Six year study of abnormal brain changes in chronic fatigue syndrome patients


by Sasha Nimmo

An Australian six year study evaluating progressive brain changes associated with chronic fatigue syndrome (Fukuda and Canadian Consensus Criteria definitions) shows patients’ brains deteriorate at an abnormal rate.

The study used optimized voxel based morphometry (VBM), a commonly-used automated tool for studying patterns of brain change in neurological diseases. It shows chronic fatigue syndrome (Fukuda & CCC) is a chronic illness with abnormal connections among brain regions and white matter deficits which continue to deteriorate.

The study, Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study, was published in the Journal of Magnetic Imaging in April 2016.

The authors are from Griffith University’s National Centre for Neuroimmunology and Emerging Diseases and South Australia’s Lyell McEwin Hospital and Royal Adelaide Hospital. Many of this paper’s authors also published a paper about brain connectivity problems causing signalling problems in March 2016.

The six year study looked at the brains of 15 patients and 10 controls and found white matter decreased over time in the CFS patients. It also says hypoxia, which is a deficiency in the amount of oxygen reaching the tissues, could be causing neurodegeneration.

The rate-of-change of regional white matter volumes in CFS patients was significantly different from that in controls in the left posterior part of the inferior fronto-occipital fasciculus (IFOF) and/or arcuate fasciculus. In this location, white matter volume relative to global white matter volume decreased with time in the CFS group while in controls it was unchanged.

This study detected continuing shrinkage of white matter in the left IFOF in patients with CFS, but not in controls. This result was consolidated by the pooled inter group comparisons revealing decreased regional white matter volumes in adjacent regions and decreased GM and blood volumes in contralateral regions and by regression analysis showing significant correlations of white matter and grey matter volumes and T2w intensities with CFS symptom scores in those regions.

The IFOF connects networks of cognitive control, attention, language processing and working memory.

The study may explain symptoms such as impaired concentration, working memory loss, inability to focus vision and poor motor coordination.

This seems to agree with the findings of Boissoneault et al 2005 in the their paper Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study, which said “results demonstrate altered functional connectivity of several regions associated with cognitive, affective, memory, and higher cognitive function in ME/CFS (Fukuda criteria) patients. Connectivity to memory related brain areas (parahippocampal gyrus) was correlated with clinical fatigue ratings, providing supporting evidence that brain network abnormalities may contribute to ME/CFS pathogenesis”.


Chronic functional hypoxia due to dysfunction of the neurovascular unit could also cause neurodegeneration.[34] Of interest, a recent study found seventeen single nucleotide polymorphisms (SNPs) were significantly associated with CFS.[35] Nine of these SNPs were associated with muscarinic acetylcholine receptors and eight with nicotinic ACh receptors (nAChRs). ACh, a neuromodulator in the brain, changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs. Control of synaptic Ca2+ concentration following nAChR stimulation is a major pathway for ACh to influence neuronal networks.[36] Furthermore, nAChRs are also present in the cerebral vascular endothelium and smooth muscles.[37] Thus, aberrant AChR function may impair cerebrovascular autoregulation and cause chronic functional hypoxia.

This study warrants further investigations to understand the pathomechanism of white matter deficits in the IFOF in CFS.

The study was funded by the 

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26 thoughts on “Six year study of abnormal brain changes in chronic fatigue syndrome patients

  1. In terms of the brain issues this is a bit scary. It doesn’t sound easy to solve or reverse.

    The acetylcholine receptors thing is interesting (can’t find many of the SNPs in 23andme data but I had some mentioned in that study). Has anyone done studies comparing us with myasthenia gravis patients?

    1. Following this with great interest. This could be me! Only 54, feel like I’ve had a stroke. Having an Alzheimer’s evaluation later this month at Stanford. So scary, how do we fix this?

      1. Lynna,
        I agree, very scary. Keep a close eye on all neurodegenerative research? I’ll follow up future studies and watch out for an interview with the authors of this paper here soon.
        Thank you for reading and commenting.
        I hope the Stanford evaluation gave you helpful information.

  2. I wonder does the same degenertion happen in people with Fibromyalgia? It is a similar condition.

    1. Hi Patricia,
      I don’t keep a close eye on fibromyalgia research but it would be interesting to know how it compares to it and to other diseases like MS.
      Thank you for reading and commenting,

  3. I’m wondering if patients exhibiting symptoms of Chronic Fatigue Syndrome can send their most recent MRIs to someone doing this research to determine if we are having these same issues.

    1. Pat, that would be interesting to know. Please let us know if you find out.
      It would be especially interesting if we had MRIs from before the illness to compare.
      Thank you for reading and contributing.

  4. I have been diagnosed with CANVAS and desperately looking for someone that is studying this syndrome. No one seems to know anything about it.

    1. I”m sorry, I don’t know much about CANVAS. It does sound like it shares some symptoms with ME. Best of luck with your search, and your health, and if I come across anything I will let you know.

    2. I”m sorry, I don’t know much about CANVAS. It does sound like it shares some symptoms with ME. Best of luck with your search, and your health, and if I come across anything I will let you know.

  5. i have M.E -post viral g93.3 this article applies to me but it so disappoints myself and so many other well read sufferers that those letters CFS creeps into print it simply isnt the same illness

    1. Geoffrey,
      You make an excellent point about the language that Australian researchers use, especially here where the Australian CFS guidelines bear little relation to ME.
      Writing about research, I quote their study but I will consider my language as well in future articles. I’m always interested in readers’ views. Thank you.

  6. This really frightens me! I have had ME/CFS for 22 years, & one of my many symptoms is constant headache & feeling of burning/inflammation of my brain. Occasionally I wake up with migraine type headaches. Something is going on in my head (& it hurts). I would like to ask my doctor for a brain scan, but which is the best type to have which will show what is happening in there? Something is definitely wrong in that area with me. Any advice will be much appreciated.

    1. Jacquie, My 20 yr old has been sick 8 years. Her symptoms of headaches, at times very severe in th eback of her hear tuened out to be a spinal fluid leak. A blood patch was done with positive results. She still has CFS, but the headaches are much improved.


  7. iv suffered alone over 15 years with CFS . this could just kill me one day and the drs i seen that never cared to do tests or support me. so ill keep suffering alone. shirallee south australia

  8. I still wonder if a hyperbaric oxygen study might be useful since preliminary results in Turkey in 2012 look promising, but need larger, longer term study. Need philanthropic funding to fund this and other ideas, since 17 million worldwide need cures,

  9. I found many years ago, a specialist found delta waves while I am awake. Normally delta waves are sleep waves? Unfortunately he moved to Canada, so no one else has tried. Any answers please, 34 years of M E and Fibromyalgia and back injury trapped sciatic nerves bilateral and in my shoulder in 1994.

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