CFS/ME Pathophysiology

The mechanisms and processes (pathogenesis) of Chronic Fatigue Syndrome are gradually being revealed through research, including physiological and epidemiological studies. In a basic overview of CFS for health professionals, the CDC states that "After more than 3,000 research studies, there is now abundant scientific evidence that CFS is a real physiological illness."^[

Chronic fatigue syndrome (CFS) or (ME) has been described in a 2008 Toxicology journal article as, "a constellation of multi-system dysfunctions primarily involving the neurological (nervous system), endocrine (hormone system), and immune systems." The article states recent research suggests the potential that xenobiotic (chemicals), infectious agents, stress, and other insults in early life may be a component of later-life CFS.

A 2007 article in the journal Autoimmunity summarised; “The current concept is that CFS pathogenesis is a multi factorial condition in which an infective agent cause an aberrant immune response characterized by a shift to Th-2 (cytokine) dominant response. When the response fails to be switched-off, a chronic immune activation occurs and is clinically expressed in the symptomatology of CFS".

In a 2006 update in the journal Curr Opin Psychiatry it was said; “Recent advances in understanding the pathophysiology of chronic fatigue syndrome continue to demonstrate the involvement of the central nervous system. Hyperserotonergic state and hypoactivity of the hypothalamic-pituitary-adrenal axis (HPA axis) constitute other findings, but the question of whether these alterations are a cause or consequence of chronic fatigue syndrome still remains unanswered.” Alterations in serotonin signaling can lead to physiologic and behavioral changes. A 2008 study of gene polymorphisms indicates genetic predisposition possibly resulting in enhanced activity of serotonin may be involved in the pathophysiology of CFS.

Chronic fatigue is a typical symptom of neurological diseases, including chronic fatigue syndrome, is also seen in diseases that affect the central, peripheral, and autonomic nervous systems (central fatigue). Enhanced perception of effort and limited endurance of sustained physical and mental activities are the main characteristics of central fatigue. Metabolic and structural lesions can cause muscle fatigability (peripheral fatigue) also disrupt the usual process of activation in pathways interconnecting the basal ganglia (peripheral nerves), thalamus, limbic system, and higher cortical centre are implicated in the pathophysiological process of central fatigue. A state of low cortisol might sensitize the hypothalamic-pituitary-adrenal axis (HPA axis) to development of persistent central fatigue after stress.

Chronic Fatigue Syndrome (CFS) is a disorder whose etiology and pathogenesis are still unknown. In this syndrome both abnormalities of nervous and immune systems have been reported. Nervous and immune systems mutually cooperate via release of mediators of both neurological and immunological derivation. Hormone (ACTH) is a product of the HPA axis which stimulates secretion of corticosteroids from adrenals. In turn, corticosteroids modulate the immune response by virtue of their anti-inflammatory activity. On the other hand, catecholamines, products of the sympathetic nervous system (SNS), regulate immune function by acting on specific beta-adrenergic receptors. Conversely, cytokines released by certain immune cells, upon stimulation, are able to cross the blood-brain-barrier, thus modulating nervous functions (e.g., thermoregulation, sleep, and appetite). However, cytokines are locally produced in the brain, especially in the hypothalamus, thus contributing to the development of appetite, thermoregulation, sleep and behavioural effects. In addition infections/pathogens and/or their products, the so-called stressors are able to activate both HPA axis and SNS, thus influencing immune responses.