From ‘mental fog’ to post-acute COVID-19 syndrome's executive function alteration: Implications for clinical approach, 2023, Pallanti et al

Abstract

A common symptom of the neuropsychiatric Post-Acute COVID-19 syndrome (neuro-PACS) is the so called ‘brain fog’. Patients describe the brain fog as problems with attention, memory and mental fatigue. Brain fog is experienced by 9–55% of people for months after having contracted SARS-CoV-2 virus. Several theories have been proposed to explain PACS's brain fog, including a neuroinflammatory hypothesis, but the hypothesis remains to be proven.

Here, we examined inflammatory and immunological blood profile in a cohort of patients with PACS to investigate the association between executive functions and blood inflammatory markers. Executive function was assessed by the Trail Making Test (TMT) Part A and Part B, as well as the Barkley Deficits in Executive Functioning Scale (BDEFS), in 71 patients (36 men), average age of 40 years (range: 15–82, SD: 15.7). Impairment in executive functioning (BDEFS scores and TMT B scores) correlated with increased levels of Interleukin-6 (IL-6), fibrinogen and ferritin. Moreover, elevated levels of Il-6, fibrinogen, ferritin, tumor necrosis factor-alpha and C-reactive protein have been observed in PACS. These findings demonstrate that PACS is characterized by the presence of an immuno-inflammatory process, which is associated with diminished executive functioning.

Here, we argue in favour of a shift from the non-descriptive definition of ‘mental fog’ to a characterization of a subtype of PACS, associated with alteration in executive functioning. Implication for clinical settings and prevention are discussed.

Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0022395623004284

 

[moderators, this post is intended to be more general than this paper, BUT also to refer to this paper. perhaps a new thread with links?, but idk which forum. please move this post at your own discretion if you can/want.]


what is a good, scientific, well-defined, phenotype-oriented definition of executive dysfunction?

can anybody summarize this paper's take and those scales they use?


here are some facts about my case, which i really want to udersatnd more of and find treatments for:

1. [a huge issue, simple to describe, but not as huge as #2]

i experience fog, confusion, inability to focus type of thinking, which i am guessing some also experience and call brain fog.

both this paper and an ed yong article seem to identify executive dysfunction with brain/mental fog.

unlike #2, i can push through this one SOMETIMES by extreme willpower. it takes a lot out of me and auses pem and stress.

can my foggy description above be replaced by more specific cognitive deficits/dysfunctions? similar to below?


2. [my survival is literally at stake and this contributes]

i have specific, and /extremely/ severe, cognitive deficits in such things as planning, scheduling, executing tasks, initiating tasks, assigning priorities, parsing tasks and more significantly following htat parsing, remembering tasks, decision making, problem solving, knowing what to do [on top of many other issues preventing that], getting things done [on top of many other health issues preventing that].

getting things done, by a meaningful definition, is nearly impossible or impossible most of hte time.

one thing that possibly baffles everybody else is that i can soemetimes come across as lucid and capable such as perhaps in this post. but that is a rare, coincidental, serendipitous, FLEETING, opportunistic ability that i cannot produce at will, and only works for some topics or tasks in the rare times when it is possible.

i cannot take something that matters and focus on it. i cannot do my highest priority tasks.

i usually have to struggle seriously hard to manage bathroom, eating, time management, and taking medicines, due to what seems to be specific cognitive deficits. is this executive dysfunction?

this applies to complete inability to do paperwork [on top of other health reasons preventing that], and a lot of other things, but also to really LOW-LEVEL things that might seem unrelated.

a good example of a low level version of this: i am very hungry. i want to eat. i am ready to eat [no fluoride on teeth], food is ONE FOOT AWAY on a table, within reach of my arm [i am bedridden]. i know, at least for a brief period, that the food is there. in principle, all i have to do is reach out and grab it and start eating.

but i cannot initiate the task of lifting my arm and grabbing the food. INFURIATING. is that executive dysfunciton?

[this is on top of and sometimes separate from other issues preventing eating, including forgetting the food is there a few seconds later despite my hunger; lifiting my arm and using it causing muscle fatigue, need to rest my whole body by lying on one side after doing it, an intolerable feeling where i HAVE to put down the arm, ulnar nerve numbness, what was described as unusual visible raynaud's with clear line of demarcation suggesting severe oi, no stamina, pem, and maybe other stuff.]

all my life i have had these problems. i never understood what was wrong with me. i never understood why i could not get things done despite e.g. going to top universities [one very top university invited me to apply, and i did not due so partly because the application form was too much for me]. ADD or autistic inertia might or might not be related, but it feels slightly different and sort of a collection of specifics.

it is unrelated to how much i want to do a task. it is positively correlated with the necessity of the task.

willpower cannot override it. a "panic monster" or any other incentive does not override it. i cannot do whatever it is. it causes self-hatred. trying really hard feels like it hits a wall. my brain goes awol. i get pem. i avoid trying to start things because i know pem will result. i hate the fact aht i avoid trying to start things tht i want and need to start. but i know that i need rest for m.e. ad teh stress of stareting whataever it is causes pem. and i am severe enough that pem could puysh me into extremely severe terrritory.

is this what executive dysfunction means? are there treatments?


is the first also executive dysfunction? can either be linked with il-6, fibrinogen, ferritin, or anterior cingulate cortex?

i have tested high, in a study, for il-6. at the triple- or quadruple-digit level [usually it is single digits].

i think lombardi's random forest cytokine study had il-6 and
il-8 at the top of of their cohort. unlike klimas's.

 

I have high IL6 but steroids don't lower it so I'm not sure what else I could try, there is an anti il6 antibody drug but good luck trying that one just from a suspicion of association.

But yes I think there is a small subset of ME people that have extreme executive dysfunction and nobody cares at all to try and figure out what's causing it despite the extreme, unfathomable disability it causes. I can't take care of myself even if I had energy because of it. Somehow though, I feel like if I did have energy the ED would go away. It is a weird symptom. Other patients don't really struggle with this even if they have no energy - I mean they do but nowhere near this level.

I noticed that this symptom in my case worsens dramatically when I eat something I'm intolerant to, and it improved (albeit very, very slightly) after many months of LDN. So it think it is sensible to assume it could be related to neuroinflammation (possibly in the ACC).The problem is I don't know what drugs could address this. I tried even 100+ mg methylprednisolone and it doesn't help. Celecoxib also doesn't. And others I've tried which I don't remember.

JAK inhibitors could be interesting but @Jonathan Edwards said there's no reason for them to work if steroids failed.

 

I was wondering what they meant by "implications for clinical approach." What clinical approach?

 

i have heard that mast cells relase il-6. stopping degranulation might help? idk if relevant. are tehre other sources of il-6?

i ahe taken fexofenadine and cetirizie which inhibit mast cells. but i gatin tolerance to them for allergic sympotms and sleep. idk if helped.

[note: i am told tryptase neg but have not seen test results. so dianosed by immunologist as not having mcas. also cooplement tests exist.]