Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia, 2017, Natelson et al

Paywalled at http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1280114?journalCode=rftg20

Study is from Feb 2017 but Solve have just posted a review of it:

http://solvecfs.org/elevations-of-v...th-chronic-fatigue-syndrome-and-fibromyalgia/

 

This seems to me exactly the sort of methodology people should be using. MRI spectroscopy is a hugely powerful tool for looking at in vivo metabolism in whole organs. It would be interesting to know what the levels were in the brain tissue itself.

I am surprised we have not had discussion of this before if it is from nearly a year ago. I don't remember it. It is a pity they do not give any figures. Why do papers not give numbers in the results section any more?

 

Mostly to force people to buy access to the full paper I suppose Though in this study they were combining results coming from different methods and using different scales. So instead of having numbers, we have z-scores.

More generally, they used Fukuda, and it looks like they combined data from an earlier study with new data. So some comparison groups had lactate measured via different methods. Some analyses were post-hoc.

I'd love to see this replicated with a criteria requiring PEM, and everyone having lactate measured in the same way in the same time frame, with the researchers being blinded.

 

What does that mean, elevated lactate levels in the brain (e.g. consequences, causes...)? How does that show on brain scans? Why is MRI spectroscopy such a good method? And how does this fit into other findings, like that by Fluge and Mella (-> pyruvate dehydrogenase)? How should it be used as a biomarker if the authors say it cannot, since they couldn't differentiate ME from FM? And why is this a good finding (compared to others)?

 

Elevated lactate either in brain tissue or CSF would indicate a metabolic shift actually happening all the time in the brain in ME. That may not be saying anything very specific about what the shift is due to or what its consequences are but it would be hugely important to understanding what sort of problem we are dealing with.

MR (without the I for imaging) spectroscopy is powerful because it gives direct evidence of altered metabolism in cells actually in real life circumstances. fMRI can do this for oxygen uptake in sufficient detail to give an image of variation from place to place within brain tissue but imaging only works for a very few metabolites. MR spectroscopy has been around much longer and allows you to pick up signals for a huge range of metabolites, but only if you sample quite large areas. So rather than getting picture you set your sensor to measure from an area you know to be ventricle fluid or brain and you get a single number out.

This sort of approach ugh to be particularly good for muscle, because it would allow you to measure levels of a series of metabolites in a whole muscle, like quadriceps and work out where any block metabolism was. This ought to be much better than taking muscle biopsies or measuring white cells in blood samples because it would be measuring the tissue functioning in real life. I think MR spectroscopy must have been done on muscle by people like David Jones and Richard Edwards in ME ten or twenty years ago but I have never been able to pin down exactly what was found.

Findings in brain would be of particular interest. Having read the full paper my impression is that this study was not done with the thoroughness one would like. As Valentijn says they seem to have cobbled together two lots of data on not that many cases and only reported one area. If brain was not metabolising properly I would expect the lactate in the brain itself to be abnormal. The ventricles are really the drains of the brain and might show 'waste levels' but I would like to know how that relates to brain itself.

Looking at the scatter plot against BMI one can see the spread of data. What becomes clear there is that the differences between individual ME subjects and controls for lactate are not big enough to allow this to be used as a clinical marker. There is huge overlap. The findings are purely statistical. It might be that there is an identifiable subset of people with ME who are consistently above normal but that would need further testing and analysis.

 

Would it not be better to test during flares?

 

Should 'ugh' be 'ought'?

 

Thank you, @Jonathan Edwards!

Why is it a problem to use data at different points of time (they used data from a previous study and added new data and compared that again) if they are normalized/standardized?

That was my impression, too. Good to have that confirmed.

 

I went on a research project for something else and had an fmri and meg done but never got the results unfortunately,just a souvenir mri

 

It weakens the controlled aspect, since having controls tested at the same time and in the same manner can indicate if there was a problem or major difference due to the specific equipment or procedures used.

 

But in this case, there were no major differences between CFS, FM and CFS+FM (which reproduces the previous finding), and the differences between CFS/FM and the healthy controls seem to be comparable (i.e. coharent with the previous study). Right? Would this be an indicator that the different points of time of data collection aren't a big problem?
In which way does this affect the quality of the study?

 

The real problem with combining sets of results taken at different times rather than asa single prospective study protocols that it is much more likely to lead to cherry-picking. It is very easy to forget that a first study showed an interesting result, a second study showed nothing (and was forgotten about) and then third study showed the samosa the first.Add the first and third results and you can get 'statistical significance' when neither orbits own would give you that. I amanita suggesting this was done but it is all too easy to cherry pick in science and the way to stop oneself from doing that is to make sure studies are done prospectively and systematically.

 

Tell us more about the samosa.

 

Never had an orbiting samosa with amanita sauce before? Quite a square meal.

 

Full of cherries, obviously a new fusion dish

 

That's a good point, @Jonathan Edwards, thank you

 

But it's presumably an important step to be able to distinguish PwME and PwFM from healthy controls, even though it does not distinguish them from each other.