frontiers in Medicine - Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for ME/CFS - Stanculescu, Bergquist et al

Frontiers in Medicine - Infectious Diseases - Surveillance, Prevention and Treatment
Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
by Dominic Stanculescu, Lars Larsson and Jonas Bergquist

We here provide an overview of treatment trials for prolonged intensive care unit (ICU) patients and theorize about their relevance for potential treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these treatment trials generally target: (a) the correction of suppressed endocrine axes, notably through a “reactivation” of the pituitary gland's pulsatile secretion of tropic hormones, or (b) the interruption of the “vicious circle” between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. There are significant parallels in the treatment trials for prolonged critical illness and ME/CFS; this is consistent with the hypothesis of an overlap in the mechanisms that prevent recovery in both conditions. Early successes in the simultaneous reactivation of pulsatile pituitary secretions in ICU patients—and the resulting positive metabolic effects—could indicate an avenue for treating ME/CFS. The therapeutic effects of thyroid hormones—including in mitigating O&NS and inflammation and in stimulating the adreno-cortical axis—also merit further studies. Collaborative research projects should further investigate the lessons from treatment trials for prolonged critical illness for solving ME/CFS.

 

Dr. Geraghty comments on Twitter:
I said I would share this paper for someone, some novel ideas about how to think about ME-CFS in this, not sure about everything here - one doesnt normally think of ME-CFS and ICU, interesting to have others looking at ME-CFS from different perspectives

 

The more I look at this paper, the less I know what to make of it. HPA axis* dysfunction and oxidative & nitrosative stress are (very) old ideas for the etiology of MECFS. Most of the treatments proposed in the paper - DHEA, NAC, and NADH, for instance - are known quantities. Yet MECFS is still here! I'm also unsure about the causal relevance of pathology overlap between ICU critical illness and MECFS. O&NS is such a non-specific finding, and as far as I know, the idea of HPA axis dysfunction in MECFS is, and has always been, contentious. But perhaps the devil is in the detail and there is value in clinical studies of e.g heat shock proteins and GH-releasing hormone for ME, as the paper suggests.

Also, I have to ask. This isn't a lead author n=1 recovery experience with a theory paper built on top of it, is it?

 

Here's an n=1 comment though. As far as the HPA axis is concerned, while I was in hospital with various sepsis/liver abscess investigations going on, they decided to bump up my steroids from 10mg of prednisolone to 30mg.

It was like coming out of a dark cellar into the warm summer sunshine. Suddenly my brain was back where it was, able to juggle ideas around and think things through. I can't answer for physical prowess, as I was pretty done in. But, even though I couldn't read or write much (my son sent me in some sheets of black paper and a chalk-type pen), I was playing around with Fermat's last theorem and some geometric ideas that I had. It was amazing.

So why does a boost of steroids have such an amazing effect on my mental processes? That baffles and frustrates me. Especially as it only lasted a week, as they tapered the dose back down to my usual 10mg.

I think the doctors were quite stunned when I suddenly was able to take a much more active part in their discussions, dredging up all sorts of relevant studies that they clearly didn't know about. It probably did more for their understanding that ME was not psychological than anything I had previously tried.

 

Just a wild guess, but if the researchers who think neuroinflammation is a part of the picture are correct - could it be that the steroids temporarily lowered the immune activation in the brain, thereby restoring more of the normal function?

From what I understand, some researchers (e.g. Younger and Komaroff) thinks there might be a constant level of low grade neuroinflammation/immune activation in the ME brain, that could impair cognition and various other mental processes.

 

According to Cort Johnson oxidative stress has been one of the most (if not the most) consistent biological findings in ME-patients, found by the research groups who have looked for it, so I definitely think it's an interesting aspect to take into consideration. And it seems probable that it is part of the puzzle, although I personally think it might be a downstream effect rather than the central cause.

In ME-research, so many results have been found once or a few times, and then it seems difficult to replicate them, so to me it makes sense to focus on what's been easy to replicate.