• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

BMJ: Are there sleep-specific phenotypes in patients with chronic fatigue syndrome?

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
Are there sleep-specific phenotypes in patients with chronic fatigue syndrome? A cross-sectional polysomnography analysis

  1. Zoe M Gotts1,
  2. Vincent Deary1,
  3. Julia Newton2,
  4. Donna Van der Dussen3,
  5. Pierre De Roy3,
  6. Jason G Ellis1

  1. Correspondence to Dr Jason G Ellis; Jason.ellis@northumbria.ac.uk
  • Received 5 April 2013
  • Revised 24 April 2013
  • Accepted 25 April 2013
  • Published 1 June 2013
Abstract

Objectives
Despite sleep disturbances being a central complaint in patients with chronic fatigue syndrome (CFS), evidence of objective sleep abnormalities from over 30 studies is inconsistent. The present study aimed to identify whether sleep-specific phenotypes exist in CFS and explore objective characteristics that could differentiate phenotypes, while also being relevant to routine clinical practice.

Design
A cross-sectional, single-site study.

Setting
A fatigue clinic in the Netherlands.

Participants
A consecutive series of 343 patients meeting the criteria for CFS, according to the Fukuda definition.

Measures
Patients underwent a single night of polysomnography (all-night recording of EEG, electromyography, electrooculography, ECG and respiration) that was hand-scored by a researcher blind to diagnosis and patient history.

Results
Of the 343 patients, 104 (30.3%) were identified with a Primary Sleep Disorder explaining their diagnosis.

A hierarchical cluster analysis on the remaining 239 patients resulted in four sleep phenotypes being identified at saturation.

Of the 239 patients, 89.1% met quantitative criteria for at least one objective sleep problem. A one-way analysis of variance confirmed distinct sleep profiles for each sleep phenotype.

  • Relatively longer sleep onset latencies, longer Rapid Eye Movement (REM) latencies and smaller percentages of both stage 2 and REM characterised the first phenotype.
  • The second phenotype was characterised by more frequent arousals per hour.
  • The third phenotype was characterised by a longer Total Sleep Time, shorter REM Latencies, and a higher percentage of REM and lower percentage of wake time.
  • The final phenotype had the shortest Total Sleep Time and the highest percentage of wake time and wake after sleep onset.

Conclusions
The results highlight the need to routinely screen for Primary Sleep Disorders in clinical practice and tailor sleep interventions, based on phenotype, to patients presenting with CFS. The results are discussed in terms of matching patients’ self-reported sleep to these phenotypes in clinical practice.

Full text is available - open access.

Key messages

  • Over 30% of individuals with CFS met the diagnostic criteria for Sleep Apnoea or Periodic Limb Movement (PLM) Disorder that could explain their current diagnosis.
  • The sleep in those with CFS, without Sleep Apnoea or PLM Disorder, centred around four specific sleep-disturbed phenotypes, with 89.1% demonstrating quantitative criteria for insomnia or hypersomnolence.
  • Each sleep-phenotype in CFS comprised objective characteristics that could be assessed and differentiated using patient's self-reports in primary care.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
The findings from the present study should be viewed with the limitations in mind. There was no control group to determine the extent to which the four phenotypes exist in the general population.

That said, with 6–10% of the population meeting the diagnostic criteria for insomnia56 and 5% meeting the diagnostic criteria for hypersomnia,57 the present data do not reflect this with 213 of the 239 (89.1%) participants, without apnoea or PLMS, meeting at least one quantitative criterion for insomnia or hypersomnia.

It could also be argued that a single night of polysomnography may not be enough to capture the sleep of patients with CFS due to the first-night-effect.44 The first-night-effect is a commonly observed response to the first night of sleeping in an unusual environment, such as a sleep laboratory, whereby aspects of sleep can be affected.

That said, where Le Bon and colleagues demonstrated significant differences between nights 1 and 2 in a cohort of individuals with CFS, these differences were not largely evident in the sleep architecture and many differences in the sleep continuity variables disappeared after those with psychiatric illnesses were excluded from the analysis.

Interestingly, over 25% of Le Bon et al's44 sample also demonstrated an ‘inverse first-night-effect’ whereby they slept better on the first night compared with the second night. This issue of the first-night-effect in CFS is further complicated by other studies which have shown no such effect in this population.30

It is very likely that inconsistencies in the first-night-effect reflect typical night-to-night variability5860 in addition to situation-specific factors, such as acclimating to a new environment, relating to PSG on the first and second nights.

What would be ideal, albeit expensive, is a PSG study over several nights (eg, at least 14 continuous nights are suggested for insomnia61) to ensure that these issues are accounted for. That said, what may be more practical is to determine how information from the present study can inform, in conjunction with other assessments, actual clinical practice.

One suggestion is that, ideally after ruling out PSDs, individuals should be interviewed about their sleep (usually over the last month) and provided a sleep diary. This information would provide a subjective account that could be matched to the four phenotypes (as in table 3) to inform treatment.

Overall, the results suggest a significant overlap between CFS and a variety of symptoms of sleep disturbance. One night of PSG is sufficient to tease apart, and exclude, those with apnoea and PLM disorders from four other distinct sleep phenotypes in patients with CFS. Interestingly, these four phenotypes tend to mirror symptoms related to sleep quality and quantity that are amenable to different treatment strategies. As such, clinicians tailoring sleep-based interventions for patients with CFS should be mindful of these phenotypes.

This is an interesting study. If 30% of patients can be better diagnosed, excluded and treated with something else - that is good news for them.

Those that remain in the 'pot' would benefit I believe from having this focus on sleeping assessed. If these phenotypes are subsequently proven true; then hopefully we might see some specifically targeted treatments that do not exist at present beyond the 'sleep hygiene' advice.

I am apparently being subjected to this form of testing in the next couple of weeks. I'm not holding my breath - it's been a long time coming - but these night-time/sleep disturbances/unrefreshing sleep are one of my major concerns and have been for a very long time.

I've often thought 'If only I could get some decent sleep I'd be able to see how that impacts my quality of life'. Some nights are so bad they trigger fits. Anyway, be nice to get to the bottom of it but like I said I don't think you can afford to hold your breath - this is largely unknown/untreatable territory.

Nice to see Newton involved again. Apparently the MEA Ramsay Research Fund are about to confirm funding for a similar study with this group I understand.
 
Messages
13,774
Thanks Fire.

I've never been checked for anything like this, and always had a nagging thought that maybe I should be. On the other hand, I generally feel that my sleep is pretty good. Anyone know how effective treatments are for those who do have these problems?
 

NilaJones

Senior Member
Messages
647
I have sleep apnea and am unable to use a PAP machine due to injury. I do think the apnea is a factor in my illness, maybe a major one.

I finally have an appointment with a sleep doc in July, though from what I read on the net there is not much hope for a treatment that can work for me. It would be way cool if there is, though!
 
Messages
13,774
I'm sorry to hear that Nila. Best of luck with the specialist. Hopefully they will have something helpful for you. Having an alternative to the CFS label is probably a bit helpful in itself.
 

SOC

Senior Member
Messages
7,849
One of the first treatments I got was for sleep dysfunctions, which were substantial and lifelong. I felt better as soon as I was getting better sleep with OTC meds to induce sleep and prescription meds to maintain sleep. I can't say it did anything for my core me/cfs symptoms -- PENE, flu-like symptoms, cognitive problems, joint and muscle aches.

For me, there is a difference between "tired", which I was when I wasn't getting good sleep, and "completely exhausted" which I am during an ME/CFS crash.

That said, improving my sleep provided a noticeable QOL improvement, and probably helped other body systems function better, so I think it's well worth doing. :)
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
One of the first treatments I got was for sleep dysfunctions, which were substantial and lifelong. I felt better as soon as I was getting better sleep with OTC meds to induce sleep and prescription meds to maintain sleep. I can't say it did anything for my core me/cfs symptoms -- PENE, flu-like symptoms, cognitive problems, joint and muscle aches.

For me, there is a difference between "tired", which I was when I wasn't getting good sleep, and "completely exhausted" which I am during an ME/CFS crash.

That said, improving my sleep provided a noticeable QOL improvement, and probably helped other body systems function better, so I think it's well worth doing. :)

I'd be interested to hear on this thread perhaps from anyone who has experienced these EEG tests overnight. I was told that I'd perhaps be asked to wear some device or other for 24 hours.

When I was tested with EEG for epilepsy the trouble was that it can only confirm an episode. So no episode and nothing is picked up - unless your brain waves have been affected permanently, I understand.

Maybe wearing these things for a longer period will pick-up more abnormalities and in a suitable study, in more of us. I do recall how hard it was trying to get any sleep medication from the variety of doctors I have seen in my time.

Be really nice to have something to demonstrate a need other than simply describing the experiences myself or having others describe them for me.

Be even better to receive some tailoured treatment for my issues.
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
Thanks for posting, this is an interesting study. I agree it's good to exclude people whose only issue is apnea or whatever. But it's not inconceivable that people could have both apnea and ME. I'm pretty sure there is a paper out there making the recommendation that apena and other sleep disorders not be exclusionary because they are relatively common in us.

not the paper I was looking for, but KDM found 46%+ of CFS patients have comorbid sleep disorders:
http://www.ncbi.nlm.nih.gov/pubmed/11382899
Krupp et al. (1993) found a high rate of comorbid sleep disorder:
http://www.ncbi.nlm.nih.gov/pubmed/8510058

Firestormm a 24-hour study, if it's for sleep, sounds like they might want to check for narcolepsy. There are some papers saying narcolepsy is common in CFS (not sure if they have been replicated by a second team, though Krupp found a patient with narcolepsy).
http://www.ncbi.nlm.nih.gov/pubmed/20629967 (sodium oxybate, you may recall, was denied in FM and/or CFS, apparently because the population is too large)
previous paper by Spitzer et al.: http://www.ncbi.nlm.nih.gov/pubmed/20230458

I had an overnight sleep study and the wires were not too uncomfortable to have on, but annoying because I had to watch out for them a little bit through the night. They made them all into a bundle, though, so it was just one thing for me to keep track of (the attendant came and re-stuck a wire to my forehead or chin or back a couple times, though). Not unlike using a CPAP in the end, though (which similarly has a tube).

I hope both you and NilaJones get some good help.
 
Messages
759
Location
Israel
I went once to a sleep lab. With the late falling asleep and late waking a lot of us have (They force you to wake at 8a.m) I didn't get enough sleep for them to assess. So they just diagnosed me as "delayed circadium rythm" and told me to take melatonin and come back when my sleep timing was right. I told them melatonin doesn't work for me but that didn't go down well. Then I said to them "all the reasearch says that ME/Fibro/CFS have less deep sleep than ordinary people. Is there anything you can do if you find less deep sleep?"
They answered no.
So I didn't come back. My fibro gave me bloody agony in their bed all night too and I needed a few days to recover.

I have a friend with ME with the same delayed circadium rythm. She got an invitation for a sleep study for her ME and she can NEVER make it because her sleep patterns never sort out correctly enough to go.

That's what I don't understand about this study, with so many of us having delayed sleep onset and weird sleep timing, how did they manage to do it?

I sometimes wonder if I should try again
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I laughed when I read the abstract, but I am reserving further judgement till later. First, apnoea does not necessarily exclude ME ... if your only symptoms are fatigue and poor sleep, then yes it might. Second, which sleep type am I? All of them. At different times I have had something resembling each of these stages of sleep issues. So am I all four categories? I don't think so. Different stages of ME and different secondary issues including diet are likely to have a profound effect. I don't trust these categories from the start, but to be fair I have to read the full paper.

Its been about fifteen years or more since I had a sleep study. I am planning another one for later this year ... hopefully.
 

helen1

Senior Member
Messages
1,033
Location
Canada
I had an overnight sleep study done last year. It was agony with all the disruptive things that can keep a person wakeful, starting with fluorescent lights, then all the wires on your body, the nose clip, the noisy bed, the woman snoring loudly in the next room... It took me a few days to recover. They did find periodic limb movement disorder but I don't buy it. They also said I was asleep at midnight but I know I wasn't, I had just looked at the clock and was thinking of packing it in and going home. I'm in awe of anyone who can sleep well enough at a sleep lab for viable results.
 

biophile

Places I'd rather be.
Messages
8,977
Are the CDC still denying that objective sleep abnormalities even exist in CFS, or claiming that any abnormalities in a subset do not correlate with subjective complaints? I report subjective sleep problems and I have matching objective evidence listed as phenotypes in the above study, thanks.
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
I'm about to have a sleep test. It's a portable unit so they'll wire me up and then I get to go home and sleep in my own bed. I don't know yet what info it will collect but it won't cost me anything so it will be a good start even if it's not comprehensive.
 
Messages
15,786
3Fatigue Service, VermoeidheidCentrum Nederland bv, Lelystad, The Netherlands
That's where I went, and they are a very crappy "fatigue" clinic. This is most certainly not an ME study.

But I guess it explains why they diagnosed me with Fukuda even though they advertise using the CCC, and put me in for a sleep study even though I wasn't having sleep problems. It also explains why the physiotherapist had heard of Newton and took my OI problems somewhat seriously.

Maybe it also explains why they eventually de-diagnosed me with "fatigue" on the basis of "obesity". From reading the Dutch forum on the subject, it sounded like other patients had been let go too ... either de-diagnosed like me, or being charged extra money for the same services despite already having a contract with the clinic.

But something like 95% of the patients I saw in waiting rooms at their clinic were not ME/CFS. Lots of very healthy people with burnout, so I'd be curious to know where they'd even get Fukuda patients from.
 

Little Bluestem

All Good Things Must Come to an End
Messages
4,930
I have had two sleep tests. They sent me home at 5 am for the first one, which was fine since I hadn't slept at all and wasn't going to. They sent me home at 5, or possible 6, for the second. I had finally dozed off and had one fitful sleep cycle which the dr said was not sufficient to diagnose anything. If they had let me sleep for a few more hours, they might have had some useful data.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
I'm about to have a sleep test. It's a portable unit so they'll wire me up and then I get to go home and sleep in my own bed. I don't know yet what info it will collect but it won't cost me anything so it will be a good start even if it's not comprehensive.

Thanks. It was my impression that I would be doing this experiment at home as well. I should know more next Monday after a consultation with the Neurologist. It would make sense to do this kind of thing for longer at home - providing of course I can manage the darn device and it works. I don't see why a modern device cannot be developed/has not been developed to help with sleep study. There must surely be something on the market that the NHS can use. Not every county has a sleep disorder centre after all.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
I have had two sleep tests. They sent me home at 5 am for the first one, which was fine since I hadn't slept at all and wasn't going to. They sent me home at 5, or possible 6, for the second. I had finally dozed off and had one fitful sleep cycle which the dr said was not sufficient to diagnose anything. If they had let me sleep for a few more hours, they might have had some useful data.

Thanks. This was a concern I raised above - that it must surely take several days of observation to amass truly useful and objective data. Hopefully, any further study from Newton (and anyone else) will be along these lines and include a control group. Perhaps this is where the MEA are heading.

When it comes to patient observation and testing, then it makes even more sense to do this over a period - say a week. I couldn't believe that with Epilepsy they didn't do this - that they simply popped this thing on my head for 10 minutes and thought that would be enough to spot something. Even my doctor said how arbitrary this was and how it only really ever picked up people who had been severely affected by Epilepsy. I may well read-up on the latest methods for doing such tests. It was 10 years ago that I received this diagnosis of Epilepsy and things might have changed. Will know more by next week I hope.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
With epilepsy there are huge problems. Typical EEGs read only surface brain activity. If the problem is deep in the brain, it requires (I think, I could be mis-remembering) a QEEG (quantitative EEG). This is more expensive and harder to get. EEGs are simply not sensitive enough to read all epileptic problems, but then its thought QEEG isn't either. There is a suspicion that many with deep brain epilepsy wind up diagnosed with a psychogenic illness.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
With epilepsy there are huge problems. Typical EEGs read only surface brain activity. If the problem is deep in the brain, it requires (I think, I could be mis-remembering) a QEEG (quantitative EEG). This is more expensive and harder to get. EEGs are simply not sensitive enough to read all epileptic problems, but then its thought QEEG isn't either. There is a suspicion that many with deep brain epilepsy wind up diagnosed with a psychogenic illness.

The problem still persists - I understand - that unless you can record an actually 'fitting' event any diagnosis is not entirely certain. However, when 'fits' or episodes are observed by others - most especially clinicians - I don't think they can be much doubt.

This happened to me. Trouble is - my own doubt persists. The testing that occurred did not leave me very impressed. The medications however have lessened the occurrence of these episodes. They're now wanting to focus-in on my sleep patterns to try and better understand the episodes that occur when in sleep-mode, as well as the paralysis, and general sleep disruption. So much of this needs to be observed.

I almost said 'observed to be believed'. I guess it's what we all feel sometimes: 'If only they could see (and ideally feel) what is happening to me!' As I said I'm not hoping for much this time.

The study above though is I think a way to go. Needs to be bigger, longer, controlled, and better financed. Also be interested to compare the results with other conditions. I think if it can be demonstrated, as individuals, we have other things wrong with us that have not been correctly diagnosed - the 'dustbin diagnosis' label might diminish.

And it's better for us as individuals - providing of course these other diagnoses lead to specific and effective treatment for those symptoms/conditions of course. I am ready to be proved wrong - but I don't have a lot of faith in modern medicine. Not for 14 years I am afraid.
 
Messages
13,774
Lots of very healthy people with burnout,

? I've got no idea' what 'burnout' is really, but to me it seems like a lot of people with this diagnosis can be quite seriously ill, and not be able to recover. If 'burnout' is a meaningful thing, it wouldn't surprise me if a lot of people with CFS have it (if it results from pushing oneself over a long period of time, given the 'reassurance' and advice given to patients once they had fallen ill, it would not be surprising if most did).

Also, given the initial paragraph of the paper, it does sound like the study was done by quacks. "Lots of patients diagnosed with CFS really have a primary sleep disorder... but there's no moral problem with having lumped them in to one big group and made claims about their behaviour and personalities based upon very tenuous evidence... we used to do it to the gays too, and no-one got fired for that." This time they've chosen to go for the claim that CFS is related to prior over-activity, rather than under. Given how conflicted and rubbish the evidence is in this area, I wonder if they just flick a coin.