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Concrete evidence of cognitive dysfunction in ME

62milestogojoe

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The following material is an extrapolation of data from a paper by Osaka researchers entitled Neuroninflammation in Patients with CFS/ME.

It is recommended that you read at least the abstract and discussion and view the images. The paper can be found here-
http://jnm.snmjournals.org/content/55/6/945.long#ref-24

I highly recommend watching a couple of Youtube brain function animations to help you orientate regarding the diagrams I have included below.

Key points
  • The method targeted activated astrocytes and microglia (cells of the brain's immune system). The immune cells are activated in a situation of neuroinflammation.
  • Nine ME patients and ten healthy controls were scanned. ME patients had 'inflammation scores' between 45% and 199% higher than controls.
  • Degree and localisation of neuroinflammation was correlated positively with severity and nature of symptoms.
  • High value scores in the amygdala, thalamus and midbrain correlated with cognitive impairment score.
  • High values in the cingulate and thalamus correlated with pain score.
The PET scan results show that in this cohort of ME patients neuroinflammation is centred on the limbic system, which is critically important for normal brain function.

I have attempted to synthesize some of the data form the the Osaka paper into a diagrammatic form for ease of accessibility to PR members. Please excuse my poor graphic work, it is difficult to successfully layer the components of such a complex organ as the brain.

Figure 1 Normal brain functions
Brain PR1 final.jpg

Figure 1 relates normal brain function to specific locations. It is not a comprehensive map, but isolates functional locations which the PET scans proved to be in a neuroinflammatory state and physiologically neighbouring area which may tentatively be affected by adjacent inflammation in my opinion.

Figure 2 Confirmed area of neuroinflammation
Brain PR2 Final.jpg

Orange dots marked confirmed localized areas of inflammation and crosses in red indicate associated dysfunction proven in the PET scans. Question marks indicate potential associated deregulation in my opinion only. it is worth noting that this is a generalized diagram encompassing all the scans (9 patients). Different patients have slightly different localized areas of neuroinflammatory process.

Figure 3 Correlation of neuroinflammation with ME symptoms

Brain PR3 final.jpg


Using the Canadian primer and PET scan findings, I have linked damaged brain localities to well established ME symptoms. Greyed out titles are not directly referred to in the Osaka study but again may, in my opinion suffer possible deregulation.

Key points
  • Given the success of the Osaka team's methodology why have health authorities failed to consider PET scan as the gold standard technique in ME diagnosis and monitoring?
  • The Osaka team postulates two mechanisms causing neuroinflammation. The first is overactivity of neurons in a compensatory process for functional loss in ME. The second is as a neuroimmune response to infection. (I tentatively covered this model in a blog essay called 'paper' on CFS/me pathogenesis-the brain).
  • This issue of pathogenesis/cause of neuroinflammation needs resolving.
  • Given the fact of neuroinflammation in ME patients, the urgent question is how to address it- how do we best quell inflammation to minimize brain damage? How do we promote healing-neurogenesis etc?
  • I have used nootropics for 4 years with some success but there is (as I have found out!) the contentious issue of anti-inflammatories/steroids.
  • If we conclude that severity of ME symptoms (mild to very severe) correlates with 1-severity of neuroinflammation and 2- localization of neuroinflammation to specific brain structures then can we also infer that fluctuations in symptoms also relate to extent of neuroinflammation
I would welcome any revisions/ corrections/ criticism of the post..I am not a neuroscientist.
 

62milestogojoe

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Interesting.

How, if at all, does your research fit with Dr Hyde's use of HMAPO Spect?

https://www.nightingale.ca/resources
Hi Scott, I am not familiar with that and will have a look when I can.
I checked out the wiki and they had this to say-

''A PET scanner detects these emissions "coincident" in time, which provides more radiation event localization information and, thus, higher spatial resolution images than SPECT (which has about 1 cm resolution). SPECT scans, however, are significantly less expensive than PET scans, in part because they are able to use longer-lived more easily obtained radioisotopes than PET.''

When you consider the size of say the pineal gland (5mm) it may be that PET is preferable.
 

jpcv

Senior Member
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386
Location
SE coast, Brazil
Hi @62milestogojoe , you ´re doing such a great job with your contributions. to this forum.
I see your gut treatment protocol is working great, as you show no signs of brain fog.
very interesting data, one more piece of information showing that brain damage by inflamation is important in the pathogenesis of this disease,
I suspect that in people with severe ME and lots of neurological disfunction, the neuro inflamation is more profound and maybe there is irreversible brain damage.
I reckon that Dr Hyde´s work with spect brain image supports this thesis of brain inflamation and brain damage.
questions:
- What initiates the disease process? Some kind of viral infection in the CNS or the brain damage is secondary to a imune response?
-gut brain interaction? gut inflamation perpetuates the brain damage or vice versa?
-why does steroids help some patients but not others( my case)?
- If a viral infection is indeed the first step in the pathogenesis of ME, should we treat the virus infection or it´s not relevant once the brain inflamation takes over?
 

62milestogojoe

What's a forum then?
Messages
221
Location
UK
Hi @62milestogojoe , you ´re doing such a great job with your contributions. to this forum.
I see your gut treatment protocol is working great, as you show no signs of brain fog.
very interesting data, one more piece of information showing that brain damage by inflamation is important in the pathogenesis of this disease,
I suspect that in people with severe ME and lots of neurological disfunction, the neuro inflamation is more profound and maybe there is irreversible brain damage.
I reckon that Dr Hyde´s work with spect brain image supports this thesis of brain inflamation and brain damage.
questions:
- What initiates the disease process? Some kind of viral infection in the CNS or the brain damage is secondary to a imune response?
-gut brain interaction? gut inflamation perpetuates the brain damage or vice versa?
-why does steroids help some patients but not others( my case)?
- If a viral infection is indeed the first step in the pathogenesis of ME, should we treat the virus infection or it´s not relevant once the brain inflamation takes over?
Hi jpcv and thanks for your insights. These are the kind of questions we need to be asking.
About 10 years ago I was working as a biomed in virology and did a lot of sniffing about comparing tertiary neurosyphilis degeneration in the brain in comparison to damage in HIV dementia.

Remarkably similar pathophysiological effects in the brain despite one being a spirochete bacteria and the other a retro virus as I remember.

It's probably in the attic in a box but may be worth finding because of the information it contained about the inability of the neuroimmune system to regulate itself i.e. switch off. 4 years of nootropics and associated supplements has helped me a lot I feel, but as I said somewhere else it was the weighty detox/ microbiota load and follow up treatment in India that has given me the biggest boost since I was well enough to get out of bed . I'm back for more in November.

I didn't cover as many issues from the pioneering work in Osaka as I wanted to in the interest of non science based PR members being able to get to grips with the information, but neurogenesis continues throughout life centred on the base of the hippocampus. (?is this damaged and dysfunctional in ME neuroinflammation?) The Osaka team point out that there may be interference with production of serotonin in neuroinflammatory conditions in ME patients. I've just marked it 'depression' on the diagram.

As a pragmatist I prefer to get on with trying to deal with symptoms rather than investigating the initial cause-but surely the pathogen model is a strong one? The gut-brain work some of the Invest in ME scientist are looking at is fascinating and so utterly unintuitive? So strange, we'll have to wait and see.

I think we can at least begin to repair our brains and remain hopeful.
 

lansbergen

Senior Member
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2,512
Hi lansbergen. I feel the problem in neuroinflammation may be the inability of the neuroimmune system to switch off/regulate itself as in other neurodegenerative disease. I don't know.

Maybe they are looking at the wrong place.

I have been reading the fasinating TSE literature since the BSE epidemic.

My brain problems improved a lot since I take levamisole. One of the things it does is decreasing superoxide another is it decreases cAMP and increases cGMP.

Recently I found somewhere superoxide is an early immuneresponse. I am not good in (bioi)chemistry. I would like to know more about superoxide and its place in the immune response.
 

62milestogojoe

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That's interesting lansbergen and had never occurred to me as a potential source. I will try to look into it. Strange how everything went suddenly quiet?

I'd have to get my immunolgy textbook out to help with information on superoxide, but it is essentially a weapon employed by the immune system to destroy what it sees as a pathogen. This brings up the question as to whether your drug helps to quieten an immune response in the brain. I think.

Cyclic AMP is adenosine triphosphate (ATP-the energy molecule) converted to function as a signal. I cannot see how that would benefit-.I don't know.
 

lansbergen

Senior Member
Messages
2,512
Strange how everything went suddenly quiet?

Not suddenly. It was a long slow process with tiny steps.

The first thing I noticed was it lessened the horrible pain enough to let me sleep a few hours.

Once I tried a larger dosis. That was great: pain gone and a deep relaxation but when it was used up the man with the hammer arrived. The short pain relieve was not worth the even far worse pain afterwoods. From then I stick to the low dosis every day.
 

62milestogojoe

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Hi I meant suddenly went quiet with regard to creutzfeldt-jakob disease.
Did you have pain in the head or general pain?
 

lansbergen

Senior Member
Messages
2,512
Hi I meant suddenly went quiet with regard to creutzfeldt-jakob disease.
Did you have pain in the head or general pain?

The research goes on.

I had horrible head and face pain. Sometimes I thought my head would burst.
During flares I got what I called a waterhead.

Lately I think the meningitis were working very hard to keep the agent out.
 

ljimbo423

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United States, New Hampshire
I feel the problem in neuroinflammation may be the inability of the neuroimmune system to switch off/regulate itself as in other neurodegenerative disease.

The neuro-inflammation, might cause mitochondrial dysfunction, from the oxidative stress it causes. I have read that dysfunctional mitochondria, because of the increase in oxidative stress they create.

Can cause a positive feedback loop, to some degree, keeping the neuro-inflammation in place, with excessive oxidative stress.

So it seems like it might be necessary to slow or stop the source of the neuro-inflammation and decrease the oxidative stress also, from the dysfuctional mito. that might be helping to perpetuate the neuro-inflammation/oxidative stress/mitochondrial dysfunction cycle.

Just a couple of thoughts!:)

Jim
 
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3,263
I would like to see these results replicated first before I would make much of them.

Its just that the sample was very small (9 CFS cases), and there do not appear to be any corrections applied for multiple comparisons. (When you do lots of comparisons, this raises your likelihood of getting something significant just by chance alone. Here they say they have done an ROI analysis - which means you're not required to do such stringent corrections as you would with a whole brain analysis, but they don't say what their regions of interest are, why they chose them, and why they didn't at least apply some corrections).

The correlations look impressive, but I would also like to know how many correlational analyses they performed that didn't come out significant. If its more than, say, 20, then these ones might just look good due to chance.

Until we see a good replication - preferably with a bigger sample - we can't tell whether these effects are genuine or not.