What blood tests would you get?

Local brain infection with virus would normally show up clearly on an MRI scan. Based on what we know of documented brain infection I think it is vanishingly unlikely in ME.

I think much the most likely reason that people improve while taking antiviral is that it is nothing to do with the drug. Antiviral drugs are very unlikely to do anything else of interest. I know that such ideas have been raised but not with any plausible basis I know of.

The one thing that disappointed me about Jen Brea's film was that the tiny bit of 'science' seemed muddled, speculative and out of date. There is no immunodeficiency to let viruses react I ate as far as we know. There are no inflammatory cytokines flying around. I think now we have evidence from lots of good research groups it is time to move on from this approach.

 

In acute encephalitis perhaps. But in chronic brain infections, I'm not sure this is always the case. I know there are bacterial infections that may not present on an MRI, but whose presence can be demonstrated with a CSF exam. I am not clear on why it should be any different with a virus, but I suspect you would know better.

 

@Jonathan Edwards, thanks for answering (I fear you answered that question in another thread and I forgot it sorry)

Why should that be?

What about CT, PET, SPECT, do you know maybe?

Are the papers about abnormal brain findings in ME then wrong (amongst others those by Komaroff)? Or don't I remember correctly (well... )?
Ahhh, those findings weren't about infection. Still, the question about brain abnormalities remains...and they are not shown via MRT...

 

I think the recent research of epigenetics is suggesting that an original infection can turn off and mess with genes causing subsequent cells to produce peptides that are slightly wrong. This leads to protein misfolding and therefore inefficient nutrient processing, problems with chemical synthesis, hormonal signifiers, receptors, cell mediation, programming and reproduction to name a few. All test results if taken together would show below par performance where taken in isolation a test result may be within normal range. So perhaps the future of ME diagnosis and treatment may lie in genetic testing. So since we have an unlimited budget in this hypothetical I’d like to see what is going on with the systemic function of the body that is making the immune system constantly want to target and annoy its own parts. Clearly it’s not all the immune system miscalculating it’s own recognised parts, but the parts that are becoming unrecognisable.

 

Didint Lipkin find pro inflammatory cytokines in PWME? Havent they been found by other researchers?

I also have MCAS and inflammatory cytokines are often tested as high in people with this disease. I myself have tested very high for a number of them.

 

Yes, here it is, the Lipkin study

https://www.mailman.columbia.edu/pu...-evidence-chronic-fatigue-syndrome-biological

 

The study Mady Hornig did with Ian Lipkin showed some very slight differences in one or two cytokines. I think IL-17 came up as raised. Bu the main finding was that for CFS as a whole there was little or no difference. There was a difference amongst the CFS patients according to how long they had had the illness. Most so-called pro-inflammatory cytokines were within normal limits. In comparison to something lie RA I think one would say no pro-inflammatory picture was found. I remember Mady noting that IL-6 was if anything low.

 

which confused me wrt the wpi random forest and klimas papers. those showed il-8 and il-6 high. were those insufficiently powered or the methodology unproven?

 

To be honest I think we are pretty sure that none of the inflammatory cytokines are sufficiently out of line in ME/CFS to explain anything much in relation to symptoms. The best one can say is that slight changes might be some indirect clue to something else. But in general no consistent findings have shown up and people have looked often enough for it to be unlikely anything will.

And there isn't any inflammation. Even minor inflammation produces local symptoms and can be picked up on imaging techniques. As far as I am aware there are no inflamed organs.

 

Dear Dr Edwards
What is causing the non stop 'flu' feeling that so many patients have?

 

We don't know but I don't think it has anything to do with inflammation in flu. It is an effect on the brain of circulating factors that may include gamma interferon and prostaglandins. But the brain does not get inflamed as a result. Presumably prostaglandins are not that relevant in ME, otherwise paracetamol would give major relief.

 

If this effect is not inflammation, then, in what other ways could these factors be affecting the brain? What other processes could be occurring, what would you call them? "The patient describes a feverish flu-like sensation but it's not inflammation, it's…" ? My apologies for asking so directly.

 

When prostaglandins and TNF affect the hypothalamus it alters its thermoregulatory cell activity and your temperature goes up because of autonomic signals to metabolising tissues. When cytokines reach the chemoreceptor trigger zone or nausea centre nerve cells send signals to other parts of the brain that make you feel sick and stimulate stomach contractions.

None of this is 'inflammation', which is a change in blood vessel properties that leads to redness and swelling and white blood cell accumulation. Inflammation is a term that has got dissociated from its actual meaning in popularised immunology with the result that we have a lot of very muddled theories.

 

would this also account for seemingly perpetually swollen lymph glands?

 

Not really, that is a different process again. Lymph nodes are normally stuffed full of white blood cell (lymphocytes) as is the spleen,so 'inflammation' of a lymph node is a rather dubious term. Lymph nodes usually get large and tender when the lymphocytes inside become activated and start dividing. That may be associated with inflammation somewhere nearby, but not necessarily

 

Thanks for this succinct explanation. This is one of my daughter's more frequent symptoms which would perhaps indicate immune system issues?

 

It may be deceptive to compare the modest, but statistically significant, cytokine elevations seen in short-term ME/CFS patients to the higher levels that might be seen in more transitory conditions.

In the flu, the higher cytokine levels may be limited to a few days, whereas in ME/CFS the more modest elevations seem to be chronic, lasting about three years. Might there not be a cumulative effect on the brain from these constant, low level cytokine elevations in short-term ME patients?

My impression is that many patients seem to get slowly worse in the first year or so of ME/CFS. I wonder if that may not be the gradual cumulative effect on your brain of being chronically exposed to even low levels of elevated cytokines.

My sense is that this is what Mady Hornig was talking about when she said [in relation to the Columbia cytokine studies] that early intervention in the disease may be important.

 

I have no idea if it's true, but it makes sense to me, sort of like waves on a cliff

 

Could be so, but probably not the cytokines we usually associate with inflammation. People with rheumatoid arthritis used to have sky high cytokines for years and they never got brain fog or PEM or anything. When we blocked the cytokines they were fine.