Using structural and functional MRI as a neuroimaging technique to investigate CFS/ME. Almutairi et al. 2020

[John Mac]

Full title: Using structural and functional MRI as a neuroimaging technique to investigate chronic fatigue syndrome/myalgic encephalopathy: a systematic review.

Authors: Basim Almutairi, Christelle Langley, Esther Crawley, Ngoc Jade Thai

Abstract
Objective This systematic review aims to synthesise and evaluate structural MRI (sMRI) and functional MRI (fMRI) studies in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

Methods We systematically searched Medline and Ovid and included articles from 1991 (date of Oxford diagnostic criteria for CFS/ME) to first April 2019. Studies were selected by predefined inclusion and exclusion criteria. Two reviewers independently reviewed the titles and abstracts to determine articles for inclusion, full text and quality assessment for risk of bias.

Results sMRI studies report differences in CFS/ME brain anatomy in grey and white matter volume, ventricular enlargement and hyperintensities. Three studies report no neuroanatomical differences between CFS/ME and healthy controls. Task-based fMRI investigated working memory, attention, reward and motivation, sensory information processing and emotional conflict. The most consistent finding was CFS/ME exhibited increased activations and recruited additional brain regions. Tasks with increasing load or complexity produced decreased activation in task-specific brain regions.

Conclusions There were insufficient data to define a unique neural profile or biomarker of CFS/ME. This may be due to inconsistencies in finding neuroanatomical differences in CFS/ME and the variety of different tasks employed by fMRI studies. But there are also limitations with neuroimaging. All brain region specific volumetric differences in CFS/ME were derived from voxel-based statistics that are biased towards group differences that are highly localised in space. fMRI studies demonstrated both increases and decreases in activation patterns in CFS/ME, this may be related to task demand. However, fMRI signal cannot differentiate between neural excitation and inhibition or function-specific neural processing. Many studies have small sample sizes and did not control for the heterogeneity of this clinical population. We suggest that with robust study design, subgrouping and larger sample sizes, future neuroimaging studies could potentially lead to a breakthrough in our understanding of the disease.

https://bmjopen.bmj.com/content/10/8/e031672

 

[TiredSam]

Next up is a systematic review of using structural and functional MRI as a neuroimaging technique to investigate pervasive refusal syndrome.

 

[lunarainbows]

Wait why is Esther Crawley interested in doing imaging of brains of PwME? That’s not what she usually does?

 

[TiredSam]

Perhaps she's adding another string to her bow, or another pie to her fingers.

 

[alex3619]

Does failure to find a unique neuroimaging profile of ME imply that this is secondary to the real problems? (Ignoring possible issues with cohort selection.)

There is evidence that there are problems with neuronal metabolism, and that is looking very likely to be the major issue here. If there is pervasive nerve and support cell metabolic derangement, then it could be expected that the abnormalities are more distributed and harder to profile.

 

[Trish]

Wait why is Esther Crawley interested in doing imaging of brains of PwME? That’s not what she usually does?

Perhaps the imaging department at Bristol want her to provide patients for an imaging study, so she gets to put her name on the preliminary systematic review that says more research is needed, to justify asking for funding.

 

[lunarainbows]

There is evidence that there are problems with neuronal metabolism

This is interesting - what do you mean?

 

[NelliePledge]

Perhaps she's adding another string to her bow, or another pie to her fingers.

Or a sign she’s waking up and smelling the coffee and has decided to change horses midstream

 

[rvallee]

Wait why is Esther Crawley interested in doing imaging of brains of PwME? That’s not what she usually does?

Gotta pretend to do some "bio" is my guess. Which it isn't really, doing a review of bio stuff is not doing bio stuff but then again, BPS is all pretend so it's fitting.

 

[alex3619]

This is interesting - what do you mean?

There are a number of lines of evidence, including the recent paper showing low CO2 in the brain and possibly ubiquitous orthostatic intolerance. Here is the review by Cort, but I have not read the original paper so its hard to comment. Further we have two studies showing something in the blood that is dampening energy production, one of which is about mitochondria, including the nanoneedle findings at Stanford. Neurons are very vulnerable to low energy states, they require a lot of energy to function properly. Then there was the Komaroff study some years ago, showing that the timing of neural connections was in disarray, and that there was additional neuronal recruitment. Its a highly cited study but I would have to go looking to find the reference. Finally we have the invasive CPET finding of high 02 in the returning venous blood ... this implies its not being used. Under normal conditions neurons are very oxygen hungry.

On a personal note I had an HMPAO scan of my brain metabolism in the 90s, and it was low. This was when I was still cognitively functional enough to be starting my PhD, before my first big crash. Please note that this scan was for tagged glucose, and if our brains are preferentially burning other fuels due to derangement then this might not be that atypical for us.

Nothing is conclusive right now, but the evidence of abnormal brain metabolism is growing. I think a few of our researchers are now doing studies that might show more, but we have to wait for publications in due course.

 

[Mithriel]

Note she does not consider that they problems with the studies could be the wide ranging definition used so the patients are not homogeneous.

I worry that she is taking a leaf out of the FND book. They have used dodgy research to show that FND is not a disease of exclusion but can be positively diagnosed using specific signs and tests so bringing it into the medical domain. This is a frightening development as it makes it harder to fight the diagnosis and show it for the rubbish it is.

 

[Ravn]

There seems to be a fashion for systematic imaging reviews. Here's a similar one (link below). Both conclude current studies are too few, too small and too varied to draw any firm conclusions.

Only one of the reviews feels the need to repeatedly point towards the one study that claims to have found that CBT changes the brain. No prize for guessing which review that was.

To be fair, the review wasn't quite as bad as I feared it would be after I saw the name EC. Maybe the other authors were trying to do a decent job of it but were reliant on EC to get the funding/get it published so they had to make some concessions to her like the CBT changes the brain thing?

The other review is this one:

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review; Shan et al

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02506-6

https://www.s4me.info/threads/neuro...fs-a-systematic-review-shan-et-al-2020.16633/

edit: grammar

 

[adambeyoncelowe]

Sometimes names are just on the paper because they helped out. E.g., with recruiting patients.