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The Brainstem, Vagus Nerve, Neuroinflammation and Chronic Fatigue Syndrome: The VanElzakker Way

In 2013, Michael VanElzakker produced one of the most intriguing hypotheses to date in ME/CFS. His Vagus Nerve Hypothesis proposed that an infection/inflammation near the vagus nerve was causing it to send an unending stream of messages to the brain, telling it to essentially shut the body down by producing fatigue, pain and other symptoms. Since then, he’s been particularly interested in the connection between the vagus nerve, the brainstem and the ME/CFS.

He’s not the only one interested in the brainstem. In 2019 once his brainstem compression was alleviated, Jeff completely recovered from his severe ME/CFS, POTS and MCAS. Since he published his story over a dozen people have been diagnosed with craniocervical instability – a condition which compresses the brainstem.

In this critical review paper, VanElzakker et. al. pick apart some of the research done and provide a guide to successfully getting at the brainstem and other regions of the brain. It’s called a “Critical Review” and is critical, indeed. It finds many past ME/CFS studies wanting, but then points a way to a better possible future. If brainstem problems play a role in ME/CFS these researchers demonstrate how to get at them.

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

Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods.  Michael B. VanElzakker, Sydney A. Brumfield and Paula S. Lara Mejia. Front. Neurol., 10 January 2019 https://doi.org/10.3389/fneur.2018.01033 https://www.frontiersin.org/articles/10.3389/fneur.2018.01033/full

First, VanElzakker et. al. examines one of the sacred cows in the chronic fatigue syndrome (ME/CFS) community – the preferred term for so many: myalgic encephalomyelitis (ME), which refers to muscle pain (myalgia) related to central nervous system inflammation (encephalomyelitis).

While muscle pain is common, it’s not universal. Even people with severe ME may not report pain.

Still, the core part of the definition deals with central nervous system inflammation – a description that, with the emergence of the 2015 Yakatomi and the 2019 Younger studies, seems more and more likely to stick. (A 2018 PET scan study also found neuroinflammation in fibromyalgia as well.)

The idea that inflammation plays a key role in this illness makes sense, given the infectious trigger so commonly (but not universally) found. The authors are just a few among many (Avindra Nath, Jarred Younger, Andrew Lloyd and others) who believe that an infectious event has triggered changes in the brain that are producing fatigue, pain and other problems in ME/CFS.

They point to three ways an infectious trigger could produce central nervous system inflammation in ME/CFS:

A) immune factors (e.g. cytokines) triggered by the infection could get transported across the blood-brain barrier (BBB) that protects the brain. The normally taut blood–brain barrier makes blood-borne infections of the brain rare, but it can, like the gut, become leaky in inflammatory states, allowing immune factors and pathogens entry. Once in the central nervous system, they could trigger a large inflammatory response, or

B) High concentrations of immune factors could allow pathogens to passively diffuse across the BBB, or

C) Immune factors in the blood could trigger the vagus nerve to send signals to the brainstem and brain, which then sparks an inflammatory response.

It’s the last option that primarily concerns these authors. VanElzakker is the author of the Vagus Nerve Hypothesis, which proposes that an infection/inflammation near the vagus nerve is causing it to send an unrelenting stream of signals to the brain, telling it to produce the flu-like symptoms that constitute “sickness behavior” (withdrawal to bed), which isolates infected people from the community and keeps them from spreading an infection.

The largest nerve in the body, the vagus nerve transmits sensory, autonomic, immune and other signals to the brainstem – making it potentially a key player in a possible neuroinflammatory disease like ME/CFS.

Studies indicate that inflammation in the periphery tends to produce a mirror inflammatory response from the immune cells (the glia) in the brain. Even small levels of cytokines in the periphery or body have the potential to activate the chemoreceptors in the vagus nerve, which then activate the immune system in the brain.

That brain activation, interestingly, tends to occur in regions (basal ganglia, limbic system organs (amygdala, hippocampus and hypothalamus), anterior cingulate cortex, prefrontal cortex, and thalamus), which studies suggest are also involved in ME/CFS.

The Brainstem

brainstem

The brainstem regulates many vital functions in the body

The authors believe the brainstem (which, as it name implies, is found at the very base of the brain, above the termination of the spinal cord), could play a key role in chronic fatigue syndrome (ME/CFS) for four reasons:

  1. Immune signals from the vagus nerve to the brain travel through the brainstem.
  2. The brainstem is dense with mast cells, and mast cell activation syndrome (MCAS) appears to be common in ME/CFS.
  3. The brainstem regulates autonomic nervous system functioning – a common trouble area for ME/CFS and related disorders.
  4. The brainstem also regulates immune functioning; in particular, it triggers an anti-inflammatory response that should limit the inflammatory response.

Whether caused by a structural problem (as in Jeff’s case), inflammation or an infection, the brainstem is a centrally placed brain component that produces many of the issues in ME/CFS.

Could Craniocervical Instability Be Causing ME/CFS, Fibromyalgia & POTS? Pt I – The Brainstem Series

Seeing the Brainstem in Chronic Fatigue Syndrome (ME/CFS)

Consistent inflammation of the brainstem has not, however, been found in ME/CFS. The authors argue, though, that researchers have rarely used the right kind of imaging needed to investigate this.

The most commonly used method for measuring inflammation in the brain involves measuring the 18kD translocator protein (TSPO) with a PET scan. This protein is produced when the immune cells of the brain – the microglia – become activated. Because the microglia are the chief producers of inflammation in the brain, the TSPO provides a reliable way to indirectly measure neuroinflammation and its effects.

The Nakatomi Study

Nakotomi’s small ME/CFS study using TSPO made a big splash in 2014.   Tony Komaroff called the finding of central nervous system inflammation the most important study in decades. Five years later, Van Elzakker et. al. called it “important” and potentially “groundbreaking”. The study used TSPO imaging to find widespread neuroinflammation, particularly in the areas leading from the brainstem to the thalamus.

While the authors regard Nakatomi’s study as potentially groundbreaking, the study is not without significant issues. The authors, in fact, seemed a bit shocked that Nakatomi found as many effects as he did, given the techniques used.

The neuroimaging techniques Nakatomi used (and which most researchers use) were not designed to address brainstem inflammation. Nakatomi used a spatial “registration” technique that aligns the image on the neocortex or upper part of the brain. This kind of alignment is typically done because researchers tend to focus on the upper, “higher” functioning areas of the brain. It can, however, impair the sensitivity of imaging done on the lower, more densely packed, primitive areas of the brain, such as the brainstem, and lead to false negatives.

The PK-1195 tracer

Nakatomi also used an older tracer (PK-11195) which does not penetrate deeply into the brain and can bind to unintended elements in the brain. Differences in blood-brain barrier permeability between the ME/CFS patients and healthy controls – a distinct possibility – could have confounded the results, as well. Nakatomi’s use of the cerebellum as a kind of baseline measure could have introduced further issues if problems with the cerebellum (another possibility) exist in ME/CFS.

Plus, the hypometabolism believed present in ME/CFS could have resulted in lower amounts of the tracer being metabolized than usual – causing higher amounts of the tracer to reach the brain – and producing a false positive. Because exercise may affect how much of the tracer is taken up into the cells, Nakatomi’s use of healthy, non-sedentary controls instead of sedentary controls introduced another issue.

Finally, because the brainstem actually pulses with every heartbeat, that movement needs to be accounted for – and usually isn’t in ME/CFS studies.  The very small but important nuclei in the brainstem are also often not picked up with the standard imaging techniques used in ME/CFS research.

Nakatomi’s study results make sense given what we know, and were given a sort of validation by Jarred Younger’s recent results using thermal mapping – a new technology – but we need more validation.

The takeaway is that the brainstem – because of the role it plays in autonomic nervous system functioning, immune regulation and the transmission of motor signals – could play a major role in ME/CFS, but is essentially, according to these authors, still something of a black box.

Barnden’s Brainstem – the Australian Study

It’s not completely a black box, though. Researchers using other techniques have found evidence of brainstem problems in ME/CFS. Barndem in Australia, in particular, has done a series of MRI studies which have found striking brainstem issues in ME/CFS.

(During his talk at the 2019 Emerge conference, Barnden noted how he had to shift his MRI to avoid the alignment problem (that VanElzakker mentioned) which prevented him from getting a good image of the brainstem. )

One study found that reduced brainstem grey matter volume – suggesting that damage to the neurons in the brainstem had occurred – was correlated with autonomic nervous system problems in ME/CFS.

Barnden brainstem damage ME_CFS

Using the right imaging approach Barnden found extensive evidence of damage to the neurons (myelin) in the brainstem. (From the 2019 Emerge Conference Livestream)

Another study finding of impaired communication from the brainstem nuclei to other nuclei in the brain suggested the same, and found increased signs of myelination in the sensorimotor cortex of the brain.  Barnden proposed that decreased signaling from a damaged brainstem provoked a compensatory increase in myelination in the sensorimotor region as it bulked up to try to understand the limited signaling coming from the brainstem. The impaired brainstem-sensorimotor connection might be, Barnden thought, impacting motor functioning in ME; i.e. the ability to carry out physical activity.

Signals to move muscles pass from the motor cortex to the sensorimotor cortex down to the thalamus and then through the brainstem to the muscles. (Signals from the muscles to the brain pass up through the same pathways.) Barnden proposed that the movement problems in ME/CFS could start with the brainstem’s inability to properly relay signals to the motor cortex to activate the muscles.

Barnden’s most recent brainstem study validated the idea that inadequate communication between the brainstem nuclei and other nuclei in the brain, including the vasomotor region, hypothalamus and prefrontal cortex, was affecting autonomic nervous system functioning in ME/CFS.

Other Kinds of Brain Scans

Other kinds of brain scans, such as magnetic resonance spectroscopy (MRS), can pick up signs of neuroinflammation. Although almost 10 MRS studies of the brain in ME/CFS have been done, VanElzakker et. al. report that a clear and consistent picture of metabolite alterations in the brain has yet to emerge.

They believe that’s due largely to a common theme in medical research, found in this disease in particular – lack of standardization. Different diagnostic criteria, different types of healthy controls, different brain regions examined, and different metabolites targeted make it difficult to present a clear picture of the metabolic alterations in the brains of people with ME/CFS.

The Japanese Take

The Japanese probably couldn’t agree with Barnden more. Their studies indicate that, as the healthy controls became more fatigued, two core regions – both of which communicate with the brainstem ( the prefrontal cortex and the anterior cingulate cortex) – shut down.

As these regions begin to shut down, control of autonomic functioning becomes lost.  In particular, the ability to activate the parasympathetic nervous system (i.e. the vagus nerve) and tone down the sympathetic nervous system activity, is lost.

The Japanese believe a breakdown in what they call the facilitation system in the brain has occurred.  As we become fatigued, the facilitation system jumps in to increase the signals coming from the primary motor cortex to the muscles. This increased “drive” from the motor cortex prompts the muscles to work harder and activates more and more of them so that activity can proceed.

Fatigue – the Japanese Way: A Chronic Fatigue Syndrome Perspective

So long as new, fresh muscle fibers remain to be recruited, the activity can continue.  If no muscle fibers are left to be recruited or if the brain has a problem recruiting new muscle fibers, fatigue sets in.

A 2003 study suggested that reduced muscle recruitment due to reduced motor cortex output was indeed occurring in ME/CFS. That study suggested that, “… changing motor deficits in CFS has a neurophysiological basis [which] … supports the notion of a deficit in motor preparatory areas of the brain”.  That study titled, “Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome“, to my knowledge was never followed up on.

Fatigue Explained? Japanese Assert Brain Damage Causes Fatigue in Chronic Fatigue Syndrome

Conclusion

Several studies suggest significant brainstem issues may be present in ME/CFS. Problems with the brainstem could produce everything from autonomic nervous system problems to immune issues to problems with movement.

The authors critique past brain imaging studies and provide a “how to” guide to assess the brainstem in ME/CFS. Barnden’s Australian brainstem studies suggest that when done correctly, MRI imaging studies may indeed find extensive damage is present in ME/CFS including evidence of brainstem neuron demyelination, a compensatory remyelination in parts of the brain the brainstem connects with, and lastly, a reduced connectivity between these regions.

VanELzakker et. al.  assert that future imaging studies that focus on the specific functional connectivity pathways in the brain which are activated by inflammatory processes should be able to capture the neuroinflammatory processes occurring in ME/CFS.  (Two of the three pathways they cite include the brainstem.) The thalamus’s role in sensory stimuli activity presents another fruitful pathway to assess.  Lastly, the authors suggest that researchers target the nucleus of the solitary tract (NTS) where the vagus nerve enters the brainstem.

With help from an ME/CFS donor, VanElzakker has been employing brain imagining techniques to assess the brainstem in chronic fatigue syndrome (ME/CFS). He will be speaking at the NIH ME/CFS Conference in Baltimore in April.

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

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33 Comments

  • Heidi

    March 19, 2019 at 4:44 pm - Reply

    If a virus damages the vagus nerve, which in turn causes the symptoms found in mecfs, how would a virus enter and hide within it? And why would the virus be able to damage the vagus nerve in some people but not all? The question always comes back to the outbreaks. They all got sick, but only a fewsome did not recover. The hep c study helped open up this idea, but is there a damaged gene connected to the vagus nerve which allows the virus to hide?

  • Jane

    March 19, 2019 at 5:32 pm - Reply

    In 1993 i had brain surgery, 7 hours, where they had to separate my vertebral artery from my brain stem with a piece of muscle to stop an hemifacial spasm. From that point in 1993 I developed me/CFS/fms. Could it be connected?

  • Lora

    March 19, 2019 at 5:59 pm - Reply

    Excellent work and good article..thank you!

  • Anita

    March 19, 2019 at 6:07 pm - Reply

    I think the vagus nerve is involved in my illness. I awoke from sinus surgery with a partially paralyzed diaphragm; the connection between vagus nerve and diaphragm function is well known. My breathing difficulties progressed to pneumonia, but the diaphragm did not return to almost-normal functioning for more than 9 months. I believe this complex triggered what was eventually diagnosed as ME/CFS.

  • inge jarl clausen

    March 19, 2019 at 6:13 pm - Reply

    UNSAFE HURTS
    The organism reacts to a stressful situation with inflammation. This is like a first defense wall being produced to quickly counter possible infection and injury. In vegetative training, people are activating self-regulation processes centrally, to bring about a certain change of state of consciousness, which is accompanied by a change in the autonomic nervous system. And this change now works backward, bringing you into a top-down, bottom-up loop, as described above. In the concrete example of inflammation, the parasympathetic system activated by vegetative training can now exert its anti-inflammatory effect. This explains why, for example, the clients report that this “method” accelerates their healing processes during exertion and injury.
    By releasing/transforming experiences saturated as disturbances in human physiological adaptation systems, (vegetative system) the organism starts, partly through epigenetic mechanisms a deep structural transformation and a rebuilding of brain and body.

    The method is an incredibly powerful way of putting the homeostasis/allostasis (performance characteristic) of an organism in movement, to support an in-depth
    transformation of its dynamic. One session about 45 min. Every session will gradually improve all functions of the organism. Expanding our level of biological vitality.

    Improvement starts centrally in the organism and partly through epigenetic mechanisms spread peripherally to all other biochemical, physiological, somatic, emotional and cognitive processes.

    https://vegetativetraining.wordpress.com/building-a-new-organism/Good vibes from Bayern

  • Linda

    March 19, 2019 at 7:52 pm - Reply

    This got my attention because in the past 3-4 years I have noticed changes in things controlled by the brain stem, mixed signals if you will. One of them, swallowing, seems to be getting worse fairly quickly. Swallowing any food that has the ability to tickle the throat, e.g. rice, seems to cause a fairly violent sneezing fit, which then goes into coughing. Things sometimes get stuck in my throat and swallowing in general is harder. There are other signals that get mixed up. Sometimes I don’t know if I’m about to vomit or just sneeze. I don’t know until it actually happens, so I hang out near the bathroom in case it’s the former. Also, I have had problems switching out of sympathetic mode for a very long time. This article really makes me think they’re on to something. What is the best way to get tested for this brain stem problem?

  • Cort Johnson

    March 19, 2019 at 10:11 pm - Reply

    My guess – and some evidence backs this up – that there may be a genetic predisposition for he immune system to over-respond to a pathogen. That could initiate a neuroinflammatory process which could, in turn, creak open the blood-brain barrier, allowing more cytokines and immune cells entry into the brain and increase the inflammation there.

  • Cort Johnson

    March 19, 2019 at 10:14 pm - Reply

    Certainly with Jeff’s story we’ve seen evidence that structural problems that compress the brainstem can cause all the symptoms of ME/CFS. Given the close connection between that surgery and the onset of your symptoms one has to wonder if something in this apparently quite touchy area might have gone wrong.

  • Cort Johnson

    March 19, 2019 at 10:16 pm - Reply

    Interesting! It seems that there are many pathways to ME/CFS indeed.

  • Cort Johnson

    March 19, 2019 at 10:21 pm - Reply

    Maybe Michael can chime in but it seems that we’re in, unfortunately, a rather familiar situation here. Because most of the brain scans are focused on the upper, more recently developed regions of the brain, they’re not very accurate with regards to the lower, more primitive parts of the brain such as the brainstem. Much of the review paper was on how not to do a scan of the brainstem! Note that when Barnden adjusted his scan so that it was properly aligned o n the brainstem all sorts of problems showed up.

    The problem, then, would be getting the right kind of brainscan done. VanElzakker will be speaking at the NIH conference in April. Hopefully we will learn more about his brainstem scans there and that will boost interest in doing brainscans focused properly on how to scan the brainstem.

  • Cort Johnson

    March 19, 2019 at 10:24 pm - Reply

    Barnden found problems with signaling between the brainstem and other parts of the brain. That sure sounds like it could be one explanation for what you’re experiencing.

  • Joyce

    March 19, 2019 at 11:14 pm - Reply

    https://www.rockefeller.edu/news/21415-mutation-explains-people-vulnerable-viral-brain-infection/

    Heidi, This article may answer your question. Rockefeller University’s study published in Feb 2018 showed that 1 in 10,000 have a genetic mutation in the DRB1 gene causing them to have no immune system in their brain stem. They found that when EBV, HSV1 et al get into the brain stem of these people, they cause serious illness.

  • Joyce

    March 20, 2019 at 2:04 am - Reply

    https://www.cell.com/cell/fulltext/S0092-8674(18)30163-6

    This is the full article. My comment above had a typo — the gene is DBR1. Fewer than 1 in 10,000 have ME/CFS, but not everyone with that gene mutation is unlucky enough to get an HSV1 or influenza virus that moves near enough to get into the brain stem. This would tie together the research implicating viruses, the immune system, cytokines, the vagus nerve, and the brain stem. The next research would need to be how to repair the DBR1 mutation, or how to get into the brain stem with something to suppress the virus.

  • Al

    March 20, 2019 at 3:14 am - Reply

    Dr. Raj Patel has some ideas on inflammation & the Vagus nerve here :

    medicaloptionsforwellness.net/index.php/condition/mi/mold-treatment

  • ManShadow

    March 20, 2019 at 4:03 am - Reply

    I’ve had a very long onset of CFS, somewhere around 15-20 years. My handwriting has gone bad (even after spending 4-6 weeks training it daily) and when I drink, I no longer swallow automatically – it requires conscious effort. Have also had problems with involuntary limb/head movements and muscle spasms. None of these cause any huge problems with daily living, but we’re troubling to observe as they evolved.

  • ginger bartlett

    March 21, 2019 at 3:09 am - Reply

    Head injury from either surgery, accident/sports/blunt force trauma events sounds like one of the main factors in the vegus nerve disruption compression . Prior to a car accident in which I got thrown into the windscreen and knocked out then came to it , in shock (with no breakages involved other than the usual glass abrasions to the face) . From that point onwards my emotional and mental state had changed. I had gone from an extremely laid back, confident, thick skinned cruisy type of person with tons of energy and power to a mumbling mess with multiple aiments and symptoms that required medical attention. approx. 3 years later I suffer an episode of paralysis after being vaccinated ( which I reacted badly to ) then 3 years after that episode I suffered another health collapse that left me struck down with CFS for the past 30 odd years. I believe the head trauma has triggered this condition, but could never find the evidence to support it.

    • Cort Johnson

      March 22, 2019 at 3:51 am - Reply

      Sure sounds like it. If you haven’t be sure to check out Jeff’s CCI/AAI story. Health Rising will have some more blogs on structural problems in the neck/head which can contribute to or even cause ME/CFS/FM.

  • 6String

    March 21, 2019 at 6:05 pm - Reply

    Hi Cort – In the link above to the 2013 article “One Theory to Explain Them All – The Vagus Nerve Infection Hypothesis for CFS – http://simmaronresearch.com/2013/12/one-theory-explain-vagus-nerve-infection-chronic-fatigue-syndrome/ – it says – “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.” Are you aware of any updates on Ibudilast? As a kid I had 4 major head injuries (one diving and hitting my head on the bottom of a shallow pool – jamming my head downward onto my neck) and have always wondered if any of those could have affected my Vagus nerve. Thanks

  • Scott Henderson

    March 21, 2019 at 8:33 pm - Reply

    I know of one person who was fairly early in their illness get drug treatment for an infected Vagus nerve. He improved greatly. Does any one else have stories like this?

  • Steve Hawkins

    March 21, 2019 at 9:49 pm - Reply

    Sickness behaviour is not ‘withdrawal to bed’, and this causes a huge amount of misunderstanding between the psych pseudohypothesists and patients. The term refers to *the body’s* adaptive responses to infection and other damaging processes that require ‘downtime’ for ‘maintenance and repair’. The high temperature of a fever, is the sickness behaviour that may wipe out certain bacteria that have only a narrow temperature range for optimum development, for example. The confusion arises because this behaviour that’s going on inside us, makes us feel tired, and may drive us to bed, but going to bed is not medical ‘sickness behaviour’.

    Some psych professionals like to take advantage of this confusion, and try to make out that our ‘behaviour of going to bed when we shouldn’t’ is what’s actually making us ill: hence CBT/GET–which is the last thing you need when your real internal, involuntary, bodily sickness behaviour requires that you rest your body so that maximum resources can go into repairing it.

    Please correct this, rather misleading, and certainly confusing to anyone new to the subject, misconception. it rather spoils the piece for me, as I don’t know if there are similar mistakes that I don’t have the experience to recognise.

    https://en.m.wikipedia.org/wiki/Sickness_behavior.

    Incidentally: I traced most of my symptoms and signs to the vagus and hypothalamus, quite soon after becoming ill more than 35y ago. I am still regarded as a nutcase just for knowing these words, even now, though it is very obvious when even the vibration from a guitar over my solar plexus (another name that proves you’re a nutter), sets off signs like bloating, sweating, and shortness of breath, as does bending over, or anything that increases pressure below the end of the breastbone, and, hence, compresses the diaphragm and vagus nerve junctions of the solar plexus.

    As it happens, I am seeing a neurologist again next week, but I would be a fool to even mention there is such a thing as a vagus nerve. If they can’t test it with a hammer or feather: it doesn’t exist. 🙁

    • Cort Johnson

      March 22, 2019 at 3:40 am - Reply

      Actually high temperature is not a sickness behavior – it’s a biological response. The same Wikipedia article you provide a link to states

      “Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection.[1] They usually (but not necessarily)[2] accompany fever and aid survival. Such illness responses include lethargy, depression, anxiety, malaise, loss of appetite,[3][4] sleepiness,[5] hyperalgesia,[6] reduction in grooming[1][7] and failure to concentrate.[8] Sickness behavior is a motivational state that reorganizes the organism’s priorities to cope with infectious pathogens”

      Here’s from the man – Dantzer who coined it in 2001.

      https://www.ncbi.nlm.nih.gov/pubmed/12000023

      Sickness behavior refers to a coordinated set of behavioral changes that develop in sick individuals during the course of an infection. At the molecular level, these changes are due to the brain effects of proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha). Peripherally released cytokines act on the brain via a fast transmission pathway involving primary afferent nerves innervating the bodily site of inflammation and a slow transmission pathway involving cytokines originating from the choroid plexus and circumventricular organs and diffusing into the brain parenchyma by volume transmission.

      At the behavioral level, sickness behavior appears to be the expression of a central motivational state that reorganizes the organism priorities to cope with infectious pathogens.

      I know the term irks but it is a medically recognized term that refers to the symptoms and the accompanying behavioral adaptations produced by the brain in response to infection. There’s really no other term to use.

  • Linda Keesee

    March 22, 2019 at 1:20 am - Reply

    In the space of about two years, I was in a car wreck and suffered a TBI to left temporal lobe; had an emergency appendectomy; contracted West Nile virus; and had Bell’s Palsy on the left side of my face. Within a year, I became very ill, and eventually was diagnosed with FM. My health has steadily gone down hill. Does anyone think that any of the above ailments could have been triggers?

    • Cort Johnson

      March 22, 2019 at 3:35 am - Reply

      Jeez – I would say just about all of them! I don’t know about TBI but the emergency appendectomy, West Nile Virus and Bell’s Palsy – all involve pathogens and could have triggered an immune response which resulted in ME/CFS/FM.

  • Aidan

    March 22, 2019 at 10:41 am - Reply

    I just asked on the (HATS) Hereditary Alpha Tryptasemia Syndrome Group on Facebook who have multiple copies of the tryptase gene Positives if anyone on there also have a diagnosis of hemochromatosis one Guy just mentioned he is a carrier of the illness his Mom is Positive to Genetic testing of hemochromatosis they both are also positive to (HATS) combined…It could explain food issues & it also could explain is some who have the Alpha-Gal Meat Allergy reactions if their Iron genetics are off…You can order the kit from genebygene.com they send it to your home with a Doctor referral request & also your credit card details to send the sample back you are not charged for the kit until it reaches the lab in Houston, Texas http://www.tryptasegenebygene.com no money up front is needed now…Cort Johnson, I tagged you on Facebook on a UK article of a Man in the UK diagnosed 6 years with ME/CFS he now has been diagnosed with hemochromatosis his Doctors missed the alert from the lab, I would not be surprised he also has (HATS) combined…Also, a lot of people now I am seeing have Eagle Syndrome, do they have (HATS) & hemochromatosis combined it could be as well he now goes for weekly blood draws one pint of blood taking out. Do not rely on the simple blood test for iron or ferritin look for the Genetic test instead the mouth DNA swab test is only £180.00 2 to 4 weeks results the blood test done at medichecks here in the UK is £199.00 5 days result

  • TK

    March 24, 2019 at 4:41 pm - Reply

    It’s disheartening to see none of these studies ever get replicated by independent teams.The 2014 study by Nakatomi et. al. for instance was preliminary with only 9 patients. Nobody followed up with larger study. Yet, the same team recently published another small study correlating the symptoms with inflamed regions. It’s as if people are indulging in theories without doing the real science when it comes to CFS. If it was the “most important study in decades”, why didn’t Komaroff or someone do the follow up replication study? Inquiring mind wants to know..

    • Cort Johnson

      March 25, 2019 at 9:13 pm - Reply

      I have no idea why four years later that study has still not been replicated in the U.S.. It’s incredible….If anything was an indication of the need for more funding that is…

  • Lauren Gordon

    March 26, 2019 at 10:25 am - Reply

    So, if brainstem damage is looking like a potential cause of ME/CFS, is there any information on how to heal brainstem damage?

  • Jan

    March 26, 2019 at 10:59 am - Reply

    @Scott Henderson
    Can you find out the symptoms of the affected person? Sensory Overload?
    And what was the name of the drug/therapy?

  • Nan

    March 28, 2019 at 12:48 am - Reply

    My condition of CFIDS and MCS improved utilizing techniques, based in neuroplasticity theories, that focus on the limbic part of the brain — especially an impaired amygdala. One can learn more about this by going to http://www.guptaprogram.com and reading Ashok Gupta’s hypothesis on why CFIDS, FM, MCS and other serious chronic disorders persist and do not improve until one approaches it from a neurological standpoint by focusing on the amygdala’s role in these disorders.

  • Nancy

    April 2, 2019 at 3:20 pm - Reply

    As most know, there is more than one cause for ME/CFS. Some with this syndrome develop Fibromyalgia and Multiple Chemical Sensitivity. These are all interrelated due to the relationship of the limbic part of the brain playing a key role in keeping these syndromes ongoing. My condition of CFIDS and MCS improved utilizing techniques, based in neuroplasticity theories, that focus on the limbic part of the brain — especially an impaired amygdala. One can learn more about this by going to http://www.guptaprogram.com and reading Ashok Gupta’s hypothesis on why CFIDS, FM, MCS and other serious chronic disorders persist and do not improve until one approaches it from a neurological standpoint by focusing on the amygdala’s role in these disorders.