Vagus nerve stimulation

Vagus nerve stimulation

Vagus nerve stimulation or vagal nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. It is used as an adjunctive treatment for certain types of intractable epilepsy and treatment-resistant depression.

Medical uses

Because the vagus nerve is associated with many different functions and brain regions, research is being done to determine its usefulness in treating other illnesses, including various anxiety disorders, Alzheimer's disease, migraines,[1] fibromyalgia,[2] obesity,[3] and tinnitus.[4]

  • Alcohol addiction[5]
  • Atrial fibrillation[6][7]
  • Bulimia nervosa[8]
  • Burn-induced organ dysfunction[9]
  • Chronic heart failure[10]
  • Chronic intractable hiccups[11]
  • Comorbid personality disorders[12]
  • Coronary artery disease[13]
  • Dravet syndrome[14]
  • Drop-attacks[15]
  • Heatstroke[16]
  • Heroin seeking behavior[17]
  • Intestinal epithelial barrier breakdown[18]
  • Lennox–Gastaut syndrome[19]
  • Memory[20]
  • Mood disorders in elderly population[21]
  • Multiple sclerosis[22]
  • Myocarditis[23]
  • Obsessive compulsive disorder[24]
  • Peripheral arterial occlusion disease[25]
  • Postoperative cognitive dysfunction in elderly patients[26]
  • Rasmussen's encephalitis[27]
  • Severe mental diseases[28]
  • Sepsis[29]
  • Spinal trigeminal neuronal[30]
  • Transient focal cerebral ischemia[31]
  • Trauma-hemorrhagic shock[32]
  • Traumatic brain injury[33][34]
  • Vaginal-cervical self-stimulation in women with complete spinal cord injury[35][36]
  • Vegetative states after traumatic brain injury[37]
  • Visceral pain-related affective memory[38]

Other brain stimulation techniques used to treat depression include electroconvulsive therapy (ECT) and cranial electrotherapy stimulation (CES). Deep brain stimulation is currently under study as a treatment for depression. Transcranial magnetic stimulation (TMS) is under study as a therapy for both depression and epilepsy.[39] Trigeminal Nerve Stimulation (TNS) is being researched at UCLA as a treatment for epilepsy.[40]

Adverse events

The value of the FDA's MAUDE database as an early warning system is undermined by two key problems: underreporting of the numerator (the number of adverse events), and the lack of a denominator (the total number of exposures). One cause of underreporting is that manufacturers do not have to report serious adverse events, including deaths, if they decide that the event is not related to the device. Jerome Hoffman, an expert in clinical epidemiology at the University of California, Los Angeles, is critical of the FDA's policy of allowing manufacturers to make that determination. "The manufacturer has a powerful motive to find an alternative explanation for an adverse event. There's always the possibility of a separate cause." Dr Hoffman says that the agency should insist on independent adjudication of serious adverse events.

The database's value could be further improved, says Dr Hoffman, by including denominator data. "It's often claimed that even when bad events occur, they have to be relatively rare, given the huge number of exposures. That certainly may be true in some cases. But it's hard to know for sure in any individual instance, because the FDA doesn't track the number of exposures. It shouldn't be that hard … considering that WalMart can apparently track every head of lettuce they sell, at every point of its existence. Of course the FDA would have to require that companies submit data on the quantity of devices sold, and in use."

Ultimately, says Dr Hoffman, the process of ensuring device safety will continue to be compromised unless the thorny problem of interference from politicians and industry is tackled. "None of this occurs in a vacuum, of course. If we want to see fewer of these debacles in the future, it seems only logical that we're going to have to look to root causes, such as how campaigns are financed, and how the wealthy and powerful get to have so much more influence on laws, regulations and policies, than do scientists and others who would advocate for making the public health more important than corporate profit."

Sleep apnea

Intermittent decrease in respiratory flow during sleep has consistently been demonstrated in patients with VNS implants.[41] This seems to be due to an increase in vagal tone,[42] a measure of the control the vagus nerve has over the heartbeat.[43] Clinically significant sleep disordered breathing associated with VNS has been described in pediatric[44] and adult[45] patient populations. Most patients undergoing VNS treatment experience an increase of apnoea hypopnoea index (AHI) post treatment,[45] up to approximately one third develop mild obstructive sleep apnoea post treatment,[45] and a minority of patients develop severe obstructive sleep aponea related to VNS therapy.[44] These obstructive events can be alleviated by decreasing the frequency or intensity of VNS stimulation,[41] by having the patient sleep in non-supine position or by applying positive airway pressure.[45]

Screening for obstructive sleep apnoea (OSA) in patients with a seizure disorder who are undergoing a VNS implant is also important because adequate treatment of previously undiagnosed and untreated OSA is likely to result in better seizure control in these patients.[46]

Other

VNS causes stimulation of the superior and recurrent laryngeal nerves and is associated with problems ranging from alteration of voice (66%), coughing (45%), pharyngitis (35%) and throat pain (28%)[44] and hoarseness (very common) to frank laryngeal muscle spasm and upper airway obstruction (rare).[47] "Increased muscle tension," presumably in the upper body, may be experienced during the stimulation period.[48] The left vagus has proportionally lesser number of cardiac efferent fibers and placing the stimulator on this side potentially limits the arrhythmogenic effects of vagal stimulation but reversible bradyarrhythmias associated with vagal nerve stimulators have been well described.[49] Other nonspecific symptoms include headache, nausea, vomiting, dyspepsia,[49] dyspnea and paresthesia.[39]

In the treatment of epilepsy, randomized control trials conducted in the United States indicated that one-third of the patients had some type of an increase in seizures, with 17 percent having greater than a 25 percent increase. In each of the studies, there were patients who had greater than a 100 percent increase. In the E05 study, the range went up to a 234 percent increase, while in the E04 study, it went even higher, to a 680 percent maximum range.[50][51]

Mechanism of action

Vagus, the tenth cranial nerve, arises from the medulla and carries both afferent and efferent fibers. The afferent vagal fibers connect to the nucleus of the solitary tract which in turn projects connections to other locations in the central nervous system. Little is understood about exactly how vagal nerve stimulation modulates mood and seizure control but proposed mechanisms include alteration of norepinephrine release by projections of solitary tract to the locus coeruleus, elevated levels of inhibitory GABA related to vagal stimulation and inhibition of aberrant cortical activity by reticular activation system.[52]

Anti-inflammatory activities

The discovery by Kevin J. Tracey that vagus nerve stimulation inhibits inflammation by suppressing pro-inflammatory cytokine production has led to significant interest in the potential to use this approach for treating inflammatory diseases ranging from arthritis to colitis, ischemia, myocardial infarction, and congestive heart failure.[53] Action potentials transmitted in the vagus nerve activate the efferent arm of the inflammatory reflex, the neural circuit that converges on the spleen to inhibit the production of TNF and other pro-inflammatory cytokines by macrophages there.[54] This efferent arc is also known as the cholinergic anti-inflammatory pathway.[55] Because this strategy targets the release of TNF and other pro-inflammatory cytokines, it may be possible to use vagus nerve stimulation instead of anti-inflammatory antibodies (e.g., Remicade or Enbrel) to treat inflammation.

A study published in 2011[56] demonstrated the existence of acetylcholine-synthesizing T-cells in the spleen that respond to vagal stimulation, resulting in suppression of inflammatory response / TNF-alpha via macrophages.

A clinical trial of an implantable VNS device reported in 2016 that it reduced rheumatoid arthritis markers.[57]

Direct vagus nerve stimulation

This is currently the only widely used method of therapeutic VNS. It requires the surgical implantation of a stimulator device The Cyberonics VNS devices consist of a titanium-encased generator about the size of a pocket watch with a lithium battery to fuel the generator, a lead wire system with electrodes, and an anchor tether to secure leads to the vagus nerve. The battery life for the pulse generator is "between 1 [and] 16 years, depending on the settings [ie how strong the signal being sent is, the length of time the device stimulates the nerve each time, and how frequently the device stimulates the nerve]."[58]

Implantation of the Cyberonics 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 clavicle. 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.[59] 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.[39] The device is currently only made by Cyberonics, Inc.

Transcutaneous vagus nerve stimulation (t-VNS)

"Wearable" devices are being tested and developed that involve transcutaneous stimulation and do not require surgery. Electrical impulses are targeted at the aurical (ear), at points where branches of the vagus nerve have cutaneous representation. Specifically the concha has been target for t-VNS.[60]

Approval and endorsement

In 1997, the US Food and Drug Administration’s neurological devices panel met to consider approval of a vagus nerve stimulator (VNS). The manufacturer, Cyberonics, said it could prevent or reduce seizures in patients with partial onset epilepsy who did not respond to drug treatment. The device consists of a generator the size of a matchbox that is implanted under the skin below the patient’s clavicle. 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 lasting about 30 seconds every 3–5 minutes.

Representatives from Cyberonics offered no definitive explanation during the FDA meeting of how the device stopped or reduced seizures, but they had three studies, E03, E04, and E05, to show its safety and efficacy.

Two of the studies, E03 and E05, involved 313 patients with treatment resistant partial seizures randomised to high or low dose stimulation. The low stimulation arm was intended to avoid the problem of an unblinded placebo arm because all patients would be implanted and told they were receiving stimulation. The studies did not include a medical treatment arm for comparison, leaving unanswered the question of whether either treatment arm was superior to existing care. Researchers reported that 25% of patients in the high stimulation arms of the trials achieved the primary end point: a 50% reduction in seizure frequency from baseline. However, 20% of patients in the high stimulation arm had more seizures.[61][62]

Although the use of VNS for TRD has been endorsed by the American Psychiatric Association, the FDA's approval of VNS for TRD remains controversial. According to Dr. A. John Rush, vice chairman for research in the Department of Psychiatry at the University of Texas Southwestern Medical Center at Dallas, results of the VNS pilot study showed that 40 percent of the treated patients displayed at least a 50 percent or greater improvement in their condition, according to the Hamilton Depression Rating Scale.[63][64] Many other studies concur that VNS is indeed efficacious in treating depression. However, these findings do not take into account improvements over time in patients without the device. In the only randomized controlled trial VNS failed to perform any better when turned on than in otherwise similar implanted patients whose device was not turned on.[65]

See also

References

  1. ↑ Groves, Duncan A.; Brown, Verity J. (2005). "Vagal nerve stimulation: A review of its applications and potential mechanisms that mediate its clinical effects". Neuroscience & Biobehavioral Reviews. 29 (3): 493–500. doi:10.1016/j.neubiorev.2005.01.004.
  2. ↑ Clinical trial number NCT00294281 for "Vagus Nerve Stimulation for Treating Adults With Severe Fibromyalgia" at ClinicalTrials.gov
  3. ↑ Karason K, Mølgaard H, Wikstrand J, Sjöström L (April 1999). "Heart rate variability in obesity and the effect of weight loss". The American Journal of Cardiology. 83 (8): 1242–7. PMID 10215292. doi:10.1016/S0002-9149(99)00066-1.
  4. ↑ "NIH Grant Supports Prof’s Search for Tinnitus Cure". UT Dallas News. August 9, 2010.
  5. ↑ Herremans SC, Baeken C (September 2012). "The current perspective of neuromodulation techniques in the treatment of alcohol addiction: a systematic review" (PDF). Psychiatria Danubina. 24 (Suppl 1): S14–20. PMID 22945180.
  6. ↑ Shen MJ, Shinohara T, Park HW, et al. (May 2011). "Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines". Circulation. 123 (20): 2204–12. PMC 3101282 Freely accessible. PMID 21555706. doi:10.1161/CIRCULATIONAHA.111.018028.
  7. ↑ Sha Y, Scherlag BJ, Yu L, et al. (October 2011). "Low-level right vagal stimulation: anticholinergic and antiadrenergic effects". Journal of Cardiovascular Electrophysiology. 22 (10): 1147–53. PMID 21489033. doi:10.1111/j.1540-8167.2011.02070.x.
  8. ↑ Faris PL, Eckert ED, Kim SW, et al. (May 2006). "Evidence for a vagal pathophysiology for bulimia nervosa and the accompanying depressive symptoms". Journal of Affective Disorders. 92 (1): 79–90. PMID 16516303. doi:10.1016/j.jad.2005.12.047.
  9. ↑ Niederbichler AD, Papst S, Claassen L, et al. (September 2009). "Burn-induced organ dysfunction: vagus nerve stimulation attenuates organ and serum cytokine levels". Burns. 35 (6): 783–9. PMID 19482432. doi:10.1016/j.burns.2008.08.023.
  10. ↑ Abraham WT, Smith SA (February 2013). "Devices in the management of advanced, chronic heart failure". Nature Reviews. Cardiology. 10 (2): 98–110. PMC 3753073 Freely accessible. PMID 23229137. doi:10.1038/nrcardio.2012.178.
  11. ↑ Payne BR, Tiel RL, Payne MS, Fisch B (May 2005). "Vagus nerve stimulation for chronic intractable hiccups. Case report". Journal of Neurosurgery. 102 (5): 935–7. PMID 15926725. doi:10.3171/jns.2005.102.5.0935.
  12. ↑ Effects of Vagus Nerve Stimulation (VNS) as a "Treatment of Persistent Depression With Comorbid Personality Disorders"., cpapplanet.com
  13. ↑ Zamotrinsky, A. V.; Kondratiev, B.; de Jong, J. W. (2001). "Vagal neurostimulation in patients with coronary artery disease". Auton. Neurosci. 88 (1–2): 109–116. doi:10.1016/S1566-0702(01)00227-2.
  14. ↑ Spatola M, Jeannet PY, Pollo C, Wider C, Labrum R, Rossetti AO (2013). "Effect of vagus nerve stimulation in an adult patient with Dravet syndrome: contribution to sudden unexpected death in epilepsy risk reduction?". European Neurology. 69 (2): 119–21. PMID 23207687. doi:10.1159/000345132.
  15. ↑ Zamponi N, Passamonti C, Cesaroni E, Trignani R, Rychlicki F (July 2011). "Effectiveness of vagal nerve stimulation (VNS) in patients with drop-attacks and different epileptic syndromes". Seizure. 20 (6): 468–74. PMID 21396833. doi:10.1016/j.seizure.2011.02.011.
  16. ↑ Yamakawa K, Matsumoto N, Imamura Y, et al. (2013). "Electrical vagus nerve stimulation attenuates systemic inflammation and improves survival in a rat heatstroke model". PLOS ONE. 8 (2): e56728. PMC 3570456 Freely accessible. PMID 23424673. doi:10.1371/journal.pone.0056728.
  17. ↑ Liu H, Liu Y, Yu J, et al. (April 2011). "Vagus nerve stimulation inhibits heroin-seeking behavior induced by heroin priming or heroin-associated cues in rats". Neuroscience Letters. 494 (1): 70–4. PMID 21362452. doi:10.1016/j.neulet.2011.02.059.
  18. ↑ Krzyzaniak M, Peterson C, Loomis W, et al. (May 2011). "Postinjury vagal nerve stimulation protects against intestinal epithelial barrier breakdown". The Journal of Trauma. 70 (5): 1168–75; discussion 1175–6. PMC 4241239 Freely accessible. PMID 21610431. doi:10.1097/TA.0b013e318216f754.
  19. ↑ "Vagus Nerve Stimulation". Living With LGS.
  20. ↑ Ghacibeh GA, Shenker JI, Shenal B, Uthman BM, Heilman KM (September 2006). "The influence of vagus nerve stimulation on memory". Cognitive and Behavioral Neurology. 19 (3): 119–22. PMID 16957488. doi:10.1097/01.wnn.0000213908.34278.7d.
  21. ↑ Rosenberg O, Shoenfeld N, Kotler M, Dannon PN (June 2009). "Mood disorders in elderly population: neurostimulative treatment possibilities". Recent Patents on CNS Drug Discovery. 4 (2): 149–59. PMID 19519563. doi:10.2174/157488909788453013.
  22. ↑ Polak T, Zeller D, Fallgatter AJ, Metzger FG (March 2013). "Vagus somatosensory-evoked potentials are prolonged in patients with multiple sclerosis with brainstem involvement". NeuroReport. 24 (5): 251–3. PMID 23407276. doi:10.1097/WNR.0b013e32835f00a3.
  23. ↑ Li H, Yang TD (November 2009). "Vagus nerve stimulation may be used in the therapy of myocarditis". Medical Hypotheses. 73 (5): 725–7. PMID 19481875. doi:10.1016/j.mehy.2009.04.036.
  24. ↑ "Posts Tagged 'vagus nerve stimulation'". Archived from the original on January 25, 2010.
  25. ↑ Payrits T, Ernst A, Ladits E, Pokorny H, Viragos I, Längle F (October 2011). "Vagale Stimulation–eine neue Möglichkeit zur konservativen Therapie der peripheren arteriellen Verschlusskrankheit" [Vagal stimulation - a new possibility for conservative treatment of peripheral arterial occlusion disease]. Zentralblatt für Chirurgie (in German). 136 (5): 431–5. PMID 22009541. doi:10.1055/s-0031-1283739.
  26. ↑ Xiong J, Xue FS, Liu JH, et al. (December 2009). "Transcutaneous vagus nerve stimulation may attenuate postoperative cognitive dysfunction in elderly patients". Medical Hypotheses. 73 (6): 938–41. PMID 19631475. doi:10.1016/j.mehy.2009.06.033.
  27. ↑ Grujic J, Bien CG, Pollo C, Rossetti AO (January 2011). "Vagus nerve stimulator treatment in adult-onset Rasmussen's encephalitis". Epilepsy & Behavior. 20 (1): 123–5. PMID 21130042. doi:10.1016/j.yebeh.2010.10.024.
  28. ↑ Steinberg H (July 2013). "A pioneer work on electric brain stimulation in psychotic patients. Rudolph Gottfried Arndt and his 1870s studies". Brain Stimulation. 6 (4): 477–81. PMID 23266132. doi:10.1016/j.brs.2012.11.004.
  29. ↑ Kumar V, Sharma A (January 2010). "Is neuroimmunomodulation a future therapeutic approach for sepsis?". International Immunopharmacology. 10 (1): 9–17. PMID 19840870. doi:10.1016/j.intimp.2009.10.003.
  30. ↑ Lyubashina OA, Sokolov AY, Panteleev SS (October 2012). "Vagal afferent modulation of spinal trigeminal neuronal responses to dural electrical stimulation in rats". Neuroscience. 222: 29–37. PMID 22800563. doi:10.1016/j.neuroscience.2012.07.011.
  31. ↑ Hiraki T, Baker W, Greenberg JH (April 2012). "Effect of vagus nerve stimulation during transient focal cerebral ischemia on chronic outcome in rats". Journal of Neuroscience Research. 90 (4): 887–94. PMC 3306061 Freely accessible. PMID 22420043. doi:10.1002/jnr.22812.
  32. ↑ Levy G, Fishman JE, Xu D, et al. (January 2013). "Parasympathetic stimulation via the vagus nerve prevents systemic organ dysfunction by abrogating gut injury and lymph toxicity in trauma and hemorrhagic shock". Shock. 39 (1): 39–44. PMC 3547655 Freely accessible. PMID 23247120. doi:10.1097/SHK.0b013e31827b450d.
  33. ↑ Lopez NE, Krzyzaniak MJ, Costantini TW, et al. (June 2012). "Vagal nerve stimulation decreases blood-brain barrier disruption after traumatic brain injury". The Journal of Trauma and Acute Care Surgery. 72 (6): 1562–6. PMID 22695423. doi:10.1097/TA.0b013e3182569875.
  34. ↑ Kumaria A, Tolias CM (June 2012). "Is there a role for vagus nerve stimulation therapy as a treatment of traumatic brain injury?". British Journal of Neurosurgery. 26 (3): 316–20. PMID 22404761. doi:10.3109/02688697.2012.663517.
  35. ↑ Komisaruk BR, Whipple B, Crawford A, Liu WC, Kalnin A, Mosier K (October 2004). "Brain activation during vaginocervical self-stimulation and orgasm in women with complete spinal cord injury: fMRI evidence of mediation by the vagus nerves". Brain Research. 1024 (1–2): 77–88. PMID 15451368. doi:10.1016/j.brainres.2004.07.029.
  36. ↑ Whipple B, Komisaruk BR (2002). "Brain (PET) responses to vaginal-cervical self-stimulation in women with complete spinal cord injury: preliminary findings". Journal of Sex & Marital Therapy. 28 (1): 79–86. PMID 11928182. doi:10.1080/009262302317251043.
  37. ↑ "Vagus Nerve Stimulation to Augment Recovery From Minimally Conscious or Persistently Vegetative States After Traumatic Brain Injury". ClinicalTrialsFeeds.org. December 14, 2010.
  38. ↑ Zhang X, Cao B, Yan N, et al. (January 2013). "Vagus nerve stimulation modulates visceral pain-related affective memory". Behavioural Brain Research. 236 (1): 8–15. PMID 22940455. doi:10.1016/j.bbr.2012.08.027.
  39. 1 2 3 George, M; Sackeim, HA; Rush, AJ; Marangell, LB; Nahas, Z; Husain, MM; Lisanby, S; Burt, T; et al. (2000). "Vagus nerve stimulation: A new tool for brain research and therapy*". Biological Psychiatry. 47 (4): 287–95. PMID 10686263. doi:10.1016/S0006-3223(99)00308-X.
  40. ↑ "UCLA Develops Unique Nerve-stimulation Epilepsy Treatment; "Brain Pacemaker" Designed as External or Implant Device" (Press release). 2006-07-25. Retrieved 2006-07-26.
  41. 1 2 Malow, BA; Edwards, J; Marzec, M; Sagher, O; Fromes, G (2000). "Effects of vagus nerve stimulation on respiration during sleep: A pilot study". Neurology. 55 (10): 1450–4. PMID 11094096. doi:10.1212/wnl.55.10.1450.
  42. ↑ Marzec, Mary; Edwards, Jonathan; Sagher, Oren; Fromes, Gail; Malow, Beth A. (2003). "Effects of Vagus Nerve Stimulation on Sleep-related Breathing in Epilepsy Patients". Epilepsia. 44 (7): 930–5. PMID 12823576. doi:10.1046/j.1528-1157.2003.56202.x.
  43. ↑ "HP-5A: Heart Rate and Blood Pressure" (PDF). iWorx Systems Inc. Retrieved 12 May 2014.
  44. 1 2 3 Hsieh, T; Chen, M; McAfee, A; Kifle, Y (2008). "Sleep-Related Breathing Disorder in Children with Vagal Nerve Stimulators". Pediatric Neurology. 38 (2): 99–103. PMID 18206790. doi:10.1016/j.pediatrneurol.2007.09.014.
  45. 1 2 3 4 Marzec, Mary; Edwards, Jonathan; Sagher, Oren; Fromes, Gail; Malow, Beth A. (2003). "Effects of Vagus Nerve Stimulation on Sleep-related Breathing in Epilepsy Patients". Epilepsia. 44 (7): 930–5. PMID 12823576. doi:10.1046/j.1528-1157.2003.56202.x.
  46. ↑ Vaughn, B; Dcruz, O; Beach, R; Messenheimer, J (1996). "Improvement of epileptic seizure control with treatment of obstructive sleep apneoa". Seizure. 5 (1): 73–8. PMID 8777557. doi:10.1016/S1059-1311(96)80066-5.
  47. ↑ Bernards, Christopher M. (2004). "An Unusual Cause of Airway Obstruction during General Anesthesia with a Laryngeal Mask Airway". Anesthesiology. 100 (4): 1017–8. PMID 15087642. doi:10.1097/00000542-200404000-00037.
  48. ↑ "Vagus Nerve Stimulation". University of Michigan Depression Center. Retrieved 28 August 2013.
  49. 1 2 Hatton, Kevin W.; McLarney, J Thomas; Pittman, Thomas; Fahy, Brenda G. (2006). "Vagal Nerve Stimulation: Overview and Implications for Anesthesiologists". Anesthesia & Analgesia. 103 (5): 1241–9. doi:10.1213/01.ane.0000244532.71743.c6.
  50. ↑ "Neurological Devices Panel: Tenth Meeting transcript" (PDF). Food and Drug Administration. p. 125.
  51. ↑ http://www.vnsmessageboard.com/index.php/topic,4117.0.html%5B%5D
  52. ↑ Ghanem, T; Early, S (2006). "Vagal nerve stimulator implantation: An otolaryngologist's perspective". Otolaryngology - Head and Neck Surgery. 135 (1): 46–51. PMID 16815181. doi:10.1016/j.otohns.2006.02.037.
  53. ↑ Tracey, Kevin J. (2007). "Physiology and immunology of the cholinergic antiinflammatory pathway". Journal of Clinical Investigation. 117 (2): 289–96. PMC 1783813 Freely accessible. PMID 17273548. doi:10.1172/JCI30555.
  54. ↑ Rosas-Ballina, M.; Ochani, M.; Parrish, W. R.; Ochani, K.; Harris, Y. T.; Huston, J. M.; Chavan, S.; Tracey, K. J. (2008). "Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia". Proceedings of the National Academy of Sciences. 105 (31): 11008–13. PMC 2504833 Freely accessible. PMID 18669662. doi:10.1073/pnas.0803237105.
  55. ↑ Tracey, Kevin J. (2009). "Reflex control of immunity". Nature Reviews Immunology. 9 (6): 418–28. PMID 19461672. doi:10.1038/nri2566.
  56. ↑ Rosas-Ballina, M.; Olofsson, P. S.; Ochani, M.; Valdés-Ferrer, S. I.; Levine, Y. A.; Reardon, C.; Tusche, M. W.; Pavlov, V. A.; Andersson, U.; Chavan, S.; Mak, T. W.; Tracey, K. J. (2011). "Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit". Science. 334 (6052): 98–101. PMID 21921156. doi:10.1126/science.1209985.
  57. ↑ Zapping RA: Electrical Stimulation as Novel Treatment? - A first step for bioelectronic medicine in arthritis. July 2016
  58. ↑ Cyberonics, Inc. (2007.) VNS Therapy Patient Essentials: Depression.
  59. ↑ Panescu, D. (2005). "Emerging Technologies: Vagus Nerve Stimulation for the Treatment of Depression". IEEE Engineering in Medicine and Biology Magazine. 24 (6): 68–72. doi:10.1109/MEMB.2005.1549737.
  60. ↑ Leusden, J; Sellare, R; et al. (2015). "Transcutaneous Vagal Nerve Stimulation (tVNS): a new neuromodulation tool in healthy humans?". Frontiers in Psychology. 6 (102): 287–95. PMC 4322601 Freely accessible. PMID 25713547. doi:10.3389/fpsyg.2015.00102.
  61. ↑ Lenzer J, Brownlee S (2010). "Why the FDA can't protect the public". BMJ. 341: c4753. doi:10.1136/bmj.c4753.
  62. ↑ "Investigation raises concerns about the post-approval surveillance of medical devices". ScienceDaily. November 4, 2010. Retrieved July 10, 2016.
  63. ↑ Doctor's Guide: Vagus Nerve Stimulation Successful For Depression
  64. ↑ Neurology Channel: Vagus Nerve Stimulation Archived October 27, 2005, at the Wayback Machine.
  65. ↑ FDA Summary of VNS Data

Further reading

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.