What if ME is simply brain damage after encephalitis?

[aaron_c]

@Woolie I'm curious what your take is on both Erikson's and Elzaker's theories?

 

[silky]

I'm a neuropsychologist/cognitive neuroscientist.

That's great! Thankful you're here and willing to give so freely of your time and expertise

And thanks for taking the time to read through those links

I have no doubt that CFS will change your brain. But then going for a jog or having a good nap will also change your brain. Most studies, if they're measuring real effects at all, are measuring effects, not causes.

Do you think the brain changes imply a permanent damage or something that can go back to normal?

Simple is good. Complex usually means there's something in the explanation that isn't doing much explanatory work, something we need to let go of.

Yes I agree, which is what lead me to my original train of thought given the brain's centrality as the governing organ. What do you think of Byron Hyde's definition of ME which requires an acquired injury to the CNS?

So, to answer the original question, I think parts of the disease are a result of initial CNS damage

You seem to know a lot! What noticible effects do you think the CNS damage has?

 

[Woolie]

@aaron_c, when you get outside of the central nervous system (CNS), you're outside my area of expertise. But FWIW, I'm sceptical of the van Elzakker idea. The vagus nerve hypothesis seems to have evolved from central sensitization theories of pain, which are based on the idea that chronic pain is a phenomenon generated entirely by the CNS. This kind of account suffers from the same problem as psychological accounts - its an argument from ignorance. "If there are no peripheral markers of the pain, then it MUST be in the central nervous system". (substitute mind for CNS, and you have the classic psychological explanation for MECFS).

The complexity of the account is also a huge red flag. This means the theorist had to invoke all kinds of mechanisms to explain the full picture, because none of them on their own "fitted". But if an explanation doesn't fit, we should drop it and look for something else, not pile an extra mechanism on top to deal with its inadequacies.

I suspect the ultimate explanation for MECFS is going to be much simpler. And that there are many things to detect perhipherally, we just need to work out what to look for.

EDIT: I also think its huge that MECFS can develop as a consequence of a large number of very different kinds of infection. Any explanation that rests on just one virus has a lot of explaining to do.

But I'll leave it to those with the right expertise to comment further.

I don't know the other guy - can you provide a link?

 

[Woolie]

That's great! Thankful you're here and willing to give so freely of your time and expertise

I'm just like you. Stuck in bed right now with nothing better to do (not enough cognitive ability right now to do any real science). There are lots of us here at PR that either had scientific careers before our illness or who still maintain them somehow, despite the illness (that's me right now, although I'm not sure how long I can keep it up). Others, like @Tom Kindlon, got sick long before they could train in anything, so have self trained. His level of accomplishment is nothing short of amazing.

Do you think the brain changes imply a permanent damage or something that can go back to normal?

The second one.

Yes I agree, which is what lead me to my original train of thought. What do you think of Byron Hyde's definition of ME which requires an acquired injury to the CNS?

I didn't have one, did you? If we are supposed to believe we all had injuries we're not aware of, then that's starting to look like a dodgy and unfalisifiable explanation to me.

 

[Hip]

The idea that ME/CFS is due to some "hit and run" damage in the brain resulting from an acute viral infection has been around a long time, and is an interesting idea.

However, one argument against this hit and run theory is the fact that improvements and remissions from ME/CFS that can be obtained from virus- or immune-targeted treatments such as interferon, oxymatrine, low-dose naltrexone, IVIG, Valcyte or Valtrex, and of course autoimmune-targeted therapies like rituximab. If ME/CFS were mainly due brain damage, you would not expect antiviral treatments or autoimmune therapies to help.

Although I take your point and suggestion that infections, inflammation and autoimmunity may be involved in addition to the brain damage, and that the therapies help by addressing the infection, inflammation or autoimmunity side, but not the brain damage side of the illness.



In fact my own ME/CFS appeared not that long after an unpleasant episode of viral meningitis and/or encephalitis (I am not sure which, you can also have both together as meningoencephalitis). During this brain infection, it felt as if someone was going through my brain and surgically cauterizing or removing various connections and functional areas, as immediately after the episode (which only seemed to last an hour), several aspects of my personality and mental faculties were irrevocably altered or destroyed. So there seemed to be definite and permanent brain damage from this brain infection, and in fact I have never been the same person since.

Some of my lost faculties restored themselves within a few months (for example, I lost the ability to recognize faces after my brain infection, except for very familiar faces like my immediate family; but fortunately this faculty slowly returned after some months).

However, my ME/CFS did not appear in its full aspect until around at least a year after this brain infection. So in my case there was no clear connection between my brain infection and the onset of my ME/CFS, although I guess the brain damage it caused may have played a role in my gradual onset into ME/CFS.

Or another possibility is that my acute meningitis/encephalitis resulted in the virus initially entering the brain (and causing some damage), and then once in the brain, this virus over the coming months slowly infected more areas of the brain, leading to ME/CFS. Enteroviruses can produce fierce acute infections like my initial brain infection; but they can also cause slow, low level, chronic smoldering infections that linger in the tissues indefinitely (non-cytolytic infections).

One study on those who suffered an episode of viral meningitis found there was a higher prevalence (12.6%) of ME/CFS after meningitis compared to the prevalence in the general population (0.2%). So it does seem like a viral infection in or around the brain can be a risk factor for developing ME/CFS (although one has to be careful with such studies, because viral and bacterial meningitis was found to cause pituitary dysfunction leading to growth hormone deficiency in 29% of cases, and growth hormone deficiency can closely mimic the symptoms of ME/CFS; so you may think you developed ME/CFS after meningitis, but in fact it may be growth hormone deficiency, which is treatable).



In general though, meningitis and encephalitis do not seem to be common precursors to ME/CFS, and this also tends to argue against the hit and run brain damage theory as a major cause of ME/CFS: because if the hit and run theory were generally true, then you might expect that most ME/CFS patients would report a meningitis or encephalitis brain infection prior to the first appearance of their illness, which they don't. I've only come across one or two other ME/CFS patients on this forum who experienced meningitis or encephalitis.

 

[silky]

I didn't have one, did you? If we are supposed to believe we all had injuries we're not aware of, then that's starting to look like a dodgy and unfalisifiable explanation to me.

I don't know! Too scared to get a SPECT scan but my MRI seemed ok.

Why do you think so many ME SPECT studies show hypofusion to the brain stem, which in my understanding isn't in other conditions like depression?

Also I have one other study to throw at you, forgive me

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1562448/

The author writes:

"The loss of grey matter in the brain, especially in Brodmann's area 9, was related to physical impairment, but not to the duration of the symptoms. Although other explanations were considered as well, this may indicate the occurrence of a major trauma to the brain at the start of the disease. This could also explain the low recovery rate in adults, because repair in adult brain is limited [4]."

I'm just like you. Stuck in bed right now with nothing better to do (not enough cognitive ability right now to do any real science). There are lots of us here at PR that either had scientific careers before our illness or who still maintain them somehow, despite the illness (that's me right now, although I'm not sure how long I can keep it up).

Ah shoot! Well I'm impressed you are still working even though I'm sure it's very very hard

However, my ME/CFS did not appear in its full aspect until around at least a year after this brain infection. So in my case there was no clear connection between my brain infection and the onset of my ME/CFS, although I guess the brain damage it caused may have played a role in my gradual onset into ME/CFS.

Hip! I have read many many of your posts, and I'm embarrassingly excited you have answered my thread

What were your ME symptoms like?

How has your cognition and personality changed?

And do you think if you got the right antiviral or immunemodulator your neurological symptoms might improve?

 

[aaron_c]

I don't know the other guy - can you provide a link?

This thread discusses a paper of his.

 

[Woolie]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1562448/

The author writes:

"The loss of grey matter in the brain, especially in Brodmann's area 9, was related to physical impairment, but not to the duration of the symptoms. Although other explanations were considered as well, this may indicate the occurrence of a major trauma to the brain at the start of the disease. This could also explain the low recovery rate in adults, because repair in adult brain is limited [4]."

Link to the abstract of the articles cited in relation to this claim are here and here.

The first study (Okada et al) is the one that finds loss of grey matter in BA9 (Brodmann's area 9). They claim the BA9 abnormalities are the source of the fatigue problem in CFS. That's a pretty wild claim that is not based on anything we know about what BA9 actually does.

But the usual problem - the finding is not replicable. The second study mentioned (de Lange et al) fails to find any reliable evidence of localised grey matter atrophy, but does report a general reduction in grey matter. A recent study by Okada et al, which someone posted on PR recently, found white matter (tiny, tiny changes) but no grey matter changes at all.

Its all over the place.

Interestingly, the de Lange et al study put a behavioural spin on their results, claiming they reflect mere deconditioning (even though they did not bother to test any deconditioned non-CFS controls). They claim this on the basis that the grey matter loss correlated negatively with physical activity levels. Which of course is a total mess, because the more severe the CFS, the less activity you're likely to do. One of the authors on de Lange et al is a well known proponent of the psychological view of CFS, so that's what's going on there.

Just goes to show, you can use brain data to serve your interests whatever they are. If we want to refute psychobabble, we will need to look elsewhere.

 

[Woolie]

PS. Some people in the field are saying now that the methods we use to detect volume loss in white matter or grey matter, or even qualitative changes in these, might actually be picking up on really, really temporary things, such as changes in blood perfusion (the flow of blood through the brain tissues). This would certainly explain why these measurements are so all over the place, and are so vulnerable to really short-term interventions - even one bout of exercise!

 

[silky]

Thanks for the take @Woolie

Isn't it strange that all these studies are finding something wrong in the brain even if it's different? Or are these differences possibly the result of random variance in any population?

 

[silky]

Some people in the field are saying now that the methods we use to detect volume loss in white matter or grey matter, or even qualitative changes in these, might actually be picking up on really, really temporary things, such as changes in blood perfusion (the flow of blood through the brain tissues).

That is a comforting thought

Why do you think so many ME SPECT studies show hypofusion to the brain stem, which in my understanding isn't in other conditions like depression?

 

[Woolie]

Isn't it strange that all these studies are finding something wrong in the brain even if it's different?

They would never get published if they didn't find some difference.

Fortunately, with methods like VBM, which is used in these studies, there are hundreds of thousands of opportunities to find something, so pretty much no-one goes home empty handed. If you selected a group of people with an entirely pretend condition, and compared them to "controls", you would probably find something.

Your warning sign that the findings are not real is that they're not replicable.

Now, have I totally destroyed your faith in science? That tends to happen when you spend too much time looking into CFS. So much BS out there.

 

[Woolie]

Why do you think so many ME SPECT studies show hypofusion to the brain stem, which in my understanding isn't in other conditions like depression?

Not sure, but blood perfusion is a function of activity levels, so you would need an equally deconditioned control group first.

 

[silky]

Now, have I totally destroyed your faith in science? That tends to happen when you spend too much time looking into CFS. So much BS out there.

Haha yes, all faith gone

Not sure, but blood perfusion is a function of activity levels, so you would need an equally deconditioned control group first.

Setting aside evidence or reproducibility, in your mind is there any conceptual validity to Hyde's theory of microvascular viral injury / immunological cuffing cutting off blood flow to select parts of the brain?

 

[Woolie]

Setting aside evidence or reproducibility, in your mind is there any conceptual validity to Hyde's theory of microvascular viral injury / immunological cuffing cutting off blood flow to select parts of the brain?

Yeeeh, and I haven't responded to @aaron_c yet either about the Erikson theory (thanks for that link, aaron_c).

Okay, warnings apply here - once you leave the CNS, then I'm just a normal person with no particular expertise.

But the idea that peripheral factors, like immunological ones, could affect blood flow to different parts of the brain, sounds perfectly plausible to me. Once you start thinking of the brain as a body part - and a very greedy one at that - then it seems completely logical that any systemic illness will massively affect brain function.

One thing that's really reliable and super replicable in CFS are the neuropsychological deficits. All these fall into the general category of abilities that rely on efficient blood perfusion. They are things like working memory tasks, which we succeed in only if we can recruit the right resources - people who do well in such tasks exhibit preparatory changes in their blood pressure and heart rate variability, and these changes are predictive of good performance. It seems logical then, that an illness that affected one's ability to recruit the right resources would disproportionately affect performance on these tasks.

Dr Hyde sounds pretty out there to me, but this part of his claims seems plausible.

 

[silky]

Once you start thinking of the brain as a body part - and a very greedy one at that - then it seems completely logical that any systemic illness will massively affect brain function.

Ah! So then might lack of blood flow cause long term damage? Or could something like vinpocetine or hyperbaric oxygen revive "sleeping" neurons?

 

[halcyon]

You seem to know a lot! What noticible effects do you think the CNS damage has?

One example would be vestibular issues. A number of people report onset of vestibulitis with ME onset, I am one of them. My balance has never returned to normal and probably never will.

 

[Woolie]

Ah! So then might lack of blood flow cause long term damage? Or could something like vinpocetine or hyperbaric oxygen revive "sleeping" neurons?

I think if that were the case, after 27 years, I wouldn't stlll be in a job. And there would be no patient-researchers.

In all seriousness, though, there's quite a variable range of blood perfusion within normal. You don't get brain damage from falling asleep, do you? Even though blood perfusion to most regions drops massively.

I have never heard of "sleeping" neurons. They're either active or they're not. If you have a stroke, they're dead, but you can't wake them up again, alas.

 

[kangaSue]

Am I right in thinking that all types of encephalitis are autoimmune based?

If so, autoimmune encephalitis syndromes may occur in the presence of cancer (paraneoplastic) or absence of cancer, as in, paraneoplastic encephalitis syndromes are autoimmune, and autoimmune encephalitis may be paraneoplastic but autoimmune encephalitis refers specifically to syndromes that are associated with antibodies to neuronal cell surface/synaptic proteins so the obvious answer to rule it out would be in doing an antibody panel such as the Mayo PAVAL or ENS1 panel would it not?
http://www.mayomedicallaboratories.com/test-catalog/Overview/83380
http://www.mayomedicallaboratories.com/test-catalog/Overview/48401

 

[silky]

One example would be vestibular issues. A number of people report onset of vestibulitis with ME onset, I am one of them. My balance has never returned to normal and probably never will.

I'm sorry to hear that but I hope it's not true. Maybe future stem cell treatment or artificial brain cells can restore it. I don't have vestibulitis but I do have POTS, do you think that's in the same category?

I now think my condition maybe linked to Th-17

Why do you think Th-17?

That's what Mady Hornig said too. Do you ever think about trying to get Consentyx?

I have never heard of "sleeping" neurons. They're either active or they're not. If you have a stroke, they're dead, but you can't wake them up again, alas.

Hmm what is the name of the state you would say they're in if they're not getting enough blood? At what point does not enough blood equal neuron death? And would that then show up on an MRI?