There are good reasons for thinking that central nervous system pathology is important in ME/CFS, and some indications that inflammation of the brain (neuroinflammation) might be involved. However, proving the existence of neuroinflammation requires specific neuroimaging methods, and these had never been applied to ME/CFS patients – until Japanese researchers bit the bullet.
The team at Osaka City University in Japan, which has been studying ME/CFS for many years, have used PET imaging to try to obtain direct evidence of neuroinflammation. In essence, they measured the density of the ‘translocator protein’ (TSPO) produced when certain brain cells are activated – it’s the activation of these cells which indicates that inflammation is taking place. In this case, the brain cells were microglia (thought to be the main form of active immune defense in the central nervous system) and astrocytes (the most numerous brain cells, with functions including nutrient supply, repair, and nerve impulse transmission). The researchers recruited 9 people with ME/CFS (Fukuda 1994 and ME-ICC 2011 definitions) and 10 healthy controls, who underwent PET scanning involving the injection of a tracer followed by dynamic scanning over 60 min. Participants also completed questionnaires about symptoms, including fatigue, pain, and neurocognitive problems.
Their report in the Journal of Nuclear Medicine reveals that protein levels (indicating inflammation) were higher in ME/CFS patients than controls in “widespread brain regions”, including the cingulate cortex (199% higher), hippocampus (81%), thalamus (66%), midbrain (47%), and pons (45%). And, intriguingly, protein levels in some brain regions were significantly associated with the severity of particular symptoms; some of these associations were quite striking (despite the small number of patients), as in the correlation between protein level and cognitive impairment scores (r=0.94, p<0.0002).
The authors conclude that “neuroinflammation is present in widespread brain areas” in ME/CFS patients compared with healthy people. As they point out, this may be due to an immune response to an underlying infectious process, or possibly to over-activation of nerve cells (for whatever reason). There are several things to bear in mind, however. First, numbers are small (in essence, this is pilot data), and would need replication – one swallow doesn’t make a summer, and one scientific report does not convince, though it might fascinate. Second, protein levels were relatively low in absolute terms, raising intricate methodological issues associated with standardization in PET imaging. The authors are to explore this particular aspect in the next phase of their work on ME/CFS patients, an international collaboration study that will use a different, second-generation tracer and have a refined methodology. Lastly, inflammation (as measured with PET imaging from higher-than-normal translocator protein density, as in this report) occurs in many conditions. Similar PET findings have been reported in patients with brain injury, cancer or peripheral inflammation, as well as in more chronic inflammatory conditions like Parkinson’s and MS (see the 2011 review ‘The Translocator Protein’). So, the importance of this study is probably not that the evidence of inflammation is ‘specific’ to ME/CFS, but that it has been demonstrated so clearly. For instance, these results will have come as a surprise to anyone – including some healthcare professionals – sceptical about the ‘reality’ of the illness.
If these dramatic and fascinating results can be reproduced, objective evidence of an inflammatory process in the brain of people with ME/CFS may become readily available for incorporation into diagnostic protocols and for treatment-monitoring purposes, with enormous consequences for patients and their families.
Toward a clearer diagnosis of chronic fatigue syndrome (press release for the paper)
First Direct Evidence of Neuroinflammation (Phoenix Rising site)
Baffling Chronic Fatigue Syndrome Set for Diagnostic Overhaul (Scientific American)