Capturing post-exertional exacerbation of fatigue after physical & cognitive challenge in CFS

[Marco]

Which would suggest that habituation, i.e. behavioural adaption, is not the answer.

?

I'm pretty sure the authors were referring to the neurological process of inhibition whereby the nervous system screens out or 'gates' redundant or innocuous sensory data that would otherwise overwhelm the higher brain regions.

One example is sitting down on a cold hard wooden chair. At first it's uncomfortable but it's useful to know that you're safely sitting on a hard surface and there isn't a nail sticking through but that becomes redundant data and 'normally' within a few minutes you're not even aware of the sensations (in my case not only do I not habituate to the sensations but the feeling of discomfort increases until I have to get up and move).

It's likely that inhibitory circuits contribute to this habituation but in terms of the brain's electrical response to signals; filtering of 'gating' of sensory input is largely pre-conscious (around 100ms after stimulus onset) whereas 'attentional' processes don't kick in until around 300ms.

This happens well before higher order 'behavioural' factors can intervene.

 

[Snow Leopard]

It's likely that inhibitory circuits contribute to this habituation but in terms of the brain's electrical response to signals; filtering of 'gating' of sensory input is largely pre-conscious (around 100ms after stimulus onset) whereas 'attentional' processes don't kick in until around 300ms.

This happens well before higher order 'behavioural' factors can intervene.

This is one thing that I've wondered about, the effect of periodicity on perception. High frequency nerve signalling is percieved as sharp and intense, but low frequency persistent nerve signalling... What relationship does that have with fatigue, I wonder?

Lastly, as with A.B.'s comment, the impact of what we're talking about must also have peripheral/metabolic consequences (to explain the results of repeat exercise testing, which is what I was suggesting when I said drop in performance). Also, the time frame of PEM doesn't really match that of interoception - unless there is something deeper going wrong, more than just 'wind-up' or 'kindling'.

 

[jimells]

A novel finding was the gradual and reasonably linear increase in the perception of exertion over the course of each challenge, despite the constant level of task demand. This inability to habituate to the task was not reflected physiologically; for example, during the exercise challenge all participants exercised at the same relative heart rate and other markers of physiological capacity, such as VO2and respiratory markers, plateaued permanently once‘steady-state’ was achieved early in the challenge. As such, this suggests that an abnormal perception of effort during physical or cognitive activity is a component of CFS.

To me, this suggests their patient cohort is not very ill. Boatloads of anecdotal reports on the forum demonstrate quite clearly that heart rates increase as patients continue to exceed their energy envelope. For me, if I ignore the perception of increased exertion, I will trigger a crash, or end up on the floor. But maybe those bruises are just figments of my imagination...

 

[jimells]

We're all aware of examples where fatigue signals can be overridden by motivational factors (marathon runners, in instances of extreme danger etc).

As I understand it, fatigue does not equal muscle failure, but is instead a warning. I experienced this regularly in my face, when I could still play saxophone. Wind instruments require continuous contraction of muscles around the mouth. When those muscles started complaining, I kept playing, until the muscles simply gave out. I kinda had to stop and rest at that point. No amount of psychobabble could convince those muscles to work again, until they rested a while.

 

[Dolphin]

Participants in the EXER and COG studies were approached only after the treating clinicians had resolved that they had a stable pattern of symptoms, and optimised sleep-wake cycle patterns and mood profiles, to minimise confounding influences on the fatigue experience.

Seems sensible

 

[Dolphin]

Results

Focus group study

Many participants indicated that the term fatigue did not adequately describe the sensation they experienced on a daily basis. Five descriptive themes emerged: feeling exhausted or tired; feeling heaviness in the limbs or whole-body; sensing fogginess in the head; feeling weakness in the muscles; and feeling drained of energy. These descriptors were nominated consistently across the groups, and no new themes emerged in the last group.Table 1 shows the word frequency analysis of the key descriptors within each of the nominated themes.

These themes revealed distinct‘physical’ and‘mental’ fatigue domains, and participants consistently suggested a clear differentiation, for example: “I still suffer not just physical fatigue, but the biggest thing I find for me personally is the mental fatigue,”(1:2);“I find that mental fatigue also makes you physically fatigued,”(1:3);“If I let myself get really mentally fatigued, I'm that much closer to being physically fatigued, and vice versa. They definitely feed into each other but they are quite separate to me.”(5:4).

This sense of distinct mental fatigue was commonly associated with patients' reduced cognitive performance:“I've read one novel in 14 years. I just cannot get through a novel. I pick bits out of books or I read the headlines in the paper every day and that's about it, really.” (3:1);“When I'm fatigued, I feel very overwhelmed and [it's] very hard to make a decision—even simple things, it's just overwhelming…” (5:1). The functional impact of the cognitive difficulties was commonly reported to be pronounced while driving:“I'm going home, thinking, ‘This is dangerous. I am so tired. I shouldn't be driving.’ I mean I've certainly been in that situation.”(4:6).“I probably shouldn't drive as much as I do at the moment because sometimes I just find myself driving and it's like,‘whoa! I've just been driving for 15 min and I can't remember a thing about it.’”(2:1). Reduced cognitive performance was occasionally associated with the sense of being cognitively wired (e.g.“Some days it's almost like I go hyper, my brain just goes so fast. If I'm really tired and have to lie down a lot, my brain goes even faster. It's really hard to settle my brain down.”3:1) or disoriented (e.g. feeling spaced out, or out of it, or like being in a dream)

 

[Dolphin]

This is perhaps interesting given a recent discussion I saw on the forum about how post-exertional malaise/similar should be described incl. whether a delay response should be mentioned:

Patient descriptions of the post-exertional exacerbation of fatigue were variable, and while these descriptions were not used to inform the design of the FES, they are instructive for better understanding the phenomenon. For instance, the time of onset of worsening of the symptom complex after activity was reported as either immediate: “It comes on so quickly.”(2:2); delayed: “It's kind of like the next day or the day after.”(2:3); or a combination of both: “I can tell straight away when I've overdone it because my ears get blocked and I feel dizzy. And I start feeling actual fatigue the next day.”(5:6). The time of onset was generally related to the intensity of the activity: “If I'm doing something more intense, physically or cognitively like carrying heavy shopping or doing tax returns, the fatigue will hit me straight afterwards. But if I'm doing something that's less intense but kind of a lot of it—say if I walk 6000 steps in a day—then it'll hit me the next day.”(2:2). The factors reported as precipitating an exacerbation of symptoms included: physical activity—“I tried jogging for a period of time…and yeah, that doesn't work. That gives me an instant like [smack in the face]”(2:4); cognitive activity—“Sometimes I watch an hour or two of television but then I pay for it a day to two days later.”(3:3); or emotional stress —“Someone rings me and says,“Uncle John died.”It's like I used to have kind of a built-in protection system and like a buffer, but now it just almost knocks me over and I just fall to pieces.”(2:1). Some participants were able to reasonably predict the threshold of activity which would induce a post-exertional exacerbation; others could not: “Some days you might be feeling quite well and so you might think,“I'll do an extra 15 minutes,”but you find that you pay for it later on.”(1:1).

 

[Dolphin]

Interesting in terms of the question about whether people with CFS should drive:

For the COG study, all control participants and 10 of the 11 patients with CFS completed the driving simulator scenario; one patient stopped 5 min prior to planned completion due to nausea. There were no significant between-group differences in driving performance, as determined by the number of mistakes made (CFS: 31.3 ± 17.2; CON: 31.5 ± 14.3; p = 0.97) or the number of ‘crashes’ (CFS: 0.5 ± 0.7; CON: 0.64 ± 0.67; p = 0.67).

 

[SOC]

I'm willing to bet that a lot of these conclusions would vary significantly if patients were categorized by severity level. As with most research studies, the patients (assuming they actually are PWME and not chronic fatigue patients), are probably all mild patients since they got to the study location and performed moderate-intensity aerobic exercise. My guess is their conclusions, however interesting, apply to a very limited subset of PWME. Nevertheless, this could lead to valuable further research, so it has it's place in the research base, unlike PACE.

 

[Marco]

This is one thing that I've wondered about, the effect of periodicity on perception. High frequency nerve signalling is percieved as sharp and intense, but low frequency persistent nerve signalling... What relationship does that have with fatigue, I wonder?

Lastly, as with A.B.'s comment, the impact of what we're talking about must also have peripheral/metabolic consequences (to explain the results of repeat exercise testing, which is what I was suggesting when I said drop in performance). Also, the time frame of PEM doesn't really match that of interoception - unless there is something deeper going wrong, more than just 'wind-up' or 'kindling'.

Yes indeed, there's got to be something more going on than interoception/nociception but it could be what kicks of the process plus we also need to explain why cognitive challenge has similar results (as supported by the subjective focus group findings) where it's highly unlikely that physiological parameters such as VO2max will have shifted.

 

[Dolphin]

The analysis of convergent validity showed global FES scores correlated strongly (r = 0.79; p b0.01) with the SOMA sub-scale of the SPHERE, which specifically addresses fatigue and related physical symptoms (Table 3). Both of the dimensions of the FES (physical fatigue; mental fatigue) also correlated significantly with the SOMA.

 

[Dolphin]

Comparison with a previous factor analysis of fatigue:

Jason et al. [9] used factor analysis to find five qualitative factors relevant to the CFS phenotype, which were termed: post-exertional fatigue (i.e. an altered state attributable to physical or mental effort); brain fog (i.e. cognitive difficulty that affects various several domains, such as memory); energy fatigue (i.e. depletion of energy resources needed for daily activities); wired fatigue (i.e. an aroused state of mind or body concomitant with feelings of tiredness); and flu-like fatigue (i.e. the global sense of illness typically associated with an acute infective or inflammatory state). Two of the descriptors are reasonably synonymous with those frequently described by our patient group (e.g. brain fog and energy fatigue), but there was no mention of ‘wired fatigue’ or ‘flu-like fatigue’ in our dataset to warrant inclusion of additional items.

Note that "wired" is actually included in the scale and was actually mentioned in this paper:

Reduced cognitive performance was occasionally associated with the sense of being cognitively wired (e.g.“Some days it's almost like I go hyper, my brain just goes so fast. If I'm really tired and have to lie down a lot, my brain goes even faster. It's really hard to settle my brain down.”3:1)

 

[Dolphin]

AK was supported by funding from the Mason Foundation (RG114143). AL is supported by a fellowship from the National Health and Medical Research Council of Australia (No. 510246).

AL = Andrew Lloyd. I vaguely recall hearing he got money from the NHMRC but thought it was for a specific grant (may have got that too).

 

[Dolphin]

The scale itself:

Appendix B. The Fatigue and Energy Scale (FES)

Fatigue and Energy Scale

Please rate how much of each symptom you are feeling right now (circle your chosen number for each item below). Carefully note the descriptive terms used, especially for the loss of energy levels section.

Feeling

Descriptions

None: 0
Just noticeable: 1
Minimal: 2
Mild: 3
Mild–moderate: 4
Moderate: 5
Moderate–high: 6
High: 7
Very high: 8
Extremely high: 9
Absolute maximum: 10

Physical
(i) General fatigue

‘exhaustion’/‘tired’

(ii) Physical function

‘heaviness in the limbs’

(iii) Loss of Energy levels

‘drained of physical energy’/‘low in vitality’

Mental

(iv) General fatigue

‘brain fog’/‘cloudy’

(v) Cognitive function

difficulties with memory or concentration/‘wired’/‘disoriented’

(vi) Loss of Energy levels

‘drained of mental energy’

 

[Marco]

@Snow Leopard

You might find this Alan Light video covering fatigue, pain and PEM interesting (and his other ones on the same site) :

 

[Sean]

The analysis of convergent validity showed global FES scores correlated strongly (r = 0.79; p b0.01) with the SOMA sub-scale of the SPHERE,

Be aware that SPHERE is Ian Hickie's baby, and it claims to show that 60% of patients in the GP clinic have depression, and is used for diagnosing somatisation.

(While since I read up on it, so grain of salt time. More details are buried somewhere in this article. Eyes & brain not up to reading much at the moment.)