≡ Menu

First Direct Evidence of Neuroinflammation – ‘Encephalitis’ – in ME/CFS

Simon McGrath reports on the new study that indicates low-grade encephalitis in ME/CFS …

A small study with just nine patients has captured the attention of patients and researchers alike after reporting direct evidence of inflammation in the brain of ME/CFS patients. The finding was one of the highlights picked out by Professor Anthony Komaroff in his IACFS/ME conference round up.

Neuroinflammation may lead to ME/CFS symptoms.  credit: Canstock

Neuroinflammation may be behind ME/CFS symptoms
Photo credit: Canstock, www.canstock.com

Back to the future

What makes this study so fascinating is that it provides tantalising evidence supporting not only of current views that inflammation in the brain is central to understanding the disease, but also of Melvin Ramsay’s original name of ‘myalgic encephalomyelitis‘.

Encephalomyelitis is inflammation of the brain and spinal column, and critics of the name pointed to the lack of direct evidence for inflammation of either. This study only looked at the brain, not the spinal column (so could only find encephalitis), but the immune cells found to be activated in the brain are also present in the spinal column.

The study

Yasuyoshi Watanabe

Dr. Yasuyoshi Watanabe

To see if there is immune activation in the brain, researchers need to look inside the brain — which is not so easy if you want patients to still be alive when your study is done.

The scientists in this study, led by Dr. Yasuyoshi Watanabe from the RIKEN institute in Japan, used PET & MRI imaging to peer into the brain.

What make this study work is the use of tiny quantities of a radioactive tracer that binds to specific proteins that appear on activated  microglia (the main immune cells of the brain) but crucially doesn’t bind to non-activated microglia. The marker also binds to activated astrocytes, which play an immune role in the brain. The brains of nine ME/CFS patients meeting both Fukuda and International Consensus Criteria were compared with those of 10 healthy controls.

The results showed that neuroinflammation markers were higher for patients than controls across many brain areas including the thalamus, the pons and the midbrain. They also found that the severity of symptoms correlated with the degree of inflammation in multiple brain regions, particularly for cognitive functioning.

It was the correlation between a biological finding — neuroinflammation — and clinical problems that Komaroff found so exciting about this work, because it suggests a biologically plausible explanation for the symptoms of ME/CFS:

“[If replicated] it would, for me, say that there is a low-grade, chronic encephalitis in these patients, that the image we clinicians have of encephalitis as an acute and often dramatic clinical presentation that can even be fatal has — may have — blinded us to the possibility that there may be that long-lasting — many years long — cyclic chronic neuroinflammation is underlying the symptoms of this illness.”

Representative PET scans showing activated microglia in a CFS/ME patient. AMY, amygdala; CC, cingulate cortex; HIP, hippocampus; MID, midbrain; THA, thalamus; and PON: pons. Credit: Image courtesy of RIKEN

Representative PET scans showing activated microglia in a CFS/ME patient.
Key to brain regions: AMY, amygdala; CC, cingulate cortex; HIP, hippocampus; MID, midbrain; THA, thalamus; and PON: pons.
Photo credit: Image courtesy of RIKEN

Intriguingly, the midbrain, thalamus and amygdala — all regions where cognitive problems correlate with neuroinflammation — are also all part of neural circuits involved in awareness, arousal and attention. Concentration problems are typical of ME/CFS, and one of the problems found most consistently in laboratory testing.

Harvard Professor Tony Komaroff on these PET findings, and their potential importance

Starts at 30′ 10″, Q&A re encephalomyelitis @ 37′.

Replication needed

While tantalising, these findings are far from conclusive, as the authors acknowledge. The study has only nine patients, albeit diagnosed with ICC criteria. The tracer used to identify activated immune cells produces a very ‘noisy’ signal, giving rather indistinct readings, and the overall level of neuroinflammation was relatively low.

Although cognitive issues correlated with neuroinflammation in several areas, generally other symptoms, including fatigue, did not significantly correlate with inflammation.

There was almost no sign of inflammation in the prefrontal cortex, the region of the brain most involved in higher cognitive functions, that might be expected to be a problem in ME/CFS. And there was a potential technical weakness in the way the study was run.

Commenting on the neuroinflammation, Komaroff emphasised the need for replication:

“If it were confirmed by multiple other investigators … these data are consistent with [encephalitis], but I would feel more strongly if other labs using same technology came up with the same result.”

The good news is that the authors of this study are already working on a new study using the same patients but with a newer and more sensitive tracer to pick up neuroinflammation. They will address the earlier technical issue, and to make the study more powerful they will also be looking at neurotransmitter activity in the brain, following up their previous findings of neurotransmitter abnormalities.

Hopefully independent groups will try to replicate this finding too – and in the U.K., Dr. Charles Shepherd of the ME Association has already said it would welcome applications to fund a replication attempt.

Microglia — key to ME/CFS?

microgliawikimedia

Microglial cells (green).
Photo credit: Gary Shaw, Wikimedia, CC 3.0 licence

So neuroinflammation — specifically activation of microglia — correlates with cognitive problems, but how might microglial activation cause the problem?

The most plausible answer is through what is termed ‘sickness behaviour’ — a characteristic set of responses to infection, including fatigue, malaise joint and muscle pain and problems concentrating — which might just sound familiar to ME/CFS sufferers. (‘Sickness behaviour’ is a lousy name for biological phenomenon, as Dr. Dan Peterson has noted).

Microglia are known to play a key role in regulating sickness behaviour, and that’s a big reason this study has attracted so much attention in ME/CFS.

sick

‘Sickness Behaviour’ is driven by biology: infection leads to a rise in pro-inflammatory cytokines in the blood, triggering activation of brain microglia and their production of cytokines. This triggers sickness behaviour.

The fatigue, malaise, problems concentrating, etc., of sickness behaviour help us survive an infection by forcing us to rest so our body can devote all its resources to the energy-greedy immune system.

However, sickness behaviour is normally a short-lived response to an acute infection, designed to temporarily divert resources to ensure a swift recovery. If that doesn’t happen, e.g., if there is a chronic infection, or the process goes wrong, for instance, if microglia remain activated after an infection has been cleared, then sickness behaviour can itself be a problem. ME/CFS may be an example of this.

Cytokines in the spotlight

Cytokines are a key trigger for sickness behaviour, and researchers have often found elevated cytokines in patients, but the findings have been inconsistent and in small studies. The new studies reported on by Dr. Jose Montoya at the Stanford conference and Dr. Mady Hornig at the IACFS/ME conference are helping to firm up these findings in huge cohorts.

Probably the most important piece of work on the role of sickness behaviour — and cytokines — in ME/CFS came from the landmark “Dubbo” studies.

The researchers found that about 11% of those with glandular fever and two other infections developed CFS after six months. And crucially, what predicted the length of the illness (and chance of developing CFS) wasn’t psychological factors, but the severity of the initial ‘acute illness’, or sickness behaviour.

The researchers also showed that those with more active genes for the pro-inflammatory cytokine Interferon-gamma had a more severe sickness behaviour (and longer illness) than those with regular versions, linking cytokine response to sickness behaviour and ME/CFS.

The Dubbo study did not look at inflammation in the brain, but the authors did speculate that the cause of CFS could be long-term activation of microglia and astrocytes. And that is exactly what was found in this new PET imaging study.

As with all research findings, replication is essential, and a new version of the Dubbo study is currently under way in Sydney, Australia.

The new imaging study from Japan has found provisional evidence of activated astrocytes and microglia cells (both types of glial cell) in the brain of ME/CFS patients. This is support for the suggestion from the Dubbo team that ME/CFS develops from certain infections as a result of activation of brain microglia.

Dr. Michael VanElzakker’s recent vagus nerve infection hypothesis also features glial cells heavily. And recently Professor Hugh Perry, who has studied microglial cells in neurodegenerative diseases such as Parkinson’s disease, proposed that primed microglia and sickness behaviour lie at the heart of ME/CFS.

Neuroinflammation and Sickness Behaviour the final common path in ME/CFS?

It may prove to be that ‘neuroinflammation’ — i.e., activated microglia in the brain/spinal column — is a common endpoint of numerous triggers, including glandular fever (EBV), other infections, vaccines — or even, as Dr. Lipkin has proposed, disturbances in the microbiome.

Discovering if this is the case — and firming up the finding of neuroinflammation is key — could be a big step forward in understanding and then treating ME/CFS. And those it is still very early days, it is possible this approach could eventually show that Dr Ramsay was right about ‘encephalomyeltitis’.

See the next blog on sickness behaviour, microglia, cytokines and their role in ME/CFS.

Simon McGrath tweets on ME/CFS research:

 

'I was completely lost and in the dark before I found this website. I can never express what this place means to me.' Phoenix Rising forum member

{ 133 comments… add one }

  • November Girl May 9, 2014, 6:35 pm

    Many, many things including lots of time. Some of them, in no particular order –
    REST
    Omega 3, at least 3,000 a day – don't remember if that is iu or mg

    I'm exhausted at the moment – will come back later when thinking better

  • Leopardtail June 13, 2014, 2:33 am

    I think its very important her to pay close attention to the conclusions of the study. It states that immune activation could be causing the SYMPTOMS of the disease. That is very far from stating that an Etiology of enduring cause has been found. For example and underfuctioning immune system could case relentless low level infection and permanent activation, as could poor mito function.
    This confirms what we already know – immunity is problematic and that the name ME is as good as any…

  • osisposis June 15, 2014, 9:26 pm

    Acta Neuropathol. 2014 Apr;127(4):459-75. doi: 10.1007/s00401-014-1261-7. Epub 2014 Feb 20.
    Olfactory bulb involvement in neurodegenerative diseases.
    Attems J1, Walker L, Jellinger KA.
    Author information
    Abstract

    [
    Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases, particularly of Parkinson's disease and other synucleinopathies, Alzheimer's disease (AD), and mild cognitive impairment heralding its progression to dementia. The neuropathologic changes of olfactory dysfunction in neurodegenerative diseases may involve the olfactory epithelium, olfactory bulb/tract, primary olfactory cortices, and their secondary targets. Olfactory dysfunction is related to deposition of pathological proteins, α-synuclein, hyperphosphorylated tau protein, and neurofilament protein in these areas, featured by neurofibrillary tangles, Lewy bodies and neurites inducing a complex cascade of molecular processes including oxidative damage, neuroinflammation, and cytosolic disruption of cellular processes leading to cell death. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with severe anosmia. Recent studies of olfactory dysfunction have focused its potential as an early biomarker for the diagnosis of neurodegenerative disorders and their disease progression. Here, we summarize the current knowledge on neuropathological and pathophysiological changes of the olfactory system in the most frequent neurodegenerative diseases, in particular AD and synucleinopathies. We also present neuropathological findings in the olfactory bulb and tract in a large autopsy cohort (n = 536, 57.8 % female, mean age 81.3 years). The severity of olfactory bulb HPτ, Aβ, and αSyn pathology correlated and increased significantly (P < 0.001) with increasing neuritic Braak stages, Thal Aβ phases, and cerebral Lewy body pathology, respectively. Hence, further studies are warranted to investigate the potential role of olfactory biopsies (possibly restricted to the olfactory epithelium) in the diagnostic process of neurodegenerative diseases in particular in clinical drug trials to identify subjects showing early, preclinical stages of neurodegeneration and to stratify clinically impaired cohorts according to the underlying cerebral neuropathology.

    /QUOTE]

    http://www.ncbi.nlm.nih.gov/pubmed/24554308

    J Clin Invest. 2014 Mar 3;124(3):1228-41. doi: 10.1172/JCI71544. Epub 2014 Feb 24.
    Immune cell trafficking from the brain maintains CNS immune tolerance.

    http://www.ncbi.nlm.nih.gov/pubmed/24569378

    Front Neurosci. 2014 Apr 29;8:92. eCollection 2014.
    Neurogenic and non-neurogenic functions of endogenous neural stem cells.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010760/

    J Neurosci Res. 2012 Sep;90(9):1693-700. doi: 10.1002/jnr.23054. Epub 2012 Jun 5.
    Olfactory dysfunctions in neurodegenerative disorders.
    Ruan Y1, Zheng XY, Zhang HL, Zhu W, Zhu J.

    http://www.ncbi.nlm.nih.gov/pubmed/22674288

  • osisposis June 15, 2014, 9:28 pm
  • osisposis June 15, 2014, 9:30 pm

    Biofilms in Chronic Rhinosinusitis February 2014
    1
    TITLE
    :
    Biofilms in Chronic Rhinosinusitis
    SOURCE: Grand Rounds Presentation,
    The University of Texas Medical Branch in Galveston, Department of Otolaryngology
    DATE: February 19, 2014
    RESIDENT PHYSICIAN:
    Angelia Natili, MD
    ATTENDING PHYSICIAN
    AND DISCUSSANT
    :
    Bruce Leipzig, MD
    SERIES EDITOR: Francis B. Quinn, Jr., MD, FACS
    ARCHIVIST: Melinda Stoner Quinn, MSICS
    http://www.utmb.edu/otoref/Grnds/2014-02-19-biofilm-sinus-Natali/biofilm-2014-02.pdf

  • osisposis June 15, 2014, 9:37 pm

    Clin Exp Allergy. 2014 Jan;44(1):121-9. doi: 10.1111/cea.12225.
    High prevalence of anaphylaxis in patients with systemic mastocytosis – a single-centre experience.

    http://www.ncbi.nlm.nih.gov/pubmed/24164252

    Int Arch Allergy Immunol. 2012;157(4):399-405. doi: 10.1159/000329218. Epub 2011 Nov 25.
    Severe life-threatening or disabling anaphylaxis in patients with systemic mastocytosis: a single-center experience.

    http://www.ncbi.nlm.nih.gov/pubmed/22123213

  • Izola June 16, 2014, 10:51 pm
    Simon

    Thanks. Yes, as Tony Komaroff pointed out, encephalitis is normally an acute, dramatic and sometimes fatal condition – whereas these results point to a much lower level of inflammation which simply hasn't been considered by many.

    That is the big question (and I thought you might suggest autoimmunity :)). One possibility is that there is an ongoing stimulus, such as a chronic infection – or autoimmunity. Another possibility is that something has gone wrong with regulation of microglia and astrocytes, so that they become 'stuck' in an activated position, so that the neuroinflammation continues long after the original stimulus has been cleared – the 'hit and run' scenario. The Dubbo group propose this possibility, and it is the severity of the initial illness that somehow sets of excessively prolonged activation of microglia in the brain.

    My illness started out with a serious encephalitis so pronounced that through the thicket of the encephalitis I knew immediately, well, within a short time, what it was. I couldn't speak properly so I faked it. Several of my daughter's neurologists (she had a serious childhood illness) sat and conversed with me for long periods. I think they were trying to figure it out. I never told them I was ill. Newly divorced, I didn't want to lose custody to her party guy dad. Yes, he was a lot of fun until responsibility set in and he couldn't handle it. My own doctors ignored the ongoing encephalitis. Boy, do I ever have some skeery stories about being mentally impaired and hiding it. Still am impaired. Don't like it. This new research is exciting! I wish I could still understand the new research, but my head has holes! Iz

  • Leopardtail June 17, 2014, 1:10 am
    osisposis

    Acta Neuropathol. 2014 Apr;127(4):459-75. doi: 10.1007/s00401-014-1261-7. Epub 2014 Feb 20.
    Olfactory bulb involvement in neurodegenerative diseases.
    Attems J1, Walker L, Jellinger KA.
    Author information
    Abstract

    are those papers all ME related?

  • osisposis June 17, 2014, 2:24 am

    I think they could, it might depend on how you got to this point. I got ill from WDB/water damaged building/home exposure, my sinuses/brain route was very involved and I know my olfactory system is damaged, I'm guessing beyond self repair. sorry, not up to much writing at this time. new here but been around long time, been researching about 8+ years.

  • osisposis June 17, 2014, 2:31 am
    Leopardtail

    are those papers all ME related?

    sorry again, that was meant as reply to you.

  • AbbyDear June 19, 2014, 12:13 am

    @osisposis i pretty sure i got olfactory damage also.

  • Aerose91 June 19, 2014, 2:11 am
    Izola

    Boy, do I ever have some skeery stories about being mentally impaired and hiding it.

    I sympathize with you completely on this. Nothing harder than fighting the hardest battle a human can possibly fight while trying to keep normal daily activities appear unaffected. I don't know which is worse, the torture of feeling yourself slip into psychosis and having no power to help it, or having that happen at the same time you're around people that think you're lying anyway and trying to hold a dinner conversation.

  • alex3619 June 19, 2014, 4:24 am
    Aerose91

    I sympathize with you completely on this. Nothing harder than fighting the hardest battle a human can possibly fight while trying to keep normal daily activities appear unaffected. I don't know which is worse, the torture of feeling yourself slip into psychosis and having no power to help it, or having that happen at the same time you're around people that think you're lying anyway and trying to hold a dinner conversation.

    You might like to read my blog: http://forums.phoenixrising.me/index.php?entries/masks.680/

    Its not only that we feel driven to pretend to be normal. Its that we can operate on learned responses, even speech. Ask me how I am and unless I have lost enough cognitive function that either I cannot understand you or cannot speak any more, then I can give a reply. Its just not a considered reply unless my brain is operating at an OK level.

    An amusing side note is that some people think I am too far gone to notice what they say. They forget I get short periods of OK brain capacity … and then I rethink what they said. Presuming I can even remember it of course.;)

  • alex3619 June 19, 2014, 4:28 am

    Biofilms are getting more and more attention. A biofilm in one spot could lead to heart attack or stroke. In another it could lead to neurological damage. One cause, different locations, different consequences.

    Biofilms in the vasculature of the brain, for example, could constantly trigger a brain inflammatory response. Say, that sounds like something …

  • osisposis June 20, 2014, 4:55 pm

    Gulf War Illness: New Report Lauds Treatment Research, Confirms Toxic Causes
    http://www.bu.edu/sph/2014/04/28/gu…uds-treatment-research-confirms-toxic-causes/

  • osisposis June 25, 2014, 7:09 pm

    Trigeminal nerve stimulation triggers oral mast cell activation and vascular
    permeability

    http://www.annallergy.org/article/S1081-1206(13)00784-9/pdf

    http://www.ncbi.nlm.nih.gov/pubmed/24331392

  • SDSue June 25, 2014, 8:37 pm
    taniaaust1

    Its similar to POTS in which you know you get that urge that you NEED to go and lay down (or you know something bad will occur) but with the brain thing instead its the urge that you know you need to stop doing something which is making you think too much and rest the brain (highly uncomfortable).

    I definitely feel increased brain inflammation when I read or think too much. The POTS analogy is accurate. Stopping the activity at hand isn't an option; it's mandatory. Even then, once over that line it can take hours or days to recover from the buzzing, increase fog, and pain.

    I know that my brain is inflamed – I feel it, I hear it, and I live with it daily.

    Aerose91

    He did state, however, that brain inflammation is a much different monster than inflammation in the body and described trying to stop it as akin to "trying to stop a speeding train without any brakes" He said that no matter what the initial offender, once microgliol activation reaches a certain level it can go on for the rest of your life unless direct action is taken.

    Did he say what that direct action might be? A "friend" wants to know.;)

  • MeSci June 26, 2014, 8:01 am
    osisposis

    Trigeminal nerve stimulation triggers oral mast cell activation and vascular
    permeability

    http://www.annallergy.org/article/S1081-1206(13)00784-9/pdf

    http://www.ncbi.nlm.nih.gov/pubmed/24331392

    in rats.

  • Aerose91 June 26, 2014, 6:37 pm
    SDSue

    Did he say what that direct action might be? A "friend" wants to know.;)

    His opinion was anti-psychotic medication and steroids. Needless to say I moved on to another doctor

  • SDSue June 26, 2014, 6:47 pm

    @Aerose91 How silly of me to get a wee bit hopeful. After all, you did say "psychiatrist". 😆

  • osisposis June 26, 2014, 9:43 pm
    MeSci

    in rats.

    Trigeminal nerve stimulation actives dura mast cells and increases vascular permeability

    Int J Immunopathol Pharmacol. 2013 Jul-Sep;26(3):597-600.
    Impact of capsaicin on mast cell inflammation.
    Frydas S1, Varvara G, Murmura G, Saggini A, Caraffa A, Antinolfi P, Tete' S, Tripodi D, Conti F, Cianchetti E, Toniato E, Rosati M, Speranza L, Pantalone A, Saggini R, Di Tommaso LM, Theoharides TC, Conti P, Pandolfi F.
    Author information
    Abstract

    Mast cells are inflammatory cells, and they are prominent in inflammatory diseases such as allergy and asthma. Mast cells possess high-affinity receptors for IgE (FcERI) and the cross-linking of these receptors is essential to trigger the secretion of granules containing arachidonic acid metabolism (such as prostaglandin (PG) D2, leukotriene (LT) B4, and LTC4), histamine, cytokines, chemokines, and proteases, including mast cell-specific chymases and tryptases. Activation of mast cells provokes the secretion of cytokines and mediators that are responsible for the pathologic reaction of immediate hypersensitivity. Sensory nerve stimulation by irritants and other inflammatory mediators provokes the release of neuropeptides, causing an increase in vascular permeability, plasma extravasation and edema. Trigeminal nerve stimulation actives dura mast cells and increases vascular permeability, effects inhibited by capsaicin. Capsaicin causes release of sensory neuropeptide, catecholamines and vasodilation. Several studies have reported that capsaicin is effective in relief and prevention of migraine headaches, improves digestion, helps to prevent heart disease, and lowers blood cholesterol and blood pressure levels. The findings reported in these studies may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders.

    http://www.ncbi.nlm.nih.gov/pubmed/24067456

  • osisposis June 26, 2014, 10:01 pm
    AbbyDear

    @osisposis i pretty sure i got olfactory damage also.

    sorry to hear that AbbyDear.

  • Leopardtail June 29, 2014, 10:29 pm
    Simon

    Good question. If it is sickness behaviour then it would be the same basic idea of activated microglia (and astrocytes). Whether the level of neuroinflammation/activation would be the same, I don't know.

    As for fever, that turns out to be a separate pathway from sickness behaviour – though again fever is a host response, not something caused by the pathogen: turns out we can generally take the heat better than bugs. One amazing thing I learned on an immunology course I did recently is that reptiles – who are cold-blooded so can't control their body temp – will move to a hotter area if they are sick, say 40 degC, same as a mammalian fever. And experiments have shown moving to the higher temp improves their survival rates.

    Half true?

    Simon, do you mean sickness behaviour as in promoting rest, or sickness behaviour as in immune response here?

    The fever response (according to my understanding) tends to kick in after several days of infection and failure of the immune system to deal with the problem. As you indicate microbes are more temperature sensitive than our cells and the immune response uses fever to weaken them. It is because it may indicate a more severe infection that medics are concerned by it.

    The info re reptilian response to infection was in interesting tit bit, may I ask where you picked that up?

    Leo

  • Leopardtail June 29, 2014, 10:31 pm
    Simon

    Thanks :). And if you are talking about mecfs research on neuroinflammation, I totally agree it should be a priority.

    Great question

    I think for all of this, the first step needed is replication by the original authors using their improved design, which I understand has already started or will soon do so. Then other Qs come into play, including how it compares with other chronic illnesses and with acute infection. As Tony Komaroff said, what's needed is independent confirmation by multiple different labs. I wouldn't normally blog on such a small study, but as the findings tie in with so many other theories, and as an improved version of the study is already planned, I think this study deserves more attention.

    Re encephalitis, I took my cue from Tony Komaroff:

    As for encephalomyelitis, the microglial and astrocytes that showed up as activated in the brain PET scan are also present in the spinal column, so it's plausible they too are activated – that would need a different PET scan to investigate. Again, this would be low-grade which as I understand it is not what is normally meant by encephalomyelitis. There again, my understanding was that Ramsay used encephalomyelitis because he thought that would explain the clinical symptoms he found (he didn't have direct evidence).

    If the neuroinflammation evidence checks out Ramsay may have been on exactly the right lines – that's the only point I'm trying to make. I wouldn't want to push it too far, esp as this is a study on only 9 patients and didn't even look at the spinal column.

    We must talk before I write my next blog! Hugh Perry's hypothesis is about microglial priming, so that people have an exaggerated immune response.

    got a link for that, would like to follow up?

    still working on replies to others, got to go lie down and rest….

    More importantly how this compares with depression in order to put the psychiatric dogma to sleep permanently..

  • MeSci June 30, 2014, 3:32 pm
    Leopardtail

    The fever response (according to my understanding) tends to kick in after several days of infection and failure of the immune system to deal with the problem.

    My own understanding is that fever is actually one of the early responses to infection – part of the innate immune system.

    This page appears to support this, e.g. this bit:

    Innate immunity also comes in a protein chemical form, called innate humoral immunity. Examples include the body's complement system and substances called interferon and interleukin-1 (which causes fever).

    If an antigen gets past these barriers, it is attacked and destroyed by other parts of the immune system.

  • Leopardtail June 30, 2014, 8:39 pm
    MeSci

    My own understanding is that fever is actually one of the early responses to infection – part of the innate immune system.

    This page appears to support this, e.g. this bit:

    The page is slightly misleading (re fever at least). In so far as we are born with innate immunity it obviously comes first in two respects. Aspects of it also kick in a little quicker than the th1 system. What's described as innate immunity includes most b-cell activity, natural killer cells etc as well as fever.
    Fever actually commences after NK cells, T-cells etc and is primarily an endocrine response to infection. We don't fever ever time we get a cold due to it being the bodies 'emergency response'.

    It was the length of time about which I had my doubts.

  • osisposis July 9, 2014, 5:40 pm

    Neuroinflammation and Comorbidity of Pain and Depression

    http://pharmrev.aspetjournals.org/content/66/1/80.abstract

  • Aerose91 July 31, 2014, 5:28 pm
    alex3619

    You might like to read my blog: http://forums.phoenixrising.me/index.php?entries/masks.680/

    Its not only that we feel driven to pretend to be normal. Its that we can operate on learned responses, even speech. Ask me how I am and unless I have lost enough cognitive function that either I cannot understand you or cannot speak any more, then I can give a reply. Its just not a considered reply unless my brain is operating at an OK level.

    An amusing side note is that some people think I am too far gone to notice what they say. They forget I get short periods of OK brain capacity … and then I rethink what they said. Presuming I can even remember it of course.;)

    "Learned responses" that's a great way to put it. I have been saying I operate solely on logic. I would feel horrible for a child that has to go through this because they haven't had a chance to learn the correct behaviors and responses to things.

    I never get periods of OK brain function though. Never fluctuates, ever, not even 1%

  • alex3619 July 31, 2014, 7:49 pm
    Aerose91

    "Learned responses" that's a great way to put it. I have been saying I operate solely on logic. I would feel horrible for a child that has to go through this because they haven't had a chance to learn the correct behaviors and responses to things.

    I never get periods of OK brain function though. Never fluctuates, ever, not even 1%

    By OK brain capacity I mean times when I can think at 30% or more of normal capacity, rather than times when I am at 1%.

  • helperofearth123 August 18, 2014, 5:15 pm
    beaverfury
    searcher

    Dr Younger listed potential microglial inhibitors that he thinks may be worth investigating at the Stanford and IACFS/ME conferences. Other than naltrexone I don't think most have been studied in fibromyalgia or ME but I think several are very promising. For example, I know many people are using minocycline for its neuroprotective qualities. The list is split into prescription drugs and supplements (primarily from chinese medicine.)
    The full list is at http://forums.phoenixrising.me/inde…-me-21-march-day-two.29098/page-3#post-443598

    I'm doing great on minocycline. Don't want to jinx it, but i've had a significant increase in activity, no PEM (so far), clearer head, no pain, no POTs-like symptoms.
    Some of the improvement maybe could be attributed to buhner herbs i am also taking, but i noticed the shift to lack of PEM and lack of POTs-like symptoms particularly after taking minocycline.
    I have been on other lyme Abx for a year, and am now into my third week on mino.

    It stuffs up sleep, but i'm managing that with some add-ons.

    Fingers crossed this bout of better health continues. One often looks like a dickhead when touting a cure after a couple of weeks of remission, but it's clear i have improved since minocycline.

    Fantastic beaverfury, I'm glad to hear you're improving. :)

  • funkyqueen March 12, 2016, 11:06 am

    Nobody know if this study will be replicated ??

  • *GG* March 31, 2016, 5:09 pm

    Is the article available as a PDF?

  • Hasz December 24, 2017, 5:56 am

    This is a study that describes how I felt at worst and during every relapse. My most recent one pretty bad and I described it to a doctor saying: it feels upon waking up as if my brain was full of some sort of yellow pus which has to get out but wont. It makes my head soinning at first and then impacts the most basic funtions from sleeping, eating and peeing to standing speaking, holding anything in my hands. It is all tragic that makes me laugh at times how bad can it be this time? I seem to develop more and more symptoms with most recent addition tightness round my throat and problems swallowing as well as getting food into my stomach it all seem to go up involuntary (yes some muscles freak up and soasm while some other seem to stop working). Basically my brain seems to be so inflammed that it stop to function and so my body shuts down. All due to another silly docile virus my kid brought home. Any help for temporary flare ups in brain inflammation? Which btw was not recognised by basic blood tests CRP was very low but I had low grade fever. Merry Xmas everyone.