Opinion How federal research continues failing people with myalgic encephalomyelitis, 2024, Janna Moen

Janna Moen, a neuroscientist who's working in Akiko Iwasaki's lab at Yale and has Long Covid/ME herself, has just written a piece on the history of ME/CFS as part of her substack "Long Covid Research Breakdown."

https://open.substack.com/pub/lcbre...rch-continues-failing?r=1n4374&utm_medium=ios

Here is a breakdown of the narrative:

• Research about myalgic encephalomyelitis dates back to the early 20th century, when at least 14 major outbreaks of a mysterious neurological disorder occurred around the world. At first it was thought to represent an unusual manifestation of paralytic polio.
  
  
• ME was classified as a neurological disorder by the WHO in 1969 and was immediately met by pushback from a group of doctors who insisted that mass hysteria was the real culprit. The major rationale for this was that the disease mainly impacted women.
  
  
• In the 1980s, three major outbreaks in the US and the UK drew the attention of health agencies and officials. Doctors treating these patients noted many had antibodies suggestive of recent infection or reactivation of the common viral pathogen Epstein-Barr Virus (EBV).
  
  
• Officials at the CDC conducted a small trial measuring the impact of the antiviral agent acyclovir on symptoms and basic blood markers. Acyclovir failed to outperform placebo, although the majority of their physiological data was omitted from the publication. Many researchers incorrectly interpreted the negative results in this study to mean that the disease had no biological drivers.
  
  
• Around the same time, officials at the NIH and CDC convened a panel of “expert” physicians who rebranded the disease as chronic fatigue syndrome (CFS) and significantly changed the diagnostic criteria to focus on medically unexplained fatigue. Officials like Dr. Stephen Straus would go on record to state that CFS was not a specific disease but instead the result of unstable personalities or stress from unrealistic expectations.
  
  
• A group of psychiatrists in the UK had similar beliefs about the nature of CFS and began promoting the “biopsychosocial” model of the syndrome, which posits that CFS is driven by physical deconditioning and chronic activity avoidance. Essentially, they believe that patients try to return to baseline levels of exertion too quickly following an acute illness, which causes them to feel worse. This results in patients avoiding exercise, leading to further physical deconditioning and reinforcing “unhelpful” cognitions about exercise causing symptoms.
  
  
• One of the largest interventional trials for CFS was conducted in the UK testing the impact of graded exercise therapy (GET) and cognitive-behavioral therapy (CBT) versus what they called adaptive pacing or standard medical care. The study authors claimed the GET+CBT approach led to moderate improvements in self-reported fatigue and physical function, but critics quickly highlighted a variety of methodological and ethical issues. The study was largely debunked.
  
  
• Despite low rates of funding, more and more evidence has accumulated showing that ME is a biological disorder. This includes replicated findings that people with ME exhibit significant deterioration in performance and capacity on the second day of a two-day cardiopulmonary exercise test, whereas controls and people with other conditions repeat or even exceed their previous performance. Other studies have shown marked changes in gene expression following exercise, and demonstrated sustained neuroinflammation in people with ME.
  
  
• In 2015 the NIH announced its plan to launch a integrative cross-institutional study to deeply profile people with ME, although advocates quickly noted potential conflicts of interest and points of concern with the proposed studies.

 

That's a great breakdown.

I remain very sceptical about 2-day CPETs being anything close to replicated biological findings and am very wary of people making claims that there's studies demonstrating that we have any idea about what's going on or that some anomalies have been found, which in reality are far more likely to be noise. I understand the notion behind doing so, but one should bear in mind that this hasn't lead to anything fruitful in the past and can just as easily be used against us, when indeed studies can't be replicated (recall the recent LC headlines around the Kleinschmitz study "cortisol isn't a marker for LC, so it has to be psychological", because some people overinterpreted cortisol to be some sort of marker for which there was never any evidence as @Hutan has carefully explained multiple times in the past).

 

But none of these differences that are found seem to be in any way consistent from what I can tell and the largest 2-day CPET study found no differences at all, so what exactly is the thing that was replicated, what about all the differences in Workload at VT1 if that is supposed to be the most meaningful result? That may all have to do with differences in methodology and especially recruitment criteria, but from what I see one should at least try to explain why these results aren't consistent to be able to move forward. The only thing I see being reproduced are inconsistent anomalies.

I believe someone mentioned in a different thread that Workwell is sitting on data of hundreds of patients that hasn't been published?

 

Unpublished data from Vermeulen on roughly 500 ME/CFS patients (presented here). Note: Of course this data was never published (publication bias?) and this doctor is very controversial, however if that's any reason for me to neglect these results then I would think I would have to also neglect his other 2-day CPET results.

Together with what Simon wrote here (Workwell having data on 400 subjects) that simply means that there is far more unpublished data on the 2-day CPET in ME/CFS than there is published data and I'm wary of something like publication bias.