Hyperintense sensorimotor T1 spin echo MRI is associated with brainstem abnormality in CFS, 2018, Barnden et al

https://www.sciencedirect.com/science/article/pii/S2213158218302237

 

Brainstem issues, yet again.

 

Yes.

 

My understanding of this [which might be horribly wrong...]

When signaling in the brainstem becomes weaker, certain nerve fibers in the white matter carrying the signals become better insulated (with more myelin), so as to carry the weaker signals as fast as possible. This presumed compensation was observed in both CFS patients and in healthy controls.

In CFS patients, however, the brainstem signaling was weaker and the white matter nerve insulation was greater than in controls. This supports the apparent causal nature of the relationship and provides evidence that brainstem signaling in CFS patients really is weaker than that seen in the healthy controls.


[ETA: NOW! With fewer assumptions on my part!]

When less myelin is detected in the brainstem, more myelin is seen in certain nerves fibers in another region of brain, i.e. in the sensorimotor cortex white matter. This study reported this relationship for the first time. It was seen in both CFS patients and in healthy controls.

In CFS patients, however, there appears to be less myelin in the brainstem than controls, as well as more myelin in the sensorimotor cortex than in controls.

The authors raise the possibility that the decrease of myelin is the driving force in the relationship and that its deficit in the brainstem may be impairing signal conduction there - with the gain of myelin in the sensorimotor complex being a means of balancing the "conduction factor" between the two areas.

 

I think this paper is potentially very interesting. It is the sort of finding I might have guessed might one day turn up - suggesting that there is a connectivity problem in the brain involving brain stem and hypothalamus. I find it more interesting than the Japanese PET study for instance.

In MS damage occurs in patches randomly throughout the brain. These are clearly 'inflammatory' immune attacks based on cells arriving from the bloodstream. But the present study is showing a very balanced symmetrical increase in myelin signal in the parts of the cortex directly associated with sensing things and doing things rather than the bits involved in concepts or emotions or whatever. Interestingly it does not seem to affect visual cortex.

For me the message is that this change is not due to inflammatory damage but due to a change in the way the brain is being used. The authors suggest it is secondary to something going on in the brain stem and that would make sense. The problem in the brainstem is also unlikely to be inflammatory in the usual sense because the brain stem is a small structure and even a minimal dose of inflammation there tends to wipe out function to the extent of coma.

So it makes me think again along the lines of maybe ME is a bit like narcolepsy or tinnitus, in both of which loss of specific cells in a specific part of the brain leave the person with a malfunction of a control system. In narcolepsy the sleep-wake signalling flips about. In tinnitus the gain control on the acoustic nerve does not operate.

I have not been very impressed by the immunology from this group but that is no reason not to take the neuroimaging seriously. If this finding holds up this could provide the sort of 'proof of pathology' that everyone is trying to find. The scatter plots of the two populations look bona fide too.

It is also nice to have a paper that makes absolutely no mention of the affected areas probably being related to emotion or self-image or whatever. The bits of the brain lighting up here are the low level interaction with world areas that control sensations and actions.

 

And I think that something could come from the craninal nerves.

 

This might be the first time i read you being excited about a ME paper @Jonathan Edwards. Your threshold is usually high. Thank you for sharing these comments.

 

This is really interesting. Is the paper suggesting less myelin in the brainstem too? Is that the cause of the reduced signal? Or can we not tell yet?

 

I always feel bad about being unexcited so often. But my excitement about ME papers is no different from the way it was about rheumatoid arthritis papers. Nineteen out of twenty papers are boring or bad. But all you need is one good one!

There seems to be less myelin in the brainstem in ME. I would not suggest even trying to decide what that might mean in terms of 'more' or 'less' of any signalling capacity or in terms of what causes what. All we ned it to be is an objective finding (that will probably not change after CBT).

 

How much would this fit with the symptoms?

Some sort of regulation failure seems consistent with marked symptom fluctuations.

 

This work was originally being conducted by a team at Queen Elizabeth Hospital in Adelaide, but they ran out of money, so they moved to NCNED to access funding and equipment. The lead author of this paper is from the Queen Elizabeth Hospital team.

 

And what?

 

It would have been useful if some of the controls in the experiment were only suffering from clinical depression so that scientists would be able to compare the 2 sets of results and conclude with a good degree of accuracy that ME/CFS isn't a depression related disorder... the results form this study still leave the door wide open to those parallels being drawn as it has unfortunately not been proven otherwise.

It would be interesting to understand where the tube that links the stomach to the brain enters the brain as I have CFS/ME and have noticed that a lot of my symptoms are made much better by changing the habitat in my stomach!

 

Is this a finding that is also seen in clinical depression?

(other wise I'm not sure why anyone would even think of that)

 

I doubt this sort of finding has been reported in any other illness. But depression has been used as a positive illness control for several US neurological studies. I think it would be useful both to confirm specificity and to make the point that ME and depression are distinct.

 

What they seem to be saying is that whether you are healthy or have ME the less myelination you have in the brainstem the more you have in these sensorimotor cortex areas. There is a suggestion that this is how the brain somehow 'balances out' its activity. It might be a bit like finding that plants with very short stems tend to have long leaves - indicating that there is some general rule about the relative levels of myelination in the two areas.

On top of that they found that PWME fall to the end of the spectrum with low myelination in brain stem and high myelination in cortex. One way to explain that would be that something has interfered with brainstem leading to loss of myelin and that the cortex develops more myelin because of the balancing rule.