ME is considered a neurological illness by the World Health Organisation.
In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic Treatment Protocols, edited by Kenny De Meirleir and Neil McGregor, Carruthers et al wrote, 'Immunological abnormalities, indications of pituitary and hypothalamic involvement, abnormal basal plasma levels of certain neurotransmitter metabolites and cerebral perfusion abnormalities point to central nervous system involvement in ME/CFS.' They go on to conclude: 'It is apparent that a primary target organ of these illnesses is the brain'.
Nakatomi et al (2014) showed inflammation of the brain, including activation of the microglial cells, that correlated with the extent of cognitive difficulties in and pain in ME. These were visible by PET scan. Microglia are thought to be involved in chronic pain.
Finkelmeyer confirmed the white and grey matter changes of earlier studies. The changes were located in the midbrain, brainstem and areas related to processing of interoceptive signals (internal bodily signals, including those from the gut) and stress. The link with the gut is interesting, because the microbiome is a growing area of interest for ME researchers.
Shan found a 'significant decrease in WM volumes in the left inferior fronto-occipital fasciculus', which continued to deteriorate at an abnormal rate.
Barnden et al wrote that brain MRI scans were 'consistent with an insult to the midbrain at fatigue onset that affects multiple feedback control loops to suppress cerebral motor and cognitive activity and disrupt local CNS homeostasis, including resetting of some elements of the autonomic nervous system'. White matter volume was seen to reduce with fatigue duration. There was also evidence of impaired cerebrovascular autoregulation and astrocyte dysfunction.
Puri argued that these 'significant neuroanatomical changes' might be consistent with problems with memory, visual processing and discrepencies between 'intended actions and consequent movements' (apparent clumsiness). Zeineh thought that the distinctive 'right anterior arcuate FA [fasciculus abnormality] may serve as a biomarker'.
Lange (see above) also compared patients with ME with and without psychiatric complaints. Those patients without psychiatric complaints nevertheless had more lesions on the brain than those with psychiatric complaints, and had more than healthy controls. These lesions took the form of 'small, punctuate, subcortical white matter hyperintensities (WHM), found predominantly in the frontal lobes'. WHMs are thought to represent demyelination and axonal loss, as well as endothelial and immune activation, and are a key feature of neurological conditions (including MS). The neurocognitive side-effects of ME (brain fog, balance problems, etc) may be a result of these lesions.
Ichise et al 1992 showed that patients with ME had greater hypoperfusion (reduced cerbral bloodflow) than healthy controls. 80% of patients had this trait, suggesting a possible confirmatory test for ME diagnoses. Hypoperfusion is thought to be a factor in orthostatic intolerance or POTS in ME patients, which is more common in ME diagnostic criteria than CFS criteria.
Brostoff et al 1995 showed that patients with ME and no psychiatric illnesses had greater brain and brainstem hypoperfusion than those with depression, suggesting that this was a characteristic feature of the illness. That study stated that the hypoperfusion in ME had a 'particular pattern' that might be useful for diagnosis. A 1996 study by Fischler et al, found that while hypoperfusion was not significantly different to controls in this study, there was instead a noticeable right to left asymmetry of tracer uptake at parietotemporal level.
A 2000 study by MacHale et al again confirmed that people with ME (who had no concurrent psychiatric diagnoses) had greater hypoperfusion of the brain than patients with depression, although there were some similarities. It's possible that patients without OI/POTS do not have the same problems with hypoperfusion.
Glucose metabolism may be deranged in ME, with decreased neuronal metabolism evident in the brain stem.
The vagus nerve appears to be implicated in autonomic dysfunction according to Morris and Maes (2013). This may support Michael VanElzakker's vagus nerve infection hypothesis.
Cardiac failure is the number one cause of death for ME patients. Maes 2009 suggested this was due to oxidative and nitrosative stress pathways and inflammation.
In Lerner 1993, 24-hour Holter monitor revealed repetitively flat to inverted T waves alternating with normal T waves in 100% of patients with ME. Conversely, only 22.4% of patients without ME had abnormal results, indicating another possible confirmatory test for the illness.
More studies will be added as they become available . . .