@Sarah94 here is a partial summary, I will need to take a break before I can finish it.
3:00 Mike van Elzakker understands that the current tools will not get at the root cause of ME so is instead looking at brain correlates to ME to try to understand the mechanisms involved in driving the symptoms
5:00 The tools he is using are MRI, FMRI arterial spin labelling, magnetic spectroscopy (metabolites), diffusion tensor imaging looking at water moving along axons, PET with a tagged translator protein which proxy for neuroinflammation, and EEG.
In talks to get an EEG study but has used all of the other tools.
9:00 He is in the middle of gathering data. So the following is preliminary, n= something too small and we are not to get excited.
In the scans pwme's peripheral measures of physiology: HR, blood pressure, pulse ox, inhaled gas exchange, respiration in and out. These should correlate with the measurements in the brain and in pwme they don't correlate as well as well as they do in controls. Which suggests a problem with perfusion in the brain.
13:00 The problem with perfusion is an issue at baseline.
Pwme then do invasive cardiopulmonary test to induce PEM and then they are tested again.
This poor correlation between perfusion in the body and the brain is not worsened by the exercise.
He notes that just because something has not worsened as the symptoms worsened does not mean it cannot be the driver of symptoms.
It is possible that the failure of proper perfusion during exercise may have longer term consequences that take time to kick in.
Mentions a difference between the way PEM was used by Ramsey and the way it is used now. He thinks that there is likely to be a different mechanism between PEM caused by physical and mental exertion even if they share the same endpoint.
Note that he sees not post-PEM change in the brain only means that he sees no change with that measure, it is not the same as saying there is no change in the brain.
18:00 mechanisms
Two plausible models
The first is about IL6 which is an apex cytokine and triggers a lot of pathways.
He notes that one distinction between people who are very fit and people who are decoditioned is that deconditioned people produce more IL6 for a given level of exertion.
(He notes that he is NOT endorsing the idea that ME is deconditioning when saying this.)
After multiple infectious hits people can develop a sensitised afferent signal system for the detection of cytokines. The afferent vagus nerve serves as a diffuse system for detecting inflammation for the brain.
He thinks that a slight increase in the production of IL6 coming into contact with a sensitised system leads to glial activation (20:30)
He knows that some studies in pwme see no change in IL6. But he thinks that these sorts of experiments are difficult because you have to control for an absurd number of variables and you cannot control for the sensitivity of the system. So he does not think that the failure to find this in some experiments means that it cannot be the case.
The second plausible mechanism is to do with the problems of perfusion in the brain. The failure of perfusion will cause a low level ischaemic response which could last from days to a week. This would cause glial activation. This would lead to brainfog and sensory sensitivity. 22min