Subjective and objective cognitive function in adolescent with chronic fatigue following Epstein-Barr virus infection 2022 Øie, Wyller et al

[Andy]

Highlights

• Adolescents with CFS report cognitive difficulties.
• Adolescents with CFS report more cognitive difficulties than those with CF.
• There were no impairments in objective measures of cognitive function.

Abstract

Objective
Cognitive difficulties are among the most disruptive and disabling problems reported by chronic fatigue syndrome (CFS) sufferers. Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue (CF) and CFS. The aim of this study was to investigate subjectively reported and objectively measured cognitive functioning in fatigued and non-fatigued adolescents six months after EBV infection.

Methods
A total of 195 adolescents (12–19 years) with acute EBV infection were followed prospectively for six months, after which they were grouped as chronically fatigued (CF+) and non-fatigued (CF−) cases based on questionnaire score; the CF+-group was further subgrouped according to CFS diagnosis. A group of 70 healthy controls was also included. Groups were cross-sectionally compared on objective measures of processing speed, executive functions and memory, and subjective cognitive functioning.

Results
There were no group differences regarding objective cognitive measures, but the CF+-group reported significantly (p < 0.001) more cognitive problems (cognitive symptoms sum score = 9.5) compared to the CF−-group (cognitive symptoms sum score = 5.3) and the healthy control group (cognitive symptoms sum score = 6.4). The CFS subgroup rated symptoms scores even higher but did not differ on cognitive performance tests.

Conclusion
Subjective experiences of cognitive difficulties characterize adolescents with CF and CFS six months after acute EBV infection, whereas objective measures of cognitive impairment are inconspicuous.

Open access, https://www.sciencedirect.com/science/article/pii/S0022399922003488

 

[CRG]

A couple of oddities - the gender ratio of the post EBV cohort (total 195) was 1 to 2 M to F, the authors make no comment on this but it seems notable that such a gender bias would exist purely on the basis of infection. Also the physical capacity of the cohorts at 6 months showed only very limited difference as measured by steps per day - suggesting that the small number of (ME!) CFS patients were either only very mildly affected, or their numbers were swamped by the full cohort numbers.

Steps per day: CF+ = 8710, CF- = 9329, HC = 10094

I'm sure we'd all be ecstatic if we could rack up 86% of the walking output of a healthy person day in day out !

As to the paper as whole - the conclusions seem to be going the expected route of - deconditioning, perfectionism etc, although care seems to have been taken to avoid those specific terms.

 

[Trish]

Unsurprisingly the diagnostic method used for CF was 4 or more on the Chalder Fatigue Questionnaire, and for CFS PEM was diagnosed by the addition of a single question:

In order to investigate post-exertional malaise (PEM), the following question was set as a single item proxy: “How often do you feel more fatigued the day after an exertion?” This formulation is in line with previously used definitions of post-exertional malaise [25]. Response was given on a five-point Likert scale; a higher score implies more severe symptoms.

Combining that very weak definition of PEM, and the barely reduced step count, I'd say they included lots of people who didn't have ME/CFS.

Add to that the testing was done in a 3.5 hour visit, including breakfast followed by a long battery of cognitive tests, anyone with moderate, severe or very severe ME/CFS would have been precluded from participating.

It looks to me like the study was set up to fail to find cognitive differences by only including the very mildest ME/CFS, diluted further with people who don't have ME/CFS.

Note also out of the 195 EBV patients, 91 we classed as chronic fatigue at 6 months by the Chalder scale, but only 19 met Canadian Criteria for ME/CFS, and even those PEM was inaccurately diagnosed as PEF.

Fig. 1. Patient flow overview. EBV = Ebstein- Barr Viurs. CF = Chronic fatigue. CF+ = those who developed chronic fatigue 6 months after acute EBV infection (including a subgroup satisfying diagnostic criteria for Chronic Fatigue Syndrome (CFS)). CF− = those who did not develop chronic fatigue 6 months after acute EBV infection. HC = healthy controls. Fu = Diagnosed CFS according to the Fukuda criteria. Ca = Diagnosed CFS according to the Canada criteria.

 

[rvallee]

whereas objective measures of cognitive impairment are inconspicuous

Well of course if you try to measure the temperature of some water using a voltmeter you're going to have a bad time, even more so if you're trying to gauge how the water is feeling, which is not even measurable.

If you don't do the right tests you won't get anything useful out of those tests. I don't understand why some professor of medicine needs to be taught this stuff but, come on, at least pretend to be serious here.

Also:

the healthy control group (cognitive symptoms sum score = 6.4)

If your control rates that high on what is supposed to be the ground truth, your whole setup is bad. Tare your damn scale before you measure. And that's when you can measure, here it's just ratings on an arbitrary scale.

 

[Sean]

No 2-day test protocol?

 

[Ravn]

In sum, it is possible that the adolescents with CF/CFS in the current study are guided by cognitive processes that lead them to become more susceptible to overestimate their cognitive difficulties, have higher perceptions of cognitive effort, and develop more negative response outcome expectancies.

Rather than tying oneself in knots over faulty perceptions, a much simpler explanation here would be that these relatively mildly affected (ref step count) participants are able to perform normally for a limited period of time but that they need to use more brain resources to achieve the this. So these participants report - accurately - greater fatigue and greater effort (something I seem to vaguely recall has already been shown in some brain scan study?)

 

[inox]

So these participants report - accurately - greater fatigue and greater effort (something I seem to vaguely recall has already been shown in some brain scan study?)

I’m even pretty sure Wyller himself did a brain scan study that showed this?

 

[Milo]

First I didn't open the link and have not read the paper.

I agree that the number of steps does not reflect that of a moderate or severe patient.

I am reminded of an imaging paper mentioning that patients with ME activated more brain regions than healthy controls for a similar cognitive task. I am not sure that this has been considered for this paper. I am not sure these authors had intentions of performing fMRI and other imaging methods for real objective measures, for this paper of in future papers.

 

[Esther12]

Anyone have any views on the forms of objective testing used? Would we expect these to be useful tests for the sorts of cognitive problems ME/CFS patients report?

 

[Jonathan Edwards]

Anyone have any views on the forms of objective testing used? Would we expect these to be useful tests for the sorts of cognitive problems ME/CFS patients report?

I rather doubt it. These look like the sort of tests that might show low scores after stroke or encephalitis with slowing of times of basic perceptual mechanisms. I suspect my mother at 100 with established dementia might be normal on several of them.

The sort of thing I would suggest would be what I have had for my Spanish class homework this week. To read an imaginary holiday travel contract of about 1500 words and then answer questions about whether imaginary travellers' claims for recompense were justified. You have to be quite motivated to read the whole contract in the first place. Some of the answers depend on specific conditions for specific cases - such as information on price rises at least twenty days in advance - but others just depend on remembering the scope of the contract clauses. The test could be done with the contract available to refer back to but against the clock.

 

[Joan Crawford]

Only had a brief look over the tests chosen. All seem remarkably easy. Not in line with the literature and my clinical experience where tests need to be complex and require time pressure and/or endurance to show up pwME's cognitive difficulties.

Poor choice of tests.
Poor choice of subjective measures too. HADS, for example, cannot just be given out to fill in as some questions need interpretation so as not to conflate ME symptoms with low mood.
Perhaps poor choice of participants too (not read that part).

Pw severe ME are beyond are often deficient in more than one cognitive domain and meet criteria for Mild Neurocognitive disorder (not mild but to differentiate from Severe Cognitive disorder in dementia etc).

Biased and unhelpful.

 

[Joan Crawford]

I rather doubt it. These look like the sort of tests that might show low scores after stroke or encephalitis with slowing of times of basic perceptual mechanisms. I suspect my mother at 100 with established dementia might be normal on several of them.

The sort of thing I would suggest would be what I have had for my Spanish class homework this week. To read an imaginary holiday travel contract of about 1500 words and then answer questions about whether imaginary travellers' claims for recompense were justified. You have to be quite motivated to read the whole contract in the first place. Some of the answers depend on specific conditions for specific cases - such as information on price rises at least twenty days in advance - but others just depend on remembering the scope of the contract clauses. The test could be done with the contract available to refer back to but against the clock.

These types of tests exist.

Researchers made poor choices.