Tuesday, 24 January 2017

One theory to explain them all - Vagus nerve infection


One Theory To Explain Them All? The Vagus Nerve Infection Hypothesis for Chronic Fatigue Syndrome

Big Theory

It could explain the Chronic Fatigue Initiatives pathogen study results.  It could show how an infection could cause chronic fatigue syndrome, and then seemingly disappear.  It integrates two of the biggest players in ME/CFS; the autonomic nervous system and the immune system. It focuses on the herpesviruses. It includes sensory nerves, an increasingly hot topic in ME/CFS/FM, and it follows an  established model of fibromyalgia.
light bult
If it’s correct VanElzakker’s hypothesis could explain a lot about chronic fatigue syndrome
It’s the Vagus Nerve Infection Hypothesis (VNIH) for chronic fatigue syndrome, and it could change how this disorder is viewed, researched and treated.
Created by Michael VanElzakker, a Tufts neuroscientist,  the VNIH proposes that nerve loving viruses trigger a difficult to detect  immune response which produces the fatigue and other symptoms present in chronic fatigue syndrome.

Location, Location, Location

VanElzakker proposes that an infection triggers ME/CFS, but if his theory is right the most important thing about that infection is not what it is but where it is.   That ‘where’  is the biggest nerve in the body; the vagus nerve – a ‘wandering nerve’ that stretches over much of our torso and sends its roots into most of the organs of the body.
The vagus nerve isn’t just any nerve; it’s the nervous system’s immune conduit to the brain. VE believes that an infection there doesn’t need to be large to cause havoc in the brain; it just needs to be present.
In some ways, vagus nerve appears, in fact, to be ripe for infection in ME/CFS. As it ‘wanders’ through the body it comes into contact with virus havens such as the esophagus, stomach, lungs and spleen, all of which have likely at one time or another harbored the herpesviruses (HHV6, HHV-5 [cytomegalovirus], HHV-4 [Epstein-Barr virus]) that have been thought to be associated with ME/CFS for decades.
Most humans carry several of these herpesviruses in latent form unless some stressor or biological event allows them to become reactivated.
Van Elzakker suggests ME/CFS is caused by localized infections associated with the vagus nerve
VanElzakker believes that upon reactivation these viruses replicate and move outside the nerves where they run into glial cells that attempt to gobble them up.  The glial cells perk up remarkably in the presence of viruses, releasing all manner of pro-inflammatory and neuroexcitatory compounds (proinflammatory cytokines [IL-1B, IL-6, TNF-a], glutamate, prostaglandins, nitric oxide and free radicals. )
Receptors on the vagus nerve that sniff out these alarm signals tell the brain an infection is present, which then shuts the body down by sending out  signals  (fatigue, flu-like symptoms, pain, etc.) that slow the body down, tell it to stop moving, stop eating, stop thinking.
Because these infections are localized right on the main immune conduit to the brain, VanElzakker believes they don’t need to produce the outsized cytokine response researchers have been looking for.   All they need to do is tweak the vagus nerve and let it and the brain the do the rest.
You don’t need a ‘big’ infection to produce ME/CFS; all you need is a little infection  in the right place.

The Key Component – Glial Cells

The glial cells that surround and protect the vagus nerve are the key. Once thought to be mere structural scaffolding for the nerves, these cells  (e.g., astrocytes) are  now known to regulate nervous system signaling, a fact that’s been borne out in chronic fatigue syndrome’s sister disease,  fibromyalgia.
Immune system
VE believes pathogen triggered,but localized immune system activation around the vagus nerves may be causing ME/CFS
Glial cell  release of cytokines, glutamate, free radicals, etc.  in the dorsal horn of the spinal cord causes  increased pain sensitivity and allodynia in susceptible individuals. At some point the constant production of these excitatory substances  causes  a switch to get flipped sending the pain response spiraling upwards instead of shutting down.
At its most extreme (allodynia), the nervous system can interpret even the slightest touch as eliciting pain.   The pain response  system at this point, as VanElzakker, puts it,  has become, ‘pathological’.
That model of pain production has been solidly documented. VanElzakker proposes the same process  causing pain sensitization in the dorsal horn is  causing fatigue and other symptoms in chronic fatigue syndrome, except this time it’s associated with glial cells surrounding the vagus nerve.

A New Model of Fatigue

There is no  reason to suspect  that vagus-nerve associated glia would function any different than pain associated glia. VanElzakker
Nobody knows what a herpesvirus infection  of the vagus nerve would look like,  but VanElzakker doesn’t see any  reason it should look any different  from an infection in other parts of the body.
Herpesvirus infections of the trigeminal nerve cause shingles. Do herpesvirus infections of the vagus nerve cause chronic fatigue syndrome?
We know a  herpesvirus infection of your trigeminal nerve gets you shingles and chronic pain.  Researchers believe a chronic infection in the dorsal horn of your spinal cord will can  get you fibromyalgia and allodynia.  Would  an  infection of the vagus nerve get you sickness behavior and  chronic fatigue syndrome?
There’s a good chance it might.  Animal studies indicate that fatigue/flu-like symptoms go gangbusters when the vagus nerve gets infected. In fact, it’s  possible  the flu-like symptoms associated  with infections wouldn’t even exist without the vagus nerve.  Rodents with their vagus nerves cut don’t act sick even after they’ve been infected with a pathogen; the fevers, fatigue, the desire for isolation – are gone.
What if the vagus nerve receptors were…ceaselessly bombarded with these cytokines?  The symptoms of sickness behavior would be severe and intractable.
If the glial cells surrounding the vagus nerve function the same way they do in the dorsal horn, a lingering or even a ‘smoldering’ infection (aka Dr. Lerner’s theory), could trigger the similar type of hypersensitive reaction in the vagus nerve. In this ‘immune sensitization’ model, it takes only very small amounts of cytokines to trigger fatigue and flu-like behavior.
In fact, VanElzakker suggests chronic fatigue syndrome and fibromyalgia could both be ‘glial cell diseases’.

How to Have an Infection That Doesn’t Show Up in the Blood

“Cytokines Responding to a Local Infection Stay Local” VanElzakker
If VanElzakker is right, the  same group of viruses are wreaking  havoc in different locations in different ME/CFS patients.  The problem is it’s just darn hard to get at them.  You can’t find them in the blood and you sure as heck can’t biopsy the vagus nerve.
A series of fascinating studies exploring how central nervous system infections cause chronic nerve pain may, however, illuminate what’s happening in ME/CFS.  First, researchers mimicked a localized nervous system infection by dropping an HIV protein known to activate glial cells  into rodents’  spinal cord.
The vagus nerve is the immune conduit to the brain; mice studies suggest it plays a key role in producing ‘sickness behavior’
They found that the glial cells  reared up and starting producing pro-inflammatory cytokines to take care of the intruder. Not surprisingly,  the rodents looked and acted sick – the cytokines were doing their job to keep the animal down and isolated – but  no trace of those cytokines could be found  in their bloodstream.  Only if the animal’s spinal cord was sampled near where the ‘infection’ was  it possible to find any evidence of increased cytokine levels.
If VanElzakker is right, then blood  cytokine levels in ME/CFS are a function of where your vagus nerve is infected. If it’s infected in your  abdominal area, you might find cytokines in the blood, but it might be hard to find them in your spinal fluid. If your vagus nerve is infected near your brainstem you might find cytokines  in the spinal fluid, but you probably won’t find them in your blood.
Wherever the infection is there’s a good chance you may not find cytokines in the blood  at all.  This isn’t a  completely surprising fact or even restricted to the vagus nerve infections; cytokines in  mice with lung infections, for instance, showed up only when the lungs themselves were sampled.

Next Steps

VanElzakker suggests animal studies to better understand infections of the vagus nerve and to ultimately to build a chronic fatigue syndrome rodent model would be helpful.  Magnetic resonance imaging (MRI) may be able to detect viral lesions in central nervous system tissues. It is not yet known if  PET scans can detect the activation of a different type of glial cells; the satellite glia that are in vagus nerve ganglia and paraganglia, but special PET scans might be able to be used to assess microglial activation.
Cadaver studies of people who had ME/CFS definitely aren’t his first choice, but they could find activated glia, inflammation and viral infections of the vagus nerve and associated structures.  Finally,  novel protocols should be developed to assess the vagus nerve and brainstem functioning in ME/CFS.  The severely ill should be given a prominent place in future studies.


prescription drugs
If VanElzakker is correct different treatments could be in store for people with ME/CFS

A New Treatment Approach

“Glial cell inhibitors could become standard treatment for CFS (caused by CNS vagus nerve infection)” VanElzakker

Glial Cell Inhibitors

If VE’s theory is correct then glial cell inhibitors to stop the immune activation, antivirals to attack the pathogens, vagus nerve stimulation and surgical alteration of the vagus nerve might be possible treatments sometime in the future.
Glial cell inhibitors have a good safety profile, have been helpful at curbing neuropathic pain and are not used much in chronic fatigue syndrome or fibromyalgia.
If VanElzakker is right then Ibudilast, a drug in clinical trials now for another disorder, is a possibility.
Ibudilast (AV411/MN166), a drug used mostly in Japan, knocks down glial cell activation by inhibiting the production of a proflammatory cytokine called macrophage-migration-inhibitory factor (MIF)  and TNF-a.  Reduced levels of TNF-a could provide a bonus by increasing the breakdown of  a excitatory neurotransmitter called glutamate that may be helping to keep your central nervous system on edge.
Ibudilast is also  known to have neuroprotective and vasodilative effects and is usually used to treat asthma and stroke. It’s ability to suppress glial cell activation has made it useful in the treatment of neuropathic pain, and it’s currently undergoing clinical trials to treat neuropathic pain in Australia.  Ibudilast can also prevent viral activation of the microglia.
The NIH is funding Ibudilast trials in the US to see if it’s effective against drug addiction. If successful the drug could be available here for off-label use in ME/CFS  in three or four years.
Other general microglial inhibitors exist (minocyline, pentoxyfilline, propentfylline) but have undesirable side effects.


Stopping glial cell activation may be easier than getting at the viruses themselves.  Herpesviruses living in the sensory ganglia may be protected from antiviral drugs and antibodies.  (One new herpesvirus drug may be coming on the market soon, however.) Alternately, viruses other than the herpesviruses could be infecting the vagus nerve.

Behavioral Therapy

VanElzakker also notes that while behavioral therapies are not curative and may only apply to a subset of patients, they can help moderate symptoms and improve quality of life in some.


The VNIT may be able to explain more puzzling aspects of chronic fatigue syndrome than any other.  Next up we talk with Dr. VanElzakker about how he got interested in ME/CFS and what his theory may mean for this disorder.

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  • Gail Williamson

    December 28, 2013 at 9:13 pm - Reply
    This is exciting news and FYI: here’s a tweet from VE – check out what he says on Aug. 10th: http://www.immunesystemmasterkey.com/basic/ – Says he is putting together a pilot study with Anthony Komaroff. VE also tweeted that the vagus nerve could be infected by a variety of things, not just viruses. It could be bacteria or mold and would explain why people under drastically different circumstances would be sick.
    Any chance you could find out more about the pilot study?
    Looking forward to a breakthrough in this area in 2014. I believe he’s on the right track! Maybe Simmaron would be interested in helping with the study?
    Thanks for all that you do!
    Gail Williamson
    • Cort Johnson

      December 28, 2013 at 9:36 pm - Reply
      I will definitely ask him about that. I know he’s gotten a really good response from the research community. Interested about the mold and bacteria! Thanks for the info :)
      • Laura L

        May 8, 2016 at 12:13 am - Reply
        wondering if a study was done; think I have this problem. Thanks, Laura
    • Lynne

      December 30, 2013 at 2:02 am - Reply
      Given the similarity in symptoms between those with ME/CFS, FMS and Lyme (and related bacterial/protozoal) infections, I’m with Gail here… study shouldn’t be limited to viral pathogens in the vagus nerve. Any source of inflammation/activation of the vagal glial cells might be causative if this theory holds up (see Mark’s comment as well).
      Thanks for very interesting article, Cort!
    • barbara

      January 1, 2014 at 3:09 pm - Reply
      And don’t forget about parasites. Dr Klinghardt and others have stated that 80% CFS’ers have the parasite c. pulmoni,
      hidden lung worm, discovered by Dr Larry Klapowi. I strongly believe that I have this parasite. It’s thought to have been a bat parasite that jumped species when we bombed the hell out of VietNam, and it came to the US with returning vets. It is not contagious, but gets around via food and drink. It is so small it is almost invisible. There is much info re this on Google.
      • Catherine

        May 9, 2015 at 10:31 pm - Reply
        Dr. Klinghardt believes a lot of things. His list of causes and treatments increases every year since he needs them to keep in business. Having said that, I do agree that parasites may be contributing to our illnesses, just not as per Klinghardt and his wacky, non-scientific ART testing system.
        • Leigh

          December 17, 2015 at 4:18 pm - Reply
          I am sorry that you are so ignorant about pathogens. I personally have had my life saved by a doctor who does similar testing and treatment as Dr. Klinghardt here in Canada-the doctor saved my life. Another friend who has been sick for years was too complicated for this doctor so she went to Dr Klinghardt for treatment and for the first time in years she is getting better and has some energy to pay attention to her daughter. Conventional blood tests and the conventional sick care system have a lot of errors and vested interests directing it. My vitamins have not cost one life but every year 100, 000 people die in north america from taking prescribed medication. My brother and father didn’t get proper testing or treatment for Lyme disease and they died horrible deaths at premature ages. Dr. Klinghardt and other doctors warn of frying your mind/body on the Wifi but we still use our wifi and cordless and cellular phones that hurt us. More importantly doctor klinghardt did the studies that showed EMF’s increase the rate of replication of bacteria’s by 600 times. We ignore this to our peril too just look at our sick and fat and tired society all things have a cause! I have done the hard work of healing from many Lyme infections plus coinfections using alternative testing and treatments I am so glad to be alive to talk to you about it today to let you know that Dr. Klinghardt is one of the best doctors in North America for complicated and idiopthic diseases because nothing is idiopathic everything has a cause as to how it came to be. All the Best.
          • gary brookshire

            July 28, 2016 at 1:48 am -
            My son has a be\ad Lymes disuease infection. I am concerned that it is not getting nay better. I would approceate tlking to- you regardging hia case. thanks-
    • lisa

      September 14, 2016 at 11:07 pm - Reply
      I had fibromyalgia for 12.5 years. It’s gone. I am left with the tingling activation of a virus in my spine area. It I take 2000-3000 mg of L-LYSINE, it goes dormant, starting within 30 minutes or so. If I do not take it every single day,, the virus flares my vagus. It starts in the center and flares up and down my spine and neck. I know that my fibromyalgia was an immune system response gone haywire. I did all kinds of things to learn what I know, including long term fasts. Now I know Arginine and stress and sunlight in my eyes will activate it. L-lysine shuts it up. You can get it at any drugstore, it is over yhe counter. Go get some relief.
  • Deb

    December 28, 2013 at 9:30 pm - Reply
    • Cort Johnson

      December 28, 2013 at 9:34 pm - Reply
      The answer is Yes! I hope so :)
  • Spamlet

    December 28, 2013 at 9:36 pm - Reply
    Half a lifetime ago–before I even had my ME diagnosis–my attempts at explaining all my symptoms led me to suspect an infection of the vagus. I was, of course–and still am–laughed out of doctors’ surgeries and psychiatrists lairs, when I suggested that such things might be possible. It is good to read that it is now acceptable to entertain such theories!
  • Darlene

    December 28, 2013 at 9:42 pm - Reply
    This is so exciting! It sounds very promising. Thanks so much for the clear explanation.
  • Carol Carlson

    December 28, 2013 at 9:54 pm - Reply
    I didn’t have to read too far into the blog to realize that it all fits with the history and the present of my daughter’s suffering. She is a “perfect” example of what this disease is about, unfortunately. I strongly hope that Dr. VanElzakker’s scientific theory is proven to be based on solid fact. There are so many research projects going on around the world, focusing on an official diagnosis; however, it seems prudent to hope that Dr. VanElzakker has the correct answer. It was kind of scary to read his description of the source of the disease: it made so much sense to me, a lay person. Why can’t the research and medical experts realize what, it seems to me, to be there right in front of everyone’s nose?
    • Cort Johnson

      December 28, 2013 at 10:00 pm - Reply
      One nice thing about VE’s hypothesis is how well he lays out. It has gotten a good response. Kristin Loomis (interview upcoming) of the HHV-6 Foundation loved it and hopefully it prompt some research efforts.
      I think may fit in well with Pridgen’s theory of Fibromyalgia, by the way. I could be wrong, but I think Pridgen is looking at similar nerve ganglia in the gut.
    • CFS Facts

      December 28, 2013 at 10:35 pm - Reply
      The doctors can’t acknowledge what’s right in front of them because that would require admitting that they were wrong and the patient was right.
  • Kristi

    December 28, 2013 at 10:00 pm - Reply
    This makes a lot of sense! I would be interested in future updates on the treatment.
  • Nan

    December 28, 2013 at 10:59 pm - Reply
    How interesting, and yes, it makes a LOT of sense. Thanks for your hard work, by the way and Merry Christmas or Happy Holidays, whichever you prefer (people are so TOUCHY these days!)
  • Issie

    December 28, 2013 at 11:01 pm - Reply
    EXCITING, hypothesis!!!! I hope more concrete research is done and treatment will be less hit and miss. A faulty immune system seems to continue to show up. If we could get the immune system to detect what shouldn’t be there and destroy it, we would be better off. My doc is using minocycline and doxycycline (as part of the treatment) with his patients. ( Depends on which pathogens are detected. ) It seems more doctors are on this path of treatment. So wonderful that some of us are getting good results from it.
  • est_sunshine

    December 29, 2013 at 1:14 am - Reply
    This rings true for me – I have POTS and I have palpitations which I thought were heart related and had a holter monitor which found nothing serious. I believe the palpitations are in fact an overstimulated vagus nerve firing off, as they feel like an electric jolt in the centre of my chest – they are worse after eating or with stomach gas or when changing positions – all of which would put pressure on the vagus nerve. I know lots of people have them but I also have cold sores, including one in my nose that has been there for 3+ months!! I hope the research continues to be fruitful.
    • Tracey

      November 1, 2014 at 2:31 am - Reply
      I am seeing people here dealing with the same thing I have been dealing with since March 2011. I need to be a part of and be aware so i can learn. I’m with someone else here who said sometimes they get to feeling like their next breath may be their last
  • Raquel

    December 29, 2013 at 1:21 am - Reply
    It seems this hypothesis would be aligned with Dr Martinez Lavin proposal “Heart rate variability (HRV) analyses provide a quantitative marker of autonomic nervous system Activity” in Lerma et al. Arthritis Research & Therapy 2011, 13:R185 http://arthritis-research.com/content/13/6/R185.
    See his (Matinez Lavin) kindle book FIBROMYALGIA. “How stress becomes real pain and what to do about” or “Fibromialgia” paperback Spanish edition .(both books in Amazon.com)
    Martinez Lavin said there is Autonomic Nervous System Dysfunction in Fibromyalgia The sympathetic nervous system is overactive and the parasympathetic (read vagus nerve) is not acting..
    We should add to this the results of Dr. Daniel Dantini “The new Fibromyalgia Remedy”, (book 2008, Amazon.com). Dantini assumes (and shows some analyses) there is a hidden infection and treat his patients with antiviral drugs (70% success)
    We have the puzzles with almost all the pieces in!!!
    Raquel from Brazil, sorry for my English, is not perfect!
    • Cort Johnson

      December 29, 2013 at 1:22 am - Reply
      Thanks for the plug on the Martinez-Lavin book….I’m looking forward to reading it..
    • Naiara

      December 3, 2016 at 6:43 am - Reply
      Hello Raquel, are you a patient or a doctor? I’m Brazilian too and desperately looking for help.
  • Susan

    December 29, 2013 at 1:26 am - Reply
    This sounds like an exciting direction to be going in to me too. But one thing I don’t understand. If the elevated cytokines are only found near the site of the infection, how do they cause general sickness behavior? Wouldn’t they have to be in high enough levels in the circulation to affect the brain and how it is running the body? So then be detectable in blood samples? Or am I missing something here?
    Susan J.
    • Cort Johnson

      December 29, 2013 at 1:37 am - Reply
      My understanding is that the cytokines trigger the vagus nerve to tell the brain an infection is present. It appears that the vague nerves is the main immune nervous system conduit to the brain. Instead of cytokines in the blood getting to the brain and telling it that an infection is present, nervous system signals from the vagus nerve go straight to the brain telling it the same thing. If that’s true all you need is a local chronic infection near the vagus nerve to cause sickness behavior.
      I think VE’s suggestion that ME/CFS and FM could be disorders of the microglia is very interesting. Maybe the microglia are oversensitized to signs of infection or maybe they get damaged and keep pumping out cytokines…
  • Kathy R

    December 29, 2013 at 1:39 am - Reply
    This makes so much sense to me. I am compound heterozygous for MTHFR variants, so I got one from mother (1298) and one from father (677). Mother, in her old age, used to have vagus nerve attacks that mimicked heart attacks, but which would pass in a short time. Then she would be fine. She seemed to have chronic fatigue and FM all her life, especially when stressed out. I struggled along for decades, much like mother, until I finally got a CFS diagnosis. I hope this theory proves correct and that an effective treatment can be found. It will simplify things for the medical community and help many people.
    • Cort Johnson

      December 29, 2013 at 1:40 am - Reply
      Really interesting Kathy :)
      • Judy

        December 30, 2013 at 4:49 am - Reply
        Can I email this doctor who did this research? I was diagnosed with Fibromyalgia since 1991. This is the first time all of this made sense and actually seems like a possible answer to a lot of questions and help for my pain. Thank you.
        • Pat

          March 1, 2014 at 2:12 pm - Reply
          If you get anything information on fibromylgia could you please forward it to me I suffer from this, and I am in constant pain, I find the cold makes it worse. I would appreciate any information you get if you could pass it on to me.
  • Mark

    December 29, 2013 at 12:49 pm - Reply
    Great to see others getting in on this.
    I’m pretty convinced that he’s getting to the core problem but glial activation doesn’t require infection. Micro and macro glia respond to tissue injury also (whether mechanical, due to hypoxia or ischemia) and peripheral injuries can result in the same systemic glial neuroinflammation (as seen in complex regional pain syndrome). Small fibre polyneuropathy may be a similar driver in fibro.
    So given the difficulties in confirming a vagal nerve infection I’d prefer them to go after the neuronflammation. as you know one (unpublished) study appears to confirm microglial activation in ME/CFS using PET but there are also metabolic markers and Peterson’s CSF samples could well be ‘gold dust’.
    PS – Low dose Naltraxone is another glial inhibitor.
    Exciting stuff all round though which begs the question of what exactly Lipkin found in the CSF samples?
  • TheGodofPleasure

    December 29, 2013 at 1:44 pm - Reply
    I would be very interested to see how this hypothesis fits with those people who respond to Rituximab (if at all.)
    Maybe they represent what is currently considered to be a sub-group, but who actually have a completely different pathology, (i.e. a B cell infection) and yet one which yields very similar symptoms.
  • Kathy M

    December 29, 2013 at 4:18 pm - Reply
    I understand how the ‘sickness behavior’ could occur, especially with POTS and post exertional malaise, but does this theory address the immune problems resulting in actual sickness that so many CFS patients have? My initial symptoms were many, many colds, sinus infections, and very low B cells. My colds were contagious, not ‘sickness behavior’. Does sickness behavior cause immune suppression?
    • Cort Johnson

      December 29, 2013 at 6:40 pm - Reply
      In VE’s model an initial infection or viral reactivation (or bacterial infection or mold) triggers everything; the problem I believe is that the infection got to your vagus nerve and it settled in there – and never stopped. The infection continues – it keeps tweaking the microglial cells – which pump out the cytokines which trigger the vagus nerve to tell the brain to produce sickness behavior. I think he’s more focused on microglial inhibitors because he thinks its easier to stop the microglial activation than get at the infection.
      I suppose it is possible, though, that the microglia are keeping the infection down…In that case, I don’t know if you’d want to shut them off (???)
    • Issie

      December 29, 2013 at 8:11 pm - Reply
      In addition to POTS, MCAS and EDS I also have Hypogammaglobulinemia – which is low IGG levels and supposedly it would be hard for me to fight off infections. I seldom get sick (colds, flu, etc.) But, interestingly -have autoimmune diseases where my body attacks itself. (Vitiligo, allopecia, etc.) So, you can have both things going on.
      With me there was found a protozoa (FL1953) and a co-infection related to Lyme. Treating this and addressing my immune system and inflammation has been a HUGE help for me. Much inmprovement over the last year. It’s not a quick fix thing, takes time. But the end results are what matter and I’m so much better than I was.
      • Alicia

        November 22, 2016 at 9:30 pm - Reply
        Issie, or others, what did you do to combat PR (Protozoa and co-infections) to get your health back?
        Alicia in CT
  • Trish

    December 29, 2013 at 9:01 pm - Reply
    Interesting to read. ME came on after Glandular Fever in 1984. I now have widespread peripheral and autonomic neuropathy. Something’s going on and the neuro-immune systems are tightly linked.
    • Cort Johnson

      December 29, 2013 at 9:07 pm - Reply
      Thanks Trish. This next year is going to be interesting for you, I think, as studies on peripheral neuropathy and nerve damage come out in FM and hopefully ME/CFS.
  • Albert

    December 30, 2013 at 1:33 am - Reply
    I wonder if the CFS/ME scientific community has also embraced (or at least considered) the possibility of “altered ganglionic function” as a subset or a main reason of autonomic nervous system dysfunction. The possibility that this “alteration” being the result of latent-residing, neurotropic Herpesviruses. The basis for my curiosity goes back to the recent study that proved direct causality of gut dysmotility (weakened strength of involuntary gut muscle) following primary infection of Herpes Simplex infection in gastrointestinal tract of rat: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0072648
    The presumption here is that primary infection within the gut would subsequently have the virus travel up the Vegus nerve or establish latent infection in the associated Ganglion — Messenteric Ganglion or Celiac Ganglion.
  • Albert

    December 30, 2013 at 1:40 am - Reply
    The scary part about any infection by Herpesviruses is that the virus has the potential to reside in ANY ganglion. And if dysmotility is truly a hallmark of latent infection, i wonder what omnipresent ganglionic infection would cause in our body. Would humans continue to experience autonomic dysfunction regardless of persistent infection?
  • Albert

    December 30, 2013 at 6:31 am - Reply
    Imagine if the medical and science community proved that latent infection was the cause of a specific syndrome, e.g. Celiac infection of VZV or HSV was the cause of Irritable Bowel Syndrome. I would hope that the same theory would be applied to just about every other “random” experience: random elevated heart rate, random asthmatic attacks, Acid Reflux Disease, Diahrea, Swallowing Difficulties, etc. In fact, my belief on Acid Reflux disease is that the underlying cause is a disturbance of outside pathology or autonomic dysfunction not associated with latent infection. Acid Reflux just doesn’t come randomly…
    I offer this analogy: imagine riding a bicycle, and each pedal isn’t tight and snug, but loose and wobbly. Try pedaling. You’ll notice that the ability to transfer energy from you to the wheels, and to ultimately move the bicycle is ultimately disrupted. Our brains transfer electrical signals and other “stuff” (hormone, and probably things I have never heard of) to your muscles and organs THROUGH the ganglion. Ganglions are essentially conduits, or interfaces. Interfere with those interfaces, and you may have something similar to the bicycle analogy I gave above, or something like Irritable Bowel Syndrome…
    So kudos to Cort for writing thisblog!
  • Albert

    December 30, 2013 at 9:48 am - Reply
    I want to add another thing: given the subject of a single nerve being infected, imagine Herpes infection in any of the organs within the lungs — airway, alveolars, broncheal tubes, etc. In a situation with persistent infection, and a dysfunctional immune system, the viruses will simply continue to infect and spread, claiming cell upon cell upon cell, until those cells are destroyed, causing necrosis. Now, there are case studies that demonstrate Herpes Simplex to be associated with Idiopathic Pulmonary Fibrosis: one of the most devastating and insidious diseases known to man. All it takes is someone who is suffering one of these automimmune diseases, and somehow getting the virus into the airways. Perhaps by accidental inhalation of HSV-containing saliva. http://jcm.asm.org/content/41/6/2633.full
    Definitely don’t wish this disease upon anyone, but it is simply another example of the endless number of organs or tissue that these viruses can infect, and cause persistent problems.
    • Cort Johnson

      December 30, 2013 at 7:01 pm - Reply
      Albert thanks for all your insightful comments. They provide much food for thought :)
  • Celeste Cooper

    December 30, 2013 at 3:37 pm - Reply
    Glial cell involvement is certainly not a new theory, we discuss it in our BIG book, but to see this follow up, to see scientists getting excited and carrying past research into the present is encouraging. It is especially helpful for future generations. My own children are starting to show signs of living with these horrible disorders. Your blog has been particularly helpful on a personal level. Thank you Cort.
  • Aravir

    December 30, 2013 at 3:50 pm - Reply
    I like this theory, it is elegant and it confirms what dr. Klinghardt has been saying: that CFS and Lyme are the same disease.
    • Cort Johnson

      December 30, 2013 at 6:58 pm - Reply
      Interesting…I didn’t know Klinghardt felt that way…Very interesting…
      • Aravir

        January 1, 2014 at 5:28 pm - Reply
        I remember I read on a Betterhealthguy webpage that Klinghardt said CFS of unknown causes is probably Lyme. Before that I spoke to a Lyme patient and she kept telling me that my CFS symptoms were Lyme so I started googling and I found that website. I guess it doesn’t matter the type of infection, what it matters is that it affects the vagus nerve.
  • Janet Comerford

    December 30, 2013 at 4:16 pm - Reply
    Any serious research into ME/CFS/FM is always welcome news – however… I don’t see how this hypothesis can explain the numerous occasions where a large number of people have developed ME at the same time?
    • Cort Johnson

      December 30, 2013 at 6:58 pm - Reply
      I think it could actually. It would just take a bug that was quite virulent and that happened, perhaps because of genetic susceptibility or because they were under stress, to get further into the body (I assume) than normal. One of the nice things about VE’s hypothesis is that its kind of agnostic towards what kind of pathogen is present; it simply requires one to start the process off. Herpesviruses are the most obvious suspects because we know that they take up residence in those sites anyway.
  • Ros

    December 31, 2013 at 12:30 am - Reply
    Yes! Yes! Yes! l have been on this for some time in my own trying to get some one to talk to about this.
    l am just so happy to see this can not read it all now but l feel this is so key. It also explains my eye problem and not being able to read very much, and the viral feeling in my optic nerve. l believe that the virus has not gone as my CT scan showed a UBO in the mid brain.
    Happy is not the enough to express how l feel.
    Thankyou to all. May this next year be a very promising one indeed. Happy New Year XXX
  • floydguy

    December 31, 2013 at 1:43 pm - Reply
    Interesting hypothesis. Unfortunately, we appear to have another researcher completely ignorant of the day to day interactions patients have with the medical delivery industry. He seems to be quite taken with the idea that CBT and GET can be very helpful to 30% of the patient population. He doesn’t seem to understand that most clinicians believe CBT and GET to be curative NOT complementary. He seems to have a better grasp of infectious diseases and immunology than the shenanigans occurring in his own field in regards to ME [from his research paper]:
    “Patients should be helped to understand that this is not the case and that resistance to psycho- logical and behavioral intervention is misguided. Both cognitive behavioral therapy and graded exercise therapy have been shown in a randomized trial to be helpful for approximately 30% of indi- viduals with CFS [137]. While these effects were moderate, the fact that 30% of patients significantly improved from psychological and behavioral interventions – without any drugs or surgery – should not be ignored.
    There are two reasons that both psychological and behavioral interventions should be strongly recommended, along with the treatment options discussed above, to individuals with CFS….”
    As if….
    • Cort Johnson

      December 31, 2013 at 7:37 pm - Reply
      Even patients surveys show CBT is helpful in about 30 percent of patients. Other people get benefits from meditation, Amygdala, etc. I think you added the ‘very helpful’ part as well. Your quote says the effects were ‘moderate’ and they affected about 30% of the patients. That’s a pretty moderate statement in my view and doesn’t affect his main thesis at all – which is that an ongoing infection of the spinal cord causes ME/CFS. He’s not calling for more CBT studies; he’s calling for better imaging, etc. studies and developing animal models and those are the kinds of things that this paper will spark.
      • floydguy

        December 31, 2013 at 9:30 pm - Reply
        No, I am not missing his point which I think is very positive. You seem to be missing the point that he doesn’t recognize that many clinicians think that “CFS” is a psychological condition and can be CURED by CBT & GET. Do you not think there is harm in telling patients that they can be cured by these therapies? I am for anything that brings relief to people – including CBT, GET or listening to TV static; whatever works for individual circumstances.
        He did state: “30% of patients significantly improved from psychological and behavioral interventions – without any drugs or surgery – should not be ignored.” I am not sure how you can have a moderate effect and at the same time significantly improve. Which is it?
        It’s too bad he had to sully an otherwise interesting paper on glowing references to the PACE trial that folks on PR have done a good job deconstructing.
  • Valerie

    December 31, 2013 at 6:08 pm - Reply
    Cort, I wonder how Enteroviruses fit in with this theory? Dr. Chia’s work – the biopsies he has studied of the parietal cells of the stomach (which I was extremely positive on) seems like it could relate to the vagus nerve easily since it seems to be everywhere else in the body in his research. I also have high antibodies for at least three forms of enterovirus including a couple Coxsackie viruses, in lab findings from ARUP Labs in Utah. I don’t hear enough about his work and the relationship to these theories and I don’t understand why. Even Dr. Lipkin did not talk about this type of biopsy looking for viruses in his last report of his testings and findings. All I remember is that when I got a stomach flu, it affected my brain and whole system in days. I could track it.
    • Cort Johnson

      December 31, 2013 at 7:31 pm - Reply
      I don’t see why they wouldn’t fit. So long as they can get to those nerves and infect them they should work.
  • Deb

    January 1, 2014 at 10:03 pm - Reply
    Michael VanElzakker : I’m making my vagus nerve infection hypothesis #VNIH of #CFS paper available for free here, so pass it on.
  • Deb

    January 1, 2014 at 10:06 pm - Reply
    Sorry for double..triple posting link..augh.
  • Donna

    January 3, 2014 at 2:32 am - Reply
    I was diagnosed with Gastroparesis after having CFS. I believe the Vagus Nerve is at risk at being damaged permanently from having CFS on any patient with the disease. This disease damages more and more that is just starting to be discovered. I think more will come to be known in the future. Having Gastroparesis has been a very difficult challenge along with all the other symptoms of CFS/ME.
    • Kristi

      January 3, 2014 at 4:40 pm - Reply
      Yes, I have gastroparesis also. I just found out what it is. I have to take multiple digestive enzymes with food. I don’t eat after 6 pm, which helps a lot.
      • Dona

        December 18, 2014 at 1:22 pm - Reply
        I too have been told I have gastroparesis…. I got this diagnosis after I had my gallbladder removed ( a mistake on my part for not following through on my end and just believing the doctor when he said it needed to come out, still not sure why) but afer that surgery, I became VERY ill. I had a throat scope (EKG?) and the GI said my stomach was FULL of food, and I had barely eaten in at least a month. She said since I’m not diabetic, my vagus nerve had been nicked during surgery. Yet of course NO tests were mentioned to show this, and I’ve been on the “vagus nerve” information search for over a year, meanwhile declining in health. I’ve lost 50 lbs, down to 101. I’m SURE I have vagus nerve damage due to something gone wrong during surgery… I’ve see many others post the same thing, GP after a surgery, gall bladder removal included. How can I find out more info on this? I just want to get better! But NO doctor will help me or discuss the vegus nerve. I’d appreciate any advice or more links to help me on my endless, tiring search..
        • Jan

          February 21, 2015 at 11:31 pm - Reply
          I have gastroparesis, too (for about the last 18 months, diagnosed, but had symptoms much longer). I don’t have CFS/ME, but I do have hypersomnia, and saw a link to this post and was curious because of my constant fatigue, even though it is different diagnostically from your illness. There is no cure for gastroparesis, and in my experience, most gastroenterologists are not very knowledgeable, unless they specialize in motility disorders (mine does not). I have learned a lot from support groups on Facebook, such as taking digestive enzymes, when to utilize liquid meal replacements, what foods to avoid, helpful websites, etc. I still have flares, but it has been much better lately than when I first diagnosed. My doctor really was of no help. Luckily, I have realized that it could be much worse, but I think I’ve learned to minimize the effects even more. It is possible that your gastroparesis is idiopathic — that is, from an unknown cause. That’s how we’re classifying mine for now (though I pushed to investigate dysautonomia, the doctor brushed me off). The important part is learning to manage the symptoms anyway. The Facebook groups are very supportive, even if a little inconsistent (the administrators get sick, too, and can’t always post every day). Just wanted to make you aware, and let you know there are kindred souls out there! :) There are some CFS/ME folks in our Major Somnolence Disorder support group, too if you’re looking for fellow sleepyheads, although most there have a hypersomnia or narcolepsy diagnosis! I do hope you find a way to manage your symptoms and feel better. It’s a hard illness to deal with, especially when you’re battling with other ones, too.
    • barbara

      January 3, 2014 at 4:59 pm - Reply
      Look into the possibility that you guys may have a parasite. Some parasites cause symptoms that are the same as gastroparesis. If your parasite/s is located in the stomach, digestive, there are many parasite cleanses that could work
      for you. US doctors know next to nothing about parasites and many parasites don’t show up in blood or feces. If a lab says you test negative, all clear, it doesn’t mean that you are.
  • Brianna

    April 12, 2014 at 2:48 am - Reply
    Daughter age 8 diagnosed with cyclic vomiting syndrome. She also ha 2 seizures. Age 12 started having migraines and neurocardiogenic syncope (fainting). Age 14 acid reflux. Age 16 fibromyalgia and chronic fatigue. Age 19 grand mal seizures and memory loss. Age 20 mesialtemporal schlorosis. She is in severe pain, vomits, sleeps a lot or not at all, she can’t remember things, and she feels as if she is going to faint and sometimes does on a daily basis. All that we have been told by Drs and the research I have conducted her whole life has stemmed from the vagal nerve. She is in great need of someone to do something to help her!
    • Cort Johnson

      April 19, 2014 at 8:17 pm - Reply
      What a difficult road she’s had. I wonder if a autonomic nervous system specialist would help? Dysautonomia International has a list of them. Good luck!
  • william

    April 19, 2014 at 2:59 pm - Reply
    for every thing ive read how this ties in with multiple sclerosis ,is it posable
  • Sandra

    June 6, 2014 at 6:06 pm - Reply
    Hi Cort – from the UK
    My Husband Dave has just been diagnosed with CFS/ME and whilst researching I came across your article, which is very interesting and make sense when there is so much conflicting information relating to this debilitating condition out there.
    I would like to ask you or anyone out there if you think that been over exposed to diesel fumes -working in the construction industry for nearly 3 years delivering millions of litres without any protection- could have impaired the immune system and lead to this condition ? After working this job for around 4 months Dave developed daily headaches and lived on painkillers, then after around 6 or 7 months he contacted the worse bout of flu ever and still kept on working. after around a year of exposure we went on holiday and he spent most of the 2 weeks in bed weak and wiped out – which we put down to over working – this happened over the next 3 holidays we had ,he also started getting regular and more severe ear, sinus and throat infections- along with dizziness, so since being in that job from 2009 until 2012 here we are 2014 with a diagnosis of CFS/ME- any comments/feedback much appreciated. Thank you
    • Ann

      January 29, 2015 at 4:07 am - Reply
      Sandra In 1978 I was diagnosed with Multiple Chemical Sensitivity. I have tried to avoid chemicals as much as possible.Has helped as well as watching foods. Have been getting physicalm therapy treatments off and on for about 25 years. But still do not feel well. I believe that there is a problem with the Vegas nerve. Check out some of the sites about chemical sensitivity, I don’t feel that I am at the bottom of my problem yet, but some relief is better than none
      • Dawn

        June 8, 2016 at 5:40 pm - Reply
        Sounds like it could be a virus hiding out which gets triggered. There are herbals to kill these viruses such as EBV, strep, and others. Some of them include cat’s claw, lemon balm, licorice root, silver hydrosol, monolaurin, star anise. The book “Medical Medium” by Anthony William (sold on Amazon) outlines the herbs and supplements to recover from the chronic infections often associated with the triggered viruses which hide out in our bodies and vital organs ready to surface at a later time when triggered. Diet is key, as well. It’s working for me, finally. Good luck!
      • Dawn

        June 8, 2016 at 5:40 pm - Reply
        Sounds like it could be a virus hiding out which gets triggered. There are herbals to kill these viruses such as EBV, strep, and others. Some of them include cat’s claw, lemon balm, licorice root, silver hydrosol, monolaurin, star anise. The book “Medical Medium” by Anthony William (sold on Amazon) outlines the herbs and supplements to recover from the chronic infections often associated with the triggered viruses which hide out in our bodies and vital organs ready to surface at a later time. Diet is key to healing, as well. It’s working for me, finally. Good luck!
  • Lisa Griffiths

    June 26, 2014 at 12:43 pm - Reply
    SOOO interesting. I just found this after suffering a really weird reaction post-training session and then having my osteopath saying that she suspected a trapped vagus nerve. I had the eye pain, the head pain and the indescribable but undoubtedly strange feeling that something was very wrong – I actually passed out for an hour on the floor after stretching. Within minutes of being manipulated, the symptoms eased off really quickly.
    In addition, what is your opinion about POTS being related to this? There is an explosion of cases of this syndrome across the Western world, and nobody knows how to treat it. And yet, this hypothesis makes such sense, as the symptom pictures seem extraordinarily similar. I would welcome a further discussion on this. Thanks for the article.
    • Cort Johnson

      June 29, 2014 at 5:28 pm - Reply
      Never heard of a trapped vagus nerve before. That’s fascinating…..
  • Ara

    June 29, 2014 at 6:58 pm - Reply
    For many years Steven Rochlitz Phd has suggested that an irritation to the Vagus nerve caused by an undiagnosed hiatal hernia is what is making many people chronically unwell. He does not agree with the vagus nerve infection theory. You can find the info in his book Hiatal Hernia Syndrome/Vagus Nerve Imbalance
    • Cort Johnson

      July 4, 2014 at 3:51 pm - Reply
      Interesting….I’ll bet both are right. I thought I had a hiatal hernia early on in ME/CFS but the doctors couldn’t find it. I’ll look into the book .
      • Ara

        July 12, 2014 at 7:26 pm - Reply
        Thank you Cort. I spoke with Dr. Rochlitz and he had a chance to clarify some things for me.
        Prof. Steven Rochlitz’ work actually makes clear that (usually hidden) porphyria [it is not a rare disease] is the ultimate cause of vagus nerve imbalance—not just the hiatal hernia syndrome. His book, PORPHYRIA: The Ultimate Cause of Common, Chronic, & Environmental Illnesses cites autopsies on people unknown during their lifetimes to have had porphyria. In some cases, the vagus nerve was even found to be demyelinated.
        After having read Prof. Rochlitz’ books, I’d suggest to you, to check them out or at least the one I just cited. It has many other little known factors, besides porphyria that can cause CFS or M.E. or just go to the testimonials page at his site wellatlast . com and see what many physicians and laypeople said after reading it. Be well.
    • Brahms

      May 27, 2015 at 10:50 pm - Reply
      Strongly agree with this. This is it. My hypothesis is anything that causes inflammation on the vagus nerve will cause CFS. Infection, nearby infection, pinched vagus nerve. How the symptom appear — whether slowly or suddenly — is another clue that can possibly lead to the causes diagnosis.
  • Ruth

    August 27, 2014 at 5:24 am - Reply
    I am relieved to find others who are experiencing, and working on understanding, the same difficulties I am. I have been diagnosed with CFS, Fibro, Sjogren’s, accompanied by IBS and a host of other alphabet soup labels. I am so tired of being exhausted, of having painful attacks involving my heart area that suggest that my next breath will be my last. I am having an attack as I type and have nothing but Clonazepam 0.25 to manage it. I have been to the Emergency Room on numerous occasions believing that I was dying. The last time I arrived with a bp of 113/70. I think the doc wanted to admit me to the Psych ward. I have had a barrage of cardiac studies excluding catheterization. They found nothing. I would need a dictionary to understand all of what you are describing about the research etc. But what I can understand in symptom descriptions says I have found the right place. I plan to watch this conversation intently. Please, if there are any known resources or specialists known in South Central Pennsylvania I would appreciate the input.
    • Cort Johnson

      August 27, 2014 at 8:58 pm - Reply
      Hang in there Ruth and stay engaged. Good luck!
    • Diana

      March 8, 2016 at 6:01 am - Reply
      I had heart pain also, even with a perfect catheterization. I had a cold sore and my dermatologist prescribed a large dose of Valtrex. I improved so much! This is the first web site I’ve found that has come close to explaining why Valtrex made a coronary spasm better. (I went to the E.R. often also. I went from cardiologist to cardiologist. I was put on antidepressants and was even given a book on marriage!) I think there may be something to this theory.
      • Don Sorenson

        March 18, 2016 at 9:56 pm - Reply
        I have a similar story. Multiple trips to the ER, doctors and specialists of all kinds with no benefit for nearly four years, and was getting steadily worse. That is until my sister, who unbeknownst to me, was dealing with a similar problem in her neck and face, was put on Veltrex by her dentist. Which dramatically helped her condition so she suggested that I try either Veltrex or Acyclovir. Sure enough, after literally begging a doctor to give me an Acyclovir prescription it made a huge difference and I’ve been taking it daily now for 10 years.
        Subsequently I’ve found that during an outbreak (this stuff occasionally gets worse, particularly during periods of high stress) combining Benadryl with Acyclovir amplifies Acyclovir’s benefit by a factor of 2 or 3. So you may want to keep that in mind the next time you might have a surge in virus symptoms.
  • Sara

    November 15, 2014 at 6:33 am - Reply
    BIG NEWS! Open Medicine Foundation (OMF) and top experts under the guidance of world-renowned geneticist Ronald W. Davis, PhD are launching a bold new project to unlock the mystery of ME/CFS. See the END ME/CFS Project and the remarkable new END ME/CFS Scientific Advisory Board. http://www.openmedicinefoundation.org/
  • Don

    December 24, 2014 at 1:35 am - Reply
    Just adding a comment that might be useful for individuals that by whatever means have established that their CFS symptoms are due to a herpes infection of the vagus nerve. I’ve struggled for the past 15 years with periodic herpes outbreaks in my left vagus nerve system along with the usual extensive array of uncorrelated and potentially debilitating symptoms all down the interior left side of my body. However, for myself, I have learned how to effectively manage the problem.
    I take a daily dose of acyclovir which I’ve found minimizes the severity and frequency of the virus outbreaks. When an outbreak does begin (they still do occur) I double acyclovir dose to two/day and add one Benadryl (diphenhydramine) tablet to each acyclovir dose. For me the Benadryl reduces the secondary symptoms and appears to significantly enhance the effectiveness of the acyclovir. Base on the research discussed here the antihistamine may be inhibiting the glial cell response to the virus which in turn reduces the vagus nerve illness signaling (strange symptoms) and inflammation adjacent to the nerve cells. The reduced inflammation may then allow easier access to the interior of the cell by the acyclovir improving its effectiveness.
    I’m hoping this might help someone else who is struggling with related problems, I know it can be very difficult to deal with. This combination/technique has definitely worked for me, is easy to follow, and it would seem that this recent research may explain why it has been effective.
    • Diana

      March 8, 2016 at 6:12 am - Reply
      This is similar to the regimen I follow for coronary spasm, esophageal spasm, and gallbladder spasm. I have a strange problem that doctors couldn’t solve. I just happened to take my son to the dermatologist and she noticed a cold sore. She prescribed large dose of valacylovir and it gave me my life back! Now I take a daily regimen and sometimes my body becomes overtaken by the virus and a daily regimen isn’t enough to hold the virus at bay so I take a larger dose again. This seems to happen every few weeks. If I don’t take the medicine my symptoms come back with a vengeance. Angina, gallbladder attacks, esophageal spasms, difficulty swallowing, etc.. This web site is the first I’ve come across that might explain why Valtrex helped me.
  • Rhonda

    January 18, 2015 at 3:13 am - Reply
    Pretty exciting. I think someone’s finally on the right track. It’s the only thing that’s made sense to me. Something that popped out at me above when speaking about Ibudilast, he mentioned it “increasing the breakdown of excitatory neurotransmitter glutamate that may be helping to keep your central nervous system on edge”. Isn’t this like the flavor enhancer Monosodium Glutamate (MSG) found in so many of our foods? I feel so much worse and nerves on edge when I consume it.
  • Lane

    January 21, 2015 at 6:27 pm - Reply
    Is there a Facebook group where this could be discussed in more detail? I would like to follow this research and help others find it, as it’s such a clear explanation and is actually being researched.
  • Mike

    January 22, 2015 at 6:35 am - Reply
    All of this is very interesting. When I got shingles 20 years ago, it was concentrated in the middle of my back. A couple months ago, a blister reappeared at the old Shingles site, and now the spot is numb to the touch. I have a family history of heart disease, Left Branch Bundle Block, and my Left Ventricle Ejection Fraction is in the mid 30’s% (but clean heart arteries); and recently, when the blister reappeared, I started to have shortness of breath. Anybody seen any research or literature that deals with the possibility of a shingles infection of the vagus nerve that could result in or exacerbate heart and breathing issues?
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