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Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in CFS

Discussion in 'Latest ME/CFS Research' started by Ecoclimber, Apr 5, 2016.

  1. Ecoclimber

    Ecoclimber Senior Member

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    This is an Open Access Article click here for more:

    Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome
    Leighton R. Barndena, Richard Kwiatekc, Benjamin Croucha, Richard Burnetd, Peter Del Fantee,

    Abstract
    Autonomic changes are often associated with the chronic fatigue syndrome (CFS), but their pathogenetic role is unclear and brain imaging investigations are lacking.

    The vasomotor centre and, through it, nuclei in the midbrain and hypothalamus play a key role in autonomic nervous system regulation of steady state blood pressure (BP) and heart rate (HR). In this exploratory cross-sectional study, BP and HR, as indicators of autonomic function, were correlated with volumetric and T1- and T2-weighted spin-echo (T1w and T2w) brain MRI in 25 CFS subjects and 25 normal controls (NC).

    Steady state BP (systolic, diastolic and pulse pressure) and HR in two postures were extracted from 24 h blood pressure monitoring.

    We performed (1) MRI versus autonomic score interaction-with-group regressions to detect locations where regression slopes differed in the CFS and NC groups (collectively indicating abnormality in CFS), and (2) MRI regressions in the CFS and NC groups alone to detect additional locations with abnormal correlations in CFS.

    Significant CFS regressions were repeated controlling for anxiety and depression (A&D).
    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.

    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.

    MRI CFS Brain stem.gif

    5. Conclusion

    This cross-sectional study detected local abnormal correlations in CFS between brain MRI and steady state peripheral BP and HR. Among other regions, nuclei in the vasomotor centre, midbrain CnF, hypothalamus, cerebellar vermis and PCC were prominent. We suggest that reciprocal connectivity between these regulatory nuclei is impaired, which in turn affects signalling to/from peripheral effectors/sensors and culminates in the observed abnormal correlations. More research should be directed to investigating brainstem/midbrain status and function in CFS.



     
    Last edited: Apr 5, 2016
  2. halcyon

    halcyon Senior Member

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    Haven't read it in depth yet but I'm a bit confused about the choice of patients. They wanted to look at autonomic abnormalities and yet none of the patients chosen had POTS?
     
  3. Marco

    Marco Grrrrrrr!

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    Near Cognac, France
    Abnormal signalling in brain-stem/mid-brain areas - if confirmed - would be an interesting finding.
     
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  4. lansbergen

    lansbergen Senior Member

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    Yes, and it would comfirm what I have been thinking for a long time.

    I do not have enough knownledge of the technic to judge the research. Anybody on here who can?
     
    Ninan likes this.
  5. Gijs

    Gijs Senior Member

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    What are you thinking for a long time Landsbergen?
     
  6. Ninan

    Ninan Senior Member

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    Seems interesting. Anyone who can translate this into English?
     
  7. Valentijn

    Valentijn The Diabolic Logic

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    They used the CCC to recruit patients. The lack of strictly-defined POTS isn't that unexpected ... older research showed most ME patients have a different form of orthostatic intolerance, Neurally Mediated Hypotension.

    Pulse pressure was low when sitting up, however, and heart rate was elevated:
    However, they shouldn't be using HADS questionnaire in patients with a chronic, untreated, multi-system illness who are also not hospitalized. It doesn't account for untreated disability and pain, etc, so it ultimately equates physical and cognitive limitations with depression.

    The Barnden paper cited above found a statistical difference (adjusted for multiple comparisons) in pulse pressure between controls and CFS patients ... but barely, and the CFS values they found were completely normal, with an average of 46.9 seated. Though if they did it after 10-30 minutes on a Tilt Table or leaning against a wall, they might get some more interesting values.

    But overall, it's nice to see someone seriously looking into the cause of pulse pressure abnormalities in ME patients, though it'd be nice if they looked beyond the brain as well.

    They also mostly rule out psychological stress, which is useful:
     
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  8. jimells

    jimells Senior Member

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    northern Maine
    In spite of my autonomic problems, I am not convinced my autonomic system is dysfunctional. Rather, I suspect it is compensating for some other problem, like an inability to create sufficient energy to keep everything operating "normally", plus low blood volume, etc.

    I'm not able to understand enough of the abstract to determine if their results suggest autonomic dysfunction or not. @Valentijn does this paper confirm autonomic dysfunction?
     
    Last edited: Apr 6, 2016
  9. anciendaze

    anciendaze Senior Member

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    While I am always interested in physiological measurements related to these diagnostic categories, I am bothered by the concentration on structures deep within the brain which are unlikely to be the first regions in which impairment takes place. I could point to changes in the brains of patients with severe osteoarthritis in the knees which is apparently the result of prolonged pain originating at knee joints, not part of the etiology of the condition. I'm not aware of psychobabblers suggesting mental illness in osteoarthritis, but without gross damage to easily accessible tissues I could imagine this argument appearing.

    Do any patients with autonomic problems report chronic pain? If so, this could account for changes in the CNS far downstream from causation.

    There are numerous autonomic ganglia where infection is a real possibility, and measurements are easier. Why are these being ignored?

    A second aspect of damage to structures deep in the brain would be due to immune response, and this does happen in serious known diseases. This is also more likely to originate far outside the brain in areas where autonomic nerves are vulnerable to pathogens. Even if the nerves are not subject to damage they could easily trigger the immune response behind diffuse neurological impairment to nerves associated with autonomic system activities. I'll remind people that conditions as familiar as shingles result from VZV infection of dorsal root ganglia lasting a large part of a lifetime.

    The central nervous system is not entirely responsible for autonomic function, and autonomic function is intimately involved with regulation of certain immune activities. We talk about autonomic dysfunction and immune dysfunction, but we keep falling back to the idea these are really controlled by the brain. Anything not under conscious control must then be subconscious.
     
  10. Valentijn

    Valentijn The Diabolic Logic

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    I don't know if could be said to confirm autonomic dysfunction ... my impression is that it's just a significant difference from controls regarding autonomic function. It would primarily depend on what the specific criteria are for autonomic dysfunction.
     
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  11. halcyon

    halcyon Senior Member

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    Which research is that?
     
  12. Sidereal

    Sidereal Senior Member

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    Ramsay included orthostatic tachycardia on his ME symptom list back in the 1980s before POTS had even been characterised.
     
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  13. lansbergen

    lansbergen Senior Member

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    The brainstem is the favorite spot of the infection I suspect.

    I think it is not so much structure damage but communication dysfunction.

    I would like to know how many patients get transient swelling at the cerebral base.
     
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  14. halcyon

    halcyon Senior Member

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    It seems like the one structure that keeps coming up again and again, in the MRI studies, PET studies, SPECT studies, postmortem viral testing, etc.
     
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  15. anciendaze

    anciendaze Senior Member

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    In evolutionary terms the brainstem is one of the oldest parts of the brain, and injuries there are likely to be fatal. This is one of the best protected parts of the nervous system. I'm having trouble imagining an infection starting there without causing really deadly effects, as happens in bulbar polio. If this is happening there should be a progressive disease which parallels ME/CFS, and has many serious consequences we don't see.

    An autoimmune response secondary to infection elsewhere in the nervous system still sounds more likely to me.
     
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  16. Gemini

    Gemini Senior Member

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    Interestingly 14 of 25 CFS patients in this study had an infectious onset (7 caused by serologically proven EBV).

    As EBV miRNA's appear to be signaling mediators of MS pathogenesis, perhaps the researchers could test miRNA profiles in the CFS patient cohort used in this study...

    "Limitations" section of the paper states the results are "indirect" and "direct" measurements are warranted.

    Anyone here know what's required for "direct" measurement given the importance of this area of research?
     
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  17. lansbergen

    lansbergen Senior Member

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    Nobody can convince me the immune system attacks self for no reason. I did not believe it 40 years ago and still don't.
     
  18. Valentijn

    Valentijn The Diabolic Logic

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    Rowe, I think?
     
  19. halcyon

    halcyon Senior Member

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    Thanks. I was curious if there was anything newer looking at NMH in CCC/ICC patients.
     
  20. anciendaze

    anciendaze Senior Member

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    Have you looked into the association between autoantibodies and cancer, retroviral infection, etc.?

    At present I'm trying to make sense of the bewildering array of problems showing up in mast cell activation syndrome (MCAS), and there are definite patterns appearing. This is not to say I understand it.

    Human immune systems operate on a considerably more sophisticated level than human explanations about immune response. The distinction between "self" and "other" is not at all simple along interfaces with the outside world where living cells have to come into contact with oxygen or nutrient molecules in the presence of a complex microbiota. We have fairly good explanations for what goes on in exceptional cases like wounds to skin, and poor explanations for what goes on across square meters of lung and gut tissue in situations where there is very little immune activation. There are real pathogens in these places, as becomes obvious when someone is shot in the gut or lungs, but most of the time otherwise there is not any kind of crisis. It looks like a false trigger for a powerful response can happen in many ways.

    In any case, we still don't have anything approaching a complete list of normal biota in the lungs or gut, including viruses which control potentially pathogenic microbes. We are probably talking about thousands of species.
     
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