Preprint Biological Insights from Genome-Wide Association Studies and Whole Genome Sequencing of [ME/CFS], 2026, Maccallini et al

V.R.T. said:
People do not improve or recover to the extent that people clearly do in e.g. Fluge and Mella's studies in degenerative diseases.

How would your own experience of getting better for 12 months track with the idea of irreversible neuron loss causing MECFS?
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or perhaps it only concerns the most severe cases... the gap is so wide between mild and severe, there may indeed be a loss of neurons in a specific area.
 
neophyte32 said:
or perhaps it only concerns the most severe cases... the gap is so wide between mild and severe, there may indeed be a loss of neurons in a specific area.
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But again, you've got people who improve from severe or very severe to moderate or mild, like the prominent German advocate Martin (pausedME is his username in various places i think) you've got people like me who improve back to the top end of severe from borderline very severe and highly sensitive to all stimuli. You have many case studies and reports of severe people who are much better after x or y drug. So even if those drugs don't work, those people really improved. If severe symptoms were caused by irreversible neuron loss that wouldn't happen.

I suppose until we know the mechinism enough for effective treatments to be developed there is always a possibility of the whole permanent untreatable thing, but I'm not sure I buy it.
 
ScoutB said:
and @V.R.T. (if I'm remembering correctly), I *was* trying to jog my way out of it right up until I was properly disable
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Actually i didnt do much exercise at all during my prodromal phase. I tried to jog my way back into health 3 and a half years into mild MECFS after being gaslit by doctors.


ScoutB said:
My sense is the prodrome phase involves a lot of feeling ill/awful, not responding normally to exercise, plus cognitive, brain fog and/or mood problems (not to mention various gut and other 'autonomic' things seemingly going a bit haywire).
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This is about right though. No PEM to speak of (at least not that I could be certain of) but something wasn't right.
 
V.R.T. said:
But again, you've got people who improve from severe or very severe to moderate or mild, like the prominent German advocate Martin (pausedME is his username in various places i think) you've got people like me who improve back to the top end of severe from borderline very severe and highly sensitive to all stimuli. You have many case studies and reports of severe people who are much better after x or y drug. So even if those drugs don't work, those people really improved. If severe symptoms were caused by irreversible neuron loss that wouldn't happen.

I suppose until we know the mechinism enough for effective treatments to be developed there is always a possibility of the whole permanent untreatable thing, but I'm not sure I buy it.
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I've talked to Martin privately on Twitter a lot, and I know about his treatment. Huge doses of pregabalin every other day, and very high daily doses of lorazepram. He added lamotrigine a few months ago. He's a very rare example of someone with very severe symptoms who has recovered (he fluctuates between mild and moderate now). The treatment is very, very heavy and dangerous in the long term, he knows it.

You're right, there's no proof of neuronal damage. Paolo doesn't know either, but he doesn't rule out the possibility.

LDA helped me go from 300 steps (I'm back to that unfortunately) to 1700 steps for 5 months without too much trouble, with no sensitivity to light, etc. The effect was too short-lived... I'm trying again after a two-month break, but well... it doesn't seem to be working again.

Yes, there's definitely something possible. We are still a long way from knowing, but perhaps with people like Paolo and Edwards we will eventually make progress.
 
Andy said:
So he hasn't recovered, as most people would understand it. A better word to use in my opinion is that he has improved.
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Yes, you're right, I misspoke. He has made enormous progress, and VRT is right to point that out. He was bedridden, immobilized, and fed through a tube for years. But his treatment is extremely intensive.
 
I suspect most pwME would argue it can be degenerative, and at some point (probably early on?) absolutely is - but also in a very peculiar manner, can halt its downward spiral, or continue after the wrong provocation to plummet.

I know for a fact my first eight years were a constant downward arc.

The last 20 years have vacillated.

It's also not a single tune. There are melodies over melodies, only none is pleasant, and they lack harmony. Each symptom acts like it's its own entity, like it has discreet volition in deciding when to lessen its volume or blare it.
 
ScoutB said:
I would actually say, for those of us with a prodrome phase, step count may be one of the last things to crash? To be fair, I wasn't running marathons, but like @DHagen and @V.R.T. (if I'm remembering correctly), I *was* trying to jog my way out of it right up until I was properly disabled.

My sense is the prodrome phase involves a lot of feeling ill/awful, not responding normally to exercise, plus cognitive, brain fog and/or mood problems (not to mention various gut and other 'autonomic' things seemingly going a bit haywire). And yet at this point you are still trying to maintain a normal lifestyle with all the walking and exercise that entails.
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This pretty well describes it for me. I would also add that one aspect of the attempt to "jog" one's way out of things in my case was that, for a very long while, the jogging or walking itself really didn't seem to be a problem - in the moment, it was an effective distraction from everything else that was going on. That is to say, when I couldn't think at all I could just walk, which, for a while, had something like a meditative effect.

Obvious PEM was a late arrival.
 
DHagen said:
This pretty well describes it for me. I would also add that one aspect of the attempt to "jog" one's way out of things in my case was that, for a very long while, the jogging or walking itself really didn't seem to be a problem - in the moment, it was an effective distraction from everything else that was going on. That is to say, when I couldn't think at all I could just walk, which, for a while, had something like a meditative effect.

Obvious PEM was a late arrival.
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I also ran until I was practically bedridden. I was doing brisk walking towards the end. It lasted three years.

The prodromal phase was strange, characterized by small fiber neuropathy, intense fatigue after cognitive exertion, and oddly, less physical fatigue at the beginning.
Then came the second trigger, the same one (alcohol and tramadol), and a strange phase of increased physical fatigue with panic attacks (amygdal hyperexcitability) after exertion, and sometimes a sensation of my head exploding while jogging. But I kept going.

In short, yes, as Paolo said, I had a warning sign in 2016, a long time before, with very strange fatigue for a week... again after alcohol. Then I started getting sick more often with intestinal problems (irritable bowel syndrome, gastroenteritis) and recurring genital warts. My cholesterol has increased... it was long time before prodomic phase.
This corroborates a lot of what Paolo said.
 
Like most, I didn't know my first symptoms were symptoms. Hindsight granted me that insight.

My very first was a balance issue that affected my drive to work. And driving at night. I say "balance" because I cannot think of a better word. Equilibrium?

Then came the issues with writing and reading and comprehension, sleep, weakness....all very gradual, but inexorably worsening.

Even PEM was a lightbulb-on moment which I had to read about before I recognized it.
 
@paolo, is this chart based on your genetic findings?
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If so, what genetic findings are there in pwME/CFS that related to diabetes?
I had signs that something was wrong before I came down with what one would actually consider ME/CFS, and hypoglycemia was the symptom that brought on severe inability to stay awake.

Sleep issues (insomnia) had started long before that. Sore throat that didn't respond to antibiotics was one of the pre symptoms. I actually was intolerant of most medicines I had tried, and then started having multiple chemical sensitivity and difficulty finding food that didn't bother me.

I hope someone figures out how to get out of this condition, I don't want to get Alzheimer's.

PS: Alzheimer's is considered Diabetes T3 by some.
 
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