Advancing ME/CFS Research: Identifying Targets for Intervention and Learning from Long COVID Dec. 12-13, 2023

Kitty said:
I don't know what those pictures mean
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I can talk you through them. Left image pair patient, right image pair control. They aren't quite matched to the same (coronal) plane front-to-back but very near enough for the purpose. Michelle James did comment that the left image set was not optimal and you can see the colour mapping is more noisy. A new machine is to be installed that will help. The two are matched for age and sex but you can see the patient does have more subcutaneous fat, which could be a confounder (though I suspect not significant). That likely contributed to the more noise in her image though. The larger dataset with a range of patients will be able to tell us.

Between the two image sets is a colour bar, which is a pretty typical map where "cold" is blue, progressing through green and yellow to red which is "hot". This represents the uptake of TSPO. As @Fizzlou says the control shows where TSPO has uptake in normal people: left ventricle, small bowel > liver > marrow.

The patient has significantly increased uptake (red) in marrow seen in the spine and pelvis. And although to a lower level, there is widespread increased uptake in the muscles.

(Cross-posting with FizzLou, but I'd half typed out anyway)
 
The most obvious difference seems to be in the bones (presumably marrow). So whatever the difference means, if it is real, it isn't particularly about muscle.

Another cross post!

Added: Another factor is that the individuals are vastly different in terms of BMI (i.e. the first one is very overweight). And the lungs and abdomen have a much higher noise signal.
 
SNT Gatchaman said:
The two are matched for age and sex but you can see the patient does have more subcutaneous fat, which could be a confounder (though I suspect not significant). That likely contributed to the more noise in her image though.
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Yep, I'd seen that, but it's not so much the noise as that her muscles and thigh bones look an altogether different colour. It would be interesting to see the results with a different target, and comparisons of other sets of patients. It's a really interesting approach.

I hope they will try for better matching with body type for the future, as mismatches are bound to introduce doubts even if there's no reason they should be relevant.
 
“Structural and Oxygen Metabolic Magnetic Resonance Imaging of long-COVID and ME/CFS” Xiang Xu (Icahn/Mt Sinai)

They devised an MRI sequence to measure the oxygen level in the superior sagittal sinus, one of the major draining veins for the brain. This was correlated with both estimated arterial oxygen saturation (via pulse oximetry) and cerebral blood flow inflow (arterial spin labelling).

They found significantly reduced venous oxygen saturation in LC, but not in ME/CFS or HC. This was not due to reduced oxygen inflow, but instead to higher cerebral oxygen extraction. Note that patients are supine, so that excludes orthostatic effects on CBF.

Screenshot 2023-12-14 at 7.32.13 AM Large.jpeg

This is the sort of thing I've been hoping to get insight into for a while, so I will be looking forward to publication on this —

SNT Gatchaman said:
I'd like to know whether short-term and long-term ME patients (vs LC vs HC) have low peripheral venous oxygen saturations. This was such a striking abnormality in many Long Covid patients (short-term by definition), yet Systrom's evaluations showed central measurements to be abnormally high. [...]

(I wonder if the metabolic abnormalities might vary with body site, such that limb muscles hyperextract, but central organs and brain aren't, for example. The net effect might be less O2 extraction as measured centrally. Perhaps impaired O2 or glucose availability is compensated for by lactate as the universal fuel for load balancing. Just an idea.)
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SNT Gatchaman said:
No, not capillary (estimated arterial) oxygen saturation, I mean venous oxygen saturation from blood. We're still starting at 96-100% in oxygenated arterial blood, and it should be around 60-70% after it's been through the tissues. There is evidence of peripheral hyperextraction in many of us, eg I was walking (shuffling actually) around with sats of 15-46%. This is jaw-droppingly abnormal - as in my intensive care colleagues wanted to know "why I wasn't dead" as they typically see that late in resuscitation scenarios. (ETA finger pulse oximetry - ICU grade - was 99%.)
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Fizzlou said:
Online attendance less than 400 and a nearly empty auditorium.

Very strong lived experience testimony so far.
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Not sure if this was sarcasm @Fizzlou (and it very well could have been, so apologies if so), but for those that know more than me have stated that's actually a pretty-to-really impressive turnout for a NIH conference (the 400+ number of attendees virtually tuning in), just to state.

Again, apologies if you already had that hunch though and said that comment tongue in cheek.
 
David M. Tuller: Conversation with #MEAction's Jaime Seltzer about last week's NIH gathering

Description:

Last Tuesday and Wednesday (December 12th and 13th), the US National Institutes of Health--and, specifically, the National Institute of Allergy and Infectious Diseases--held a two-day meeting called "Advancing ME/CFS Research: Identifying Targets for Intervention and Learning from Long COVID." In 2019, I'd physically attended a similar NIH gathering in person; this time, I caught many of the presentations online instead. Jaime Seltzer, MEAction's scientific director, was there in person. In an interview last Friday, she shared some of her impressions of the event.

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Medscape New Research Aims to Unravel Both ME/CFS and Long COVID by Miriam Tucker

quote:

Wilder, the patient advocate, reminded the audience that "There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life…They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease…They keep waiting and waiting, year after year, missing more and more of their lives with each passing day…We're all depending on you."
 
Andy said:
Miriam on Twitter,

"During discussion, @DrMaureenHanson suggested that there is now enough evidence of brain inflammation to justify simply calling the illness "myalgic encephalomyelitis" and dropping "chronic fatigue syndrome" entirely."
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Would be good. I've gotten the diagnosis ME but I've been calling it ME/CVS myself recently because (some) people know what that is. Chronisch vermoeidheidssyndroom(chronic fatigue syndrome) is a name that obviously elicits responses focusing on being tired. If that could be scrapped and we once more had a universally agreed upon name for the disease that does some justice to the seriousness of it, huge stride forward for advocacy.
 
My question would be what evidence Hanson has seen to support her view. I wasn't aware that we have seen sufficient testing of patients to establish the idea that everybody with a diagnosis has evidence of brain inflammation.
 
SNT Gatchaman said:
They found significantly reduced venous oxygen saturation in LC, but not in ME/CFS or HC. This was not due to reduced oxygen inflow, but instead to higher cerebral oxygen extraction.
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Contrast with Reduced Oxygen Extraction Fraction in Deep Cerebral Veins Associated with Cognitive Impairment in Multiple Sclerosis (2024, Preprint: MedRxiv) which looked at the internal cerebral veins rather than the superior sagittal sinus (ie deep white matter and central grey nuclei vs cortex in the above) and found higher oxygen levels in MS.

In this study, we observed a reduced susceptibility of ICVs in RRMS patients compared to age and sex-matched controls, indicating decreased deoxyhemoglobin levels in venous blood in ICVs. Consequently, there was an increased SvO2 in these patients, implicating a decreased OEF in the corresponding cerebral regions draining into the ICVs. These imaging biomarkers were correlated with cognitive impairment in these MS patients, as measured by PASAT. The high intra- and inter-rater ICC scores affirm the repeatability and reproducibility of the method.
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