Do childhood sleep issues "have a causal role" in 'chronic disabling fatigue' in adolescence?

There's those words again: 'chronic disabling fatigue' or CDF, being used as a proxy for chronic fatigue syndrome (CFS, also known as 'ME') as per the findings reported by Simon Collin and colleagues [1].

Elements of this authorship group seem to be using CDF quite a bit (see here and see here) in their various research studies, and I have to say it's starting to get a little confusing (see here). I'll come back to my thoughts on the term CDF in a moment...

On this research occasion, Collin et al set out to explore whether "sleep might be a causal risk factor for CFS/ME" (or should that just be CDF) on the basis that sleep issues have been reported in that context previously [2]. Once again, "data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort" was the research source material, and researchers were specifically looking at: "sleep patterns of children aged 6 months to 11 years, who were subsequently classified as having (or not having) 'chronic disabling fatigue'... between the ages 13 and 18 years." Sleep duration was quite a big element to this study.

So yeah, shorter night-time sleep duration from 6 months to 11 years of age did seem to show some connection to CDF. To quote: "The odds of CDF at age 13 years were 39% lower... for each additional hour of night-time sleep at age nine years, and the odds of CDF at age 16 years were 51% lower... for each additional hour of night-time sleep at age 11 years." This and a few other observations led authors to conclude that sleep abnormalities might have a role to play in relation to CFS/ME (sorry, CDF).

I have to say however, that I'm not particularly impressed with these findings. I say that on the basis that one set of variables (sleep) are being *correlated* with another later variable (CDF) and well, correlation does not necessarily equal causation. As per other work from this authorship group [2], they've also previously suggested that level of physical activity *might* also correlate with CFS/ME (sorry CDF) albeit with a reduced timescale between the variables. This dual research based on the same cohort I assume, kinda disqualifies any one variable from being related to CDF. Assuming that is, that sleep and physical activity are not somehow connected...

And then there's the issue of how sleep duration was measured in the latest Collin paper: "The sleep durations in our study were obtained from parents’ (mostly mothers’) answers to questions about the child’s usual bedtime and waking time, rather than from data collected in a sleep/wake diary or by actigraphy." So, they basically asked what time children went to bed and what time they woke up. There's nothing wrong with asking such questions but likewise there is little to confirm that children actually closed their eyes and nodded off the minute they went to bed and/or woke up the minute of parental report on waking. Anyone who has children knows that this is 'optimistic' at best (and indeed, takes no account of things like duration of night waking or quality of sleep for examples). The lack of use of actigraphy - that fabulous wearable tech that allows us to objectively chart sleep and activity cycles - is a real problem for elements of CFS/ME research (see here), and is something that is getting harder and harder to overlook. This includes the lack of use in this particular research study too.

Then, back to CDF. CDF basically comes about because we are told that "children in [the] study were not examined by a physician" when it comes to CFS/ME. Further: "CDF at ages 13 and 16 years was defined as fatigue (feeling tired or lacking in energy) of >6 months’ duration that was associated with absence from full-time school or that had prevented the child from taking part in activities ‘quite a lot’ or ‘a great deal’, excluding fatigue possibly associated with sport, snoring, and other illnesses." So fatigue is a primary symptom. But how can you exclude fatigue associated 'other illnesses'? Did the authors for example, screen for something like fatigue due to mitochondrial issues or disorders (see here)? No, they didn't appear to. Similarly there is no mention as far as I can see of another primary symptom of CFS/ME: post-exertional malaise (PEM). Important too was another quote from the authors: "Our definition of CDF did not exclude children with comorbid depressive symptoms." I'll say little more on this topic.

So, again, unfortunately I have to say that I'm left unimpressed by these latest findings from Collin and colleagues. And once again, I have to point out that CDF whilst described as "a proxy for chronic fatigue syndrome/ME" is not necessarily CFS or ME (and indeed, neither it seems, could it be both).

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[1] Collin SM. et al. Childhood sleep and adolescent chronic fatigue syndrome (CFS/ME): evidence of associations in a UK birth cohort. Sleep Med. 2018 Jun;46:26-36.

[2] Collin SM. et al. Physical activity at age 11 years and chronic disabling fatigue at ages 13 and 16 years in a UK birth cohort. Arch Dis Child. 2018 Jun;103(6):586-591.

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"Due to the definitions of ME and CFS, “ME/CFS” does not exist..."

Today, May 12th, is ME/CFS and Fibromyalgia International Awareness Day, a day to designed to "bring awareness to ME/CFS patients, families, caregivers, and researchers." Keep that terminology in mind...

The quote heading the title of this post - "Due to the definitions of ME and CFS, “ME/CFS” does not exist..." - comes from the viewpoint paper published by Frank Twisk [1]. The report covers an important topic in the realms of chronic fatigue syndrome (CFS) also known as myalgic encephalomyelitis (ME) also known as systemic exertion intolerance disease (SEID) in terms of whether it is appropriate to use such terms of defining the illness in a mixed or interchangeable fashion. Indeed, whether the connections between all those 'also known as' words I just used are actually accurately reflective of current diagnostic descriptions...

It's no secret that science and clinical practice is still coming to grips with some of the fundamentals of CFS, ME and SEID (see here and see here for examples) in terms of what to call it, how to define it and how to test for some of the fundamental diagnostic characteristics (see here). It's also still dealing with things like the definition of recovery (see here), which might seem like common sense (a complete and sustained remission of symptoms) but hasn't been particularly straightforward in this area for quite a few reasons.

Twisk takes the reader through some of the history of the terminology used and, how, whilst there is overlap in the way that ME, CFS and SEID are defined (chronic and long-lasting weakness or fatigue is a commonality), there are also some important differences. Take for example the authors description of the Ramsay criteria for ME and specifically onset: "Illness commonly initiated by respiratory and/or gastrointestinal infection, but an insidious or more dramatic onset following neurological, cardiac, or endocrine disability occurs." This contrasts with the onset criteria for CFS and SEID which basically says little about how symptoms start or come about.

Twisk concludes that: "ME is a neuromuscular disease" and should typically not to be viewed as 'equivalent' to CFS. CFS, he argues, tends to rely heavily on a single mandatory 'chronic fatigue' symptom, something that might intersect with ME but does not go far enough to evoke a full diagnosis of ME. As for SEID, well, trumpeted as being the solution to all the diagnostic confusion, SEID has it's own issues according to Twisk. Not least that it can't serve both masters (ME and CFS) in diagnostic terms. Also important: "SEID case criteria are also applicable to subsets of people with other diseases, for example, Multiple Sclerosis (MS) and lupus; and psychological conditions, for example, major depression." There is the propensity for diagnostic confusion.

I do think that Twisk is on to something with his observations. I know quite a few people who don't like the confusion caused by combination terminology like 'ME/CFS'; often seeing it as conflating two (or even more!) quite different conditions. Add in yet another potentially important variable to such an argument - the addition of chronic disabling fatigue (CDF) as "a proxy for clinically diagnosed CFS/ME" as some authors have (see here) - and things get even more muddled. I daresay a lot of this confusion might also intersect with discussions/debates/arguments as to how far something like the biopsychosical (BPS) model should or rather shouldn't be applied to such fatigue related conditions (see here)...

You want to do something for ME/CFS and Fibromyalgia International Awareness Day? Well, first thing you could do is watch 'Unrest', then follow the #millionsmissing hashtag and then push for more research, biological research...

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[1] Twisk FNM. Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Systemic Exertion Intolerance Disease: Three Distinct Clinical Entities. Challenges. 2018; 9(1): 19.

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Is early adolescent physical activity protective against later "chronic disabling fatigue"?

TIE fighter crossing the moon?

One particular detail in the recent paper by Simon Collin and colleagues [1] (open-access available here) talking about higher physical activity potentially being *protective* against subsequent adolescent 'fatigue', immediately caught my attention: "CDF [chronic disabling fatigue], a proxy for clinically diagnosed CFS/ME [chronic fatigue syndrome/myalgic encephalomyelitis]."

This is not the first time that this authorship group have used the term CDF and seen it's use 'merging' into meaning something close to or like CFS/ME (see here) and I doubt that it will be the last. Far be it from me to put myself forward as some sort of expert on diagnosing CFS/ME - I'm not - but CDF as representing a proxy for CFS/ME does not mean that CDF is the same as CFS/ME. And that's also bearing in mind that the issue of diagnosis of CFS/ME is still the topic of lots and lots of (continuing) discussion (see here)...

Keeping all that in mind, I do want to briefly talk about the new paper from Collin et al. The Avon Longitudinal Study of Parents and Children (ALSPAC) was, once again, the data source for their findings, and yet again, this was a study looking at adolescent and young adults. The aim of the study was to: "investigate whether levels and patterns of physical activity at age 11 years are associated with ‘chronic disabling fatigue’... at ages 13 and 16 years."

A strength of the Collin research is that authors looked at more than just subjective 'how much exercise did you do' questionnaire via their use of actigraphy. So: "All ALSPAC children who attended research clinics at age 11 years... were asked to wear an Actigraph AM7164 2.2 accelerometer (Actigraph LLC, Fort Walton Beach, Florida, USA) for 7 days." Further: "Data from children who had worn the accelerometer for at least 10 hours a day for at least 3 days were considered valid" and from such data various calculations were made in terms of sedentary time, total physical activity and the proportion of "moderate-to-vigorous physical activity." Such data was analysed in the context of CDF measurements at ages 13 and 16 using methods previously described in their other research [2].

Results: "Children who had CDF at age 13 years had lower levels of physical activity at age 11 years." The authors translated this into various stats including: "For each additional 1% of monitored time spent in moderate-to-vigorous activity, the odds of CDF were reduced by 16%" and "Each additional hour of sedentary time per day was associated with 35% higher odds of CDF."

But just before anyone thinks that pushing children off the sofa and into some moderate-to-vigorous exercise in early adolescence is some kind of magical shield protecting against CDF, a few words of caution from the authors might also be important. Namely: "the lower levels of physical activity at age 11 years [may be] a consequence of chronic fatigue which is already present or developing and which persists until the child is 13 years old." In other words, there could be an alternative explanation for the lower physical activity (PA) levels *causing* chronic disabling fatigue; those who didn't do much PA were already developing and manifesting CDF...

"The main limitation of our study is that children were not assessed by a doctor, which is why we describe our outcome as ‘chronic disabling fatigue’, a proxy for CFS/ME." Yup, no arguments there; also reiterating why one needs to be quite careful about the terminology used around CFS/ME. The suggestions that lower physical activity might show a *correlation* with CDF also needs to be carefully handled given some continuing conversations about 'exercise therapy' in the context of CFS/ME (see here) and in particular, what various patients have been reporting from interventions in this area (see here)...

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[1] Collin SM. et al. Physical activity at age 11 years and chronic disabling fatigue at ages 13 and 16 years in a UK birth cohort. Arch Dis Child. 2018 Jan 30. pii: archdischild-2017-314138.

[2] Norris T. et al. Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents. Arch Dis Child. 2017 Jun;102(6):522-528.

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