Discussion of full IOM report

[Valentijn]

Do they really need to emphasise the fact that sleep is not curative in this way?

Based on some of the media coverage regarding "chronic fatigue"? Yes, they do need to clarify that I'm not sure it's appropriate to include a clarification in the primary criteria, however.

 

[Sidereal]

Page 80-81:

A few studies that compared ME/CFS with other diseases found that, although PEM was experienced by 19 to 20 percent of subjects with major depressive disorder (Hawk et al., 2006a; Komaroff et al., 1996b) and 52 percent of patients with multiple sclerosis (Komaroff et al., 1996b), it was still much more common in ME/CFS patients than in comparison groups. One study found that 64 percent of patients with major depressive disorder experienced PEM, but the authors did not describe how PEM was assessed (Zhang et al., 2010). As mentioned earlier, these prevalence estimates may vary depending on how PEM was defined and queried for, and thus need to be interpreted with caution.

Has anyone read these three studies? I find it very surprising to hear that 64% of patients with depression have PEM. If true, this would have important implications. I wonder if the way PEM was elicited in these studies was inappropriate in that it could have been DOMS (e.g. Do you feel tired and have muscle aches the day after exercise? duh) which of course they would get due to inactivity.

 

[Valentijn]

Has anyone read these three studies? I find it very surprising to hear that 64% of patients with depression have PEM. If true, this would have important implications. I wonder if the way PEM was elicited in these studies was inappropriate in that it could have been DOMS (e.g. Do you feel tired and have muscle aches the day after exercise? duh) which of course they would get due to inactivity.

Some studies describe PEM very badly, basically as DOMS.

 

[Forbin]

Some studies describe PEM very badly, basically as DOMS.

Yes, it's not even clear that PEM is universally understood as a delayed "malaise" that peaks 24 hours later. The Lights' gene expression study showed significantly increased production of certain immune / sensory / adrenergic proteins by white blood cells peaking 24 hours after exercise. It seems likely that this is connected to PEM.

"Malaise" has an unfortunate common connotation of "aimlessness" and "inertia" but it also has a fairly specific medical meaning, i.e. "a condition of general bodily weakness and discomfort, often marking the onset of disease" [Webster's Dictionary].

This is pretty much my experience - a period of intensified "flu-like" sensations - by which I mean the intense sense of immune system activation in tandem with the weariness and muscle pains that comes with the flu - especially during the initial hours of the flu. This, of course, is on top of the usually elevated levels of these symptoms that are a constant companion in ME/SEID regardless of exertion.

I recall Dr. Komaroff describing PEM as being "wiped out," the way you get with the flu. He also said he has never seen it in any patient with any disease other than Chronic Fatigue Syndrome.

 

[Sidereal]

I recall Dr. Komaroff describing PEM as being "wiped out," the way you get with the flu. He also said he has never seen it in any patient with any disease other than Chronic Fatigue Syndrome.

Interesting, since he's the first author on a 1996 study cited in the report as showing that

PEM was experienced by 19 to 20 percent of subjects with major depressive disorder (Hawk et al., 2006a; Komaroff et al., 1996b) and 52 percent of patients with multiple sclerosis (Komaroff et al., 1996b)

 

[Forbin]

Interesting, since he's the first author on a 1996 study cited in the report as showing that

Well, here is the quote from an audio recording I have. I think this was from the Q&A session following a 2010 presentation to the Massachusetts CFIDS Association. Videos of that presentation are on youtube but I can't find the Q&A session at the moment.

Q:"'How do patients with depression compare to CFS patients?'"

A: "As a doctor who has taken of care of patients with major depression for many years, I can't recall a single instance of someone with major depression saying, 'The strangest thing has been happening to me, Doctor. Whenever I do anything, any physical exertion, the next day I feel completely beat up.'"

"I've never heard that - from any patient with any illness, other than people with Chronic Fatigue Syndrome."

 

[Bob]

I posted this elsewhere, and thought it might be of interest in this thread...

The full report includes an interesting history of ME and CFS, including a description of the historic ME outbreaks in the UK, and the outbreaks in the USA that led to the introduction of the CFS moniker. It dismisses the historic claims that the UK ME outbreaks were a case of hysteria. The report acknowledges that patients protested about the IOM process and wanted the money to be used for biomedical research instead, and it acknowledges the letter sent from the expert clinicians that demanded the use of the CCC.

 

[Sidereal]

Well, here is the quote from an audio recording I have. I think this was from the Q&A session following a 2010 presentation to the Massachusetts CFIDS Association. Videos of that presentation are on youtube but I can't find the Q&A session at the moment.

Q:"'How do patients with depression compare to CFS patients?'"

A: "As a doctor who has taken of care of patients with major depression for many years, I can't recall a single instance of someone with major depression saying, 'The strangest thing has been happening to me, Doctor. Whenever I do anything, any physical exertion, the next day I feel completely beat up.'"

"I've never heard that - from any patient with any illness, other than people with Chronic Fatigue Syndrome."

Right, exactly. I'm very surprised to see those rates of alleged PEM in depression samples. I'm not a clinician but I spent some years doing clinical research on depression and I've never heard anyone say this to me either.

 

[Forbin]

Right, exactly. I'm very surprised to see those rates of alleged PEM in depression samples. I'm not a clinician but I spent some years doing clinical research on depression and I've never heard anyone say this to me either.

The study referred to in the IOM paper might be...

An examination of the working case definition of chronic fatigue syndrome.
Komaroff AL,Fagioli LR,Geiger AM,Doolittle TH,Lee J,Kornish RJ,Gleit MA,Guerriero RT.

Conclusion: Patients meeting the major criteria of the current CDC working case definition of CFS reported symptoms that were clearly distinguishable from the experience of healthy control subjects and from disease comparison groups with multiple sclerosis and depression. Eliminating three symptoms (ie, muscle weakness, arthralgias, and sleep disturbance) and adding two others (ie, anorexia and nausea) would appear to strengthen the CDC case definition of CFS.

 

[Sidereal]

Full abstract: http://www.ncbi.nlm.nih.gov/pubmed/8579088

Am J Med. 1996 Jan;100(1):56-64.
An examination of the working case definition of chronic fatigue syndrome.
Komaroff AL1, Fagioli LR, Geiger AM, Doolittle TH, Lee J, Kornish RJ, Gleit MA, Guerriero RT.
Author information

Abstract
PURPOSE:
Chronic fatigue syndrome (CFS) currently is defined by a working case definition developed under the leadership of the United States Centers for Disease Control and Prevention (CDC) based on a consensus among experienced clinicians. We analyzed the experience from one large center to examine the adequacy of the case definition.

PATIENTS AND METHODS:
Predefined clinical and laboratory data were collected prospectively from 369 patients with debilitating fatigue, of whom 281 (76%) met the major criteria of the original CDC case definition for CFS: (1) fatigue of at least 6 months' duration, seriously interfering with the patient's life; and (2) without evidence of various organic or psychiatric illnesses that can produce chronic fatigue. The same clinical data were obtained from 311 healthy control subjects and two comparison groups with diseases that can present in a similar fashion; relapsing-remitting multiple sclerosis (n = 25) and major depression (n = 19).

RESULTS:
All of the minor criteria symptoms from the original CDC case definition distinguished patients with debilitating chronic fatigue from healthy control subjects, and many distinguished the patients with chronic fatigue from the comparison groups with multiple sclerosis and depression: myalgias, postexertional malaise, headaches, and a group of infectious-type symptoms (ie, chronic fever and chills, sore throat, swollen glands in the neck or underarm areas). In addition, two other symptoms not currently part of the case definition discriminated the chronic fatigue patients from the control/comparison groups: anorexia and nausea. Physical examination criteria only infrequently contributed to the diagnosis. Patients meeting the CDC major criteria for CFS also met the minor criteria in 91% of cases.

CONCLUSION:
Patients meeting the major criteria of the current CDC working case definition of CFS reported symptoms that were clearly distinguishable from the experience of healthy control subjects and from disease comparison groups with multiple sclerosis and depression. Eliminating three symptoms (ie, muscle weakness, arthralgias, and sleep disturbance) and adding two others (ie, anorexia and nausea) would appear to strengthen the CDC case definition of CFS.

 

[Forbin]

Yeah. I was changing my post as you were putting up the correct one.

 

[Sidereal]

Yeah. I was changing my post as you were putting up the correct one.

Without the full paper we won't know how they phrased/elicited PEM question(s).

 

[MeSci]

I think the emphasis here is on unrefreshing. The point is not whether we sleep well or not. The point is that sleep does not relieve the fatigue/exhaustion, as it does with healthy people. Sleep does not refresh us. Our lack of energy is much more complex than a simple need for a good night's sleep. I think that's the point they're trying to make.

OK - thanks to @Bob's help, I now have the full report (they did well to get 305 pages into 1.3 Mb!).

The bit that I had been struggling to read online was (my bolding):

Frequency and severity of symptoms should be assessed. The diagnosis of ME/CFS should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.

This refers to the asterisked symptoms in the diagnostic criteria, which include unrefreshing sleep and PEM, which answers my question.

(I do sometimes wake very refreshed, but I still have the propensity to suffer PEM, etc. And I have had spells when I could exert myself substantially without PEM, but sadly they haven't lasted.)

 

[Simon]

"Unrefreshing sleep"

Are there qualifications for the key symptom of unrefreshing sleep? Some of us have found solutions to this, and now sleep quite well, but we still have ME/SEID. I also believe that I read here that some people don't have that symptom. Does that definitely mean they don't have ME? (It's still ME in the UK, so I don't want to switch yet!)

I too sleep quite well and awake 'refreshed' in the sense I don't feel fatigued, but I quickly fatigue once I start dong things. And clearly that applies to quite a few poeple eg this (From another thread)

Why I dont meet it well is I dont at all currently wake up unrefreshed. (It only happens if Im having a crash and if I stay out of crashes (which I try very hard to do as that can cause me to end up in hospital) ..it doesnt happen at all.

Like @taniaust1, after a relapse, or overdoing things, I feel ill and unrefreshed; for me it's linked to PEM.

It is clear, however, that people with ME/CFS universally report experiencing unrefreshing sleep,

Er, never seen a study where sleep problems are reported by 100%, or even close, this sounds like slightly wishful justification for a chosen criteria. If the question of sleep was posed more widely eg to include PEM problems, or 'unrefreshing' meaning 'not restoring energy levels to normal' then maybe. I'm still unclear why this is up there with PEM. Maybe I should read their sleep section next. Just as soon as I have the energy...

Edit:
Thanks @MeSci

Frequency and severity of symptoms should be assessed. The diagnosis of ME/CFS should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.

Would like to see the evidence of this being universal for unrefreshing sleep.

 

[Joss]

I would have preferred 'slerp dysfunction' or 'disordered sleep. ? Not 'unrefreshibg sleep'.

 

[adreno]

If the question of sleep was posed more widely eg to include PEM problems, or 'unrefreshing' meaning 'not restoring energy levels to normal' then maybe.

Yes, I think this is the main point of the criteria, that sleep does not ameliorate PEM, or "exertion intolerance" (i.e., it does not "refresh" the patient). In other words, SEID is not caused by a lack of sleep.

 

[Mij]

It seems to be quite common to start with hypersomnia and later switch to insomnia/hyposomnia. Is there any reference to that?

The ME specialist I saw 24yrs ago told me this would happen down the road. He was right. He told me that hypersomnia is common in the acute stages (but I've had it occur off and on throughout the years). So he knew this based on experience? Or he had scientific references.

"Dysfunction in the posterior hypothalamus and the upper part of the mid-brain"

http://www.hfme.org/themesymptomlist.htm

 

[Bob]

Er, never seen a study where sleep problems are reported by 100%, or even close, this sounds like slightly wishful justification for a chosen criteria. If the question of sleep was posed more widely eg to include PEM problems, or 'unrefreshing' meaning 'not restoring energy levels to normal' then maybe. I'm still unclear why this is up there with PEM.

I don't understand why they've included unrefreshing sleep either, but the idea is more appealing to me as I think about it more.

They say that unrefreshing sleep is not related to sleep pathology and that there is not consistent evidence for sleep pathology in ME/CFS. (See my earlier quote from the report.) I might be wrong but my interpretation is that "unrefreshing sleep" is not related to sleep itself, but is related to function not being restored upon waking. And obviously, a night's sleep does not lead to any sort of recovery for ME patients, whereas sleep does restore function in a healthy person if they are feeling fatigued when they go to sleep. That's my current interpretation anyway, but perhaps I've misinterpreted it. I like the contrast between the restorative sleep in healthy people vs non-restorative sleep in ME patients.

 

[Bob]

I would have preferred 'slerp dysfunction' or 'disordered sleep. ? Not 'unrefreshibg sleep'.

I wouldn't want that to be a criteria, because many of us sleep soundly, and many of us have fairly normal sleep patterns.

 

[Mij]

@MeSci

http://www.slideshare.net/dennis43/neurological-abnormalities

Saiki Tajima, M.D. The actigraphy (activity) study found that there were four different types of fatigue; long sleepers (hypersomnia-like), severe insomnia, short sleep (‘wired but tired’ – hyposomnia), and delayed sleepers. When this researcher looked at heart beat variability he found that parasympathetic nervous system activation was significantly decreased during sleep in CFS patients. This is an interesting finding given the number of sleep studies that have not found sleep problems in many CFS patients.