features. Mean CSAs were significantly larger in CIDP patients than controls, especially at proximal and non-entrapment sites. CSAs were significantly correlated with muscle strength at initial presentation, but not at the time of ultrasonography. The CSAs of the median and ulnar nerves at the mid-forearm, tibial nerve at 7 cm proximal to the medial malleolus, and sural nerve correlated with the nerve conduction velocity of the corresponding region. Ultrasonography revealed widely distributed nerve enlargement, especially in proximal regions and non-entrapment sites, in patients with CIDP compared with healthy controls. Nerve enlargement correlated well with the electrophysiologic function of the nerve, but not current clinical status. Pattern analysis of nerve enlargement using ultrasonography is a supportive tool in the diagnosis of CIDP. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

PubMed Central

Cruzat, Andrea; Qazi, Yureeda; Hamrah, Pedram

2016-01-01

In vivo confocal microscopy (IVCM) is becoming an indispensable tool for studying corneal physiology and disease. Enabling the dissection of corneal architecture at a cellular level, this technique offers fast and noninvasive in vivo imaging of the cornea with images comparable to that of ex vivo histochemical techniques. Corneal nerves bear substantial relevance to clinicians and scientists alike, given their pivotal roles in regulation of corneal sensation, maintenance of epithelial integrity, and proliferation and promotion of wound healing. Thus, IVCM offers a unique method to study corneal nerve alterations in a myriad of conditions, such as ocular and systemic diseases and following corneal surgery, without altering the tissue microenvironment. Of particular interest has been the correlation of corneal subbasal nerves to their function, which has been studied in normal eyes, contact lens wearers, and patients with keratoconus, infectious keratitis, corneal dystrophies, and neurotrophic keratopathy. Longitudinal studies have applied IVCM to investigate the effects of corneal surgery on nerves, demonstrating their regenerative capacity. IVCM is increasingly important in the diagnosis and management of systemic conditions such as peripheral diabetic neuropathy and, more recently, in ocular diseases. In this review, we outline the principles and applications of IVCM in the study of corneal nerves in various ocular and systemic diseases. PMID:27771327

[Damage to cranial and peripheral nerves following patency restoration of the internal carotid artery].

PubMed

Myrcha, P; Ciostek, P; Szopiński, P; Noszczyk, W

2001-01-01

The aim of the study was an assessment of the incidence of injury to cranial and peripheral nerves as complication of patency restoration of the internal carotid artery, and analysis of the effect of peripheral nerve injury on the results of carotid patency restoration. From Oct 1987 to Sept 1999 543 procedures were carried out for restoration of patency of the internal carotid artery. After the operation hypoglossus nerve injury was found in 7 cases (1.4%), vagus injury in 9 (1.8%). Signs of exclusively recurrent laryngeal nerve damage were found in 6 cases (1.2%). Glossopharyngeus nerve was damaged in 2 cases (0.4%), transient phrenic nerve palsy as a result of conduction anaesthesia was noted in 2 cases (0.4%). Damage to the transverse cervical nerve was found in 96 cases (60%). In 2 patients (1.2%) lower position of mouth angle was due to section of the mandibular ramus of the facial nerve. In another 2 cases skin sensation disturbances were a consequence of lesion of the auricularis magnus nerve and always they coexisted with signs of transverse cervical nerve damage. damage to the cranial nerves during operation for carotid patency restoration are frequent but mostly they are not connected with any health risks and often they regress spontaneously.

The lower cranial nerves: IX, X, XI, XII.

PubMed

Sarrazin, J-L; Toulgoat, F; Benoudiba, F

2013-10-01

The lower cranial nerves innervate the pharynx and larynx by the glossopharyngeal (CN IX) and vagus (CN X) (mixed) nerves, and provide motor innervation of the muscles of the neck by the accessory nerve (CN XI) and the tongue by the hypoglossal nerve (CN XII). The symptomatology provoked by an anomaly is often discrete and rarely in the forefront. As with all cranial nerves, the context and clinical examinations, in case of suspicion of impairment of the lower cranial nerves, are determinant in guiding the imaging. In fact, the impairment may be located in the brain stem, in the peribulbar cisterns, in the foramens or even in the deep spaces of the face. The clinical localization of the probable seat of the lesion helps in choosing the adapted protocol in MRI and eventually completes it with a CT-scan. In the bulb, the intra-axial pathology is dominated by brain ischemia (in particular, with Wallenberg syndrome) and multiple sclerosis. Cisternal pathology is tumoral with two tumors, schwannoma and meningioma. The occurrence is much lower than in the cochleovestibular nerves as well as the leptomeningeal nerves (infectious, inflammatory or tumoral). Finally, foramen pathology is tumoral with, outside of the usual schwannomas and meningiomas, paragangliomas. For radiologists, fairly hesitant to explore these lower cranial pairs, it is necessary to be familiar with (or relearn) the anatomy, master the exploratory technique and be aware of the diagnostic possibilities. Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Recurrent largngeal nerve paralysis: a laryngographic and computed tomographic study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agha, F.P.

Vocal cord paralysis is a relatively common entity, usually resulting from a pathologic process of the vagus nerve or its recurrent larynegeal branch. It is rarely caused by intralargngeal lesions. Four teen patients with recurrent laryngeal nerve paralysis (RLNP) were evaluated by laryngography, computed tomography (CT), or both. In the evaluation of the paramedian cord, CT was limited in its ability to differentiate between tumor or RLNP as the cause of the fixed cord, but it yielded more information than laryngography on the structural abnormalities of the larynx and pre-epiglottic and paralaryngeal spaces. Laryngography revealed distinct features of RLNP andmore » is the procedure of choice for evaluation of functional abnormalities of the larynx until further experience with faster CT scanners and dynamic scanning of the larynx is gained.« less

Ultrasonographic nerve enlargement of the median and ulnar nerves and the cervical nerve roots in patients with demyelinating Charcot-Marie-Tooth disease: distinction from patients with chronic inflammatory demyelinating polyneuropathy.

PubMed

Sugimoto, Takamichi; Ochi, Kazuhide; Hosomi, Naohisa; Takahashi, Tetsuya; Ueno, Hiroki; Nakamura, Takeshi; Nagano, Yoshito; Maruyama, Hirofumi; Kohriyama, Tatsuo; Matsumoto, Masayasu

2013-10-01

Demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyneuropathy (CIDP) are both demyelinating polyneuropathies. The differences in nerve enlargement degree and pattern at multiple evaluation sites/levels are not well known. We investigated the differences in nerve enlargement degree and the distribution pattern of nerve enlargement in patients with demyelinating CMT and CIDP, and verified the appropriate combination of sites/levels to differentiate between these diseases. Ten patients (aged 23-84 years, three females) with demyelinating CMT and 16 patients (aged 30-85 years, five females) with CIDP were evaluated in this study. The nerve sizes were measured at 24 predetermined sites/levels from the median and ulnar nerves and the cervical nerve roots (CNR) using ultrasonography. The evaluation sites/levels were classified into three regions: distal, intermediate and cervical. The number of sites/levels that exhibited nerve enlargement (enlargement site number, ESN) in each region was determined from the 24 sites/levels and from the selected eight screening sites/levels, respectively. The cross-sectional areas of the peripheral nerves were markedly larger at all evaluation sites in patients with demyelinating CMT than in patients with CIDP (p < 0.01). However, the nerve sizes of CNR were not significantly different between patients with either disease. When we evaluated ESN of four selected sites for screening from the intermediate region, the sensitivity and specificity to distinguish between demyelinating CMT and CIDP were 0.90 and 0.94, respectively, with the cut-off value set at four. Nerve ultrasonography is useful to detect nerve enlargement and can clarify morphological differences in nerves between patients with demyelinating CMT and CIDP.

Recording of electroneurograms from the nerves innervating the pancreas of a dog.

PubMed

Rozman, J; Zorko, B; Bunc, M

2001-12-15

Electroneurograms (ENGs) from the vagus, splanchnic and pancreatic nerves innervating the pancreas of a dog, were recorded with chronically implanted silicone multi-electrode circular cuffs in an intact pancreas and in a pancreas partly disabled with alloxan. The cuffs contained 33 platinum electrodes (0.6x1.5 mm) arranged in three parallel circular groups integrated into the inner surface of the cuff. Each circular group contained 11 electrodes at a distance of 0.5 mm apart, with 6 mm between the circular groups. The cuffs had an inner diameter of 2.5 mm and the length of 18 mm. In a 2-year study, the cuffs were implanted into two adult Beagle dogs (one female and one male). In the vagus nerve, the cuff was installed on the nerve at the neck, whilst in the splanchnic nerve, the cuff was installed on the nerve before the celiac ganglion, and in the pancreatic nerve, the cuff was installed on the nerve just before it enters the pancreas. In each of the three implanted cuffs, the electrodes of the central circular group were connected to each other and this signal provided one input to a multi-channel ENG amplifying system. The electrodes of each of the two outer spiral groups were connected to each other and then both these groups were short-circuited. This signal then provided another input to the multi-channel ENG amplifying system. The ENG amplifying system was designed to amplify the ENGs 100000 times and to pass frequencies of between 500 and 10 kHz. In our study, three recordings in each animal were conducted. Recordings in the intact pancreas were conducted 2 and 6 months after the implantation, while the recording in the partly disabled pancreas, was conducted 10 months after the implantation and 10 days after the disablement. Due to the fact that the results obtained in both animals were actually quite similar, we present the results of the recordings obtained in one animal. In both animals the cuffs were left implanted for more than 1 year and were used

Innervation of the human cricopharyngeal muscle by the recurrent laryngeal nerve and external branch of the superior laryngeal nerve.

PubMed

Uludag, Mehmet; Aygun, Nurcihan; Isgor, Adnan

2017-06-01

The major component of the upper esophageal sphincter is the cricopharyngeal muscle (CPM). We assessed the contribution of the laryngeal nerves to motor innervation of the CPM. We performed an intraoperative electromyographic study of 27 patients. The recurrent laryngeal nerve (RLN), vagus nerve, external branch of the superior laryngeal nerve (EBSLN), and pharyngeal plexus (PP) were stimulated. Responses were evaluated by visual observation of CPM contractions and electromyographic examination via insertion of needle electrodes into the CPM. In total, 46 CPMs (24 right, 22 left) were evaluated. PP stimulation produced both positive visual contractions and electromyographic (EMG) responses in 42 CPMs (2080 ± 1583 μV). EBSLN stimulation produced visual contractions of 28 CPMs and positive EMG responses in 35 CPMs (686 ± 630 μV). Stimulation of 45 RLNs produced visible contractions of 37 CPMs and positive EMG activity in 41 CPMs (337 ± 280 μV). Stimulation of 42 vagal nerves resulted in visible contractions of 36 CPMs and positive EMG responses in 37 CPMs (292 ± 229 μV). Motor activity was noted in 32 CPMs by both RLN and EBSLN stimulation, 9 CPMs by RLN stimulation, and 3 CPMs by EBSLN stimulation; 2 CPMs exhibited no response. This is the first study to show that the EBSLN contributes to motor innervation of the human CPM. The RLN, EBSLN, or both of the nerves innervate the 90, 75, and 70 % of the CPMs ipsilaterally, respectively.

Acute Autonomic Engagement Assessed by Heart Rate Dynamics During Vagus Nerve Stimulation in Patients With Heart Failure in the ANTHEM-HF Trial.

PubMed

Nearing, Bruce D; Libbus, Imad; Amurthur, Badri; Kenknight, Bruce H; Verrier, Richard L

2016-09-01

Chronic vagus nerve stimulation (VNS) applied to produce biomimetic levels of parasympathetic activation is feasible, well tolerated, safe, improves left ventricular ejection fraction, NYHA class, heart rate variability, and baroreflex function, and reduces T-wave alternans (TWA) in patients with chronic heart failure. However, the acute effects of VNS on beat-to-beat heart rate dynamics have not been systematically characterized in humans. We evaluated acute effects of VNS on R-R-interval dynamics during the VNS titration period in patients (n = 59) enrolled in ANTHEM-HF trial by quantifying effects during continuous cyclic VNS (14-seconds on-time, 66-seconds off-time) adjusted to the maximum tolerable dose without excessive (<4 bpm) bradycardia during the 10-week titration period. VNS elicited an immediate change in heart rate that was correlated to VNS current amplitude, pulse width, and frequency. Heart rate decreased more in the 28 patients with right-sided stimulation (-2.22 ± 0.13 bpm) than in the 31 patients with left-sided stimulation (-0.60 ± 0.08 bpm, P < 0.001). The linear correlation between stimulus intensity and lengthening of the R-R interval was stronger among the 28 patients with right-sided VNS implantation (r = 0.88, P < 0.0001) than among the 31 patients with left-sided VNS implantation (r = 0.49, P < 0.002). In all patients, the heart rate change elicited by VNS was significantly greater than the change during the same timing intervals in 10 randomly selected patients without stimulation (+0.08 ± 0.06 bpm, P < 0.001). Instantaneous heart rate change during therapeutic levels of VNS in patients with heart failure indicates consistent modulation of the autonomic nervous system for both left- and right-sided stimulation. © 2016 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals, Inc.

Silicon central pattern generators for cardiac diseases

PubMed Central

Nogaret, Alain; O'Callaghan, Erin L; Lataro, Renata M; Salgado, Helio C; Meliza, C Daniel; Duncan, Edward; Abarbanel, Henry D I; Paton, Julian F R

2015-01-01

Cardiac rhythm management devices provide therapies for both arrhythmias and resynchronisation but not heart failure, which affects millions of patients worldwide. This paper reviews recent advances in biophysics and mathematical engineering that provide a novel technological platform for addressing heart disease and enabling beat-to-beat adaptation of cardiac pacing in response to physiological feedback. The technology consists of silicon hardware central pattern generators (hCPGs) that may be trained to emulate accurately the dynamical response of biological central pattern generators (bCPGs). We discuss the limitations of present CPGs and appraise the advantages of analog over digital circuits for application in bioelectronic medicine. To test the system, we have focused on the cardio-respiratory oscillators in the medulla oblongata that modulate heart rate in phase with respiration to induce respiratory sinus arrhythmia (RSA). We describe here a novel, scalable hCPG comprising physiologically realistic (Hodgkin–Huxley type) neurones and synapses. Our hCPG comprises two neurones that antagonise each other to provide rhythmic motor drive to the vagus nerve to slow the heart. We show how recent advances in modelling allow the motor output to adapt to physiological feedback such as respiration. In rats, we report on the restoration of RSA using an hCPG that receives diaphragmatic electromyography input and use it to stimulate the vagus nerve at specific time points of the respiratory cycle to slow the heart rate. We have validated the adaptation of stimulation to alterations in respiratory rate. We demonstrate that the hCPG is tuneable in terms of the depth and timing of the RSA relative to respiratory phase. These pioneering studies will now permit an analysis of the physiological role of RSA as well as its any potential therapeutic use in cardiac disease. PMID:25433077

Palatal insufficiency as isolated sign of GQ1b antibody syndrome.

PubMed

Verhelst, Helene; Maes, Michaela; Deblaere, Karel; Van Coster, Rudy

2011-04-01

Antiganglioside GQ1b antibodies mediate a continuum of disorders with overlapping features, fostering the concept of anti-GQ1b antibody syndrome. We present a patient whose palatal insufficiency was the only clinical sign of postinfectious GQ1b antibody syndrome. Cerebral magnetic resonance imaging confirmed involvement of the glossopharyngeal nerve and vagus nerve bilaterally, revealing gadolinium enhancement of both nerves bilaterally and thickening of the left nervus vagus. Magnetic resonance imaging may help in diagnosing postinfectious GQ1b antibody syndrome, especially at early stages and in monosymptomatic patients. Early diagnosis may lead to early therapy, resulting in a milder disease course by preventing further deterioration leading to the ataxia and ophthalmoplegia usually observed in patients with postinfectious GQ1b antibody syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

Evoked Pain Analgesia in Chronic Pelvic Pain Patients using Respiratory-gated Auricular Vagal Afferent Nerve Stimulation

PubMed Central

Napadow, Vitaly; Edwards, Robert R; Cahalan, Christine M; Mensing, George; Greenbaum, Seth; Valovska, Assia; Li, Ang; Kim, Jieun; Maeda, Yumi; Park, Kyungmo; Wasan, Ajay D.

2012-01-01

Objective Previous Vagus Nerve Stimulation (VNS) studies have demonstrated anti-nociceptive effects, and recent non-invasive approaches; termed transcutaneous-VNS, or t-VNS, have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Design counterbalanced, crossover study. Patients patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. Interventions/Outcomes We evaluated evoked pain analgesia for Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) compared with Non-Vagal Auricular Stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least one week apart. Outcome measures included deep tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. Results RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N=15 CPP patients, compared to NVAS, with moderate to large effect sizes (eta2>0.2). Conclusion Chronic pain disorders such as CPP are in great need of effective, non-pharmacological options for treatment. RAVANS produced promising anti-nociceptive effects for QST outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. PMID:22568773

Synaptic transmission in the superior cervical ganglion of the cat after reinnervation by vagus fibres

PubMed Central

Ceccarelli, B.; Clementi, F.; Mantegazza, P.

1971-01-01

1. A vagus-sympathetic anastomosis was performed in the cat by connecting end to end the cranial trunk of the vagus to the cranial end of the cervical sympathetic trunk, both severed under the ganglia. 2. Forty to sixty days after the anastomosis, the ocular signs of sympathetic paralysis (such as myosis and prolapse of the nictitating membrane) which had developed shortly after the operation, had completely disappeared, thus suggesting the recovery of synaptic transmission in the ganglion. In case of plain preganglionic denervation after the same period the ocular signs of cervical sympathetic paralysis were still present. 3. Contraction of the nictitating membrane could be induced by electrical stimulation of both the vagus preanastomotic and the sympathetic postanastomotic—preganglionic trunks. Ganglionic blocking agents induced the blockade of the `new' ganglionic synaptic function, while nicotine and pilocarpine provoked a marked contraction of the nictitating membrane. 4. Electron microscopy showed that the preganglionic regeneration of vagus fibers resulted in the formation of new synapses, mainly of axodendritic type, identical to normal ganglionic synapses. Moreover, after cutting the preanastomotic trunk of the vagus, these new ganglionic presynaptic profiles degenerated, thus proving their vagal origin. 5. During restoration of the synaptic contacts readjustment of dendritic tips occurred. ImagesText-fig. 2Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 16Fig. 17Fig. 14Fig. 15Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 7Fig. 8 PMID:4326851

Vagus Nerve Stimulation

MedlinePlus

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Reflex regulation of airway sympathetic nerves in guinea-pigs

PubMed Central

Oh, Eun Joo; Mazzone, Stuart B; Canning, Brendan J; Weinreich, Daniel

2006-01-01

Sympathetic nerves innervate the airways of most species but their reflex regulation has been essentially unstudied. Here we demonstrate sympathetic nerve-mediated reflex relaxation of airway smooth muscle measured in situ in the guinea-pig trachea. Retrograde tracing, immunohistochemistry and electrophysiological analysis identified a population of substance P-containing capsaicin-sensitive spinal afferent neurones in the upper thoracic (T1–T4) dorsal root ganglia (DRG) that innervate the airways and lung. After bilateral vagotomy, atropine pretreatment and precontraction of the trachealis with histamine, nebulized capsaicin (10–60 μm) evoked a 63 ± 7% reversal of the histamine-induced contraction of the trachealis. Either the β-adrenoceptor antagonist propranolol (2 μm, administered directly to the trachea) or bilateral sympathetic nerve denervation of the trachea essentially abolished these reflexes (10 ± 9% and 6 ± 4% relaxations, respectively), suggesting that they were mediated primarily, if not exclusively, by sympathetic adrenergic nerve activation. Cutting the upper thoracic dorsal roots carrying the central processes of airway spinal afferents also markedly blocked the relaxations (9 ± 5% relaxation). Comparable inhibitory effects were observed following intravenous pretreatment with neurokinin receptor antagonists (3 ± 7% relaxations). These reflexes were not accompanied by consistent changes in heart rate or blood pressure. By contrast, stimulating the rostral cut ends of the cervical vagus nerves also evoked a sympathetic adrenergic nerve-mediated relaxation that were accompanied by marked alterations in blood pressure. The results indicate that the capsaicin-induced reflex-mediated relaxation of airway smooth muscle following vagotomy is mediated by sequential activation of tachykinin-containing spinal afferent and sympathetic efferent nerves innervating airways. This sympathetic nerve-mediated response may serve to oppose airway

Insecticide resistance of Anopheles sinensis and An. vagus in Hainan Island, a malaria-endemic area of China.

PubMed

Qin, Qian; Li, Yiji; Zhong, Daibin; Zhou, Ning; Chang, Xuelian; Li, Chunyuan; Cui, Liwang; Yan, Guiyun; Chen, Xiao-Guang

2014-03-03

Malaria is one of the most important public health problems in Southeast Asia, including Hainan Island, China. Vector control is the main malaria control measure, and insecticide resistance is a major concern for the effectiveness of chemical insecticide control programs. The objective of this study is to determine the resistance status of the main malaria vector species to pyrethroids and other insecticides recommended by the World Health Organization (WHO) for indoor residual sprays. The larvae and pupae of Anopheles mosquitoes were sampled from multiple sites in Hainan Island, and five sites yielded sufficient mosquitoes for insecticide susceptibility bioassays. Bioassays of female adult mosquitoes three days after emergence were conducted in the two most abundant species, Anopheles sinensis and An. vagus, using three insecticides (0.05% deltamethrin, 4% DDT, and 5% malathion) and following the WHO standard tube assay procedure. P450 monooxygenase, glutathione S-transferase and carboxylesterase activities were measured. Mutations at the knockdown resistance (kdr) gene and the ace-1 gene were detected by DNA sequencing and PCR-RFLP analysis, respectively. An. sinensis and An. vagus were the predominant Anopheles mosquito species. An. sinensis was found to be resistant to DDT and deltamethrin. An. vagus was susceptible to deltamethrin but resistant to DDT and malathion. Low kdr mutation (L1014F) frequency (<10%) was detected in An. sinensis, but no kdr mutation was detected in An. vagus populations. Modest to high (45%-75%) ace-1 mutation frequency was found in An. sinensis populations, but no ace-1 mutation was detected in An. vagus populations. Significantly higher P450 monooxygenase and carboxylesterase activities were detected in deltamethrin-resistant An. sinensis, and significantly higher P450 monooxygenase, glutathione S-transferase and carboxylesterase activities were found in malathion-resistant An. vagus mosquitoes. Multiple insecticide resistance was

Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies.

PubMed

Tashiro, Yasura; Oyabu, Akiko; Imura, Yoshio; Uchida, Atsuko; Narita, Naoko; Narita, Masaaki

2011-06-01

Autism is often associated with multiple developmental anomalies including asymmetric facial palsy. In order to establish the etiology of autism with facial palsy, research into developmental abnormalities of the peripheral facial nerves is necessary. In the present study, to investigate the development of peripheral cranial nerves for use in an animal model of autism, rat embryos were treated with valproic acid (VPA) in utero and their cranial nerves were visualized by immunostaining. Treatment with VPA after embryonic day 9 had a significant effect on the peripheral fibers of several cranial nerves. Following VPA treatment, immunoreactivity within the trigeminal, facial, glossopharyngeal and vagus nerves was significantly reduced. Additionally, abnormal axonal pathways were observed in the peripheral facial nerves. Thus, the morphology of several cranial nerves, including the facial nerve, can be affected by prenatal VPA exposure as early as E13. Our findings indicate that disruption of early facial nerve development is involved in the etiology of asymmetric facial palsy, and may suggest a link to the etiology of autism. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Gastric vagus mediates immobilization-induced hypocalcemia in rats.

PubMed

Ma, J; Aou, S; Matsui, H; Hori, T

1993-09-01

The involvement of the parasympathetic nervous system in the etiology of stress-induced hypocalcemia was investigated in the rat. Atropine methyl bromide (0.1 and 0.6 mg/kg ip) given 20 min before immobilization (IMB) was observed to suppress the induction of hypocalcemia in a dose-dependent manner. A vagotomy of the bilateral cervical trunks also abolished the IMB-induced hypocalcemia. A vagotomy on either the thyroid/parathyroid branches or the celiac branches had no effect on the IMB-induced hypocalcemia, but a vagotomy on the gastric branches completely abolished it. Pretreatment with either secretin (2 and 6 micrograms/kg ip), an inhibitor of gastrin release, or cimetidine (5 and 10 mg/kg ip), a histamine H2-receptor antagonist, diminished the IMB-induced hypocalcemia. The concentration of serum gastrin increased significantly during IMB. It is thus concluded that the decreased levels of plasma calcium caused by IMB are due to the activation of the vagus innervating the stomach. Gastrin and histamine are also involved as a consequence of the activation of the vagus.

Clinically relevant anatomy of recurrent laryngeal nerve.

PubMed

Haller, Justin M; Iwanik, Michael; Shen, Francis H

2012-01-15

An anatomic study of anterior cervical dissection of 11 embalmed cadavers. To determine the anatomic relationship of the recurrent laryngeal nerve (RLN) to the cervical spine and demonstrate vulnerability of the nerve during anterior surgical approach. The most common complications of anterior neck surgery are dysphagia and RLN palsy. The morbidity of these complications has led to the investigation of the impact of sidedness in anterior cervical spine surgery. Eleven adult cadavers (5 male/6 female) were dissected bilaterally to expose the path of the recurrent laryngeal nerve. The right RLN branched from the vagus nerve at the level of T1-T2 or inferior in all specimens. After looping around the subclavian artery, the right RLN became invested in the tracheoesophageal fascia greater than 0.5 cm inferior to C7-T1 in all specimens. The RLN traveled superiorly, slightly anterior to the tracheoesophageal groove, before coursing between the trachea and the thyroid. In 82% (9 of 11) of right-sided dissections, the RLN entered the larynx at or inferior to C6-C7. After looping around the aortic arch, the left RLN was invested in the tracheoesophageal fascia inferior to the T2 level in 100% (10 of 10) of cadavers. The nerve traveled slightly anterior to the tracheoesophageal groove and within the tracheoesophageal fascia before coursing between the trachea and thyroid. In all the left-sided dissections, the RLN entered the larynx at or inferior to C6-C7. This study found that superior to C7-T1, both RLNs had similar anatomic courses and received similar protection via surrounding soft-tissue structures. From an anatomic perspective, the authors did not appreciate a side-to-side difference superior to this level that could place either nerve under greater risk for injury.

Autonomic deficit not the cause of death in West Nile virus neurological disease.

PubMed

Wang, Hong; Siddharthan, Venkatraman; Hall, Jeffery O; Morrey, John D

2014-02-01

Some West Nile virus (WNV)-infected patients have been reported to manifest disease signs consistent with autonomic dysfunction. Moreover, WNV infection in hamsters causes reduced electromyography amplitudes of the gastrointestinal tract and diaphragm, and they have reduced heart rate variability (HRV), a read-out for the parasympathetic autonomic function. HRV was measured in both hamsters and mice using radiotelemetry to identify autonomic deficits. To identify areas of WNV infection within the medulla oblongata mapping to the dorsal motor nucleus of vagus (DMNV) and the nucleus ambiguus (NA), fluorogold dye was injected into the cervical trunk of the vagus nerve of hamsters. As a measurement of the loss of parasympathetic function, tachycardia was monitored contiguously over the time course of the disease. Decrease of HRV did not occur in all animals that died, which is not consistent with autonomic function being the mechanism of death. Fluorogold-stained cells in the DMNV were not stained for WNV envelope protein. Fourteen percent of WNV-stained cells were co-localized with fluorogold-stained cells in the NA. These data, however, did not suggest a fatal loss of autonomic functions because tachycardia was not observed in WNV-infected hamsters. Parasympathetic autonomic function deficit was not a likely mechanism of death in WNV-infected rodents and possibly in human patients with fatal WN neurological disease.

Optic nerve head biomechanics in aging and disease.

PubMed

Downs, J Crawford

2015-04-01

This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optic Nerve Head Biomechanics in Aging and Disease

PubMed Central

Downs, J. Crawford

2015-01-01

This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. PMID:25819451

Demyelination of vestibular nerve axons in unilateral Ménière's disease.

PubMed

Spencer, Robert F; Sismanis, Aristides; Kilpatrick, Jefferson K; Shaia, Wayne T

2002-11-01

We conducted a study to determine whether vestibular nerves in patients with unilateral Ménière's disease whose symptoms are refractory to medical management exhibit neuropathologic changes. We also endeavored to determine whether retrocochlear abnormalities are primary or secondary factors in the disease process. To these ends, we obtained vestibular nerve segments from five patients during retrosigmoid (posterior fossa) neurectomy, immediately fixed them, and processed them for light and electron microscopy. We found that all five segments exhibited moderate to severe demyelination with axonal sparing. Moreover, we noted that reactive astrocytes produced an extensive proliferation of fibrous processes and that the microglia assumed a phagocytic role. We conclude that the possible etiologies of demyelination include viral and/or immune-mediated factors similar to those seen in other demyelinating diseases, such as multiple sclerosis and Guillain-Barré syndrome. Our findings suggest that some forms of Ménière's disease that are refractory to traditional medical management might be the result of retrocochlear pathology that affects the neuroglial portion of the vestibular nerve.

Phrenic Nerve Conduction Abnormalities Correlate with Diaphragmatic Descent in Chronic Obstructive Pulmonary Disease.

PubMed

El-Tantawi, Gihan A Younis; Imam, Mohamed H; Morsi, Tamer S

2015-01-01

Diaphragmatic weakness in chronic obstructive pulmonary disease (COPD) is ascribed to hyperinflation-induced diaphragm shortening as well as impairment in cellular and subcellular structures. Although phrenic neuropathy is known to cause diaphragmatic weakness, phrenic neuropathy is rarely considered in COPD. This work aimed at assessing phrenic nerve conduction in COPD and its relation to radiographic hyperinflation and pulmonary function. Forty COPD patients were evaluated. Radiographic parameters of lung hyperinflation were measured on postero-anterior and lateral chest x-ray films. Flow volume loop parameters were obtained from all patients. Motor conduction study of the phrenic nerves was performed and potentials were recorded over the xiphoid process and the ipsilateral 7th intercostal space. Twenty-seven healthy subjects were enrolled as controls. Parameters of phrenic nerve conduction differed significantly in patients compared to controls. Phrenic nerve abnormalities were detected in 17 patients (42.5%). Electrophysiological measures correlated with diaphragmatic angle of depression on lateral view films and with lung height on postero-anterior films. They did not correlate with the flow volume loop data or disease severity score. Phrenic nerve conduction abnormality is an appreciated finding in COPD. Nerve stretching associated with diaphragmatic descent can be a suggested mechanism for nerve lesion. The presence of phrenic neuropathy may be an additional contributing factor to diaphragmatic dysfunction in COPD patients.

A PILOT STUDY OF DIAGNOSTIC NEUROMUSCULAR ULTRASOUND IN BELL'S PALSY

PubMed Central

TAWFIK, EMAN A.; WALKER, FRANCIS O.; CARTWRIGHT, MICHAEL S.

2015-01-01

Background and purpose Neuromuscular ultrasound of the cranial nerves is an emerging field which may help in the assessment of cranial neuropathies. The aim of this study was to evaluate the role of neuromuscular ultrasound in Bell's palsy. A second objective was to assess the possibility of any associated vagus nerve abnormality. Methods Twenty healthy controls and 12 Bell's palsy patients were recruited. The bilateral facial nerves, vagus nerves, and frontalis muscles were scanned using an 18 MHz linear array transducer. Facial nerve diameter, vagus nerve cross-sectional area, and frontalis thickness were measured. Results Mean facial nerve diameter was 0.8 ± 0.2 mm in controls and 1.1 ± 0.3 mm in patients group. The facial nerve diameter was significantly larger in patients than controls (p = 0.006, 95% CI for the difference between groups of 0.12-0.48), with a significant side-to-side difference in patients as well (p = 0.004, 95% CI for side-to-side difference of 0.08-0.52). ROC curve analysis of the absolute facial nerve diameter revealed a sensitivity of 75 % and a specificity of 70 %. No significant differences in vagus nerve cross-sectional area or frontalis thickness were detected between patients and controls. Conclusions Ultrasound can detect facial nerve enlargement in Bell's palsy and may have a role in assessment, or follow-up, of Bell's palsy and other facial nerve disorders. The low sensitivity of the current technique precludes its routine use for diagnosis, however, this study demonstrates its validity and potential for future research. PMID:26076910

Peptide-containing nerve fibres in the gut wall in Crohn's disease.

PubMed Central

Sjölund, K; Schaffalitzky, O B; Muckadell, D E; Fahrenkrug, J; Håkanson, R; Peterson, B G; Sundler, F

1983-01-01

Neurones containing VIP, substance P, or enkephalin were studied by immunocytochemistry in intestinal specimens from 27 patients with Crohn's disease. Also several endocrine cell systems in the gut were examined. The results were compared with those from a control group of 26 patients. The relative frequency of various endocrine cells did not differ overtly from that in controls. Vasoactive intestinal polypeptide and substance P nerve fibres were distributed in all layers of the gut wall, including the submucosal and myenteric plexuses, whereas enkephalin fibres were restricted to the smooth muscle layer and the myenteric plexus. The distribution and frequency of the peptide-containing nerve fibres were the same in Crohn's disease patients as in control patients. A proportion of these nerve fibres, however, were notably coarse in the Crohn's disease patients. This was particularly apparent in the afflicted parts of the intestine although it was noted also in non-afflicted parts. The concentration of VIP and substance P (expressed as pmol/g wet weight) did not, however, exceed that of the control group. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6192043

CHANGES IN THE PERCENTAGE OF CALCIUM AND PHOSPHORUS OF THE BLOOD FOLLOWING SECTION OF THE SYMPATHETIC AND VAGUS NERVES

PubMed Central

Berg, Benjamin N.; Hess, Alfred F.; Sherman, Elizabeth

1928-01-01

When a splanchnic nerve or the celiac plexus was severed a definite fall in serum calcium resulted, the level falling to 6 mg. per cent and remaining low for 1 or 2 weeks. Tetany, however, did not develop. The inorganic phosphate was slightly altered. On the other hand, when the vagi nerves were severed, the serum calcium rose. The equilibrium of both calcium and phosphorus was rendered less stable by the division of the sympathetic or the parasympathetic nerves. PMID:19869390

Evaluation of feasibility of 1.5 Tesla prostate MRI using body coil RF transmit in a patient with an implanted vagus nerve stimulator.

PubMed

Favazza, Christopher P; Edmonson, Heidi A; Ma, Chi; Shu, Yunhong; Felmlee, Joel P; Watson, Robert E; Gorny, Krzysztof R

2017-11-01

To assess risks of RF-heating of a vagus nerve stimulator (VNS) during 1.5 T prostate MRI using body coil transmit and to compare these risks with those associated with MRI head exams using a transmit/receive head coil. Spatial distributions of radio-frequency (RF) B1 fields generated by transmit/receive (T/R) body and head coils were empirically assessed along the long axis of a 1.5 T MRI scanner bore. Measurements were obtained along the center axis of the scanner and laterally offset by 15 cm (body coil) and 7 cm (head coil). RF-field measurements were supplemented with direct measurements of RF-heating of 15 cm long copper wires affixed to and submerged in the "neck" region of the gelled saline-filled (sodium chloride and polyacrylic acid) "head-and-torso" phantom. Temperature elevations at the lead tips were measured using fiber-optic thermometers with the phantom positioned at systematically increased distances from the scanner isocenter. B1 field measurements demonstrated greater than 10 dB reduction in RF power at distances beyond 28 cm and 24 cm from isocenter for body and head coil, respectively. Moreover, RF power from body coil transmit at distances greater than 32 cm from isocenter was found to be lower than from the RF power from head coil transmit measured at locations adjacent to the coil array at its opening. Correspondingly, maximum temperature elevations at the tips of the copper wires decreased with increasing distance from isocenter - from 7.4°C at 0 cm to no appreciable heating at locations beyond 40 cm. For the particular scanner model evaluated in this study, positioning an implanted VNS farther than 32 cm from isocenter (configuration achievable for prostate exams) can reduce risks of RF-heating resulting from the body coil transmit to those associated with using a T/R head coil. © 2017 American Association of Physicists in Medicine.

Microsurgical Anatomy of the Hypoglossal and C1 Nerves: Description of a Previously Undescribed Branch to the Atlanto-Occipital Joint.

PubMed

Iwanaga, Joe; Fisahn, Christian; Alonso, Fernando; DiLorenzo, Daniel; Grunert, Peter; Kline, Matthew T; Watanabe, Koichi; Oskouian, Rod J; Spinner, Robert J; Tubbs, R Shane

2017-04-01

Distal branches of the C1 nerve that travel with the hypoglossal nerve have been well investigated but relationships of C1 and the hypoglossal nerve near the skull base have not been described in detail. Therefore, the aim of this study was to investigate these small branches of the hypoglossal and first cervical nerves by anatomic dissection. Twelve sides from 6 cadaveric specimens were used in this study. To elucidate the relationship among the hypoglossal, vagus, and first and cervical nerve, the mandible was removed and these nerves were dissected under the surgical microscope. A small branch was found to always arise from the dorsal aspect of the hypoglossal nerve at the level of the transverse process of the atlas and joined small branches from the first and second cervical nerves. The hypoglossal and C1 nerves formed a nerve plexus, which gave rise to branches to the rectus capitis anterior and rectus capitis lateralis muscles and the atlanto-occipital joint. Improved knowledge of such articular branches might aid in the diagnosis and treatment of patients with pain derived from the atlanto-occipital joint. We believe this to be the first description of a branch of the hypoglossal nerve being involved in the innervation of this joint. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural Control of the Immune System

ERIC Educational Resources Information Center

Sundman, Eva; Olofsson, Peder S.

2014-01-01

Neural reflexes support homeostasis by modulating the function of organ systems. Recent advances in neuroscience and immunology have revealed that neural reflexes also regulate the immune system. Activation of the vagus nerve modulates leukocyte cytokine production and alleviates experimental shock and autoimmune disease, and recent data have…

Acetylcholine and the alpha 7 nicotinic receptor: a potential therapeutic target for the treatment of periodontal disease?

PubMed Central

2013-01-01

Objectives The aim of this review is to examine the evidence for a functional cholinergic system operating within the periodontium and determine the evidence for its role in periodontal immunity. Introduction Acetylcholine can influence the immune system via the ‘cholinergic anti-inflammatory pathway’. This pathway is mediated by the vagus nerve which releases acetylcholine to interact with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) on proximate immuno-regulatory cells. Activation of the α7nAChR on these cells leads to down-regulated expression of pro-inflammatory mediators and thus regulates localised inflammatory responses. The role of the vagus nerve in periodontal pathophysiology is currently unknown. However, non-neuronal cells can also release acetylcholine and express the α7nAChR; these include keratinocytes, fibroblasts, T cells, B cells and macrophages. Therefore, by both autocrine and paracrine methods non-neuronal acetylcholine can also be hypothesised to modulate the localised immune response. Methods A Pubmed database search was performed for studies providing evidence for a functional cholinergic system operating in the periodontium. In addition, literature on the role of the ‘cholinergic anti-inflammatory pathway’ in modulating the immune response was extrapolated to hypothesise that similar mechanisms of immune regulation occur within the periodontium. Conclusion The evidence suggests a functional nonneuronal ‘cholinergic anti-inflammatory pathway’ may operate in the periodontium and that this may be targeted therapeutically to treat periodontal disease. PMID:22777144

Bell palsy in lyme disease-endemic regions of canada: a cautionary case of occult bilateral peripheral facial nerve palsy due to Lyme disease.

PubMed

Ho, Karen; Melanson, Michel; Desai, Jamsheed A

2012-09-01

Lyme disease caused by the spirochete Borrelia burgdorferi is a multisystem disorder characterized by three clinical stages: dermatologic, neurologic, and rheumatologic. The number of known Lyme disease-endemic areas in Canada is increasing as the range of the vector Ixodes scapularis expands into the eastern and central provinces. Southern Ontario, Nova Scotia, southern Manitoba, New Brunswick, and southern Quebec are now considered Lyme disease-endemic regions in Canada. The use of field surveillance to map risk and endemic regions suggests that these geographic areas are growing, in part due to the effects of climate warming. Peripheral facial nerve palsy is the most common neurologic abnormality in the second stage of Lyme borreliosis, with up to 25% of Bell palsy (idiopathic peripheral facial nerve palsy) occurring due to Lyme disease. Here we present a case of occult bilateral facial nerve palsy due to Lyme disease initially diagnosed as Bell palsy. In Lyme disease-endemic regions of Canada, patients presenting with unilateral or bilateral peripheral facial nerve palsy should be evaluated for Lyme disease with serologic testing to avoid misdiagnosis. Serologic testing should not delay initiation of appropriate treatment for presumed Bell palsy.

Effect of interconnection between cervical vagus trunk, epicardial fat pad on sinus node function, and atrial fibrillation.

PubMed

Zhou, Qina; Zhang, Ling; Wang, Kun; Xu, Xiaoxia; Ji, Meng; Zhang, Feng; Wang, Hongli; Hou, Yuemei

2014-03-01

The epicardial fat pad (FP) integrates the autonomic innervation between the extrinsic and intrinsic cardiac autonomic nervous system and affects atrial electrophysiology and pathophysiology. Eighteen dogs were divided into two groups: sequential ablation of sinoatrial node FP (SAN-FP) and atrioventricular node FP (AVN-FP). Sinus rate (SR), atrial fibrillation (AF) inducibility, and effective refractory period (ERP) changes during electrical stimulation of the vagus trunk were detected before and after ablation. In the SAN-FP group, the SR slowing, increasing AF inducibility, and ERP shortening that induced by vagus trunk stimulation were significantly attenuated by isolated SAN-FP ablation, compared with the same group prior to ablation (all P < 0.05). Subsequent AVN-FP ablation following SAN-FP ablation almost cannot produce further attenuation during vagus trunk stimulation, compared with isolated SAN-FP ablation (P > 0.05). In the AVN-FP group, SR slowing, increasing AF inducibility, and ERP shortening that induced by vagus trunk stimulation were completely eliminated by isolated AVN-FP ablation, compared with the same group prior to ablation (all P < 0.05). Subsequent SAN-FP ablation following AVN-FP ablation produced no further attenuation, compared with isolated AVN-FP ablation (P > 0.05). A neural pathway from the cervical vagus trunk to the sinus node and atrium runs through the SAN-FP, but eventually converges at the AVN-FP and also suggested that the AVN-FP serves as an "integration center" for the SAN-FP to modulate sinus node function. The AVN-FP may play a more critical role in the initiation and maintenance of AF. ©2013 First Affilated Hospital of Xingiang Medical University Pacing and Clinical Electrophysiology ©2013 Wiley Periodicals, Inc.

An autopsy case of minamata disease (methylmercury poisoning)--pathological viewpoints of peripheral nerves.

PubMed

Eto, Komyo; Tokunaga, Hidehiro; Nagashima, Kazuo; Takeuchi, Tadao

2002-01-01

The outbreak of methylmercury poisoning in the geographic areas around Minamata Bay, Kumamoto, Japan in the 1950s has become known as Minamata disease. Based on earlier reports and extensive pathological studies on autopsied cases at the Kumamoto University School of Medicine, destructive lesions in the anterior portion of the calcarine cortex and depletion predominantly of granular cells in the cerebellar cortex came to be recognized as the hallmark and diagnostic yardstick of methylmercury poisoning in humans. As the number of autopsy cases of Minamata disease increased, it became apparent that the cerebral lesion was not restricted to the calcarine cortex but was relatively widespread. Less severe lesions, believed to be responsible for the motor symptoms of Minamata patients, were often found in the precentral, postcentral, and lateral temporal cortices. These patients also frequently presented with signs of sensory neuropathy affecting the distal extremities. Because of few sufficiently comprehensive studies, peripheral nerve degeneration has not been universally accepted as a cause of the sensory disturbances in Minamata patients. The present paper describes both biopsy and autopsy findings of the peripheral nerves in a male fisherman who died at the age of 64 years and showed the characteristic central nervous system lesions of Minamata disease at autopsy. A sural nerve biopsy with electron microscopy performed 1 month prior to his death showed endoneurial fibrosis and regenerated myelin sheaths. At autopsy the dorsal roots and sural nerve showed endoneurial fibrosis, loss of nerve fibers, and presence of Büngner's bands. The spinal cord showed Wallerian degeneration of the fasciculus gracilis (Goll's tract) with relative preservation of neurons in sensory ganglia. These findings support the contention that there is peripheral nerve degeneration in Minamata patients due to toxic injury from methylmercury.

Carotid Space Mass Proximal to Vagus Nerve Causing Asystole and Syncope.

PubMed

Leviter, Julie; Wiznia, Daniel H

2016-01-01

Manipulation of vagal nerve rootlets, whether surgical or through mass effect of a neoplasm, can result in asystole and hypotension, accompanied by ST depression and right bundle branch block. There are few case reports of a neoplasm causing these effects, and this case describes a patient with such a mass presenting with syncopal episodes. A 43-year-old man with a past medical history of HIV, bipolar disorder, and epilepsy was admitted to the neurology service for a video electroencephalogram (vEEG) to characterize syncopal episodes that were felt to be epileptic in origin. During the study, he experienced symptoms of his typical aura, which correlated with a transient symptomatic high degree AV block on telemetry, and an absence of epileptic findings on vEEG. Magnetic Resonance Imaging (MRI) of the brain showed a mass in the left posterior carotid space at the skull base. The patient underwent permanent dual chamber MRI-compatible pacemaker placement for his heart block. His syncopal episodes resolved, but presyncopal symptoms persisted. We discuss the presentation and treatment of vagal neoplasms.

The Kölliker-Fuse nucleus: a review of animal studies and the implications for cranial nerve function in humans.

PubMed

Browaldh, Nanna; Bautista, Tara G; Dutschmann, Mathias; Berkowitz, Robert G

2016-11-01

To review the scientific literature on the relationship between Kölliker-Fuse nucleus (KF) and cranial nerve function in animal models, with view to evaluating the potential role of KF maturation in explaining age-related normal physiologic parameters and developmental and acquired impairment of cranial nerve function in humans. Medical databases (Medline and PubMed). Studies investigating evidence of KF activity responsible for a specific cranial nerve function that were based on manipulation of KF activity or the use of neural markers were included. Twenty studies were identified that involved the trigeminal (6 studies), vagus (9), and hypoglossal nerves (5). These pertained specifically to a role of the KF in mediating the dive reflex, laryngeal adductor control, swallowing function and upper airway tone. The KF acts as a mediator of a number of important functions that relate primarily to laryngeal closure, upper airway tone and swallowing. These areas are characterized by a variety of disorders that may present to the otolaryngologist, and hence the importance of understanding the role played by the KF in maintaining normal function.

Brain Stimulation in Alzheimer's Disease.

PubMed

Chang, Chun-Hung; Lane, Hsien-Yuan; Lin, Chieh-Hsin

2018-01-01

Brain stimulation techniques can modulate cognitive functions in many neuropsychiatric diseases. Pilot studies have shown promising effects of brain stimulations on Alzheimer's disease (AD). Brain stimulations can be categorized into non-invasive brain stimulation (NIBS) and invasive brain stimulation (IBS). IBS includes deep brain stimulation (DBS), and invasive vagus nerve stimulation (VNS), whereas NIBS includes transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), electroconvulsive treatment (ECT), magnetic seizure therapy (MST), cranial electrostimulation (CES), and non-invasive VNS. We reviewed the cutting-edge research on these brain stimulation techniques and discussed their therapeutic effects on AD. Both IBS and NIBS may have potential to be developed as novel treatments for AD; however, mixed findings may result from different study designs, patients selection, population, or samples sizes. Therefore, the efficacy of NIBS and IBS in AD remains uncertain, and needs to be further investigated. Moreover, more standardized study designs with larger sample sizes and longitudinal follow-up are warranted for establishing a structural guide for future studies and clinical application.

Extralaryngeal branching of the recurrent laryngeal nerve: a meta-analysis of 28,387 nerves.

PubMed

Henry, Brandon Michael; Vikse, Jens; Graves, Matthew J; Sanna, Silvia; Sanna, Beatrice; Tomaszewska, Iwona M; Tubbs, R Shane; Tomaszewski, Krzysztof A

2016-11-01

The recurrent laryngeal nerves (RLN) are branches of the vagus nerve that go on to innervate most of the intrinsic muscles of the larynx. Historically, the RLN has been considered to branch after it enters the larynx, but numerous studies have demonstrated that it often branches before. The wide variability of this extralaryngeal branching (ELB) has significant implications for the risk of iatrogenic injury. We aimed to assess the anatomical characteristics of ELB comprehensively. Articles on the ELB of the RLN were identified by a comprehensive database search. Relevant data were extracted and pooled into a meta-analysis of the prevalence of branching, branching pattern, distance of ELB point from the larynx, and presence of positive motor signals in anterior and posterior ELB branches. A total of 69 articles (n = 28,387 nerves) from both intraoperative and cadaveric modalities were included in the meta-analysis. The overall pooled prevalence of ELB was 60.0 % (95 % CI 52.0-67.7). Cadaveric and intraoperative subgroups differed with prevalence rates of 73.3 % (95 % CI 61.0-84.0) and 39.2 % (95 % CI 29.0-49.9), respectively. Cadavers most often presented with a ELB pattern of bifurcation, with a prevalence of 61.1 %, followed by no branching at 23.4 %. Branching of the RLN occurred most often at a distance of 1-2 cm (74.8 % of cases) prior to entering the larynx. A positive motor signal was most often noted in anterior RLN branches (99.9 %) but only in 1.5 % of posterior branches. The anatomy of the RLN is highly variable, and ELB is likely to have been underreported in intraoperative studies. Because of its high likelihood, the possibility of ELB needs to be assessed in patients to prevent iatrogenic injury and long-term postoperative complications.

Evaluation of Insecticides Susceptibility and Malaria Vector Potential of Anopheles annularis s.l. and Anopheles vagus in Assam, India

PubMed Central

Dhiman, Sunil; Yadav, Kavita; Rabha, Bipul; Goswami, Diganta; Hazarika, S.; Tyagi, Varun

2016-01-01

During the recent past, development of DDT resistance and reduction to pyrethroid susceptibility among the malaria vectors has posed a serious challenge in many Southeast Asian countries including India. Current study presents the insecticide susceptibility and knock-down data of field collected Anopheles annularis sensu lato and An. vagus mosquito species from endemic areas of Assam in northeast India. Anopheles annularis s.l. and An. vagus adult females were collected from four randomly selected sentinel sites in Orang primary health centre (OPHC) and Balipara primary health centre (BPHC) areas, and used for testing susceptibility to DDT, malathion, deltamethrin and lambda-cyhalothrin. After insecticide susceptibility tests, mosquitoes were subjected to VectorTest™ assay kits to detect the presence of malaria sporozoite in the mosquitoes. An. annularis s.l. was completely susceptible to deltamethrin, lambda-cyhalothrin and malathion in both the study areas. An. vagus was highly susceptible to deltamethrin in both the areas, but exhibited reduced susceptibility to lambda-cyhalothrin in BPHC. Both the species were resistant to DDT and showed very high KDT50 and KDT99 values for DDT. Probit model used to calculate the KDT50 and KDT99 values did not display normal distribution of percent knock-down with time for malathion in both the mosquito species in OPHC (p<0.05) and An. vagus in BPHC (χ2 = 25.3; p = 0.0), and also for deltamethrin to An. vagus in BPHC area (χ2 = 15.4; p = 0.004). Minimum infection rate (MIR) of Plasmodium sporozoite for An. vagus was 0.56 in OPHC and 0.13 in BPHC, while for An. annularis MIR was found to be 0.22 in OPHC. Resistance management strategies should be identified to delay the expansion of resistance. Testing of field caught Anopheles vectors from different endemic areas for the presence of malaria sporozoite may be useful to ensure their role in malaria transmission. PMID:27010649

Intraoperative monitoring of lower cranial nerves in skull base surgery: technical report and review of 123 monitored cases.

PubMed

Topsakal, Cahide; Al-Mefty, Ossama; Bulsara, Ketan R; Williford, Veronica S

2008-01-01

The fundamental goal of skull base surgery is tumor removal with preservation of neurological function. Injury to the lower cranial nerves (LCN; CN 9-12) profoundly affects a patient's quality of life. Although intraoperative cranial nerve monitoring (IOM) is widely practiced for other cranial nerves, literature addressing the LCN is scant. We examined the utility of IOM of the LCN in a large patient series. One hundred twelve patients underwent 123 skull base operations with IOM between January 1994 to December 1999. The vagus nerve (n=37), spinal accessory nerve (n=118), and the hypoglossal nerve (n=83) were monitored intraoperatively. Electromyography (EMG) and compound muscle action potentials (CMAP) were recorded from the relevant muscles after electrical stimulation. This data was evaluated retrospectively. Patients who underwent IOM tended to have larger tumors with more intricate involvement of the lower cranial nerves. Worsening of preoperative lower cranial nerve function was seen in the monitored and unmonitored groups. With the use of IOM in the high risk group, LCN injury was reduced to a rate equivalent to that of the lower risk group (p>0.05). The immediate feedback obtained with IOM may prevent injury to the LCN due to surgical manipulation. It can also help identify the course of a nerve in patients with severely distorted anatomy. These factors may facilitate gross total tumor resection with cranial nerve preservation. The incidence of high false positive and negative CMAP and the variability in CMAP amplitude and threshold can vary depending on individual and technical factors.

Spraguea (Microsporida: Spraguidae) infections in the nervous system of the Japanese anglerfish, Lophius litulon (Jordan), with comments on transmission routes and host pathology.

PubMed

Freeman, M A; Yokoyama, H; Osada, A; Yoshida, T; Yamanobe, A; Ogawa, K

2011-06-01

Anglerfish from the genus Lophius are a globally important commercial fishery. The microsporidian Spraguea infects the nervous system of these fish resulting in the formation of large, visible parasitic xenomas. Lophius litulon from Japan were investigated to evaluate the intensity and distribution of Spraguea xenomas throughout the nervous system and to assess pathogenicity to the host and possible transmission routes of the parasite. Spraguea infections in L. litulon had a high prevalence; all fish over 403 mm in standard length being infected, with larger fish usually more heavily infected than smaller fish. Seventy percent of all fish examined had some gross visible sign of infection. The initial site of development is the supramedullary cells on the dorsal surface of the medulla oblongata, where all infected fish have parasitic xenomas. As the disease progresses, a number of secondary sites typically become infected such as the spinal, trigeminal and vagus nerves. Fish with infection in the vagus nerve bundles often have simultaneous sites of infection, in particular the spinal nerves and along the ventral nerve towards the urinary bladder. Advanced vagus nerve infections sometimes form xenomas adjacent to kidney tissue. Spraguea DNA was amplified from the contents of the urinary bladders of two fish, suggesting that microsporidian spores may be excreted in the urine. We conclude that supramedullary cells on the hindbrain are the primary site of infection, which is probably initiated at the cutaneous mucous glands where supramedullary cells are known to extend their peripheral axons. The prevalence of Spraguea infections in L. litulon was very high, and infections often extremely heavy; however, no associated pathogenicity was observed, and heavily infected fish were otherwise normal. © 2011 Blackwell Publishing Ltd.

Auricular acupuncture and biomedical research--A promising Sino-Austrian research cooperation.

PubMed

Rong, Pei-Jing; Zhao, Jing-Jun; Li, Yu-Qing; Litscher, Daniela; Li, Shao-yuan; Gaischek, Ingrid; Zhai, Xu; Wang, Lu; Luo, Man; Litscher, Gerhard

2015-12-01

Treatment by auricular acupuncture has a long history. Ear-acupoint research has been advancing step by step in China and also in Europe. Auricles are rich in nerves, therefore a close relationship with different functions of the human body has been proved by the research teams of the two main authors of this article from China and Austria. In recent years, great progress has been made in the research of regulating human body functions through electroacupuncture at the auricular branch of the vagus nerve, which is part of auricular acupuncture therapy. It is well known that the auricular branch of the vagus nerve is the only peripheral pathway to the cerebral cortex. Studies of the Chinese team on hypertension, diabetes, epilepsy and depression have shown that the mechanism of auricular vagus nerve stimulation (VNS) may be comparable with cervical VNS in terms of pathways. Auricular VNS has a broad clinical application prospect.

Combination of bypassing stomach and vagus dissection in high-fat diet-induced obese rats-a long-term investigation.

PubMed

Wang, Yong; Liu, Jingang

2010-03-01

Gastric bypass is the most popular technique in obesity therapy. We hypothesize that bypass surgery can help to control the body weight in morbid obesity, and this effect can be enhanced by vagus dissection. Thirty-six Wistar rats were used in this investigation. They were randomly allocated into six groups. Rats in the gastric bypass group (GB1 and GB2) and the bypass with vagus dissection group (VD1 and VD2) received surgery. Rats in the control group (CO1 and CO2) received sham operation. Twenty days later, rats in the CO1, GB1, and VD1 groups were killed and data on body weights, food intakes, fasting glucose, plasma ghrelin and leptin levels, and GHS-R1a and leptin receptor protein expression in the hypothalamus were collected and summarized. One hundred days later, rats in the CO2, GB2, and VD2 groups were also killed and the same experiments were repeated. Body weights of rats were 258 +/- 4.2 and 232 +/- 2.4 g in the GB1 and VD1 groups, respectively, much lower than the CO1 group (303 +/- 6.9 g). Body weights of rats were 316 +/- 12.3 and 315 +/- 10.3 g in the GB2 and VD2 groups, respectively, much lower than the CO2 group. Food intake in the VD1 group was lower than in the GB1 group, while there were no statistical differences between the VD2 and GB2 groups. Fasting glucose in the GB1 and GB2 groups was much lower than the CO1 and CO2 groups. Plasma ghrelin concentrations were much lower in the GB1 and VD1 groups compared to the CO1 group. One hundred days after surgery, the ghrelin concentrations in the GB2 and VD2 groups were also much lower than the CO2 group. Leptin concentrations decreased significantly with weight loss after bypass surgery. GHS-R1a protein expression in the hypothalamus was much lower in the GB1 and VD1 groups compared to the CO1 group. GHS-R1a protein expressions in the GB2 and VD2 groups were lower than the CO2 group. There were no statistical differences in leptin receptor expression in the hypothalamus (not shown). Vagus nerve

Electromechanical Nerve Stimulator

NASA Technical Reports Server (NTRS)

Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

1993-01-01

Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

Gastrointestinal Dysfunctions in Parkinson's Disease: Symptoms and Treatments

PubMed Central

Aubé, Benoit; Côté, Mélissa; Morin, Nicolas; Di Paolo, Thérèse

2016-01-01

A diagnosis of Parkinson's disease is classically established after the manifestation of motor symptoms such as rigidity, bradykinesia, and tremor. However, a growing body of evidence supports the hypothesis that nonmotor symptoms, especially gastrointestinal dysfunctions, could be considered as early biomarkers since they are ubiquitously found among confirmed patients and occur much earlier than their motor manifestations. According to Braak's hypothesis, the disease is postulated to originate in the intestine and then spread to the brain via the vagus nerve, a phenomenon that would involve other neuronal types than the well-established dopaminergic population. It has therefore been proposed that peripheral nondopaminergic impairments might precede the alteration of dopaminergic neurons in the central nervous system and, ultimately, the emergence of motor symptoms. Considering the growing interest in the gut-brain axis in Parkinson's disease, this review aims at providing a comprehensive picture of the multiple gastrointestinal features of the disease, along with the therapeutic approaches used to reduce their burden. Moreover, we highlight the importance of gastrointestinal symptoms with respect to the patients' responses towards medical treatments and discuss the various possible adverse interactions that can potentially occur, which are still poorly understood. PMID:28050310

Use of tripolar electrodes for minimization of current spread in uncut peripheral nerve stimulation.

PubMed

Ohsawa, Ichiro; Inui, Koji

2009-05-01

The electrical stimulation of an uncut peripheral nerve requires a countermeasure to avoid the spread of current through a loop pathway formed outside the electrode array. Here the use of tripolar electrodes (TE) is proposed. By binding the two end poles, current spread through the loop pathway can theoretically be eliminated since both end poles are held equipotential. Experimentally, we tested the validity of this approach. In chloralose-urethane anesthetized rats, the left cervical vagus (LCV) was placed on TE which could function as such or as bipolar electrodes (BE) by the use of a selector switch. The spread of current to the adjacent tissues (rectus capitis muscle underlying the LCV, and the right cervical vagus (RCV) incised and translocated beside the target, LCV) was compared between TE and BE. When the stimulus intensity was increased, contraction occurred in the capitis muscle with BE, but not TE. Compound spike potentials of A fiber origin were evoked in the non-target RCV on high-intensity stimulation with BE, but not TE. Constant voltage stimulation of the LCV with TE produced bradycardia of the same magnitude as that with BE. In conclusion, constant voltage stimulation using TE can minimize current spread without changing the stimulus's effects.

Artificial voice modulation in dogs by recurrent laryngeal nerve stimulation: electrophysiological confirmation of anatomic data.

PubMed

Broniatowski, Michael; Grundfest-Broniatowski, Sharon; Tucker, Harvey M; Tyler, Dustin J

2007-02-01

We hypothesized that voice may be artificially manipulated to ameliorate dystonias considered to be a failure in dynamic integration between competing neuromuscular systems. Orderly intrinsic laryngeal muscle recruitment by anodal block via the recurrent laryngeal and vagus nerves has allowed us to define specific values based on differential excitabilities, but has precluded voice fluency because of focused breaks during stimulation and the need to treat several neural conduits. Such problems may be obviated by a circuit capable of stimulating some axons while simultaneously blocking others in the recurrent laryngeal nerve, which carries innervation to all intrinsic laryngeal muscles, including the arguably intrinsic cricothyroideus. In 5 dogs, both recurrent laryngeal nerves received 40-Hz quasi-trapezoidal pulses (0 to 2000 microA, 0 to 2000 micros, 0 to 500 micros decay) via tripolar electrodes. Electromyograms were matched with audio intensities and fundamental frequencies recorded under a constant flow of humidified air. Data were digitized and evaluated for potential correlations. Orderly recruitment of the thyroarytenoideus, posterior cricoarytenoideus, and cricothyroideus was correlated with stimulating intensities (p < .001), and posterior cricoarytenoideus opposition to the thyroarytenoideus and cricothyroideus was instrumental in manipulating audio intensities and fundamental frequencies. Manipulation of canine voice parameters appears feasible via the sole recurrent laryngeal nerve within appropriate stimulation envelopes, and offers promise in human laryngeal dystonias.

Nerve ultrasound shows subclinical peripheral nerve involvement in neurofibromatosis type 2.

PubMed

Telleman, Johan A; Stellingwerff, Menno D; Brekelmans, Geert J; Visser, Leo H

2018-02-01

Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce. We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings. HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018. © 2017 Wiley Periodicals, Inc.

Association of Vagotomy and Decreased Risk of Subsequent Ischemic Stroke in Complicated Peptic Ulcer Patients: an Asian Population Study.

PubMed

Fang, Chu-Wen; Tseng, Chun-Hung; Wu, Shih-Chi; Chen, William Tzu-Liang; Muo, Chih-Hsin

2017-12-01

The primary management of peptic ulcers is medical treatment. Persistent exacerbation of a peptic ulcer may lead to complications (perforation and/or bleeding). There has been a trend toward the use of a less invasive surgical simple suture, simple local suture or non-operative (endoscopic/angiography) hemostasis rather than acid-reducing vagotomy (i.e., vagus nerve severance) for treating complicated peptic ulcers. Other studies have shown the relationship between high vagus nerve activity and survival in cancer patients via reduced levels of inflammation, indicating the essential role of the vagus nerve. We were interested in the role of the vagus nerve and attempted to assess the long-term systemic effects after vagus nerve severance. Complicated peptic ulcer patients who underwent truncal vagotomy may represent an appropriate study population for investigating the association between vagus nerve severance and long-term effects. Therefore, we assessed the risks of subsequent ischemic stroke using different treatment methods in complicated peptic ulcer patients who underwent simple suture/hemostasis or truncal vagotomy/pyloroplasty. We selected 299,742 peptic ulcer patients without a history of stroke and Helicobacter pylori infection and an additional 299,742 matched controls without ulcer, stroke, and Helicobacter pylori infection from the National Health Insurance database. The controls were frequency matched for age, gender, Charlson comorbidity index (CCI) score, hypertension, hyperlipidemia history, and index year. Then, we measured the incidence of overall ischemic stroke in the two cohorts. The hazard ratio (HR) and the 95% confidence intervals (CIs) were estimated by Cox proportional hazard regression. Compared to the controls, peptic ulcer patients had a 1.86-fold higher risk of ischemic stroke. There were similar results in gender, age, CCI, hypertension, and hyperlipidemia stratified analyses. In complicated peptic ulcer patients, those who received

Neurostimulation for Drug-Resistant Epilepsy

PubMed Central

DeGiorgio, Christopher M.; Krahl, Scott E.

2013-01-01

Purpose of Review: The purpose of this review is to provide an evidence-based update on the neurostimulation options available for patients with drug-resistant epilepsy in the United States and in European countries. Recent Findings: The field of neurostimulation for epilepsy has grown dramatically since 1997, when vagus nerve stimulation became the first device to be approved for epilepsy by the US Food and Drug Administration (FDA). New data from recently completed randomized controlled trials are available for deep brain stimulation of the anterior thalamus, responsive neurostimulation, and trigeminal nerve stimulation. Although vagus nerve stimulation is the only device currently approved in the United States, deep brain stimulation and responsive neurostimulation devices are awaiting FDA approval. Deep brain stimulation, trigeminal nerve stimulation, and transcutaneous vagus nerve stimulation are now approved for epilepsy in the European Union. In this article, the mechanisms of action, safety, and efficacy of new neurostimulation devices are reviewed, and the key advantages and disadvantages of each are discussed. Summary: The exponential growth of the field of neuromodulation for epilepsy is an exciting development; these new devices provide physicians with new options for patients with drug-resistant epilepsy. PMID:23739108

Reliability, reference values and predictor variables of the ulnar sensory nerve in disease free adults.

PubMed

Ruediger, T M; Allison, S C; Moore, J M; Wainner, R S

2014-09-01

The purposes of this descriptive and exploratory study were to examine electrophysiological measures of ulnar sensory nerve function in disease free adults to determine reliability, determine reference values computed with appropriate statistical methods, and examine predictive ability of anthropometric variables. Antidromic sensory nerve conduction studies of the ulnar nerve using surface electrodes were performed on 100 volunteers. Reference values were computed from optimally transformed data. Reliability was computed from 30 subjects. Multiple linear regression models were constructed from four predictor variables. Reliability was greater than 0.85 for all paired measures. Responses were elicited in all subjects; reference values for sensory nerve action potential (SNAP) amplitude from above elbow stimulation are 3.3 μV and decrement across-elbow less than 46%. No single predictor variable accounted for more than 15% of the variance in the response. Electrophysiologic measures of the ulnar sensory nerve are reliable. Absent SNAP responses are inconsistent with disease free individuals. Reference values recommended in this report are based on appropriate transformations of non-normally distributed data. No strong statistical model of prediction could be derived from the limited set of predictor variables. Reliability analyses combined with relatively low level of measurement error suggest that ulnar sensory reference values may be used with confidence. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Cannabinoids suppress synaptic input to neurones of the rat dorsal motor nucleus of the vagus nerve

PubMed Central

Derbenev, Andrei V; Stuart, Thomas C; Smith, Bret N

2004-01-01

Cannabinoids bind central type 1 receptors (CB1R) and modify autonomic functions, including feeding and anti-emetic behaviours, when administered peripherally or into the dorsal vagal complex. Western blots and immunohistochemistry indicated the expression of CB1R in the rat dorsal vagal complex, and tissue polymerase chain reaction confirmed that CB1R message was made within the region. To identify a cellular substrate for the central autonomic effects of cannabinoids, whole-cell patch-clamp recordings were made in brainstem slices to determine the effects of CB1R activation on synaptic transmission to neurones of the dorsal motor nucleus of the vagus (DMV). A subset of these neurones was identified as gastric related after being labelled retrogradely from the stomach. The CB1R agonists WIN55,212-2 and anandamide decreased the frequency of spontaneous excitatory or inhibitory postsynaptic currents in a concentration-related fashion, an effect that persisted in the presence of tetrodotoxin. Paired pulse ratios of electrically evoked postsynaptic currents were also increased by WIN55,212-2. The effects of WIN55,212-2 were sensitive to the selective CB1R antagonist AM251. Cannabinoid agonist effects on synaptic input originating from neurones in the nucleus tractus solitarius (NTS) were determined by evoking activity in the NTS with local glutamate application. Excitatory and inhibitory synaptic inputs arising from the NTS were attenuated by WIN55,212-2. Our results indicate that cannabinoids inhibit transfer of synaptic information to the DMV, including that arising from the NTS, in part by acting at receptors located on presynaptic terminals contacting DMV neurones. Inhibition of synaptic input to DMV neurones is likely to contribute to the suppression of visceral motor responses by cannabinoids. PMID:15272041

Neurological Complications in Thyroid Surgery: A Surgical Point of View on Laryngeal Nerves

PubMed Central

Varaldo, Emanuela; Ansaldo, Gian Luca; Mascherini, Matteo; Cafiero, Ferdinando; Minuto, Michele N.

2014-01-01

The cervical branches of the vagus nerve that are pertinent to endocrine surgery are the superior and the inferior laryngeal nerves: their anatomical course in the neck places them at risk during thyroid surgery. The external branch of the superior laryngeal nerve (EB) is at risk during thyroid surgery because of its close anatomical relationship with the superior thyroid vessels and the superior thyroid pole region. The rate of EB injury (which leads to the paralysis of the cricothyroid muscle) varies from 0 to 58%. The identification of the EB during surgery helps avoiding both an accidental transection and an excessive stretching. When the nerve is not identified, the ligation of superior thyroid artery branches close to the thyroid gland is suggested, as well as the abstention from an indiscriminate use of energy-based devices that might damage it. The inferior laryngeal nerve (RLN) runs in the tracheoesophageal groove toward the larynx, close to the posterior aspect of the thyroid. It is the main motor nerve of the intrinsic laryngeal muscles, and also provides sensory innervation to the larynx. Its injury finally causes the paralysis of the omolateral vocal cord and various sensory alterations: the symptoms range from mild to severe hoarseness, to acute airway obstruction, and swallowing impairment. Permanent lesions of the RNL occur from 0.3 to 7% of cases, according to different factors. The surgeon must be aware of the possible anatomical variations of the nerve, which should be actively searched for and identified. Visual control and gentle dissection of RLN are imperative. The use of intraoperative nerve monitoring has been safely applied but, at the moment, its impact in the incidence of RLN injuries has not been clarified. In conclusion, despite a thorough surgical technique and the use of intraoperative neuromonitoring, the incidence of neurological complications after thyroid surgery cannot be suppressed, but should be maintained in a low range. PMID

Neurostimulation of the Cholinergic Anti-Inflammatory Pathway Ameliorates Disease in Rat Collagen-Induced Arthritis

PubMed Central

Levine, Yaakov A.; Koopman, Frieda A.; Faltys, Michael; Caravaca, April; Bendele, Alison; Zitnik, Ralph; Vervoordeldonk, Margriet J.; Tak, Paul Peter

2014-01-01

Introduction The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferent arm, termed the cholinergic anti-inflammatory pathway. To explore this, we determined whether electrical neurostimulation of the cholinergic anti-inflammatory pathway reduced disease severity in the collagen-induced arthritis model. Methods Rats implanted with vagus nerve cuff electrodes had collagen-induced arthritis induced and were followed for 15 days. Animals underwent active or sham electrical stimulation once daily from day 9 through the conclusion of the study. Joint swelling, histology, and levels of cytokines and bone metabolism mediators were assessed. Results Compared with sham treatment, active neurostimulation of the cholinergic anti-inflammatory pathway resulted in a 52% reduction in ankle diameter (p = 0.02), a 57% reduction in ankle diameter (area under curve; p = 0.02) and 46% reduction overall histological arthritis score (p = 0.01) with significant improvements in inflammation, pannus formation, cartilage destruction, and bone erosion (p = 0.02), accompanied by numerical reductions in systemic cytokine levels, not reaching statistical significance. Bone erosion improvement was associated with a decrease in serum levels of receptor activator of NF-κB ligand (RANKL) from 132±13 to 6±2 pg/mL (mean±SEM, p = 0.01). Conclusions The severity of collagen-induced arthritis is reduced by neurostimulation of the cholinergic anti-inflammatory pathway delivered using an implanted electrical vagus nerve stimulation cuff electrode, and supports the rationale for testing this approach in human inflammatory disorders. PMID:25110981

The cholinergic anti-inflammatory pathway revisited.

PubMed

Murray, K; Reardon, C

2018-03-01

Inflammatory bowel disease negatively affects the quality of life of millions of patients around the world. Although the precise etiology of the disease remains elusive, aberrant immune system activation is an underlying cause. As such, therapies that selectively inhibit immune cell activation without broad immunosuppression are desired. Inhibition of immune cell activation preventing pro-inflammatory cytokine production through neural stimulation has emerged as one such treatment. These therapeutics are based on the discovery of the cholinergic anti-inflammatory pathway, a reflex arc that induces efferent vagal nerve signaling to reduce immune cell activation and consequently mortality during septic shock. Despite the success of preclinical and clinical trials, the neural circuitry and mechanisms of action of these immune-regulatory circuits are controversial. At the heart of this controversy is the protective effect of vagal nerve stimulation despite an apparent lack of neuroanatomical connections between the vagus and target organs. Additional studies have further emphasized the importance of sympathetic innervation of these organs, and that alternative neural circuits could be involved in neural regulation of the immune system. Such controversies also extend to the regulation of intestinal inflammation, with the importance of efferent vagus nerve signals in question. Experiments that better characterize these pathways have now been performed by Willemze et al. in this issue of Neurogastroenterology & Motility. These continued efforts will be critical to the development of better neurostimulator based therapeutics for inflammatory bowel disease. © 2018 John Wiley & Sons Ltd.

Vagus nerve is involved in the changes in body temperature induced by intragastric administration of 1,8-cineole via TRPM8 in mice.

PubMed

Urata, Tomomi; Mori, Noriyuki; Fukuwatari, Tsutomu

2017-05-22

Transient Receptor Potential Melastatin 8 (TRPM8) is a cold receptor activated by mild cold temperature (<28°C). TRPM8 expressed in cutaneous sensory nerves is involved in cold sensation and thermoregulation. TRPM8 mRNA is detected in various tissues, including the gastrointestinal mucosa, and in the vagal afferent nerve. The relationship between vagal afferent nerve-specific expression of TRPM8 and thermoregulation remains unclear. In this study, we aimed to investigate whether TRPM8 expression in the vagal afferent nerve is involved in autonomic thermoregulation. We found that intragastric administration of 1,8-cineole, a TRPM8 agonist, increased intrascapular brown adipose tissue and colonic temperatures, and M8-B-treatment (TRPM8 antagonist) inhibited these responses. Intravenous administration of 1,8-cineole also showed similar effects. In vagotomized mice, the responses induced by intragastric administration of 1,8-cineole were attenuated. These results suggest that TRPM8 expressed in tissues apart from cutaneous sensory nerves are involved in autonomic thermoregulation response. Copyright © 2017 Elsevier B.V. All rights reserved.

A pediatric case with peripheral facial nerve palsy caused by a granulomatous lesion associated with cat scratch disease.

PubMed

Nakamura, Chizuko; Inaba, Yuji; Tsukahara, Keiko; Mochizuki, Mie; Sawanobori, Emi; Nakazawa, Yozo; Aoyama, Kouki

2018-02-01

Cat scratch disease is a common infectious disorder caused by Bartonella henselae that is transmitted primarily by kittens. It typically exhibits a benign and self-limiting course of subacute regional lymphadenopathy and fever lasting two to eight weeks. The most severe complication of cat scratch disease is involvement of the nervous system, such as encephalitis, meningitis, and polyneuritis. Peripheral facial nerve palsy associated with Bartonella infection is rare; few reported pediatric and adult cases exist and the precise pathogenesis is unknown. A previously healthy 7-year-old boy presented with fever, cervical lymphadenopathy, and peripheral facial nerve palsy associated with serologically confirmed cat scratch disease. The stapedius muscle reflex was absent on the left side and brain magnetic resonance imaging revealed a mass lesion at the left internal auditory meatus. The patient's symptoms and imaging findings were gradually resolved after the antibiotics and corticosteroids treatment. The suspected granulomatous lesion was considered to have resulted from the host's immune reaction to Bartonella infection and impaired the facial nerve. This is the first case report providing direct evidence of peripheral facial nerve palsy caused by a suspected granulomatous lesion associated with cat scratch disease and its treatment course. Copyright © 2017. Published by Elsevier B.V.

The effect of transcutaneous electrical nerve stimulation in patients with acute exacerbation of chronic obstructive pulmonary disease: randomised controlled trial.

PubMed

Öncü, Emine; Zincir, Handan

2017-07-01

The aim of the present study was to assess the efficacy of transcutaneous electrical nerve stimulation in patients with acute exacerbation of chronic obstructive pulmonary disease. In patients with stable chronic obstructive pulmonary disease, transcutaneous electrical nerve stimulation has been known to attain improvement in forced expiratory volume in 1 seconds, physical activity, and quality of life. However, information about the effects of transcutaneous electrical nerve stimulation on acute exacerbation of chronic obstructive pulmonary disease is quite limited. A single-blind, randomised controlled trial. Data were collected between August 2013-May 2014. Eighty-two patients who were hospitalised with a diagnosis of acute exacerbation of chronic obstructive pulmonary disease were randomly assigned to a transcutaneous electrical nerve stimulation group receiving transcutaneous electrical nerve stimulation treatment for 20 seance over the acupuncture points with pharmacotherapy or placebo group receiving the same treatment without electrical current output from the transcutaneous electrical nerve stimulation device. Pulmonary functional test, six-minute walking distance, dyspnoea and fatigue scale, and St. George's Respiratory Questionnaire scores were assessed pre- and postprogram. The program started at the hospital by the researcher was sustained in the patient's home by the caregiver. All patients were able to complete the program, despite the exacerbation. The 20 seance transcutaneous electrical nerve stimulation program provided clinically significant improvement in forced expiratory volume in 1 seconds 21 ml, 19·51% but when compared with the placebo group, the difference was insignificant (p > 0·05). The six-minute walking distance increased by 48·10 m more in the placebo group (p < 0·05). There were no significant differences between the two groups' St. George's Respiratory Questionnaire, dyspnoea and fatigue score (p > 0·05). Adding

Tibial nerve (image)

MedlinePlus

... nerve is commonly injured by fractures or other injury to the back of the knee or the lower leg. It may be affected by systemic diseases such as diabetes mellitus. The nerve can also be damaged by pressure from a tumor, abscess, or bleeding into the ...

Release of “neurokinin” on nervous and electrical stimulation of a frog stomach muscle preparation

PubMed Central

Singh, I.

1964-01-01

Activation of a frog stomach muscle preparation by electrical stimulation of a vagus nerve or by direct stimulation released two polypeptides. One was destroyed by trypsin or chymotrypsin in about 10 min; the activity of the other was enhanced by trypsin for about 10 min, but was destroyed by chymotrypsin. Similar stimulation of dog stomach muscle did not release these polypeptides. Correspondingly, the transmission from vagus nerve to stomach muscle in the frog was resistant to atropine, but was blocked by atropine in the dog. PMID:14190475

Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

PubMed

Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno

2014-01-01

Crohn's disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

Relationship between Vagal Tone, Cortisol, TNF-Alpha, Epinephrine and Negative Affects in Crohn’s Disease and Irritable Bowel Syndrome

PubMed Central

Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno

2014-01-01

Crohn’s disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8∶00 AM and 10∶00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r = −0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r = −0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases. PMID

High genetic connectivity among estuarine populations of the riverbream Acanthopagrus vagus along the southern African coast

NASA Astrophysics Data System (ADS)

Oosthuizen, Carel J.; Cowley, Paul D.; Kyle, Scotty R.; Bloomer, Paulette

2016-12-01

Physical and/or physiological constraints are assumed to isolate fish populations confined to or dependent on estuarine habitats. Strong isolation by distance is thus expected to affect connectivity. Such structuring has important implications for sustainable utilisation and replenishment of estuarine stocks that are heavily exploited. Here we present a preliminary investigation of the phylogenetic relationships of the riverbream (Acanthopagrus species) along the southern African coast and the geographic genetic structure of what appears to be a locally endemic species or lineage. Mitochondrial DNA (mtDNA) cytochrome b sequences support the notion that the species occurring along the southern African coast is A. vagus and not A. berda as previously thought. Yet, the taxonomy of this widespread Indo-West Pacific species or species-complex requires more in-depth investigation. No genetic differentiation was detected among estuarine populations of A. vagus based on the analyses of mtDNA ND2 gene sequences and 10 polymorphic nuclear microsatellite markers. The star-like genealogy and statistical analyses are consistent with a recent population expansion event. Spatial analyses of microsatellite genotypes fail to reject the null hypothesis of panmixia, indicative of a recent population expansion or ongoing gene flow between different estuaries. The northern localities were identified as containing most of the observed variation. This study not only provides insight into the phylogenetic relationship of A. vagus relative to other Acanthopagrus species but also sheds light on the demographic history and contemporary gene flow of the species.

The Non-Recurrent Laryngeal Nerve: a meta-analysis and clinical considerations

PubMed Central

Sanna, Silvia; Graves, Matthew J.; Vikse, Jens; Sanna, Beatrice; Tomaszewska, Iwona M.; Tubbs, R. Shane; Walocha, Jerzy A.; Tomaszewski, Krzysztof A.

2017-01-01

Background The Non-Recurrent Laryngeal Nerve (NRLN) is a rare embryologically-derived variant of the Recurrent Laryngeal Nerve (RLN). The presence of an NRLN significantly increases the risk of iatrogenic injury and operative complications. Our aim was to provide a comprehensive meta-analysis of the overall prevalence of the NRLN, its origin, and its association with an aberrant subclavian artery. Methods Through March 2016, a database search was performed of PubMed, CNKI, ScienceDirect, EMBASE, BIOSIS, SciELO, and Web of Science. The references in the included articles were also extensively searched. At least two reviewers judged eligibility and assessed and extracted articles. MetaXL was used for analysis, with all pooled prevalence rates calculated using a random effects model. Heterogeneity among the included studies was assessed using the Chi2 test and the I2 statistic. Results Fifty-three studies (33,571 right RLNs) reported data on the prevalence of a right NRLN. The pooled prevalence estimate was 0.7% (95% CI [0.6–0.9]). The NRLN was found to originate from the vagus nerve at or above the laryngotracheal junction in 58.3% and below it in 41.7%. A right NRLN was associated with an aberrant subclavian artery in 86.7% of cases. Conclusion The NRLN is a rare yet very clinically relevant structure for surgeons and is associated with increased risk of iatrogenic injury, most often leading to temporary or permanent vocal cord paralysis. A thorough understanding of the prevalence, origin, and associated pathologies is vital for preventing injuries and complications. PMID:28344898

Unilateral or bilateral vagotomy induces ovulation in both ovaries of rats with polycystic ovarian syndrome.

PubMed

Linares, Rosa; Hernández, Denisse; Morán, Carolina; Chavira, Roberto; Cárdenas, Mario; Domínguez, Roberto; Morales-Ledesma, Leticia

2013-07-17

Injecting estradiol valerate (EV) to pre-pubertal or adult female rat results in effects similar to those observed in women with polycystic ovarian syndrome (PCOS). One of the mechanisms involved in PCOS development is the hyperactivity of the sympathetic nervous system. In EV-induced PCOS rats, the unilateral sectioning of the superior ovarian nerve (SON) restores ovulation of the innervated ovary. This suggests that, in addition to the sympathetic innervation, other neural mechanisms are involved in the development/maintenance of PCOS. The aims of present study were analyze if the vagus nerve is one of the neural pathways participating in PCOS development. Ten-day old rats were injected with EV dissolved in corn oil. At 24-days of age sham-surgery, unilateral, or bilateral sectioning of the vagus nerve (vagotomy) was performed on these rats. The animals were sacrificed at 90-92 days of age, when they presented vaginal estrous preceded by a pro-estrus smear. In EV-induced PCOS rats, unilateral or bilateral vagotomy restored ovulation in both ovaries. Follicle-stimulating hormone (FSH) levels in PCOS rats with unilateral or bilateral vagotomy were lower than in control rats. This result suggests that in EV-induced PCOS rats the vagus nerve is a neural pathway participating in maintaining PCOS. The vagus nerve innervates the ovaries directly and indirectly through its synapsis in the celiac-superior-mesenteric ganglion, where the somas of neurons originating in the SON are located. Then, it is possible that vagotomy effects in EV-induced PCOS rats may be explained as a lack of communication between the central nervous system and the ovaries.

Routine exposure of recurrent laryngeal nerve in thyroid surgery can prevent nerve injury.

PubMed

Shen, Chenling; Xiang, Mingliang; Wu, Hao; Ma, Yan; Chen, Li; Cheng, Lan

2013-06-15

To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients undergoing thyroidectomy. Among these cases, 548 underwent dissection of the recurrent laryngeal nerve, while 4 796 did not. There were 12 cases of recurrent laryngeal nerve injury following recurrent laryngeal nerve dissection (injury rate of 2.2%) and 512 cases of recurrent laryngeal nerve injury in those not undergoing nerve dissection (injury rate of 10.7%). This difference remained statistically significant between the two groups in terms of type of thyroid disease, type of surgery, and number of surgeries. Among the 548 cases undergoing recurrent laryngeal nerve dissection, 128 developed anatomical variations of the recurrent laryngeal nerve (incidence rate of 23.4%), but no recurrent laryngeal nerve injury was found. In addition, the incidence of recurrent laryngeal nerve injury was significantly lower in patients with the inferior parathyroid gland and middle thyroid veins used as landmarks for locating the recurrent laryngeal nerve compared with those with the entry of the recurrent laryngeal nerve into the larynx as a landmark. These findings indicate that anatomical variations of the recurrent laryngeal nerve are common, and that dissecting the recurrent laryngeal nerve during thyroid surgery is an effective means of preventing nerve injury.

Routine exposure of recurrent laryngeal nerve in thyroid surgery can prevent nerve injury★

PubMed Central

Shen, Chenling; Xiang, Mingliang; Wu, Hao; Ma, Yan; Chen, Li; Cheng, Lan

2013-01-01

To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients undergoing thyroidectomy. Among these cases, 548 underwent dissection of the recurrent laryngeal nerve, while 4 796 did not. There were 12 cases of recurrent laryngeal nerve injury following recurrent laryngeal nerve dissection (injury rate of 2.2%) and 512 cases of recurrent laryngeal nerve injury in those not undergoing nerve dissection (injury rate of 10.7%). This difference remained statistically significant between the two groups in terms of type of thyroid disease, type of surgery, and number of surgeries. Among the 548 cases undergoing recurrent laryngeal nerve dissection, 128 developed anatomical variations of the recurrent laryngeal nerve (incidence rate of 23.4%), but no recurrent laryngeal nerve injury was found. In addition, the incidence of recurrent laryngeal nerve injury was significantly lower in patients with the inferior parathyroid gland and middle thyroid veins used as landmarks for locating the recurrent laryngeal nerve compared with those with the entry of the recurrent laryngeal nerve into the larynx as a landmark. These findings indicate that anatomical variations of the recurrent laryngeal nerve are common, and that dissecting the recurrent laryngeal nerve during thyroid surgery is an effective means of preventing nerve injury. PMID:25206452

Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia

PubMed Central

Pavlov, Valentin A.; Ochani, Mahendar; Gallowitsch-Puerta, Margot; Ochani, Kanta; Huston, Jared M.; Czura, Christopher J.; Al-Abed, Yousef; Tracey, Kevin J.

2006-01-01

TNF has a critical mediator role in inflammation and is an important therapeutic target. We recently discovered that TNF production is regulated by neural signals through the vagus nerve. Activation of this “cholinergic antiinflammatory pathway” inhibits the production of TNF and other cytokines and protects animals from the inflammatory damage caused by endotoxemia and severe sepsis. Here, we describe a role for central muscarinic acetylcholine receptors in the activation of the cholinergic antiinflammatory pathway. Central muscarinic cholinergic activation by muscarine, the M1 receptor agonist McN-A-343, and the M2 receptor antagonist methoctramine inhibited serum TNF levels significantly during endotoxemia. Centrally administered methoctramine stimulated vagus-nerve activity measured by changes in instantaneous heart-rate variability. Blockade of peripheral muscarinic receptors did not abolish antiinflammatory signaling through the vagus nerve, indicating that peripheral muscarinic receptors on immune cells are not required for the cytokine-regulating activities of the cholinergic antiinflammatory pathway. The role of central muscarinic receptors in activating the cholinergic antiinflammatory pathway is of interest for the use of centrally acting muscarinic cholinergic enhancers as antiinflammatory agents. PMID:16549778

Experimental studies of gastric dysfunction in motion sickness: The effect of gastric and vestibular stimulation on the vagal and splanchnic gastric efferents

NASA Technical Reports Server (NTRS)

Niijima, A.; Jiang, Z. Y.; Daunton, Nancy G.; Fox, Robert A.

1991-01-01

The experiments were conducted in anaesthetized rats. In the first part of the experiments, the effect of CuSO4 on the afferent activity in the gastric branch of the vagus nerve was investigated. Gastric perfusion of CuSO4 solution (0.04 percent and 0.08 percent) provoked an increase in afferent activity. In the second part of the experiments, the reflex effects of gastric perfusion of CuSO4 solution, repetitive stimulation of the gastric vagus nerve, and caloric stimulation of the right vestibular apparatus (5-18 C water) on gastric autonomic outflow were investigated. The results of these experiments showed that these three different types of stimulation caused an inhibition in efferent activity of the gastric vagus nerve and a slight activation of the splanchnic gastric efferents. The summation of the effect of each stimulation was also observed. These results, therefore, provide evidence for a possible integrative inhibitory function of the vagal gastric center as well as an excitatory function of gastric sympathetic motoneurons in relation to motion sickness.

Vagal activity is quadratically related to prosocial traits, prosocial emotions, and observer perceptions of prosociality.

PubMed

Kogan, Aleksandr; Oveis, Christopher; Carr, Evan W; Gruber, June; Mauss, Iris B; Shallcross, Amanda; Impett, Emily A; van der Lowe, Ilmo; Hui, Bryant; Cheng, Cecilia; Keltner, Dacher

2014-12-01

In the present article, we introduce the quadratic vagal activity-prosociality hypothesis, a theoretical framework for understanding the vagus nerve's involvement in prosociality. We argue that vagus nerve activity supports prosocial behavior by regulating physiological systems that enable emotional expression, empathy for others' mental and emotional states, the regulation of one's own distress, and the experience of positive emotions. However, we contend that extremely high levels of vagal activity can be detrimental to prosociality. We present 3 studies providing support for our model, finding consistent evidence of a quadratic relationship between respiratory sinus arrhythmia--the degree to which the vagus nerve modulates the heart rate--and prosociality. Individual differences in vagal activity were quadratically related to prosocial traits (Study 1), prosocial emotions (Study 2), and outside ratings of prosociality by complete strangers (Study 3). Thus, too much or too little vagal activity appears to be detrimental to prosociality. The present article provides the 1st theoretical and empirical account of the nonlinear relationship between vagal activity and prosociality.

[Application of pylorus-vagus-preserving gastrectomy in early gastric cancer in middle third of stomach].

PubMed

Hu, Junfeng; Shao, Qinshu; Sun, Yuanshui; Xu, Xiaodong; Xu, Ji

2015-04-14

To evaluate the long-term outcomes of pylorus-vagus-preserving partial gastrectomy for early gastric cancer in middle third of stomach. Between January 2004 and June 2009, 46 patients with early gastric cancer in middle third of stomach underwent pylorus-vagus-preserving partial gastrectomy (PPG) while another 85 patients had conventional distal gastrectomy (DG). Clinicopathologic data and follow-up results of two groups were analyzed retrospectively, including the results of subjective nutritional assessments, laboratory blood biochemical data, endoscopic findings of remnant stomach and total 5-year survival rates. Postprandial dumping syndrome occurred in 7 patients (8.2%) in DG group while no syndrome occurred in PPG group. The incidence of gallbladder stones at 18 months after operation in DG group was higher than that in PPG group. Significant difference existed between two groups (P<0.05). Even though no significant difference existed in laboratory blood biochemical data and endoscopic findings, PPG group recovered better and regurgitation was frequently found in DG group. Food residue in gastric remnant was frequently observed in PPG (31.1%) than in DG (10.8%, P<0.05) by endoscopic findings. At 2 years post-operation, the postoperative 5-year recurrence rate was 6.5% (2/46) in PPG group versus 8.2% (7/85) in DG group. However no significant difference existed between 2 groups (P=0.724). No significant difference existed between PPG group (91.3%) and DG group (90.6%) in overall 5-year survival rate. For early gastric cancer in middle third of stomach, pylorus-vagus-preserving partial gastrectomy is effective in maintaining postoperative function. And it has the same postoperative survival rate as conventional distal gastrectomy.

Efficacy and safety of nerve growth factor for the treatment of neurological diseases: a meta-analysis of 64 randomized controlled trials involving 6,297 patients

PubMed Central

Zhao, Meng; Li, Xiao-yan; Xu, Chun-ying; Zou, Li-ping

2015-01-01

OBJECTIVE: China is the only country where nerve growth factor is approved for large-scale use as a clinical medicine. More than 10 years ago, in 2003, nerve growth factor injection was listed as a national drug. The goal of this article is to evaluate comprehensively the efficacy and safety of nerve growth factor for the treatment of neurological diseases. DATA RETRIEVAL: A computer-based retrieval was performed from six databases, including the Cochrane Library, PubMed, EMBASE, Sino Med, CNKI, and the VIP database, searching from the clinical establishment of nerve growth factor for treatment until December 31, 2013. The key words for the searches were “nerve growth factor, randomized controlled trials” in Chinese and in English. DATA SELECTION: Inclusion criteria: any study published in English or Chinese referring to randomized controlled trials of nerve growth factor; patients with neurological diseases such as peripheral nerve injury, central nerve injury, cranial neuropathy, and nervous system infections; patients older than 7 years; similar research methods and outcomes assessing symptoms; and measurement of nerve conduction velocities. The meta-analysis was conducted using Review Manager 5.2.3 software. MAIN OUTCOME MEASURES: The total effective rate, the incidence of adverse effects, and the nerve conduction velocity were recorded for each study. RESULTS: Sixty-four studies involving 6,297 patients with neurological diseases were included. The total effective rate in the group treated with nerve growth factor was significantly higher than that in the control group (P < 0.0001, RR: 1.35, 95%CI: 1.30–1.40). The average nerve conduction velocity in the nerve growth factor group was significantly higher than that in the control group (P < 0.00001, MD: 4.59 m/s, 95%CI: 4.12–5.06). The incidence of pain or scleroma at the injection site in the nerve growth factor group was also higher than that in the control group (P < 0.00001, RR: 6.30, 95%CI: 3.53�

Imaging acetylcholinesterase density in peripheral organs in Parkinson's disease with 11C-donepezil PET.

PubMed

Gjerløff, Trine; Fedorova, Tatyana; Knudsen, Karoline; Munk, Ole L; Nahimi, Adjmal; Jacobsen, Steen; Danielsen, Erik H; Terkelsen, Astrid J; Hansen, John; Pavese, Nicola; Brooks, David J; Borghammer, Per

2015-03-01

Parkinson's disease is associated with early parasympathetic dysfunction leading to constipation and gastroparesis. It has been suggested that pathological α-synuclein aggregations originate in the gut and ascend to the brainstem via the vagus. Our understanding of the pathogenesis and time course of parasympathetic denervation in Parkinson's disease is limited and would benefit from a validated imaging technique to visualize the integrity of parasympathetic function. The positron emission tomography tracer 5-[(11)C]-methoxy-donepezil was recently validated for imaging acetylcholinesterase density in the brain and peripheral organs. Donepezil is a high-affinity ligand for acetylcholinesterase-the enzyme that catabolizes acetylcholine in cholinergic synapses. Acetylcholinesterase histology has been used for many years for visualizing cholinergic neurons. Using 5-[(11)C]-methoxy-donepezil positron emission tomography, we studied 12 patients with early-to-moderate Parkinson's disease (three female; age 64 ± 9 years) and 12 age-matched control subjects (three female; age 62 ± 8 years). We collected clinical information about motor severity, constipation, gastroparesis, and other parameters. Heart rate variability measurements and gastric emptying scintigraphies were performed in all subjects to obtain objective measures of parasympathetic function. We detected significantly decreased (11)C-donepezil binding in the small intestine (-35%; P = 0.003) and pancreas (-22%; P = 0.001) of the patients. No correlations were found between the (11)C-donepezil signal and disease duration, severity of constipation, gastric emptying time, and heart rate variability. In Parkinson's disease, the dorsal motor nucleus of the vagus undergoes severe degeneration and pathological α-synuclein aggregations are also seen in nerve fibres innervating the gastro-intestinal tract. In contrast, the enteric nervous system displays little or no loss of cholinergic neurons. Decreases in (11)C

The central projections of the laryngeal nerves in the rat

PubMed Central

Pascual-Font, Arán; Hernández-Morato, Ignacio; McHanwell, Stephen; Vázquez, Teresa; Maranillo, Eva; Sañudo, Jose; Valderrama-Canales, Francisco J

2011-01-01

The larynx serves respiratory, protective, and phonatory functions. The motor and sensory innervation to the larynx controlling these functions is provided by the superior laryngeal nerve (SLN) and the recurrent laryngeal nerve (RLN). Classical studies state that the SLN innervates the cricothyroid muscle and provides sensory innervation to the supraglottic cavity, whereas the RLN supplies motor innervation to the remaining intrinsic laryngeal muscles and sensory innervation to the infraglottic cavity, but recent data suggest a more complex anatomical and functional organisation. The current neuroanatomical tracing study was undertaken to provide a comprehensive description of the central brainstem connections of the axons within the SLN and the RLN, including those neurons that innervate the larynx. The study has been carried out in 41 adult male Sprague–Dawley rats. The central projections of the laryngeal nerves were labelled following application of biotinylated dextran amines onto the SLN, the RLN or both. The most remarkable result of the study is that in the rat the RLN does not contain any afferent axons from the larynx, in contrast to the pattern observed in many other species including man. The RLN supplied only special visceromotor innervation to the intrinsic muscles of the larynx from motoneurons in the nucleus ambiguus (Amb). All the afferent axons innervating the larynx are contained within the SLN, and reach the nucleus of the solitary tract. The SLN also contained secretomotor efferents originating from motoneurons in the dorsal motor nucleus of the vagus, and special visceral efferent fibres from the Amb. In conclusion, the present study shows that in the rat the innervation of the larynx differs in significant ways from that described in other species. PMID:21599662

Recent advances in nerve tissue engineering.

PubMed

Zhang, Bill G X; Quigley, Anita F; Myers, Damian E; Wallace, Gordon G; Kapsa, Robert M I; Choong, Peter F M

2014-04-01

Nerve injury secondary to trauma, neurological disease or tumor excision presents a challenge for surgical reconstruction. Current practice for nerve repair involves autologous nerve transplantation, which is associated with significant donor-site morbidity and other complications. Previously artificial nerve conduits made from polycaprolactone, polyglycolic acid and collagen were approved by the FDA (USA) for nerve repair. More recently, there have been significant advances in nerve conduit design that better address the requirements of nerve regrowth. Innovations in materials science, nanotechnology, and biology open the way for the synthesis of new generation nerve repair conduits that address issues currently faced in nerve repair and regeneration. This review discusses recent innovations in this area, including the use of nanotechnology to improve the design of nerve conduits and to enhance nerve regeneration.

Mixed evidence for the potential of non-invasive transcutaneous vagal nerve stimulation to improve the extinction and retention of fear.

PubMed

Burger, A M; Verkuil, B; Fenlon, H; Thijs, L; Cools, L; Miller, H C; Vervliet, B; Van Diest, I

2017-10-01

Extinction memories are fragile and their formation has been proposed to partially rely on vagus nerve activity. We tested whether stimulating the auricular branch of the vagus (transcutaneous VNS; tVNS) accelerates extinction and reduces spontaneous recovery of fear. Forty-two healthy students participated in a 3-day fear conditioning study, where we tested fear acquisition (day 1), fear extinction (day 2) and the retention of the extinction memory (day 3). During extinction, participants were randomly allocated to receive tVNS or sham stimulation concurrently with each CS presentation. During the acquisition and retention phases, all participants received sham stimulation. Indexes of fear included US-expectancy, startle blink EMG and skin conductance responses. Results showed successful acquisition and extinction of fear in all measures. tVNS facilitated the extinction of declarative fear (US expectancy ratings), but did not promote a stronger retention of the declarative extinction memory. No clear effects of tVNS on extinction and retention of extinction were found for the psychophysiological indexes. The present findings provide tentative indications that tVNS could be a promising tool to improve fear extinction and call for larger scale studies to replicate these effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies

ClinicalTrials.gov

2018-03-21

Congenital Fibrosis of Extraocular Muscles; Duane Retraction Syndrome; Duane Radial Ray Syndrome; Mobius Syndrome; Brown Syndrome; Marcus Gunn Syndrome; Strabismus Congenital; Horizontal Gaze Palsy; Horizontal Gaze Palsy With Progressive Scoliosis; Facial Palsy; Facial Paresis, Hereditary, Congenital; Third Nerve Palsy; Fourth Nerve Palsy; Sixth Nerve Palsy; Synkinesis; Ocular Motility Disorders; Levator-Medial Rectus Synkinesis; Athabaskan Brainstem Dysgenesis; Tongue Paralysis; Ninth Nerve Disorder; Fifth Nerve Palsy; Seventh Nerve Palsy; Eleventh Nerve Disorder; Twelfth Nerve Disorder; Vagus Nerve Paralysis; Moebius Sequence

Vagal-immune interactions involved in cholinergic anti-inflammatory pathway.

PubMed

Zila, I; Mokra, D; Kopincova, J; Kolomaznik, M; Javorka, M; Calkovska, A

2017-09-22

Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-alpha and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.

Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

PubMed Central

Bravo, Javier A.; Forsythe, Paul; Chew, Marianne V.; Escaravage, Emily; Savignac, Hélène M.; Dinan, Timothy G.; Bienenstock, John; Cryan, John F.

2011-01-01

There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABAB1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut–brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression. PMID:21876150

[Facial nerve neurinomas].

PubMed

Sokołowski, Jacek; Bartoszewicz, Robert; Morawski, Krzysztof; Jamróz, Barbara; Niemczyk, Kazimierz

2013-01-01

Evaluation of diagnostic, surgical technique, treatment results facial nerve neurinomas and its comparison with literature was the main purpose of this study. Seven cases of patients (2005-2011) with facial nerve schwannomas were included to retrospective analysis in the Department of Otolaryngology, Medical University of Warsaw. All patients were assessed with history of the disease, physical examination, hearing tests, computed tomography and/or magnetic resonance imaging, electronystagmography. Cases were observed in the direction of potential complications and recurrences. Neurinoma of the facial nerve occurred in the vertical segment (n=2), facial nerve geniculum (n=1) and the internal auditory canal (n=4). The symptoms observed in patients were analyzed: facial nerve paresis (n=3), hearing loss (n=2), dizziness (n=1). Magnetic resonance imaging and computed tomography allowed to confirm the presence of the tumor and to assess its staging. Schwannoma of the facial nerve has been surgically removed using the middle fossa approach (n=5) and by antromastoidectomy (n=2). Anatomical continuity of the facial nerve was achieved in 3 cases. In the twelve months after surgery, facial nerve paresis was rated at level II-III° HB. There was no recurrence of the tumor in radiological observation. Facial nerve neurinoma is a rare tumor. Currently surgical techniques allow in most cases, the radical removing of the lesion and reconstruction of the VII nerve function. The rate of recurrence is low. A tumor of the facial nerve should be considered in the differential diagnosis of nerve VII paresis. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Pilot Study of Optical Coherence Tomography Measurement of Retinal Blood Flow in Retinal and Optic Nerve Diseases

PubMed Central

Wang, Yimin; Fawzi, Amani A.; Varma, Rohit; Sadun, Alfredo A.; Zhang, Xinbo; Tan, Ou; Izatt, Joseph A.

2011-01-01

Purpose. To investigate blood flow changes in retinal and optic nerve diseases with Doppler Fourier domain optical coherence tomography (OCT). Methods. Sixty-two participants were divided into five groups: normal, glaucoma, nonarteritic ischemic optic neuropathy (NAION), treated proliferative diabetic retinopathy (PDR), and branch retinal vein occlusion (BRVO). Doppler OCT was used to scan concentric circles of 3.4- and 3.75-mm diameters around the optic nerve head. Flow in retinal veins was calculated from the OCT velocity profiles. Arterial and venous diameters were measured from OCT Doppler and reflectance images. Results. Total retinal blood flow in normal subjects averaged 47.6 μL/min. The coefficient of variation of repeated measurements was 11% in normal eyes and 14% in diseased eyes. Eyes with glaucoma, NAION, treated PDR, and BRVO had significantly decreased retinal blood flow compared with normal eyes (P < 0.001). In glaucoma patients, the decrease in blood flow was highly correlated with the severity of visual field loss (P = 0.003). In NAION and BRVO patients, the hemisphere with more severe disease also had lower blood flow. Conclusions. Doppler OCT retinal blood flow measurements showed good repeatability and excellent correlation with visual field and clinical presentations. This approach could enhance our understanding of retinal and optic nerve diseases and facilitate the development of new therapies. PMID:21051715

Extrinsic nerves are not involved in branchial 5-HT dynamics or pulsatile urea excretion in Gulf toadfish, Opsanus beta.

PubMed

Cartolano, Maria C; Amador, Molly H B; Tzaneva, Velislava; Milsom, William K; McDonald, M Danielle

2017-12-01

Gulf toadfish (Opsanus beta) can switch from continuously excreting ammonia as their primary nitrogenous waste to excreting predominantly urea in distinct pulses. Previous studies have shown that the neurotransmitter serotonin (5-HT) is involved in controlling this process, but it is unknown if 5-HT availability is under central nervous control or if the 5-HT signal originates from a peripheral source. Following up on a previous study, cranial nerves IX (glossopharyngeal) and X (vagus) were sectioned to further characterize their role in controlling pulsatile urea excretion and 5-HT release within the gill. In contrast to an earlier study, nerve sectioning did not result in a change in urea pulse frequency. Total urea excretion, average pulse size, total nitrogen excretion, and percent ureotely were reduced the first day post-surgery in nerve-sectioned fish but recovered by 72h post-surgery. Nerve sectioning also had no effect on toadfish urea transporter (tUT), 5-HT transporter (SERT), or 5-HT 2A receptor mRNA expression or 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) abundance in the gill, all of which were found consistently across the three gill arches except 5-HIAA, which was undetectable in the first gill arch. Our findings indicate that the central nervous system does not directly control pulsatile urea excretion or local changes in gill 5-HT and 5-HIAA abundance. Copyright © 2017 Elsevier Inc. All rights reserved.

Cutaneous Surgical Denervation: A Method for Testing the Requirement for Nerves in Mouse Models of Skin Disease.

PubMed

Peterson, Shelby C; Brownell, Isaac; Wong, Sunny Y

2016-06-26

Cutaneous somatosensory nerves function to detect diverse stimuli that act upon the skin. In addition to their established sensory roles, recent studies have suggested that nerves may also modulate skin disorders including atopic dermatitis, psoriasis and cancer. Here, we describe protocols for testing the requirement for nerves in maintaining a cutaneous mechanosensory organ, the touch dome (TD). Specifically, we discuss methods for genetically labeling, harvesting and visualizing TDs by whole-mount staining, and for performing unilateral surgical denervation on mouse dorsal back skin. Together, these approaches can be used to directly compare TD morphology and gene expression in denervated as well as sham-operated skin from the same animal. These methods can also be readily adapted to examine the requirement for nerves in mouse models of skin pathology. Finally, the ability to repeatedly sample the skin provides an opportunity to monitor disease progression at different stages and times after initiation.

Localization and expression of ciliary neurotrophic factor (CNTF) in postmortem sciatic nerve from patients with motor neuron disease and diabetic neuropathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, D.A.; Gross, L.; Wittrock, D.A.

1996-08-01

Ciliary neurotrophic factor (CNTF) is thought to play an important role in the maintenance of the mature motor system. The factor is found most abundantly in myelinating Schwann cells in the adult sciatic nerve. Lack of neuronal growth factors has been proposed as one possible etiology of amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Growth factor replacement therapies are currently being evaluated as a treatment for motor neuron disease. In this report we determined whether the expression of CNTF in sciatic nerve differed in patients with motor neuron disease compared to controls or patients with another form ofmore » axonopathy. We identified 8 patients (7 with ALS and 1 with SMA) with motor neuron disease and 6 patients with diabetic motor neuropathy who had autopsy material available. Immunoperoxidase staining showed reduced CNTF expression in nerves of patients with motor neuron disease but not in patients with diabetic motor neuropathy. Decreased CNTF appears be associated with primary motor neuron disease rather than a generalized process of axon loss. This result supports suggestions that CNTF deficiency may be an important factor in the development of motor neuron disease. 20 refs., 4 figs., 1 tab.« less

Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy.

PubMed

Willemze, Rose A; Luyer, Misha D; Buurman, Wim A; de Jonge, Wouter J

2015-06-01

Studies in neuroscience and immunology have clarified much of the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. As with other organs, intestinal immune responses and the development of immunity seems to be modulated by neural reflexes. Sympathetic immune modulation and reflexes are well described, and in the past decade the parasympathetic efferent vagus nerve has been added to this immune-regulation network. This system, designated 'the inflammatory reflex', comprises an afferent arm that senses inflammation and an efferent arm that inhibits innate immune responses. Intervention in this system as an innovative principle is currently being tested in pioneering trials of vagus nerve stimulation using implantable devices to treat IBD. Patients benefit from this treatment, but some of the working mechanisms remain to be established, for instance, treatment is effective despite the vagus nerve not always directly innervating the inflamed tissue. In this Review, we will focus on the direct neuronal regulatory mechanisms of immunity in the intestine, taking into account current advances regarding the innervation of the spleen and lymphoid organs, with a focus on the potential for treatment in IBD and other gastrointestinal pathologies.

Endogenous acetylcholine increases alveolar epithelial fluid transport via activation of alveolar epithelial Na,K-ATPase in mice.

PubMed

Li, Xia; Yan, Xi Xin; Li, Hong Lin; Li, Rong Qin

2015-10-01

The contribution of endogenous acetylcholine to alveolar fluid clearance (AFC) and related molecular mechanisms were explored. AFC was measured in Balb/c mice after vagotomy and vagus nerve stimulation. Effects of acetylcholine chloride on AFC in Kunming mice and Na,K-ATPase function in A549 alveolar epithelial cells also were determined. AFC significantly decreased in mice with left cervical vagus nerve transection compared with controls (48.69 ± 2.57 vs. 66.88 ± 2.64, P ≤ 0.01), which was reversed by stimulation of the peripheral (60.81 ± 1.96, P ≤ 0.01). Compared with control, acetylcholine chloride dose-dependently increased AFC and elevated Na,K-ATPase activity, and these increases were blocked or reversed by atropine. These effects were accompanied by recruitment of Na,K-ATPase α1 to the cell membrane. Thus, vagus nerves participate in alveolar epithelial fluid transport by releasing endogenous acetylcholine in the infusion-induced pulmonary edema mouse model. Effects of endogenous acetylcholine on AFC are likely mediated by Na,K-ATPase function through activation of muscarinic acetylcholine receptors on alveolar epithelia. Copyright © 2015 Elsevier B.V. All rights reserved.

Epilepsy

PubMed Central

Saipetch, Chutima; Sachs, Ezekiel

2016-01-01

Abstract Purpose of review: Technological advance has revolutionized epilepsy management recently. Herein, we review some recent developments. Recent findings: Responsive neurostimulation (Food and Drug Administration [FDA]-approved 2013) works by continuous analysis of brain rhythms and direct brain stimulation on detecting patterns thought to be epileptogenic, thereby aborting seizures. Cardio-responsive vagus nerve stimulation (FDA-approved 2015) is an improvement over traditional vagus nerve stimulation systems, taking advantage of the fact that 80% of seizures are associated with tachycardia. Automated tachycardia detection leads to vagus nerve stimulation to abort seizures. In MRI-guided stereotactic laser ablation (developed 2012), a directed laser emitting fiberoptic catheter is used to ablate epileptogenic lesions. The procedure can be completed in 3 to 4 hours, potentially under local anesthesia and with next-day discharge. Perampanel (FDA-approved 2012) is a promising new class of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-antagonist antiseizure therapy. Meanwhile, a millennia-old remedy for epilepsy, cannabis, is staging a comeback with recent legal and social permissiveness accelerating research into this use. Summary: The coming years will demonstrate how these recent advances in device and drug management will improve the care of epilepsy. PMID:29443283

Conditioned taste aversion induced by motion is prevented by selective vagotomy in the rat

NASA Technical Reports Server (NTRS)

Fox, Robert A.; Mckenna, Susan

1991-01-01

The role of the vagus nerve in motion-induced conditioned taste aversion (CTA) was studied in hooded rats. Animals with complete, selective gastric vagotomy failed to form conditioned taste aversion after multiple conditioning sessions in which the conditioned stimulus (a cider vinegar solution) was drunk immediately before a 30-min exposure to vertical axis rotation at 150 deg/s. Results are discussed with reference to the use of CTA as a measure of motion-induced 'sickness' or gastrointestinal disturbance, and because motion-induced CTA requires that both the vagus nerve and the vestibular apparatus be intact, in light of the possible convergence of vegal and vestibular functions.

Recurrent laryngeal nerve landmarks during thyroidectomy.

PubMed

Ngo Nyeki, A-R; Njock, L-R; Miloundja, J; Evehe Vokwely, J-E; Bengono, G

2015-11-01

This study was designed to describe the various anatomical relations of the recurrent laryngeal nerve (RLN) during thyroid surgery in a Central African population. A prospective study was conducted between January 2012 and December 2012 in 5 otorhinolaryngology and head and neck surgery departments in Cameroon and Gabon. All patients undergoing total or subtotal thyroidectomy or loboisthmectomy with recurrent laryngeal nerve dissection, with no history of previous thyroid surgery, RLN dissection or tumour infiltration of the RLN, were included. Fifty-six patients were included, corresponding to 36 loboisthmectomies and 20 total or subtotal thyroidectomies. A total of 62 recurrent laryngeal nerves were identified: 32 on the right and 30 on the left. The course of the recurrent laryngeal nerve in relation to branches of the inferior thyroid artery (ITA) was retrovascular in 53.1% of cases on the right and 76.6% of cases on the left; transvascular in 15.6% of cases on the right and 13.4% of cases on the left. The course of the recurrent laryngeal nerve was modified by thyroid disease in 12.9% of cases. Six cases (9.7%) of extralaryngeal division of the recurrent laryngeal nerve were observed. No case of non-recurrent nerve was observed in this series. The anatomical relations of the recurrent laryngeal nerve with the inferior thyroid artery were very inconstant in this series and were predominantly retrovascular or transvascular in relation to the branches of the artery. The presence of extralaryngeal branches and modification of the course of the nerve by thyroid disease also introduced additional difficulties during recurrent laryngeal nerve dissection. The anatomical relations of the right recurrent laryngeal nerve in this African population differ from the classically described prevascular course. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

PubMed Central

Ayala-Caminero, Radamés; Pinzón-Herrera, Luis; Martinez, Carol A. Rivera; Almodovar, Jorge

2018-01-01

Understanding peripheral nerve repair requires the evaluation of 3D structures that serve as platforms for 3D cell culture. Multiple platforms for 3D cell culture have been developed, mimicking peripheral nerve growth and function, in order to study tissue repair or diseases. To recreate an appropriate 3D environment for peripheral nerve cells, key factors are to be considered including: selection of cells, polymeric biomaterials to be used, and fabrication techniques to shape and form the 3D scaffolds for cellular culture. This review focuses on polymeric 3D platforms used for the development of 3D peripheral nerve cell cultures. PMID:29515936

Renal sympathetic nerve ablation for treatment-resistant hypertension

PubMed Central

Krum, Henry; Schlaich, Markus; Sobotka, Paul

2013-01-01

Hypertension is a major risk factor for increased cardiovascular events with accelerated sympathetic nerve activity implicated in the pathogenesis and progression of disease. Blood pressure is not adequately controlled in many patients, despite the availability of effective pharmacotherapy. Novel procedure- as well as device-based strategies, such as percutaneous renal sympathetic nerve denervation, have been developed to improve blood pressure in these refractory patients. Renal sympathetic denervation not only reduces blood pressure but also renal as well as systemic sympathetic nerve activity in such patients. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which suggests absence of re-innervation of renal sympathetic nerves. Safety appears to be adequate. This approach may also have potential in other disorders associated with enhanced sympathetic nerve activity such as congestive heart failure, chronic kidney disease and metabolic syndrome. This review will focus on the current status of percutaneous renal sympathetic nerve denervation, clinical efficacy and safety outcomes and prospects beyond refractory hypertension. PMID:23819768

Blockade of hyperpolarization-activated channels modifies the effect of beta-adrenoceptor stimulation.

PubMed

Zefirov, T L; Ziyatdinova, N I; Gainullin, A A; Zefirov, A L

2002-05-01

Experiments on rats showed that blockade of hyperpolarization-activated currents moderates tachycardia induced by beta-adrenoceptor agonist isoproterenol and potentiates the increase in stroke volume produced by this agonist. Electrical stimulation of the vagus nerve against the background of isoproterenol treatment augmented bradycardia and increased stroke volume. Blockade of hyperpolarization-activated currents followed by application of isoproterenol moderated vagus-induced bradycardia and had no effect on the dynamics of stroke volume.

[Surgical treatment in otogenic facial nerve palsy].

PubMed

Feng, Guo-Dong; Gao, Zhi-Qiang; Zhai, Meng-Yao; Lü, Wei; Qi, Fang; Jiang, Hong; Zha, Yang; Shen, Peng

2008-06-01

To study the character of facial nerve palsy due to four different auris diseases including chronic otitis media, Hunt syndrome, tumor and physical or chemical factors, and to discuss the principles of the surgical management of otogenic facial nerve palsy. The clinical characters of 24 patients with otogenic facial nerve palsy because of the four different auris diseases were retrospectively analyzed, all the cases were performed surgical management from October 1991 to March 2007. Facial nerve function was evaluated with House-Brackmann (HB) grading system. The 24 patients including 10 males and 14 females were analysis, of whom 12 cases due to cholesteatoma, 3 cases due to chronic otitis media, 3 cases due to Hunt syndrome, 2 cases resulted from acute otitis media, 2 cases due to physical or chemical factors and 2 cases due to tumor. All cases were treated with operations included facial nerve decompression, lesion resection with facial nerve decompression and lesion resection without facial nerve decompression, 1 patient's facial nerve was resected because of the tumor. According to HB grade system, I degree recovery was attained in 4 cases, while II degree in 10 cases, III degree in 6 cases, IV degree in 2 cases, V degree in 2 cases and VI degree in 1 case. Removing the lesions completely was the basic factor to the surgery of otogenic facial palsy, moreover, it was important to have facial nerve decompression soon after lesion removal.

Simultaneous central retinal artery occlusion and optic nerve vasculitis in Crohn disease.

PubMed

Coussa, Razek Georges; Ali-Ridha, Andre; Vila, Natalia; Alshareef, Rayan; Chen, John

2017-04-01

To describe a case of Crohn disease presenting as occlusive vasculitis resulting in a central retinal artery occlusion (CRAO) in one eye and transient ischemic optic neuropathy in the fellow eye. An 18-year-old patient recently diagnosed with biopsy-proven Crohn disease presented with CRAO OD after a previous episode of transient visual loss OS. Extensive workup was negative for other autoimmune or infectious etiologies. The patient was started on intravenous methylprednisolone for 72 h followed by maintenance dose of azathioprine and oral prednisone. Signs of inflammation resolved gradually with some improvement of visual acuity despite developing optic atrophy. To our knowledge, this is the first case of unilateral CRAO and bilateral optic nerve occlusive vasculitis in Crohn disease, which should be considered as an etiology of retinal vascular occlusive disorders especially in young patients. It is important for ophthalmologists to be aware of the ophthalmic risks associated with Crohn disease as aggressive treatment with systemic steroids and immunosuppressive agents is often needed.

CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study.

PubMed

Kraus, Thomas; Kiess, Olga; Hösl, Katharina; Terekhin, Pavel; Kornhuber, Johannes; Forster, Clemens

2013-09-01

limbic structures and the brain stem during electrical stimulation of the left anterior auditory canal. BOLD signal decreases in the area of the nuclei of the vagus nerve may indicate an effective stimulation of vagal afferences. In contrast, stimulation at the posterior wall seems to lead to unspecific changes of the BOLD signal within the solitary tract, which is a key relay station of vagal neurotransmission. The results of the study show promise for a specific novel method of cranial nerve stimulation and provide a basis for further developments and applications of non-invasive transcutaneous vagus stimulation in psychiatric patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Optic Nerve Lymphoma. Report of Two Cases and Review of the Literature

PubMed Central

Kim, Jennifer L.; Mendoza, Pia; Rashid, Alia; Hayek, Brent; Grossniklaus, Hans E.

2014-01-01

Lymphoma may involve the optic nerve as isolated optic nerve lymphoma or in association with CNS or systemic lymphoma. We present two biopsy-proven non-Hodgkin lymphomas of the optic nerve and compare our findings with previously reported cases. We discuss the mechanism of metastasis, classification of optic nerve involvement, clinical features, radiologic findings, optic nerve biopsy indications and techniques, histologic features, and treatments. We propose a classification system of optic nerve lymphoma: isolated optic nerve involvement, optic nerve involvement with CNS disease, optic nerve involvement with systemic disease, and optic nerve involvement with primary intraocular lymphoma. Although it is an uncommon cause of infiltrative optic neuropathy, optic nerve metastasis should be considered in patients with a history of lymphoma. The recommended approach to a patient with presumed optic nerve lymphoma includes neuroimaging, and cerebrospinal fluid evaluation as part of the initial work-up, then judicious use of optic nerve biopsy, depending on the clinical situation. PMID:25595061

The first radiographic image of a peripheral nerve disorder? Lipomatous macrodactyly (unrecognized lipomatosis of nerve).

PubMed

Mahan, Mark A; Prasad, Nikhil; Spinner, Robert J

2015-06-01

Lipomatosis of nerves (LN) involves benign fibro-fatty infiltration and is often associated with territorial overgrowth of soft tissue and bone; this distinctive disease pattern can be visualized on plain radiographs. We recently discovered a case (presented by Sir Robert Jones in 1898 to the Pathological Society of London) that indirectly represents a historical landmark in the imaging of peripheral nerves. The clinical findings and image, with obvious soft tissue and bone overgrowth, are pathognomonic for LN, making this one of the earliest radiological observations of a peripheral nerve lesion.

[Sex difference of functional and structural alterations in the myocardium of rats with hypothyroidism].

PubMed

Khara, M R; Pavlovych, S I; Mykhaĭliuk, V M

2013-01-01

In experiments on sexually mature rats we studied specific cholinergic regulations of the heart and the degree of its structural damage in hypothyroidism, depending on gender and hormone-productive activity of the gonads. Hypothyroidism in sexually mature males and females was modelled with mercazolil intragastric administration (75 mg/kg) daily during 15 days. We also studied the intensity of bradycardia, which occurred in response to electrical stimulation of vagus nerve and intravenous acetylcholine administration. The degree of structural heart damage was assessed by the percentage of damaged cardiomyocytes in the ventricles of myocardium. It was found that one of the mechanisms of bradycardia in merkazolil-induced hypothyroidism is an increase of the sensitivity of sinus node cholinergic receptors and release of more quanta of acetylcholine from stimulated nerves vagus endings, what was more intense in females. The intensity of bradycardia in hypothyroidism was more significant in gonadectomized animals than in individuals with preserved gonads. The mechanisms of its occurrence in males consist of release of greater amount of acetylcholine from the endings of the nerves vagus, and in females it was the result of significant increase of the sensitivity of sinus node cholinergic receptors. Regardless of the gonads activity, structural damage of the myocardium in merkazolil-induced hypothyroidism was more intensive in female rats.

Afferent Nerve Regulation of Bladder Function in Health and Disease

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2012-01-01

The afferent innervation of the urinary bladder consists primarily of small myelinated (Aδ) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract. PMID:19655106

The role of nerve monitoring to predict postoperative recurrent laryngeal nerve function in thyroid and parathyroid surgery.

PubMed

Eid, Issam; Miller, Frank R; Rowan, Stephanie; Otto, Randal A

2013-10-01

To determine the role and efficacy of intraoperative recurrent laryngeal nerve (RLN) stimulation in the prediction of early and permanent postoperative nerve function in thyroid and parathyroid surgery. A retrospective review of thyroid and parathyroid surgeries was performed with calculation of sensitivity and specificity of the response of intraoperative stimulation for different pathological groups. Normal electromyography (EMG) response with 0.5 mAmp stimulation was considered a positive stimulation response with postoperative function determined by laryngoscopy. No EMG response at >1-2 mAmps was considered a negative response. The rates of early and permanent paralysis, as well as sensitivity, specificity, and positive and negative predictive values for postoperative nerve function were calculated for separate pathological groups. The number of nerves at risk analyzed was 909. The overall early and permanent paralysis rates were 3.1% and 1.2%, respectively, with the highest rate being for Grave's disease cases. The overall sensitivity was 98.4%. The specificity was lower at 62.5% but acceptable in thyroid carcinoma and Grave's disease patients. The majority of nerves with a positive stimulation result and postoperative paralysis on laryngoscopy recovered function in 3 to 12 weeks, showing positive stimulation to be a good predictor of eventual recovery. Stimulation of the RLN during thyroid and parathyroid surgery is a useful tool in predicting postoperative RLN function. The sensitivity of stimulation is high, showing positive stimulation to be an excellent predictor of normal nerve function. Negative stimulation is more predictive of paralysis in cases of thyroid carcinoma and Grave's disease. 2b. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Nerve stripper-assisted sural nerve harvest.

PubMed

Hassanpour, Esmail; Yavari, Masoud; Karbalaeikhani, Ali; Saremi, Hossein

2014-03-01

Sural nerve has the favorite length and size for nerve graft interposition. Here two techniques, that is, "stocking seam" and "stair-step" or "stepladder," have been used for harvesting sural nerve. The first technique results in an unsightly scar at the posterior calf, and the latter one takes a long time to perform and exert undue traction to the graft during harvesting. The purpose of this article is to describe our experience in harvesting the sural nerve by a nerve stripper. A nerve stripper was used for harvesting sural nerve in 35 adult patients (in 6 patients, sural harvesting was done bilaterally), 27 men and 8 women. Thirty-one sural nerve harvests were done by closed technique (i.e., harvesting of sural nerve only by two incisions, one in the posterior of the lateral malleolus and the other in popliteal fossa), in 8 others by limited open technique, and in 2 cases, there was early laceration of the sural nerve at the beginning of the study. The contralateral sural nerve was harvested in one patient and medial antebrachial nerve in another by open technique. The mean length of the retrieved sural nerve was 34.5 cm in the closed technique group and 35 cm in the limited open technique group. We detected advancing Tinel's sign in all nerve stripper-assisted sural nerve harvested group members in both the closed and limited open groups. Sural nerve harvesting by the nerve stripper is a reliable and simple technique, and it is applicable as a routine technique. Applying controlled rotatory movements of the nerve stripper instead of pushing can result in satisfactory harvesting of the sural nerve without early laceration. Georg Thieme Verlag KG Stuttgart · New York.

The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.

PubMed

van Riel, Debby; Verdijk, Rob; Kuiken, Thijs

2015-01-01

The olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (CNS). Each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. Viruses that can use the olfactory nerve as a shortcut into the CNS include influenza A virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis virus, rabies virus, parainfluenza virus, adenoviruses, Japanese encephalitis virus, West Nile virus, chikungunya virus, La Crosse virus, mouse hepatitis virus, and bunyaviruses. However, mechanisms of transport via the olfactory nerve and subsequent spread through the CNS are poorly understood. Proposed mechanisms are either infection of olfactory receptor neurons themselves or diffusion through channels formed by olfactory ensheathing cells. Subsequent virus spread through the CNS could occur by multiple mechanisms, including trans-synaptic transport and microfusion. Viral infection of the CNS can lead to damage from infection of nerve cells per se, from the immune response, or from a combination of both. Clinical consequences range from nervous dysfunction in the absence of histopathological changes to severe meningoencephalitis and neurodegenerative disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

QUANTITATIVE ASSESSMENT OF INTEGRATED PHRENIC NERVE ACTIVITY

PubMed Central

Nichols, Nicole L.; Mitchell, Gordon S.

2016-01-01

Integrated electrical activity in the phrenic nerve is commonly used to assess within-animal changes in phrenic motor output. Because of concerns regarding the consistency of nerve recordings, activity is most often expressed as a percent change from baseline values. However, absolute values of nerve activity are necessary to assess the impact of neural injury or disease on phrenic motor output. To date, no systematic evaluations of the repeatability/reliability have been made among animals when phrenic recordings are performed by an experienced investigator using standardized methods. We performed a meta-analysis of studies reporting integrated phrenic nerve activity in many rat groups by the same experienced investigator; comparisons were made during baseline and maximal chemoreceptor stimulation in 14 wild-type Harlan and 14 Taconic Sprague Dawley groups, and in 3 pre-symptomatic and 11 end-stage SOD1G93A Taconic rat groups (an ALS model). Meta-analysis results indicate: 1) consistent measurements of integrated phrenic activity in each sub-strain of wild-type rats; 2) with bilateral nerve recordings, left-to-right integrated phrenic activity ratios are ~1.0; and 3) consistently reduced activity in end-stage SOD1G93A rats. Thus, with appropriate precautions, integrated phrenic nerve activity enables robust, quantitative comparisons among nerves or experimental groups, including differences caused by neuromuscular disease. PMID:26724605

Quantitative assessment of integrated phrenic nerve activity.

PubMed

Nichols, Nicole L; Mitchell, Gordon S

2016-06-01

Integrated electrical activity in the phrenic nerve is commonly used to assess within-animal changes in phrenic motor output. Because of concerns regarding the consistency of nerve recordings, activity is most often expressed as a percent change from baseline values. However, absolute values of nerve activity are necessary to assess the impact of neural injury or disease on phrenic motor output. To date, no systematic evaluations of the repeatability/reliability have been made among animals when phrenic recordings are performed by an experienced investigator using standardized methods. We performed a meta-analysis of studies reporting integrated phrenic nerve activity in many rat groups by the same experienced investigator; comparisons were made during baseline and maximal chemoreceptor stimulation in 14 wild-type Harlan and 14 Taconic Sprague Dawley groups, and in 3 pre-symptomatic and 11 end-stage SOD1(G93A) Taconic rat groups (an ALS model). Meta-analysis results indicate: (1) consistent measurements of integrated phrenic activity in each sub-strain of wild-type rats; (2) with bilateral nerve recordings, left-to-right integrated phrenic activity ratios are ∼1.0; and (3) consistently reduced activity in end-stage SOD1(G93A) rats. Thus, with appropriate precautions, integrated phrenic nerve activity enables robust, quantitative comparisons among nerves or experimental groups, including differences caused by neuromuscular disease. Copyright © 2015 Elsevier B.V. All rights reserved.

IN VITRO RESEARCH OF THE ALTERATION OF NEURONS IN VAGAL CORE IN MEDULLA OBLONGATA AT ASPHYXIC DEATHS

PubMed Central

Haliti, Naim; Islami, Hilmi; Elezi, Nevzat; Shabani, Ragip; Abdullahu, Bedri; Dragusha, Gani

2010-01-01

The aim of this study was to research the morphological changes of neurons in the vagus nerve nuclei in medulla oblongata in asphyxia related death cases. Morphological changes that were investigated were mainly in the dorsal motor respiratory center (DMRC), nucleus tractus solitarius (nTS) and nucleus ambigus (nA) in the medulla oblongata. In our research, the autopsy material from asphyxia related death cases was used from various etiologies: monoxide carbon (CO), liquid drowning, strangulation, electricity, clinical-pathological death, firing weapon, explosive weapon, sharp and blunt objects and death cases due to accident. The material selected for research was taken from medulla oblongata and lungs from all lobes. The material from the medulla oblongata and lungs was fixed in a 10% solution of buffered formalin. Special histochemical methods for central nervous system (CNS) were employed like: Cresyl echt violet, toluidin blue, Sevier-Munger modification and Grimelius. For stereometrical analysis of the quantitative density of the neurons the universal testing system Weibel M42 was used. The acquired results show that in sudden asphyxia related death cases, there are alterations in the nuclei of vagal nerve in form of: central chromatolysis, axonal retraction, axonal fragmentation, intranuclear vacuolization, cytoplasmic vacuolization, edema, condensation and dispersion of substance of Nissl, proliferation of oligodendrocytes, astrocytes and microglia. The altered population of vagus nerve neurons does not show an important statistica! significarne compared to the overall quantity of the neurons in the nuclei of the vagus nerve (p<0,05). PMID:20846134

Improved Walking Claudication Distance with Transcutaneous Electrical Nerve Stimulation: An Old Treatment with a New Indication in Patients with Peripheral Artery Disease.

PubMed

Labrunée, Marc; Boned, Anne; Granger, Richard; Bousquet, Marc; Jordan, Christian; Richard, Lisa; Garrigues, Damien; Gremeaux, Vincent; Sénard, Jean-Michel; Pathak, Atul; Guiraud, Thibaut

2015-11-01

The aim of this study was to determine whether 45 mins of transcutaneous electrical nerve stimulation before exercise could delay pain onset and increase walking distance in peripheral artery disease patients. After a baseline assessment of the walking velocity that led to pain after 300 m, 15 peripheral artery disease patients underwent four exercise sessions in a random order. The patients had a 45-min transcutaneous electrical nerve stimulation session with different experimental conditions: 80 Hz, 10 Hz, sham (presence of electrodes without stimulation), or control with no electrodes, immediately followed by five walking bouts on a treadmill until pain occurred. The patients were allowed to rest for 10 mins between each bout and had no feedback concerning the walking distance achieved. Total walking distance was significantly different between T10, T80, sham, and control (P < 0.0003). No difference was observed between T10 and T80, but T10 was different from sham and control. Sham, T10, and T80 were all different from control (P < 0.001). There was no difference between each condition for heart rate and blood pressure. Transcutaneous electrical nerve stimulation immediately before walking can delay pain onset and increase walking distance in patients with class II peripheral artery disease, with transcutaneous electrical nerve stimulation of 10 Hz being the most effective.

[Changes in the electrical activity of the rabbit proximal colon in vivo by stimulation of the vagus and splanchnic nerves].

PubMed

Julé, Y

1975-05-01

1. Using extracellular electrodes placed on the serosa, we recorded the modifications of the electrical activity of the colonic muslce fibers caused by the stimulation of vagal and splanchnic nerve fibers. 2. Vagal stimulation produces two types of junction potentials: excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs). The IJPs are elicited by stimulation of vagal fibers which innervate intramural non-adrenergic inhibitory neurons. 3. The conduction velocity of the nerve impulse along the vagal pre-ganglionic fibers is 1.01 m/sec for excitatory fibers and 0.5. m/sec for inhibitory fibers. 4. Splanchnic fiber stimulation causes EJP disappearance, blocking transmission between preganglionic fibers and intramural excitatory neurons, and a decrease in IJP amplitude that most likely indicates a previous hyperpolarization of the smooth muscle. 5. IJP persistence during splanchnic stimulation proves that sympathetic inhibition does not modify the transmission of the vagal influx onto the non-adrenergic inhibitory neurons of the intramural plexuses. 6. Through a comparative study of proximal and distal colonic innervation, we are able to show that there is a similar organization of both regions, that is a double inhibitory innervation: an adrenergic one of a sympathetic origin, and a non adrenergic one of a parasympathetic origin.

CASE SERIES: Malignant Peripheral Nerve Sheath Tumor in the Course of the Mandibular Nerve.

PubMed

Monika, Probst; Steffen, Koerdt; Maximilian, Ritschl Lucas; Oliver, Bissinger; Friederike, Liesche; Jens, Gempt; Bernhard, Meyer; Egon, Burian; Nina, Lummel; Andreas, Kolk

2018-06-05

Malignant peripheral nerve sheath tumors (MPNST) are infiltrating, aggressive tumors belonging to the group of soft tissue sarcomas. This report refers to three patients with a tumorous swelling in the entire inferior alveolar nerve (IAN) with similar disease courses suspect for a MPNST, which is particularly rare in the trigeminal nerve. Diagnostic tools, surgical proceedings and reconstructive procedures were highlighted. Three male patients (58-68 years), who suffered from numbness, pain and mild swelling in the sensation area served by the mental nerve presented at the department of oral and maxillofacial surgery and underwent diagnostic workup including CT, MRI, F18-PET-CT, as well as a biopsy of the clinical visible tumor mass with histopathological and molecular pathological analysis. MR imaging revealed the full extent of the tumor comprising the course of the entire mandibular nerve (one case bilateral) starting in the trigeminal ganglion through the IAN and ending in the mental foramen. Hence, both a neurosurgical and maxillofacial intervention with jaw replacement were necessary. Adjuvant radiation of the intracranial closed resection margins, and in one case of parts of the mandible was required. In order to reveal the full extent of tumor spread of MPNSTs sufficient preoperative imaging is crucial as it is an important step in therapy planning. MRI and PET-CT are the imaging modalities with the best prospect of success in depicting the whole extent of the disease. Radical surgical management is the treatment of choice whereas radiochemotherapy shows an ancillary part. Copyright © 2018 Elsevier Inc. All rights reserved.

[Sural nerve removal using a nerve stripper].

PubMed

Assmus, H

1983-03-01

In 19 patients the sural nerve was removed for nerve grafting by a specially designed nerve stripper. This technique provides a safe and time-saving removal of the nerve in length up to 34 cm (depending on the length of the stripper used). From a single short incision at the level of the lateral malleolus the nerve is stripped proximally tearing some small branches of the distal nerve. The relatively blunt tip avoids inadvertent transection of the nerve at a lower level or dissection of the nerve at a point where branching occurs. Finally the nerve is cut by the divided cylinder at the tip of the stripper.

Omega-3 supplementation is neuroprotective to corneal nerves in dry eye disease: a pilot study.

PubMed

Chinnery, Holly R; Naranjo Golborne, Cecilia; Downie, Laura E

2017-07-01

To investigate whether oral, long-chain omega-3 (ω-3) essential fatty acid (EFA) supplementation, for 3 months, induces changes to the central corneal sub-basal nerve plexus in dry eye disease and whether nerve alterations correlate with clinical findings. This prospective, comparative study involved the final 12 participants enrolled in a randomised, double-masked, placebo-controlled clinical trial of 60 participants with moderate dry eye disease. Participants received either placebo (olive oil 1500 mg/day; n = 4) or ω-3 EFA supplements (~1000 mg/day eicosapentaenoic acid + ~500 mg/day docosahexaenoic acid; n = 8) for 90 days. The main outcome measure was the mean change in central corneal sub-basal plexus nerve parameters between days one and 90, quantified using in vivo confocal microscopy. Secondary outcomes included mean change in tear osmolarity, corneal dendritic cell density and basal epithelial cell density. Compared with baseline, the reduction in OSDI score and tear osmolarity at day 90 were greater in the ω-3 EFA group than the placebo group (OSDI: ω-3 EFA, mean ± SEM: -15.6 ± 2.8 vs placebo: -2.8 ± 4.1 units, t 5 = 2.6, p = 0.04; tearosmolarity: ω-3 EFA: -22.63 ± 5.7 vs placebo: -8 ± 2.7 mOsmol/L, t 9 = 2.3, p = 0.04). At day 90, corneal total nerve branch density (CTBD: 91.1 ± 8.6 vs 45.1 ± 13.4 branches/mm 2 , F 1,10 = 14, p = 0.004) and corneal nerve branch density on the main fibre (CNBD: 63.4 ± 6.5 vs 27.9 ± 11.5 branches/mm 2 , F 1,10 = 6, p = 0.03) were higher in the ω-3 EFA group compared with placebo. Relative to day 1, CNBD (branches/mm 2 ) increased at day 90 in the ω-3 EFA group (+20.0 ± 9.2, t 8 = 3.2 p = 0.01) compared with placebo (-10.8 ± 3.2). Similar changes were evident for corneal nerve fibre length (CNFL, mm/mm 2 ), which increased from baseline at day 90 in the omega-3 EFA group (+2.9 ± 1.6, t 8 = 3.4 p = 0.01) compared with placebo (-2.7 ± 0.5). There was a negative correlation between CTBD and tear osmolarity

Effects of non-invasive vagus nerve stimulation on attack frequency over time and expanded response rates in patients with chronic cluster headache: a post hoc analysis of the randomised, controlled PREVA study.

PubMed

Gaul, Charly; Magis, Delphine; Liebler, Eric; Straube, Andreas

2017-12-01

In the PREVention and Acute treatment of chronic cluster headache (PREVA) study, attack frequency reductions from baseline were significantly more pronounced with non-invasive vagus nerve stimulation plus standard of care (nVNS + SoC) than with SoC alone. Given the intensely painful and frequent nature of chronic cluster headache attacks, additional patient-centric outcomes, including the time to and level of therapeutic response, were evaluated in a post hoc analysis of the PREVA study. After a 2-week baseline phase, 97 patients with chronic cluster headache entered a 4-week randomised phase to receive nVNS + SoC (n = 48) or SoC alone (n = 49). All 92 patients who continued into a 4-week extension phase received nVNS + SoC. Compared with SoC alone, nVNS + SoC led to a significantly lower mean weekly attack frequency by week 2 of the randomised phase; the attack frequency remained significantly lower in the nVNS + SoC group through week 3 of the extension phase (P < 0.02). Attack frequencies in the nVNS + SoC group were significantly lower at all study time points than they were at baseline (P < 0.05). Response rates were significantly greater with nVNS + SoC than with SoC alone when response was defined as attack frequency reductions of ≥25%, ≥50%, and ≥75% from baseline (≥25% and ≥50%, P < 0.001; ≥75%, P = 0.009). The 100% response rate was 8% with nVNS + SoC and 0% with SoC alone. Prophylactic nVNS led to rapid, significant, and sustained reductions in chronic cluster headache attack frequency within 2 weeks after its addition to SoC and was associated with significantly higher ≥25%, ≥50%, and ≥75% response rates than SoC alone. The rapid decrease in weekly attack frequency justifies a 4-week trial period to identify responders to nVNS, with a high degree of confidence, among patients with chronic cluster headache.

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration.

PubMed

Yu, Qing; Zhang, She-Hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-Dong

2017-10-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration

PubMed Central

Yu, Qing; Zhang, She-hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-dong

2017-01-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy. PMID:29171436

The neuropsychological outcome of pediatric patients with refractory epilepsy treated with VNS--A 24-month follow-up in Taiwan.

PubMed

Tsai, Jeng-Dau; Chang, Ying-Chao; Lin, Lung-Chang; Hung, Kun-Long

2016-03-01

Multiple studies have reported the benefits of vagus nerve stimulation (VNS) on neuropsychological outcomes. The aim of this study was to investigate how VNS affects cognition and psychosocial adjustment in children with refractory epilepsy (RE), and to determine the efficacy of VNS in a Taiwanese population. We conducted a one-group pretest-posttest study on pediatric patients with RE. The study comprised 19 males and 18 females, all aged <18 years. We recorded seizure frequency at 3, 12, and 24 months after VNS device implantation. Intelligence quotients (IQ) were assessed using the Wechsler Intelligence Scale for Children - IV. The Parental Stress Index (PSI) scores were evaluated by a pediatric psychologist. Vagus nerve stimulation device implantation significantly reduced seizure frequency at 3, 12 and 24 months, especially in young children (<12 years). No significant improvement in IQ test performance was observed, though there were significant improvements in the PSI, especially in young children. Vagus nerve stimulation device implantation does not significantly improve cognition function, but it does significantly reduce seizure frequency and stress in parent-child relationships, especially in young children (<12 years). These findings suggest that VNS should be considered as an alternative therapy for patients proven to have seizures that are medically refractory, especially those younger than 12 years of age. Copyright © 2015 Elsevier Inc. All rights reserved.

Monitoring of the posterior cricoarytenoid muscle represents another option for neural monitoring during thyroid surgery: Normative vagal and recurrent laryngeal nerve posterior cricoarytenoid muscle electromyographic data.

PubMed

Liddy, Whitney; Barber, Samuel R; Lin, Brian M; Kamani, Dipti; Kyriazidis, Natalia; Lawson, Bradley; Randolph, Gregory W

2018-01-01

Intraoperative neural monitoring (IONM) of laryngeal nerves using electromyography (EMG) is routinely performed using endotracheal tube surface electrodes adjacent to the vocalis muscles. Other laryngeal muscles such as the posterior cricoarytenoid muscle (PCA) are indirectly monitored. The PCA may be directly and reliably monitored through an electrode placed in the postcricoid region. Herein, we describe the method and normative data for IONM using PCA EMG. Retrospective review. Data were reviewed retrospectively for thyroid and parathyroid surgery patients with IONM of laryngeal nerves from January to August 2016. Recordings of vocalis and PCA EMG amplitudes and latencies with stimulation of laryngeal nerves were obtained using endotracheal (ET) tube-based and postcricoid surface electrodes. Data comprised EMG responses in vocalis and PCA recording channels with stimulation of the vagus, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve from 20 subjects (11 left, 9 right), as well as PCA EMG threshold data with RLN stimulation from 17 subjects. Mean EMG amplitude was 725.69 ± 108.58 microvolts (µV) for the ipsilateral vocalis and 329.44 ± 34.12 µV for the PCA with vagal stimulation, and 1,059.75 ± 140.40 µV for the ipsilateral vocalis and 563.88 ± 116.08 µV for the PCA with RLN stimulation. There were no statistically significant differences in mean latency. For threshold cutoffs of the PCA with RLN stimulation, mean minimum and maximum threshold intensities were 0.37 milliamperes (mA) and 0.84 mA, respectively. This study shows robust and reliable PCA EMG waveforms with direct nerve stimulation. Further studies will evaluate feasibility and application of the PCA electrode as a complementary quantitative tool in IONM. 4. Laryngoscope, 128:283-289, 2018. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve fiber layer and optic nerve appearance.

PubMed

Lim, Michele C; Tanimoto, Suzana A; Furlani, Bruno A; Lum, Brent; Pinto, Luciano M; Eliason, David; Prata, Tiago S; Brandt, James D; Morse, Lawrence S; Park, Susanna S; Melo, Luiz A S

2009-07-01

To determine if panretinal photocoagulation (PRP) alters retinal nerve fiber layer (RNFL) thickness and optic nerve appearance. Patients with diabetes who did and did not undergo PRP and nondiabetic control subjects were enrolled in a prospective study. Participants underwent optical coherence tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve photographs were graded in a masked fashion. Ninety-four eyes of 48 healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and 37 eyes of 24 subjects with diabetes who underwent PRP were included in this study. Eyes that had been treated with PRP had thinner peripapillary RNFL compared with the other groups; this was statistically significantly different in the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not increase with severity of disease classification, but the proportion of optic nerves graded as suspicious for glaucoma or as having nonglaucomatous optic neuropathy did (P = .008). These grading categories were associated with thinner RNFL measurements. Diabetic eyes that have been treated with PRP have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP are more likely to be graded as abnormal, but their appearance is not necessarily glaucomatous and may be related to thinning of the RNFL.

Central vagal sensory and motor connections: human embryonic and fetal development.

PubMed

Cheng, Gang; Zhou, Xiangtian; Qu, Jia; Ashwell, Ken W S; Paxinos, G

2004-07-30

The embryonic and fetal development of the nuclear components and pathways of vagal sensorimotor circuits in the human has been studied using Nissl staining and carbocyanine dye tracing techniques. Eight fetal brains ranging from 8 to 28 weeks of development had DiI (1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate) inserted into either the thoracic vagus nerve at the level of the sternal angle (two specimens of 8 and 9 weeks of gestation) or into vagal rootlets at the surface of the medulla (at all other ages), while a further five were used for study of cytoarchitectural development. The first central labeling resulting from peripheral application of DiI to the thoracic vagus nerve was seen at 8 weeks. By 9 weeks, labeled bipolar cells at the ventricular surface around the sulcus limitans (sl) were seen after DiI application to the thoracic vagus nerve. Subnuclear organization as revealed by both Nissl staining and carbocyanine dye tracing was found to be advanced at a relatively early fetal age, with afferent segregation in the medial Sol apparent at 13 weeks and subnuclear organization of efferent magnocellular divisions of dorsal motor nucleus of vagus nerve noticeable at the same stage. The results of the present study also confirm that vagal afferents are distributed to the dorsomedial subnuclei of the human nucleus of the solitary tract, with particular concentrations of afferent axons in the gelatinosus subnucleus. These vagal afferents appeared to have a restricted zone of termination from quite early in development (13 weeks) suggesting that there is no initial exuberance in the termination field of vagal afferents in the developing human nucleus of the solitary tract. On the other hand, the first suggestion of afferents invading 10N from the medial Sol was not seen until 20 weeks and was not well developed until 24 weeks, suggesting that direct monosynaptic connections between the sensory and effector components of the vagal

Quantifying Demyelination in NK venom treated nerve using its electric circuit model

NASA Astrophysics Data System (ADS)

Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

2016-03-01

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

Quantifying Demyelination in NK venom treated nerve using its electric circuit model

PubMed Central

Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

2016-01-01

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination. PMID:26932543

Quantifying Demyelination in NK venom treated nerve using its electric circuit model.

PubMed

Das, H K; Das, D; Doley, R; Sahu, P P

2016-03-02

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

Help With Depression

MedlinePlus

... techniques that focus on neuromodulation, which incorporates electrical, magnetic or other forms of energy to stimulate brain ... electroconvulsive therapy (ECT), vagus-nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and the experimental deep-brain stimulation ( ...

Epilepsy in Adults with TSC

MedlinePlus

... brain. Devices to treat epilepsy include vagus nerve stimulation and responsive neurostimulation. Who Treats Epilepsy? A general ... Many men with epilepsy will experience changes in sexual drive and performance. For example, many men report ...

Autonomic regulation of mucociliary transport rate in the oesophagus of the frog, Rana temporaria.

PubMed Central

Morley, J; Sanjar, S

1984-01-01

Transport of lead particles along the mucosal surface of the frog oesophagus has been measured by direct observation with the aid of video recording. Electrical stimulation of the vagus nerve increased the rate of particle transport. This acceleration was suppressed by atropine or by hexamethonium. Acetylcholine and other parasympathomimetic agents accelerated particle transport rate. Such acceleration was abolished by atropine. Nicotine increased the rate of particle transport and this effect was suppressed by hexamethonium or by atropine. Atropine did not significantly alter basal particle transport rate. Neither basal particle transport rate nor the response to vagal nerve stimulation were affected by eserine. Adrenaline, noradrenaline or isoprenaline did not affect basal particle transport rate. Adrenaline or noradrenaline were without effect on the increased particle transport rate due to electrical stimulation of the vagus. PMID:6332901

Detailed Anatomy of the Cranial Cervical Ganglion in the Dromedary Camel (Camelus dromedarius).

PubMed

Nourinezhad, Jamal; Mazaheri, Yazdan; Biglari, Zahra

2015-08-01

The detailed morphology and topography of the cranial cervical ganglion (CCG) with its surrounding structures were studied in 10 sides of five heads of adult one-humped camel to determine its general arrangement as well as its differences and similarities to other animals. The following detailed descriptions were obtained: (1) the bilateral CCG was constantly present caudal to cranial base at the rostroventral border of the occipital condyle over the caudolateral part of nasopharynx; (2) the CCG was always in close relations medially with the longus capitis muscle, rostrolaterally with the internal carotid artery, and caudally with the vagus nerve; and (3) the branches of the CCG were the internal carotid and external carotid nerves, jugular nerve, cervical interganglionic branch, laryngopharyngeal branch, carotid sinus branch and communicating branches to the vagus, and first spinal nerves. In conclusion, there was no variation regarding topography of dromedary CCG among the specimens, in spite of typical variations in number, and mainly in origin of nerve branches ramifying from the CCG. In comparative anatomy aspect, the close constant relations, and presence of major nerves (internal/external carotid and jugular nerves) of dromedary CCG exhibited a typical reported animal's pattern. However, the shape, structures lateral to the CCG, the origin and course pattern of external carotid and jugular nerves, the number of the major nerves branches, the communicating branches of the CCG to the spinal and cranial nerves, and the separation of most rostral parts of vagosympathetic trunk of dromedary were different from those of most reported animals. © 2015 Wiley Periodicals, Inc.

The cholinergic anti-inflammatory pathway: An innovative treatment strategy for neurological diseases.

PubMed

Han, Bin; Li, Xiuping; Hao, Junwei

2017-06-01

Acetylcholine (ACh), as a classical neurotransmitter, regulates the neuronal network in response to internal and external stimuli. In recent decades, the biology of ACh has been endowed with unparalleled new insights, especially with respect to cholinergic anti-inflammatory properties in non-neuronal cells. In fact, a mechanism frequently referred to as the "cholinergic anti-inflammatory pathway" has been termed to describe interactions between the central nervous system (CNS) and the immune system via vagus nerve. As well documented, immune cells express choline acetyltransferase, a direct synthetase for ACh, and other corresponding cholinergic components. Alternatively, the ACh released from immune cells or cholinergic neurons modulates immune function in an autocrine/paracrine manner by acting on its receptors. Moreover, muscarinic or nicotinic ACh receptors on various immune cells and CNS glial cells administer the work of their respective agonists, causing functional and biochemical changes. In this review, we focus on the anti-inflammatory benefits of non-neuronal and neuronal ACh as a means of providing new insights into treating inflammation-related neurological diseases, as exemplified by those described herein. Copyright © 2017 Elsevier Ltd. All rights reserved.

Overview of pediatric peripheral facial nerve paralysis: analysis of 40 patients.

PubMed

Özkale, Yasemin; Erol, İlknur; Saygı, Semra; Yılmaz, İsmail

2015-02-01

Peripheral facial nerve paralysis in children might be an alarming sign of serious disease such as malignancy, systemic disease, congenital anomalies, trauma, infection, middle ear surgery, and hypertension. The cases of 40 consecutive children and adolescents who were diagnosed with peripheral facial nerve paralysis at Baskent University Adana Hospital Pediatrics and Pediatric Neurology Unit between January 2010 and January 2013 were retrospectively evaluated. We determined that the most common cause was Bell palsy, followed by infection, tumor lesion, and suspected chemotherapy toxicity. We noted that younger patients had generally poorer outcome than older patients regardless of disease etiology. Peripheral facial nerve paralysis has been reported in many countries in America and Europe; however, knowledge about its clinical features, microbiology, neuroimaging, and treatment in Turkey is incomplete. The present study demonstrated that Bell palsy and infection were the most common etiologies of peripheral facial nerve paralysis. © The Author(s) 2014.

Digestive physiology of the pig symposium: detection of dietary glutamate via gut-brain axis.

PubMed

Bannai, M; Torii, K

2013-05-01

Gustatory and visceral stimulation from food regulates digestion and nutrient use. Free L-glutamate (Glu) release from digested protein is responsible for umami taste perception in the gut. Moreover, monosodium Glu (MSG) is widely used as a flavor enhancer to add umami taste in various cuisines. Recent studies indicate that dietary Glu sensors and their signal transduction system exist in both gut mucosa and taste cells. Oral Glu sensing has been well studied. In this review, we focus on the role of Glu on digestion and absorption of food. Infusion of Glu into the stomach and intestine increase afferent nerve activity of the gastric and the celiac branches of the vagus nerve, respectively. Luminal Glu also evokes efferent nerve activation of the abdominal vagus nerve branches simultaneously. Additionally, intragastric infusion of Glu activates the insular cortex, limbic system, hypothalamus, nucleus tractus solitaries, and amygdala, as determined by functional magnetic resonance imaging, and is able to induce flavor-preference learning as a result of postingestive effects in rats. These results indicate that Glu signaling via gustatory and visceral pathways plays an important role in the processes of digestion, absorption, metabolism, and other physiological functions via activation of the brain.

Nerve injuries do occur in elbow arthroscopy.

PubMed

Hilgersom, Nick F J; van Deurzen, Derek F P; Gerritsma, Carina L E; van der Heide, Huub J L; Malessy, Martijn J A; Eygendaal, Denise; van den Bekerom, Michel P J

2018-01-01

The purpose is to create more awareness as well as emphasize the risk of permanent nerve injury as a complication of elbow arthroscopy. Patients who underwent elbow arthroscopy complicated by permanent nerve injury were retrospectively collected. Patients were collected using two strategies: (1) by word-of-mouth throughout the Dutch Society of Shoulder and Elbow Surgery, and the Leiden University Nerve Centre, and (2) approaching two medical liability insurance companies. Medical records were reviewed to determine patient characteristics, disease history and postoperative course. Surgical records were reviewed to determine surgical details. A total of eight patients were collected, four men and four women, ageing 21-54 years. In five out of eight patients (62.5%), the ulnar nerve was affected; in the remaining three patients (37.5%), the radial nerve was involved. Possible causes for nerve injury varied among patients, such as portal placement and the use of motorized instruments. A case series on permanent nerve injury as a complication of elbow arthroscopy is presented. Reporting on this sequel in the literature is little, however, its risk is not to be underestimated. This study emphasizes that permanent nerve injury is a complication of elbow arthroscopy, concurrently increasing awareness and thereby possibly aiding to prevention. IV, case series.

Effects of nerve cells and adhesion molecules on nerve conduit for peripheral nerve regeneration

PubMed Central

Fiorellini, Joseph P.

2017-01-01

Background For peripheral nerve regeneration, recent attentions have been paid to the nerve conduits made by tissue-engineering technique. Three major elements of tissue-engineering are cells, molecules, and scaffolds. Methods In this study, the attachments of nerve cells, including Schwann cells, on the nerve conduit and the effects of both growth factor and adhesion molecule on these attachments were investigated. Results The attachment of rapidly-proliferating cells, C6 cells and HS683 cells, on nerve conduit was better than that of slowly-proliferating cells, PC12 cells and Schwann cells, however, the treatment of nerve growth factor improved the attachment of slowly-proliferating cells. In addition, the attachment of Schwann cells on nerve conduit coated with fibronectin was as good as that of Schwann cells treated with glial cell line-derived neurotrophic factor (GDNF). Conclusions Growth factor changes nerve cell morphology and affects cell cycle time. And nerve growth factor or fibronectin treatment is indispensable for Schwann cell to be used for implantation in artificial nerve conduits. PMID:29090249

HMGB1 in Health and Disease

PubMed Central

Kang, Rui; Chen, Ruochan; Zhang, Qiuhong; Hou, Wen; Wu, Sha; Cao, Lizhi; Huang, Jin; Yu, Yan; Fan, Xue-gong; Yan, Zhengwen; Sun, Xiaofang; Wang, Haichao; Wang, Qingde; Tsung, Allan; Billiar, Timothy R.; Zeh, Herbert J.; Lotze, Michael T.; Tang, Daolin

2014-01-01

Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly

Performance standards of the nerve conduction study technologist.

PubMed

Neal, Peggy J; Katirji, Bashar

2008-06-01

The primary performance standard of the nerve conduction study technologist is to perform nerve conduction studies (NCS) on patients with trauma or diseases of the peripheral nervous system. However, to be in compliance with various healthcare/medical accreditation agencies, such as Occupational Safety and Health Administration (OSHA), Centers for Disease Control and Prevention (CDC), or The Joint Commission [formerly known as the Joint Commission on Accreditation of Healthcare Organizations (JCAHO)], there are many other important performance objectives that must be met as well. It is the responsibility of the NCS technologist to meet these standards on a daily basis. Once these standards become an expected responsibility of the NCS technologist's position, the patient undergoing a nerve conduction study should be assured of a high quality test performed in an optimal safety environment.

Reinnervation of the diaphragm by the inferior laryngeal nerve to the phrenic nerve in ventilator-dependent tetraplegic patients with C3-5 damage.

PubMed

Verin, Eric; Morelot-Panzini, Capucine; Gonzalez-Bermejo, Jesus; Veber, Benoit; Perrouin Verbe, Brigitte; Soudrie, Brigitte; Leroi, Anne Marie; Marie, Jean Paul; Similowski, Thomas

2017-10-01

The aim of this study was to evaluate the feasibility of unilateral diaphragmatic reinnervation in humans by the inferior laryngeal nerve. This pilot study included chronically ventilated tetraplegic patients with destruction of phrenic nerve motoneurons. Five patients were included. They all had a high level of tetraplegia, with phrenic nerve motor neuron destruction. They were highly dependent on ventilation, without any possibility of weaning. They did not have other chronic pathologies, especially laryngeal disease. They all had diaphragmatic explorations to diagnose the destruction of the motoneurons of the phrenic nerves and nasoendoscopy to be sure that they did not have laryngeal or pharyngeal disease. Then, surgical anastomosis of the right phrenic nerve was performed with the inferior laryngeal nerve, by a cervical approach. A laryngeal reinnervation was performed at the same time, using the ansa hypoglossi. One patient was excluded because of a functional phrenic nerve and one patient died 6 months after the surgery of a cardiac arrest. The remaining three patients were evaluated after the anastomosis every 6 months. They did not present any swallowing or vocal alterations. In these three patients, the diaphragmatic explorations showed that there was a recovery of the diaphragmatic electromyogram of the right and left hemidiaphragms after 1 year. Two patients had surgical diaphragmatic explorations for diaphragmatic pacing 18-24 months after the reinnervation with excellent results. At 36 months, none of the patients could restore their automatic ventilation. In conclusion, this study demonstrated that diaphragmatic reinnervation by the inferior laryngeal nerve is effective, without any vocal or swallowing complications.

Induction of apoptosis by thrombin in the cultured neurons of dorsal motor nucleus of the vagus.

PubMed

Wu, X; Zhang, W; Li, J-Y; Chai, B-X; Peng, J; Wang, H; Mulholland, M W

2011-03-01

A previous study demonstrated the presence of protease-activated receptor (PAR) 1 and 2 in the dorsal motor nucleus of vagus (DMV). The aim of this study is to characterize the effect of thrombin on the apoptosis of DMV neurons. The dorsal motor nucleus of vagus neurons were isolated from neonatal rat brainstems using micro-dissection and enzymatic digestion and cultured. Apoptosis of DMV neurons were examined in cultured neurons. Apoptotic neuron was examined by TUNEL and ELISA. Data were analyzed using anova and Student's t-test. Exposure of cultured DMV neurons to thrombin (0.1 to 10 U mL(-1)) for 24 h significantly increased apoptosis. Pretreatment of DMV neurons with hirudin attenuated the apoptotic effect of thrombin. Similar induction of apoptosis was observed for the PAR1 receptor agonist SFLLR, but not for the PAR3 agonist TFRGAP, nor for the PAR4 agonist YAPGKF. Protease-activated receptors 1 receptor antagonist Mpr(Cha) abolished the apoptotic effect of thrombin, while YPGKF, a specific antagonist for PAR4, demonstrated no effect. After administration of thrombin, phosphorylation of JNK and P38 occurred as early as 15 min, and remained elevated for up to 45 min. Pretreatment of DMV neurons with SP600125, a specific inhibitor for JNK, or SB203580, a specific inhibitor for P38, significantly inhibited apoptosis induced by thrombin. Thrombin induces apoptosis in DMV neurons through a mechanism involving the JNK and P38 signaling pathways. © 2010 Blackwell Publishing Ltd.

Evidence of nonvagal neural stimulation of canine gastric acid secretion.

PubMed

Tansy, M F; Probst, S J; Martin, J S

1975-06-01

In this study, we confirmed our original findings that central vagus stimulation is significantly associated with a subsequent increase in gastric mucus secretion. Central vagus stimulation following phenoxybenzamine hydrochloride administration was associated significantly with protracted elevations in secretory volume and titratable acid. We were unable to conclude that phenoxybenzamine itself in several pharmacologic dosages was associated with an increase in titratable acid. The acid secretory responses could be abolished by transection of the splanchnic nerves. Electrical stimulation of the peripheral part of the splanchnic nerve following administration of phenoxybenzamine was also associated with significant increases in secretory volume and titrable acidity. These secretory responses were not blocked by atropine but were diminished by burimamide. It is concluded that, in the dog, a largely heretofore unsuspected second neural pathway exists which is capable of influencing gastric acid secretion.

Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

NASA Astrophysics Data System (ADS)

Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

2017-02-01

The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival

PubMed Central

Tang, Zhongshu; Zhang, Shuihua; Lee, Chunsik; Kumar, Anil; Arjunan, Pachiappan; Li, Yang; Zhang, Fan; Li, Xuri

2011-01-01

Injury to the optic nerve can lead to axonal degeneration, followed by a gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. Examples of such diseases in human include traumatic optic neuropathy and optic nerve degeneration in glaucoma. It is characterized by typical changes in the optic nerve head, progressive optic nerve degeneration, and loss of retinal ganglion cells, if uncontrolled, leading to vision loss and blindness. The optic nerve crush (ONC) injury mouse model is an important experimental disease model for traumatic optic neuropathy, glaucoma, etc. In this model, the crush injury to the optic nerve leads to gradual retinal ganglion cells apoptosis. This disease model can be used to study the general processes and mechanisms of neuronal death and survival, which is essential for the development of therapeutic measures. In addition, pharmacological and molecular approaches can be used in this model to identify and test potential therapeutic reagents to treat different types of optic neuropathy. Here, we provide a step by step demonstration of (I) Baseline retrograde labeling of retinal ganglion cells (RGCs) at day 1, (II) Optic nerve crush injury at day 4, (III) Harvest the retinae and analyze RGC survival at day 11, and (IV) Representative result. PMID:21540827

Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate.

PubMed

Bonvini, Sara J; Birrell, Mark A; Grace, Megan S; Maher, Sarah A; Adcock, John J; Wortley, Michael A; Dubuis, Eric; Ching, Yee-Man; Ford, Anthony P; Shala, Fisnik; Miralpeix, Montserrat; Tarrason, Gema; Smith, Jaclyn A; Belvisi, Maria G

2016-07-01

Sensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored. We hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung. We used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues. Here we show TRPV4-induced activation of guinea pig airway-specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough. This study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP-mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Facial nerve paralysis in children

PubMed Central

Ciorba, Andrea; Corazzi, Virginia; Conz, Veronica; Bianchini, Chiara; Aimoni, Claudia

2015-01-01

Facial nerve palsy is a condition with several implications, particularly when occurring in childhood. It represents a serious clinical problem as it causes significant concerns in doctors because of its etiology, its treatment options and its outcome, as well as in little patients and their parents, because of functional and aesthetic outcomes. There are several described causes of facial nerve paralysis in children, as it can be congenital (due to delivery traumas and genetic or malformative diseases) or acquired (due to infective, inflammatory, neoplastic, traumatic or iatrogenic causes). Nonetheless, in approximately 40%-75% of the cases, the cause of unilateral facial paralysis still remains idiopathic. A careful diagnostic workout and differential diagnosis are particularly recommended in case of pediatric facial nerve palsy, in order to establish the most appropriate treatment, as the therapeutic approach differs in relation to the etiology. PMID:26677445

Adverse Effects and Surgical Complications in Pediatric Patients Undergoing Vagal Nerve Stimulation for Drug-Resistant Epilepsy.

PubMed

Trezza, A; Landi, A; Grioni, D; Pirillo, D; Fiori, L; Giussani, C; Sganzerla, E P

2017-01-01

Vagal nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy that is not suitable for resective surgery, both in adults and in children. Few reports describe the adverse effects and complications of VNS. The aim of our study was to present a series of 33 pediatric patients who underwent VNS for drug-resistant epilepsy and to discuss the adverse effects and complications through a review of the literature.The adverse effects of VNS are usually transient and are dependent on stimulation of the vagus and its efferent fibers; surgical complications of the procedure may be challenging and patients sometimes require further surgery; generally these complications affect VNS efficacy; in addition, hardware complications also have to be taken into account.In our experience and according to the literature, adverse effects and surgical and hardware complications are uncommon and can usually be managed definitely. Careful selection of patients, particularly from a respiratory and cardiac point of view, has to be done before surgery to limit the incidence of some adverse effects.

Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

PubMed Central

Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

2011-01-01

Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

Nerve Transfer Versus Nerve Graft for Reconstruction of High Ulnar Nerve Injuries.

PubMed

Sallam, Asser A; El-Deeb, Mohamed S; Imam, Mohamed A

2017-04-01

To assess the efficacy of nerve transfer versus nerve grafting in restoring motor and sensory hand function in patients with complete, isolated high ulnar nerve injuries. A retrospective chart review was performed, at a minimum 2 years of follow-up, of 52 patients suffering complete, isolated high ulnar nerve injury between January 2006 and June 2013 in one specialized hand surgery unit. Twenty-four patients underwent motor and sensory nerve transfers (NT group). Twenty-eight patients underwent sural nerve grafting (NG group). Motor recovery, return of sensibility and complications were examined as outcome measures. The Medical Research Council scale was applied to evaluate sensory and motor recovery. Grip and pinch strengths of the hand were measured. Twenty of 24 patients (83.33%) in the NT group regained M3 grade or greater for the adductor pollicis, the abductor digiti minimi, and the medial 2 lumbricals and interossei, compared with only 16 of 28 patients (57.14%) in the NG group. Means for percentage recovery of grip strengths compared with the other healthy hand were significantly higher for the NT group than the NG group. Sensory recovery of S3 or greater was achieved in more than half of each group with no significant difference between groups. Nerve transfer is favored over nerve grafting in managing high ulnar nerve injuries because of better improvement of motor power and better restoration of grip functions of the hand. Therapeutic IV. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Phrenic and hypoglossal nerve activity during respiratory response to hypoxia in 6-OHDA unilateral model of Parkinson's disease.

PubMed

Andrzejewski, Kryspin; Budzińska, Krystyna; Kaczyńska, Katarzyna

2017-07-01

Parkinson's disease (PD) patients apart from motor dysfunctions exhibit respiratory disturbances. Their mechanism is still unknown and requires investigation. Our research was designed to examine the activity of phrenic (PHR) and hypoglossal (HG) nerves activity during a hypoxic respiratory response in the 6-hydroxydopamine (6-OHDA) model of PD. Male adult Wistar rats were injected unilaterally with 6-OHDA (20μg) or the vehicle into the right medial forebrain bundle (MFB). Two weeks after the surgery the activity of the phrenic and hypoglossal nerve was registered in anesthetized, vagotomized, paralyzed, and mechanically ventilated rats under normoxic and hypoxic conditions. Lesion effectiveness was confirmed by the cylinder test, performed before the MFB injection and 14days after, before the respiratory experiment. 6-OHDA lesioned animals showed a significant increase in normoxic inspiratory time. Expiratory time and total time of the respiratory cycle were prolonged in PD rats after hypoxia. The amplitude of the PHR activity and its minute activity were increased in comparison to the sham group at recovery time and during 30s of hypoxia. The amplitude of the HG activity was increased in response to hypoxia in 6-OHDA lesioned animals. The degeneration of dopaminergic neurons decreased the pre-inspiratory/inspiratory ratio of the hypoglossal burst amplitude during and after hypoxia. Unilateral MFB lesion changed the activity of the phrenic and hypoglossal nerves. The altered pre-inspiratory hypoglossal nerve activity indicates modifications to the central mechanisms controlling the activity of the HG nerve and may explain respiratory disorders seen in PD, i.e. apnea. Copyright © 2017 Elsevier Inc. All rights reserved.

Different nerve ultrasound patterns in charcot-marie-tooth types and hereditary neuropathy with liability to pressure palsies.

PubMed

Padua, Luca; Coraci, Daniele; Lucchetta, Marta; Paolasso, Ilaria; Pazzaglia, Costanza; Granata, Giuseppe; Cacciavillani, Mario; Luigetti, Marco; Manganelli, Fiore; Pisciotta, Chiara; Piscosquito, Giuseppe; Pareyson, Davide; Briani, Chiara

2018-01-01

Nerve ultrasound in Charcot-Marie-Tooth (CMT) disease has focused mostly on the upper limbs. We performed an evaluation of a large cohort of CMT patients in which we sonographically characterized nerve abnormalities in different disease types, ages, and nerves. Seventy patients affected by different CMT types and hereditary neuropathy with liability to pressure palsies (HNPP) were evaluated, assessing median, ulnar, fibular, tibial, and sural nerves bilaterally. Data were correlated with age. Nerve dimensions were correlated with CMT type, age, and nerve site. Nerves were larger in demyelinating than in axonal neuropathies. Nerve involvement was symmetric. CMT1 patients had larger nerves than did patients with other CMT types. Patients with HNPP showed enlargement at entrapment sites. Our study confirms the general symmetry of ultrasound nerve patterns in CMT. When compared with ultrasound studies of nerves of the upper limbs, evaluation of the lower limbs did not provide additional information. Muscle Nerve 57: E18-E23, 2018. © 2017 Wiley Periodicals, Inc.

Reinnervation of the diaphragm by the inferior laryngeal nerve to the phrenic nerve in ventilator-dependent tetraplegic patients with C3-5 damage

PubMed Central

Morelot-Panzini, Capucine; Gonzalez-Bermejo, Jesus; Veber, Benoit; Perrouin Verbe, Brigitte; Soudrie, Brigitte; Leroi, Anne Marie; Marie, Jean Paul; Similowski, Thomas

2017-01-01

The aim of this study was to evaluate the feasibility of unilateral diaphragmatic reinnervation in humans by the inferior laryngeal nerve. This pilot study included chronically ventilated tetraplegic patients with destruction of phrenic nerve motoneurons. Five patients were included. They all had a high level of tetraplegia, with phrenic nerve motor neuron destruction. They were highly dependent on ventilation, without any possibility of weaning. They did not have other chronic pathologies, especially laryngeal disease. They all had diaphragmatic explorations to diagnose the destruction of the motoneurons of the phrenic nerves and nasoendoscopy to be sure that they did not have laryngeal or pharyngeal disease. Then, surgical anastomosis of the right phrenic nerve was performed with the inferior laryngeal nerve, by a cervical approach. A laryngeal reinnervation was performed at the same time, using the ansa hypoglossi. One patient was excluded because of a functional phrenic nerve and one patient died 6 months after the surgery of a cardiac arrest. The remaining three patients were evaluated after the anastomosis every 6 months. They did not present any swallowing or vocal alterations. In these three patients, the diaphragmatic explorations showed that there was a recovery of the diaphragmatic electromyogram of the right and left hemidiaphragms after 1 year. Two patients had surgical diaphragmatic explorations for diaphragmatic pacing 18–24 months after the reinnervation with excellent results. At 36 months, none of the patients could restore their automatic ventilation. In conclusion, this study demonstrated that diaphragmatic reinnervation by the inferior laryngeal nerve is effective, without any vocal or swallowing complications. PMID:29181382

Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

PubMed Central

2015-01-01

There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986

Characterizing Intraorbital Optic Nerve Changes on Diffusion Tensor Imaging in Thyroid Eye Disease Before Dysthyroid Optic Neuropathy.

PubMed

Lee, Hwa; Lee, Young Hen; Suh, Sang-Il; Jeong, Eun-Kee; Baek, Sehyun; Seo, Hyung Suk

The aim of this study was to determine whether the optic nerve is affected by thyroid eye disease (TED) before the development of dysthyroid optic neuropathy with diffusion-tensor imaging (DTI). Twenty TED patients and 20 controls were included. The mean, axial, and radial diffusivities and fractional anisotropy (FA) value were measured at the optic nerves in DTI. Extraocular muscle diameters were measured on computed tomography. The diffusivities and FA of the optic nerves were compared between TED and controls and between active and inactive stages of TED. The correlations between these DTI parameters and the clinical features were determined. The mean, axial, and radial diffusivities were lower in TED compared with the controls (P < 0.05). In contrast, FA was higher in TED (P = 0.001). Radial diffusivity was lower in the active stage of TED than the inactive stage (P = 0.035). The FA was higher in the TED group than in the control group (P = 0.021) and was positively correlated with clinical activity score (r = 0.364, P = 0.021), modified NOSPECS score (r = 0.469, P = 0.002), and extraocular muscle thickness (r = 0.325, P = 0.041) in the TED group. Radial diffusivity was negatively correlated with modified NOSPECS score (r = -0.384, P = 0.014), and axial diffusivity was positively correlated with exophthalmos degree (r = 0.363, P = 0.025). The diffusivities and FA reflected changes in the optic nerve before dysthyroid optic neuropathy in TED. The FA, in particular, reflected TED activity and severity.

The Blood Volume of the Guinea Pig: Effects of Epinephrine and Isoproterenol upon the Red Cell and Plasma Volumes, Heart Rate, and Mean Arterial Pressure,

DTIC Science & Technology

1987-09-01

capillaries (4), blood volumes calculated from plasma volume measures must correct for label that has left the system between the time of the injected dose...Splenic sequestration and contraction are mediated by the autonomic nervous system and blood-borne agents (10). Sympathetic nerve fibers from the truncus...sympathlcus and parasympathetic neurons of the nervus vagus (cranial nerve X) innervate the celiac plexus (8, 11). A subdivision of the celiac plexus

Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer's disease.

PubMed

Faustino, Célia; Rijo, Patrícia; Reis, Catarina Pinto

2017-06-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with amyloid-β peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood-brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell-based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease-modifying approach toward AD. Lipid- and polymer-based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF-based therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preoperative transcutaneous electrical nerve stimulation for localizing superficial nerve paths.

PubMed

Natori, Yuhei; Yoshizawa, Hidekazu; Mizuno, Hiroshi; Hayashi, Ayato

2015-12-01

During surgery, peripheral nerves are often seen to follow unpredictable paths because of previous surgeries and/or compression caused by a tumor. Iatrogenic nerve injury is a serious complication that must be avoided, and preoperative evaluation of nerve paths is important for preventing it. In this study, transcutaneous electrical nerve stimulation (TENS) was used for an in-depth analysis of peripheral nerve paths. This study included 27 patients who underwent the TENS procedure to evaluate the peripheral nerve path (17 males and 10 females; mean age: 59.9 years, range: 18-83 years) of each patient preoperatively. An electrode pen coupled to an electrical nerve stimulator was used for superficial nerve mapping. The TENS procedure was performed on patients' major peripheral nerves that passed close to the surgical field of tumor resection or trauma surgery, and intraoperative damage to those nerves was apprehensive. The paths of the target nerve were detected in most patients preoperatively. The nerve paths of 26 patients were precisely under the markings drawn preoperatively. The nerve path of one patient substantially differed from the preoperative markings with numbness at the surgical region. During surgery, the nerve paths could be accurately mapped preoperatively using the TENS procedure as confirmed by direct visualization of the nerve. This stimulation device is easy to use and offers highly accurate mapping of nerves for surgical planning without major complications. The authors conclude that TENS is a useful tool for noninvasive nerve localization and makes tumor resection a safe and smooth procedure. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

High Spatial Resolution Imaging Mass Spectrometry of Human Optic Nerve Lipids and Proteins

NASA Astrophysics Data System (ADS)

Anderson, David M. G.; Spraggins, Jeffrey M.; Rose, Kristie L.; Schey, Kevin L.

2015-06-01

The human optic nerve carries signals from the retina to the visual cortex of the brain. Each optic nerve is comprised of approximately one million nerve fibers that are organized into bundles of 800-1200 fibers surrounded by connective tissue and supportive glial cells. Damage to the optic nerve contributes to a number of blinding diseases including: glaucoma, neuromyelitis optica, optic neuritis, and neurofibromatosis; however, the molecular mechanisms of optic nerve damage and death are incompletely understood. Herein we present high spatial resolution MALDI imaging mass spectrometry (IMS) analysis of lipids and proteins to define the molecular anatomy of the human optic nerve. The localization of a number of lipids was observed in discrete anatomical regions corresponding to myelinated and unmyelinated nerve regions as well as to supporting connective tissue, glial cells, and blood vessels. A protein fragment from vimentin, a known intermediate filament marker for astrocytes, was observed surrounding nerved fiber bundles in the lamina cribrosa region. S100B was also found in supporting glial cell regions in the prelaminar region, and the hemoglobin alpha subunit was observed in blood vessel areas. The molecular anatomy of the optic nerve defined by MALDI IMS provides a firm foundation to study biochemical changes in blinding human diseases.

Stereotactic radiotherapy for malignancies involving the trigeminal and facial nerves.

PubMed

Cuneo, K C; Zagar, T M; Brizel, D M; Yoo, D S; Hoang, J K; Chang, Z; Wang, Z; Yin, F F; Das, S K; Green, S; Ready, N; Bhatti, M T; Kaylie, D M; Becker, A; Sampson, J H; Kirkpatrick, J P

2012-06-01

Involvement of a cranial nerve caries a poor prognosis for many malignancies. Recurrent or residual disease in the trigeminal or facial nerve after primary therapy poses a challenge due to the location of the nerve in the skull base, the proximity to the brain, brainstem, cavernous sinus, and optic apparatus and the resulting complex geometry. Surgical resection caries a high risk of morbidity and is often not an option for these patients. Stereotactic radiosurgery and radiotherapy are potential treatment options for patients with cancer involving the trigeminal or facial nerve. These techniques can deliver high doses of radiation to complex volumes while sparing adjacent critical structures. In the current study, seven cases of cancer involving the trigeminal or facial nerve are presented. These patients had unresectable recurrent or residual disease after definitive local therapy. Each patient was treated with stereotactic radiation therapy using a linear accelerator based system. A multidisciplinary approach including neuroradiology and surgical oncology was used to delineate target volumes. Treatment was well tolerated with no acute grade 3 or higher toxicity. One patient who was reirradiated experienced cerebral radionecrosis with mild symptoms. Four of the seven patients treated had no evidence of disease after a median follow up of 12 months (range 2-24 months). A dosimetric analysis was performed to compare intensity modulated fractionated stereotactic radiation therapy (IM-FSRT) to a 3D conformal technique. The dose to 90% (D90) of the brainstem was lower with the IM-FSRT plan by a mean of 13.5 Gy. The D95 to the ipsilateral optic nerve was also reduced with IM-FSRT by 12.2 Gy and the D95 for the optic chiasm was lower with FSRT by 16.3 Gy. Treatment of malignancies involving a cranial nerve requires a multidisciplinary approach. Use of an IM-FSRT technique with a micro-multileaf collimator resulted in a lower dose to the brainstem, optic nerves and chiasm

A micro-scale printable nanoclip for electrical stimulation and recording in small nerves

NASA Astrophysics Data System (ADS)

Lissandrello, Charles A.; Gillis, Winthrop F.; Shen, Jun; Pearre, Ben W.; Vitale, Flavia; Pasquali, Matteo; Holinski, Bradley J.; Chew, Daniel J.; White, Alice E.; Gardner, Timothy J.

2017-06-01

Objective. The vision of bioelectronic medicine is to treat disease by modulating the signaling of visceral nerves near various end organs. In small animal models, the nerves of interest can have small diameters and limited surgical access. New high-resolution methods for building nerve interfaces are desirable. In this study, we present a novel nerve interface and demonstrate its use for stimulation and recording in small nerves. Approach. We design and fabricate micro-scale electrode-laden nanoclips capable of interfacing with nerves as small as 50 µm in diameter. The nanoclips are fabricated using a direct laser writing technique with a resolution of 200 nm. The resolution of the printing process allows for incorporation of a number of innovations such as trapdoors to secure the device to the nerve, and quick-release mounts that facilitate keyhole surgery, obviating the need for forceps. The nanoclip can be built around various electrode materials; here we use carbon nanotube fibers for minimally invasive tethering. Main results. We present data from stimulation-evoked responses of the tracheal syringeal (hypoglossal) nerve of the zebra finch, as well as quantification of nerve functionality at various time points post implant, demonstrating that the nanoclip is compatible with healthy nerve activity over sub-chronic timescales. Significance. Our nerve interface addresses key challenges in interfacing with small nerves in the peripheral nervous system. Its small size, ability to remain on the nerve over sub-chronic timescales, and ease of implantation, make it a promising tool for future use in the treatment of disease.

A micro-scale printable nanoclip for electrical stimulation and recording in small nerves.

PubMed

Lissandrello, Charles A; Gillis, Winthrop F; Shen, Jun; Pearre, Ben W; Vitale, Flavia; Pasquali, Matteo; Holinski, Bradley J; Chew, Daniel J; White, Alice E; Gardner, Timothy J

2017-06-01

The vision of bioelectronic medicine is to treat disease by modulating the signaling of visceral nerves near various end organs. In small animal models, the nerves of interest can have small diameters and limited surgical access. New high-resolution methods for building nerve interfaces are desirable. In this study, we present a novel nerve interface and demonstrate its use for stimulation and recording in small nerves. We design and fabricate micro-scale electrode-laden nanoclips capable of interfacing with nerves as small as 50 µm in diameter. The nanoclips are fabricated using a direct laser writing technique with a resolution of 200 nm. The resolution of the printing process allows for incorporation of a number of innovations such as trapdoors to secure the device to the nerve, and quick-release mounts that facilitate keyhole surgery, obviating the need for forceps. The nanoclip can be built around various electrode materials; here we use carbon nanotube fibers for minimally invasive tethering. We present data from stimulation-evoked responses of the tracheal syringeal (hypoglossal) nerve of the zebra finch, as well as quantification of nerve functionality at various time points post implant, demonstrating that the nanoclip is compatible with healthy nerve activity over sub-chronic timescales. Our nerve interface addresses key challenges in interfacing with small nerves in the peripheral nervous system. Its small size, ability to remain on the nerve over sub-chronic timescales, and ease of implantation, make it a promising tool for future use in the treatment of disease.

Autologous transplantation with fewer fibers repairs large peripheral nerve defects

PubMed Central

Deng, Jiu-xu; Zhang, Dian-yin; Li, Ming; Weng, Jian; Kou, Yu-hui; Zhang, Pei-xun; Han, Na; Chen, Bo; Yin, Xiao-feng; Jiang, Bao-guo

2017-01-01

Peripheral nerve injury is a serious disease and its repair is challenging. A cable-style autologous graft is the gold standard for repairing long peripheral nerve defects; however, ensuring that the minimum number of transplanted nerve attains maximum therapeutic effect remains poorly understood. In this study, a rat model of common peroneal nerve defect was established by resecting a 10-mm long right common peroneal nerve. Rats receiving transplantation of the common peroneal nerve in situ were designated as the in situ graft group. Ipsilateral sural nerves (10–30 mm long) were resected to establish the one sural nerve graft group, two sural nerves cable-style nerve graft group and three sural nerves cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long. To reduce the barrier effect due to invasion by surrounding tissue and connective-tissue overgrowth between neural stumps, small gap sleeve suture was used in both proximal and distal terminals to allow repair of the injured common peroneal nerve. At three months postoperatively, recovery of nerve function and morphology was observed using osmium tetroxide staining and functional detection. The results showed that the number of regenerated nerve fibers, common peroneal nerve function index, motor nerve conduction velocity, recovery of myodynamia, and wet weight ratios of tibialis anterior muscle were not significantly different among the one sural nerve graft group, two sural nerves cable-style nerve graft group, and three sural nerves cable-style nerve graft group. These data suggest that the repair effect achieved using one sural nerve graft with a lower number of nerve fibers is the same as that achieved using the two sural nerves cable-style nerve graft and three sural nerves cable-style nerve graft. This indicates that according to the ‘multiple amplification’ phenomenon, one small nerve graft can provide a good therapeutic effect for a large peripheral nerve defect. PMID

Observations on the bony bridging of the jugular foramen in man.

PubMed

Dodo, Y

1986-02-01

The anatomical nature and pattern of incidence of bony bridging of the jugular foramen was investigated using 64 fetal crania aged nine months to term and 222 adult crania of Japanese. In addition, the region of the jugular foramen of an adult cadaver was carefully dissected in order to clarify the relationship between the cranial nerves passing through the jugular foramen and the intrajugular processes of the jugular foramen. The general conclusions concerning the anatomical nature of the bony bridging of the jugular foramen were as follows. (1) The intrajugular process of the temporal bone is situated posterior to the triangular depression (as described in Gray's Anatomy) of the petrous part. (2) The bony bridging of the jugular foramen is established by the contact of the intrajugular process of the temporal bone with the bony process of the occipital bone projecting either from just above the hypoglossal canal (Type I) or from posterior to the hypoglossal canal (Type III). (3) If both the processes of the occipital bone reach the intrajugular process of the temporal bone simultaneously, the jugular foramen is divided into three compartments. (4) In the case of Type I bridging, the anteromedial compartment transmits the glossopharyngeal nerve, while the posterolateral compartment gives passage to the vagus nerve, the accessory nerve and the internal jugular vein. (5) In the case of Type II bridging, the anteromedial compartment contains the glossopharyngeal, vagus and accessory nerves, and the posterolateral compartment transmits the internal jugular vein. (6) When tripartite division of the jugular foramen occurs, the anteromedial compartment transmits the glossopharyngeal nerve, the middle compartment contains the vagus and accessory nerves, and the posterolateral compartment transmits the internal jugular vein. Concerning the pattern of incidence of jugular foramen bridging in the Japanese fetal and adult cranial series, this is similar to that of the bony

Observations on the bony bridging of the jugular foramen in man.

PubMed Central

Dodo, Y

1986-01-01

The anatomical nature and pattern of incidence of bony bridging of the jugular foramen was investigated using 64 fetal crania aged nine months to term and 222 adult crania of Japanese. In addition, the region of the jugular foramen of an adult cadaver was carefully dissected in order to clarify the relationship between the cranial nerves passing through the jugular foramen and the intrajugular processes of the jugular foramen. The general conclusions concerning the anatomical nature of the bony bridging of the jugular foramen were as follows. (1) The intrajugular process of the temporal bone is situated posterior to the triangular depression (as described in Gray's Anatomy) of the petrous part. (2) The bony bridging of the jugular foramen is established by the contact of the intrajugular process of the temporal bone with the bony process of the occipital bone projecting either from just above the hypoglossal canal (Type I) or from posterior to the hypoglossal canal (Type III). (3) If both the processes of the occipital bone reach the intrajugular process of the temporal bone simultaneously, the jugular foramen is divided into three compartments. (4) In the case of Type I bridging, the anteromedial compartment transmits the glossopharyngeal nerve, while the posterolateral compartment gives passage to the vagus nerve, the accessory nerve and the internal jugular vein. (5) In the case of Type II bridging, the anteromedial compartment contains the glossopharyngeal, vagus and accessory nerves, and the posterolateral compartment transmits the internal jugular vein. (6) When tripartite division of the jugular foramen occurs, the anteromedial compartment transmits the glossopharyngeal nerve, the middle compartment contains the vagus and accessory nerves, and the posterolateral compartment transmits the internal jugular vein. Concerning the pattern of incidence of jugular foramen bridging in the Japanese fetal and adult cranial series, this is similar to that of the bony

Chitin biological absorbable catheters bridging sural nerve grafts transplanted into sciatic nerve defects promote nerve regeneration.

PubMed

Wang, Zhi-Yong; Wang, Jian-Wei; Qin, Li-Hua; Zhang, Wei-Guang; Zhang, Pei-Xun; Jiang, Bao-Guo

2018-06-01

To investigate the efficacy of chitin biological absorbable catheters in a rat model of autologous nerve transplantation. A segment of sciatic nerve was removed to produce a sciatic nerve defect, and the sural nerve was cut from the ipsilateral leg and used as a graft to bridge the defect, with or without use of a chitin biological absorbable catheter surrounding the graft. The number and morphology of regenerating myelinated fibers, nerve conduction velocity, nerve function index, triceps surae muscle morphology, and sensory function were evaluated at 9 and 12 months after surgery. All of the above parameters were improved in rats in which the nerve graft was bridged with chitin biological absorbable catheters compared with rats without catheters. The results of this study indicate that use of chitin biological absorbable catheters to surround sural nerve grafts bridging sciatic nerve defects promotes recovery of structural, motor, and sensory function and improves muscle fiber morphology. © 2018 John Wiley & Sons Ltd.

Brainstem abnormalities and vestibular nerve enhancement in acute neuroborreliosis.

PubMed

Farshad-Amacker, Nadja A; Scheffel, Hans; Frauenfelder, Thomas; Alkadhi, Hatem

2013-12-21

Borreliosis is a widely distributed disease. Neuroborreliosis may present with unspecific symptoms and signs and often remains difficult to diagnose in patients with central nervous system symptoms, particularly if the pathognomonic erythema chronica migrans does not develop or is missed. Thus, vigilance is mandatory in cases with atypical presentation of the disease and with potentially severe consequences if not recognized early. We present a patient with neuroborreliosis demonstrating brain stem and vestibular nerve abnormalities on magnetic resonance imaging. A 28-year-old Caucasian female presented with headaches, neck stiffness, weight loss, nausea, tremor, and gait disturbance. Magnetic resonance imaging showed T2-weighted hyperintense signal alterations in the pons and in the vestibular nerves as well as bilateral post-contrast enhancement of the vestibular nerves. Serologic testing of the cerebrospinal fluid revealed the diagnosis of neuroborreliosis. Patients infected with neuroborreliosis may present with unspecific neurologic symptoms and magnetic resonance imaging as a noninvasive imaging tool showing signal abnormalities in the brain stem and nerve root enhancement may help in establishing the diagnosis.

Lyme disease with facial nerve palsy: rapid diagnosis using a nested polymerase chain reaction-restriction fragment length polymorphism analysis.

PubMed

Hashimoto, Y; Takahashi, H; Kishiyama, K; Sato, Y; Nakao, M; Miyamoto, K; Iizuka, H

1998-02-01

A 64-year-old woman with Lyme disease and manifesting facial nerve palsy had been bitten by a tick on the left frontal scalp 4 weeks previously. Erythema migrans appeared on the left forehead, accompanied by left facial paralysis. Nested polymerase chain reaction-restriction fragment length polymorphism analysis (nested PCR-RFLP) was performed on DNA extracted from a skin biopsy of the erythema on the left forehead. Borrelia flagellin gene DNA was detected and its RFLP pattern indicated that the organism was B. garinii, Five weeks later, B. garinii was isolated by conventional culture from the erythematous skin lesion, but not from the cerebrospinal fluid. After treatment with ceftriaxone intravenously for 10 days and oral administration of minocycline for 7 days, both the erythema and facial nerve palsy improved significantly. Nested PCR and culture taken after the lesion subsided, using skin samples obtained from a site adjacent to the original biopsy, were both negative. We suggest that nested PCR-RFLP analysis might be useful for the rapid diagnosis of Lyme disease and for evaluating therapy.

Hypothesis that vagal reinervation of diaphragm could sensitise it to electrical stimulation.

PubMed

Pavlovic, Dragan; Wendt, Michael

2003-03-01

The hypothesis proposed is that restoration of functional capacity of denervated diaphragm may be achieved by reinervating it with vagus nerve. Following trauma, carcinomatose infiltration, and/or large thoracic surgery and neck surgery, phrenic nerve is frequently injured. Reinervation even in the most favourable conditions would not follow and diaphragm would rest permanently denervated and paralysed. This results in unilateral or bilateral paralysis of diaphragm. In principle, intermittent electrical stimulation of the phrenic nerve or diaphragm could elicit regular diaphragm contractions and maintain satisfactory respiration. While this technique could be used in upper motor neurone injury, in lower motor neurone injury and denervated diaphragm, that imposes too high electrical resistance, direct diaphragm pacing is practically impossible. In these cases, long term artificial ventilation is often necessary. Nevertheless, those patients are at high risk to suffer from atelectasis and respiratory infections. We project a hypothesis that reinervation of denervated diaphragm by vagus nerve could re-establishes its sensitivity to intramuscular electrical stimulation and may allow stimulation of the diaphragm by implanted pace-maker electrodes. An appropriate electrical stimulation might then be possible and diaphragm pacing could replace prolonged artificial ventilation in those patients. Restoration of functional capacity of denervated diaphragm could open a perspective for long term diaphragm pacing in patients with irreversible phrenic nerve injury and diaphragm paralysis.

External laryngeal nerve in thyroid surgery: is the nerve stimulator necessary?

PubMed

Aina, E N; Hisham, A N

2001-09-01

To find out the incidence and type of external laryngeal nerves during operations on the thyroid, and to assess the role of a nerve stimulator in detecting them. Prospective, non-randomised study. Teaching hospital, Malaysia. 317 patients who had 447 dissections between early January 1998 and late November 1999. Number and type of nerves crossing the cricothyroid space, and the usefulness of the nerve stimulator in finding them. The nerve stimulator was used in 206/447 dissections (46%). 392 external laryngeal nerves were seen (88%), of which 196/206 (95%) were detected with the stimulator. However, without the stimulator 196 nerves were detected out of 241 dissections (81%). The stimulator detected 47 (23%) Type I nerves (nerve > 1 cm from the upper edge of superior pole); 86 (42%) Type IIa nerves (nerve < 1 cm from the upper edge of superior pole); and 63 (31%) Type IIb nerves (nerve below upper edge of superior pole). 10 nerves were not detected. When the stimulator was not used the corresponding figures were 32 (13%), 113 (47%), and 51 (21%), and 45 nerves were not seen. If the nerve cannot be found we recommend dissection of capsule close to the medial border of the upper pole of the thyroid to avoid injury to the nerve. Although the use of the nerve stimulator seems desirable, it confers no added advantage in finding the nerve. In the event of uncertainty about whether a structure is the nerve, the stimulator may help to confirm it. However, exposure of the cricothyroid space is most important for good exposure in searching for the external laryngeal nerve.

Correlation of nerve ultrasound, electrophysiological and clinical findings in chronic inflammatory demyelinating polyneuropathy.

PubMed

Kerasnoudis, A; Pitarokoili, K; Behrendt, V; Gold, R; Yoon, M-S

2015-01-01

We present the nerve ultrasound findings in chronic inflammatory demyelinating polyneuropathy (CIDP) and examine their correlation with electrophysiology and functional disability. A total of 75 healthy controls and 48 CIDP patients underwent clinical, sonographic and electrophysiological evaluation a mean of 3.9 years(SD+/-2.7) after disease onset. Nerve ultrasound revealed statistically significant higher cross-sectional area (CSA) values of the median (P<.0001), ulnar (P<.0001), radial (P<.0001), tibial (P<.0001), fibular nerve(P<.0001) in most of the anatomic sites and brachial plexus (supraclavicular, P<.0001;interscalene space, P = .0118),when compared to controls. The electroneurography documented signs of permanent axonal loss in the majority of peripheral nerves. A correlation between sonographic and electrophysiological findings was found only between the motor conduction velocity and CSA of the tibial nerve at the ankle (r = -.451, P = .007). Neither nerve sonography nor electrophysiology correlated with functional disability. The CSA of the median nerve in carpal tunnel and the ulnar nerve in Guyon's canal correlated with disease duration (P = .036, P = .027 respectively). CIDP seems to show inhomogenous CSA enlargement in brachial plexus and peripheral nerves, with weak correlation to electrophysiological findings. Neither nerve sonography nor electrophysiology correlated with functional disability in CIDP patients. Multicenter, prospective studies are required to proof the applicability and diagnostic values of these findings. Copyright © 2014 by the American Society of Neuroimaging.

Massive nerve root enlargement in chronic inflammatory demyelinating polyneuropathy.

PubMed Central

Schady, W; Goulding, P J; Lecky, B R; King, R H; Smith, C M

1996-01-01

OBJECTIVE: To report three patients with chronic inflammatory demyelinating polyneuropathy (CIDP) presenting with symptoms suggestive of cervical (one patient) and lumbar root disease. METHODS: Nerve conduction studies, EMG, and nerve biopsy were carried out, having found the nerve roots to be very enlarged on MRI, CT myelography, and at surgery. RESULTS: Clinically, peripheral nerve thickening was slight or absent. Subsequently one patient developed facial nerve hypertrophy. This was mistaken for an inner ear tumour and biopsied, with consequent facial palsy. Neurophysiological tests suggested a demyelinating polyneuropathy. Sural nerve biopsy showed in all cases some loss of myelinated fibres, inflammatory cell infiltration, and a few onion bulbs. Hypertrophic changes were much more prominent on posterior nerve root biopsy in one patient: many fibres were surrounded by several layers of Schwann cell cytoplasm. There was an excellent response to steroids in two patients but not in the third (most advanced) patient, who has benefited only marginally from intravenous immunoglobulin therapy. CONCLUSIONS: MRI of the cauda equina may be a useful adjunct in the diagnosis of CIDP. Images PMID:8971116

Structural parameters of collagen nerve grafts influence peripheral nerve regeneration.

PubMed

Stang, Felix; Fansa, Hisham; Wolf, Gerald; Reppin, Michael; Keilhoff, Gerburg

2005-06-01

Large nerve defects require nerve grafts to allow regeneration. To avoid donor nerve problems the concept of tissue engineering was introduced into nerve surgery. However, non-neuronal grafts support axonal regeneration only to a certain extent. They lack viable Schwann cells which provide neurotrophic and neurotopic factors and guide the sprouting nerve. This experimental study used the rat sciatic nerve to bridge 2 cm nerve gaps with collagen (type I/III) tubes. The tubes were different in their physical structure (hollow versus inner collagen skeleton, different inner diameters). To improve regeneration Schwann cells were implanted. After 8 weeks the regeneration process was monitored clinically, histologically and morphometrically. Autologous nerve grafts and collagen tubes without Schwann cells served as control. In all parameters autologous nerve grafts showed best regeneration. Nerve regeneration in a noteworthy quality was also seen with hollow collagen tubes and tubes with reduced lumen, both filled with Schwann cells. The inner skeleton, however, impaired nerve regeneration independent of whether Schwann cells were added or not. This indicates that not only viable Schwann cells are an imperative prerequisite but also structural parameters determine peripheral nerve regeneration.

Noninvasive transcranial stimulation of rat abducens nerve by focused ultrasound.

PubMed

Kim, Hyungmin; Taghados, Seyed Javid; Fischer, Krisztina; Maeng, Lee-So; Park, Shinsuk; Yoo, Seung-Schik

2012-09-01

Nonpharmacologic and nonsurgical transcranial modulation of the nerve function may provide new opportunities in evaluation and treatment of cranial nerve diseases. This study investigates the possibility of using low-intensity transcranial focused ultrasound (FUS) to selectively stimulate the rat abducens nerve located above the base of the skull. FUS (frequencies of 350 kHz and 650 kHz) operating in a pulsed mode was applied to the abducens nerve of Sprague-Dawley rats under stereotactic guidance. The abductive eyeball movement ipsilateral to the side of sonication was observed at 350 kHz, using the 0.36-msec tone burst duration (TBD), 1.5-kHz pulse repetition frequency (PRF), and the overall sonication duration of 200 msec. Histologic and behavioral monitoring showed no signs of disruption in the blood brain barrier (BBB), as well as no damage to the nerves and adjacent brain tissue resulting from the sonication. As a novel functional neuro-modulatory modality, the pulsed application of FUS has potential for diagnostic and therapeutic applications in diseases of the peripheral nervous system. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Vagal innervation of the aldosterone-sensitive HSD2 neurons in the NTS

PubMed Central

Shin, Jung-Won; Geerling, Joel C.; Loewy, Arthur D.

2009-01-01

The nucleus of the solitary tract (NTS) contains a unique subpopulation of aldosterone-sensitive neurons. These neurons express the enzyme 11-β-hydroxysteroid dehydrogenase type 2 (HSD2) and are activated by sodium deprivation. They are located in the caudal NTS, a region which is densely innervated by the vagus nerve, suggesting that they could receive direct viscerosensory input from the periphery. To test this possibility, we injected the highly sensitive axonal tracer biotinylated dextran amine (BDA) into the left nodose ganglion in rats. Using confocal microscopy, we observed a sparse input from the vagus to most HSD2 neurons. Roughly 80% of the ipsilateral HSD2 neurons exhibited at least one close contact with a BDA-labeled vagal bouton, although most of these cells received only a few total contacts. Most of these contacts were axo-dendritic (~80%), while ~20% were axo-somatic. In contrast, the synaptic vesicular transporters VGLUT2 or GAD7 labeled much larger populations of boutons contacting HSD2-labeled dendrites and somata, suggesting that direct input from the vagus may only account for a minority of the information integrated by these neurons. In summary, the aldosterone-sensitive HSD2 neurons in the NTS appear to receive a small amount of direct viscerosensory input from the vagus nerve. The peripheral sites of origin and functional significance of this projection remain unknown. Combined with previously-identified central sources of input to these cells, the present finding indicates that the HSD2 neurons integrate humoral information with input from a variety of neural afferents. PMID:19010311

Diffusion tensor imaging of the sural nerve in normal controls☆

PubMed Central

Kim, Boklye; Srinivasan, Ashok; Sabb, Brian; Feldman, Eva L; Pop-Busui, Rodica

2016-01-01

Objective To develop a diffusion tensor imaging (DTI) protocol for assessing the sural nerve in healthy subjects. Methods Sural nerves in 25 controls were imaged using DTI at 3 T with 6, 15, and 32 gradient directions. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed from nerve regions of interest co-registered with T2-weighted images. Results Coronal images with 0.5(RL)×2.0(FH)×0.5(AP) mm3 resolution successfully localized the sural nerve. FA maps showed less variability with 32 directions (0.559±0.071) compared to 15(0.590±0.080) and 6(0.659±0.109). Conclusions Our DTI protocol was effective in imaging sural nerves in controls to establish normative FA/ADC, with potential to be used non-invasively in diseased nerves of patients. PMID:24908367

Non-invasive transcranial stimulation of rat abducens nerve by focused ultrasound

PubMed Central

Kim, Hyungmin; Taghados, Seyed Javid; Fischer, Krisztina; Maeng, Lee-So; Park, Shinsuk; Yoo, Seung-Schik

2012-01-01

Non-pharmacological and non-surgical transcranial modulation of the nerve function may provide new opportunities in evaluation and treatment of cranial nerve diseases. This study investigates the possibility of using low-intensity transcranial focused ultrasound (FUS) to selectively stimulate the rat abducens nerve located above the base of the skull. FUS (frequencies of 350 kHz and 650 kHz) operating in a pulsed mode was applied to the abducens nerve of Sprague-Dawley rats under stereotactic guidance. The abductive eyeball movement ipsilateral to the side of sonication was observed at 350 kHz, using the 0.36 msec tone burst duration (TBD), 1.5 kHz pulse repetition frequency (PRF), and the overall sonication duration of 200 msec. Histological and behavioral monitoring showed no signs of disruption in the blood brain barrier (BBB) as well as no damage to the nerves and adjacent brain tissue resulting from the sonication. As a novel functional neuro-modulatory modality, the pulsed application of FUS has potential in diagnostic and therapeutic applications in diseases of the peripheral nervous system. PMID:22763009

Correlative CT and anatomic study of the sciatic nerve

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pech, P.; Haughton, V.

1985-05-01

Sciatica can be caused by numerous processes affecting the sciatic nerve or its components within the pelvis including tumors, infectious diseases, aneurysms, fractures, and endometriosis. The CT diagnosis of these causes of sciatica has not been emphasized. This study identified the course and appearance of the normal sciatic nerve in the pelvis by correlating CT and anatomic slices in cadavers. For purposes of discussion, the sciatic nerve complex is conveniently divided into three parts: presacral, muscular, and ischial. Each part is illustrated here by two cryosections with corresponding CT images.

High Ulnar Nerve Injuries: Nerve Transfers to Restore Function.

PubMed

Patterson, Jennifer Megan M

2016-05-01

Peripheral nerve injuries are challenging problems. Nerve transfers are one of many options available to surgeons caring for these patients, although they do not replace tendon transfers, nerve graft, or primary repair in all patients. Distal nerve transfers for the treatment of high ulnar nerve injuries allow for a shorter reinnervation period and improved ulnar intrinsic recovery, which are critical to function of the hand. Copyright © 2016 Elsevier Inc. All rights reserved.

Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects

PubMed Central

Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying

2013-01-01

Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635

Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus

PubMed Central

The, FO; Cailotto, C; van der Vliet, J; de Jonge, WJ; Bennink, RJ; Buijs, RM; Boeckxstaens, GE

2011-01-01

BACKGROUND AND PURPOSE Electrical stimulation of the vagus nerve reduces intestinal inflammation following mechanical handling, thereby shortening post-operative ileus in mice. Previous studies in a sepsis model showed that this cholinergic anti-inflammatory pathway can be activated pharmacologically by central administration of semapimod, an inhibitor of p38 mitogen-activated protein kinase. We therefore evaluated the effect of intracerebroventricular (i.c.v.) semapimod on intestinal inflammation and post-operative ileus in mice. EXPERIMENTAL APPROACH Mice underwent a laparotomy or intestinal manipulation 1 h after i.c.v. pre-treatment with semapimod (1 µg·kg−1) or saline. Drugs were administered through a cannula placed in the left lateral ventricle 1 week prior to experimentation. Twenty-four hours after surgery, gastric emptying was measured using scintigraphy, and the degree of intestinal inflammation was assessed. Finally, activation of brain regions was assessed using quantitative immunohistochemistry for c-fos. KEY RESULTS Intestinal manipulation induced inflammation of the manipulated intestine and significantly delayed gastric emptying, 24 h after surgery in saline-treated animals. Semapimod significantly reduced this inflammation and improved gastric emptying. Vagotomy enhanced the inflammatory response induced by intestinal manipulation and abolished the anti-inflammatory effect of semapimod. Semapimod but not saline induced a significant increase in c-fos expression in the paraventricular nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. CONCLUSIONS AND IMPLICATIONS Our findings show that i.c.v. semapimod reduces manipulation-induced intestinal inflammation and prevented post-operative ileus. This anti-inflammatory effect depends on central activation of the vagus nerve. PMID:21371006

Neurotrophic factors and corneal nerve regeneration

PubMed Central

Sacchetti, Marta; Lambiase, Alessandro

2017-01-01

The cornea has unique features that make it a useful model for regenerative medicine studies. It is an avascular, transparent, densely innervated tissue and any pathological changes can be easily detected by slit lamp examination. Corneal sensitivity is provided by the ophthalmic branch of the trigeminal nerve that elicits protective reflexes such as blinking and tearing and exerts trophic support by releasing neuromediators and growth factors. Corneal nerves are easily evaluated for both function and morphology using standard instruments such as corneal esthesiometer and in vivo confocal microscope. All local and systemic conditions that are associated with damage of the trigeminal nerve cause the development of neurotrophic keratitis, a rare degenerative disease. Neurotrophic keratitis is characterized by impairment of corneal sensitivity associated with development of persistent epithelial defects that may progress to corneal ulcer, melting and perforation. Current neurotrophic keratitis treatments aim at supporting corneal healing and preventing progression of corneal damage. Novel compounds able to stimulate corneal nerve recovery are in advanced development stage. Among them, nerve growth factor eye drops showed to be safe and effective in stimulating corneal healing and improving corneal sensitivity in patients with neurotrophic keratitis. Neurotrophic keratitis represents an useful model to evaluate in clinical practice novel neuro-regenerative drugs. PMID:28966630

[Cholinergic anti-inflammatory pathway of some non-pharmacological therapies of complementary medicine: possible implications for treatment of rheumatic and autoimmune diseases].

PubMed

Gamus, Dorit

2011-08-01

Rheumatologic and autoimmune diseases are among foremost diseases for which patients seek complementary and integrative medicine options. Therefore, physicians should be informed on the advances in research of these therapies, in order to be able to discuss possible indications and contraindications for these treatment modalities with their patients. This review summarizes several therapeutic modalities of complementary medicine that may be involved in the cholinergic anti-inflammatory pathway. The analysis of systematic reviews of acupuncture for rheumatic conditions has concluded that the evidence is sufficiently sound to warrant positive recommendations of this therapy for osteoarthritis, low back pain and lateral elbow pain. There is relatively strong evidence to support the use of hypnosis in pain treatment, such as in cases of fibromyalgia. A recent controlled study that evaLuated tai-chi in fibromyalgia has reported reductions in pain, improvements in mood, quality of Life, self efficacy and exercise capacity. There is also cumulative evidence that acupuncture, hypnosis and tai-chi may decrease the high frequency of heart rate variability, suggesting enhancement of vagus nerve activity. Hence, it has been hypothesized that these modalities might impact the cholinergic anti-inflammatory pathway to modulate inflammation. Further clinical and basic research to confirm this hypothesis should be performed in order to validate integration of these therapies in comprehensive treatment for some inflammatory and autoimmune diseases.

The First Experience of Triple Nerve Transfer in Proximal Radial Nerve Palsy.

PubMed

Emamhadi, Mohammadreza; Andalib, Sasan

2018-01-01

Injury to distal portion of posterior cord of brachial plexus leads to palsy of radial and axillary nerves. Symptoms are usually motor deficits of the deltoid muscle; triceps brachii muscle; and extensor muscles of the wrist, thumb, and fingers. Tendon transfers, nerve grafts, and nerve transfers are options for surgical treatment of proximal radial nerve palsy to restore some motor functions. Tendon transfer is painful, requires a long immobilization, and decreases donor muscle strength; nevertheless, nerve transfer produces promising outcomes. We present a patient with proximal radial nerve palsy following a blunt injury undergoing triple nerve transfer. The patient was involved in a motorcycle accident with complete palsy of the radial and axillary nerves. After 6 months, on admission, he showed spontaneous recovery of axillary nerve palsy, but radial nerve palsy remained. We performed triple nerve transfer, fascicle of ulnar nerve to long head of the triceps branch of radial nerve, flexor digitorum superficialis branch of median nerve to extensor carpi radialis brevis branch of radial nerve, and flexor carpi radialis branch of median nerve to posterior interosseous nerve, for restoration of elbow, wrist, and finger extensions, respectively. Our experience confirmed functional elbow, wrist, and finger extensions in the patient. Triple nerve transfer restores functions of the upper limb in patients with debilitating radial nerve palsy after blunt injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

Tissue-engineered spiral nerve guidance conduit for peripheral nerve regeneration.

PubMed

Chang, Wei; Shah, Munish B; Lee, Paul; Yu, Xiaojun

2018-06-01

Recently in peripheral nerve regeneration, preclinical studies have shown that the use of nerve guidance conduits (NGCs) with multiple longitudinally channels and intra-luminal topography enhance the functional outcomes when bridging a nerve gap caused by traumatic injury. These features not only provide guidance cues for regenerating nerve, but also become the essential approaches for developing a novel NGC. In this study, a novel spiral NGC with aligned nanofibers and wrapped with an outer nanofibrous tube was first developed and investigated. Using the common rat sciatic 10-mm nerve defect model, the in vivo study showed that a novel spiral NGC (with and without inner nanofibers) increased the successful rate of nerve regeneration after 6 weeks recovery. Substantial improvements in nerve regeneration were achieved by combining the spiral NGC with inner nanofibers and outer nanofibrous tube, based on the results of walking track analysis, electrophysiology, nerve histological assessment, and gastrocnemius muscle measurement. This demonstrated that the novel spiral NGC with inner aligned nanofibers and wrapped with an outer nanofibrous tube provided a better environment for peripheral nerve regeneration than standard tubular NGCs. Results from this study will benefit for future NGC design to optimize tissue-engineering strategies for peripheral nerve regeneration. We developed a novel spiral nerve guidance conduit (NGC) with coated aligned nanofibers. The spiral structure increases surface area by 4.5 fold relative to a tubular NGC. Furthermore, the aligned nanofibers was coated on the spiral walls, providing cues for guiding neurite extension. Finally, the outside of spiral NGC was wrapped with randomly nanofibers to enhance mechanical strength that can stabilize the spiral NGC. Our nerve histological data have shown that the spiral NGC had 50% more myelinated axons than a tubular structure for nerve regeneration across a 10 mm gap in a rat sciatic nerve

High-Resolution Nerve Ultrasound and Electrophysiological Findings in Restless Legs Syndrome.

PubMed

Pitarokoili, K; Fels, M; Kerasnoudis, A; Toenges, L; Gold, R; Yoon, M-S

2018-05-11

Restless legs syndrome (RLS) is a multifactorial network disorder of a sensorimotor system extending from dopaminergic and glutamatergic cerebral structures to the spinal neurons and peripheral nerves. The role of peripheral nerve damage in the causality and severity progression for RLS patients remains unclear. We performed a clinical and epidemiological study on a cohort of 34 RLS patients focusing on RLS risk factors and disease severity. We investigated the peripheral nerves with nerve conduction studies and with high-resolution nerve ultrasound (HRUS). In 18 of the 34 patients (mean age 67.4 ± 15 years old), a sensorimotor axonal neuropathy was diagnosed. These patients presented with late-onset RLS were treated with membrane stabilizing agents, whereas no neuropathy predisposing comorbidity could be identified for the majority of them. We could show an inverse correlation between the amplitudes of the tibial nerve for the patients with polyneuropathy and the RLS severity index. Neuropathy patients were characterized by an increase of the cross-sectional area (CSA) of the tibial nerve in the popliteal fossa and by increased intranerve and internerve variability values showing an asymmetry of CSA distribution. This pattern resembles previous studies on diabetic neuropathy. Early diagnosis, characterization, and treatment of neuropathy are increasingly relevant for RLS patients as it correlates with disease severity. HRUS revealed a pattern resembling diabetic neuropathy, which implies a similar pathophysiology with metabolic and ischemic origin of RLS-related axonal neuropathy. Copyright © 2018 by the American Society of Neuroimaging.

Cranial Nerve II

PubMed Central

Gillig, Paulette Marie; Sanders, Richard D.

2009-01-01

This article contains a brief review of the anatomy of the visual system, a survey of diseases of the retina, optic nerve and lesions of the optic chiasm, and other visual field defects of special interest to the psychiatrist. It also includes a presentation of the corticothalamic mechanisms, differential diagnosis, and various manifestations of visual illusions, and simple and complex visual hallucinations, as well as the differential diagnoses of these various visual phenomena. PMID:19855858

An unusual case of isolated sixth cranial nerve palsy in leprosy.

PubMed

Vaishampayan, Sanjeev; Borde, Priyanka

2012-08-15

Cranial nerve involvement is not common in leprosy. The fifth and seventh cranial nerves are the most commonly affected in leprosy. Herein we present a patient with Hansen disease (BL) with type I reaction who developed isolated involvement of the sixth cranial nerve leading to lateral rectus muscle palsy. He responded to timely anti-reactional therapy and it produced a good response. Careful observation of patients with lepra reaction is needed to avoid damage to important organs.

Direct Administration of Nerve-Specific Contrast to Improve Nerve Sparing Radical Prostatectomy

PubMed Central

Barth, Connor W.; Gibbs, Summer L.

2017-01-01

Nerve damage remains a major morbidity following nerve sparing radical prostatectomy, significantly affecting quality of life post-surgery. Nerve-specific fluorescence guided surgery offers a potential solution by enhancing nerve visualization intraoperatively. However, the prostate is highly innervated and only the cavernous nerve structures require preservation to maintain continence and potency. Systemic administration of a nerve-specific fluorophore would lower nerve signal to background ratio (SBR) in vital nerve structures, making them difficult to distinguish from all nervous tissue in the pelvic region. A direct administration methodology to enable selective nerve highlighting for enhanced nerve SBR in a specific nerve structure has been developed herein. The direct administration methodology demonstrated equivalent nerve-specific contrast to systemic administration at optimal exposure times. However, the direct administration methodology provided a brighter fluorescent nerve signal, facilitating nerve-specific fluorescence imaging at video rate, which was not possible following systemic administration. Additionally, the direct administration methodology required a significantly lower fluorophore dose than systemic administration, that when scaled to a human dose falls within the microdosing range. Furthermore, a dual fluorophore tissue staining method was developed that alleviates fluorescence background signal from adipose tissue accumulation using a spectrally distinct adipose tissue specific fluorophore. These results validate the use of the direct administration methodology for specific nerve visualization with fluorescence image-guided surgery, which would improve vital nerve structure identification and visualization during nerve sparing radical prostatectomy. PMID:28255352

Direct Administration of Nerve-Specific Contrast to Improve Nerve Sparing Radical Prostatectomy.

PubMed

Barth, Connor W; Gibbs, Summer L

2017-01-01

Nerve damage remains a major morbidity following nerve sparing radical prostatectomy, significantly affecting quality of life post-surgery. Nerve-specific fluorescence guided surgery offers a potential solution by enhancing nerve visualization intraoperatively. However, the prostate is highly innervated and only the cavernous nerve structures require preservation to maintain continence and potency. Systemic administration of a nerve-specific fluorophore would lower nerve signal to background ratio (SBR) in vital nerve structures, making them difficult to distinguish from all nervous tissue in the pelvic region. A direct administration methodology to enable selective nerve highlighting for enhanced nerve SBR in a specific nerve structure has been developed herein. The direct administration methodology demonstrated equivalent nerve-specific contrast to systemic administration at optimal exposure times. However, the direct administration methodology provided a brighter fluorescent nerve signal, facilitating nerve-specific fluorescence imaging at video rate, which was not possible following systemic administration. Additionally, the direct administration methodology required a significantly lower fluorophore dose than systemic administration, that when scaled to a human dose falls within the microdosing range. Furthermore, a dual fluorophore tissue staining method was developed that alleviates fluorescence background signal from adipose tissue accumulation using a spectrally distinct adipose tissue specific fluorophore. These results validate the use of the direct administration methodology for specific nerve visualization with fluorescence image-guided surgery, which would improve vital nerve structure identification and visualization during nerve sparing radical prostatectomy.

A novel PLP1 mutation associated with optic nerve enlargement in two siblings with Pelizaeus-Merzbacher disease: A new MRI finding.

PubMed

Pavlidou, Efterpi; Ramachandran, Vijaya; Govender, Veronica; Wilson, Clare; Das, Rini; Vlachou, Victoria; Pavlou, Evangelos; Saggar, Anand; Mankad, Kshitij; Kinali, Maria

2017-03-01

Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked disorder characterized by hypomyelination of the Central Nervous System due to mutations in the PLP1 gene. Certain mutations of the PLP1 gene correlate with specific clinical phenotypes and neuroimaging findings. We herein report a novel mutation of the PLP1 gene in two siblings with PMD associated with a rare and protean neuroimaging finding of optic nerve enlargement. To the best of our knowledge this is the first time that this novel mutation H133P of PLP1 gene is identified and clinically associated with optic nerve enlargement in PMD patients. Copyright © 2016 The Japanese Society of Child Neurology. All rights reserved.

Nerve regeneration in nerve grafts conditioned by vibration exposure.

PubMed

Bergman, S; Widerberg, A; Danielsen, N; Lundborg, G; Dahlin, L B

1995-01-01

Regeneration distances were studied in nerves from vibration-exposed limbs. One hind limb of anaesthetized rats was attached to a vibration exciter and exposed to vibration (80 Hz/32 m/s2) for 5 h/day for 2 or 5 days. Seven days after the latest vibration period a 10-mm long nerve graft was taken from the vibrated sciatic nerve and sutured into a corresponding defect in the con-tralateral sciatic nerve and vice versa, thereby creating two different models within the same animal: (i) regeneration from a freshly transected unvibrated nerve into a vibrated graft and (ii) regeneration from a vibrated nerve into a fresh nerve graft (vibrated recipient side). Four, 6 or 8 days postoperatively (p.o.) the distances achieved by the regenerating axons were determined using the pinch reflex test. Two days of vibration did not influence the regeneration, but 5 days of vibration reduced the initial delay period and a slight reduction of regeneration rate was observed. After 5 days of vibration an increased regeneration distance was observed in both models at day 4 p.o. and at day 6 p.o. in vibrated grafts. This study demonstrates that vibration can condition peripheral nerves and this may be caused by local changes in the peripheral nerve trunk and in the neuron itself.

The role of great auricular-facial nerve neurorrhaphy in facial nerve damage.

PubMed

Sun, Yan; Liu, Limei; Han, Yuechen; Xu, Lei; Zhang, Daogong; Wang, Haibo

2015-01-01

Facial nerve is easy to be damaged, and there are many reconstructive methods for facial nerve reconstructive, such as facial nerve end to end anastomosis, the great auricular nerve graft, the sural nerve graft, or hypoglossal-facial nerve anastomosis. However, there is still little study about great auricular-facial nerve neurorrhaphy. The aim of the present study was to identify the role of great auricular-facial nerve neurorrhaphy and the mechanism. Rat models of facial nerve cut (FC), facial nerve end to end anastomosis (FF), facial-great auricular neurorrhaphy (FG), and control (Ctrl) were established. Apex nasi amesiality observation, electrophysiology and immunofluorescence assays were employed to investigate the function and mechanism. In apex nasi amesiality observation, it was found apex nasi amesiality of FG group was partly recovered. Additionally, electrophysiology and immunofluorescence assays revealed that facial-great auricular neurorrhaphy could transfer nerve impulse and express AChR which was better than facial nerve cut and worse than facial nerve end to end anastomosis. The present study indicated that great auricular-facial nerve neurorrhaphy is a substantial solution for facial lesion repair, as it is efficiently preventing facial muscles atrophy by generating neurotransmitter like ACh.

Intracranial nonvestibular neurinomas: Young neurosurgeons’ experience

PubMed Central

Chowdhury, Forhad Hossain; Haque, Mohammod R.; Kawsar, Khandkar A.; Sarker, Mainul H.; Hasan, Mahmudul; Goel, Atul H.

2014-01-01

Background and Objectives: Neurinoma arising from other than nonvestibular cranial nerves is less prevalent. Here we present our experiences regarding the clinical profile, investigations, microneurosurgical management, and the outcome of nonvestibular cranial nerve neurinomas. Materials and Methods: From January 2005 to December 2011, the recorded documents of operated nonvestibular intracranial neurinomas were retrospectively studied for clinical profile, investigations, microneurosurgical management, complications, follow-up, and outcomes. Results: The average follow-up was 24.5 months. Total number of cases was 30, with age ranging from 9 to 60 years. Sixteen cases were males and 14 were females. Nonvestibular cranial nerve schwannomas most commonly originated from trigeminal nerve followed by glossopharyngeal+/vagus nerve. There were three abducent nerve schwannomas that are very rare. There was no trochlear nerve schwannoma. Two glossopharyngeal+/vagus nerve schwannomas extended into the neck through jugular foramen and one extended into the upper cervical spinal canal. Involved nerve dysfunction was a common clinical feature except in trigeminal neurinomas where facial pain was a common feature. Aiming for no new neurodeficit, total resection of the tumor was done in 24 cases, and near-total resection or gross total resection or subtotal resection was done in 6 cases. Preoperative symptoms improved or disappeared in 25 cases. New persistent deficit occurred in 3 cases. Two patients died postoperatively. There was no recurrence of tumor till the last follow-up. Conclusion: Nonvestibular schwannomas are far less common, but curable benign lesions. Surgical approach to the skull base and craniovertebral junction is a often complex and lengthy procedure associated with chances of significant morbidity. But early diagnosis, proper investigations, and evaluation, along with appropriate decision making and surgical planning with microsurgical techniques are the

Barriers to Seizure Management in Schools: Perceptions of School Nurses.

PubMed

Terry, Debbie; Patel, Anup D; Cohen, Daniel M; Scherzer, Daniel; Kline, Jennifer

2016-12-01

The purpose of this study was to assess school nurses' perceptions of barriers to optimal management of seizures in schools. Eighty-three school nurses completed an electronic survey. Most agreed they felt confident they could identify a seizure (97.6%), give rectal diazepam (83.8%), and handle cluster seizures (67.1%), but fewer were confident they could give intranasal midazolam (63.3%), had specific information about a student's seizures (56.6%), or could swipe a vagus nerve stimulator magnet (47.4%). Nurses were more likely to be available at the time of a seizure in rural (17/20) (85%) versus suburban (21/34) (62%) or urban (8/25) (32%) schools (P = .001). School nurses are comfortable managing seizures in the school setting. However, a specific seizure plan for each child and education on intranasal midazolam and vagus nerve stimulator magnet use are needed. A barrier in urban schools is decreased availability of a nurse to identify seizures and administer treatment. © The Author(s) 2016.

The effects of area postrema lesions and selective vagotomy on motion-induced conditioned taste aversion

NASA Technical Reports Server (NTRS)

Fox, Robert A.; Sutton, R. L.; Mckenna, Susan

1991-01-01

Conditioned taste aversion (CTA) is one of several behaviors which was suggested as a putative measure of motion sickness in rats. A review is made of studies which used surgical disruption of area postrema or the vagus nerve to investigate whether CTA and vomiting induced by motion may depend on common neural pathways or structures. When the chemoreceptive function of the area postrema (AP) is destroyed by complete ablation, rats develop CTA and cats and monkeys develop CTA and vomit. Thus the AP is not crucially involved in either CTA or vomiting induced by motion. However, after complete denervation of the stomach or after labyrinthectomy rats do not develop CTA when motion is used as the unconditioned stimulus. Studies of brainstem projections of the vagus nerve, the area postrema, the periaqueductal grey, and the vestibular system are used as the basis for speculation about regions which could mediate both motion-induced vomiting and behavioral food aversion.

Assessment of nerve regeneration across nerve allografts treated with tacrolimus.

PubMed

Haisheng, Han; Songjie, Zuo; Xin, Li

2008-01-01

Although regeneration of nerve allotransplant is a major concern in the clinic, there have been few papers quantitatively assessing functional recovery of animals' nerve allografts in the long term. In this study, functional recovery, histopathological study, and immunohistochemistry changes of rat nerve allograft with FK506 were investigated up to 12 weeks without slaughtering. C57 and SD rats were used for transplantation. The donor's nerve was sliced and transplanted into the recipient. The sciatic nerve was epineurally sutured with 10-0 nylon. In total, 30 models of transplantation were performed and divided into 3 groups that were either treated with FK506 or not. Functional recovery of the grafted nerve was serially assessed by the pin click test, walking track analysis and electrophysiological evaluations. A histopathological study and immunohistochemistry study were done in the all of the models. Nerve allografts treated with FK506 have no immune rejection through 12 weeks. Sensibility had similarly improved in both isografts and allografts. There has been no difference in each graft. Walk track analysis demonstrates significant recovery of motor function of the nerve graft. No histological results of difference were found up to 12 weeks in each graft. In the rodent nerve graft model, FK506 prevented nerve allograft rejection across a major histocompatibility barrier. Sensory recovery seems to be superior to motor function. Nerve isograft and allograft treated with FK506 have no significant difference in function recovery, histopathological result, and immunohistochemistry changes.

Patients with Dry Eye Disease and Low Subbasal Nerve Density are at High Risk for an Accelerated Corneal Endothelial Cell Loss

PubMed Central

Kheirkhah, Ahmad; Satitpitakul, Vannarut; Hamrah, Pedram; Dana, Reza

2016-01-01

Purpose To evaluate the changes in corneal endothelial cell density (CECD) over time in patients with dry eye disease (DED) and to correlate the endothelial cell loss with corneal subbasal nerve density. Methods This retrospective study included 40 eyes of 20 patients with DED. Laser in vivo confocal microscopy had been performed in the central cornea of both eyes at an initial visit and repeated after a mean follow-up of 33.2 ± 10.2 months. The densities of corneal endothelial cells and subbasal nerves were measured in both visits and compared with 13 eyes of 13 normal age-matched controls. Results At the initial visit, the DED group had lower densities of corneal endothelial cells (2620 ± 386 cells/mm2) and subbasal nerves (17.8 ± 7.5 mm/mm2) compared with the control group (2861 ± 292 cells/mm2 and 22.8 ± 3.0 mm/mm2, with P=0.08 and P=0.01, respectively). At the end of follow-up, although there was no significant change in subbasal nerve density (16.7 ± 7.2 mm/mm2, P=0.43), the mean CECD significantly decreased to 2465 ± 391 cells/mm2 (P=0.01), with a mean corneal endothelial cell loss of 2.1 ± 3.6% per year. The endothelial cell loss showed a statistically significant negative correlation with the initial subbasal nerve density (Rs= −0.55, P=0.02). Conclusion Patients with DED have an accelerated corneal endothelial cell loss which is more than what has been reported in the literature for normal aging. Those with lower subbasal nerve density, in particular, are at a higher risk for endothelial cell loss over time. PMID:28060067

Suprascapular nerve block (using bupivacaine and methylprednisolone acetate) in chronic shoulder pain.

PubMed

Shanahan, E M; Ahern, M; Smith, M; Wetherall, M; Bresnihan, B; FitzGerald, O

2003-05-01

Shoulder pain from inflammatory arthritis and/or degenerative disease is a common cause of morbidity in the community. It is difficult to treat and there are limited data on the efficacy of most interventions. Suprascapular nerve block has shown promise in limited trials in reducing shoulder pain. There have been no large randomised placebo controlled trials examining the efficacy of suprascapular nerve block for shoulder pain in arthritis and/or degenerative disease using pain and disability end points. To perform a randomised, double blind, placebo controlled trial of the efficacy of suprascapular nerve block for shoulder pain in rheumatoid arthritis (RA) and/or degenerative disease of the shoulder. 83 people with chronic shoulder pain from degenerative disease or RA took part in the trial. If a person had two painful shoulders, these were randomised separately. A total of 108 shoulders were randomised. Patients in the group receiving active treatment had a single suprascapular nerve block following the protocol described by Dangoisse et al, while those in the other group received a placebo injection of normal saline administered subcutaneously. The patients were followed up for 12 weeks by an observer who was unaware of the randomisation and reviewed at weeks 1, 4, and 12 after the injection. Pain, disability, and range of movement data were gathered. Clinically and statistically significant improvements in all pain scores, all disability scores, and some range of movement scores in the shoulders receiving suprascapular nerve block compared with those receiving placebo were seen at weeks 1, 4, and 12. There were no significant adverse effects in either group. Suprascapular nerve block is a safe and efficacious treatment for the treatment of shoulder pain in degenerative disease and/or arthritis. It improves pain, disability, and range of movement at the shoulder compared with placebo. It is a useful adjunct treatment for the practising clinician to assist in the

Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

DTIC Science & Technology

2016-04-01

faster regeneration and functional recovery. Peripheral nerve injury is a common complication of complex tissue trauma and often results in significant...having poor regeneration overall, the areas of regenerating nerve tissue could often be found in sections of the nerve guide where luminal spaces of...conducted in this Aim also provided important insight into the NGC design parameters necessary to allow for maximum nerve tissue ingrowth and regeneration

The role of great auricular-facial nerve neurorrhaphy in facial nerve damage

PubMed Central

Sun, Yan; Liu, Limei; Han, Yuechen; Xu, Lei; Zhang, Daogong; Wang, Haibo

2015-01-01

Background: Facial nerve is easy to be damaged, and there are many reconstructive methods for facial nerve reconstructive, such as facial nerve end to end anastomosis, the great auricular nerve graft, the sural nerve graft, or hypoglossal-facial nerve anastomosis. However, there is still little study about great auricular-facial nerve neurorrhaphy. The aim of the present study was to identify the role of great auricular-facial nerve neurorrhaphy and the mechanism. Methods: Rat models of facial nerve cut (FC), facial nerve end to end anastomosis (FF), facial-great auricular neurorrhaphy (FG), and control (Ctrl) were established. Apex nasi amesiality observation, electrophysiology and immunofluorescence assays were employed to investigate the function and mechanism. Results: In apex nasi amesiality observation, it was found apex nasi amesiality of FG group was partly recovered. Additionally, electrophysiology and immunofluorescence assays revealed that facial-great auricular neurorrhaphy could transfer nerve impulse and express AChR which was better than facial nerve cut and worse than facial nerve end to end anastomosis. Conclusions: The present study indicated that great auricular-facial nerve neurorrhaphy is a substantial solution for facial lesion repair, as it is efficiently preventing facial muscles atrophy by generating neurotransmitter like ACh. PMID:26550216

Nerve Blocks

MedlinePlus

... turn off" a pain signal along a specific distribution of nerve. Imaging guidance may be used to place the needle in the most appropriate location for maximum benefit. A nerve block may allow a damaged nerve time to heal, provide temporary pain relief and help ...

[Regeneration and repair of peripheral nerves: clinical implications in facial paralysis surgery].

PubMed

Hontanilla, B; Vidal, A

2000-01-01

Peripheral nerve lesions are one of the most frequent causes of chronic incapacity. Upper or lower limb palsies due to brachial or lumbar plexus injuries, facial paralysis and nerve lesions caused by systemic diseases are one of the major goals of plastic and reconstructive surgery. However, the poor results obtained in repaired peripheral nerves during the Second World War lead to a pessimist vision of peripheral nerve repair. Nevertheless, a well understanding of microsurgical principles in reconstruction and molecular biology of nerve regeneration have improved the clinical results. Thus, although the results obtained are quite far from perfect, these procedures give to patients a hope in the recuperation of their lesions and then on function. Technical aspects in nerve repair are well established; the next step is to manipulate the biology. In this article we will comment the biological processes which appear in peripheral nerve regeneration, we will establish the main concepts on peripheral nerve repair applied in facial paralysis cases and, finally, we will proportionate some ideas about how clinical practice could be affected by manipulation of the peripheral nerve biology.

Sensory neuropathy in two Border collie puppies.

PubMed

Vermeersch, K; Van Ham, L; Braund, K G; Bhatti, S; Tshamala, M; Chiers, K; Schrauwen, E

2005-06-01

A peripheral sensory neuropathy was diagnosed in two Border collie puppies. Neurological, electrophysiological and histopathological examinations suggested a purely sensory neuropathy with mainly distal involvement. Urinary incontinence was observed in one of the puppies and histological examination of the vagus nerve revealed degenerative changes. An inherited disorder was suspected.

Electroencephalogram and Heart Rate Regulation to Familiar and Unfamiliar People in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Van Hecke, Amy Vaughan; Lebow, Jocelyn; Bal, Elgiz; Lamb, Damon; Harden, Emily; Kramer, Alexis; Denver, John; Bazhenova, Olga; Porges, Stephen W.

2009-01-01

Few studies have examined whether familiarity of partner affects social responses in children with autism. This study investigated heart rate regulation (respiratory sinus arrhythmia [RSA]: The myelinated vagus nerve's regulation of heart rate) and temporal-parietal electroencephalogram (EEG) activity while nineteen 8- to 12-year-old children with…

Fibrolipomatous hamartoma of the inferior calcaneal nerve (Baxter nerve).

PubMed

Zeng, Rong; Frederick-Dyer, Katherine; Ferguson, N Lynn; Lewis, James; Fu, Yitong

2012-09-01

Fibrolipomatous hamartoma (FLH) is a rare, benign lesion of the peripheral nerves most frequently involving the median nerve and its digital branches (80 %). Pathognomonic MR features of FLH such as coaxial-cable-like appearance on axial planes and a spaghetti-like appearance on coronal planes have been described by Marom and Helms, obviating the need for diagnostic biopsy. We present a case of fibrolipomatous hamartoma of the inferior calcaneal nerve (Baxter nerve) with associated subcutaneous fat proliferation.

Rational identification of a novel soy-derived anxiolytic-like undecapeptide acting via gut-brain axis after oral administration.

PubMed

Ota, Ami; Yamamoto, Akane; Kimura, Saeko; Mori, Yukiha; Mizushige, Takafumi; Nagashima, Yoshiki; Sato, Masaru; Suzuki, Hideyuki; Odagiri, Saori; Yamada, Daisuke; Sekiguchi, Masayuki; Wada, Keiji; Kanamoto, Ryuhei; Ohinata, Kousaku

2017-05-01

Here we found that the chymotryptic digest of soy β-conglycinin, a major storage protein, exhibited anxiolytic-like effects in mice. We then searched for anxiolytic-like peptides in the digest. Based on a comprehensive peptide analysis of the chymotryptic digest by high performance liquid chromatograph connected to an LTQ Orbitrap mass spectrometer and the structure-activity relationship of known peptides, we explored anxiolytic-like peptides present in the digest. FLSSTEAQQSY, which corresponds to 323-333 of the β-conglycinin α subunit [βCGα(323-333)] emerged as a candidate. Oral administration of synthetic βCGα(323-333) exhibited anxiolytic-like effects in the elevated plus-maze and open-field test in male mice. Orally administered βCGα(323-333) exhibited anxiolytic-like effects in sham-operated control mice but not in vagotomized mice. In addition, oral administration of βCGα(323-333) increased the expression of c-Fos, a marker of neuronal activity, in the nucleus of the solitary tract, which receives inputs from the vagus nerve. These results suggest that the anxiolytic-like effects were mediated by the vagus nerve. The anxiolytic-like effects of βCGα(323-333) were also blocked by antagonists of the serotonin 5-HT 1A , dopamine D 1 and GABA A receptors. However βCGα(323-333) had no affinity for these receptors, suggesting it stimulates the release of endogenous neurotransmitters to activate the receptors. Taken together, a soy-derived undecapeptide, βCGα(323-333), may exhibit anxiolytic-like effects after oral administration via the vagus nerve and 5-HT 1A , D 1 and GABA A systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus.

PubMed

The, Fo; Cailotto, C; van der Vliet, J; de Jonge, W J; Bennink, R J; Buijs, R M; Boeckxstaens, G E

2011-07-01

Electrical stimulation of the vagus nerve reduces intestinal inflammation following mechanical handling, thereby shortening post-operative ileus in mice. Previous studies in a sepsis model showed that this cholinergic anti-inflammatory pathway can be activated pharmacologically by central administration of semapimod, an inhibitor of p38 mitogen-activated protein kinase. We therefore evaluated the effect of intracerebroventricular (i.c.v.) semapimod on intestinal inflammation and post-operative ileus in mice. Mice underwent a laparotomy or intestinal manipulation 1 h after i.c.v. pre-treatment with semapimod (1 µg·kg(-1) ) or saline. Drugs were administered through a cannula placed in the left lateral ventricle 1 week prior to experimentation. Twenty-four hours after surgery, gastric emptying was measured using scintigraphy, and the degree of intestinal inflammation was assessed. Finally, activation of brain regions was assessed using quantitative immunohistochemistry for c-fos. Intestinal manipulation induced inflammation of the manipulated intestine and significantly delayed gastric emptying, 24 h after surgery in saline-treated animals. Semapimod significantly reduced this inflammation and improved gastric emptying. Vagotomy enhanced the inflammatory response induced by intestinal manipulation and abolished the anti-inflammatory effect of semapimod. Semapimod but not saline induced a significant increase in c-fos expression in the paraventricular nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. Our findings show that i.c.v. semapimod reduces manipulation-induced intestinal inflammation and prevented post-operative ileus. This anti-inflammatory effect depends on central activation of the vagus nerve. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection

PubMed Central

Wang, Hongkui; Zhu, Hui; Guo, Qi; Qian, Tianmei; Zhang, Ping; Li, Shiying; Xue, Chengbin; Gu, Xiaosong

2017-01-01

Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration. PMID:29085283

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection.

PubMed

Wang, Hongkui; Zhu, Hui; Guo, Qi; Qian, Tianmei; Zhang, Ping; Li, Shiying; Xue, Chengbin; Gu, Xiaosong

2017-01-01

Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration.

Electrophysiology of Cranial Nerve Testing: Spinal Accessory and Hypoglossal Nerves.

PubMed

Stino, Amro M; Smith, Benn E

2018-01-01

Multiple techniques have been developed for the electrodiagnostic evaluation of cranial nerves XI and XII. Each of these carries both benefits and limitations, with more techniques and data being available in the literature for spinal accessory than hypoglossal nerve evaluation. Spinal accessory and hypoglossal neuropathy are relatively uncommon cranial mononeuropathies that may be evaluated in the outpatient electrodiagnostic laboratory setting. A review of available literature using PubMed was conducted regarding electrodiagnostic technique in the evaluation of spinal accessory and hypoglossal nerves searching for both routine nerve conduction studies and repetitive nerve conduction studies. The review provided herein provides a resource by which clinical neurophysiologists may develop and implement clinical and research protocols for the evaluation of both of these lower cranial nerves in the outpatient setting.

Pectoral nerves (PECS) and intercostal nerve block for cardiac resynchronization therapy device implantation.

PubMed

Fujiwara, Atsushi; Komasawa, Nobuyasu; Minami, Toshiaki

2014-01-01

A 71-year-old man was scheduled to undergo cardiac resynchronization therapy device (CRTD) implantation. He was combined with severe chronic heart failure due to ischemic heart disease. NYHA class was 3 to 4 and electrocardiogram showed non-sustained ventricular. Ejection fraction was about 20% revealed by transthoracic echocardiogram. He was also on several anticoagulation medications. We planned to implant the device under the greater pectoral muscle. As general anesthesia was considered risky, monitored anesthesia care utilizing peripheral nerve block and slight sedation was scheduled. Pectoral nerves (PECS) block and intercostal block was performed under ultrasonography with ropivacaine. For sedation during the procedure, continuous infusion of dexmedetomidine without a loading dose was performed. The procedure lasted about 3 hours, but the patient showed no pain or restlessness. Combination of PECS block and intercostal block may provide effective analgesia for CRTD implantation.

A historical perspective on the role of sensory nerves in neurogenic inflammation.

PubMed

Sousa-Valente, João; Brain, Susan D

2018-05-01

The term 'neurogenic inflammation' is commonly used, especially with respect to the role of sensory nerves within inflammatory disease. However, despite over a century of research, we remain unclear about the role of these nerves in the vascular biology of inflammation, as compared with their interacting role in pain processing and of their potential for therapeutic manipulation. This chapter attempts to discuss the progress in understanding, from the initial discovery of sensory nerves until the present day. This covers pioneering findings that these nerves exist, are involved in vascular events and act as important sensors of environmental changes, including injury and infection. This is followed by discovery of the contents they release such as the established vasoactive neuropeptides substance P and CGRP as well as anti-inflammatory peptides such as the opioids and somatostatin. The more recent emergence of the importance of the transient receptor potential (TRP) channels has revealed some of the mechanisms by which these nerves sense environmental stimuli. This knowledge enables a platform from which to learn of the potential role of neurogenic inflammation in disease and in turn of novel therapeutic targets.

A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.

PubMed

Archibald, S J; Krarup, C; Shefner, J; Li, S T; Madison, R D

1991-04-22

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP

[Herpes zoster of the trigeminal nerve: a case report and review of the literature].

PubMed

Carbone, V; Leonardi, A; Pavese, M; Raviola, E; Giordano, M

2004-01-01

Herpes zoster (shingles) is caused when the varicella zoster virus that has remained latent since an earlier varicella infection (chicken-pox) is reactivated. Herpes Zoster is a less common and endemic disease than varicella: factors causing reactivation are still not well known, but it occurs in older and/or immunocompromised individuals. Following reactivation, centrifugal migration of herpes zoster virus (HZV) occurs along sensory nerves to produce a characteristic painful cutaneous or mucocutaneous vesicular eruption that is generally limited to the single affected dermatome. Herpes zoster may affect any sensory ganglia and its cutaneous nerve: the most common sites affected are thoracic dermatomes (56%), followed by cranial nerves (13%) and lumbar (13%), cervical (11%) and sacral nerves (4%). Among cranial nerves, the trigeminal and facial nerves are the most affected due to reactivation of HZV latent in gasserian and geniculated ganglia. The 1st division of the trigeminal nerve is commonly affected, whereas the 2nd and the 3rd are rarely involved. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist, since many diseases can cause orofacial pain, and the diagnosis must be established before final treatment. A literature review of herpes zoster of the trigeminal nerve is presented and the clinical presentation, differential diagnosis and treatment modalities are underlined. A case report is presented.

Histone deacetylase expression patterns in developing murine optic nerve

PubMed Central

2014-01-01

Background Histone deacetylases (HDACs) play important roles in glial cell development and in disease states within multiple regions of the central nervous system. However, little is known about HDAC expression or function within the optic nerve. As a first step in understanding the role of HDACs in optic nerve, this study examines the spatio-temporal expression patterns of methylated histone 3 (K9), acetylated histone 3 (K18), and HDACs 1–6 and 8–11 in the developing murine optic nerve head. Results Using RT-qPCR, western blot and immunofluorescence, three stages were analyzed: embryonic day 16 (E16), when astrocyte precursors are found in the optic stalk, postnatal day 5 (P5), when immature astrocytes and oligodendrocytes are found throughout the optic nerve, and P30, when optic nerve astrocytes and oligodendrocytes are mature. Acetylated and methylated histone H3 immunoreactivity was co-localized in the nuclei of most SOX2 positive glia within the optic nerve head and adjacent optic nerve at all developmental stages. HDACs 1–11 were expressed in the optic nerve glial cells at all three stages of optic nerve development in the mouse, but showed temporal differences in overall levels and subcellular localization. HDACs 1 and 2 were predominantly nuclear throughout optic nerve development and glial cell maturation. HDACs 3, 5, 6, 8, and 11 were predominantly cytoplasmic, but showed nuclear localization in at least one stage of optic nerve development. HDACs 4, 9 and10 were predominantly cytoplasmic, with little to no nuclear expression at any time during the developmental stages examined. Conclusions Our results showing that HDACs 1, 2, 3, 5, 6, 8, and 11 were each localized to the nuclei of SOX2 positive glia at some stages of optic nerve development and maturation and extend previous reports of HDAC expression in the aging optic nerve. These HDACs are candidates for further research to understand how chromatin remodeling through acetylation, deacetylation

Optic Nerve Decompression

MedlinePlus

... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Optic Nerve Decompression John Lee, MD Introduction Optic nerve decompression is a surgical procedure aimed at ...

Tissue resident macrophages are sufficient for demyelination during peripheral nerve myelin induced experimental autoimmune neuritis?

PubMed

Taylor, Jude Matthew

2017-12-15

The contribution of resident endoneurial tissue macrophages versus recruited monocyte derived macrophages to demyelination and disease during Experimental Autoimmune Neuritis (EAN) was investigated using passive transfer of peripheral nerve myelin (PNM) specific serum antibodies or adoptive co-transfer of PNM specific T and B cells from EAN donors to leukopenic and normal hosts. Passive transfer of PNM specific serum antibodies or adoptive co-transfer of myelin specific T and B cells into leukopenic recipients resulted in a moderate reduction in nerve conduction block or in the disease severity compared to the normal recipients. This was despite at least a 95% decrease in the number of circulating mononuclear cells during the development of nerve conduction block and disease and a 50% reduction in the number of infiltrating endoneurial macrophages in the nerve lesions of the leukopenic recipients. These observations suggest that during EAN in Lewis rats actively induced by immunization with peripheral nerve myelin, phagocytic macrophages originating from the resident endoneurial population may be sufficient to engage in demyelination initiated by anti-myelin antibodies in this model. Copyright © 2017 Elsevier B.V. All rights reserved.

[Recent progress of mitochondrial quality control in ischemic heart disease and its role in cardio-protection of vagal nerve].

PubMed

Xue, Run-Qing; Xu, Man; Yu, Xiao-Jiang; Liu, Long-Zhu; Zang, Wei-Jin

2017-10-25

Ischemic heart disease (IHD) is the life-threatening cardiovascular disease. Mitochondria have emerged as key participants and regulators of cellular energy demands and signal transduction. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission, fusion and mitophagy, which plays an important role in maintaining healthy mitochondria and cardiac function. Recently, dysfunction of each process in mitochondrial quality control has been observed in the ischemic hearts. This review describes the mechanism of mitochondrial dynamics and mitophagy as well as its performance linked to myocardial ischemia. Moreover, in combination with our study, we will discuss the effect of vagal nerve on mitochondria in cardio-protection.

The Vagal Nerve Stimulates Activation of the Hepatic Progenitor Cell Compartment via Muscarinic Acetylcholine Receptor Type 3

PubMed Central

Cassiman, David; Libbrecht, Louis; Sinelli, Nicoletta; Desmet, Valeer; Denef, Carl; Roskams, Tania

2002-01-01

In the rat the hepatic branch of the nervus vagus stimulates proliferation of hepatocytes after partial hepatectomy and growth of bile duct epithelial cells after bile duct ligation. We studied the effect of hepatic vagotomy on the activation of the hepatic progenitor cell compartment in human and rat liver. The number of hepatic progenitor cells and atypical reactive ductular cells in transplanted (denervated) human livers with hepatitis was significantly lower than in innervated matched control livers and the number of oval cells in vagotomized rat livers with galactosamine hepatitis was significantly lower than in livers of sham-operated rats with galactosamine hepatitis. The expression of muscarinic acetylcholine receptors (M1-M5 receptor) was studied by immunohistochemistry and reverse transcriptase-polymerase chain reaction. In human liver, immunoreactivity for M3 receptor was observed in hepatic progenitor cells, atypical reactive ductules, intermediate hepatocyte-like cells, and bile duct epithelial cells. mRNA for the M1-M3 and the M5 receptor, but not the M4 receptor, was detected in human liver homogenates. In conclusion, the hepatic vagus branch stimulates activation of the hepatic progenitor cell compartment in diseased liver, most likely through binding of acetylcholine to the M3 receptor expressed on these cells. These findings may be of clinical importance for patients with a transplant liver. PMID:12163377

Review: Tauopathy in the retina and optic nerve: does it shadow pathological changes in the brain?

PubMed Central

Ho, Wing-Lau; Leung, Yen; Tsang, Andrea Wing-Ting; So, Kwok-Fai; Chiu, Kin

2012-01-01

Tau protein’s versatility lies in its functions within the central nervous system, including protein scaffolding and intracellular signaling. Tauopathy has been one of the most extensively studied neuropathologies among the neurodegenerative diseases. Because the retina and optic nerve are parts of the central nervous system, we hypothesize that tauopathy also plays a role in various eye diseases. However, little is known about tauopathy in the retina and optic nerve. Here, we summarize the findings from histopathological studies on animal models and human specimens with distinct neurodegenerative diseases. Similar pathological changes of tau protein can be found in Alzheimer’s disease, frontotemporal lobe dementia, and glaucoma. In view of the important roles of tauopathy in the brain, it is hoped that this review can stimulate research on eye diseases of the retina and optic nerve. PMID:23170062

Reconstruction of peripheral nerves using acellular nerve grafts with implanted cultured Schwann cells.

PubMed

Frerichs, Onno; Fansa, Hisham; Schicht, Christoph; Wolf, Gerald; Schneider, Wolfgang; Keilhoff, Gerburg

2002-01-01

The bridging of nerve gaps is still one of the major problems in peripheral nerve surgery. The present experiment describes our attempt to engineer different biologic nerve grafts in a rat sciatic nerve model: cultured isogenic Schwann cells were implanted into 2-cm autologous acellular nerve grafts or autologous predegenerated nerve grafts. Autologous nerve grafts and predegenerated or acellular nerve grafts without implanted Schwann cells served as controls. The regenerated nerves were assessed histologically and morphometrically after 6 weeks. Predegenerated grafts showed results superior in regard to axon count and histologic appearance in comparison to standard grafts and acellular grafts. The acellular nerve grafts showed the worst histologic picture, but axon counts were in the range of standard grafts. The implantation of Schwann cells did not yield significant improvements in any group. In conclusion, the status of activation of Schwann cells and the stadium of Wallerian degeneration in a nerve graft might be key factors for regeneration, rather than total number of Schwann cells. Predegenerated nerve grafts are therefore superior to standard grafts in the rat model. Acellular grafts are able to bridge nerve gaps of up to 2 cm in the rat model, but even the addition of cultivated Schwann cells did not lead to results as good as in the group with autologous nerve grafts. Copyright 2002 Wiley-Liss, Inc. MICROSURGERY 22:311-315 2002

Imaging of Cranial Nerves III, IV, VI in Congenital Cranial Dysinnervation Disorders

PubMed Central

Kim, Jae Hyoung

2017-01-01

Congenital cranial dysinnervation disorders are a group of diseases caused by abnormal development of cranial nerve nuclei or their axonal connections, resulting in aberrant innervation of the ocular and facial musculature. Its diagnosis could be facilitated by the development of high resolution thin-section magnetic resonance imaging. The purpose of this review is to describe the method to visualize cranial nerves III, IV, and VI and to present the imaging findings of congenital cranial dysinnervation disorders including congenital oculomotor nerve palsy, congenital trochlear nerve palsy, Duane retraction syndrome, Möbius syndrome, congenital fibrosis of the extraocular muscles, synergistic divergence, and synergistic convergence. PMID:28534340

Imaging of Cranial Nerves III, IV, VI in Congenital Cranial Dysinnervation Disorders.

PubMed

Kim, Jae Hyoung; Hwang, Jeong Min

2017-06-01

Congenital cranial dysinnervation disorders are a group of diseases caused by abnormal development of cranial nerve nuclei or their axonal connections, resulting in aberrant innervation of the ocular and facial musculature. Its diagnosis could be facilitated by the development of high resolution thin-section magnetic resonance imaging. The purpose of this review is to describe the method to visualize cranial nerves III, IV, and VI and to present the imaging findings of congenital cranial dysinnervation disorders including congenital oculomotor nerve palsy, congenital trochlear nerve palsy, Duane retraction syndrome, Möbius syndrome, congenital fibrosis of the extraocular muscles, synergistic divergence, and synergistic convergence. © 2017 The Korean Ophthalmological Society.

Vagus nerve stimulator implantation for epilepsy in a paediatric hospital: outcomes and effect on quality of life.

PubMed

Ulate-Campos, A; Cean-Cabrera, L; Petanas-Argemi, J; García-Fructuoso, G; Aparicio, J; López-Sala, A; Palacio-Navarro, A; Mas, M J; Muchart, J; Rebollo, M; Sanmartí, F X

2015-10-01

Epilepsy, which is present in 0.5% to 1% of the paediatric population, is one of the most frequent childhood neurological disorders. Approximately 20% to 30% of these cases will be drug-resistant. The objective of this study is to describe the impact of vagal nerve stimulation (VNS) on seizures and quality of life in a sample of 30 patients. Descriptive, retrospective study of all patients with a VNS device implanted between 2008 and 2013 in a single paediatric hospital, based on patients' medical records. Quality of life was assessed using the Spanish scale for quality of life in children with epilepsy, completed by means of a telephone interview. We describe a population of 19 boys (64%) and 11 girls (36%) with a mean age at seizure onset of 21 months (1-144 months). The mean age of VNS implantation was 11.89 years. Follow-up periods ranged from 6 to 36 months. Mean reduction in seizures at 6 months was 38%, with a reduction of 43% at 12 months, 42% at 24 months, and 54% at 36 months. At least half of all patients were classified as responders. According to the quality of life scale, 54% of the families rated the effect of VNS as either very good or good while 39% rated it as fair. VNS is a safe palliative treatment that is generally well tolerated. It is partially effective for controlling drug-resistant epilepsy and exerts a positive effect on quality of life. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

My gut feeling says rest: Increased intestinal permeability contributes to chronic diseases in high-intensity exercisers.

PubMed

Van Houten, Jason M; Wessells, Robert J; Lujan, Heidi L; DiCarlo, Stephen E

2015-12-01

Chronic diseases are the leading cause of death and disability worldwide, and many of these conditions are linked to chronic inflammation. One potential cause of chronic inflammation is an increased intestinal epithelial permeability. Recent studies have demonstrated that parasympathetic stimulation via the efferent abdominal vagus nerve increases the expression and proper localization of tight junction proteins and decreases intestinal epithelial permeability. This finding may provide a novel approach for treating and preventing many chronic conditions. Importantly, physical activity is associated with increased resting parasympathetic (vagal) activity and lower risk of chronic diseases. However, high intensity long duration exercise can be harmful to overall health. Specifically, individuals who frequently exercise strenuously and for longer time intervals have the same mortality rates as sedentary individuals. This may be explained, in part, by longer periods of reduced vagal activity as vagal activity is markedly reduced both during and after intense exercise. We hypothesize that one mechanism by which exercise provides its health benefits is by increasing resting vagal activity and decreasing intestinal epithelial permeability, thus decreasing chronic inflammation. Additionally, we hypothesize that long periods of reduced vagal activity in individuals who exercise at high intensities and for longer durations, decrease the integrity of the intestinal barrier, putting them at greater risk of chronic inflammation and a host of chronic diseases. Thus, this hypothesis provides a conceptual link between the well-established benefits of frequent exercise and the paradoxical deleterious effects of prolonged, high-intensity exercise without adequate rest. Copyright © 2015. Published by Elsevier Ltd.

Radial nerve palsy

PubMed Central

Bumbasirevic, Marko; Palibrk, Tomislav; Lesic, Aleksandar; Atkinson, Henry DE

2016-01-01

As a result of its proximity to the humeral shaft, as well as its long and tortuous course, the radial nerve is the most frequently injured major nerve in the upper limb, with its close proximity to the bone making it vulnerable when fractures occur. Injury is most frequently sustained during humeral fracture and gunshot injuries, but iatrogenic injuries are not unusual following surgical treatment of various other pathologies. Treatment is usually non-operative, but surgery is sometimes necessary, using a variety of often imaginative procedures. Because radial nerve injuries are the least debilitating of the upper limb nerve injuries, results are usually satisfactory. Conservative treatment certainly has a role, and one of the most important aspects of this treatment is to maintain a full passive range of motion in all the affected joints. Surgical treatment is indicated in cases when nerve transection is obvious, as in open injuries or when there is no clinical improvement after a period of conservative treatment. Different techniques are used including direct suture or nerve grafting, vascularised nerve grafts, direct nerve transfer, tendon transfer, functional muscle transfer or the promising, newer treatment of biological therapy. Cite this article: Bumbasirevic M, Palibrk T, Lesic A, Atkinson HDE. Radial nerve palsy. EFORT Open Rev 2016;1:286-294. DOI: 10.1302/2058-5241.1.000028. PMID:28461960

Charcot-Marie-Tooth Disease

MedlinePlus

Charcot-Marie-Tooth disease (CMT) is a group of genetic nerve disorders. It is named after the three doctors who first identified it. ... a nerve biopsy. There is no cure. The disease can be so mild you don't realize ...

Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson's Disease Patients.

PubMed

Mu, Liancai; Chen, Jingming; Sobotka, Stanislaw; Nyirenda, Themba; Benson, Brian; Gupta, Fiona; Sanders, Ira; Adler, Charles H; Caviness, John N; Shill, Holly A; Sabbagh, Marwan; Samanta, Johan E; Sue, Lucia I; Beach, Thomas G

2015-08-01

Dysphagia is common in Parkinson's disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia.

Electrophysiology of Cranial Nerve Testing: Trigeminal and Facial Nerves.

PubMed

Muzyka, Iryna M; Estephan, Bachir

2018-01-01

The clinical examination of the trigeminal and facial nerves provides significant diagnostic value, especially in the localization of lesions in disorders affecting the central and/or peripheral nervous system. The electrodiagnostic evaluation of these nerves and their pathways adds further accuracy and reliability to the diagnostic investigation and the localization process, especially when different testing methods are combined based on the clinical presentation and the electrophysiological findings. The diagnostic uniqueness of the trigeminal and facial nerves is their connectivity and their coparticipation in reflexes commonly used in clinical practice, namely the blink and corneal reflexes. The other reflexes used in the diagnostic process and lesion localization are very nerve specific and add more diagnostic yield to the workup of certain disorders of the nervous system. This article provides a review of commonly used electrodiagnostic studies and techniques in the evaluation and lesion localization of cranial nerves V and VII.

Continuous intraoperative neuromonitoring (CIONM) of the recurrent laryngeal nerve is sufficient as the only neuromonitoring technique in thyroidectomy performed because of benign goitre.

PubMed

Adamczewski, Zbigniew; Chwałkiewicz, Michał; Lewiński, Andrzej; Brzeziński, Jan; Dedecjus, Marek

2015-01-01

Recently, intraoperative neurophysiological neuromonitoring (IONM) of recurrent laryngeal nerves (RLN) has been evolving quickly. This evolution touched many aspects of the technique, leading to continuous stimulation of the RLN with real time analysis of the electrical signal. The aim of the study was to estimate the value of continuous intraoperative neuromonitoring (CIONM) as the only technique for intraoperative neuromonitoring in thyroidectomy performed because of benign goitre. The study comprised 80 women qualified for thyroidectomy due to nodular goitre. The patients were divided into 4 groups depending on the technique used for RLN integrity verification: group 1 - thyroidectomy with CIONM; group 2 - thyroidectomy with direct, intermittent stimulation of RLN and vagus nerve (NX); group 3 - both CIONM and intermittent stimulation of RLN and NX; group 4 - thyroidectomy without any IONM. Mean operation time did not differ significantly among the groups with IONM, but was significantly longer in comparison to group 4, as well as the operation's cost. In the analysed groups there was no significant difference in complication ratio. CIONM with RLN visualization in thyroidectomy performed because of benign goitre is as safe as other methods of IONM and gives a continuous confirmation of the electrical integrity of the loop NX-RLN-vocal folds during almost the entire procedure. There is a clinical need for the development of external stimulation of NX (transdermal or trancranial), particularly for minimally invasive techniques in which access to NX is limited (i.e. transoral thyroidectomy).

[Blood-nerve barrier and peripheral nerve regeneration].

PubMed

Kanda, Takashi

2013-01-01

Blood-nerve barrier (BNB) restricts the movement of soluble mediators and leukocytes from the blood contents to the peripheral nervous system (PNS) parenchyma and thus maintains the endoneurial homeostasis. However, it interferes the supply of various neurotrophic factors from the blood constituents and stops the drainage of toxic substances out of the PNS parenchyma, resulting in the inhibition of peripheral nerve regeneration. If the manipulation of BNB function is possible, regeneration of peripheral nerve may be facilitated via the alteration of peripheral nerve microenvironment and ample supply of neurotrophic substances. A possible method to manipulate the BNB for therapeutic purposes is to modify the endothelial function using siRNAs, oligonucleotides and virus vectors. Another possible method is to modify BNB pericytes: small hydrophobic substances that can reach the pericyte membrane through the endothelial monolayer and strengthen the pericytic activity, including the release of various cytokines/chemokines that influence endothelial function, may also be useful as drug candidates to control the BNB function.

Some Non-FDA Approved Uses for Neuromodulation in Treating Autonomic Nervous System Disorders: A Discussion of the Preliminary Support.

PubMed

Lee, Samuel; Abd-Elsayed, Alaa

2016-12-01

Neuromodulation, including cavernous nerve stimulation, gastric electrical stimulation, deep brain stimulation, and vagus nerve stimulation, has been used with success in treating several functional disease conditions. The FDA has approved the use of neuromodulation for a few indications. We discuss in our review article the evidence of using neuromodulation for treating some important disorders involving the autonomic nervous system that are not currently FDA approved. This was a review article that included a systematic online web search for human clinical studies testing the efficacy of neuromodulation in treating erectile dysfunction, gastroparesis, gastroesophageal reflux disease, obesity, asthma, and heart failure. Our review includes all feasibility studies, nonrandomized clinical trials, and randomized controlled trials. Our systematic literature search found 3, 4, 5, 4, 1, and 4 clinical studies relating to erectile dysfunction, gastroparesis, gastroesophageal reflux disease, obesity, asthma, and heart failure, respectively. This review article shows preliminary support based on clinical studies that neuromodulation can be of benefit for patients with important autonomic nervous system disease conditions that are not currently approved by the FDA. All of these investigational uses are encouraging; further studies are necessary and warranted for all indications discussed in this review before achieving FDA approval. © 2016 International Neuromodulation Society.

Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury.

PubMed

Lin, Tao; Qiu, Shuai; Yan, Liwei; Zhu, Shuang; Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin

2018-05-01

Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018. © 2017 Wiley Periodicals, Inc.