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Komaroff: The Biology of Chronic Fatigue Syndrome - Is CFS 'real'?

Firestormm

Senior Member
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5,055
Location
Cornwall England
I hadn't seen this one on the forum and couldn't find it anywhere on here either.

It was published on 28 March 2014 and follows a presentation Prof. Antony Komaroff gave to Stanford on 26 March 2014. He was introduced by Dr Jose Montoya:

I'm just listening/watching slides now. Pretty good overview thus far... :)

Just came up on Co-cure (Thanks to Tate :thumbsup:)
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
If anybody is looking for - or wants to hear - a summary of the 'state of play' in terms of biological understanding and the science relating to CFS: then you can't do better than listen/watch and perhaps copy from this presentation.

Bearing in mind this presentation came after the IACFS/ME and Stanford conferences earlier in March, it really is a good round-up of where we are. To my mind, Professor Komaroff is one of the best at doing this kind of thing. I don't of course understand all the science in detail, but he really does help even me to understand its significance.

And having it all in one place is very useful of course for helping us to help others to see where things stand with this condition, especially perhaps in terms of advocacy and raising awareness.

Cheers Professor. Another nice job :thumbsup:
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
I'd like to see an annual review paper being published in the medical journals. It's no good expecting doctors or anybody else who's got other demands on their time to watch a video. There's no single paper that we can point to, that I'm aware of, and say, 'Look, here's the evidence that this is a real disease and here's the current state of research'. We really need that.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
In case anyone is wondering, the short answer by Komaroff to is CFS real, is YES. :) If this is the same version I watched, you might want to skip the first six and a half minutes as its all musac.

Similar to what I have been repeating for some time, in Komoroff's way of putting things, we have established biological abnormalities that could explain our symptoms, and these in fact correlate with our symptoms. What we lack is proven causal mechanisms that drive the pathophysiology.

He mentions a single brain abnormality that I think I need to look into: (Using MRI Michael Zeinah at Stanford found)
Reduced fractional anisotropy anisotoprophy (FA) in right arcuate fasciculus, correlating with degree and distinguishing CFS from healthy
(that has high value in discriminating CFS from controls).

I have not checked that statement for typos yet.

Edit: corrected typo.
 
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Sidereal

Senior Member
Messages
4,856
Nice overview of the state-of-the-art. He mentioned (as he did at the recent conference Q&A) that this may be low-grade chronic encephalitis which is what some of us have thought all along.
 

Forbin

Senior Member
Messages
966
His presentation is excellent, as usual, but there seems to be a bit of an undercurrent suggesting that Stanford has previously been a lion's den for those who believe in the biology of CFS.

He says, jokingly, that he has some trepidation about giving his talk because there has been, in the past, a "healthy skepticism" at Stanford regarding the biology of CFS. Then, he puts up a still of Russell Crowe in "Gladiator" - suggesting he's ready to be challenged.

In his presentation, he's careful to point out several recent studies of CFS biology which have come from Stanford.

And, at the end of this talk, he puts up a cartoon showing a speaker announcing that he is now ready to "fend off" questions from the audience, and he again puts up the "Gladiator" image.

This is all kind of amusing, but also kind of chilling - in that it's a reminder of the years of skepticism that the disease has endured.

Off hand, I don't know the history Stanford's attitude toward CFS, but the questions from the audience this time did not seem confrontational.
 
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alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
http://en.wikipedia.org/wiki/Arcuate_fasciculus

Evidence for the role of the arcuate fasciculus in language use is best represented by conduction aphasia, caused by damage to the inferior parietal lobule that extends into the subcortical white matter and damages the arcuate fasciculus.[7] This type of aphasia inhibits the patient from repeating unfamiliar sounds. A study by Catani, Jones, and Ffytche (2005) provided the first anatomical evidence for the presence of two pathways between Wernicke’s area and Broca’s area.[8][9] They found one deep pathway, interpreted to directly connect these two regions, and a shallower pathway that consists of two segments; the anterior segment connects frontal cortex with inferior parietal cortex, and the posterior segment connects Wernicke’s area with the inferior parietal cortex. Damage to the direct pathway may produce conduction aphasia, whereas damage to the indirect pathway spares the ability to repeat speech but impairs comprehension. The symptoms of conduction aphasia suggest that the connection between posterior temporal cortex and frontal cortex plays a vital role in short-term memory of words and speech sounds that are new or have just been heard. The arcuate fasciculus connects these two regions and circulates information back and forth, possibly contributing to short-term memory.

In nine out of ten people with tone deafness, the superior arcuate fasciculus in the right hemisphere could not be detected, suggesting a disconnection between the posterior superior temporal gyrus and the posterior inferior frontal gyrus. Researchers suggested the posterior superior temporal gyrus was the origin of the disorder.
[My underlining]

Edit: Please be aware that, alas, this is another area in which Wikipedia may be wrong. The role of the AF in language is under question, given that much of the neuroanatomy seems to be about motor centers and not language centers.
 
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alex3619

Senior Member
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13,810
Location
Logan, Queensland, Australia
http://www.ajnr.org/content/28/2/226.long

BACKGROUND AND PURPOSE: Fractional anisotropy (FA) is a useful measure of connectivity in the brain that can be derived from the diffusion tensor imaging (DTI) dataset. This study investigated the relationship between FA and selected measures of cognition across a broad age group to explore a possible structural basis for cognitive changes with age.

Fractional anisotopy is simply a measure, a metric, of how connected things are. Loss of connectivity means loss of signal and communication, which means either degraded function or loss of function.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
http://www.biomedcentral.com/1471-2377/14/46

Relation between aphasia and arcuate fasciculus in chronic stroke patients
Hyung Jun Tak and Sung Ho Jang
According to our findings, the remaining volume of the left AF, irrespective of directionality and diffusivity, showed moderate positive correlation with language function in chronic stroke patients with aphasia. Discontinuation or non-construction of the left AF was also an important factor for language function

The left arcuate fasciculus is clearly implicated in aphasia. I am still looking for a good paper on the right arcuate fasciculus.

The left AF is also known to be underdeveloped in autism.

There is very little out there on the right AF, as the left AF is thought to be dominant in language. However, women tend to have slightly smaller left AF, and larger right AF, which might be important in ME.
 
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pemone

Senior Member
Messages
448
I hadn't seen this one on the forum and couldn't find it anywhere on here either.

It was published on 28 March 2014 and follows a presentation Prof. Antony Komaroff gave to Stanford on 26 March 2014. He was introduced by Dr Jose Montoya:

I'm just listening/watching slides now. Pretty good overview thus far... :)

Just came up on Co-cure (Thanks to Tate :thumbsup:)

This was interesting but it was also very broad. It was simply a laundry list of associated markers, and there was a huge number of those markers. It's hard to listen to this and come away with any real understanding of what causes CFS, or what the core defect actually is.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
This was interesting but it was also very broad. It was simply a laundry list of associated markers, and there was a huge number of those markers. It's hard to listen to this and come away with any real understanding of what causes CFS, or what the core defect actually is.

That's because nobody knows ;)

All the 'positive science' desperately needs replication on a larger and more thorough scale - as has ever been the case with regards to ME research in my view.

Until that happens we will forever be 'going round in circles' and clinging desperately to the latest finding(s) as patients, but in order to gain wider acceptance and for the development of effective treatments we need this better replication.

What we can say, is that there is something there. That CFS/ME is real. I think this has been proved (not to everyone's satisfaction), and will/has helped in terms of awareness and acceptance: but we are still left without an effective treatment/management approach, which as a patient is what I am ultimately interested in.

It would be nice to know what is contributing/causing my illness: but I don't think all of us with this diagnosis as it currently stands, will be determined as having the same constituent parts.

That said I think it more likely we are on a 'spectrum' but some of us may well find that other things can account for our illness and symptoms but that we have not yet been properly diagnosed or the other illness has not developed sufficiently to be noticed e.g. there may be alternate explanations and we need to better educate doctors into looking for them at the start and throughout our period of incapacity...

Phone is ringing :)
 

pemone

Senior Member
Messages
448
Firestormm, what would be more interesting to me is for the presentation to take one central hypothesis about the cause of CFS, and then try to show how deeply that has been investigated.

I am very very taken with the idea that this disease is being caused by a failure of metabolism to generate NAD+ and a failure to convert NADH to NAD+. It explains the symptoms completely: massive collapse in energy production by the body. I would have much rather seen someone describe how deeply that idea has been investigated and what additional research is needed.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
That's because nobody knows ;)

That about sums it up. ;) We do have lots of clues. Its like a million piece 3D jigsaw, and we are starting to assemble it now, but we don't know if we have all the pieces, and different people think they know how different pieces fit together, but other people think they are wrong.

At some point we will begin to see the big picture, someone will take a stab at how it will finally look, and suddenly we will see the whole thing. At that point people will be saying its so darn obvious, why couldn't we see it before? We will also be making funny faces at the experts huddled in the corner who will still probably be saying that its a psychosocial problem.

One thing we have to keep in mind though is that there may not be a core defect that describes the syndrome, only core defects in subgroups.
 

NK17

Senior Member
Messages
592
I beg to disagree on some points with Dr. Komaroff, this is from a patient's point of view (living with it since 1981 post infectious mono and finally diagnosed in 2011 by Dr. Kogelnik a well respected ME/CFS doctor and a colleague of Dr. Montoya @Stanford):

1. ME/CFS can be and has been the cause of death and from epidemiological studies we know the 3 main causes of death among patients are heart failure, cancer and suicide (heart failure and I think cancer too at a much younger age than the rest of the population).
Dr. Lily Chu stated the same at or after the IAMECFS conference this past
March.

2. There are post-mortem biopsy findings of dorsal root ganglionitis, a clear and evident pathology (Sophia Mirza in the UK).

3. I suspect that many cases of what doctors call Fibromyalgia, are in fact a symptom due to immune dysfunction and rampant tissues inflammation, maybe driven by chronic viral and bacterial reactivation. In other word overlapping Fibro with CFS is actually the manifestation of the Myalgic painful side of the Encephalitis/Encephalomyelitis.

Other than that I'm pleased to hear that finally "they" or some of "them" are starting to get it ;).
 
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alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
1. @NK17 , the problem we face is that proper (large, long term) epidemiology studies, especially on the progression and outcomes, have never been conducted. If I recall correctly there are also studies that show no altered mortality. While Jason's study is probably the more reliable, I think there was a large Fukuda study that showed no difference from the general population. With this mix of outcomes its hard to convince anyone. Komaroff has actually been pushing for a good epidemiological study since the 80s, and had made applications for funding on a number of occasions. Funding was denied.

2. Dorsal root ganglionitis has been found in only a small number of patients. The critics will say what if this happens to be a rare event? Show me large cohort autopsy results! What I find interesting is this kind of damage was found in monkeys injected with serum from patients from the late 40s (1948-9) outbreaks in Adelaide, Australia, and published in 1955.

3. Fibromyalgia is showing distinctive biochemistry that does not appear to be shared with ME. However it could easily be an assumption that this makes fibro a different disorder. First there is the overlap problem, many with ME have fibro. Second, different biochemistry in different subgroups of a disease is known (Leishmania for example). Different subgroups, with different biochemistry, can occur because the body can respond differently to the same problem. In Leishmania for example, and I hope I have this right as I studied this maybe 13 years ago now, the difference is about what the immune system does. Th1 responders do well, the outcome for Th2 responders is poor.

Komaroff is conservative. If he says something is the case, he is fairly reliable. If something is less clear, or more speculative, he wont talk about it.
 
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pemone

Senior Member
Messages
448
He mentions a single brain abnormality that I think I need to look into: (Using MRI Michael Zeinah at Stanford found) (that has high value in discriminating CFS from controls).

Does anyone have a link to Zeinah's research at Stanford?

For me the most interesting finding in this study is the loss of grey matter (cortical volume loss).