The symptom signaling theory of ME/CFS involving neurons and their synapses

[EndME]

It sounds crackers, doesn't it?

I think it can be consistent with the sort of neurological models that are being proposed here, something along the lines of "A typically noisy network is calmed down by a specific firing constellation of neurons" (for example acting like a sink that removes too much excitation) but of course these constellations and systems are all somewhat outside of your control, just how you can't tell a person with dementia to just fire more neurons to remember stuff.

 

[Sean]

The mechanisms seem central (in the brain) rather than peripheral (in the muscle).

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 (difficult to detect) disruptions elsewhere in the body. These might not seem related until we understand that the molecular parts used are the same.

Yes, I think this is an open question at this stage. Any peripheral features may well be downstream consequences of neuronal/synaptic dysregulation in the CNS.

Another feature that needs explaining is the often highly dynamic variability of symptom expression in short time frames.

 

[poetinsf]

I'm wondering if the delay exists because could be a fault in the repair mechanisms involved in fixing the wear and tear of the exertion,

The delay is a normal part of recovery. The cytokine signal to invoke the repair usually does not kick in till 12-24 hours later. That's why you get DOMS.

The recovery time would also be prolonged because of the faulty repair mechanisms.

3-4 days for recovery is normal. That coincides the typical PEM duration.

PEM is telling us that the issue is not during exertion but later.

PEM could be thought of as pathological response to the normal recovery/repair signal which is delayed and imperceptibly low for minimal exertion. It could be a hypersensitivity to normal low grade inflammation, in other words. That can also explain hypersensitivity to alcohol, flu shot, etc.

Why is exertion in particular perceived as problematic, and not for example, an ordinary flu?

Flu involves high grade inflammation. So, both healthy people with normal threshold and ME/CFS people with low threshold respond to it the same way. Think of it as a fire alarm with high/low tolerances. They will respond the same way to thick smoke. For minute amount of smoke, only the low tolerance alarm will go off.

If the problem is a distorted signal then it must be a signal

The problem is more likely with the sensor, not the signal. No pathological signal has been found in ME/CFS patients so far.

I sudpect it's metabolic

That wouldn't explain the PEM delay.

 

[poetinsf]

Nevertheless, I am interested in the phenomenon of unrefreshing sleep and have wondered if an ongoing problem with updating/deleting daily data (via synapses) may be part of the origin of symptoms in ME/CFS.

Flu patients wake up unrefreshed. If ME/CFS is chronic flu-like sickness, unrefreshing sleep being part of it wouldn't be that remarkable.

 

[poetinsf]

So to me, PEM is a response to glial response to immune activation.

That would be my pet theory, and it explains every symptom. But I can't rule out the possibility of brain/neurons being directly responding to immune signals without the mediation of glial cells. If there is a direct (bidirectional) communication between the brain and peripheral immune system as one recent paper claims, the mediation by neuroimmune cells may not be necessary.

 

[ChronicallyOverIt]

Both rheumatoid arthritis and reactive seronegative arthritis can come in resolving forms lasting a few months. For rheumatoid the most common trigger is post-partum - after childbirth. For seronegative it is an intracellular infection. Both can also have life long forms.

To me the difference with ME/CFS from PVF is that PVF is basically monophasic. You may have good and bad days but you do not improve for weeks and then relapse for months before maybe impriving again and relapsing again. It seems like there is a prolonged period of around six months where infection signals can linger on. ME/CFS is more than that.

Rheumatic fever and Post-streptococcal glomerulonephritis also do this I believe, where they last months then resolve.

They seem to be autoimmune in nature but don’t develop into full autoimmunity for some reason.

Lots of people talk about post viral illnesses but I think it’s good to bring up this type of “post” immune challenge illness can happen with bacteria as well