Neuropathology and Neurological Manifestations in ME/CFS and Long COVID with focus on Post-Exertional Symptom Exacerbation: Lit. Rev, 2023, Rodenburg

Thesis
Rodenburg

Summary
Many of the people that get infected with the Coronavirus develop long-lasting complaints and are diagnosed with Long COVID after the acute infection is gone. These complains can last several months or years and include fatigue, cognitive impairment, sleeping problems and post-exertional symptom exacerbation (PESE). Research shows that COVID-19 patients with an acute infection have abnormalities in their brain, which could potentially lead to long-lasting neurological problems and symptoms.

However, although many researchers are trying to uncover the underlying mechanisms, Long COVID is still very new. The underlying mechanisms causing and maintaining the disease are therefore unclear. A large group of Long COVID patients resembles patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in terms of symptoms and, in many cases, the viral trigger of the disease. A core symptom of ME/CFS is PESE, which is uncommon in other fatiguing illnesses, but frequently seen in Long COVID patients. PESE involves an abnormal worsening of symptoms and cognitive and physical functions after any type of normal activity.

Because of the large symptom overlap and lack of knowledge regarding PESE, underlying brain-mechanisms associated with Long COVID and ME/CFS in general as well as after physical exertion were investigated. The findings of this review indicate that ME/CFS is associated with several abnormalities in the brain which are also proposed to be present in Long COVID patients. Such abnormalities include inflammation of the brain, shrinkage of the brain and less blood flow to the brain. After physical exertion, these abnormalities might be exacerbated in ME/CFS patients. This results in a brain that needs to work harder than the healthy brain to complete a task. It is demonstrated by increased brain activity in several brain regions after physical exertion and general symptom exacerbation.

Since the two diseases seem to have a large overlap in symptoms and underlying brain-mechanisms, this finding might apply to patients with long COVID as well. Importantly, Long COVID seems to consist of different subgroups of which a large part fulfills the criteria for ME/CFS. Treatment and therapy for ME/CFS patients is therefore likely transferable to this subgroup of Long COVID patients, with explicit attention towards the PESE phenomenon. More research is needed to uncover the underlying mechanisms as well as correct treatment approach of these diseases. Future research should take subgroups of Long COVID into account.

https://studenttheses.uu.nl/handle/20.500.12932/43647

pdf
https://studenttheses.uu.nl/bitstream/handle/20.500.12932/43647/Rodenburg_7433050_Neuropathology and neurological manifestations in MECFS and Long COVID with focus on PESE.pdf?sequence=1&isAllowed=y

 

What treatment for ME is transferable to Long COVID? There is none, unless the discredited (for ME) treatments CBT and GET are considered.

(CBT is considered a support for ME, not a treatment or cure. GET, as per patient surveys, and lack of science based evidence of rehabilitation or recovery, is explicitly excluded as a treatment for ME.)

 

I think it's part of a MASTERS degree.

 

"PESE involves an abnormal worsening of symptoms and cognitive and physical functions after any type of normal activity." My PEM did not trigger on all types of normal activity. I could do quite significant exertion for hours without triggering PEM, but other activities needed less than a minute of mild exertion to trigger PEM. Am I the only one with that sort of response, or do other people also not trigger on exertion that they are most used to? For me, pedalling a bicycle is a normal activity, but washing a window (arms above shoulders) isn't, so that stresses muscles in different ways, resulting in cell damage and immune response.

A useful project might be to question all the assumptions about ME, such as PEM being from all exertion, and unrefreshing sleep being a sleep dysfunction. Misleading assumptions are bad for research.

 

This thesis is from a student, Sanne Rodenburg,in the Netherlands, and so I would assume that English is a second language. I would therefore assume that the intention of using "normal activity" in that description was to attempt to describe how PEM can potentially be triggered by any possible activity, rather than certain specific ones. Certainly for me, as best I can tell, it depends on the amount of exertion, no matter whether it is a new or regular activity, and that would seem to be the same for the majority of other descriptions that I have seen. What you describe would definitely seem to be an outlier experience.

 

Some people laud the English language for its flexibility, but that flexibility creates problems for science, where precision is important. I can imagine research projects going down wrong paths because what they thought one study said was not what the author intended. Remember (I don't know the exact quote): "It's not what you don't know that important, it's what you know for sure that is actually wrong."

 

Have you been tested for dysautonomia? Your body might have difficulty pumping blood upward when you raise your arms? Do you feel dizzy or lightheaded afterwards?

I feel very unwell when I raise my arms or lean my neck back looking upwards. It takes a long time to recover.

 

No, I can do overhead work if I get accustomed to it. I just haven't done much of that for a long time, so those muscles (and blood vessels?) aren't adapted to that. I was adapted to pumping pedals, but climbing a few steps of a ladder (after not having done so for a long time) triggered PEM, because it worked those same muscles past the normal limits, which I assume means damage to some of the cells.

 

I have suffered something like ME for 40 years now. For most of that time, my symptoms were mild-to-moderate and I continued with a lot of gym training and outdoor sports. (I'm currently somewhat severe and can barely function.) My body's response to exertion has always been wildly erratic, and it clearly is not correlated to the volume or intensity of the exertion alone.

Diet may have been one factor (e.g., food sensitivities). Emotional and cognitive stress clearly played a role. I eventually decided that very low intensity cardio was sustainable, as was very brief but intense (heavy) weight-training at infrequent intervals. It was the middle of the road stuff - Crossfit-style "metabolic"-training - that crushed me and my ability to recover. Still, when my body was already pre-loaded from previous stressors, even a moderate jog could destroy me for a week or more. It was baffling and frustrating.

Now, I can barely get out of bed or sort out my banking.