my hypothesis

Hi, how would that explain M.E without POTS or NMH? Just curious for you to expand. Some of your hypothesis went over my head im afraid.

Sounds plausible, but how would it explain the well documented immune dysregulation/dysfunction. I know there is a lot of interaction between the CNS and immune function but could it explain reduced NK activity etc. There seems to be a fair amount of evidence that supports your hypothesis, but I'd be interested to see how you think it ties in with the Rituximab findings, specifically the wiping out of B-cells resulting in temporary remissions.

Thanks for the responses.
Justy - Some may not fit any of these catagories and there will be patients with very different problems that have been all put into the same basket.

However, I would explain ME symptoms without measurable POTS or NMH as small blood vessel disfunction and or parasympathetic withdrawal with alterations in cerebral autoregulation without profound effects on peripheral blood pressure or heart rate. So just another face of the same condition. And there is some evidence that small vessel abnormalities, perhaps altered vasodilatory responses and cerebral autoregulation can be impaired in patients without clear signs of POTS or NMH. Patients will still have reduced cerebral blood flow and signs of circulatory collapse.

Vitalic - many patients with ME, POTS and NMH have obvious signs of innate immune system activation. I think this is part of the autoimmune/inflammatory process. The immune system - perhaps due to histocompatibility or genetics either cannot get rid of a pathogen or is tricked by proteins from that pathogen or bacteria to start attacking self. Chronic innate immunity results in chronic activation of pro-inflammatory cytokines and feelings of flu and sickness, but does nothing to attack the pathogen. Meanwhile, autoantibodies or perhaps even some parts of the inflammatory process are deranging postural circulatory control and/or autonomic function.

Cytokines have significant effects on CNS function. Many pro inflammatory molecules have potent vasoactive effects - vasodilatory or opposite.

Rituximab fits perfectly into my paradigm. It has been used successfully to place refractory cases of Myasthenia gravis into remission - where similar autoantibodies to those identified in some cases of POTS (IE just different location of nicotinic acetylecholine receptors - muscular v a3 autonomic). The Rituximab finding supports an autoimmune etiology in at least some cases. As does the presentation - 80% female, onset acute or subacute after major stressor event, waxing and waning presentation in many.

I like your theory on the etiology of CFS. Makes sense. I have 3 diagnosed autoimmune diseases (celiac, Graves', Hashimoto's). Would not be surprised at all to find out in the future that CFS is an autoimmune disease.

One explanation of CFS without POTS (that is low blood pressure, right?) is that the person with CFS had low blood pressure in the past but is now older and has higher blood pressure due to age. Perhaps they used to have POTS but never got it diagnosed and now have high BP. I think that's what's going on with me.

We are still left with the question of what causes autoimmune diseases. I personally believe that it is because we (humans) have taken ourselves out of the evolutionary process and no longer are subject to "survival of the fittest". Medical technology saves the lives of babies/children who would normally die of various diseases/infections or trauma. Basically, I think people like myself, with CFS, were supposed to die in childhood. I know I had infection after infection when I was a kid. Any one of them could have killed me without medical intervention. I also had a lot of emotional stress due to a totally dysfunctional family. Probably, the emotional stress is why I had all the infections, but regardless, the end effect is that I am not fit to survive. Whether it's genetic or damage from chronic stress, my body simply can't handle the everyday stress of life.

Sadly, I believe that if we let sick children die and prevented sick adults from reproducing, the human race would be much healthier overall and perhaps free of CFS. Because we don't do that, I think that makes modern medicine and civilization the cause of CFS. There's no chronic illness in the wild. Just something to think about.

That being said, I hope we find a cure! You gotta love irony.