International ME/CFS Conference of the Charité Fatigue Center on 11./12. May 2023 in Berlin, supported by the ME/CFS Research Foundation

I'm so exhausted after today's conference, I read that as a suggestion to have mice reproducing on the forum. The mind boggled.

Spoiler: forum mice

 

It was nice to be reminded today in Leonard Jason's talk of their finding in the longitudinal EBV to ME study that the pretesting before the students even caught EBV, including both psychological questionnaires and biological specimens did not find any correlation between those whose EBV triggered ME and their psychological profiles. The only correlations were with biological factors. I know we've seen the published paper on this, but it was good to have it repeated.

He's also continuing that longitudinal study and doing LC ones too with the focus very much on biology, not psychology.

 

(My sentence was poorly written. I'll fix it.)

 

Anna Aschenbrenner
I don't think we have seen a paper on the work that she presented the conference yet (?). That is one to look out for.

 

Thanks for the details, @SNT Gatchaman. Do we know if this research has been published yet?

 

Luis Nacul - basically an extended ad for his Canadian clinic. He promoted a whole range of unevidenced therapies; they offer things like acupressure, some therapy called "Beneath the surface" - goodness knows what that is. He supports use of aripiprazole.

 

Next man - a young person's inpatient treatment centre - 5weeks. Sleep hygiene emphasised, physical activation with graded exercise has to be done carefully.
He seems well-meaning. He proclaims it works, on no real evidence. They do get their own bedrooms though, and probably do benefit form seeing others with the same symptoms.

edit to add -- the name of the programme was TIGER - a tortured acronym as usual. But the analogy was quite nice - tigers sleep 20 hours a day, but when they are awake they are very effective.

 

Michael Stingl - neuromodulation
I thought this was going to be a clip on your ear with an electrical current - but it was drugs. Dosages and side effects were given. He stresses that patients need to be informed well, due to the side effects, and the drugs are off-label. I think he said that he sees 40 patients per week, he's a neurologist. He's seen over 1000 patients.

Benzodiapines - can decrease heart rate, stabilise mast cells, reduce sensory overload. Uses low dose lorazepam, use for max 2-4 weeks

Anti-convulsants - treatment of neuropathic pain - pregabalin, start low; lociosamide, possible use in small fibre neuropathy

Antidepressants - notes that ME/CFS is not some psychiatric disease but can be secondary effects. Can have anti-inflammatory effects, but not really effective, showing ME/CFS isn't depression. He's has some good results with Fluvoxamine. But if you aren't depressed, and you take it then you can end up agitated. Mentions some others, perhaps with benefits for cognition. Could be worth trialling some.

Low dose aripiprazole - has seen some improvements in cognition in some people although it isn't magic, less sensitive to light, can reduce in effect over time

Low dose naltrexone - benefits for cognition, pain reduction, reduction of PEM. No magic bullet.

Pyridostigmine - mestinol. Inhibits acetycholinesterase. Mentions /systrom's study that found it increased Vo2max in ME/CFS. Can help with POTS. He seems to think that is work a try. Should not be used in asthma, glaucoma.

He seemed to be responsible, trialing removing the drug, to see if it is really helping.

Question from the audience - 'we all know that autoantibodies are so important in ME/CFS'.

 

Laura - talking about ME/CFS in society. Nothing we don't know - dissatisfaction with medical care, stigmatisation can be really detrimental
Two papers published
German version of DSQ

What can we do - live webinar to increase health practitioners' knowledge about ME/CFS. Paper forthcoming on this.
Recommends more education in medical training

 

Bettina Grande - psychotherapist
Psychological support in ME/CFS
Acknowledges that psychotherapy doesn't cure ME/CFS, and it can be used to mobilise people, which can results in harm. The problem is most modalities result in activation.

Need to acknowledge ME/CFS is a physical disease, there needs to be understanding of PEM, and of pacing (managing activity levels to prevent and control crashes)
Therapy by video, even emails if necessary. Can help people to understand PEM, and their limits

 

Thanks. I think I may have nodded off to sleep in the last one - not the presenter's fault at all.
Morning tea in Germany

 

Yes, my impression was that she was fully on our team.

 

Thanks for your summaries Hutan. Much more coherent than my notes.
Just a few added comments:

To try to be fair, those unevidenced things which also included mindfulness adn naturopathy were on a list of groups they provide for those who want them and also included pacing as an option. His comment about them seemed to be that they are support groups, rather than making any claim about them being treatment.

The core part seemed much more standard with consultation and advice with symptomatic treatments. And the drugs he mentioned he did talk about the importance of explaining to patients that they haven't undergone clinical trials.

I thought it was interesting that the main use he specified was for reducing the effects of PEM, and he specified no more than 2 to 3 low doses a week, or if taking continuously, no more than 2-4 weeks.

I think that only came up as an answer to a question. He seemed pretty keen on trying one drug after another and different doses - all without any clinical trial evidence or any indication that he's proposing to do any trials.

It was interesting that she gave the comparison in knowledge of ME/CFS when assessed before a webinar that when the participants were volunteers, their preexisting knowledge of ME/CFS was pretty good, and when they made it a compulsory element of inservice training for hospital clinicians, their preexisting knowledge was much worse.

She was making the point that just inviting people to learn about ME/CFS you tend to get those already pretty weil informed, so it's important that for those who should know about it, the training needs to be compulsory.

I think she's probably the only psychologist I've heard talk about ME who really gets it about the limitations of the role of psychotherapy in ME/CFS and the harm that can be done by inappropriate therapy. Her focus was on helping the patient with pacing and she emphasised how difficult pacing is and that the therapists role is to help the patient find ways to deal with barriers to pacing, not to tell the patient what to do. I hope she can spread the word among her profession.

 

Oystein Fluge
Most of you know the history; rituximab ending up with no significant differences. transient B cell depletion - targets CD20 molecule
Open label cyclophosphamide - seemed to be some good responses. Broad immune suppressive effects on lymphocytes. Might work by affecting early plasma blasts

They did a Fitbit trial ((no intervention, just looking at the technology I think) 2022 - 6 months, to see normal symptom variation

Lots of information about the studies.

New data - 6 years followup for rituximab and cyclo trials. Paper is coming
Very good participation in the followups
didn't find a difference in followup ritux; lasting benefits in the cyclo based on SF-36 PF
18% got to normal healthy level in cyclo; only around 8% in ritux and placebo
Also decreased worsening.

They are thinking about outcome measures; how to reduce patient heterogeneity

They think ME/CFS is in principle a reversible disease. they have seen severe patients recover and be ok
They have done autopsies on 5 people who committed suicide (five people ) - they haven't found histological evidence

Hypothesis - Immune disturbance > disturbed auto regulation of blood flow, hypoxia >change in metabolism to compensate
Endothelial dysfunction; reduced venous return to heart; reduced peripheral oxygen extraction (shunting to miss capillaries)

ME/CFS - a variant of an autoimmune disease with a role for mature long-lived plasma cells

Mentions the Wang et al 2022 REAP study
thinks the autoantibodies perform a beneficial effect in response to infection initially

Their work continues. Cyclophosphamide has some toxicity concerns, so can't be used for broad use.
Looking at removing autoantibodies; target plasma cells
Trialling darutumumab - pilot study. They see patients with absolutely no effect, but some that seem to respond. 6 patients so far, all had been ill for years.
Outputs are resting heart rate (Fitbit) and steps per day
One woman, ill for 34 years. Her outcomes have improved. Her objective markers dipped for a bit, associated with a viral infection, and then continued to improve. she had tried rituximab earlier with no response.

They are thinking about a new trial.

 

Didn't catch this man's name.
Edit: Speaker is Wolfgang Ries, Nephrology, Clinic for Internal Medicine, DIAKO Hospital Flensburg, Flensburg, Germany (thanks, MSEspe)

Mentions prognosis - 50% recover, (but that was K. Rowe's paper from 2019 - I think that was the one with followup of young people. Recovery was a flexible concept.)

Immunoadsorption - different systems, different efficacies
Talks about complications from immunoadsorption - there are appreciable proportions with complications, although mostly minor.
hypotension; bleeding; catheter infection;

peripheral venous access better; avoid central line
take care when working with severely affected patients; think about noise, waiting time, room for family, use of family for some nursing. allow people to sleep, fit treatment around their sleep.
mentions some very sad cases of young women, living in darkened room. hospital stays cause crashes

13 year old girl - very sick. Immunoadsorption to adsorb Ig
Dramatic increase in Bell score, now fully healthy

Improvement in 22/31, although from low baselines - no change in 6, 5 patients ongoing

Immunoadsorption is faster than rituximab

Fluge comments to the presenter - see a fast response, but then worsening again after a few days. But it does show that there is something in the blood. Very expensive but proof of concept.
Presenter says the cost is not so much the problem, availability is a problem.
Some arguments between them.

 

Woman presenter - Lisa
66 patients in a forthcoming immunoadsorption study at the Charite

GPCR autoantibodies
Mentions Freitag 2021 paper
(it's moving fast and I am slowing)
2016, 2018 studies showing immunoadsoprtion effective in ME/CFS
(all very certain)

study last October - 10 patients already included, another 10 to include.
CCC diagnosis, high levels of GPCR autoantibodies, patients get sick after Covid
(Oystein commented that they used patients with a longer duration of illness, to try to eliminate patients who might have been improving anyway)
7/10 responders - the responders will be treated again
in all 10 patients, antibodies reduced
improvement in physical function (but self-reported in unblinded trial)
less improvement in overall score and in fatigue

Responders will be selected for a trial of B cell depleting antibodies

(Quite a difference between the Charite and Norwegian groups with attention to managing bias)