I'd be curious to know if there have been any studies that don't suffer from referral bias. If you're an autonomic specialist and you study patients who make their way to your clinic, I'd expect to find more cases of NMH, postural hypotension and syncope than POTS. I don't know how it is these days but it used to be quite hard to get seen by anyone if you don't faint. Folks with POTS usually get smacked down with a diagnosis of anxiety and a beta blocker script by the primary care doc. I had to go through hell to get an official POTS diagnosis. My mother has IST and it's clearly autonomic but she'll never get near an autonomic specialist or any kind of diagnosis because the GP just keeps upping her beta blocker dose (which of course makes the fatigue even worse).
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Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in CFS
- Thread starter Ecoclimber
- Start date
I'd be curious to know if there have been any studies that don't suffer from referral bias. If you're an autonomic specialist and you study patients who make their way to your clinic, I'd expect to find more cases of NMH, postural hypotension and syncope than POTS. I don't know how it is these days but it used to be quite hard to get seen by anyone if you don't faint. Folks with POTS usually get smacked down with a diagnosis of anxiety and a beta blocker script by the primary care doc. I had to go through hell to get an official POTS diagnosis. My mother has IST and it's clearly autonomic but she'll never get near an autonomic specialist or any kind of diagnosis because the GP just keeps upping her beta blocker dose (which of course makes the fatigue even worse).
lansbergen
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I agree
lansbergen
Senior Member
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Yes it is very complicated. That is why I just tried the immune modulator which showed helpfull in the animals. It works for me too but I still don.t know exactly how. Is it because it activates macrophages? I have not found it does anything for autophagy. Lithium does and it decreases the infection level of the agent I suspect but to much autophagy makes it worse.
charles shepherd
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MEA Comment from Dr Charles Shepherd:
(This is a very basic explanation about the ANS, how this study was carried out, and what was found, for the benefit of our members)
The autonomic nervous system (ANS) is a crucial part of the nervous system.
The ANS consists of various control centres in the brain (including the hypothalamus, midbrain nuclei and brainstem) from where messages are sent to various organs in the body (heart and blood vessels, bowels, bladder etc) by two sets of nerves call the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS).
The SNS and PNS help to regulate activity in the heart, bowel, bladder etc - in particular, they can speed up or slow down activity.
So the ANS can speed up the heart/pulse rate, increase blood pressure, and affect blood flow to the brain and muscles.
If there is overactivity in this part of the nervous system, it can also cause irritable bowel type symptoms and bladder frequency.
We already know that there is good clinical and research evidence - especially from Professor Julia Newton here in the UK and Professor Peter Rowe in America - to show that there is ANS dysfunction in ME/CFS.
This plays an important role in symptoms such as orthostatic intolerance/hypotension (where blood pressure falls excessively when moving from lying down to standing), PoTS, cold hands and feet (where the blood vessels over-constrict in cold weather) as well as bowel and bladder symptoms.
And because the ANS affects blood vessel size, and consequently blood flow, it also plays a role in muscle function (muscle has a very rich blood supply) and cognitive function (as blood flow to parts of the brain may be affected).
This important new research has used a special type of brain scanning/neuroimaging (magnetic resonance imaging/MRI) to look at may be happening in the control centres in ME/CFS in relation to changes in pulse and blood pressure - research that has not been carried out before.
In what is called an exploratory cross-sectional study, blood pressure and heart rate, as indicators of autonomic function, were correlated with MRI findings in the control centres in the brain in 25 CFS subjects and 25 healthy control.
The steady state blood pressure (systolic, diastolic and pulse pressure) and heart rate in two postures were extracted from 24 h blood pressure monitoring.
Key finding:
Abnormal regressions were detected in nuclei of the brainstem vasomotor centre, midbrain reticular formation and hypothalamus, but also in limbic nuclei involved in stress responses and in prefrontal white matter.
Key conclusion:
We propose that these regulatory nuclei are functioning correctly, but that two-way communication between them is impaired in CFS and that this affects signalling to/from peripheral effectors/sensors, culminating in inverted or magnified correlations.
This is clearly complex research. In very simple terms, it indicates that while these control centres are functioning correctly, there appears to be a problem involving communication between the various control centres in the brain.
It is interesting to note that the brainstem has been implicated in ME/CFS in other studies using neuroimaging - especially the blood flow study carried out by Durval Costa et al.
So whilst this research helps to increase our understanding of ANS abnormalities in ME/CFS and why they may be occurring, it does not offer any new or immediate solutions regarding treatment of ANS dysfunction.
Dr Charles Shepherd
Hon Medical Adviser, MEA
Diagram: Autonomic nervous system - what does it do?
(This is a very basic explanation about the ANS, how this study was carried out, and what was found, for the benefit of our members)
The autonomic nervous system (ANS) is a crucial part of the nervous system.
The ANS consists of various control centres in the brain (including the hypothalamus, midbrain nuclei and brainstem) from where messages are sent to various organs in the body (heart and blood vessels, bowels, bladder etc) by two sets of nerves call the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS).
The SNS and PNS help to regulate activity in the heart, bowel, bladder etc - in particular, they can speed up or slow down activity.
So the ANS can speed up the heart/pulse rate, increase blood pressure, and affect blood flow to the brain and muscles.
If there is overactivity in this part of the nervous system, it can also cause irritable bowel type symptoms and bladder frequency.
We already know that there is good clinical and research evidence - especially from Professor Julia Newton here in the UK and Professor Peter Rowe in America - to show that there is ANS dysfunction in ME/CFS.
This plays an important role in symptoms such as orthostatic intolerance/hypotension (where blood pressure falls excessively when moving from lying down to standing), PoTS, cold hands and feet (where the blood vessels over-constrict in cold weather) as well as bowel and bladder symptoms.
And because the ANS affects blood vessel size, and consequently blood flow, it also plays a role in muscle function (muscle has a very rich blood supply) and cognitive function (as blood flow to parts of the brain may be affected).
This important new research has used a special type of brain scanning/neuroimaging (magnetic resonance imaging/MRI) to look at may be happening in the control centres in ME/CFS in relation to changes in pulse and blood pressure - research that has not been carried out before.
In what is called an exploratory cross-sectional study, blood pressure and heart rate, as indicators of autonomic function, were correlated with MRI findings in the control centres in the brain in 25 CFS subjects and 25 healthy control.
The steady state blood pressure (systolic, diastolic and pulse pressure) and heart rate in two postures were extracted from 24 h blood pressure monitoring.
Key finding:
Abnormal regressions were detected in nuclei of the brainstem vasomotor centre, midbrain reticular formation and hypothalamus, but also in limbic nuclei involved in stress responses and in prefrontal white matter.
Key conclusion:
We propose that these regulatory nuclei are functioning correctly, but that two-way communication between them is impaired in CFS and that this affects signalling to/from peripheral effectors/sensors, culminating in inverted or magnified correlations.
This is clearly complex research. In very simple terms, it indicates that while these control centres are functioning correctly, there appears to be a problem involving communication between the various control centres in the brain.
It is interesting to note that the brainstem has been implicated in ME/CFS in other studies using neuroimaging - especially the blood flow study carried out by Durval Costa et al.
So whilst this research helps to increase our understanding of ANS abnormalities in ME/CFS and why they may be occurring, it does not offer any new or immediate solutions regarding treatment of ANS dysfunction.
Dr Charles Shepherd
Hon Medical Adviser, MEA
Diagram: Autonomic nervous system - what does it do?
anciendaze
Senior Member
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@landsbergen,
After decades of speculation on how lithium salts work in bipolar disorder, I'm finally starting to see a link with GIRK channels which makes more sense. There is a connection with immune activity, but that is still more complicated.
After decades of speculation on how lithium salts work in bipolar disorder, I'm finally starting to see a link with GIRK channels which makes more sense. There is a connection with immune activity, but that is still more complicated.
Gemini
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- East Coast USA
Thank you @charles shepherd for posting a clear and comprehensive summary of the study.
As you mention the researchers used 24 h blood pressure monitoring which is excellent.
And their paper indicates the data was collected in the home setting which is good news for the homebound demonstrating such outreach is not only possible but under certain circumstances such as this study highly feasible.
Marky90
Science breeds knowledge, opinion breeds ignorance
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Well there is solid evidence that it does.
lansbergen
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I will not get engaged in a polemic.
Marky90
Science breeds knowledge, opinion breeds ignorance
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There`s no need for polemics, the evidence for autoimmunity is there.
lansbergen
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I said for no reason.
Ecoclimber
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This is a continuation from an earlier research project discussed on a couple of threads noted below. The reason I noted this fact is because the authors mentioned the relationship in their current research that some may have missed within the discussion as to a number of significant issues and discoveries as mentioned by Charles Sheparerd. Perhaps I missed the discussion in some posts as well/
"Group comparisons of CFS and NC did not find MRI differences in these locations. We propose therefore that these regulatory nuclei are functioning correctly, but that two-way communication between them is impaired in CFS and this affects signalling to/from peripheral effectors/sensors, culminating in inverted or magnified correlations. This single explanation for the diverse abnormal correlations detected here consolidates the conclusion for a brainstem/midbrain nerve conduction deficit inferred earlier (Barnden et al., 2015). Strong correlations were also detected in isolated NC regressions."
"It is possible therefore that the regulatory nuclei themselves may be unaffected, but that two-way signalling between them is compromised and this affects signals to/from peripheral autonomic effectors/sensors which culminates in the collective dysregulation in CFS expressed by the abnormal correlations here. This is consistent with the impaired midbrain nerve conduction in CFS inferred earlier (Barnden et al., 2015)."
http://forums.phoenixrising.me/index.php?threads/abstract-does-cfs-have-a-neurological-origin.42835/
http://forums.phoenixrising.me/index.php?threads/neuroimaging-research-from-adelaide.35793/
In short, it is basic confirmation but not a full replication which would require other outside researchers - of earlier research in this area.
Biomarkers such as proinflammatory cytokines produced by activated cells of the innate immune system in contact with specific pathogen-associated molecular patterns (PAMP). These cytokines include mainly interleukin (IL) 1 (IL-1α and IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Those researchers with confirmation bias can produce statistical analysis clarifying the way the brain processes information generated by the innate immune system that is accompanied by a progressive elucidation of the cellular and molecular components of the intricate system that mediates cytokine-induced sickness behavior and Depression.
Neuroimaging has its own issues with integrity and credibility. You can take an image but what does it mean? Will it carry across groups of patients with similar conditions or symptoms? Does CBV or rCBV low blood volume in brain of depressed people cause depression or does depression cause low blood volume. There is also noise factor within scans that must be eliminated through computation. For instance, fMRI signal lags for more than 2 seconds behind the neural response (that was actually more or less known before, but not measured directly). That means that it can be used to monitor only mental operations that cause patterns of activity which are fixed for seconds. Most of thinking proceeds much faster than that, so fMRI will never be useful for monitoring thinking.So the development of statistical, detection, classification and construction algorithms are developed to reduce the noise but these algorithms that are developed can have unknown confirmation bias built in.
This is the issue and concerns that many of the patient advocates surrounding the NIH study where brain abnomalities in fibromyalgia, pain, fatigue and FND are considered a reaction - not the cause - to outside enviromental factors including stress, fatigue and pain.
"Group comparisons of CFS and NC did not find MRI differences in these locations. We propose therefore that these regulatory nuclei are functioning correctly, but that two-way communication between them is impaired in CFS and this affects signalling to/from peripheral effectors/sensors, culminating in inverted or magnified correlations. This single explanation for the diverse abnormal correlations detected here consolidates the conclusion for a brainstem/midbrain nerve conduction deficit inferred earlier (Barnden et al., 2015). Strong correlations were also detected in isolated NC regressions."
"It is possible therefore that the regulatory nuclei themselves may be unaffected, but that two-way signalling between them is compromised and this affects signals to/from peripheral autonomic effectors/sensors which culminates in the collective dysregulation in CFS expressed by the abnormal correlations here. This is consistent with the impaired midbrain nerve conduction in CFS inferred earlier (Barnden et al., 2015)."
http://forums.phoenixrising.me/index.php?threads/abstract-does-cfs-have-a-neurological-origin.42835/
http://forums.phoenixrising.me/index.php?threads/neuroimaging-research-from-adelaide.35793/
In short, it is basic confirmation but not a full replication which would require other outside researchers - of earlier research in this area.
Biomarkers such as proinflammatory cytokines produced by activated cells of the innate immune system in contact with specific pathogen-associated molecular patterns (PAMP). These cytokines include mainly interleukin (IL) 1 (IL-1α and IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Those researchers with confirmation bias can produce statistical analysis clarifying the way the brain processes information generated by the innate immune system that is accompanied by a progressive elucidation of the cellular and molecular components of the intricate system that mediates cytokine-induced sickness behavior and Depression.
Neuroimaging has its own issues with integrity and credibility. You can take an image but what does it mean? Will it carry across groups of patients with similar conditions or symptoms? Does CBV or rCBV low blood volume in brain of depressed people cause depression or does depression cause low blood volume. There is also noise factor within scans that must be eliminated through computation. For instance, fMRI signal lags for more than 2 seconds behind the neural response (that was actually more or less known before, but not measured directly). That means that it can be used to monitor only mental operations that cause patterns of activity which are fixed for seconds. Most of thinking proceeds much faster than that, so fMRI will never be useful for monitoring thinking.So the development of statistical, detection, classification and construction algorithms are developed to reduce the noise but these algorithms that are developed can have unknown confirmation bias built in.
This is the issue and concerns that many of the patient advocates surrounding the NIH study where brain abnomalities in fibromyalgia, pain, fatigue and FND are considered a reaction - not the cause - to outside enviromental factors including stress, fatigue and pain.
JaimeS
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