McGregor's Hypothesis of ME/CFS

[percyval577]

And such a mechanism would be open for an interpretation with that we rather feel not tired (fatiqued)
but exhausted. I wish I would be tired.

 

[Wishful]

In addition, we have the widespread diversity of concrete symptoms, not being able to swallow e.g. Why would IFN-g (genuinely) relate to these symptoms, in such different areas?

I'd say that IFN-g has strong effects on many cellular functions, so it's quite reasonable for elevated INF-g to result in a wide variety of symptoms. It's hard to separate the symptoms specifically caused by IFN-g, but here's the side effects of one form of it:

"Actimmune (interferon gamma 1 b) is a specific interferon made from human proteins used to prevent infections in people with a condition called Chronic Granulomatous Disease. Actimmune is also used to treat a congenital bone disorder called osteopetrosis. Common side effects of Actimmune include injection site reactions (pain/swelling/redness), diarrhea, upset stomach, nausea, vomiting, problems with memory or concentration, weakness, tired feeling, lack of coordination, muscle or joint pain, or headache. Flu-like symptoms such as headache, tiredness, fever, chills, and muscle aches may occur, especially when you first start this medication. These symptoms usually last about 1 day after the injection and improve or go away after a few months of continued use."

And such a mechanism would be open for an interpretation with that we rather feel not tired (fatiqued) but exhausted. I wish I would be tired.

I don't think I feel tired, fatigue, or exhausted. I think I feel like proper function of my brain is inhibited. That might be metabolic (not enough ATP in the right places) or structural (slight changes in cells altering signal transmission) or something else, but I think it's different from the changes due to normal fatigue or sleep deprivation. I also think that most of my physical symptoms (mostly aches) are a result of improper processing of information in the brain (maybe amplifying normal signals from pain sensors) rather than actual physical changes in the muscles.

I wonder if I have the 'something in my blood' that interferes with mitochondria. On bad days, is my walking inhibited because of something physical in my muscles, or is it just neural processing? Too bad we can't just download and print one of Dr. Davis' sensors for home use.

 

[percyval577]

@Wishful
I am not convinced by your citation, but you might enjoy this: I had an uncle whom I suppose to have suffered from a pre-me/cfs. Once he got a knee issue, and the doctors wanted him to get it somehow corrected. "Do you then know what it is?" asked my uncle. "No." said the doctors. "Ok, then we won´t do anything." He continued to walk around, only his knee stayed for the rest of his life thick. Recently I tried to look it up of course, and found that elevated IFN-g blood levels in childhood are known to possibly lead to knee issues (in childhood though).
Assuming a two hit theory, I would think that my uncle had good luck not get a second impact, whatever a first impact might have been. (And assuming that there is genetical predisposition.)

I don't think I feel tired, fatigue, or exhausted. I think I feel like proper function of my brain is inhibited.

I think, as long as we don´t try to get any clue in the feelings of patients, some helpful interpretation, we won´t ease to figure out what it might be. You may be happy not to feel any "unrest" staring into nothingness. True, I like to think that being tired is an effort that must be made by the body, and I like to think that this is in an essential part a clearing of NMDR´s which normally would have built up only during action. True that I cannot proof it, and maybe it´s still not possible at all to proof it these current years, but I myself am on a good way at least.

 

[Rufous McKinney]

a quick check indicates that there is no simple way to measure fatigue.

The Japanese studies are interesting because they focus on inducing fatigue and have more opinions on it.....

From what I recall (insert ME disclaimer)...they use Executive Functions to induce fatigue and then study that with considerable interest.

Less likely to put you on a bicycle.

I just spent several hours- just sitting in perfect temperature, in a perfectly comfortable couch, chatting with two young women. I was in a kind of bliss.

And now I am completely WIPED exhausted from-just listening and making an occassional remark.

Somehow: my condition still shocks me. This just wiped condition is so: remarkable.

 

[Learner1]

I think this is a pertinent observation. My PEM has been lessened and ability to exercise increases as I brought amino acid consumption up to around 2g/kg. If I back off of that rate, markers and symptoms reflect it.

Breaking muscles down to produce energy causes a raft of metabolites to get dumped into the urine. These are the same metabolites, though, that we need to replenish in our muscles. Some energy, then, is being produced, but at a longterm cost to the muscles.

This dumping/amino acid depletion is, McGregor believes, a key issue in ME/CFS. It can help explain why ATP production is low and why the disease is so darn difficult to get out of.
...

Gut barrier problems (e.g. leaky gut), for instance, are common in hypermetabolic states. McGregor noted that Shukla showed that exercise – which is simply going to exacerbate the amino acid depletion – results in the gut leaking bacteria into the blood in ME/CFS and spiking inflammation. McGregor believes that gut barrier issues are probably producing many symptoms in ME/CFS

 

[Wishful]

I just spent several hours- just sitting in perfect temperature, in a perfectly comfortable couch, chatting with two young women. I was in a kind of bliss.

And now I am completely WIPED exhausted from-just listening and making an occassional remark.

Cognitively-induced PEM. I get the same effect from talking to (or listening to) people. While 'just listening' seems a trivial task, it's probably triggering considerable neural processing, which in some way triggers PEM. Likewise, some people find driving relaxing, but that too requires lots of visual processing, predictions, etc, so that triggers my PEM too.

While the symptoms from cognitively-induced PEM seem similar, for me it has a different delay (within hours) than for physically-induced PEM (consistent 24 hrs). Also, I can block (or reduce existing symptoms) physically-induced PEM with cumin, but it doesn't work on my cognitively-induced PEM. There seem to be two separate pathways to PEM.

 

[Learner1]

Glutathione and BCAAs relieve both mental and physical PEM. Seems to be related to the amino acid depletion problem. And, I think, oxidative and nitrosative stress.

 

[Inara]

not being able to swallow e.g.

If there are other typical symptoms (e.g. hoarseness, coughing, clearing throat - with no other apparent causes), could this point to a vagus nerve issue? Or muscle weakness? Or...?

 

[Diwi9]

Cognitively-induced PEM. I get the same effect from talking to (or listening to) people. While 'just listening' seems a trivial task, it's probably triggering considerable neural processing, which in some way triggers PEM. Likewise, some people find driving relaxing, but that too requires lots of visual processing, predictions, etc, so that triggers my PEM too.

While the symptoms from cognitively-induced PEM seem similar, for me it has a different delay (within hours) than for physically-induced PEM (consistent 24 hrs). Also, I can block (or reduce existing symptoms) physically-induced PEM with cumin, but it doesn't work on my cognitively-induced PEM. There seem to be two separate pathways to PEM.

Interesting, because this is where I am at in my illness right now. My crashes are different. I did a cardio stress test on Monday. I was tired after it (and it was damn hard), but went out for lunch afterward (I was driven to and fro). That night, the total muscle weakness and pain came, and I spent three days in bed as a result of it...with a lot of involuntary sleep episodes.

When I extend myself cognitively, I have more of an immediate onset sensory overstimulation and need to go to bed and rest with no stimulation (need eye mask and headphones), but can typically recover from this within an hour or two. This is my big obstacle to driving, I may be able to get somewhere, but do not know if I will be able to drive home.

I feel like fatigue is the wrong word, again and again; there are subtleties to our symptomatic experiences that need to be better sorted/described/understood...fatigue doesn't cut it.

 

[boolybooly]

This fatiguability due to social interaction is a familiar problem, when I first became ill I noticed a kind of unstoppable mental surge which lead to my mind running on and on. I saw a few practiced healers etc and while the first I went to see could sense what was happening for me she could not do anything to help. I later learned to live with this by trial and error and considered it an aspect of neurological hypersensitivity.

The very sad and regrettable deaths of several PWME, namely Lynn Gilderdale, Sophia Mirza and Merryn Crofts, lead to autopsies which showed dorsal ganglia inflammation.

http://www.investinme.org/Documents/Library/magical-medicine.pdf see p98

In his presentation at the Royal Society of Medicine meeting on ME and CFS held on 11th July 2009, consultant neurologist Dr Abhijit Chaudhuri demonstrated evidence from three autopsies of people who had died from ME/CFS, all of which showed inflammatory changes in the dorsal root of the spinal cord. His abstract states that all three autopsies provide “evidence of neuroinflammation in the dorsal root ganglia, which are the gatekeepers of peripheral sensory information travelling to the brain. This finding may help explain the high level of fatigue and pain”.

Its hard to know if I have the same condition they had but as a working hypothesis it would make sense if ganglial inflammation caused neurological hypersensitivity in the afferent pathways, so boosting the signal as it were, since I have read Dr Paul Cheney saying that nerve damage can lead to injury responses lowering the threshold voltage for nerve transmission effectively upregulating the nervous system (which is why he recommended magnesium and taurine supplements). I dont know whether nerve upregulation due to harms like inflammation is systemic but it would explain a few things if it was.

The afferent pathway not only transmits pain but also sensory input from touch and proprioreception. PWME commonly have trouble with excessive sensitivity to cranial sensory stimuli and need to lie still in a quiet darkened environment to recover which implies cranial afferent senses are also affected by hypersensitivity or at least contribute to its affect, so it would appear hypersensitivity is not confined to the ganglia though to date there is no evidence of comparable inflammatory processes in the brain that I know of there is evidence of lactate build up which could be consistent with overactivity.

So IMHO this begins to explain what I first encountered with the mental surge and this included visual effects which are more commonly associated with migraine like seeing halos around monochromatic lights and of course sensitivity to loud noises aka hyperacusis.

Its worth considering the brain uses a lot of metabolic energy and social awareness is considered one of the evolutionary drivers of enlarged anthropoid and human brains and has distinct centers attributable to aspects of it, like face recognition etc. So social cognition is an extra task on top of just surviving, which in a hypersensitive brain with lactic acid build up might produce overload which could be recovered from by resting a few hours.

Which would appear to be distinct from PEM from overactivity which is typically delayed upto 24 hours and then results in a 3 day crash, for me at least. Though personally I find social interaction can be a contributor to this kind of crash and severity is a question of degree and responsible pacing goes a long way towards reducing severity. Muscular activity typically makes a bigger contribution to crashes but there again pacing can make the difference though pacing with physical effort is far more restrictive than for mental effort.

 

[Wishful]

Glutathione and BCAAs relieve both mental and physical PEM. Seems to be related to the amino acid depletion problem.

Well, those amino acids do other things as well. For me, BCAAs block tryptophan transport, which lets me avoid an increase in symptoms from a TRP surge. So, it's not a depletion of BCAAs causing those symptoms, but having a surplus that is blocking them. BCAAs don't seem to relieve my PEM. I haven't tried glutathione.

 

[Wishful]

This fatiguability due to social interaction is a familiar problem, when I first became ill I noticed a kind of unstoppable mental surge which lead to my mind running on and on.

Diwi9 mentions something similar. Just conversing for a few minutes seems to put my brain in a hyperactive state. That makes it hard to fall asleep that night; my brain just keeps replaying the conversation and stays stuck in that hyperactive state. I'm relieved that I'm not alone in that.

This is my big obstacle to driving, I may be able to get somewhere, but do not know if I will be able to drive home.

I used to have that worry too, for trips longer than shopping in the nearest town. Actually, I suppose it's still a worry; I just haven't made any longer trips for the last few years. I know that ME can impair my driving (judgement, response time, etc), but I don't know how strongly it could impair it, and my judgement of how impaired I am could be the first thing to go. I did lose awareness of a road hazard one time (poisoned by mashed potato toxins) and ended up stuck on a snowbank. I hadn't been aware of how impaired I was until that point.

I feel like fatigue is the wrong word, again and again; there are subtleties to our symptomatic experiences that need to be better sorted/described/understood...fatigue doesn't cut it.

Wording is critical in how we think about things. That's why I think it might be important for the research community to change the words they use. I'm not sure what to replace 'fatigue' with, but maybe the right word or phrase would trigger a different approach to understanding what's going on in our bodies.

 

[Rufous McKinney]

Cognitively-induced PEM. I get the same effect from talking to (or listening to) people. While 'just listening' seems a trivial task, it's probably triggering considerable neural processing, which in some way triggers PEM

We were also conversing in two languages.

 

[Rufous McKinney]

Diwi9 mentions something similar. Just conversing for a few minutes seems to put my brain in a hyperactive state.

Here, it feels like a type of inertia which can only be overcome by pushing the WIRED over the TIred. In order to gain lift- I get somewhat worked up and it feels like adding a bunch of oxygen I don't have- to whatever it is that requires the lift.

Then: that mental lift...doesn;t last long and kaching, collapse on a nearby chair.

 

[Rufous McKinney]

If there are other typical symptoms (e.g. hoarseness, coughing, clearing throat - with no other apparent causes), could this point to a vagus nerve issue?

Is the throat thing: vagus?

My sore throat is a daily issue. The other nite it was so bad I was sure I was getting a cold. Next morning gone, returns at: run down PM.

 

[Rufous McKinney]

my brain just keeps replaying the conversation and stays stuck in that hyperactive state. I'm relieved that I'm not alone in that.

Me too, often!

 

[Rufous McKinney]

I did lose awareness of a road hazard one time (poisoned by mashed potato toxins) and ended up stuck on a snowbank.

We still need to do our Cognitive Comedy Channel.

A few years back, when I was still working, had to go out very early and I was still in the morning Stupor, and did some illegal U-turn...got pulled over. I decided I needed to really limit the conditions under which I agree to drive... Perhaps I had also been poisoned by Mashed Potatoe toxins.

 

[Rufous McKinney]

Why do patients feel exhausted but basically never nicely tired

No energy left in the mitochondria?

but muscles didn't get moved about, lactate is maybe building up, lymph did not get moved.

When I did the first longer walk when I pushed myself a few months back: I felt so good that night because I felt a kind of muscle tired in my legs.

LIttle did I know that I would experience my biggest crash yet, by walking around the block a second time.

My symptoms have worsened alot while I continue to fix certain symptoms..its just rather baffling.

 

[gregh286]

Glutathione and BCAAs relieve both mental and physical PEM. Seems to be related to the amino acid depletion problem. And, I think, oxidative and nitrosative stress.

100%. Glycine and proline very important. They are always most depleted in me.
Is it any wonder there are cci...chiari issues etc. Our bodys burn collagen and connective and ligament tissue aminos for energy!!!

 

[Wishful]

No energy left in the mitochondria?

I think it's possible to have normal levels of ATP, meaning proper mitochondrial function, but still feel tired/fatigued/exhausted because of something in the brain malfunctioning and creating a false perception. Phantom pain supposedly feels just like real pain, but doesn't arise from real tissue damage (the tissue is missing). Maybe what we're experiencing is 'phantom fatigue'.