Vagus nerve stimulation explained

Vagus nerve stimulation
Synonym:Vagal nerve stimulation

Vagus nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. It is used as an add-on treatment for certain types of intractable epilepsy, cluster headaches, treatment-resistant depression and stroke rehabilitation.

Medical use

Epilepsy

VNS is used to treat drug-resistant epilepsy.[1]

In the United States, VNS is approved as adjunctive therapy for those 4 years of age or older with refractory focal onset seizures. In the European Union, VNS is approved as an adjunctive therapy for patients with either generalized or focal onset seizures without any age restrictions.[2] It is recommended that VNS is only pursued following an adequate trial of at least 2 appropriately chosen anti-seizure medications and that the patient is ineligible for epilepsy surgery.[3] This is because epilepsy surgery is associated with a higher probability of resulting in seizure freedom.[4] Patients who have poor adherence or tolerance of anti-seizure medications may be good candidates for VNS.[5]

VNS may provide benefit for particular epilepsy syndromes and seizure types such as Lennox-Gastaut syndrome, tuberous sclerosis complex related epilepsy, refractory absence seizures and atonic seizures.[6] [7] [8] [9] There are also reports of VNS being successfully utilized in patients with refractory and super-refractory status epilepticus.[10]

Cluster headaches

The UK National Institute for Health and Care Excellence (NICE) in the UK recommends VNS for cluster headaches.[11]

Treatment-resistant depression

VNS is used to treat treatment-resistant major depressive disorder (TR-MDD).[12] The UK NICE guidance (from 2020) stated that "Evidence on its efficacy is limited in quality." and encouraged further research studies "in the form of randomised controlled trials with a placebo or sham stimulation arm."[13]

Stroke rehabilitation

In 2021 the U.S. Food and Drug Administration approved the MicroTransponder Vivistim Paired VNS System (Vivistim System) to treat moderate to severe upper extremity motor deficits associated with chronic ischemic stroke.[14] [15]

Beyond its use in epilepsy and depression, VNS has shown potential benefits in treating other conditions such as inflammatory diseases. Ongoing research is exploring the broader applications of VNS in various medical fields.[16]

Efficacy

Epilepsy

A meta-analysis of 74 clinical studies with 3321 patients found that VNS produced an average 51% reduction in seizures after 1 year of therapy.[17] Approximately 50% of patients had an equal to or greater than 50% reduction in seizures at the time of last follow-up. Long-term studies have shown that response to VNS increases over time. For instance, a study that followed 74 patients for 10–17 years found a seizure frequency reduction of 50-90% in 38.4%, 51.4%, 63.6% and 77.8% of patients at 1-, 2-, 10- and 17-years following implantation, respectively.[18] Approximately, 8% have total resolution of seizures.[19] VNS has also been shown to reduce rates of sudden unexpected death in epilepsy (SUDEP) and to improve quality of life metrics.[20] [21] A number of predictors of a favorable clinical response have been identified including epilepsy onset > 12 years of age, generalized epilepsy type, non-lesional epilepsy, posttraumatic epilepsy and those who have less than a 10-year history of seizures.[22]

Long-term cognitive outcomes are at least stable following VNS.[23]

One study of children with epilepsy found that a post hoc analysis revealed a dose–response correlation for VNS.[24]

Depression

A 2022 narrative review concluded that "The use of VNS is an approved, effective and well-tolerated long-term therapy for chronic and treatment-resistant depression. Further sham-controlled studies over a longer observational period are desirable".[25] [26]

The review also found that, "Many studies and case series demonstrated the efficacy of VNS as an adjuvant procedure for TRD (treatment resistant depression). The effect occurs with a latency period of 3–12 months and possibly increases with the duration of VNS."[25] One study of only 10 weeks found no effect.[27]

A 2020 review concluded "Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response.[28]

In one study higher electrical dose parameters were associated with response durability.[29]

Wellbeing

VNS may have positive wellbeing, mood and quality of life effects.[30] [31]

Studies have found improvements in standard patient-reported mood assessment scales in adult patients with epilepsy after using VNS,[3] and some have found no association between mood change and reduction in seizure frequency.[32] [33] Another study of epilepsy patients measured a general mood improvement, and suggested that VNS may improve unspecific states of indisposition and dysphoria.[34] Patients with comorbid depression have been found to have mood improvements with VNS therapy.[35]

Quality of life (QOL) improvement was also associated with VNS use.[36] One study of children with epilepsy found that better quality of life outcomes after VNS implantation were strongly associated with shorter duration of preoperative seizures and implantation at a young age.[37]

Anxiety reduction has been associated with VNS use.[38] [39] [40] Another study showed improvement in anxiety, depression and QOL scores that were not correlated with a reduction in seizure frequency.[41]

However these studies were small, and recommendations have been made that larger studies with randomised control groups be undertaken.[42]

Other possible efficacy areas

Very small studies have shown possible efficacy of VNS for reduction of Sjogren's fatigue,[43] [44] and for bowel inflammatory disease.[45]

Piezoelectric BaTiO3 particles conjugated with capsaicin were designed as orally Ingested electrostimulators to activate the vagus nervers to combat obesity. This intervention has not yet been tested on the human body. [46]

Mechanisms of action

The causes of VNS efficacy are not well understood.

Mechanisms which may account for the efficacy of VNS include:

Cortical desynchronization

There is evidence that VNS results in cortical desynchronization in epilepsy patients who had a favorable clinical response relative to those who did not.[47] [48] [49] This makes sense given that seizures consist of abnormal hypersynchronous activity in the brain.

Reducing inflammation

Multiple lines of evidence suggest that inflammation plays a significant role in epilepsy as well as associated neurobehavioral comorbidities such as depression, autism spectrum disorder and cognitive impairment.[50] There is evidence that VNS has an anti-inflammatory effect through both peripheral and central mechanisms.[51] [45]

Changing neurotransmitter activity

VNS can change the activity of several neurotransmitter systems involving serotonin, norepinephrine and GABA.[52] [53] These neurotransmitters are involved in both epilepsy and other neuropsychiatric conditions such as depression and anxiety.

Changing brain region connectivity

VNS may alter the functional connectivity in several brain regions and enhance synaptic plasticity to reduce excitatory activity involved in seizures.[54] [55] It has also been shown to change the functional connectivity of the default mode network in depressed patients.[56]

Impacting the gut-brain axis

VNS may influence the vagus nerve, which plays a role in the gut-brain axis.[57] [58]

Indirect stimulation of brain structures

Some believe that indirect stimulation of the thalamus may be a key mechanism in VNS efficacy.[59]

Adverse events

Adverse events related to the surgical procedure

A large 25-year retrospective study of 247 patients found a surgical complication rate of 8.6%.[60] The common adverse events included infection in 2.6%, hematoma at the surgical site in 1.9% and vocal cord palsy in 1.4%.

Side effects of VNS

The most common stimulation related side effect at 1 year following implantation are hoarseness in 28% and paraesthesias in the throat-chin region in 12%.[61] At the third year the rate of stimulation related adverse effects decreased substantially with shortness of breath being the most common and occurring in 3.2%. In general, VNS is well tolerated and side effects diminish over time. Also, side effects can be controlled by changing the stimulation parameters.

One small study found sleep apnea in as many as 28% of adults with epilepsy treated with VNS.[62]

Another small study found significant daytime drowsiness, which could be relieved by reducing the stimulation intensity.[41]

A range of side effects are possible but rare.[25]

Devices and procedures

Intravenous devices

The device consists of a generator the size of a matchbox that is implanted under the skin below the person's collarbone. Lead wires from the generator are tunnelled up to the patient's neck and wrapped around the left vagus nerve at the carotid sheath, where it delivers electrical impulses to the nerve.[63]

Implantation of the VNS device is usually done as an out-patient procedure. The procedure goes as follows: an incision is made in the upper left chest and the generator is implanted into a little "pouch" on the left chest under the collarbone. A second incision is made in the neck, so that the surgeon can access the vagus nerve. The surgeon then wraps the leads around the left branch of the vagus nerve, and connects the electrodes to the generator. Once successfully implanted, the generator sends electric impulses to the vagus nerve at regular intervals. The left vagus nerve is stimulated rather than the right because the right plays a role in cardiac function such that stimulating it could have negative cardiac effects.[12] [64] The "dose" administered by the device then needs to be set, which is done via a magnetic wand; the parameters adjusted include current, frequency, pulse width, and duty cycle.[12]

Example of stimulation metrics

The intravenous VNS system produced by LivaNova has stated default settings for use in depression of output power 1.25mA, frequency 20 Hz and pulse width 250 μs, with operation occurring for 30 seconds every 5 minutes (giving a work cycle of 10%).[25]

External devices

External devices work by transcutaneous stimulation and do not require surgery. Electrical impulses are targeted at the vagus nerve in the neck, or aurical (ear), at points where branches of the vagus nerve have cutaneous representation. GammaCore is recommended by The National Institute for Health and Care Excellence (NICE) for cluster headaches.[65]

History

1880s - proposed use to reduce cerebral blood flow

James L. Corning (1855-1923) was an American neurologist who developed the first device for stimulating the vagus nerve towards the end of the 19th century.[66]

At this time a widely held theory was that excessive blood flow caused seizures.

In the 1880s Corning designed a pronged instrument called the “carotid fork” to compress the carotid artery for the acute treatment of seizures. In addition, he developed the “carotid truss” for prolonged compression of the carotid arteries as a long-term preventative treatment for epilepsy. Then he developed the “electrocompressor” which allowed for the compression of the bilateral carotid arteries as well as electrical stimulation of both the vagus and cervical sympathetic nerves. The idea was to reduce cardiac output and to stimulate cervical sympathetic nerves to constrict cerebral blood vessels. Corning reported dramatic benefits however it was not accepted by his colleagues and ultimately was forgotten.

1930s - research on effects on central nervous system

In the 1930s Biley and Bremer demonstrated the direct influence of VNS on the central nervous system.[67] In the 1940s and 1950s vagal nerve stimulation was shown to affect EEG activity.[68]

1980s - use for epilepsy

In 1985 neuroscientist Jacob Zabara[69] proposed that VNS could be used to treat epilepsy.[70] He then demonstrated its efficacy in animal experiments.[71] The first human was implanted with a VNS for the treatment of epilepsy in 1988.[72]

1997 onwards - approved medical uses

In 1997, the US Food and Drug Administration's neurological devices panel met to consider approval of an implanted vagus nerve stimulator (VNS) for epilepsy, requested by Cyberonics (which was subsequently acquired by LivaNova).[63]

The FDA approved an implanted VNS for TR-MDD in 2005.[12]

In April 2017, the FDA cleared marketing of a handheld noninvasive vagus nerve stimulator, called "gammaCore" and made by ElectroCore LLC, for episodic cluster headaches, under the de novo pathway.[73] [74] In January 2018, the FDA cleared a new use of that device, for the treatment of migraine pain in adults under a 510(k) based on the de novo clearance.[75] [76]

In 2020, electroCore's non-invasive VNS was granted an Emergency Use Authorization for treating COVID-19 patients, given Research has shown this pulse train causes airways in the lungs to open its anti-inflammatory effect.[77]

Research areas

Because the vagus nerve is associated with many different functions and brain regions, clinical research has been done to determine its usefulness in treating many illnesses. These include various anxiety disorders,[78] obesity,[79] [80] alcohol addiction,[81] chronic heart failure,[82] prevention of arrhythmias that can cause sudden cardiac death,[83] autoimmune disorders,[84] irritable bowel syndrome,[85] [86] [87] Alzheimer's disease,[88] [89] Parkinson's disease,[90] hypertension,[91] [92] several chronic pain conditions,[93] inflammatory disorders, fibromyalgia and migraines.[94] [95]

A 2022 study showed that chronic VNS showed strong antidepressant and anxiolytic effects, and improved memory performance in an Alzheimer's Disease animal model.[96]

Further reading

Notes and References

  1. Panebianco . Mariangela . Rigby . Alexandra . Marson . Anthony G . Vagus nerve stimulation for focal seizures . Cochrane Database of Systematic Reviews . 14 July 2022 . 2022 . 7 . CD002896 . 10.1002/14651858.CD002896.pub3 . 9281624 . 35833911 .
  2. Wheless . James W. . Gienapp . Andrew J. . Ryvlin . Phillippe . Vagus nerve stimulation (VNS) therapy update . Epilepsy & Behavior . November 2018 . 88 . 2–10 . 10.1016/j.yebeh.2018.06.032 . 30017839 . 51679627 .
  3. Morris . George L. . Gloss . David . Buchhalter . Jeffrey . Mack . Kenneth J. . Nickels . Katherine . Harden . Cynthia . Evidence-based guideline update: Vagus nerve stimulation for the treatment of epilepsy: Report of the Guideline Development Subcommittee of the American Academy of Neurology . Neurology . 15 October 2013 . 81 . 16 . 1453–1459 . 10.1212/wnl.0b013e3182a393d1 . 23986299 . 3806910 .
  4. Fisher . Robert S. . Handforth . Adrian . Reassessment: Vagus nerve stimulation for epilepsy [RETIRED]: A Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology . Neurology . September 1999 . 53 . 4 . 666–669 . 10.1212/wnl.53.4.666 . 10489023. 20845641 . free .
  5. Helmers . Sandra L. . Duh . Mei Sheng . Guérin . Annie . Sarda . Sujata P. . Samuelson . Thomas M. . Bunker . Mark T. . Olin . Bryan D. . Jackson . Stanley D. . Faught . Edward . Clinical and economic impact of vagus nerve stimulation therapy in patients with drug-resistant epilepsy . Epilepsy & Behavior . October 2011 . 22 . 2 . 370–375 . 10.1016/j.yebeh.2011.07.020 . 21872534 . 7869407 .
  6. Grioni . Daniele . Landi . Andrea . Does Vagal Nerve Stimulation Treat Drug-Resistant Epilepsy in Patients with Tuberous Sclerosis Complex? . World Neurosurgery . January 2019 . 121 . 251–253 . 10.1016/j.wneu.2018.10.077 . 30347295 . 53034756 .
  7. Braakman . Hilde M. . Creemers . Joke . Hilkman . Danny M. . Klinkenberg . Sylvia . Koudijs . Suzanne M. . Debeij-van Hall . Mariette . Cornips . Erwin M. . 2018 . Improved seizure control and regaining cognitive milestones after vagus nerve stimulation revision surgery in Lennox–Gastaut syndrome . Epilepsy & Behavior Case Reports . 10 . 111–113 . 10.1016/j.ebcr.2018.08.002 . 30364578 . 6197149 .
  8. Arya . Ravindra . Greiner . Hansel M. . Lewis . Amanda . Mangano . Francesco T. . Gonsalves . Cornelia . Holland . Katherine D. . Glauser . Tracy A. . Vagus nerve stimulation for medically refractory absence epilepsy . Seizure . May 2013 . 22 . 4 . 267–270 . 10.1016/j.seizure.2013.01.008 . 23391567 . 14917920 . free .
  9. Rolston . John D. . Englot . Dario J. . Wang . Doris D. . Garcia . Paul A. . Chang . Edward F. . Corpus callosotomy versus vagus nerve stimulation for atonic seizures and drop attacks: A systematic review . Epilepsy & Behavior . October 2015 . 51 . 13–17 . 10.1016/j.yebeh.2015.06.001 . 26247311 . 5261864 .
  10. Dibué-Adjei . Maxine . Brigo . Francesco . Yamamoto . Takamichi . Vonck . Kristl . Trinka . Eugen . Vagus nerve stimulation in refractory and super-refractory status epilepticus – A systematic review . Brain Stimulation . September 2019 . 12 . 5 . 1101–1110 . 10.1016/j.brs.2019.05.011 . 31126871 . 153310356 . free .
  11. https://www.nice.org.uk/guidance/mtg46/documents/final-scope The Nurosym/Parasym device was used in these studies:
    • Tarn . Jessica . Evans . Evelyn . Traianos . Emmanuella . Collins . Alexis . Stylianou . Mryto . Parikh . Jehill . Bai . Yang . Guan . Yu . Frith . James . Lendrem . Dennis . Macrae . Victoria . McKinnon . Iain . Simon . Bruce S. . Blake . Justyna . Baker . Mark R. . Taylor . John Paul . Watson . Stuart . Gallagher . Peter . Blamire . Andrew . Newton . Julia . Ng . Wan-Fai . The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants With Primary Sjögren's Syndrome . Neuromodulation: Technology at the Neural Interface . April 2023 . 26 . 3 . 681–689 . 10.1016/j.neurom.2022.08.461 . 37032583 .
    • Preprint . Natelson . Benjamin H . Blate . Michelle . Soto . Tiffany . Transcutaneous Vagus Nerve Stimulation in the Treatment of Long Covid-Chronic Fatigue Syndrome . 8 November 2022 . 10.1101/2022.11.08.22281807 .
  12. Carreno FR, Frazer A . July 2017 . Vagal Nerve Stimulation for Treatment-Resistant Depression . Neurotherapeutics . 14 . 3 . 716–727 . 10.1007/s13311-017-0537-8 . 5509631 . 28585221.
  13. Web site: 1 Recommendations | Implanted vagus nerve stimulation for treatment-resistant depression | Guidance | NICE . 12 August 2020 .
  14. Web site: FDA Approves First-of-Its-Kind Stroke Rehabilitation System . . 31 August 2021 .
  15. Liu . Charles Y. . Russin . Jonathan . Adelson . David P. . Jenkins . Alistair . Hilmi . Omar . Brown . Benjamin . Lega . Bradley . Whitworth . Tony . Bhattacharyya . Dev . Schwartz . Theodore H. . Krishna . Vibhor . Williams . Ziv . Uff . Christopher . Willie . Jon . Hoffman . Caitlin . Vandergrift . William A. . Achrol . Achal Singh . Ali . Rushna . Konrad . Peter . Edmonds . Joseph . Kim . Daniel . Bhatt . Pragnesh . Tarver . Brent W. . Pierce . David . Jain . Ravi . Burress . Chester . Casavant . Reema . Prudente . Cecília N. . Engineer . Navzer D. . Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial . Journal of Clinical Neuroscience . November 2022 . 105 . 122–128 . 10.1016/j.jocn.2022.09.013 . 36182812 .
  16. Web site: June 2024 . What Is Vagus Nerve Stimulation? . live . https://web.archive.org/web/20240727090627/https://prolifehc.com/post/What-Is-Vagus-Nerve-Stimulation . July 27, 2024 . July 26, 2024 . www.prolifehc.com.
  17. Englot . Dario J. . Chang . Edward F. . Auguste . Kurtis I. . Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response: A review . Journal of Neurosurgery . December 2011 . 115 . 6 . 1248–1255 . 10.3171/2011.7.JNS11977 . 21838505 .
  18. Chrastina . Jan . Novák . Zdeněk . Zeman . Tomáš . Kočvarová . Jitka . Pail . Martin . Doležalová . Irena . Jarkovský . Jiří . Brázdil . Milan . Single-center long-term results of vagus nerve stimulation for epilepsy: A 10–17 year follow-up study . Seizure . July 2018 . 59 . 41–47 . 10.1016/j.seizure.2018.04.022 . 29738985 . 13700901 . free .
  19. Englot . Dario J. . Rolston . John D. . Wright . Clinton W. . Hassnain . Kevin H. . Chang . Edward F. . Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy . Neurosurgery . September 2016 . 79 . 3 . 345–353 . 10.1227/NEU.0000000000001165 . 4884552 . 26645965 .
  20. Englot . Dario J. . Hassnain . Kevin H. . Rolston . John D. . Harward . Stephen C. . Sinha . Saurabh R. . Haglund . Michael M. . Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data . Epilepsy & Behavior . January 2017 . 66 . 4–9 . 10.1016/j.yebeh.2016.10.005 . 27974275 . 5258831 .
  21. Ryvlin . Philippe . So . Elson L. . Gordon . Charles M. . Hesdorffer . Dale C. . Sperling . Michael R. . Devinsky . Orrin . Bunker . Mark T. . Olin . Bryan . Friedman . Daniel . Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with VNS therapy . Epilepsia . March 2018 . 59 . 3 . 562–572 . 10.1111/epi.14002 . 29336017 . 3782079 . free .
  22. Englot . Dario J. . Rolston . John D. . Wang . Doris D. . Hassnain . Kevin H. . Gordon . Charles M. . Chang . Edward F. . Efficacy of vagus nerve stimulation in posttraumatic versus nontraumatic epilepsy: Clinical article . Journal of Neurosurgery . November 2012 . 117 . 5 . 970–977 . 10.3171/2012.8.jns122 . 22978542 . free .
  23. Lam . Jordan . Williams . Marcus . Ashla . Mark . Lee . Darrin J. . Cognitive outcomes following vagus nerve stimulation, responsive neurostimulation and deep brain stimulation for epilepsy: A systematic review . Epilepsy Research . May 2021 . 172 . 106591 . 10.1016/j.eplepsyres.2021.106591 . 33711711 . 231956548 .
  24. 10.1111/epi.12762 . Vagus nerve stimulation for drug-resistant epilepsy: A European long-term study up to 24 months in 347 children . 2014 . Orosz . Iren . McCormick . David . Zamponi . Nelia . Varadkar . Sophia . Feucht . Martha . Parain . Dominique . Griens . Roger . Vallée . Louis . Boon . Paul . Rittey . Christopher . Jayewardene . Amara K. . Bunker . Mark . Arzimanoglou . Alexis . Lagae . Lieven . Epilepsia . 55 . 10 . 1576–1584 . 25231724 . 25790247 . free .
  25. Reif-Leonhard . C. . Reif . A. . Baune . B. T. . Kavakbasi . E. . Vagusnervstimulation bei schwer zu behandelnden Depressionen . Der Nervenarzt . September 2022 . 93 . 9 . 921–930 . 10.1007/s00115-022-01282-6 . 35380222 . 9452433 . free .
  26. News: Kron . Thomas . Vagus Nerve Stimulation: A Little-Known Option for Depression . Medscape . 5 May 2022 .
  27. Rush . A. John . Marangell . Lauren B. . Sackeim . Harold A. . George . Mark S. . Brannan . Stephen K. . Davis . Sonia M. . Howland . Robert . Kling . Mitchel A. . Rittberg . Barry R. . Burke . William J. . Rapaport . Mark H. . Zajecka . John . Nierenberg . Andrew A. . Husain . Mustafa M. . Ginsberg . David . Cooke . Robert G. . Vagus Nerve Stimulation for Treatment-Resistant Depression: A Randomized, Controlled Acute Phase Trial . Biological Psychiatry . September 2005 . 58 . 5 . 347–354 . 10.1016/j.biopsych.2005.05.025 . 16139580 .
  28. Assenza . Giovanni . Tombini . Mario . Lanzone . Jacopo . Ricci . Lorenzo . Di Lazzaro . Vincenzo . Casciato . Sara . Morano . Alessandra . Giallonardo . Anna Teresa . Di Bonaventura . Carlo . Beghi . Ettore . Ferlazzo . Edoardo . Gasparini . Sara . Giuliano . Loretta . Pisani . Francesco . Benna . Paolo . Bisulli . Francesca . De Falco . Fabrizio A. . Franceschetti . Silvana . La Neve . Angela . Meletti . Stefano . Mostacci . Barbara . Sartucci . Ferdinando . Striano . Pasquale . Villani . Flavio . Aguglia . Umberto . Avanzini . Giuliano . Belcastro . Vincenzo . Bianchi . Amedeo . Cianci . Vittoria . Labate . Angelo . Magaudda . Adriana . Michelucci . Roberto . Verri . Annapia . Zaccara . Gaetano . Pizza . Vincenzo . Tinuper . Paolo . Di Gennaro . Giancarlo . Antidepressant effect of vagal nerve stimulation in epilepsy patients: a systematic review . Neurological Sciences . November 2020 . 41 . 11 . 3075–3084 . 10.1007/s10072-020-04479-2 . 32524324 . 219567684 .
  29. Aaronson . Scott T. . Carpenter . Linda L. . Conway . Charles R. . Reimherr . Frederick W. . Lisanby . Sarah H. . Schwartz . Thomas L. . Moreno . Francisco A. . Dunner . David L. . Lesem . Michael D. . Thompson . Peter M. . Husain . Mustafa . Vine . Craig J. . Banov . Michael D. . Bernstein . Lawrence P. . Lehman . Robert B. . Brannon . Guy E. . Keepers . George A. . O'Reardon . John P. . Rudolph . Richard L. . Bunker . Mark . Vagus Nerve Stimulation Therapy Randomized to Different Amounts of Electrical Charge for Treatment-Resistant Depression: Acute and Chronic Effects . Brain Stimulation . July 2013 . 6 . 4 . 631–640 . 10.1016/j.brs.2012.09.013 . 23122916 .
  30. Book: 10.1016/B978-0-323-91702-5.00004-9 . Quality of life, neurocognitive outcomes, and mood effects with neurostimulation devices . Neurostimulation for Epilepsy . 2023 . 229–244 . 978-0-323-91702-5 . Arredondo K, Patel AD .
  31. Schachter . Steven C. . Vagus nerve stimulation: mood and cognitive effects . Epilepsy & Behavior . February 2004 . 5 . 56–59 . 10.1016/j.yebeh.2003.11.007 . 14725847 .
  32. Elger . Gerda . Hoppe . Christian . Falkai . Peter . Rush . A.John . Elger . Christian E . Vagus nerve stimulation is associated with mood improvements in epilepsy patients . Epilepsy Research . December 2000 . 42 . 2–3 . 203–210 . 10.1016/s0920-1211(00)00181-9 . 11074193 .
  33. Harden . Cynthia L. . Pulver . Melissa C. . Ravdin . Lisa D. . Nikolov . Blagovest . Halper . James P. . Labar . Douglas R. . A Pilot Study of Mood in Epilepsy Patients Treated with Vagus Nerve Stimulation . Epilepsy & Behavior . April 2000 . 1 . 2 . 93–99 . 10.1006/ebeh.2000.0046 . 12609137 .
  34. Hoppe . Christian . Helmstaedter . Christoph . Scherrmann . Judith . Elger . Christian E. . Self-Reported Mood Changes following 6 Months of Vagus Nerve Stimulation in Epilepsy Patients . Epilepsy & Behavior . August 2001 . 2 . 4 . 335–342 . 10.1006/ebeh.2001.0194 . 12609210 . 22552070 .
  35. Fan . Jing-Jing . Shan . Wei . Wu . Jian-Ping . Wang . Qun . Research progress of vagus nerve stimulation in the treatment of epilepsy . CNS Neuroscience & Therapeutics . November 2019 . 25 . 11 . 1222–1228 . 10.1111/cns.13209 . 6834923 . 31429206 .
  36. 10.1111/epi.12611 . The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long-term Effectiveness) trial . 2014 . Ryvlin . Philippe . Gilliam . Frank G. . Nguyen . Dang K. . Colicchio . Gabriella . Iudice . Alfonso . Tinuper . Paolo . Zamponi . Nelia . Aguglia . Umberto . Wagner . Louis . Minotti . Lorella . Stefan . Hermann . Boon . Paul . Sadler . Mark . Benna . Paolo . Raman . Pradheep . Perucca . Emilio . Epilepsia . 55 . 6 . 893–900 . 24754318 . 4283995 .
  37. 10.1007/s00381-020-04628-0 . Subgroup analysis of seizure and cognitive outcome after vagal nerve stimulator implantation in children . 2021 . Knorr . Corine . Greuter . Ladina . Constantini . Shlomi . Fried . Itzhak . Kremer . Uri . Datta . Alexandre N. . Guzman . Raphael . Soleman . Jehuda . Child's Nervous System . 37 . 1 . 243–252 . 32361930 . 218467172 . free .
  38. George . Mark S. . Ward . Herbert E. . Ninan . Philip T. . Pollack . Mark . Nahas . Ziad . Anderson . Berry . Kose . Samet . Howland . Robert H. . Goodman . Wayne K. . Ballenger . James C. . A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders . Brain Stimulation . April 2008 . 1 . 2 . 112–121 . 10.1016/j.brs.2008.02.001 . 20633378 .
  39. 10.3389/fnbeh.2014.00327 . free . Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the ventromedial prefrontal cortex to the amygdala . 2014 . Peña . David Frausto . Childs . Jessica E. . Willett . Shawn . Vital . Analicia . McIntyre . Christa K. . Kroener . Sven . Frontiers in Behavioral Neuroscience . 8 . 327 . 25278857 . 4166996 .
  40. 10.3389/fpsyt.2018.00044 . free . Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders . 2018 . Breit . Sigrid . Kupferberg . Aleksandra . Rogler . Gerhard . Hasler . Gregor . Frontiers in Psychiatry . 9 . 44 . 29593576 . 5859128 .
  41. Aihua L, Lu S, Liping L, Xiuru W, Hua L, Yuping W . A controlled trial of transcutaneous vagus nerve stimulation for the treatment of pharmacoresistant epilepsy . Epilepsy Behav . 39 . 105–10 . October 2014 . 25240121 . 10.1016/j.yebeh.2014.08.005 . 7913513 .
  42. Hoppe . Christian . Vagus nerve stimulation: Urgent need for the critical reappraisal of clinical effectiveness . Seizure . January 2013 . 22 . 1 . 83–84 . 10.1016/j.seizure.2012.10.001 . 23140994 . free .
  43. 10.1016/j.neurom.2022.08.461 . The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants with Primary Sjögren's Syndrome . 2023 . Tarn . Jessica . Evans . Evelyn . Traianos . Emmanuella . Collins . Alexis . Stylianou . Mryto . Parikh . Jehill . Bai . Yang . Guan . Yu . Frith . James . Lendrem . Dennis . MacRae . Victoria . McKinnon . Iain . Simon . Bruce S. . Blake . Justyna . Baker . Mark R. . Taylor . John Paul . Watson . Stuart . Gallagher . Peter . Blamire . Andrew . Newton . Julia . Ng . Wan-Fai . Neuromodulation: Technology at the Neural Interface . 26 . 3 . 681–689 . 37032583 . 253172246 . free .
  44. Inflammation has been associated with both fatigue (see the Wikipedia article on fatigue) and possible VNS mechanism (see below).
  45. 10.1186/s42234-023-00124-3 . free . Transcutaneous auricular vagus nerve stimulation attenuates inflammatory bowel disease in children: A proof-of-concept clinical trial . 2023 . Sahn . Benjamin . Pascuma . Kristine . Kohn . Nina . Tracey . Kevin J. . Markowitz . James F. . Bioelectronic Medicine . 9 . 1 . 23 . 37849000 . 10583463 .
  46. Mac. Cam-Hoa. Tai. Hsien-Meng. Huang. Sheng-Min. Peng. Hsu-Hsia. Sharma . Amit Kumar. Nguyen. Giang Le Thi. Chang . Pei-Ju. Wang. Jui-To. Chang. Yen. Lin. Yu-Jung. Sung. Hsing-Wen. 2024-04-09 . Orally Ingested Self-Powered Stimulators for Targeted Gut–Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders . Advanced Materials . 36 . 21 . e2310351 . en . 10.1002/adma.202310351 . 38591658 . 2024AdM....3610351M . 0935-9648.
  47. Fraschini . Matteo . Puligheddu . Monica . Demuru . Matteo . Polizzi . Lorenzo . Maleci . Alberto . Tamburini . Giorgio . Congia . Socrate . Bortolato . Marco . Marrosu . Francesco . VNS induced desynchronization in gamma bands correlates with positive clinical outcome in temporal lobe pharmacoresistant epilepsy . Neuroscience Letters . March 2013 . 536 . 14–18 . 10.1016/j.neulet.2012.12.044 . 23333601 . 25790383 .
  48. Sangare . Aude . Marchi . Angela . Pruvost-Robieux . Estelle . Soufflet . Christine . Crepon . Benoit . Ramdani . Céline . Chassoux . Francine . Turak . Baris . Landre . Elisabeth . Gavaret . Martine . The Effectiveness of Vagus Nerve Stimulation in Drug-Resistant Epilepsy Correlates with Vagus Nerve Stimulation-Induced Electroencephalography Desynchronization . Brain Connectivity . 1 December 2020 . 10 . 10 . 566–577 . 10.1089/brain.2020.0798 . 33073582 . 7757623 .
  49. Joseph . Navya Mary . Steffan . Paul . Becker . Danielle . Wernovsky . Magda . Datta . Proleta . Ernst . Lia . Effects of VNS stimulation on electrocorticography in patients with dual neuro- stimulation devices . Journal of Neurology, Neurosurgery & Psychiatry . June 2022 . 93 . 6 . A3.3–A4 . 10.1136/jnnp-2022-abn.9 . 249067601 .
  50. Paudel . Yam Nath . Shaikh . Mohd. Farooq . Shah . Sadia . Kumari . Yatinesh . Othman . Iekhsan . Role of inflammation in epilepsy and neurobehavioral comorbidities: Implication for therapy . European Journal of Pharmacology . October 2018 . 837 . 145–155 . 10.1016/j.ejphar.2018.08.020 . 30125565 . 52048111 .
  51. Wang . Yue . Zhan . Gaofeng . Cai . Ziwen . Jiao . Bo . Zhao . Yilin . Li . Shiyong . Luo . Ailin . Vagus nerve stimulation in brain diseases: Therapeutic applications and biological mechanisms . Neuroscience & Biobehavioral Reviews . August 2021 . 127 . 37–53 . 10.1016/j.neubiorev.2021.04.018 . 33894241 . 233328858 .
  52. Manta . Stella . El Mansari . Mostafa . Debonnel . Guy . Blier . Pierre . Electrophysiological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems . International Journal of Neuropsychopharmacology . March 2013 . 16 . 2 . 459–470 . 10.1017/s1461145712000387 . 22717062 . free .
  53. Furmaga . Havan . Shah . Aparna . Frazer . Alan . Serotonergic and Noradrenergic Pathways Are Required for the Anxiolytic-like and Antidepressant-like Behavioral Effects of Repeated Vagal Nerve Stimulation in Rats . Biological Psychiatry . November 2011 . 70 . 10 . 937–945 . 10.1016/j.biopsych.2011.07.020 . 21907323 . 206101850 .
  54. Alexander . Georgia M. . Huang . Yang Zhong . Soderblom . Erik J. . He . Xiao-Ping . Moseley . M. Arthur . McNamara . James O. . Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex . Journal of Neurochemistry . February 2017 . 140 . 4 . 629–644 . 10.1111/jnc.13931 . 27973753 . 6537100 .
  55. Zhu . Jin . Xu . Cuiping . Zhang . Xi . Qiao . Liang . Wang . Xueyuan . Zhang . Xiaohua . Yan . Xiaoming . Ni . Duanyu . Yu . Tao . Zhang . Guojun . Li . Yongjie . A resting-state functional MRI study on the effect of vagal nerve stimulation on spontaneous regional brain activity in drug-resistant epilepsy patients . Behavioural Brain Research . August 2020 . 392 . 112709 . 10.1016/j.bbr.2020.112709 . 32479850 . 219123829 .
  56. Fang . Jiliang . Rong . Peijing . Hong . Yang . Fan . Yangyang . Liu . Jun . Wang . Honghong . Zhang . Guolei . Chen . Xiaoyan . Shi . Shan . Wang . Liping . Liu . Rupeng . Hwang . Jiwon . Li . Zhengjie . Tao . Jing . Wang . Yang . Zhu . Bing . Kong . Jian . Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder . Biological Psychiatry . February 2016 . 79 . 4 . 266–273 . 10.1016/j.biopsych.2015.03.025 . 25963932 . 4838995 .
  57. 5859128 . 2018 . Breit . S. . Kupferberg . A. . Rogler . G. . Hasler . G. . Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders . Frontiers in Psychiatry . 9 . 44 . 10.3389/fpsyt.2018.00044 . 29593576 . free .
  58. Tarn . Jessica . Evans . Evelyn . Traianos . Emmanuella . Collins . Alexis . Stylianou . Mryto . Parikh . Jehill . Bai . Yang . Guan . Yu . Frith . James . Lendrem . Dennis . Macrae . Victoria . McKinnon . Iain . Simon . Bruce S. . Blake . Justyna . Baker . Mark R. . Taylor . John Paul . Watson . Stuart . Gallagher . Peter . Blamire . Andrew . Newton . Julia . Ng . Wan-Fai . The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants With Primary Sjögren's Syndrome . Neuromodulation: Technology at the Neural Interface . April 2023 . 26 . 3 . 681–689 . 10.1016/j.neurom.2022.08.461 . 37032583 .
  59. Book: 10.1016/B978-0-323-91702-5.00004-9 . Quality of life, neurocognitive outcomes, and mood effects with neurostimulation devices . Neurostimulation for Epilepsy . 2023 . 229–244 . 978-0-323-91702-5 . Arredondo K, Patel AD .
  60. Révész . David . Rydenhag . Bertil . Ben-Menachem . Elinor . Complications and safety of vagus nerve stimulation: 25 years of experience at a single center . Journal of Neurosurgery: Pediatrics . July 2016 . 18 . 1 . 97–104 . 10.3171/2016.1.peds15534 . 27015521 . free .
  61. Coughlin . Maryanne K. . Long-Term Treatment with Vagus Nerve Stimulation in Patients with Refractory Epilepsy . AORN Journal . October 2001 . 74 . 4 . 554 . 10.1016/s0001-2092(06)61692-x .
  62. Salvadé . Aude . Ryvlin . Philippe . Rossetti . Andrea O. . Impact of vagus nerve stimulation on sleep-related breathing disorders in adults with epilepsy . Epilepsy & Behavior . February 2018 . 79 . 126–129 . 10.1016/j.yebeh.2017.10.040 . 29287215 . 46769980 .
  63. Edwards CA, Kouzani A, Lee KH, Ross EK . Neurostimulation Devices for the Treatment of Neurologic Disorders . Mayo Clinic Proceedings . 92 . 9 . 1427–1444 . September 2017 . 28870357 . 10.1016/j.mayocp.2017.05.005 . free .
  64. Giordano F, Zicca A, Barba C, Guerrini R, Genitori L . Vagus nerve stimulation: Surgical technique of implantation and revision and related morbidity . Epilepsia . 58 . Suppl 1 . 85–90 . April 2017 . 28386925 . 10.1111/epi.13678 . free .
  65. https://www.nice.org.uk/guidance/mtg46/documents/final-scope
  66. Lanska . Douglas J. . J.L. Corning and vagal nerve stimulation for seizures in the 1880s . Neurology . 12 February 2002 . 58 . 3 . 452–459 . 10.1212/wnl.58.3.452 . 11839848 .
  67. Bailey . Percival . Bremer . Frédéric . A Sensory Cortical Representation of the Vagus Nerve: With a Note on the Effects of Low Blood Pressure on the Cortical Electrogram . Journal of Neurophysiology . September 1938 . 1 . 5 . 405–412 . 10.1152/jn.1938.1.5.405 .
  68. George . Mark S. . Sackeim . Harold A. . Rush . A.John . Marangell . Lauren B. . Nahas . Ziad . Husain . Mustafa M. . Lisanby . Sarah . Burt . Tal . Goldman . Juliet . Ballenger . James C. . Vagus nerve stimulation: a new tool for brain research and therapy∗ . Biological Psychiatry . February 2000 . 47 . 4 . 287–295 . 10.1016/s0006-3223(99)00308-x . 10686263 . 14489190 .
  69. News: Squires . Sally . Washingtonpost.com: Nation . The Washington Post . 24 March 1998 . Z07 .
  70. Zabara . J. . Peripheral control of hypersynchronous discharge in epilepsy . Electroencephalography and Clinical Neurophysiology . September 1985 . 61 . 3 . S162 . 10.1016/0013-4694(85)90626-1 .
  71. Zabara . Jacob . Inhibition of Experimental Seizures in Canines by Repetitive Vagal Stimulation . Epilepsia . November 1992 . 33 . 6 . 1005–1012 . 10.1111/j.1528-1157.1992.tb01751.x . 1464256 . 19290172 .
  72. Penry . J. Kiffin . Dean . J. Christine . Prevention of Intractable Partial Seizures by Intermittent Vagal Stimulation in Humans: Preliminary Results . Epilepsia . June 1990 . 31 . s2 . S40-3 . 10.1111/j.1528-1157.1990.tb05848.x . 2121469 . 32134763 .
  73. News: Brauser D . FDA Approves Vagus Nerve Stimulation Device for Cluster Headache . Medscape . April 18, 2017.
  74. News: GammaCore Device Classification under Section 513(f)(2)(de novo) . 6 June 2018 . FDA.
  75. News: Brauser D . FDA Clears Vagus Nerve Stimulator for Migraine Pain . Medscape . January 29, 2018.
  76. Web site: GammaCore 510(k) Premarket Notification . FDA . 6 June 2018.
  77. News: Moore . Samuel K. . Handheld Vagus Nerve Stimulator Gets Emergency Approval for COVID-19 Use . IEEE Spectrum . 22 July 2020 .
  78. Groves DA, Brown VJ . Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects . Neuroscience and Biobehavioral Reviews . 29 . 3 . 493–500 . May 2005 . 15820552 . 10.1016/j.neubiorev.2005.01.004 . 3021573 .
  79. de Lartigue G . Role of the vagus nerve in the development and treatment of diet-induced obesity . The Journal of Physiology . 594 . 20 . 5791–5815 . October 2016 . 26959077 . 5063945 . 10.1113/JP271538 .
  80. Göbel CH, Tronnier VM, Münte TF . Brain stimulation in obesity . International Journal of Obesity . 41 . 12 . 1721–1727 . December 2017 . 28663570 . 10.1038/ijo.2017.150 . 20426017 .
  81. Herremans . Sarah C. . Baeken . Chris . The current perspective of neuromodulation techniques in the treatment of alcohol addiction: a systematic review . Psychiatria Danubina . July 2012 . 24 . suppl 1 . 14–20 . 22945180 .
  82. Abraham WT, Smith SA . Devices in the management of advanced, chronic heart failure . Nature Reviews. Cardiology . 10 . 2 . 98–110 . February 2013 . 23229137 . 3753073 . 10.1038/nrcardio.2012.178 .
  83. Sabbah HN . Electrical vagus nerve stimulation for the treatment of chronic heart failure . Cleveland Clinic Journal of Medicine . 78 . 8 suppl 1 . S24–S29 . August 2011 . 21972326 . 3817894 . 10.3949/ccjm.78.s1.04 .
  84. Koopman FA, van Maanen MA, Vervoordeldonk MJ, Tak PP . Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis . Journal of Internal Medicine . 282 . 1 . 64–75 . July 2017 . 28547815 . 10.1111/joim.12626 . free . Paul-Peter Tak .
  85. Bonaz B, Sinniger V, Pellissier S . Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases . Frontiers in Neuroscience . 15 . 650971 . 2021 . 33828455 . 10.3389/fnins.2021.650971 . 8019822 . free .
  86. Payne SC, Furness JB, Burns O, Sedo A, Hyakumura T, Shepherd RK, Fallon JB . Anti-inflammatory Effects of Abdominal Vagus Nerve Stimulation on Experimental Intestinal Inflammation . Frontiers in Neuroscience . 13 . 418 . 2019 . 31133776 . 6517481 . 10.3389/fnins.2019.00418 . free .
  87. News: Hamza . Zaina . Non-Invasive Nerve Stimulation Shows Promise for Younger IBD Patients . Medpage Today . 15 December 2021 .
  88. Merrill . Charley A. . Jonsson . Michael A. G. . Minthon . Lennart . Ejnell . Hasse . Silander . Hans C-son . Blennow . Kaj . Karlsson . Mats . Nordlund . Arto . Rolstad . Sindre . Warkentin . Siegbert . Ben-Menachem . Elinor . Sjögren . Magnus J. C. . Vagus Nerve Stimulation in Patients With Alzheimer's Disease: Additional Follow-Up Results of a Pilot Study Through 1 Year . The Journal of Clinical Psychiatry . 15 August 2006 . 67 . 8 . 1171–1178 . 10.4088/jcp.v67n0801 . 16965193 .
  89. Broncel . A. . Bocian . R. . Kłos-Wojtczak . P. . Kulbat-Warycha . K. . Konopacki . J. . Vagal nerve stimulation as a promising tool in the improvement of cognitive disorders . Brain Research Bulletin . February 2020 . 155 . 37–47 . 10.1016/j.brainresbull.2019.11.011 . 31790720 . 208344249 .
  90. News: Meglio . Marco . Noninvasive Vagus Nerve Stimulation for Parkinson Disease Shows Safety, Efficacy . Neurology live . 3 June 2021 .
  91. Gierthmuehlen . Mortimer . Plachta . Dennis T T . Effect of selective vagal nerve stimulation on blood pressure, heart rate and respiratory rate in rats under metoprolol medication . Hypertension Research . February 2016 . 39 . 2 . 79–87 . 10.1038/hr.2015.122 . 26581776 . 21184892 . free .
  92. Annoni . Elizabeth M. . Van Helden . Dusty . Guo . Yugene . Levac . Brett . Libbus . Imad . KenKnight . Bruce H. . Osborn . John W. . Tolkacheva . Elena G. . Chronic Low-Level Vagus Nerve Stimulation Improves Long-Term Survival in Salt-Sensitive Hypertensive Rats . Frontiers in Physiology . 31 January 2019 . 10 . 25 . 10.3389/fphys.2019.00025 . 30766489 . 6365472 . free .
  93. Chakravarthy K, Chaudhry H, Williams K, Christo PJ . Review of the Uses of Vagal Nerve Stimulation in Chronic Pain Management . Current Pain and Headache Reports . 19 . 12 . 54 . December 2015 . 26493698 . 10.1007/s11916-015-0528-6 . 8117776 .
  94. Johnson RL, Wilson CG . A review of vagus nerve stimulation as a therapeutic intervention . Journal of Inflammation Research . 11 . 203–213 . 2018 . 29844694 . 5961632 . 10.2147/JIR.S163248 . free .
  95. Puledda F, Goadsby PJ . An Update on Non-Pharmacological Neuromodulation for the Acute and Preventive Treatment of Migraine . Headache . 57 . 4 . 685–691 . April 2017 . 28295242 . 10.1111/head.13069 . 205161411 .
  96. Yesiltepe . Metin . Cimen . Bariscan . Sara . Yildirim . Effects of chronic vagal nerve stimulation in the treatment of β-amyloid-induced neuropsychiatric symptoms . European Journal of Pharmacology . 15 September 2022 . 931 . 175179 . 10.1016/j.ejphar.2022.175179. 35973478 . 251558829 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Vagus nerve stimulation".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.