Perspective: Drawing on findings from critical illness to explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, by Dominic Stanculescu and  Jonas Bergquist in Front. Med., 08 March 2022 [doi.org/10.3389/fmed.2022.818728]

Abstract:

We propose an initial explanation for how myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) could originate and perpetuate by drawing on findings from critical illness research.

Specifically, we combine emerging findings regarding

(a) hypoperfusion [a reduced amount of blood flow] and endotheliopathy [damage to endothelial cells in the blood vessels] and

(b) intestinal injury in these illnesses with our previously published hypothesis about the role of

(c) pituitary suppression, [pituitary gland does not produce normal amounts of some or all of its hormones] and

(d) low thyroid hormone function associated with redox imbalance in ME/CFS.

Moreover, we describe interlinkages between these pathophysiological mechanisms as well as “vicious cycles” involving cytokines and inflammation that may contribute to explain the chronic nature of these illnesses. This paper summarizes and expands on our previous publications about the relevance of findings from critical illness for ME/CFS.

New knowledge on diagnostics, prognostics and treatment strategies could be gained through active collaboration between critical illness and ME/CFS researchers, which could lead to improved outcomes for both conditions.

Discussion
Hypoperfusion and endotheliopathy, intestinal injury, pituitary suppression, and low thyroid hormone function are each central to prolonged critical illness regardless of the nature of the initial severe injury or infection (101, 173, 195, 196).  We propose that, similarly, these mechanisms and their reciprocal relationships with inflammation could underlie ME/CFS regardless of the nature of the peri-onset event (i.e., infection, stressful incident, exposure to environmental toxins or other). Moreover, the severity of ME/CFS may be a function of the strength of these mechanisms.

However, each of these pathological mechanisms has largely been studied in isolation and rarely have the linkages between them been explored. Yet, the aggregate of these mechanisms is likely necessary to fully explain the perpetuation of critical illness—and to inform the understanding of ME/CFS.

Conclusion
Decades of research in the field of critical illness medicine have demonstrated that in response to the stress of severe infection or injury, the vascular system, intestines, endocrine axes and thyroid hormone function experience profound alterations. Self-reinforcing interlinkages between these pathophysiological mechanisms as well as “vicious cycles” involving cytokines and inflammation may perpetuate illness irrespective of the initial severe infection or injury.

Without excluding possible predisposing genetic or environmental factors, we propose that the pathological mechanisms—and the interlinkages between them—that prevent recovery of some critically ill patients may also underlie ME/CFS.

This initial proposal is in line with and complements several existing hypotheses of ME/CFS pathogenesis. If this hypothesis is validated, past treatment trials for critical illness may provide avenues for a cure for ME/CFS. Certainly, given the similarities described above, active collaboration between critical illness and ME/CFS researchers could lead to improved understanding of not only both conditions, but also PICS, long-COVID, PACS, and fibromyalgia.