Brain imaging reveals clues about chronic fatigue syndrome

[Simon]

The study used the Reeves 2005 population but remember that included assessment as:

The clinical visit included detailed medical history, physical examination, laboratory tests, psychiatric screen, and questionnaires to measure functional status, impairment and symptoms, and was completed by 783 persons. Participants were classified as: i) CFS cases, according to the 1994 case definition[22], [23]; i


Further the current study had an extensive exclusion process which included:

Subjects with a score >60 on the 20-item, self report Zung Self Rating Depression Scale (Zung SDS)(indicating more than mild depressive symptoms) were also excluded [25]. All subjects were required to be free of psychotropic medications including antidepressant, antipsychotic, mood stabilizer or anti-anxiety medications for at least 4 weeks prior to brain imaging procedures. No subjects were taken off psychotropic medications for the purposes of the study.

One of the criticism of Reeves work is that it didn’t distinguish between ME and depression, but it would appear that this study went to some lengths to avoid conflation. So as I read it, the study CFS cohort was Fukada, but with identifiable depression or other psychiatric confounders allowed by Fukada removed – so not a bad proxy for a wider ME/CFS population. That said I’d agree that the results are not overwhelming – another study that shows there’s ‘stuff going on’ but that the ‘stuff’ is all over the place. Some discussion about articulating the problems of definitions in the P2P context here: http://www.occupycfs.com/2014/05/22/p2p-agenda-fatigue/#comments

It would be easy to get the impression that they effectively used Fukuda, but they didn't. Ref 23 is the Reeves 'Empiric' criteria. The Empiric criteria is, in fact, based on Fukuda - hence the same exclusions, medical history etc - but the 'empiric' bit refers to thresholds for fatigue, physical function etc - and that's where the empiric gets it wrong.

@Simon , is it anywhere clearly cited as to what SF-36 PF scores are typically seen in clinics or outpatient studies? Has anyone reviewed the CFS and ME studies to determine what is commonly found (while acknowledging that most of these studies are primarily on mild patients). This would help us put studies like PACE into perspective.

See above re PACE - the PACE figures are in line with other outpatient studies as far as I recall - maybe a bit higher.

I was wondering how this study would relate to ideas of the lack of blood flowing to the brain. From my very limited understanding the fMRI scan is detecting changes in the flow of oxygenated blood. I think the oxygenated blood affects the magnetic field more than once the oxygen has been released. Then they make an assumption that areas of the brain where processing is happening require oxygen and hence they look for the change between oxygenated and non-oxygenated blood.

So my assumption (although I've not yet read the paper) is that what they are detecting is less blood flow and less oxygen being metabolized in areas of the brain where people have fatigue. It made me wonder if this may relate to work that Julia Newton is doing at Newcastle finding increased acidosis in muscles which I believe is due to the lack of oxygen available to turn something (glucose?) into energy.

The as yet unpublished muscle culture work done by Newton's group, using muscle biopsy samples from the same patients found similar problems and acidosis - oxygenation would be the same in both controls and patients in muscle culture, suggesting the problem is not oxygenation itself (They think it's a problem with the cell metabolism, which means not enough glucose gets burned in mitochondria).

 

[N.A.Wright]

It would be easy to get the impression that they effectively used Fukuda, but they didn't. Ref 23 is the Reeves 'Empiric' criteria. The Empiric criteria is, in fact, based on Fukuda - hence the same exclusions, medical history etc - but the 'empiric' bit refers to thresholds for fatigue, physical function etc - and that's where the empiric gets it wrong.

Right. I’d confused Georgia with Witchita, the Georgia study using Empirical at the outset and giving the absurd 2.54% prevalence - but I’m still puzzled by the follow up process that Miller used – if the 751 participants had already been classified as CFS, non fatigued, or ISF, what did the process : Following clinical and laboratory assessments, 71 persons met criteria for CFS, and 212 were determined to be controls involve ?

There certainly seems to have been a major sorting exercise which reduced the CFS cohort to just 10% of the study population, and it seems unlikely that could be soley down to use of the Empircal criteria.

 

[Simon]

Right. I’d confused Georgia with Witchita, the Georgia study using Empirical at the outset and giving the absurd 2.54% prevalence - but I’m still puzzled by the follow up process that Miller used – if the 751 participants had already been classified as CFS, non fatigued, or ISF, what did the process : Following clinical and laboratory assessments, 71 persons met criteria for CFS, and 212 were determined to be controls involve ?

There certainly seems to have been a major sorting exercise which reduced the CFS cohort to just 10% of the study population, and it seems unlikely that could be soley down to use of the Empircal criteria.

The 751 figure is those assessed in the Clinic, not CFS cases. The original Georgia study identified 113 CFS cases in the clinic (most of the cases assessed in the Clinic then were not CFS either). Presumably a good chunk of the original sample would have been lost to follow up 3-4 years later in any case. So they didn't reduce the CFS cases to 10% of the original.

Edit: I think the original classification was based on questionnaire answers, a crude screen before diagnosis by lab tests and clinical assessment, inc psych screen.

Edit 2: dull stuff, mainly for my notes, but further reason to assume this isn't a representative CFS sample:
As I'd pointed out earlier, the SF36 physical function score of 64 indicates are surprisingly able-bodied group. I've no checked out the fatigue score and the results are the same.

They measured fatigue with the MFI-20 (Multi-Dimensional Fatigue Inventory) scale. I'll just look at the Mental Fatigue subscale here, as that was what correlated so strongly with the fMRI results: those with more fatigue showed less basal ganglia response to the gambling test.

The mental fatigue scale scores between 4 (no problems) to 20 (worst problems)
This study mean score: Controls=5.8, CFS=12.7

So what's 12.7/20 like?

Well, here's another study using the MFI in, as it happens, the same original Georgia study. This study found a Mental Fatigue score of:
CFS-like=11.0
So here, CFS-like wasn't quite as bad as CFS for mental fatigue, but it wasn't so far off either; 56% of CFS-like cases were evaluated as full CFS cases in the clinic.

Here's the killer stats though, for that CFS-like group with similar mental fatigue scores (though a bit lower) to the CFS patients in the new study:
Full time working (>30 hours a week)=55%
Part time=11%
So two-thirds of a group of patients with similar mental fatigue scores to the basal ganglia study patients were working. That does not look like any group of CFS patients I've seen - apart from those selected with the empiric criteria.