Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Metabolic Disease or Disturbed Homeostasis? by Erifili Hatziagelaki, Maria Adamaki, Irene Tsilioni, George Dimitriadis and Theoharis C Theoharides in Journal of Pharmacology and Experimental Therapeutics August 3, 2018, jpet.118.250845

Research article abstract:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease characterized by debilitating fatigue, lasting for at least 6 months, with severe impairment of daily functioning and associated symptoms. A significant percentage of ME/CFS patients remains undiagnosed, mainly due to the complexity of the disease and the lack of reliable objective biomarkers.

ME/CFS patients display decreased metabolism and the severity of symptoms appears to be directly correlated to the degree of metabolic reduction that may be unique to each individual patient. However, the precise pathogenesis is still unknown preventing the development of effective treatments.

The ME/CFS phenotype has been associated with abnormalities in energy metabolism, mostly with mitochondrial dysfunction, resulting in reduced oxidative metabolism. Mitochondrial dysfunction may be further contributing to the ME/CSF symptomatology by extracellular secretion of mitochondrial DNA, which could create an “innate” inflammatory state in the hypothalamus, thus disrupting normal homeostasis.

We propose that stimulation of hypothalamic mast cells activates microglia leading to focal inflammation in the brain and disturbed homeostasis.