Anonymous
Not logged in
Talk
Contributions
Create account
Log in
Search
Editing
Vagus nerve infection hypothesis
From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history
Namespaces
Page
Discussion
More
More
Page actions
Read
Edit
Edit source
History
Warning:
You are not logged in. Your IP address will be publicly visible if you make any edits. If you
log in
or
create an account
, your edits will be attributed to your username, along with other benefits.
Anti-spam check. Do
not
fill this in!
{{Cleanup|reason="Evidence" section needs improvement (see Discussion) | date = 2021}} The '''Vagus Nerve Infection Hypothesis''' (VNIH) proposes that, in some individuals, the symptoms of [[chronic fatigue syndrome]] (CFS) are caused by an infection in or around the [[vagus nerve]], the longest nerve of the [[autonomic nervous system]] in the human body. In 2013, [[Michael VanElzakker]], then a graduate student at Tufts University and now a postdoctoral researcher at Harvard Medical School, published the hypothesis.<ref name="VanElzakker2013" /> The [[vagus nerve]], also called the tenth cranial nerve, starts in the brain and runs down the trunk of the body, with branches that innervate all of the major organs.<ref name="medscape_vn">{{Cite web | last1 = Medscape| title = Vagus Nerve Anatomy| date = Aug 17, 2015 | url = http://emedicine.medscape.com/article/1875813-overview}}</ref> It is responsible for the [[sickness response]], an involuntary response characterized by [[fatigue]], [[fever]], [[myalgia]], [[depression]], and other symptoms that are often observed in patients with [[Chronic fatigue syndrome|CFS]].<ref name="hhv6f-vnih">{{Cite web | last1 = HHV-6 Foundation| title = CFS: a herpesvirus infection of the vagus nerve? | date = Jul 13, 2013| url = http://hhv-6foundation.org/news/cfs-a-herpesvirus-infection-of-the-vagus-nerve}}</ref>s ==Theory== As explained by Dr. [[Michael VanElzakker]]: "The vagus nerve infection hypothesis of CFS contends that CFS symptoms are a pathologically exaggerated version of normal sickness behavior that can occur when sensory [[vagal ganglia]] [structures containing a number of nerve cell bodies] or [[paraganglia]] [non-nerve cells that surround nerves] are themselves infected with any [[virus]] or [[bacteria]].... [The] [[glial cell]]s [cells that support and protect neurons] can bombard the sensory vagus nerve with proinflammatory [[cytokine]]s and other neuroexcitatory substances, initiating an exaggerated and intractable sickness behavior signal. According to this hypothesis, any pathogenic infection of the vagus nerve can cause CFS, which resolves the ongoing controversy about finding a single [[pathogen]]." The neuroimmune cells whose job is to protect the nerve, such as [[mast cell]]s and glial cells, can sense an infectious agent and become activated, in turn signaling the vagus nerve to tell the [[brain]] there is an infection present, causing a systemic reaction.<ref name="VanElzakker2013" /> In 2015, VanElzakker stated he believed that any infectious agent with an affinity for nerve tissues can cause a vagus nerve infection, including [[Human herpesvirus 6]], [[Epstein-Barr virus]], [[Varicella zoster virus]], [[chickenpox]], certain kinds of [[enterovirus]]es and even [[Borrelia burgdorferi|borrelia]], the bacterium that causes [[Lyme disease]]. He thinks this could explain why no single infective agent has been isolated as the cause of CFS, even though all of these agents have been associated with disease.<ref name="lowhistchef-vnih">{{cite web | last1 = Ykelenstam | first1 = Yasmina | authorlink1 = Yasmina Ykelenstam | last2 = VanElzakker | first2 = MB | authorlink2 = Michael VanElzakker|title = Harvard Neuroscientist Dr. Michael VanElzakker: Chronic Fatigue Vagus Nerve Link|website = The Low Histamine Chef | date = Dec 8, 2015 | url = http://thelowhistaminechef.com/harvard-neuroscientist-dr-michael-van-elzakker-chronic-fatigue-vagus-nerve-link }}</ref> To test his hypothesis, VanElzakker is using a combined [[MRI]] and [[PET scan]] with radio labeled antibodies to look for "increased cellular activity in the [[brain stem]] in a place called the nucleus of the solitary tract, which is where about 80 percent of these sensory vagus nerve fibers have their cell bodies...The idea is that if we can see extra signal there, there’s more activity there in Chronic Fatigue Syndrome patients than there is in healthy people, that would be evidence that there’s an exaggerated signal coming from the vagus nerve into the brain."<ref name="lowhistchef-vnih" /> In addition, he suggests that one possibility is vagus nerve biopsy samples from CFS patients who have died prematurely from other causes.<ref name="hhv6f-vnih" /> However, given the size and highly intricate branching of the vagus nerve, direct evidence of infection would be difficult to demonstrate. ==Evidence== VNIH has been substantiated by researches at University Medical Center Hamburg Eppendorf in a 2023 study where they "performed a histopathological characterization of ''postmortem'' vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes". https://link.springer.com/article/10.1007/s00401-023-02612-x ==Treatment== If this theory proved correct, possible treatment approaches might include: === [[Antiviral]] treatments === Potential problems with [[antiviral]]s are that these drugs would need to be a broad spectrum antiviral because a specific virus may not be identified and that antiviral drugs tend not to be effective on the vagal paraganglia.<ref name="hhv6f-vnih" /> Dr. [[Jose Montoya]] and Dr. [[Martin Lerner]], have published studies suggesting that IV valganciclovir therapy may be effective for the subset of CFS patients suspected of having elevated IgG for [[Epstein-Barr virus|EBV]]. Lerner also included patients with elevated IgG for [[CMV]]. Both Montoya and Lerner have shown that longer treatment terms (>6 months) have achieved greater success than short-term antiviral therapy.<ref name="Lerner2010">{{Cite journal | last1 = Lerner | first1 = AM | authorlink1 = A Martin Lerner | last2 = Beqaj | first2 = S | authorlink2 = Safedin Beqaj| last3 = Fitzgerald | first3 = JT | authorlink3 = James T Fitzgerald | last4 = Gill | first4 = K | authorlink4 = Ken Gill | last5 = Gill | first5 = C | authorlink5 = Carol Gil | last6 = Edington | first6 = J | authorlink6 = James Edington| title = Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome| journal = Virus adaptation and treatment| volume = 2 | pages = 47-57 | date = 2010| url = https://www.dovepress.com/subset-directed-antiviral-treatment-of-142-herpesvirus-patients-with-c-peer-reviewed-article-VAAT}}</ref><ref name="Montoya2013">{{Cite journal | last1 = Montoya | first1 = JG | authorlink1 = Jose Montoya | last2 = Kogelnik | first2 = AM | authorlink2 = Andreas Kogelnik | last3 = Bhangoo | first3 = M | authorlink3 = | last4 = Lunn |first4 = MR | authorlink4 = | last5 = Flamand |first5 = L | author-link5 = |last6 = Merrihew |first6 = LE | author-link6 = |last7 = Watt |first7 = T | author-link7 =|last8 = Kubo |first8 = JT | author-link8 =|last9 = Paik |first9 = J | author-link9 = | last10 = Desai | first10 = M | authorlink10 =| title = Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome.| journal = Journal of Medical Virology| volume = 85 | pages = 2101-9| date = 2013| doi = 10.1002/jmv.23713| url=http://www.ncbi.nlm.nih.gov/pubmed/23959519}}</ref> Rodent studies have shown that the antiviral [[Famciclovir|Famvir]] (famciclovir) penetrates peripheral nerve ganglia better than other antivirals (e.g., Thackray & Feld 1996 J Infect Dis 173; Thackray & Feld 1998 Antimicrob Agents & Chemother 42), which makes it an attractive option if symptoms are driven by latent or active [[Herpesviruses|herpesvirus]] infection of peripheral vagus ganglia. === [[Glial cell]] inhibitors === Drugs such as [[ibudilast]] (brand names Ketas or Pinatos or in Japan), an anti-inflammatory drug used for over 20 years in Japan, mostly for asthma and post-stroke [[dizziness]].<ref name="Rolan2009" /> Ibudilast can be combined with [[opioid]]s to reduce chronic [[nerve pain]].<ref name="Rolan2009">{{Cite journal | title = Ibudilast: a review of its pharmacology, efficacy and safety in respiratory and neurological disease | date = Dec 2009|url=https://www.researchgate.net/publication/40023191_Ibudilast_A_review_of_its_pharmacology_efficacy_and_safety_in_respiratory_and_neurological_disease|journal=Expert Opinion on Pharmacotherapy|volume=10|issue=17|pages=2897–2904 | last =Rolan | first=P | authorlink = | last2 = Hutchinson | first2 = MR|author-link2 = | last3 = Johnson | first3=KW | authorlink3 = |language=en|doi=10.1517/14656560903426189|pmc=|pmid=|access-date=|issn=1465-6566|quote=|via=}}</ref> Ibudilast is also a phosphodiesterase (PDE) inhibitor, and crosses the [[blood-brain barrier]] and suppresses glial cell activation. === Vagus nerve stimulation === [[Vagus nerve stimulation]] (VNS) involves delivering electrical impulses to the vagus nerve via a medical device. Use is currently reserved as an adjunctive treatment for certain types of intractable [[epilepsy]] and treatment-resistant [[depression]], but some VNS devices have recently been approved for [[migraine]], and is being researched as a viable treatment for many other conditions, including [[myalgic encephalomyelitis|ME]], CFS, and [[fibromyalgia]].<ref name="Traianos2021">{{Cite journal | title = Ab0051 the Effects of Non-Invasive Vagus Nerve Stimulation on Immunological Responses and Patient Reported Outcome Measures of Fatigue in Patients with Chronic Fatigue Syndrome, Fibromyalgia, and Rheumatoid Arthritis | date = 2021-06-01|url=https://ard.bmj.com/content/80/Suppl_1/1057.3|journal=Annals of the Rheumatic Diseases|volume=80|issue=Suppl 1|pages=1057–1058 | last = Traianos | first = E. | last2 = Dibnah | first2 = B. | last3 = Lendrem | first3 = D. | last4 = Clark | first4 = Y. | last5 = Macrae | first5 = V. | last6 = Slater | first6 = V. | last7 = Wood | first7 = K. | last8 = Storey | first8 = D. | last9 = Simon | first9 = B. | last10 = Blake | first10 = J. | last11 = Tarn | first11 = J.|language=en|doi=10.1136/annrheumdis-2021-eular.1999|issn=0003-4967}}</ref><ref name="Chamizo2022">{{Cite journal | title = Non-Invasive Transcutaneous Vagus Nerve Stimulation for the Treatment of Fibromyalgia Symptoms: A Study Protocol | date = Jan 2022|url=https://www.mdpi.com/2076-3425/12/1/95/htm|journal=Brain Sciences|volume=12|issue=1 | pages = 95 | last =Molero-Chamizo | first = Andrés | last2 = Nitsche | first2 = Michael A. | last3 = Bolz | first3 = Armin | last4 = Andújar Barroso | first4 = Rafael Tomás | last5 = Alameda Bailén | first5 = José R. | last6 = García Palomeque | first6 = Jesús Carlos | last7 = Rivera-Urbina | first7 = Guadalupe Nathzidy|language=en|doi=10.3390/brainsci12010095|issn=2076-3425}}</ref><ref name="Kutlu2020">{{Cite journal | title = The Impact of Auricular Vagus Nerve Stimulation on Pain and Life Quality in Patients with Fibromyalgia Syndrome | date = 2020-03-02|url=https://www.hindawi.com/journals/bmri/2020/8656218/|journal=BioMed Research International|volume=2020| pages = e8656218 | last = Kutlu | first = Nazlı | last2 = Özden | first2=Ali Veysel | last3 = Alptekin | first3=Hasan Kerem | last4 = Alptekin | first4=Jülide Öncü|language=en|doi=10.1155/2020/8656218|issn=2314-6133}}</ref> Vagus nerve stimulation promotes the anti-inflammatory effects of the motor (efferent) [[vagus nerve]]. In the case of the vagus nerve infection hypothesis, it may also regulate exaggerated sensory (afferent) signaling. {{See also|Vagus nerve stimulation}} === [[Mestinon]] === [[Mestinon]] (pyridostigmine) - a drug that blocks the enzymatic breakdown of [[acetylcholine]], which is the primary [[neurotransmitter]] of the vagus nerve, especially the parasympathetic/motor/efferent branch. Mestinon is frequently prescribed for [[Postural orthostatic tachycardia syndrome|POTS]], especially to improve tachycardia, and can work synergistically with [[vagus nerve stimulation]]. === [[Celecoxib|Celebrex]] === [[Celecoxib|Celebrex]] is a [[COX-2 inhibitors|COX2 inhibitor]], which blocks an enzyme that is part of the production of [[Prostaglandin|prostaglandins]]. When glial cells become activated, they produce neuroexcitatory mediators - molecules that turn on nerve cells. According to the vagus nerve infection hypothesis, infection of vagus nerve ganglia causes activation of associated glial cells, which in turn overly-excite the vagus nerve via these mediators. Prostaglandins are one of these neuroexcitatory mediators, along with proinflammatory [[cytokine]]s, [[nitric oxide]], [[reactive oxygen species]], [[glutamate]], and nerve growth factor. Beside the antiinflammatory mechanism of COX2 inhibition, herpesviruses upregulate COX2 to aid with its own replication (e.g., Reynolds & Enquist 2006 Rev Med Virol 16). === Ampligen === [[Ampligen]] (Rintatolimod) is a drug that stimulates the production of natural [[interferon]]. ==Talks and interviews == *[http://thelowhistaminechef.com/harvard-neuroscientist-dr-michael-van-elzakker-chronic-fatigue-vagus-nerve-link Harvard Neuroscientist Dr. Michael VanElzakker: Chronic Fatigue Vagus Nerve Link] - The Low Histamine Chef ==Notable studies== *2016, Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome<ref name="Barnden2016">{{Cite journal | last1 = Barnden | first1 = LR | authorlink1 = Leighton Barnden | last2 = Kwiatek | first2 = R | authorlink2 = Richard Kwiatek | last3 = Crouch | first3 = B | authorlink3 = Benjamin Crouch | last4 = Burnet | first4 = R | authorlink4 = Richard Burnet | last5 = Del Fante | first5 = P | authorlink5 = Peter Del Fante | title = Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome |journal = NeuroImage: Clinical| volume = 11 | pages = 530-537 | date = 2016|doi = 10.1016/j.nicl.2016.03.017 | url = http://www.sciencedirect.com/science/article/pii/S2213158216300584}}</ref> - [http://www.sciencedirect.com/science/article/pii/S2213158216300584 (Full text)] * 2013, Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis<ref name="VanElzakker2013">{{Cite journal | last1 = VanElzakker | first1 = MB | authorlink1 = Michael VanElzakker| title = Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis| journal = Medical Hypotheses | volume = 81 | issue = 3 | pages = 414-423 | date = Sep 2013 | pmid = 23790471 | doi = 10.1016/j.mehy.2013.05.034 | url = http://www.pdf-archive.com/2013/06/23/vanelzakker-vnih-cfs-in-press/vanelzakker-vnih-cfs-in-press.pdf}}</ref> - [http://www.ncbi.nlm.nih.gov/pubmed/23790471 (Full text)] ==See also== *[[Vagus nerve stimulation]] *[[The spread of EBV to ectopic lymphoid aggregates may be the final common pathway in the pathogenesis of ME/CFS]] ==Learn more== * 2013, [https://hhv-6foundation.org/chronic-fatigue-syndrome/cfs-a-herpesvirus-infection-of-the-vagus-nerve CFS: a herpesvirus infection of the vagus nerve?] - HHV-6 Foundation *2013, [http://simmaronresearch.com/2013/12/one-theory-explain-vagus-nerve-infection-chronic-fatigue-syndrome/ One Theory To Explain Them All? The Vagus Nerve Infection Hypothesis for Chronic Fatigue Syndrome] - Simmaron research *2014, [http://simmaronresearch.com/2014/02/michael-vanelzakker-ph-d-talks-vagus-nerve-infection-hypothesis-chronic-fatigue-syndrome-mecfs/ Michael VanElzakker Ph.D Talks – About the Vagus Nerve Infection Hypothesis and Chronic Fatigue Syndrome (ME/CFS)] - Simmaron research ==References== {{Reflist}} [[Category:Medical hypotheses]]
Summary:
Please make sure your edits are consistent with
MEpedia's guidelines
.
By saving changes, you agree to the
Terms of use
, and you irrevocably agree to release your contribution under the
CC BY-SA 3.0 License
and the
GFDL
. You agree that a hyperlink or URL is sufficient attribution under the Creative Commons license.
Cancel
Editing help
(opens in new window)
Templates used on this page:
MediaWiki:Colon-separator/en
(
view source
)
MediaWiki:Seealso/en
(
view source
)
Template:Ambox
(
edit
)
Template:Category handler
(
edit
)
Template:Cite journal
(
edit
)
Template:Cite web
(
edit
)
Template:Cleanup
(
edit
)
Template:Cleanup reason text
(
edit
)
Template:DMC
(
edit
)
Template:DMCA
(
edit
)
Template:Dated maintenance category
(
edit
)
Template:Digits
(
edit
)
Template:FULLROOTPAGENAME
(
edit
)
Template:Full stop
(
edit
)
Template:Full stop character
(
edit
)
Template:GetFallback
(
edit
)
Template:Help improve text
(
edit
)
Template:LangSwitch
(
edit
)
Template:Last word
(
edit
)
Template:Main other
(
edit
)
Template:No fullstop
(
edit
)
Template:No fullstop/first
(
edit
)
Template:Ns has subpages
(
edit
)
Template:Reflist
(
edit
)
Template:See also
(
edit
)
Template:Str endswith
(
edit
)
Template:Str len
(
edit
)
Template:Uselang
(
edit
)
Template:Year
(
edit
)
Module:Arguments
(
edit
)
Module:Category handler
(
edit
)
Module:Category handler/blacklist
(
edit
)
Module:Category handler/config
(
edit
)
Module:Category handler/data
(
edit
)
Module:Category handler/shared
(
edit
)
Module:Check for unknown parameters
(
edit
)
Module:Citation/CS1
(
edit
)
Module:Citation/CS1/COinS
(
edit
)
Module:Citation/CS1/Configuration
(
edit
)
Module:Citation/CS1/Date validation
(
edit
)
Module:Citation/CS1/Identifiers
(
edit
)
Module:Citation/CS1/Utilities
(
edit
)
Module:Citation/CS1/Whitelist
(
edit
)
Module:Message box/configuration
(
edit
)
Module:Message box by year
(
edit
)
Module:Namespace detect/config
(
edit
)
Module:Namespace detect/data
(
edit
)
Module:No globals
(
edit
)
Module:Ns has subpages
(
edit
)
Module:String
(
edit
)
Module:Unsubst
(
edit
)
Module:Yesno
(
edit
)
This page is a member of 3 hidden categories:
Category:All articles needing cleanup from 2021
Category:Articles needing cleanup from 2021
Category:Cleanup tagged articles with a reason field from 2021
Navigation
Navigation
Skip to content
Main page
Browse
Become an editor
Random page
Popular pages
Abbreviations
Glossary
About MEpedia
Links for editors
Contents
Guidelines
Recent changes
Pages in need
Search
Help
Wiki tools
Wiki tools
Special pages
Page tools
Page tools
User page tools
More
What links here
Related changes
Page information
Page logs