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First Direct Evidence of Neuroinflammation - 'Encephalitis' - in ME/CFS

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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 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



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.
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?


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.

'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 12% 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'.

Watch out for a new blog on sickness behaviour, microglia, cytokines and their role in ME/CFS, coming soon.



Phoenix Rising is a registered 501 c.(3) non profit. We support ME/CFS and NEID patients through rigorous reporting, reliable information, effective advocacy and the provision of online services which empower patients and help them to cope with their isolation.

There are many ways you can help Phoenix Rising to continue its work. If you feel able to offer your time and talent, we could really use some more authors, proof-readers, fundraisers, technicians etc. We’d also love to expand our Board of Directors. So, if you think you can help in any way then please contact Mark through the Forums.

And don’t forget: you can always support our efforts at no cost to yourself as you shop online! To find out more, visit Phoenix Rising’s Donate page by clicking the button below.


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Thank you for your reply, I'm asking because inflammation would mean celldeath (right?) and I know it sounds (and looks, I sent you the link to a video) ridiculous but I think mine are recuperating which wouldn't be possible if...well.....dead. The same thing is happening throughout my body but it manifests differently (brain; májor pressure, eyes; trembling, and so on).
 
Simon, excellent survey of the terrain !

I'm cautious about what the Osaka study actually found - as I wrote on another thead:

"The Osaka City University study is promising but even that need not require actual inflamation of the brain, merely that the usual products of inflammation be present and caused by some as yet unexplained disease process. There's also the possibility that this small Japanese study has revealed something specific to a localised gene variant and replication needs to be done in diverse populations to address that, along with the usual prcesses of replication."

Of course one would hope that nature is abiding by Occam's Razor and the simplest explanation of 'evidence of inflamation = inflamation' is the right one, but in the case of ME I don't think that we can be certain without some very weighty numbers. It's become a sort of accepted coda amongst patients that - "the answer is out there" - and if only researchers had been looking in the right place then 'the answer' to ME would have been found years ago. And again of course that would be ideal because good, focussed and sustained research should be certain of getting the answer. But it may not be like that - ME may just be something that is very difficult to get at, something where there is an awful lot of evidence to be found, but where little or none of the evidence quite means what it is expected to mean.
 
Great write up Simon. We seem to have taken as slightly different although complementary slant in reporting this.
...

My own feeling is that future research should be aimed at replicating and expanding our understanding of this as the central mechanism and common end point resulting from a range of potential triggers. I am slightly biased though !:)
Thanks :). And if you are talking about mecfs research on neuroinflammation, I totally agree it should be a priority.

I'd like to know how the findings of this study compare to that of other medical conditions.
Great question

or a gliopathy, as described here?
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.

Marco said:
I'm not sure I'd agree with the conclusion that this represent 'encephalitis' though - certainly not the encephalomyelitis as envisaged by Ramsey as discussed here :
Re encephalitis, I took my cue from Tony Komaroff:
Prof Komaroff said:
"[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."


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.

I wasn't aware that the Dubbo work was continuing which is great news as a predisposition to an enhanced immune response to common infections could be a key component in a 'multi-hit' scenario (conversely this enhanced response could be a symptom of already primed/activated glia - normal aging involves glial priming and the elderly have an often catastrophic enhanced immune reaction to minor stressors). Another possible contributor is SNPs that result in exaggerated microglial activation.

As @Legendrew says, there is a vast range of possible triggers that could lead to glial priming and activation....
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.

As posted on another thread...
got a link for that, would like to follow up?

still working on replies to others, got to go lie down and rest....
 
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As Tony Komaroff said, what's needed is independent confirmation by multiple different labs.

Will this happen within a year or two though? How much importance does the medical community attribute to these findings? Is this a mere curiosity or highly significant?
 
Thanks :). And if you are talking about mecfs research on neuroinflammation, I totally agree it should be a priority.

Yes indeed.

Re encephalitis, I took my cue from Tony Komaroff:

I appreciate that and I agree that its an 'itis' but this type of neuroinflammation is also found in conditions such as post concussion syndrome, complex regional pain syndrome, in normal aging (as previously mentioned) neurodegenerative diseases and in what were considered 'classic' psychiatric disorders such as major depression, bipolar and OCD. It may just be semantics but I doubt few would refer to these conditions as reflecting 'encephalitis' even if neuroinflammation is now recognised as playing a central role.

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

http://www.molecularneurodegeneration.com/content/4/1/47

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

Good idea! :)
 
Yes indeed.
:thumbsup:

I appreciate that and I agree that its an 'itis' but this type of neuroinflammation is also found in conditions such as post concussion syndrome, complex regional pain syndrome, in normal aging (as previously mentioned) neurodegenerative diseases and in what were considered 'classic' psychiatric disorders such as major depression, bipolar and OCD. It may just be semantics but I doubt few would refer to these conditions as reflecting 'encephalitis' even if neuroinflammation is now recognised as playing a central role.
Fair point. Just found Charles Shepherd's quote on this:
the presence of neuroinflammation (which our post-mortem group has already reported in relation to dorsal root ganglionitis – part of the peripheral nervous system) does not necessarily mean that encephalomyelitis is present.
A lot of autoimmune and inflammatory diseases, as well as neurological diseases, have a neuroinflammatory component – but the clinical presentation and pathology is not an encephalomyelitis

Lupus for example: http://www.sciencedirect.com/science/article/pii/S0889159108000342

I continue to take the view that ME/CFS has a neuroinflammatory component

But I still don’t think that ME/CFS is going to turn out to be what neurologists and pathologists would regard as an encephalomyelitis. – i.e. extensive inflammation involving the brain and spinal cord
So to avoid confusion I will stick with neuroinflammation. However, I do think that Ramsay's implicit point, that the symptoms indicated a problem in the brain, may eventually prove right.

Terrific, another highly relevant paper I need to digest. Thanks ;)
 
Well I think it's fairly well known I'm a fan of the autoimmune hypothesis but the interesting thing with this form of neuroinflammation is that there are a plethora of ways to arrive at the same state, as you mention. If this research holds true during replication (and I know that's a very big if!) then we could perhaps be looking at differing sub-groups. It's only logical that if autoimmunity is perpetuating your neuroinflmmation that the treatment would be different than if it was a virus causing it and the same goes for nearly ever different event that could perpetuate it.
I agree with that, but there are other possibilities. Certainly, if you can treat the underlying cause of the chronic inflammation that would be best, but people have suggested tackling the 'downstream' neuroinflammation with microglial inhibitors. I can't remember where I saw that but did find this recent study:
Antiviral drug ganciclovir is a potent inhibitor of microglial proliferation and neuroinflammation

I'm not suggesting this is a treatment for ME/CFS or any other case of neuroinflammation, but it does suggest another route to treatment, even if it wasn't treating the cause.

Another possibility is that the chronic neuroinflammation is chronic because of a problem with the microglia, and not because of any stimulus outside the brain, and again in that case a microglial inhibitor might be appropriate. Though of course, you need your microglia to get active some of the time, that's what they are there for.

Guess we need the 'Big If' of replication sorted first!
 
I'm a little concerned about this bit, do you know if the scans were analyzed blind ?
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.
 
Another great article, Simon.

Small point:

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 typically, 20% 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.
What the study found was:
Prolonged illness characterised by disabling fatigue, musculoskeletal pain, neurocognitive difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronicfatiguesyndrome.
 
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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 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


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.
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?


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.

'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'.

Watch out for a new blog on sickness behaviour, microglia, cytokines and their role in ME/CFS, coming soon.

Simon McGrath tweets on ME/CFS research:






Phoenix Rising is a registered 501 c.(3) non profit. We support ME/CFS and NEID patients through rigorous reporting, reliable information, effective advocacy and the provision of online services which empower patients and help them to cope with their isolation.

There are many ways you can help Phoenix Rising to continue its work. If you feel able to offer your time and talent, we could really use some more authors, proof-readers, fundraisers, technicians etc. We’d also love to expand our Board of Directors. So, if you think you can help in any way then please contact Mark through the Forums.

And don’t forget: you can always support our efforts at no cost to yourself as you shop online! To find out more, visit Phoenix Rising’s Donate page by clicking the button below.



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I'm a little concerned about this bit, do you know if the scans were analyzed blind ?

I'd imagine you would compare the scans of controls and patients alongside one another and it would allow you to clean up a lot of the 'noise', it's far from a perfect way to analyse this kind of data but it lets you see on a qualitative level whether there is any significant difference which is what I believe this study is reporting.
 
I'm a little concerned about this bit, do you know if the scans were analyzed blind ?
Not sure, but they did prespecify which areas they considered:
Image Data Analysis
All 11C-(R)-PK11195 BPND images were normalized to the Montréal
Neurologic Institute space, smoothed with an isotropic 8-mm
gaussian kernel, and analyzed by Statistical Parametric Mapping 5
software (SPM5; Wellcome Department of Cognitive Neurology) using
a categoric design. The between-group comparison (CFS/ME
patients vs. healthy controls) of 11C-(R)-PK11195 BPND and correlation
analysis of 11C-(R)-PK11195 BPND values and clinical scores
were performed on a voxel-by-voxel basis using t statistics with the
statistical threshold set at a P value of less than 0.005 at the voxel level
and a P value of less than 0.05 with a correction for multiple comparisons
at the cluster level for the entire brain (familywise error). The
regions of interest for the cingulate cortex, hippocampus, amygdala,
thalamus, midbrain, and pons were defined from the Wake Forest
University PickAtlas (21) and applied to the smoothed images.
Does this help? there is more like it....

Another great article, Simon.

Small point:[I got the numbers wrong in the blog :bang-head:]
What the study found was:
re Dubbo study: 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronicfatiguesyndrome
Thanks on both counts. I was finishing the blog off yesterday and was having a rough one - I was sure the figure was around 12% but could only find one suggesting 20% so lazily went with that. Blog now corrected.

Thank you for your reply, I'm asking because inflammation would mean celldeath (right?) and I know it sounds (and looks, I sent you the link to a video) ridiculous but I think mine are recuperating which wouldn't be possible if...well.....dead. The same thing is happening throughout my body but it manifests differently (brain; májor pressure, eyes; trembling, and so on).
Activation of the microglia (or astrocytes) themselves does not cause their cell death. Their activation will lead to other changes which may or may not lead to cell death/apoptosis for other cells - I think it would depend on other things too, such as other signalling molecules in the micro environment.
 
its worth looking into memantine as a treatment for inflammation in ME as this drug has been around awhile and can be repurposed, so no having to wait for long trials and studies for its approval, possibly get a doctor now to prescribe it off label.

Memantine has effects on lowering tnf as well as nmda/glutamate, another cause of inflammation. It also helps increase dopamine which is useful for increasing mood and energy, decreasing pain and many other functions. Its also known to increase cortisol in certain parts of the brain which would also enhance energy. The nmda antagonist effects can also improve gaba sensitivity, so maybe help those with that tired wired feeling??

I think its an interesting drug that could be very useful in this reguard??

cheers!!
 
I think the evidence of neuro-inflammation, whether or not you consider that to be encephalitis, goes back to 1955. After the outbreaks in Adelaide, Australia, in the late 1940s they did some research. One line of research injected patient blood into animals. In 1955 it was published that the blood in monkeys resulted in particular kinds of spinal lesions, with immune infiltration. That is, I think not coincidentally, the kind of thing they have found in ME autopsy results.

In inflammation there is growing evidence that brain cells do not so much die as become dormant. So long as inflammation persists they do not function. Remove the inflammation and they have restored function. This is still a new and controversial area though.