Trial Report Can a consensus occur on a research case definition for ME/CFS?, 2024, Jason

https://www.tandfonline.com/doi/full/10.1080/21641846.2024.2314409

Research Article
Can a consensus occur on a research case definition for ME/CFS?
Leonard A. Jason,
Suvetha Ravichandran
&
Aiden Rathmann
Received 05 Dec 2023, Accepted 11 Jan 2024, Published online: 13 Feb 2024

• https://doi.org/10.1080/21641846.2024.2314409

ABSTRACT

Introduction: Many controversies have emerged around developing a consensus on a research case definition for ME and ME/CFS. To determine if there might be a consensus among patients, healthcare workers, and researchers, a brief questionnaire was distributed to an international group of patients to assess key issues involving ME and ME/CFS case definitions.

Method: Respondents were asked questions about core symptoms and other critical case definition issues.

Results: Overall, post-exertional malaise, cognitive impairment, fatigue, and unrefreshing sleep were the most endorsed core symptoms with at least 80% consensus among participants. Considerable support occurred for the ME-ICC (Myalgic Encephalomyelitis-International Consensus Criteria) and the Canadian Consensus Criteria (CCC), whereas the Fukuda Criteria received the least support. Items rated as important for a research case definition included the severity of the illness, onset type, duration of illness, illness course, exclusions, and comorbidities.

Conclusions: The implications of these findings for developing a consensus on research case definition criteria are discussed.

KEYWORDS:

• ME/CFS; research criteria; case definition; consensus; patient perspectives

 

Which aligns very closely with the Institute of Medicine case definition (I think the only difference is that this allows orthostatic issues in place of cognitive ones). For reasons I never understood, Lenny Jason vociferously opposed this. Which might be why the abstract talks up the ICC and Ccc definitions and fails to mention the IOM one.
All the same, it does look like an interesting study – though, unfortunately, I can’t read it because it’s paywalled .

 

@Simon M - As you say, Jason has long been opposed to the inclusion of OI. I wish I knew why, since it is so prevalent in PwME and even more so in pediatric age people with ME....

 

Although I can understand why unrefreshing sleep might be mentioned so frequently, how often is it a feature in other illnesses? A very quick Google presents this study suggesting around 10% of all people would report it.

Prevalence and Correlates of Nonrestorative Sleep Complaints, 2005, Ohayon

Abstract
Background Nonrestorative sleep (NRS) has been little studied in the general population, even though this symptom has an important role in several medical conditions such as heart disease, fibromyalgia, and chronic fatigue syndrome, as well as various sleep disorders.

Methods A total of 25 580 individuals (age range, 15-100 years) from the noninstitutionalized general population representative of 7 European countries (France, the United Kingdom, Germany, Italy, Portugal, Spain, and Finland) were interviewed by telephone using the Sleep-EVAL system. Nonrestorative sleep was analyzed in relationship to sociodemographic determinants, environmental factors, life habits, health, sleep-wake schedule, and psychological factors.

Results The prevalence of NRS was 10.8% (95% confidence interval, 10.4%-11.2%) in the sample, was higher in women than in men (12.5% vs 9.0%; P<.001), and decreased with age. The United Kingdom (16.1%) and Germany (15.5%) had the highest prevalence of NRS and Spain (2.4%), the lowest. In multivariate analyses, several factors were positively associated with NRS. The most important were younger age, dissatisfaction with sleep, difficulty getting started in the morning, stressful life, presence of anxiety, bipolar or a depressive disorder, and having a physical disease. When compared with subjects who have difficulty initiating or maintaining sleep (without NRS), subjects with NRS reported more frequently a variety of daytime impairment (irritability, physical, and mental fatigue) and consulted a physician twice as frequently for their sleeping difficulties than did other subjects with insomnia.

Conclusions Nonrestorative sleep is a frequent symptom in the general population, but its prevalence largely varies between countries. It is often associated with mental disorders and characteristics of sleep deprivation (such as extra sleep time on weekends). Nonrestorative sleep affected more frequently the active classes of the population and caused greater daytime impairment than difficulty initiating or maintaining sleep.

It has been documented that sleep disturbances cause nonrestorative sleep (NRS), which, in turn, is associated with greater daytime sleepiness and deterioration in performance. However, usually in community-based studies, the assessment of insomnia is limited to difficulty initiating or maintaining sleep.1-6

Nonrestorative sleep appeared as an insomnia symptom in the DSM-III-R of the American Psychiatric Association in 1987.7 It was also the first time that a chapter was devoted to sleep disorders in the DSM classification. It is described as the feeling that sleep is restless, light, or of poor quality even though the duration may appear normal.

However, epidemiological studies have been slow to include NRS. Outside of the works of Ohayon et al,8-10 virtually no community study has paid attention to this symptom. Therefore, little information exists about these subjects and the frequency and severity of daytime impairment in the general population.

There is growing evidence of the importance of NRS in various clinical conditions. It has been associated with a poor prognosis in women with coronary heart disease,11 obesity,12 fibromyalgia, and chronic fatigue syndrome.13 It is also associated with various sleep disorders such as obstructive sleep apnea syndrome, restless legs syndrome, and periodic limb movement disorders.14,15 However, these clinical findings have not been followed by general population surveys. This report presents the prevalence of NRS in 7 European countries and the factors associated with NRS.

Open access, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486352

 

Could there not be substantial differences to what is meant by unrefreshing sleep in the general context? The study for example suggests that "nonrestorative sleep (NRS)...is associated with greater daytime sleepiness", however I'm not aware that, that would be the case for pwME. From what I've gathered they are typically awake and not sleepy in a classical sense, more so fatigued irrespectively of how their sleep was.

"Furthermore Nonrestorative sleep...is described as the feeling that sleep is restless, light, or of poor quality even though the duration may appear normal." I was under the impression that for pwME it is often more than that, they wake up more fatigued then when they initally went to bed, a sort of feeling as being hit by a truck when the morning arrives, that for a subset of people improves as the day goes by.

I think similar problems apply to most areas of ME/CFS, where at least to me, it's not always clear what is meant by terms such as cognitive dysfunction or what "brain fog" in LC precisely means. Many of the terminologies used seem to be quite unexplored.

 

Yes, the comparison with other illnesses would be very interesting.

However -
1. Clinicians who came up with these definitions are presumably familiar with other chronic illnesses, yet still felt NRS stood out for ME.
2. The initial DecodeME study found NRS was reported by almost all of the 17k participants, which is very different from the 10% seen in a general population (and also different from, say, headaches, which are very common in ME but also in the general population).
3. As @EndME says, the general population and PwME might not mean the same things by NRS (or the same frequency) - though we don't know if the two groups are talking about different things.

 

My n=1 experience isn't necessarily that I wake up more fatigued but that it takes a while for, in particular, my cognitive processing to get up to speed. So the feeling I have before bed and on waking is different, but both are not normal, and it is quite possible that both states could be described as fatigued.

Yes, definitely. I think far more effort needs to go into better defining all the woolly terms that are currently used rather than trying to come up with yet another research criteria.

 

That's a good point and a great idea. It also shouldn't be too hard to do. Ideally looking at prevalence in both healthy and sick comparisons.

 

1. I'm not convinced - my concern is that their experience with ME/CFS patients blinds them to how frequently the same symptom might feature in other illnesses.
2. As you know, DecodeME worked hard to recruit only ME/CFS patients, therefore it should be no surprise that it reports such high levels.
3. Which is the problem having it as a core symptom.

 

If we look at MS - a widely used comparator to ME - about half of people with MS report sleep problems. In other words, lots of people have MS without having sleep problems, so it would not be a good mandatory symptom for MS.

DecodeME did not require any specific case definition to be met - sleep problems were not mandatory (many doctors don't seem to diagnose to specific criteria, not even Nice's). Yet almost everyone with a diagnosis had sleep problems - that's why I believe the survey is good evidence that it is an almost universal symptom. I can't think of a bigger survey .

Sleep on its own would be a useless criterion, but having it as a required symptom seems to me to be a decent shout.

 

Yes, I think it is important to take into account the fact that when categorising diseases, like animal species, it is very often combinations that are crucial.

Having wings is pretty non-specific for creatures. But a four-legged creature with wings is unique - a Hippogriff. Insects have six legs and birds, angels and bats two.

NRS for me would be a way of picking out ME from other conditions where fatigue or exhaustion was not associated with any features that would make one think it was likely to be in a causal set with those with PEM, for instance. For arthritis, a rash allows you to put a patient in a group in this way, despite rashes being two a penny.

 

I found this snippet interesting, because in me at least, non-restorative doesn't result in greater daytime sleepiness. It just makes me feel leaden and energy-depleted, in the usual ME way. (I occasionally get a night of normal sleep due to being unwell with a cold or something, and it's a different experience altogether.)

Not sleeping at all would make me want to nap during the day, but six to eight hours of crap sleep seems to work fine from the point of view of keeping me awake. I'm fatigued, but never tired or sleepy. I wonder if that's true for others?

 

I agree that we need to clarify what is meant by unrefreshing sleep. I always understood it to be different to disrupted sleep patterns, rather I understood it to be even when I have a good seven or eight hours sleep I wake up feeling worse than when I went to bed. On such mornings I may need two or three hours rest lying down to recover from having been asleep.

I would agree disturbed and disrupted sleep patterns are a feature of ME, but I would see that as unrefreshing sleep periods. I would see this as distinct from unrefreshing sleep itself which is also a feature, for some at least, of ME. I don’t know how common this paradoxical sleep outcome is in other conditions.

 

I think that NRS does need to be 'cleaned up' though as a term, it might say non-restorative, but that is often heard or interpreted as 'non-refreshing sleep' and that term is a big red herring. There are many of us for whom (once we get there - if we have over-exerted and end up 'wired' I hate that term as that's also misleading) hypersleep was an important part of recovery from short-term fatiguability and PEM/over-exertion.

Even non-restorative doesn't leave enough space within its meaning most will take from it, and I suspect like me they will be cautious

It was non-refreshing/restorative definitely in the sense that it could never as per normal people refresh us back to our health in any kind of normal timeframe (let's say a month in bed). But I think other words could better define this, ones which do not carry the baggage of anyone assuming 'sleep needs to be sorted'.

Because it was vitally refreshing as part of just surviving after I'd exerted (NB a lot more than a normal person would either need or imagine would be needed vs the exertion) in trying to minimise long-term impact of exertion - I'd say restore to pre-exertion, but now so many years on with more info on PEM one wonders whether each week I did that to get through work I took 1% more off my health, and you just keep adjusting.

But I do think the term NRS needs sharpening to 'sleep that does not make the illness go away long-term' or something, because someone mild might well find a good weekend's kip makes them feel like they are on the mend for a few days until Mon-Wed catches up with them. Yet another week, another person there might be combinations of different things due to the rolling PEM (and them not getting it is PEM) situation meaning it might be unrefreshing or no sleep or refreshing and need loads.

But then saying your illness isn't cured by a good sleep is sort of classic CFS troping we've been lumbered with isn't it. And getting people to look out for and term things in terms of 'sleep issues' (as defined in non-PEM but more behavioural 'mental health dept' terms) is also another misleader for the future of tackling the illness given I think a lot of the sleep symptoms relate to and are driven by PEM.


I have a real issue with getting this correct because it plays into the behavioural/common sense presumptions that go with sleep hygeine and routines, and I've picked up there is a key segment of us which isn't a minority for whom that rest post-exertion being 'interfered with' is as dangerous as exertion itself is.



It took me a lifetime to be heard that in a choice between 'trying to only sleep on a routine' with poor sleep/no sleep/unrefreshing sleep that all escalates very quickly on your health and then sleep and vice-versa; and sleeping as your body requires it and 'getting it over and done with' then it naturally tending more into a routine as it irons out and if you don't over-exert; it's an illogical pretence of a choice. Your body goes haywire because it is being deprived of the rest that would enable it to ever get to a health level there could be sleep and then a routine.

I strongly suspect these sleep differences relate to PEM and over-exertion and proper management one day being written down (people taking noise, cognitive and exertion seriously)

...and so given the sticky-wicket we are on of how to anticipate those new to the illness who are in rolling-PEM and not knowing it what sort of sleep situation they are going to be describing 'as a history/list of perceived symptoms' vs it being inaccurate without breaking boundaries a bit on how illnesses are described/diagrammed in the orthodoxy I don't know.

 

same, tbh i often long to be sleepy in the day - it'd be great to sleep through a lot of thesuffering. And sleeping in the day only helpss me sleep at night - the more i get the easier it is to get more

 

Yes, I agree.

I'm not thinking very clearly, but what I'm trying to get at is whether there's a particular type of ME sleep that would look on paper like normal sleep. It's well-maintained; it might be disturbed by a toilet break or a partner coming to bed/getting up, but it's quickly re-established; and the number of hours is age-appropriate. Yet it's anything but normal, because as @Peter Trewhitt says, you need time to recover from it. *

I wondered if that description might separate this type of normal ME-sleep from other definitions of unrefreshing sleep ... but I'm not even sure if other people experience the same thing.

As you say, PEM-sleep is a different animal again. I often can't sleep at all; even if I do, it's fitful and I need to visit the bathroom eight or nine times a night.

* ETA: I'd probably call it exhausting sleep rather than unrefreshing sleep!

 

I should probably clarify when I describe this that I've had few days not in PEM or over-exertion in my life, and to survive have to performatively recover just enough just to perform the thing I need to that will put me back in PEM badly etc. but never/rarely 'recovered'/from that PEM bout. which might contextualise where my 'picking out a certain bit of the PEM thing' comes from. I've few days to speak of that PEM-free.

Ah yes I get that (just what you've described) as 'PEM' for an entire night - and the rest. But I just know from having had so many different levels of PEM and severity over the years that the next part of it (what I described) is still PEM - if that makes sense? It is like an acute cycle then finally you can sleep and then utter debilitation sleep, then sleep that is even more obviously refreshing feeling (because you've rested enough from before it is now more refreshing and in less pain and the other symptoms) and then slowly it eases off back into a cycle. WHich of course you then have to slowly cycle it round.

I basically spent years of my life eventually having to live backwards (never been allowed a situation where I can avoid PEM). So I can describe this sleep more easily as a recovery-process from when I finally had my week of work (every 6 weeks the sleeping weekends and as soon as I got home would 'burst' otherwise as a 'keep me just about performing in rolling PEM' holding pattern where I was getting worse every year on year, but had no choice but to keep attending work).So the cumulative part of never getting to properly recover from PEM or over-exertion and you are carrying forward that constant roller you have to then take the edge off it, with sleep being the only thing possible and indeed absolutely life-savingly essential.

It relates to PEM - is completely linked to it in a way the sleep is as vital a part of the balance equation as exertion, and is absolutely the antithesis to the sleep nonsense models of sleep hygeine and the terms used - but I'm not 'just' describing 'PEM sleep' , I'm describing the refreshing part if that makes sense? The bit you only get to once you've got enough rest to get through the first parts (except the other parts require utter rest to get through it to the next parts so rest must be 'restorative' or 'medicine' for those too?). But most people who saw me then would see me as utterly debilitated, it's just the sleep begins to actually heal, different to when you can't sleep for the pain and are exerting.

I have major concerns that we have terms that mislead people into thinking sleep isn't vital to those with ME, or helpful, or that what others would term as 'too much sleep' isn't actually what isn't just 'medicine' but almost oxygen (vital at that point and it will top you up and get you on the road again to go back out and put yourself through the same thing again). And the ridiculousness of the idea that fiddling with it so that it 'looks more normal' is more important than our health and lives is what I've experienced is what people see. In fact I think that this bias is at least as vicious and strong as the 'being productive' - I mean both are from the same place, we are hated for 'not being able to be made normal'.

I find the term 'hypersomnia' rightly offensive. It isn't my body misbehaving or dysfunctioning it is exactly like if someone had a horrendous flu and finally after x days of a terrible sore throat and aches got the medication right and passed out. That refreshing bit is like someone who had just walked the Pennines overnight for 2 days would expect their long catch-up sleep to be vs hypersomnia sounding like depression or sleeping for no reason. It is reminiscent of glandular fever in a way maybe only those who had that (or something near it with other conditions severely) might get where you might wake for 1hr and be fine then sleep another 23hrs, or be woken but be 'out of it'.

But there is a part of it - which is the bit I'm picking out - the bit which is 'recovery sleep'. NOt recovering you to where you were, and by no means a small amount of time lost vs strenght gained, but you go from agony and can't function back to nearer where you were pre-exertion/threshold crossing (for that time). There is a heck of a lot of other PEM stuff around it.

I can have 'unrefreshing sleep' in the standard sense. And have sleep hugely disturbed by pain and needing the loo constantly and RLS and all the rest. But I also have and need sleep, if not being peed around with it is refreshing if allowed to run its needed course (intensity and time) - and it is vital, and very sensitive (to being fiddled with by others the same as the health issues) . And that only comes when I've rested enough (ironically) to get there.

 

Absolutely. And I think OI is a reasonable name for it, because it doesn't try to suggest the underlying cause—which may actually be several issues, or different ones in different people.

Yes, I hadn't thought of it like that. Symptom suggests a single feature, like a headache or knee pain, whilst PEM encompasses a couple of dozen symptoms at least. Phenomenon, maybe?