Limbic kindling vs. central sensitization in ME.

I don’t believe in the trem “ME/CFS” any more. I know I wrote a post about previously, but I was still a newbie. There is a disease called Myalgic Encephalomyelitis (ME), which is diagnosed by the International Consensus Criteria. It always involves the appearance of neurological symptoms (Post-Exertional Neuroimmune Exhaustion) shortly after exercise. These symptoms may or may not include fatigue.

Chronic Fatigue Syndrome (CFS) is characterized by severe fatigue, which may or may not be exacerbated by exercise. It is not a disease, it is a syndrome, a cluster of symptoms. I maintain that it is a result of any one of 200 undiagnosed autoimmune diseases.

ME and CFS should not be combined. They are opposite in important ways.

Would you believe I never saw this research by Leonard Jason (and Jason’s paper) before now. I don’t read ME/CFS research at all. I go by symptoms, what has happened to me, and how they relate to other diseases.

But I got the same general outline of ME as he does with ME/CFS. He has the idea of limbic kindling in the limbic cortex. I have central sensitization in the limbic cortex.

He has the movement towards Th2 dominance (T-helper cells that promote allergy, not autoimmunity), because Th1 is downregulated, like I do. But for me, this is due to the initial viral infection (enterovirus, EBV, HHV-6 etc. which downgrade Th1) and radioactive toxins promoting TGF-beta, which also downgrade Th1. He has overactivity in the pituitary doing it. My pituitary is trashed, and all it was doing was spitting out prolactin and TSH from a pituitary tumor. Everything else was underactive.

They mention leaky gut. This is caused by anti-inflammatory TGF-beta wiping out Th22 cells.

Jason talks about increased NMDA receptor activity. But this is because of an increase in the number of NMDA receptors, not an upgrade in the activity per cell. And glutamate and GABA have to be created for all these cells, and the body robs alpha-ketoglutarate from the Krebs cycle to power them, reducing ATP in the mitochondria. There’s not enough of anything to go around with all these neurons sprouting.

He doesn’t have an explanation for post-exertional neuroimmine exhaustion, which results from TGF-beta being released from muscles 24 hours after exercise, which reduces follistatin levels, weakens muscles, leads to fibrotic tissue replacing muscle fiber, and further reduces Th1. This is key.

And of course nothing about reduced IDO, which is a straight-up inference from depleted Th1, which reduces catabolism of tryptophan and leads to disturbances in the kynurenine pathway (a classic neurological effect), and too much serotonin. Insulin delivers tryptophan to cells, and is part of the disease process. He acknowledges high serotonin levels without giving the reason, or mentioning that this might lead to the central sensitization in the first place, where too many neurons are produced. Serotonin receptors also give off more TGF-beta.

Since the neurons connect to a place in the hippocampus that involves the default mode network (DMN), and there is not enough GABA, the brain cannot switch out of the resting state to perform tasks, or multitask. This leads to paralysis is severe ME.

Since the publication of the ICC in 2011, Jason has published studies using the ICC, to his credit. And his research (along with Maes) is better than the run-of-the-mill ME/CFS quackery. But we need experts in internal medicine, neurology, and immunology involved in ME research. Most of all, we need to abolish the ME/CFS label, which contaminates studies with heterogeneity, and causes harm to ME patients.

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