Entire issue of Post Graduate Medical Journal (11/1978) devoted to ME

[alex3619]

It didn't take long ... and I will be citing Streeton and Bell.

http://www.name-us.org/ResearchPage...latoryArticles/BellCirculatingBloodVolume.pdf

ABSTRACT. Chronic fatigue syndrome (CFS) is an illness associated with severe activity limitation and a characteristic pattern of symptoms despite a relatively normal physical examination and routine laboratory evaluation. The recent description of delayed orthostatic hypotension in patients with CFS, and previous findings of reduced red blood cell (RBC) mass in other patients with orthostatic hypotension not known to have CFS, led us to measure RBC mass and plasma volume in 19 individuals (15 female, four male) with well characterized, severe CFS. RBC mass was found to be significantly reduced (p < 0.001) below the published normal range in the 16 women, being subnormal in 15 (93.8%) of them as well as in two of the four men. Plasma volume was subnormal in 10 (52.6%) patients and total blood volume was below normal in 12 (63.2%). The high prevalence and frequent severity of the low RBC mass suggest that this abnormality might contribute to the symptoms of CFS by reducing the oxygen-carrying power of the blood reaching the brain in many of these patients.

I am unsure if this was published in a peer reviewed journal. I am checking, and reading for details.

PS Journal of Chronic Fatigue Syndrome, Vol. 4(1) 1998 copyright 1998

 

[alex3619]

See also this paper - https://www.researchgate.net/public...encephalomyelitis_and_orthostatic_intolerance

There are two other related papers on Research Gate by the same author.

 

[alex3619]

I would like to add that both articles suggest low blood volume is part of the OI component of ME, and is a common finding in OI.

 

[MeSci]

I would like to add that both articles suggest low blood volume is part of the OI component of ME, and is a common finding in OI.

I would think it common in people who report excessive urination, which seems to be quite a lot of us. (Unless we drink an equivalent amount of fluid)

 

[Forbin]

[University of Miami - 2009]

Clin Sci (Lond). 2009 Oct 19;118(2):125-35. doi: 10.1042/CS20090055.
Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function.
Hurwitz BE1, Coryell VT, Parker M, Martin P, Laperriere A, Klimas NG, Sfakianakis GN, Bilsker MS.

Abstract
The study examined whether deficits in cardiac output and blood volume in a CFS (chronic fatigue syndrome) cohort were present and linked to illness severity and sedentary lifestyle. Follow-up analyses assessed whether differences in cardiac output levels between CFS and control groups were corrected by controlling for cardiac contractility and TBV (total blood volume). The 146 participants were subdivided into two CFS groups based on symptom severity data, severe (n=30) and non-severe (n=26), and two healthy non-CFS control groups based on physical activity, sedentary (n=58) and non-sedentary (n=32). Controls were matched to CFS participants using age, gender, ethnicity and body mass. Echocardiographic measures indicated that the severe CFS participants had 10.2% lower cardiac volume (i.e. stroke index and end-diastolic volume) and 25.1% lower contractility (velocity of circumferential shortening corrected by heart rate) than the control groups. Dual tag blood volume assessments indicated that the CFS groups had lower TBV, PV (plasma volume) and RBCV (red blood cell volume) than control groups. Of the CFS subjects with a TBV deficit (i.e. > or = 8% below ideal levels), the mean+/-S.D. percentage deficit in TBV, PV and RBCV were -15.4+/-4.0, -13.2+/-5.0 and -19.1+/-6.3% respectively. Lower cardiac volume levels in CFS were substantially corrected by controlling for prevailing TBV deficits, but were not affected by controlling for cardiac contractility levels. Analyses indicated that the TBV deficit explained 91-94% of the group differences in cardiac volume indices. Group differences in cardiac structure were offsetting and, hence, no differences emerged for left ventricular mass index. Therefore the findings indicate that lower cardiac volume levels, displayed primarily by subjects with severe CFS, were not linked to diminished cardiac contractility levels, but were probably a consequence of a co-morbid hypovolaemic condition. Further study is needed to address the extent to which the cardiac and blood volume alterations in CFS have physiological and clinical significance.

https://www.ncbi.nlm.nih.gov/pubmed/19469714

 

[adambeyoncelowe]

In 1997, Simpson also wrote about changes to blood shape in fatiguing illnesses, and how it might be a proxy measure of fatigue: http://orthomolecular.org/library/jom/1997/articles/1997-v12n02-p069.shtml

Perhaps more interesting is that he also mentions that medical literature as early as 1921 was calling for vague terms like fatigue and malaise to be dropped. It's interesting how, a century later, they are still firmly with us (and causing all kinds of problems with subjectivity).

 

[Paradoxfloss]

There is an interesting discussion in 1993 Chronic Fatigue Syndrome, Wiley, Chichester, Ciba Foundation Symposium 173 @ p234 following Wesselys presentation on The neuropsychiatry of chronic fatigue syndrome.

Komaroff. In discussing your prospective study, Dr Wessely, you say that patients who develop a fatigue syndrome after a viral infection are not like CFS patients. Could you amplify on that?

Wessely. The difference is that these patients are not very ill. They are not well either, but they are not badly disabled, or polysymptomatic, and their social class is different. The whole feel of these postinfectious patients is different from the patients I see in the CFS hospital.

White. To follow up on that, I have been studying the people with acute postinfectious fatigue, whereas SW has been looking at chronically fatigued people and we are both aware of the contrast. It suggests that what we are seeing in patients who feel tired six months after having influenza is possibly the start of a long process, where the perpetuating factors then produce more symptoms and give the chronicity and disability.

Wessely. I doubt it. I think these are totally different people.


If they are different people, why lump them for research?

It’s so frustrating... here he is basically acknowledging that ME isnt CFS... his whole BPS schtick was never designed for or directed at us. Shit really got out of hand and wasted 30 years of viable research time ‍

 

[Paradoxfloss]

What amazes me is that in the early 90’s Behan did a muscle biopsy study that found that 39 of 50 patients had Type II muscle atrophy.

Reasonably recent papers state that Disuse tends to more Type I atrophy whereas Type II atrophy can be caused by inflammatory/metabolic factors, e.g., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327989/#!po=24.0385

I wrote to Behan and asked why as far as I could find the Type II muscle fiber atrophy findings seemed to have never become a key target but I didn’t hear back...

I also agree with @Trish regarding having never seen a better descriptor for the disease I have than severe muscle fatigeability (+ add in post exertion shutdowns)- I am very glad to hear that the NIH study is including muscle biopsies in their study and so wish more would do so

This is very interesting in relation to the issues with muscle spasms, seizure like contractions and even the CCI issues recently illustrated by Jen Brea & Jeff... type 2 muscles stabilise the spine and are heavily dependant on mitochondrial function. My physio has commented that these slow twitch stabilising muscles in my spine don’t seem to be working. This is also a neurological issue.

 

[Paradoxfloss]

I actually doubt it. If there is a metabolic problem with muscle that is causing symptoms directly then MR spectroscopy of basic metabolites should pick it up. It is a bit like saying if someone is tired because of anaemia a full blood count should pick it up - it should.

I read through one of Behan's papers yesterday and I am not that surprised the findings were not replicated. They are very preliminary and in many cases not very well described. I think in this case failure to get comparable results is pretty good evidence that the original findings were by chance or weak methodology.

That does not mean that it may not be worth looking yet again but I am doubtful anything will be found just in terms of metabolism that is enough to explain symptoms. What might be the case is that there are subtle change in metabolic pathways in mitochondria that lead to powerful signalling mechanisms. This was the suggestion that Mike Murphy made at IiME. The symptoms would not be due to metabolic deficit as such, which would not really seem to fit with the type of symptoms anyway, but to stimulation of nerve endings by by-products that are used as danger messages.

There are mitochondrial/metabolic issues in the muscles though. They just werent a type previously known and able to be recognised. Eg poor microcirculation of oxygen, abnormal metabolism in the plasma, calcium ions abnormalities etc

[I see this was established further down in the thread ]

 

[Paradoxfloss]

In general regarding hypovolemia, I’m aware it’s also a symptom of deconditioning. So it’s difficult to assess whether it’s causative or occurs as a consequence of the illness (my feeling is the latter). I have a vague recollection of reading that it may also be a compensatory mechanism, which somehow alleviates the metabolic and aerobic problems

 

[Hoopoe]

I have a vague recollection of reading that it may also be a compensatory mechanism, which somehow alleviates the metabolic and aerobic problems

Do you remember where you read this or any further information that would help me find out?

 

[Inara]

This is very interesting in relation to the issues with muscle spasms, seizure like contractions and even the CCI issues recently illustrated by Jen Brea & Jeff... type 2 muscles stabilise the spine and are heavily dependant on mitochondrial function. My physio has commented that these slow twitch stabilising muscles in my spine don’t seem to be working. This is also a neurological issue.

It seems muscle weakness is a well-known symptom in neuropathies (especially (inherited) peripheral neuropathies) which includes fast fatiguability. As a consequence, orthopaedic issues are not uncommon, like scoliosis and other consequences for joints, tendons etc. due to too weak and/or fast fatiguable muscles.
So, in some, it could be a neurological issue.

 

[alex3619]

In general regarding hypovolemia, I’m aware it’s also a symptom of deconditioning.

I have not looked into this, so I could be wrong, but it would be surprising if the extent of hypovolemia in ME, enough to often cause or be associated with heart preload failure, is found in deconditioning. Nobody doubts deconditioning can occur in ME, especially with the bed bound, but its like a candle to a forest fire. If deconditioning were argued as the main problem in most patients, then they fail to explain how we can be fine one day, deconditioned the next, and some time later fine again after a single day. Deconditioning does not have an on/off switch like that.

The part of deconditioning that most concerns me in ME is not muscle deconditioning, its bone deconditioning. There are too many bone disorders occurring in long term bedbound patients. Osteo- problems are not easy to reverse. Whereas many ME patients will automatically increase activity when they improve.

 

[weyland]

What is missing from the CDC document is not just the early work reported in the 1978 volume but all the subsequent work done in the early 1980s, much of it by Richard Edwards's (no relation) unit, then at UCL. From 1982-6 I shared a lab with people working on muscle metabolism in a range of conditions including ME - David Jones, Joan Round, Mike Rennie etc.

Edwards work is later referenced in the early 90s by Professor Mowbray. It seems he was pretty convinced that ME muscle is normal and it’s actually a neuromuscular problem that produces Ramsay’s primary (and objective) sign of the disease. This is the view I subscribe to, it makes a lot more sense.

I think the autoimmune hypothesis is crashing and burning. I think this second, “rediscovery” of the metabolic hypothesis will also crash and burn. We’ll only be left with the obvious, that ME is an inflammatory neurological disease.

 

[weyland]

I read everything here with keen interest. What's especially interesting to me is the implication that there's a form with a greater number of neurological symptoms (hence the myalgic encephalomyelitis label), and one with fewer (hence epidemic neuromyasthenia), and that was why they couldn't agree on one name (to do so would misrepresent the other group).

There is another form seen in the US outbreak in Texas that was largely biased towards dysautonomia symptoms that led the investigator towards the idea that it was very similar (to Iceland disease in his example) but different.

I think in reality all these investigators were highly focused on the presenting symptoms of the early stage of their sudden onset, but if you looked at the patients that didn’t recover years down the road it would be harder to tell them apart.

 

[Mithriel]

In MS, individual patients have a wide range of symptoms depending on which nerves are affected by the disease. This is apparent in the early stages and in the more mildly affected. In contrast, as the disease progresses all patients begin to look the same. It is felt that this is because the brain is overwhelmed and can no longer compensate for the damage.

It is very likely that the same thing happens in ME. If mitochondria are damaged in specific tissues that will be where the disease is most obvious.

I am having trouble explaining what I mean but mild or early disease all different, later or severe disease more homogeneous.