Second study might confirm neuroinflammation in ME subcortical brain

pattismith

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That's a very interesting paper @pattismith . Thanks for sharing. Even though the hippocampus is more vulnerable to oxidative stress due to its higher metabolic rate, it's also a prominent site of neurogenesis, unlike in the cortical brain. So, to oversimplify it a little, the hippocampus may be easily damaged, but it is also easily repaired.
The hippocampus is particularly vulnerable to brain iron deficiency either (for the same reasons)

The Effects of Early-Life Iron Deficiency on Brain Energy Metabolism


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Thomas W Bastian
, Raghavendra Rao, Phu V Tran, ...
First Published June 29, 2020 Review Article
https://doi.org/10.1177/2633105520935104



Abstract
Iron deficiency (ID) is one of the most prevalent nutritional deficiencies in the world.

Iron deficiency in the late fetal and newborn period causes abnormal cognitive performance and emotional regulation, which can persist into adulthood despite iron repletion.

Potential mechanisms contributing to these impairments include deficits in brain energy metabolism, neurotransmission, and myelination.

Here, we comprehensively review the existing data that demonstrate diminished brain energetic capacity as a mechanistic driver of impaired neurobehavioral development due to early-life (fetal-neonatal) ID.

We further discuss a novel hypothesis that permanent metabolic reprogramming, which occurs during the period of ID, leads to chronically impaired neuronal energetics and mitochondrial capacity in adulthood, thus limiting adult neuroplasticity and neurobehavioral function.

We conclude that early-life ID impairs energy metabolism in a brain region- and age-dependent manner, with particularly strong evidence for hippocampal neurons. Additional studies, focusing on other brain regions and cell types, are needed.
 

Consul

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Appears to be quite a bit of inflammation in healthy controls as well tbh. Perhaps an indication that brain inflammation is downstream rather than a cause.
 

SNT Gatchaman

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MVE sub-tweeted:

As a disclaimer, say it with me: "Just because inflammation is seen in a condition, does not mean that inflammation is the core cause of that condition."
Will be interesting to see if they can establish how much of this locally increased uptake is due to activated microglia vs inflamed vascular endothelium.
 

Consul

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Also from Corts blog today

https://pubmed.ncbi.nlm.nih.gov/34815320/

No Signs of Neuroinflammation in Women With Chronic Fatigue Syndrome or Q Fever Fatigue Syndrome Using the TSPO Ligand [ 11 C]-PK11195

Results: No statistically significant differences in BPND were found for patients with CFS or patients with QFS compared with HSs. BPND of [11C]-PK11195 correlated with symptom severity scores in patients with QFS, but a negative correlation was found in patients with CFS.
 

Pyrrhus

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Does the increased intake of [11C] PBR28 in the cingulate cortex mean there is increased metabolism there, and therefore inflammation?
It is generally held to mean that the tissue-resident immune cells inside the brain are activated. (neuroinflammation) It doesn't tell us anything about metabolism. Caveats apply.
 

Violeta

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What does anyone think of the Perrin technique Perrin's view that varicosed and malfunctioning lymph is creating a backflow into the lymphatic system in the brain, inflaming and poisoning the brain?
This might explain intracranial hypertension while at the same time hypotension in the rest of the body.
 

Research 1st

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Also from Corts blog today

https://pubmed.ncbi.nlm.nih.gov/34815320/

No Signs of Neuroinflammation in Women With Chronic Fatigue Syndrome or Q Fever Fatigue Syndrome Using the TSPO Ligand [ 11 C]-PK11195

Results: No statistically significant differences in BPND were found for patients with CFS or patients with QFS compared with HSs. BPND of [11C]-PK11195 correlated with symptom severity scores in patients with QFS, but a negative correlation was found in patients with CFS.
I read that negative paper a while ago and unfortunately it's the age-old phenomena of a heterogeneous group of Chronic Fatigue patients producing a negative association to a previous positive association - a well known problem that has plagued CFS research since the 1990's due to our current inability to filter who actually has the disease and who doesn’t, as we lack a reliable non invasive diagnostic test.

In other words it's worth not worrying about and it doesn't disprove neuroinflammation occurs commonly in CFS.

Weak CFS criterias matter (the worst offender being the British 'Oxford' CFS criteria). If you look at the CDC Fukuda Criteria they are poor and don't describe what people on this forum experience - Orthostatic Intolerance, Dysautonomia with or without POTS, Post Exertional Relapse, profoundly weak muscles, chronic inflammation, allergies, MCAS, cardiac problems, circulatory issues, vertigo, migraine, infections plus a plethora of issues CDC Fukuda criteria don't require.

Researchers, especially ones looking for neuroinflammation should avoid these 'ancient' 1980's criteria and stick to ME-ICC and also try and include the severely affected by arranging ambulance transfers to hospitals so the severely affected can be represented in research.

If the participants in the study had been ME-ICC patients (stricter criteria more pertaining to possible ME) and or severely affected, and there has been 50-200 of them, it might have been a relevance to ME research that is investigating brain inflammation, but they weren't.

Inflammation is definitely a factor in organic CFS, but it will be sub groups for now 'detected' in research and pot luck if these sub groups end up under a brain scanner if the study size is miniscule.

Note that only 9 CFS patients were scanned. If you scanned 100 CFS patients using CDC Fukuda criteria, non severe, it wouldn't surprise me in the least if at least 9% (9 of 100) showed zero brain inflammation.

Without a diagnostic test, this will always happen, you could argue that the brain scan itself is a diagnostic test (if no inflammation is found), yet there are other factors to consider why this may occur, such as if the radiotracer injected into patients, in this case PK1195, is sensitive enough.

A group of ME CFS researchers are aware of this technical problem, and actively trying to decide on 'the best' (most sensitive) tracer/ligand to select, in the aim of detecting neuroinflammation in ME, CFS. Last time I looked, it was something like [18F] DPA 714/715 and not the tracer used in this negative study. Yet this will be surpassed also.

In conclusion:

The phenomena of negative association to brain inflammation in CFS is thus inevitable until we know that 90%+ of the people in a research study have ME (Myalgic Encephalomyelitis), rather than probably or maybe, which is the current catch 22 we face and why no progress can be made in CFS research, meaning studies will always end up conflicting one another.

This is why it's outrageous the American NIH won't approve research grants to Professor Ron Davis (Stanford) or his colleauges who are trying to get a possible CFS diagnostic test off the ground. No government health agency will fund them, so we the patients suffer and Science is artificially stalled.
 

mitoMAN

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I read that negative paper a while ago and unfortunately it's the age-old phenomena of a heterogeneous group of Chronic Fatigue patients producing a negative association to a previous positive association - a well known problem that has plagued CFS research since the 1990's due to our current inability to filter who actually has the disease and who doesn’t, as we lack a reliable non invasive diagnostic test.

In other words it's worth not worrying about and it doesn't disprove neuroinflammation occurs commonly in CFS.

Weak CFS criterias matter (the worst offender being the British 'Oxford' CFS criteria). If you look at the CDC Fukuda Criteria they are poor and don't describe what people on this forum experience - Orthostatic Intolerance, Dysautonomia with or without POTS, Post Exertional Relapse, profoundly weak muscles, chronic inflammation, allergies, MCAS, cardiac problems, circulatory issues, vertigo, migraine, infections plus a plethora of issues CDC Fukuda criteria don't require.

Researchers, especially ones looking for neuroinflammation should avoid these 'ancient' 1980's criteria and stick to ME-ICC and also try and include the severely affected by arranging ambulance transfers to hospitals so the severely affected can be represented in research.

If the participants in the study had been ME-ICC patients (stricter criteria more pertaining to possible ME) and or severely affected, and there has been 50-200 of them, it might have been a relevance to ME research that is investigating brain inflammation, but they weren't.

Inflammation is definitely a factor in organic CFS, but it will be sub groups for now 'detected' in research and pot luck if these sub groups end up under a brain scanner if the study size is miniscule.

Note that only 9 CFS patients were scanned. If you scanned 100 CFS patients using CDC Fukuda criteria, non severe, it wouldn't surprise me in the least if at least 9% (9 of 100) showed zero brain inflammation.

Without a diagnostic test, this will always happen, you could argue that the brain scan itself is a diagnostic test (if no inflammation is found), yet there are other factors to consider why this may occur, such as if the radiotracer injected into patients, in this case PK1195, is sensitive enough.

A group of ME CFS researchers are aware of this technical problem, and actively trying to decide on 'the best' (most sensitive) tracer/ligand to select, in the aim of detecting neuroinflammation in ME, CFS. Last time I looked, it was something like [18F] DPA 714/715 and not the tracer used in this negative study. Yet this will be surpassed also.

In conclusion:

The phenomena of negative association to brain inflammation in CFS is thus inevitable until we know that 90%+ of the people in a research study have ME (Myalgic Encephalomyelitis), rather than probably or maybe, which is the current catch 22 we face and why no progress can be made in CFS research, meaning studies will always end up conflicting one another.

This is why it's outrageous the American NIH won't approve research grants to Professor Ron Davis (Stanford) or his colleauges who are trying to get a possible CFS diagnostic test off the ground. No government health agency will fund them, so we the patients suffer and Science is artificially stalled.
very good post imo
 
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