Brainstem evoked responses.

ContextNeuromodulation is an expanding field of study for headache treatment to reduce pain by targeting structures within the nervous system that are commonly involved in headache pathophysiology, such as the vagus nerve (VNS), occipital nerves, or sphenopalatine ganglion (SPG) for stimulation. Pharmaceutical medical therapies for abortive and prophylactic treatment, such as triptans, NSAIDs, beta-blockers, TCAs, and antiepileptics, are effective for some individuals, but the role that technology plays in investigating other therapeutic modalities is essential. Peripheral neuromodulation has gained popularity and FDA approval for use in treating certain headaches and migraine headache conditions, particularly in those who are refractory to treatment. Early trials found FDA approved neurostimulatory implant devices, including Cephaly and SpringTMS, improved patient-oriented outcomes with reductions in headaches per month (frequency) and severity.Evidence AcquisitionThis was a narrative review. The sources for this review are as follows: Searching on PubMed, Google Scholar, Medline, and ScienceDirect from 1990 - 2019 using keywords: Peripheral Neuromodulation, Headache, vagus nerve, occipital nerves, sphenopalatine ganglion.ResultsThe first noninvasive neurostimulator device approved for migraine treatment was the Cefaly device, an external trigeminal nerve stimulation device (e-TNS) that transcutaneously excites the supratrochlear and supraorbital branches of the ophthalmic nerve. The second noninvasive neurostimulation device receiving FDA approval was the single-pulse transcranial magnetic stimulator, SpringTMS, positioned at the occiput to treat migraine with aura. GammaCore is a handheld transcutaneous vagal nerve stimulator applied directly to the neck at home by the patient for treatment of cluster headache (CH) and migraine. Several other devices are in development for the treatment of headaches and target headache evolution at different levels and inputs. The Scion device is a caloric vestibular stimulator (CVS) which interfaces with the user through a set of small cones resting in the ear canal on either side and held in place by modified over-ear headphones. The pulsante SPG Microstimulator is a patient-controlled device implanted in the patient’s upper jaw via an hour-long oral procedure to target the sphenopalatine ganglion. The occipital nerve stimulator (ONS) is an invasive neuromodulation device for headache treatment that consists of an implanted pulse generator on the chest wall connected to a subcutaneous lead with 4 - 8 electrodes that is tunneled the occiput.ConclusionsThe aim of this review is to provide a comprehensive overview of the efficacy, preliminary outcomes, and limitations of neurostimulatory implants available for use in the US and those pending further development.

Occipital nerve stimulation (ONS), an established treatment for medically intractable headache syndromes, has lead migration rates quoted up to 24%. In a series of patients with ideal characteristics for this treatment modality, we describe an operative technique for ONS involving the novel use of narrow paddle electrodes: "S8 Lamitrode" (St. Jude Medical [SJM], St. Paul, MN, USA).Five patients (occipital neuralgia [ON] = 4; chronic migraine [CM] = 1) were treated with ONS between 2010 and 2011. All patients had a successful trial of peripheral neurostimulation (Algotec Ltd, Crawley, UK) therapy. Operative technique involved the use of a park-bench position, allowing simultaneous exposure of the occipital and infraclavicular regions. Through a retromastoid/occipital incision just beneath the external occipital protruberance, exposing the extrafascial plane, the S8 Lamitrode is implanted to intersect both greater occipital nerves for bilateral pain or unilateral greater and lesser occipital nerves for unilateral ON or with significant component of the pain relating to the lesser occipital nerve.Over the median follow-up of 12 months, there were no episodes of lead migration or revision. There also was significant improvement in symptoms in all patients.This is the first reported use of S8 Lamitrode electrode for ONS. This narrow electrode is suited for this role leading to minimal trauma during surgical placement, facilitates resolution of problems with lead migration, and optimizes effect with stimulation focused more in direction of the occipital nerves without skin involvement. To date, the SJM Genesis neurostimulation system, with percutaneous electrodes only, is CE mark approved in Europe for peripheral nerve stimulation of the occipital nerves for the management of pain and disability for patients diagnosed with intractable CM. Further developments and studies are required for better devices to suit ONS, thereby avoiding frequently encountered problems and which may clarify the role of paddle leads in ONS.

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

The trigeminal autonomic cephalalgias (TACs) are highly disabling primary headache disorders. There are several issues that remain unresolved in the understanding of the pathophysiology of the TACs, although activation of the trigeminal-autonomic reflex and ipsilateral hypothalamic activation both play a central role. The discovery of the central role of the hypothalamus led to its use as a therapeutic target. After the good results obtained with hypothalamic stimulation, other peripheral neuromodulation targets were tried in the management of refractory cluster headache (CH) and other TACs. This review is a summary both of CH pathophysiology and of efficacy of the different neuromodulation techniques. In chronic cluster headache (CCH) patients, hypothalamic deep brain stimulation (DBS) produced a decrease in attack frequency of more than 50% in 60% of patients. Occipital nerve stimulation (ONS) also elicited favorable outcomes with a reduction of more than 50% of attacks in around 70% of patients with medically intractable CCH. Stimulation of the sphenopalatine ganglion (SPG) with a miniaturized implanted stimulator produced a clinically significant improvement in 68% of patients (acute, preventive, or both). Vagus nerve stimulation (VNS) with a portable device used in conjunction with standard of care in CH patients resulted in a reduction in the number of attacks. DBS and ONS have been used successfully in some cases of other TACs, including hemicrania continua (HC) and short-lasting unilateral headache attacks (SUNHA). DBS has good results, but it is a more invasive technique and can generate serious adverse events. ONS has good results, but frequent and not serious adverse events. SPG stimulation (SPGS) is also efficacious in the acute and prophylactic treatment of refractory cluster headache. At this moment, ONS and SPG stimulation techniques are recommended as first line therapy in refractory cluster patients. New recent non-invasive approaches such as the non-invasive vagal nerve stimulator (nVNS) have shown efficacy in a few trials and could be an interesting alternative in the management of CH, but require more testing and positive randomized controlled trials.

During early development, peripheral sensory systems generate physiological activity prior to exposure to normal environmental stimuli. This activity is thought to facilitate maturation of these neurons and their connections, perhaps even promoting efficacy or modifying downstream circuitry. In the mammalian auditory system, initial connections form at embryonic ages, but the functional characteristics of these early neural connections have not been assayed. We investigated processes of embryonic auditory development using a whole-head slice preparation that preserved connectivity between peripheral and brainstem stations of the auditory pathway. Transgenic mice expressing fluorescent protein provided observation of spiral ganglion and cochlear nucleus neurons to facilitate targeted electrophysiological recording. Here we demonstrate an apparent peripheral-to-central order for circuit maturation. Spiral ganglion cells acquire action potential-generating capacity at embryonic day 14 (E14), the earliest age tested, and action potential waveforms begin to mature in advance of comparable states for neurons of the ventral cochlear nucleus (VCN) and medial nucleus of the trapezoid body (MNTB). In accordance, auditory nerve synapses in the VCN are functional at E15, prior to VCN connectivity with the MNTB, which occurs at least 1 day later. Spiral ganglion neurons exhibit spontaneous activity at least by E14 and are able to drive third-order auditory brainstem neurons by E17. This activity precedes cochlear-generated wave activity by 4 days and ear canal opening by at least 2 weeks. Together, these findings reveal a previously unknown initial developmental phase for auditory maturation, and further implicate the spiral ganglion as a potential controlling centre in this process.

The Extensive Study of Adygean Ethno- Music and Sound Therapy in the North Caucasus Mountains Influenced the Hypothetical Design of a Therapeutical Sound System Capable of Creating Balance and Symmetry in the Human Body With Energetically Forced, Sympathetic Resonance and Entrainment

Stimulation of the greater occipital nerve increases metabolic activity in the trigeminal nucleus caudalis and cervical dorsal horn of the cat

There is growing interest in neuromodulation for primary headache conditions. Invasive modalities such as occipital nerve stimulation, deep brain stimulation and sphenopalatine ganglion stimulation are reserved for the most severe and intractable patients. Non-invasive options such as vagal nerve stimulation (nVNS), supraorbital nerve stimulation (nSONS) and transcranial magnetic nerve stimulation (TMS) have all emerged as potentially useful headache treatments. This review examines the evidence base for non-invasive neuromodulation in trigeminal autonomic cephalalgias and migraine. Although a number of open-label series of non-invasive neuromodulation devices have been published, there is very little controlled evidence for their use in any headache condition. Open-label evidence suggests that nVNS may have a role in the prophylactic treatment of cluster headache and there is limited evidence to suggest it may be useful in the acute treatment of cluster and potentially migraine attacks. There is limited controlled evidence to suggest a role for nSONS in the prophylactic treatment of episodic migraine but there is no evidence to support its use in cluster headache. TMS may be efficacious in the acute treatment of episodic migraine has no controlled evidence to support its use as a preventative in any headache condition. Non-invasive neuromodulation techniques are an attractive treatment option with excellent safety profiles but their use is not yet supported by high-quality randomised controlled trials.

Occipital nerve stimulation (ONS) is a treatment with evidence in refractory chronic cluster headache (CCH). However, the variable response rate and cost make it necessary to investigate predictors of response. This is a cross-sectional study conducted through the review of medical records of CCH patients from six hospitals in Madrid. Epidemiological and clinical variables were compared between patients with ONS failure and the rest. ONS failure was defined as the need for device withdrawal or switch off because of lack of response or adverse events. From a series of 88 CCH, 26 (29.6%) underwent ONS surgery, of whom 13/26 (50.0%) failed because lack of response. ONS failure group had an earlier headache onset (mean ± SD) of 27.7 ± 6.9 vs. 36.7 ± 11.8 years, p = 0.026) and a higher smoking rate (100% vs. 42.9%, p = 0.006). Stational fluctuations (58.3% vs. 7.7%, p = 0.007) and nocturnal exacerbations (91.7% vs. 53.9%, p = 0.035) were more frequent in the ONS failure group as well. There was no difference between groups in diagnostic delay, years of evolution prior to surgery, mental illness, comorbidity with other headache disorders or chronic pain conditions or prior response to occipital nerves anesthetic blocks. Some clinical features such as an early debut, smoking and seasonal or circadian fluctuations could be related to failure of ONS in refractory CCH.

E 36 (Zusanli) “punto maestro” de la inmunidad

To the Editor We would like to congratulate Dr. Levy and all coauthors on their experimental study showing that vagus nerve stimulation (VNS) abrogated gut injury and lymph toxicity in trauma and hemorrhagic shock (1). This interesting and important study shows that mechanical VNS reduced gut injury upon combined trauma and hemorrhagic shock. Although VNS resulted in significant protective effects, the authors mention that the clinical use of VNS is limited and therefore strive toward a pharmacological intervention. It was previously shown that apart from mechanical or pharmaceutical stimulation, the autonomic nervous system can also be stimulated in a physiological way via dietary fat (2). Ingestion of dietary lipids, proteins, and peptides triggers release of cholecystokinin that predominantly binds to cholecystokinin 1 receptors located on afferent vagal fibers (3). In this way, the autonomic nervous system is rapidly activated via vagal afferents resulting in a reduction of the inflammatory response by binding of acetylcholine to α7 nicotinic receptors on inflammatory cells (2). Furthermore, nutritional stimulation of the vagus nerve preserves intestinal barrier function at an early stage. Reduction of mast cell activation and reduction of neutrophil influx (4) are involved in this process. This protection of intestinal barrier function by lipid-enriched enteral nutrition results in reduced bacterial translocation to mesenteric lymph nodes and distant organs and reduced circulating endotoxin levels following hemorrhagic shock (5). Besides hemorrhagic shock, the protective effects of this nutritional intervention with dietary fat have been proven to be very efficient in various other experimental models including a two-hit model of hemorrhagic shock and bacterial infection and a model of bowel manipulation (6, 7). Recently, we expanded the experimental animal data in a human preclinical study showing that continuous administration of enriched enteral nutrition resulted in a rapid anti-inflammatory effect in a human model of endotoxemia (8). Timing of the intervention is essential, and VNS is most effective when given just before the inciting event, as was done in the article of Levy et al. However, our group has also shown that nutritional stimulation of the vagus nerve via dietary lipids preserves intestinal barrier integrity when given after the hemorrhagic shock (9). Stimulation of the vagus nerve following events such as severe trauma may therefore be a potential therapy to attenuate gut injury and its sequelae. Besides mechanical and pharmacological activation of the vagus nerve, nutritional stimulation is a simple and physiological way to achieve this stimulation also in a clinical setting. Misha D. Luyer Department of Surgery Catharina Hospital Eindhoven The Netherlands Jacco-Juri de Haan Department of Internal Medicine Medisch Spectrum Twente Enschede, The Netherlands Tim Lubbers Department of Surgery Maastricht University Medical Centre The Netherlands Jan Willen M. Greve Department of Surgery Atrium Medisch Centrum Heerlen, The Netherlands Wim A. Buurman Institute Nutrim Maastricht University The Netherlands

Occipital nerve stimulation has shown promising results in attack prevention in patients with chronic cluster headache, but evidence from controlled trials is scarce. Conventional (tonic) occipital nerve stimulation elicits paresthesia, hampering blinded comparison to placebo. Using paresthesia-free burst occipital nerve stimulation, we conducted a randomized, placebo-controlled trial. The study is an investigator-initiated, double-blind, randomized, placebo-controlled clinical trial involving participants with chronic cluster headache. It comprised a four-week baseline, a 12-week trial with transcutaneous electrical nerve stimulation, occipital nerve stimulator implantation, a 12-week randomized, double-blind burst occipital nerve stimulation treatment period, and a 12-week open-label tonic occipital nerve stimulation treatment period. The primary outcomes were safety and the proportion of participants reporting a ≥30% reduction in attack frequency in the randomized and open-label trial phases. Participants were enrolled between August 2021 and October 2023. 116 chronic cluster headache patients were assessed for eligibility. Sixty-five were excluded, and 51 entered baseline observation. Before occipital nerve stimulator implantation and randomization, an additional 13 were excluded. Thirty-eight participants underwent occipital nerve stimulator implantation and were randomly assigned to burst occipital nerve stimulation (n = 19) or placebo (n = 19). After the randomized trial phase, the proportion of ≥30% responders was 18.81% (95%CI 0.28%–37.87%) in the burst occipital nerve stimulation group and 50.02% (95%CI 26.87%–73.09%) in the placebo group. The likelihood of reaching the primary endpoint was 31.20% (95%CI 1.29%–61.23%, p = 0.042) higher in the placebo group. After the open-label phase, 42.09% (95%CI 19.91%–64.34%) in the burst occipital nerve stimulation group and 51.11% (95%CI 27.32%–74.88%) in the placebo group had ≥30% frequency reduction. In total, 20 adverse events were registered; eight were treatment-related serious adverse events. The most common adverse event was temporary occipital dysesthesia in eight participants. Occipital nerve stimulation reduced attack frequency but was not superior to placebo. The treatment had an acceptable safety profile and was well-tolerated. The results call for attention to sufficient placebo control when planning further studies. The trial is registered at clinicaltrials.gov (identifier NCT05023460).Study registration date: July 27th 2021.

The role of the vagus nerve on the renal circulation was investigated on mongrel dogs using the cross circulation method. The stimulation of the efferent cervical vagus nerve caused a decrease in renal blood flow in a half of the experiments. The denervation of the barore-ceptors abolished the change in renal blood flow on stimulation of the efferent cervical vagus nerve. The stimulation of the efferent thoracic vagus nerve did not affect the renal blood flow. The efferent renal vasomotor fibers were not demonstrated in the vagus nerve.

Vagus nerve stimulation in rheumatoid arthritis - Authors' reply.

Editorial| April 2023 Modulating the Cardiac Autonomic Nervous System: Stay Close to My Heart or Keep Your Distance? This article has an Audio Podcast Karsten Bartels, M.D., Ph.D., M.B.A.; Karsten Bartels, M.D., Ph.D., M.B.A. 1Department of Anesthesiology, University of Nebraska Medical Center, Omaha, Nebraska; Outcomes Research Consortium, Cleveland, Ohio. https://orcid.org/0000-0003-2028-4664 Search for other works by this author on: This Site PubMed Google Scholar Amanda A. Fox, M.D., M.P.H. Amanda A. Fox, M.D., M.P.H. 2Department of Anesthesiology and Pain Management, and McDermott Center for Human Growth and Development/Center for Human Genetics, University of Texas Southwestern Medical Center, Dallas, Texas. Search for other works by this author on: This Site PubMed Google Scholar Author and Article Information This editorial accompanies the article on p. 372. Accepted for publication February 1, 2023. Address correspondence to Dr. Bartels: karbartels@unmc.edu Anesthesiology April 2023, Vol. 138, 348–350. https://doi.org/10.1097/ALN.0000000000004529 Connected Content Article: GABAergic Signaling during Spinal Cord Stimulation Reduces Cardiac Arrhythmias in a Porcine Model Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Search Site Citation Karsten Bartels, Amanda A. Fox; Modulating the Cardiac Autonomic Nervous System: Stay Close to My Heart or Keep Your Distance?. Anesthesiology 2023; 138:348–350 doi: https://doi.org/10.1097/ALN.0000000000004529 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll PublicationsAnesthesiology Search Advanced Search Topics: autonomic nervous system, heart Perioperative cardiac protection research is needed to determine how to prevent and mitigate cardiac injury that can lead to cardiovascular morbidity and mortality. In this month’s issue of Anesthesiology, Howard-Quijano et al.1 report effects of high thoracic spinal cord stimulation on decreasing sympathetic stimulation of the heart and corresponding ventricular arrhythmias. What is particularly meaningful about this paper is that the authors do experiments on Yorkshire pigs in order to define the biology underlying the favorable cardiac effects of high thoracic spinal cord stimulation. In their manuscript, the authors report findings from an elegant sequence of experiments demonstrating specifically that (1) spinal cord stimulation therapy during cardiac ischemia resulted in fewer ventricular arrhythmias, (2) intrathecal γ-aminobutyric acid type A (GABAA) and γ-aminobutyric acid type B (GABAB) receptor blockade eliminated the protective effects of spinal cord stimulation, (3) intrathecal administration of γ-aminobutyric acid (GABA) transaminase... You do not currently have access to this content.