Search results

But wouldn't CNS injury be relatively easy to see on scans? And wouldn't we have the same discrepancy as explained in the introduction: that the fatigue in CNS injury is often less than in ME/CFS and if CNS injury was involved wouldn't it eventually be visible as ME/CFS severity increases to...

Ah yes apologies. I think I'm a bit confused because those low p-values shown in the graph are in purple and for the category: 0.01 ≤ MAF < 0.04, but I thought that the hits found had MAF > 10%?

Agree with this. So my counterpoint would be that the theory does not really state this, just that it is more likely that the key to ME/CFS lies in the neural pathway involved in generating symptom perception. Whatever else will be found in the future, it will probably have some special...

Perhaps AIDS (before it was adequately treated) might also be a good comparison to highlight. This is an example of a persistent virus that causes widespread immune dysfunction, a popular theory in ME/CFS and Long Covid research. Yet several physicians (Peterson, Klimas etc.) commented that...

By symptom burden I mean the fatigue/malaise/lack of energy and overall sense of feeling awful, not pain or suffering in general which in other disease can obviously be truly horrible.

I also get this lactic-acid feeling in my muscles and other patients suffer from weakness such as not being able to walk. But there are several reasons to think these are central rather than peripheral: due to things happening in the brain rather than in the muscle. 'oxygen tab gets closed...

I doubt it because we know what happens when those illnesses become more severe and it looks very different from ME/CFS. The pathology builds up and destroys parts of the body: muscles stop working, tumors develop, or there's brain damage, memory loss, joints get destroyed, organ failure, and...

Thanks for the comments @Grigor! To clarify: it was not my intention to minimize things or argue that peripheral pathology isn't possible in ME/CFS or that it is stupid to suspect or research it. Also agree that we still know very little about ME/CFS, that it hasn't been well researched in the...

Which study does this refer to?

I also read that the intercept of an LD score regression can be interpreted in a similar way (an indicator of inflation). But I don't see this measure reported in the DecodeME preprint: anyone saw it somewhere?

Don't think we have discussed this plot yet: Basically, the idea is that if the difference between groups is driven by selection bias, stratification effects, ancestry differences etc., then there will be lower p-values across the board. It would look like a systematic shift where many SNPs are...

Yes, the theory isn't very specific, but I don't think anyone can be at this stage. It does predict that studying the neural pathways that cause sickness behavior and synapse communication involved in this will be more fruitful for ME/CFS than all the things the field is pursuing now. I think...

I don't think so. I think if we found strong evidence of things like this, it would refute the theory. It leaves some room for subtle peripheral pathology because biology likes to recycle things in different parts of the body. So whatever is causing the synapses to go wrong might cause some...

Could be both, I guess. My hunch is that they are different. For example that post-viral fatigue results in pressing the button of the symptom signal a bit longer, while ME/CFS is mainly about the button being broken (and constantly on).

For simplicity, I would place the pathology in (or as close to) the symptom-causing pathway itself. The pathways that interpret/evaluate signals coming from the body or help with the transmission of those signals seem less crucial. A major difference is that thoughts and behavior do not really...

I don't think it does; merely wanted to suggest how it leaves room for it. It would view overexertion as the body not responding to the symptom signal. Hence, the need to make the symptoms worse and cause PEM. This would help explain why any type of exertion (cognitive tasks, physical exercise...

Yes, many patients also report early muscle weakness/cramping/lactic acid feeling that seems similar to what Ramsay described in his descriptions of ME. Anecdotally, severe patients also seem to suffer from muscle weakness that does not appear to be due to deconditioning. I'm not sure if these...

My hunch is to follow Ockham's razor, keep things simple, and only add things if we really need to. At this point, I think there is strong evidence of an immune trigger, but not necessarily of immune pathology maintaining the illness.

Thanks for all the useful comments and suggestions! Lowered intelligence, drop in IQ level. But I generally meant that ME/CFS does not suggest brain damage or a neural development disorder. The cognitive problems are disabling but more vague and diffuse in nature, such as brain fog. Like Jo...

Conclusion Overall, I think this is convincing evidence that should make this the most plausible framework for understanding ME/CFS. When I think about other theories for ME/CFS, they often fit into this concept as an addition (for example, by giving a plausible explanation of how the signaling...