Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla, 2021, Godlewska et al

[Andy]

Abstract

Rationale
Chronic fatigue syndrome (CFS) is a common and burdensome illness with a poorly understood pathophysiology, though many of the characteristic symptoms are likely to be of brain origin. The use of high-field proton magnetic resonance spectroscopy (MRS) enables the detection of a range of brain neurochemicals relevant to aetiological processes that have been linked to CFS, for example, oxidative stress and mitochondrial dysfunction.

Methods
We studied 22 CFS patients and 13 healthy controls who underwent MRS scanning at 7 T with a voxel placed in the anterior cingulate cortex. Neurometabolite concentrations were calculated using the unsuppressed water signal as a reference.

Results
Compared to controls, CFS patients had lowered levels of glutathione, total creatine and myo-inositol in anterior cingulate cortex. However, when using N-acetylaspartate as a reference metabolite, only myo-inositol levels continued to be significantly lower in CFS participants.

Conclusions
The changes in glutathione and creatine are consistent with the presence of oxidative and energetic stress in CFS patients and are potentially remediable by nutritional intervention. A reduction in myo-inositol would be consistent with glial dysfunction. However, the relationship of the neurochemical abnormalities to the causation of CFS remains to be established, and the current findings require prospective replication in a larger sample.

Open access, https://link.springer.com/article/10.1007/s00213-021-05986-6

 

[ME/CFS Skeptic]

The authors write:

As far as we are aware, there are no published MRS studies in CFS patients using ultra-high-feld (7 T) approaches;

So this could have been rather interesting. Unfortunately, these authors from Oxford University used the Fukuda criteria (10/22 patients were taking antidepressants) and they focused on a brain region (the pregenual ACC) because of their previous work on depression.

They write:

We chose this voxel because we have carried out previous MRS work in this brain region in patients with depression (Godlewska et al. 2018) whom we thought would form a useful comparison group for patients with CFS, many of whom have depressive symptoms. Also, the pgACC has potential relevance in the pathophysiology of CFS. It is involved in emotional and cognitive processing, and its function is crucial for associative processing requiring integration of various levels of information. It is a critical area for many of the mental functions shown to be disturbed in CFS, such as ability to evaluate and respond to bodily sensations, experience of the body state, pain inhibition, and cognitive processes, such as sustained and selective attention.

So I'm a bit concerned that they might have focused their powerful MRI imaging on the wrong area because of their model and views of CFS.

Nonetheless, the lower levels of myo-inositol levels in patients could be interesting as it might be related to the functioning of glial cells.

 

[DokaGirl]

Is there scientific evidence that pwME have "disturbed mental function" in: "evaluating bodily sensations, experience of the body state, (and) pain inhibition?

Do the authors mean this in a physiological sense, or just a functional somatic syndrome sense?

The belief that pwME intensely focus on symptoms is highly questionable.

Many pwME are working as hard as they can. We have to ignore symptoms such as OI to get things done. For example shopping and waiting in line. Symptoms of faintness and weakness have to be coped with somehow in order that pwME can get their groceries. All other activities of daily living have to be dealt with the same way. With shear determination.

 

[Kitty]

Is there scientific evidence that pwME have "disturbed mental function" in: "evaluating bodily sensations, experience of the body state, (and) pain inhibition?

It's a difficult one to pin down, as it can just mean that our brains are giving us duff information. We get bulletins telling us that we're too hot / too cold/ in pain, even though there's no physiological reason for those signals to be sent. It doesn't make the sensations any less uncomfortable, though, and there's little we can do to stop the signals. A goodly proportion of healthy women find that their thermostats and pain sensors go totally off-piste around the menopause, so it's hardly uncommon or unknown.

On the other hand, some researchers are clearly suggesting that we're obsessing over our symptoms and if we just went outside for a nice walk in the fresh air, we'd soon forget about them...

 

[Peter T]

even though there's no physiological reason for those signals to be sent.

To be pedantic technically we can only say that there is no environmental or external reason for ‘these signals to be sent’ or these sensations to be experienced. There could a physiological reason for theses sensations, we just do not currently know.

 

[Creekside]

I can't recall anyone claiming reduction in ME symptoms from taking lecithin (leads to myo-inositol ) oranges or cantaloupes. Oranges (a source of myo-inositol) were the initial immediate trigger of what became my ME, although that might not be related to myo-inositol (but can't rule that out).

 

[Marky]

Why on earth would they include patients who took antidepressants. That clearly makes the results highly questionable

 

[Campanula]

It's a difficult one to pin down, as it can just mean that our brains are giving us duff information. We get bulletins telling us that we're too hot / too cold/ in pain, even though there's no physiological reason for those signals to be sent. It doesn't make the sensations any less uncomfortable, though, and there's little we can do to stop the signals.

I'm not so sure about this...

I take it your refering to the theory that ME-symptoms are caused by central sensitization here? I've not seen convincing data that this is the main mechanism behind ME-symptoms, although it could certainly be a part of the reason. I find it more plausible that pain signals come from lactate accumulation or oxidative stress or some sort of physiological process that's not been described yet, precisely because so many researchers have taken for granted that there is no dysfunction in the muscles.

It's hard to find strong evidence for something when the majority of the medical community have gone out of their way not to search for it...

 

[Kitty]

I take it your refering to the theory that ME-symptoms are caused by central sensitization here?

I don't really have a theory, I've no medical training or understanding.

I just know that when my brain was sending out signals that I was so hot my upper body needed to be drenched in sweat – my clothes and hair would literally look as if I'd just been out in a downpour – I could find no evidence that I wasn't at absolutely normal temperature. It's a routine feature of the menopause, though it's not always quite that bad for everyone (I needed to change my top half clothing every hour or so ).

The dysregulation in ME is less severe, but it could be the result of the same faulty thermostat mechanism. It certainly feels just like it.

 

[Denise]

I know male PwME who have hyperhidrosis and similar to @Kitty have had to change top half clothing with great frequency.
Have also heard that some of these folks who also have POTS have had sympatholysis done in the thoracic region to try to ameliorate the POTS and as a "side effect" it has helped alleviate some of the underarm sweating though the sweating has transferred to other areas (in one person, the scalp) but is less of a problem than before the sympatholysis.

 

[Kitty]

Have you seen the video mango posted today?

No, not yet – swimming and laundry day, so I've only just sat down! I'll come back on later when I've had some food.

 

[Kitty]

I know male PwME who have hyperhidrosis and similar to @Kitty have had to change top half clothing with great frequency.

I don't know if it works for ME hyperhidrosis and/or guys, but I wouldn't have been able to carry on working if my GP hadn't talked to colleagues about relief for people who can't take HRT, and someone had suggested gabapentin. LITERALLY save my sanity! I think I took it for about three and a half years, easing the dose down every few months to see if the symptoms had subsided enough for me to wean myself off it. And they did.

16 years later they still haven't gone away completely, but are a mere shadow of what they used to be!

 

[ME/CFS Skeptic]

Nonetheless, the lower levels of myo-inositol levels in patients could be interesting as it might be related to the functioning of glial cells.

Just had a look and this 2019 paper by Younger found higher levels of myo-inositol (compared to creatine in the Right Palladium) while this paper reports lower levels (compared to water or N-acetylaspartate in the anterior cingulate cortex).