Trial Report Can a consensus occur on a research case definition for ME/CFS?, 2024, Jason

Yes, I think IOM is good: useful and straightforward in both clinical and research domains. I appreciated the NICE 21 recommendation to refine IOM and reduce time to diagnosis from 6 months to 3 months, along with the clear call for more research into understanding PEM as a key part of the classification.

However, I would favour retaining the "orthostatic intolerance and/or cognitive dysfunction" criteria, rather than mandatory/should be present cognitive difficulties per NICE. OI appears to be present in most patients but sometimes not overt to clinicians, as in POTS/OH symptoms and signs. Cognitive dysfunction doesn't seem present in all, although clearly affects very many.

From my own experience to date, it's not a necessary feature. Perhaps I am an outlier (or I don't recognise mild cognitive impairment in myself, for which there is some evidence in LC cohorts).

I wonder how much of cognitive dysfunction is due to cerebral blood flow +/- oxygen transfer issues, rather than primary brain problems such as dysfunctional mitochondria in neurons and glia or neuroinflammation. I suspect the problem is more the former, as things like mitochondrial badness and neuroinflammation might be expected to be progressive over the long term as a neurodegenerative phenotype, which is not obviously the case even in lifelong ME.