Brain abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome: Evaluation by diffusional

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Brain abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome: Evaluation by diffusional kurtosis imaging and neurite orientation dispersion and density imaging.
Kimura Y1, Sato N1, Ota M2,3, Shigemoto Y1, Morimoto E1, Enokizono M1, Matsuda H4, Shin I5, Amano K6, Ono H7, Sato W7, Yamamura T7.
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Abstract

BACKGROUND:
Diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) metrics provide more specific information regarding pathological changes than diffusion tensor imaging (DTI).

PURPOSE:
To detect microstructural abnormalities in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS) patients by using DKI and NODDI metrics.

STUDY TYPE:
Prospective.

POPULATION:
Twenty ME/CFS patients and 23 healthy controls were recruited.

FIELD STRENGTH/SEQUENCE:
Three-b value DWI (b-values = 0, 1000, and 2000 sec/mm2 ) and 3D T1 -weighted images were at 3.0T.

ASSESSMENT:
Mean kurtosis (MK), neurite density index (NDI), orientation dispersion index (ODI), fractional anisotropy (FA), and mean diffusivity (MD) were calculated.

STATISTICAL TESTING:
The two-sample t-test analysis in SPM12 software was used to compare the differences between ME/CFS and control groups.

RESULTS:
In the ME/CFS patients, we observed significant FA decreases in the genu of the corpus callosum and the anterior limb of the right internal capsule (P < 0.05), but no significant difference in MD (P = 0.164); there were also significant MK decreases in the right frontal area, anterior cingulate gyrus, superior longitudinal fasciculus (SLF), and left parietal area (P < 0.05). Significant NDI decreases were observed in the right posterior cingulate gyrus, SLF, and left frontal area of the ME/CFS patients (P < 0.05). Significant ODI decreases were seen in the bilateral occipital areas, right superior temporal gyrus, the anterior limb of internal capsule, and the posterior cingulate gyrus (P < 0.05), and significant ODI increases were revealed in the bilateral occipital and right temporal areas (P < 0.05).

DATA CONCLUSION:
Right SLF abnormalities may be a diagnostic marker for ME/CFS.

LEVEL OF EVIDENCE:
1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

© 2018 International Society for Magnetic Resonance in Medicine.

KEYWORDS:
chronic fatigue syndrome; density imaging; diffusional kurtosis imaging; neurite orientation dispersion

PMID:
30430664
DOI:
10.1002/jmri.26247
 
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I don't know. Are we at a stage yet where finding yet more "potential biomarkers" with little to no chance of leading to treatments is a low priority?

I've seen plenty of papers like this and I know they add to the great big pile of evidence for it being a physical condition but I fear they're not where you would invest if you were racing to find a cure? tell me I'm wrong.
 

ljimbo423

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I don't know. Are we at a stage yet where finding yet more "potential biomarkers" with little to no chance of leading to treatments is a low priority?
From my perspective, yes. From somebody else's that is trying to get a ME/CFS diagnosis, maybe not.

I've seen plenty of papers like this and I know they add to the great big pile of evidence for it being a physical condition but I fear they're not where you would invest if you were racing to find a cure? tell me I'm wrong.
I can't tell you your wrong, because I agree.:)
 

Hufsamor

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I do agree of course, but :
Biomarkers help in early diagnosis, disease prevention, drug target identification, drug response etc. (From the very scientific correct and trustworthy Wikipedia :))

I wouldn't put my money in those kind of research either, but they all puts bits to the puzzle?
And maybe, in the long run, those small pieces helps to target the right kind of treatment?
 
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I do agree of course, but :
Biomarkers help in early diagnosis, disease prevention, drug target identification, drug response etc. (From the very scientific correct and trustworthy Wikipedia :))

I wouldn't put my money in those kind of research either, but they all puts bits to the puzzle?
And maybe, in the long run, those small pieces helps to target the right kind of treatment?
I agree they are puzzle pieces.

But are they the corner pieces of the jigsaw that really help you get cracking!?
 

HowToEscape?

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I don't know. Are we at a stage yet where finding yet more "potential biomarkers" with little to no chance of leading to treatments is a low priority?

I've seen plenty of papers like this and I know they add to the great big pile of evidence for it being a physical condition but I fear they're not where you would invest if you were racing to find a cure? tell me I'm wrong.
Not you nor me not researchers knows where the leads and breaks will come from. Science proceeds by turning over many rocks, having an unusual degree of perception about the stuff under them, and hundreds of steps later some unexpected combination comes together and you get a new bio mechanism, find a new little organism, etc etc. Then someone sees connections that lead to your original goal. Edison had to find "999 ways to not make a light bulb" before getting to the tungsten wire filament. Bio is more complex than wire. To work our problem, we need an effort on the scale of what was done for HIV. Unfortunately we don't have the media, Hollywood, and other forces working for us.

If science was a straight line from 'I Want This' to "Here Ya Go" it would be automated and it would have all been done 200 years ago.
 

HowToEscape?

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I agree they are puzzle pieces.

But are they the corner pieces of the jigsaw that really help you get cracking!?
You use whatever pieces you can find from under the placemats, go scout for more, imagine 772 ways they could fit together and see if any old pieces from other puzzles fit. Also try making more pieces, poke around the puzzle hobbyists next door, then go back to searching for just the pieces you want. Then try something else. Then find a new way to put together what you have. If you wait for just the right pieces, you'll be done with the puzzle around when the roof has fallen in.
 

Hufsamor

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I don't know. Are we at a stage yet where finding yet more "potential biomarkers" with little to no chance of leading to treatments is a low priority?

I've seen plenty of papers like this and I know they add to the great big pile of evidence for it being a physical condition but I fear they're not where you would invest if you were racing to find a cure? tell me I'm wrong.
https://www.frontiersin.org/article...bmJ-Burzm_O2Sc1m1p_YUrFxGQ427rgbAM29e70yflSg4

@Murph

I thougt of you when i read the intro to this paper:):
(I haven't read the actual article.)

Full paper now published by VanElzakker et al. The paper is a comprehensive review of ME/CFS neuroimaging studies.

"The ME/CFS research field has been stuck in a somewhat defensive posture, with a focus on demonstrating “this is a real condition” by showing significant biological differences between patients and controls. We believe this has led to a situation in which too much is made of the specifics reported by descriptive studies (such as the average “cytokine profile” present in cases vs. controls at the moment of assay) and not enough emphasis has been placed on potential mechanisms driving symptoms. The field is ready to move past proving “this is a real condition” and to start elucidating the specific relationship of ME/CFS symptoms to neuroinflammation."
 

Chris

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I agree--and this is one reason why I am following Naviaux so keenly--he may be proved right or wrong, but he has formulated an overall picture and even strategy (in his latest paper) that makes sense and holds some hope. Let's hope he can get hold of more Suramin and money and get that trial going! I want to be like one of those luck ASD kids--except that may be unlikely given that I am 85 and not 5!
 
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https://www.frontiersin.org/article...bmJ-Burzm_O2Sc1m1p_YUrFxGQ427rgbAM29e70yflSg4

@Murph

I thougt of you when i read the intro to this paper:):
(I haven't read the actual article.)

Full paper now published by VanElzakker et al. The paper is a comprehensive review of ME/CFS neuroimaging studies.

"The ME/CFS research field has been stuck in a somewhat defensive posture, with a focus on demonstrating “this is a real condition” by showing significant biological differences between patients and controls. We believe this has led to a situation in which too much is made of the specifics reported by descriptive studies (such as the average “cytokine profile” present in cases vs. controls at the moment of assay) and not enough emphasis has been placed on potential mechanisms driving symptoms. The field is ready to move past proving “this is a real condition” and to start elucidating the specific relationship of ME/CFS symptoms to neuroinflammation."
Ha! Van Elzakker is a smart guy and now we know why - it looks like he's been reading my comments. ;)

That's a good paper. he's positive on the technique being used by Younger to image brains, but extremely negative on cytokine studies. He has a lot to say about cytokines:

"The core problem with looking for cytokines in peripheral blood is that cytokines generally do not function as endocrine signalers, but are rather normally autocrine and paracrine signalers (see Box 1). In other words, cytokines do not function by flowing through blood (where many studies hope to measure them due to easy access) but rather by acting locally, directly in the vicinity of infection or injury."

"An experienced immunology lab, led by a PI with decades of experience and over 100 publications, conducted a within- and between-lab comparison study. Breen et al. (188) compared the ability of four multiplex kits to detect 13 cytokines in human plasma and serum. The four kits were tested on the same sample across six different laboratories and across multiple lots of the same kit. Their results showed a large amount of variance both within the same lab and across multiple labs. While all 13 cytokines were detected by at least one kit, none of the kits were able to detect all 13 cytokines. Additionally, their results alarmingly indicate that each cytokine within each multiplex kit had at least one significant lab and/or lot effect. In other words, measuring the same sample twice with the same kit in the same laboratory following the same strict protocol yielded significant differences in absolute cytokine values"

"Factors that can significantly affect circulating cytokine levels within an individual include: time of day (192194), status of alcohol, nicotine, or other drug use (195201), quality and amount of sleep (202), acute and chronic stress (203), acute and chronic fitness habits specific to type of exercise (204206), sex (207, 208), phase of menstrual cycle (209, 210), age (211), chronic dietary patterns (212), and acute differences immediately following a meal (213, 214). Thus, even eating a spicy burrito with extra guacamole the day of sample collection will result in a different cytokine profile than eating Indian food or a slice of chocolate cake. A research participant adding sour cream to the mashed potatoes they had for lunch will alter their cytokine profile."