Preprint Hypothesis: Myalgic Encephalomyelitis (ME) as a Mast Cell Activation Disorder (MCAD), 2026, Carroll

[EndME]

There are anecdotal reports of some ME/CFS patients experiencing significant improvements, in some cases even going from being bedridden to being able to function again

The same anecdotal reports exist for CBT and GET, which is you find people that swear by them. What about those that report improvements whilst on a placebo, should we be handing out those as well? I think the answer is provided by clinical trials which show when something is a moot point. When everyone is in the dark, it is hard to know what is what, but once the light gets turned on things become much clearer.

But I also understand patients who seek out doctors because they are desperate to try something that might help, even when the evidence is still limited.

I think everyone understand the patients and their families. They are not to be blamed for anything.

If clinicans hand out drugs like lollipops, they also have a responsibility to supply evidence or look at the available evidence. That is all I'm demanding. You can't hand out something 200 times without even looking at the evidence or trying to build some (and this routinely happens in ME/CFS). The situation in ME/CFS is really quite horrible, where the involved clinicans often don't care about evidence or understand the basics of clinical trial methodology. We are talking about something that will one day give historians a nice hobby, a land of psychobabble vs a land of biobabble, with little land in-between. But it seems that there is also a sane island in-between. I'd like to think that is now the way forward.

 

[Tom Hill]

But why pick out the trigeminal? It is just a convenient bunch of wires at your top end. There are lots of other bunches of wires.

I’m still wondering if it’s the mediator of just about all of the idiosyncratic neuro-sensitivities we see associated with Me/CFS. And because of the mandibular nerves, it involves some very odd brainstem sensory neurons (the only ones inside CNS), which seem to be subjected to special protections, as they can’t regenerate.

 

[Jonathan Edwards]

Personally, I think there is room for both: being transparent about the lack of evidence and the uncertainty involved, while still being open to carefully monitored treatment trials when there is a reasonable rationale and some indication that certain patients might benefit.

I thinkmost of us would agree with that but a carefully monitored treatment trial means a properly conducted controlled trial that is capable of generating reliable data.

 

[Jonathan Edwards]

I’m still wondering if it’s the mediator of just about all of the idiosyncratic neuro-sensitivities we see associated with Me/CFS.

Well it isn't for tummyache, which is a common problem.

 

[Tom Hill]

Well it isn't for tummyache, which is a common problem.

but there’s interesting trigeminal-vagus communication

 

[Jonathan Edwards]

but there’s interesting trigeminal-vagus communication

Called the nervous system. I really don't understand the motivation for focusing on these randomly separated bundles of wires. It'sa bit like saying the bedroom windows are really important for seeing out. So are the landing windows.

 

[Tom Hill]

Called the nervous system. I really don't understand the motivation for focusing on these randomly separated bundles of wires. It'sa bit like saying the bedroom windows are really important for seeing out. So are the landing windows.

No doubt. We still need people checking every window in this building though. The grades of problems leading up to central sensitization, apparently a core feature of the worst severities of me/cfs, make me think the trigeminal system is worth a special look. The ME5 neurons idea is interesting to me as a potential candidate for filling the gaps in the Idio Sen hypothesis of what causes pem.