Evidence of widespread metabolite abnormalities in ME/CFS: assessment with whole-brain magnetic resonance spectroscopy (2019) Younger et al.

[Simon M]

Brief commentary

An interesting approach to studying "neuroinflammation“ yields only one robust finding.

Jarred Younger is looking for evidence that would support hypothesis that ME/CFS is driven by low-grade immune activation in the brain. It's an interesting approach using widely-available, affordable Magnetic Resonance Spectroscopy (MRS) technology to study metabolites and temperature as markers of neuroinflammation.

However, the study is very small (N =15) and looks at many areas of the brain (at least 47), making it prone to finding false positives. After the authors had made appropriate statistical corrections for the large number of comparisons (to control the risk of false positives, only a single finding proved significant between patients and controls. This was higher levels of the metabolite choline in the left anterior cingulate.

No other findings were significant for choline or any of the other three metabolites, or for temperature differences.

Fatigue levels did not correlate with choline levels.

The paper says that the anterior cingulate has been noted "as a critically important region mediating cytokine-induced fatigue and mood deterioration".

The paper speculates about the many other results that were significant at P <0.05, but were not significant after correction for multiple comparisons. But it also cautions against "over interpretation until results can be confirmed in an independent sample".

The authors also points out that neuroinflammation is not the only possible explanation for any changes in temperature or metabolite concentrations.

Even so, if the results are backed up by larger studies in future, this approach could prove extremely valuable in studying the role of the brain in mecfs.

 

[alex3619]

looks at many areas of the brain (100+), making it prone to finding false positives.

Correct, but incomplete. If I am understanding this right, these were contiguous areas. Such studies prove nothing, but they give us the data to design better studies with larger samples.

Contiguous areas increase the chance these findings are right. Its not like random spots all over the brain, which would be an indication the findings are due to chance.

 

[FMMM1]

I had an MRS done late last year to look for elevated lactate and I haven't seen the actual report but according to the metabolic specialist it didn't show anything abnormal. Does anyone know if even if they're looking for a specific metabolite like lactate do these scans also report on other metabolites? I wonder if the differences shown in the study are statistically significant when compared against controls but might still be within normal range for an MRS done in a clinical setting?

Haven't read this paper so these are just random thoughts. Some statistics relate to group comparisons so they say whether the control group was significantly different from the test (ME) group. I'd be interested in whether this test is good enough to diagnose people; presumably by demonstrating inflammation (temperature).

If this is readily transferable to a hospital then possibly we could see a diagnostic test and a way to evaluate treatments.

I'm not sure that this is transferable to every MRI scanner I guess sensitivity could be an issue.

I'm guessing that lactate has a specific resonance frequency so if your test used that frequency then presumably there's data for lactate. There's a guy in Hanson's lab who's worked on lactate for years; you might find one of his papers and that will give you an idea. There's a limited range of "other" metabolites that guy published (possibly an anti-oxidant called GPX); MRI doesn't pick up a lot of metabolites. To use MRI you need a strong magnetic signal (resonance) and a high concentration - not much fits that.

It's late and I'm tired.