My thoughts on why I think ME/CFS is not, at its root, a putative neuroinflammatory disease

[Jon_Tradicionali]

If you consider the latest publications by Straub et al, immune inflammation would make a lot more sense.

Pathogen invades, immune system attempts to deal with it through release of chemicals, never eliminates pathogen.
Immune system becomes "selfish" and adapts body to meet its need: divert all resources to immune system in order to remove the invader.
Brain is not the priority anymore.

The brain is the origin of symptoms but the immune system is to blame for starving the brain of essential resources.

Supplement brain with 50 supplements to enable it to part-function at its previous level.

Or

Dampen overactive immune system which again slightly helps symptoms.

Or

Aid immune system in removing the virus/bacteria so it down regulates naturally and returns to its original state.

 

[Jonathan Edwards]

What about neuroinflammation tied into vasculitis? Couldn't the end result be hypoperfusion that shows up on SPECT scans, or even MRIs if the damage is severe enough?

I think the sort of damage from vasculitis that would give hypoperfusion would constitute infarction. Brain stem infarction is usually associated with a life support machine at best. I may be wrong on this but to make head or tail of it we need more anatomical detail and a neuroradiologist. What was really encouraging about the IiME workshop was that we had imaging experts from outside actually showing interest in PET and MRI findings in ME and related problems.

 

[Marco]

Hypoperfusion would be the opposite of inflammation (where the 'flame' part is the redness of increased perfusion). This is why I think we need to disentangle the various component physiologic changes because they may not be working together in the way they do in typical inflammation. As far as I can tell microglial activation can occur without any perfusion changes. There was lots of microglial activation in the brainstem areas where that paper reports hypoperfusion. Maybe they are linked but if so we need a new word for this combination I think.

Would the link be ischemia?

 

[Jonathan Edwards]

Would the link be ischemia?

Ischaemia could lead to microglial activation I guess. And microglial activation might lead to fibrosis and ischaemia? Not sure about that. Different things would happen with different levels of severity of each factor. I think we may need a neuroradiologistWME.

 

[lansbergen]

Aid immune system in removing the virus/bacteria so it down regulates naturally and returns to its original state.

That is what I try to do.

 

[duncan]

Ok, what happens with neuroinflammation in cases of late stage neuroborreliosis, i.e., late stage Lyme that infects the brain? I ask this seriously, because markers may or may not be present in NB. That is the simple fact. Sometimes there is a slight pleocytosis in CSF in late NB, sometimes not. Sometimes elevated proteins, but not necessarily. Sometimes there is evidence of antibodies, but sometimes not. Yet it is in the brain, it impacts cognition - so you would think there is neuroinflammation.

But maybe not.

What happens with tertiary Syphilis when it is in the brain? Are there always overt signs of neuroinflammation?

Can you have chronic low grade neuroinflammation that remains below most radar, but that can be nonetheless degenerative? Do there have to be conventional or traditional overt lab signs?

 

[SOC]

In my current position at NIH I could never request this. And to make matters worse I'm work for the NIH via a contractor (which most federal jobs are like now), so I'm totally afraid that if I try to request something like this they will find some way to let me go because it's so easy to lay off a contractor for no reason at all.

Been there, done that. Completely understand.

I could do a lot better with this, it's been really hard though. In addition to full time work I'm in a relationship and live with my partner. Those of you who are married or in relationships living together know how hard it is, I can't have everything revolving around me and the entire relationship constantly being about this disease.

No, it's not healthy to have everything revolving around one partner. Still, you could adjust your lifestyle to better accommodate your health without making it all about you or making your partner have all the responsibility. It takes some creative thinking, but you're intelligent. I'm sure you could figure it out.

You need to know what your limits are, though, and that requires taking some data. Make it a little research project. Enlist the help of your partner. The goal is to not be constantly exhausted so that you can enjoy some things and be a better partner, even if you have to do less physically.

Think about what you don't have to do. What services can you pay for and thereby make life easier for you and your partner? Grocery delivery? House cleaning and yard services? Can you do more online shopping instead of bricks and mortar? Can you downsize to a smaller, less demanding home? Can you climb stairs less? Can you cook ahead, or in easier ways so that you don't have to stand a long time in the kitchen every day?

Don't stand when you can sit. Don't sit in an upright chair when you can sit with your feet up.

I think you need to enlist the help of your specialist on the techniques of proper pacing. Who is your specialist? Does s/he know anything about or do much with activity management? If not, you could probably learn a lot by starting a thread asking for energy management techniques. People here have a lot of experience learning to conserve energy while getting the most they can out of their lives.

Where would be the best place in the U.S. to get this?

The best place in the US is probably the Workwell Institute, but they are a long way from you. There is probably somewhere closer to you that would be sufficient. I'd ask your specialist first because s/he most likely knows which places are nearest you. If that doesn't work, ask here. You want a place that will do the test and write up the necessary paperwork for disability.

 

[Martial]

Ok, what happens with neuroinflammation in cases of late stage neuroborreliosis, i.e., late stage Lyme that infects the brain? I ask this seriously, because markers may or may not be present in NB. That is the simple fact. Sometimes there is a slight pleocytosis in CSF in late NB, sometimes not. Sometimes elevated proteins, but not necessarily. Sometimes there is evidence of antibodies, but sometimes not. Yet it is in the brain, it impacts cognition - so you would think there is neuroinflammation.

But maybe not.

What happens with tertiary Syphilis when it is in the brain? Are there always overt signs of neuroinflammation?

Can you have chronic low grade neuroinflammation that remains below most radar, but that can be nonetheless degenerative? Do there have to be conventional or traditional overt lab signs?

From my experience, research, and understanding. Lyme disease often causes hypo perfusion of certain tissues in the brain. It can cause chronic mild encephalopathy type states as well. They're different in symptoms case by case, and it seems the way it affects and changes brain activity differs from person to person. There is however a ton of pubmed articles that go over some of this stuff quite extensively.

 

[GONZ0hunter]

A good point, I've been thinking about this possibility for a long time, but here in the U.S. you know we don't have much of a choice.

They will never give me disability because I can work full-time still even though it's at a huge cost, they don't care about what is doing to my health or life outside of work. I basically have to get to the point where you and many others did where you work yourselves to the ground and the CFS gets so bad that you then require disability.

What sucks is that they won't give me "preemptive" disability for a period of like one year to improve. That's what's so terrible about ME/CFS, it breaks all the rules and what we need to get out of this disease just goes against anything insursance or disability would allow.

Have you received a friendly physiological review?

It might help your disability case.

 

[GONZ0hunter]

In my current position at NIH I could never request this. And to make matters worse I'm work for the NIH via a contractor (which most federal jobs are like now), so I'm totally afraid that if I try to request something like this they will find some way to let me go because it's so easy to lay off a contractor for no reason at all.



I could do a lot better with this, it's been really hard though. In addition to full time work I'm in a relationship and live with my partner. Those of you who are married or in relationships living together know how hard it is, I can't have everything revolving around me and the entire relationship constantly being about this disease.



Where would be the best place in the U.S. to get this?

One more thought. If you go part time you are limiting your income thus limiting insurance exposure to your disability.

I was in a similar position and found a great attorney.

 

[sarah darwins]

This is a fascinating thread (even if parts of it are a bit beyond me).

Q. has anyone attempted a thorough typology of the various presentations of me/cfs?

Just browsing through these forums over the last few months, I'm really struck by how many subsets there seem to be, even though certain symptoms are pretty consistent throughout. Classifications like mild/moderate/severe seem very inadequate. I wonder if medical trials are ever going to yield consistent results if subjects are recruited from across the different subsets.

 

[alex3619]

What do you call 'neuroinflammation' @leokitten? We discussed this at the IiME workshop and a number of people are unhappy with this broad brush term.

I think this might be a very important issue. Anti-inflammatories work on specific mechanisms, and its not clear that what we are calling inflammation is anything like what used to be called inflammation. So if the specific drugs or supplements do nothing for the specific mechanism, then they will not work, or will not work adequately.

Even treatment of microglial activation is not a very evolved area of medicine. Its just starting.

Once we have some specific mechanisms detailed then we will have targets to test therapies on.

I do note a 2/3-1/3 split in responses with Rituximab, Lights acid sensors etc. I wonder what overlap exists between NO therapy responders and Rtixumab responders. In particular I want to know where EDS patients are on this. I suspect we cannot talk about even ME patients as one single monolithic cohort, and under Fukuda its clear its not one cohort, and under Oxford it may be dozens of cohorts mixed together.

So there might be a subset in which anti-inflammatories work.

In my own experience the only pain relief I ever had that worked was Vioxx. Being cautious about anti-eicosanoids I was careful to only take it as a once off drug for acute pain. During those times my pain levels dropped substantially. That mode of action is dangerous if prolonged and intense, so the more effective the drug is the more dangerous it is if it works by inhibiting eicosanoid synthesis.

I have a suspicion that there are many drugs that might work, or work in combination, but the science we need to understand how to use them has barely begun.

 

[alex3619]

Maybe they are linked but if so we need a new word for this combination I think.

We need to understand enough about what is going on that we can make intelligent choices on terminology. The terminology used by everyone, from researchers and doctors to patients and the public, is largely confused. Fatigue, recovery, inflammation, ME, CFS, and functional are all terms that have so many shades of meaning that we cannot be sure we understand what is really being said unless we are very careful.

PS To that list of confusing terms you can add discussions about severity and disability.

 

[alex3619]

Would the link be ischemia?

Vascular ischemia, or biochemical ischemia? Factors which might shut down energy production all have about the same effect. We need to be open as to what is causing it until we have the scientific findings. The different factors have an intersect at the mitochondria.

 

[Marco]

Vascular ischemia, or biochemical ischemia? Factors which might shut down energy production all have about the same effect. We need to be open as to what is causing it until we have the scientific findings. The different factors have an intersect at the mitochondria.

I'm not sure what you mean by biochemical ischemia Alex or were you referring to the biochemical consequences of ischemia. In reponse to Jonathan querying what might link hypoperfusion and microglial activation I suggested ischemia - so yes (micro) vascular which also of course ties in with endothelial dysfunction.

 

[GONZ0hunter]

We need to understand enough about what is going on that we can make intelligent choices on terminology. The terminology used by everyone, from researchers and doctors to patients and the public, is largely confused. Fatigue, recovery, inflammation, ME, CFS, and functional are all terms that have so many shades of meaning that we cannot be sure we understand what is really being said unless we are very careful.

PS To that list of confusing terms you can add discussions about severity and disability.

Seems immune deficiency and autoimmune are mixed up often as well

 

[jimells]

In my current position at NIH I could never request this. And to make matters worse I'm work for the NIH via a contractor (which most federal jobs are like now), so I'm totally afraid that if I try to request something like this they will find some way to let me go because it's so easy to lay off a contractor for no reason at all.

I think you are courageous to discuss your illness and reveal your association with the NIH. Everything we do or say on the Magic Internet can and will be used against us in ways we can't even think of yet. We know these forums are monitored by Our Dear Leaders...

 

[leokitten]

What do you call 'neuroinflammation' @leokitten? We discussed this at the IiME workshop and a number of people are unhappy with this broad brush term. There does not seem to be inflammation in the sense of vascular permeability changes (which should show on MRI). There may be microglial activation - the Japanese study suggests that. But people are trying to block microglial activation in a range of other diseases like Alzheimer's and I am not aware that there is any very effective agent available yet. We did not get shown any scans losing orange spots after treatment in our seminar.

What sort of inflammation did Shungu show? I am not up on this study - although I just looked at a study of lactate levels which looks a bit weird to me.

One thing I forgot to mention @Jonathan Edwards that in addition to the Nakatomi and Shungu studies there have also been multiple small studies showing areas of cerebral atrophy in ME/CFS, and is similar to what has been found in other autoimmune and pain disorders (although the areas of the brain are different in each disease). I would imagine this is additional evidence of potential neuroinflammation (microglial activation, excitotoxicity) or possibly like has been mentioned cerebral hypoperfusion.

 

[SOC]

I think you are courageous to discuss your illness and reveal your association with the NIH. Everything we do or say on the Magic Internet can and will be used against us in ways we can't even think of yet. We know these forums are monitored by Our Dear Leaders...

Somehow I doubt "Our Dear Leaders" have the resources to read every thread at PR.

There are so many contract employees at NIH, it would be very difficult to figure out which of them could be leokitten, and I can't imagine that it's worth anyone's time and effort to do it just to pester leokitten with employment issues.

Yes, PR is a publicly searchable forum so we should all be cautious about what we put up here, but we need to be realistic about the possible consequences as well.

 

[heapsreal]

I think the sort of damage from vasculitis that would give hypoperfusion would constitute infarction. Brain stem infarction is usually associated with a life support machine at best. I may be wrong on this but to make head or tail of it we need more anatomical detail and a neuroradiologist. What was really encouraging about the IiME workshop was that we had imaging experts from outside actually showing interest in PET and MRI findings in ME and related problems.

Have you thought or considered vasospasms as in prinzmetal (spelling) angina or something similar occurring in the brain. So as in PM angina which show ST elevation on an ecg, would normally be a sign of infarction in a chest pain episode. With pm angina , glycerol trinitrate gtn relaxes the vasospasm and the ST elevation goes away. But during a myocardial infarct gtn generally doesnt stop the ST elevation and myocardial perfusion. Although through colateral circulation improvements from gtn can help perfusion and reduce size of the infarct.

so i wonder if a similar vasospasm could be occurring in cfsme and like pm angina , can come on with increased activity. This being a possible cause of hypoperfusion seen in cfsme.

food for thought ? ?