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VNS DISCUSSIONS => General VNS Discusions => Topic started by: dennis100 on February 21, 2015, 01:17:41 AM

Title: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on February 21, 2015, 01:17:41 AM
Vagus Nerve Stimulation to Augment Recovery From Minimally Conscious or Persistently Vegetative States After Traumatic Brain Injury

Verified by: VA New York Harbor Healthcare System, January 2011
First Received: December 14, 2010 | Last Updated: August 9, 2011
Phase: Phase 3 | Start Date: January 2011
Overall Status: Recruiting | Estimated Enrollment: 12

Brief Summary
Official Title: “Vagus Nerve Stimulation to Augment Recovery From Minimally Conscious or Persistently Vegetative States After Traumatic Brain Injury”

Traumatic brain injury has a high morbidity and mortality in both civilian and military populations. Blast and other mechanisms of traumatic brain injury damage the brain by causing neurons to disconnect and atrophy. Such traumatic axonal injury can lead to persistently vegetative and minimally conscious states, for which extremely limited treatment options exist, including physical, occupational, speech and cognitive therapies.

More than 50,000 patients have received vagus nerve stimulation for epilepsy and depression. In addition to decreased seizure frequency and severity, patients report enhanced mood, reduced daytime sleepiness independent of seizure control, increased slow wave sleep, and improved cognition, memory, and quality of life.

The purpose of this study is to demonstrate objective improvement in clinical outcome by placement of a vagus nerve stimulator in patients who are recovering from severe traumatic brain injury. Our hypothesis is that stimulation of the vagus nerve results in increased cerebral blood flow and metabolism in the forebrain, thalamus and reticular formation, which promotes arousal and improved consciousness, thereby improving outcome after traumatic brain injury resulting in minimally conscious or persistent vegetative states. If this study demonstrates that vagus nerve stimulation can safely and positively impact outcome, then a larger randomized prospective crossover trial will be proposed.

The investigators will achieve this objective by evaluating whether vagus nerve stimulation impacts clinical recovery from minimally conscious or persistent vegetative states caused by traumatic brain injury as assessed by the FIM™ instrument and Functional Assessment Measure (FIM+FAM) as well as the JFK Coma Recovery Scale Score. The investigators will also evaluate whether vagus nerve stimulation alters resting and activational functional MRI.

Twelve patients will be enrolled in this initial crossover pilot study. These patients will have sustained a severe traumatic brain injury (Disability Rating Scale score of 22 to 29) more than twelve months from starting the study, and have no other concurrent active severe medical problems. Baseline EEG and magnetic resonance imaging (MRI) will be performed prior to left vagus nerve stimulation implantation. Patients will be randomized to alternating three month periods with the device on or off. Outcomes will be assessed at three month intervals with the FIM™ instrument and Functional Assessment Measure (FIM+FAM) and JFK Coma Recovery Scale by a neuropsychologist blinded to the status of the device. Outcomes will also be assessed using quantitative eye movement tracking and functional magnetic resonance imaging. Patients will cross over every 3 months and be followed for at least 18 months.
Study Type: Interventional

Study Design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Title: Re: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on February 21, 2015, 02:07:06 AM
Vagus nerve stimulation inhibits heroin-seeking behavior induced by heroin priming or heroin-associated cues in rats.
Liu H1, Liu Y, Yu J, Lai M, Zhu H, Sun A, Chen W, Zhou W.

⦁   Abstract
Vagus nerve stimulation has been used for the treatment of neuropsychiatric disorders, such as epilepsy. However, little is known whether it is also effective for the treatment of heroin dependence, in particular for relapse to heroin seeking. In the present study, we investigated the effects of vagus nerve stimulation on reinstatement (relapse) of heroin-seeking behavior induced by heroin priming or heroin-associated cues. The rats were trained for heroin self-administration for 14days and followed by extinction training in which heroin was replaced by saline and heroin-associated cues were turned off. In addition, animals were also received daily electric stimulation of vagus nerve (30Hz, pulse width of 0.5ms, 0.5mA (low-intensity) or 1mA (high-intensity); 30s on, 5min off; 10 continuous cycle per day) or false stimulation during extinction training. We found that such vagus nerve stimulation significantly inhibited heroin priming (0.25mg/kg, s.c.) - or heroin-associated conditioned cue-induced reinstatement of drug-seeking behavior, when compared to false stimulation control. Further, such a behavioral inhibition was correlated to a reduction in the expression of FosB and an increase in the expression of phosphorylation of cAMP response element binding protein (p-CREB) in nucleus accumbens. The data suggest that vagus nerve stimulation may inhibit heroin- or heroin cue-induced relapse, possibly by regulation of the expression of Fos and CREB in nucleus accumbens.

Title: Re: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on February 21, 2015, 02:47:14 AM
Vagal nerve stimulation modulates gut injury and lung permeability in trauma-hemorrhagic shock.
Levy G1, Fishman JE, Xu DZ, Dong W, Palange D, Vida G, Mohr A, Ulloa L, Deitch EA.
Author information
⦁   Abstract
Hemorrhagic shock is known to disrupt the gut barrier leading to end-organ dysfunction. The vagus nerve can inhibit detrimental immune responses that contribute to organ damage in hemorrhagic shock. Therefore, we explored whether stimulation of the vagus nerve can protect the gut and recover lung permeability in trauma-hemorrhagic shock (THS).

Male Sprague-Dawley rats were subjected to left cervical vagus nerve stimulation at 5 V for 10 minutes. The right internal jugular and femoral artery were cannulated for blood withdrawal and blood pressure monitoring, respectively. Animals were then subjected to hemorrhagic shock to a mean arterial pressure between 30 mm Hg and 35 mm Hg for 90 minutes then reperfused with their own whole blood. After observation for 3 hours, gut permeability was assessed with fluorescein dextran 4 in vivo injections in a ligated portion of distal ileum followed by Evans blue dye injection to assess lung permeability. Pulmonary myeloperoxidase levels were measured and compared.

Vagal nerve stimulation abrogated THS-induced lung injury (mean [SD], 8.46 [0.36] vs. 4.87 [0.78]; p < 0.05) and neutrophil sequestration (19.39 [1.01] vs. 12.83 [1.16]; p < 0.05). Likewise, THS gut permeability was reduced to sham levels.

Neuromodulation decreases injury in the THS model as evidenced by decreased gut permeability as well as decreased lung permeability and pulmonary neutrophil sequestration in a rat model.

Title: Re: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on February 21, 2015, 04:14:03 AM
Devices in the management of advanced, chronic heart failure.
Abraham WT1, Smith SA.
Author information
⦁   Abstract
Heart failure (HF) is a global phenomenon, and the overall incidence and prevalence of the condition are steadily increasing. Medical therapies have proven efficacious, but only a small number of pharmacological options are in development. When patients cease to respond adequately to optimal medical therapy, cardiac resynchronization therapy has been shown to improve symptoms, reduce hospitalizations, promote reverse remodelling, and decrease mortality. However, challenges remain in identifying the ideal recipients for this therapy. The field of mechanical circulatory support has seen immense growth since the early 2000s, and left ventricular assist devices (LVADs) have transitioned over the past decade from large, pulsatile devices to smaller, more-compact, continuous-flow devices. Infections and haematological issues are still important areas that need to be addressed. Whereas LVADs were once approved only for 'bridge to transplantation', these devices are now used as destination therapy for critically ill patients with HF, allowing these individuals to return to the community. A host of novel strategies, including cardiac contractility modulation, implantable haemodynamic-monitoring devices, and phrenic and vagus nerve stimulation, are under investigation and might have an impact on the future care of patients with chronic HF.

Title: Re: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on February 21, 2015, 04:55:04 AM
The current perspective of neuromodulation techniques in the treatment of alcohol addiction: a systematic review.
Herremans SC1, Baeken C.
Author information
⦁   Abstract
Alcohol dependency can be considered as a chronic mental disorder characterized by frequent relapses even when treated with appropriate medical or psychotherapeutic interventions. Here, the efficacy of different neuromodulation techniques in alcohol addiction, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), vagal nerve stimulation (VNS) and electroconvulsive therapy (ECT) is critically evaluated.

A broad literature search on electronic databases such as NCBI PubMed, the Web of Knowledge, the Cochrane Library was conducted. Additionally, we searched recent handbooks on neuromodulation and/or addiction.

Studies investigating these neuromodulation techniques in alcohol addiction remain to date rather limited and especially tDCS and rTMS applications have been investigated. Overall, the clinical effects seem modest. The use of VNS and ECT has yet to be investigated in alcohol dependent patients.

Neuromodulation techniques have only recently been subject to investigation in alcohol addiction and methodological differences between the few studies restrict clear-cut conclusions. Nevertheless, the scarce results encourage further investigation in alcohol addiction.

Title: Re: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on February 21, 2015, 07:57:04 AM
Vagus nerve stimulation shows promise for stroke rehabilitation
Issued: Mon, 09 Mar 2015 16:06:00 GMT
An experimental technique to help stroke patients regain the use of their arms has shown promising results in a small-scale trial.

Vagus nerve stimulation (VNS), which aims to encourage the growth of new neural connections in the brain, was shown to help patients in Glasgow improve arm function by a greater degree than standard physiotherapy alone.

Additional patients are being invited to participate in a follow-on clinical trial to further expand the post-stroke rehabilitation program and to ascertain the potential wider benefits of the therapy.
A stroke occurs as a result of a loss of blood supply to a part of the brain, leading to tissue death and loss of functions controlled by the affected brain area. Around 85% of stroke victims seen at Glasgow’s stroke clinic in at the Western Infirmary have arm weakness, which persists to a significant degree in half of these.

Presenting his results at the International Stroke Conference in Nashville, USA last month, Dr Jesse Dawson, of the Institute of Cardiovascular & Medical Sciences at the University of Glasgow, who led the trial efforts, said: “There are no proven treatments beyond general rehabilitation strategies to improve hand function after stroke. A few methods may benefit the shoulder-elbow function, but nothing yet has worked to improve hand function.

“Vagus nerve stimulation has been suggested as a way of utilising neuroplasticity in the brain to drive the growth of new neural connections related to a specific body movement. This involves implanting a nerve stimulator, which provides electrical impulses during physiotherapy sessions.
“Our initial study demonstrates that VNS paired therapy holds promise. Greater improvements in arm function were observed in patients using VNS paired therapy compared to participants using traditional rehabilitation alone.

“We need to do larger trials to confirm our findings and determine if the widespread adoption of this technique could benefit post-stroke patients with upper limb deficits. These initial results are certainly encouraging and warrant further investigation.”

The two-year trial, which recruited 20 patients in Glasgow and Newcastle with long-term arm weakness after their stroke, involved the implantation of a small electrical device into the body.
The electrical device is similar to a pacemaker and is implanted in the chest region of the patient. It then is connected to the vagus nerve in the neck using thin wires that are also implanted.
Scientists chose to stimulate the vagus nerve since it connects to structures in the brain that are involved in recovery from injury.

The idea was to take advantage of neuroplasticity – the natural ability of the brain to form new neural connections. Pairing the vagus nerve stimulation with traditional rehabilitation encourages the brain to form new, stronger neural connections.

The researchers in this study hoped this process would significantly improve arm function during the recovery process following the stroke. The study recruited volunteers who had suffered ischaemic stroke at least six months earlier with moderately severe arm problems.

The patients were split into two groups, one group receiving intensive physiotherapy alone, the other receiving physiotherapy paired with VNS. When patients followed the study protocol in full, there was a significantly greater improvement in a measure of arm function called the upper extremity Fugl-Meyer score.

The scores of VNS treated patients were six points higher than those who did not receive VNS in addition to their physiotherapy. When patients have such a large change in their score, noticeable improvements in arm related tasks can be observed on a daily basis.

The trial was run in partnership with Texas-based biomedical company MicroTransponder, which developed the Vivistim™ device. A similar VNS device made by another company has been used for over 17 years to treat more than 80,000 people with epilepsy.

All patients received therapy three days a week for six weeks and each session took two hours and involved many repetitions of different tasks as part of the standard physiotherapy.
For the patients receiving the paired VNS, a brief half-second of stimulation is delivered while the patients perform rehabilitative tasks. The brief stimulation is initiated by a push button trigger held by the therapist, which then sends a wireless signal to the implanted device via a laptop computer and wireless transmitter.

The primary aim of the study was to assess safety and feasibility but there were pre-defined efficacy analyses which researchers hoped would provide data to help them design future studies.
No safety issues arose during the trial and a larger study is now planned in the US, in Dallas, Houston and Minneapolis. Enrolment is now open to people who live close-by and the sites are seeking patients who’ve recently had a stroke and are still experiencing upper limb movement limitations. Further information is available at

Title: Re: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on February 23, 2015, 06:00:09 PM
Rapid remission of conditioned fear expression with extinction training paired with vagus nerve stimulation.
Peña DF1, Engineer ND, McIntyre CK.
Author information
⦁   Abstract
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 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.

Male Sprague-Dawley rats were trained on an auditory fear conditioning task followed by 1 to 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.

Vagus nerve stimulation 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 with that of sham control rats. When extinction trials were extended to 10 days, paired VNS accelerated extinction of the conditioned response.

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.

Title: Re: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on February 23, 2015, 06:07:20 PM
Future Rheumatoid Arthritis Therapy: Nerve Stimulation

New research suggests that electrical impulses may one day be used to treat rheumatoid arthritis (RA).
Neurosurgeon Kevin J. Tracey, MD, president and CEO of the Feinstein Institute for Medical Research in Manhasset, N.Y., discovered that stimulating the vagus nerve, which extends from the brain stem to the stomach, could control the inflammation that is central to RA.

In healthy people, the nervous system, including the vagus nerve, maintains key bodily functions within a safe zone. One of the vagus nerve’s jobs is to control the production of tumor necrosis factor (TNF), a molecule that triggers inflammation. But in people with RA, the vagus nerve doesn’t keep TNF levels within the safe zone.

After identifying which of the 80,000-plus fibers in the vagus nerve were responsible for TNF production, Dr. Tracey developed a device to stimulate those fibers, sending a signal to turn off TNF production.
The silver dollar-sized device is implanted into the chest and delivers electrical signals (via an electrode that runs up to the neck) that in essence tells the immune system “enough inflammation already!”
Clinical trials for the device began in 2009. To date, 24 RA patients have signed on to test the device, and the initial results are promising. The majority of patients experienced significant reductions in pain, swelling, joint tenderness and reduced levels of C-reactive protein, which increase with inflammation.
“This shows that we’re targeting the biology [of inflammation], not just the symptoms,” Dr. Tracey says.
He believes it could be available in Europe as early as 2017 and in the U.S. after that.
“We’re at the stage of technology development where we can target nerve circuits for therapeutic benefit,” he says. “It’s the future of treatment.”

Title: Re: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on February 26, 2015, 08:22:21 PM
Mood disorders in elderly population: neurostimulative treatment possibilities.
Rosenberg O1, Shoenfeld N, Kotler M, Dannon PN.
Author information
Treatment of mood disorders is one of the most challenging territories in elderly. Effectiveness of different treatment strategies could be related to age, sex and physical conditions. The side effect profile in this population also affects pharmacological interventions. Our review includes the neurostimulative treatment strategies in elderly. However, possible treatment strategies such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) and deep brain stimulation (DBS) were less studied in elderly. ECT was found to be an effective treatment procedure in mood disorders. Few double-blind sham controlled studies were conducted and demonstrated effectiveness of TMS. DBS has lack of double-blind studies. ECT seems to be the golden standard for the treatment resistant elderly patients, yet side effect profile of ECT in elderly will be discussed. Double -blind sham controlled studies with larger samples are necessary to confirm preliminary results with transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST) and VNS, DBS.

Title: Re: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on February 26, 2015, 08:37:22 PM
Burn-induced organ dysfunction: vagus nerve stimulation attenuates organ and serum cytokine levels.
Niederbichler AD1, Papst S, Claassen L, Jokuszies A, Steinstraesser L, Hirsch T, Altintas MA, Ipaktchi KR, Reimers K, Kraft T, Vogt PM.
⦁   Abstract
The interaction of the CNS and the immune system is well known. A parasympathetic anti-inflammatory pathway has recently been described. Both electrical and pharmacological parasympathetic stimulation attenuate proinflammatory mediator generation. Burn induces abacterial cytokine generation and we sought to evaluate whether parasympathetic stimulation after experimental burn decreases cardiodepressive mediator generation.

A 30% TBSA full-thickness rat burn model was used. After microsurgical preparation of the cervical portion of the vagus nerve, we performed electric vagus nerve stimulation. Serum was harvested and organ samples of heart and liver were homogenized. Samples were subjected to sandwich-ELISA specific for TNF-alpha, IL-1beta and IL-6. Heart rate measurements were done using left ventricular microcatheterization. Statistical analysis was done using Student's t-tests and analysis of variance (ANOVA).

Burn induced a significant rise of TNF-alpha, IL-1beta and IL-6 in organ homogenates and serum. After cervical vagal electrostimulation, serum and organ homogenate levels of proinflammatory cytokines were markedly reduced compared to burn controls. Left ventricular microcatheter assessment demonstrated no cardiodepressive effect of the vagal stimulation itself.

Our results encourage further research regarding the neuroimmunologic background of burn, possibly leading to the development of a novel therapeutic approach to burn-induced organ dysfunction and immunodysregulation.

Title: Re: VNS For Vegetative States After Traumatic Brain Injury
Post by: dennis100 on September 12, 2016, 12:02:40 PM
I was nearly killed by that thing. Don't let what happened to me happen to you!

My Story:
Reader's Digest version.,4490.0.html

Left Cervical Vagal Nerve Stimulation Suppresses Cardiac Sympathetic Tone

Conclusion: Patients with left cervical VNS had lower heart rate and iSKNA than patients without VNS. These findings are consistent with those observed in ambulatory canines, and suggest that chronic intermittent VNS can suppress cardiac sympathetic tone in human.

First paragraph:

Stimuli mediated over cardiac sympathetic nerves increase the work output of the heart and the contractility of the myocardium. Such stimuli increase ventricular performance so that more external work is produced at a lower filling pressure. Stimuli mediated over the vagus nerves appear to decrease ventricular performance. Recent work indicates that sympathetic stimulation increases and that vagal stimulation decreases the vigor of atrial contraction. The data from these same experiments show also that the relation between mean atrial pressure and stroke work is determined by atrial as well as ventricular function.

Regulation of Ventricular Contraction Influence of Cardiac Sympathetic and Vagal Nerve Stimulation on Atrial and Ventricular Dynamics

At constant heart rates, efferent stimulation of the vagus nerve and of the left stellate ganglion revealed the following:

1. Vagal stimulation exerts a profound depressant effect on the strength of the atrial contraction and can thereby influence ventricular filling and ventricular stroke work; it elevates mean atrial pressure at any given level of ventricular stroke work. This occurs under experimental conditions wherein the vagal stimulation used does not produce an alteration in the performance characteristics of the ventricle. The effects of vagal stimulation are blocked by atropine.

2. Stellate ganglion stimulation or norepinephrine infusion augments the strength of atrial contraction and thus the atrial contribution to ventricular filling. The augmented atrial contraction takes place in a shorter period of time.

3. Stellate ganglion stimulation or norepinephrine infusion increases the external stroke work and power produced by the ventricle from any given mean atrial pressure and from any given end-diastolic pressure or fiber length.

4. There is a family of curves representing the relation between end-diastolic fiber length and stroke work, as well as a family of curves representing the relation between mean atrial or end-diastolic pressure and stroke work.

5. When taken together with the well-known sympathetic and parasympathetic effects on heart rate, the above data are believed to comprise a reasonably comprehensive description of the means available to the central nervous system for directly inducing acute changes in the activity of the heart.

How can damage to the vagus nerve cause immediate death?

Nervus vagus belongs to parasympathetic nervous system which inhibits the contraction of heart, decreases its excitability and frequency of generated nerve impulses in heart. By overstimulating n.vagus these effects on heart are more intense - it could lead to total inhibiton of heart contractions, which would eventually lead to death within a little while.

Very intense slap behind ear or intensive pressure on neck area could lead to death as n.vagus is overstimulated. It is very rare though.

Vagal Inhibition,4227.0.html