Saturday, 21 September 2013

Reduced grey matter bloodflow in early MS

Early blood flow problems to cortex in MSers is associated with cognitive impairment. #MSBlog #MSResearch

"There has been an extensive debate on this blog about the possibility of there being a vascular hypothesis that underpins MS. This debate has largely been driven by the social phenomenon of CCSVI. Now that CCSVI has been discredited as a MS-specific entity we must not discard the possibility that blood flow, or perfusion, is not involved in the pathogenesis of MS."

"In this study below, in early RRMS, the investigators show that prior to loss of grey matter that occurs in MS there is a perfusion deficit to this area of the brain. Perfusion means a lack of blood flow. What does this mean? It does not necessarily mean that the reduced blood flow is the problem. A more likely explanation is that the tissue requirements for blood are reduced. Various tissues of the body, grey matter included, have mechanisms to regulate their own blood supply. If you need more oxygen and energy the tissues lower their pH, which cause the arterioles (small arteries) to dilate, or get larger, which increases the blood flow to the tissues and vice versa. This process is very efficient and maximises the use of oxygen and energy (glucose and fats) both locally in organs and throughout the body. If you study biology this is part of what we call homeostasis."

"This reduced grey matter perfusion is telling us that the cortex needs less blood, i.e. oxygen and/or energy, hence there must be a problem with its functioning. To me this indicates that the grey matter neurones are either dying, dead or sick and hence don't need as much blood. This blood flow or perfusion deficit occurs before overt atrophy or shrinking of the grey matter is seen. This is what you would expect; tissue damage always precedes shrinkage or atrophy which is a delayed response. The timing of this delay between tissue damage and atrophy is important; is it 6, 12 or 24 months? We need to know this as we are beginning to use brain and focal grey matter atrophy as an outcome measure in clinical trials and possibly in clinical practice to monitor the effects of DMTs. It is not surprising that reduced blood flow is associated with reduced cognition; the grey matter is the stuff that makes us think and remember things."


"This study indicates that there must be a more diffuse disease process occurring in the grey matter of MSers that precedes focal lesions and brain atrophy. The fact that it is occurring in the cortex an area of brain that abuts on the cerebrospinal fluid or CSF suggests it may have something to do with the CSF. Could there be a toxin or virus in the CSF? Could this toxin be the toxin from MS-related human endogenous retrovirus or HERV? Other contenders for this could be immunoglobulins or antibodies in the CSF or one of the many soluble inflammatory mediators. What this study also exposes so brutally is how little we know about the disease processes of early MS and how much we still have to learn."

Epub: Debernard et al. Reduced grey matter perfusion without volume loss in early relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Sep 13.

BACKGROUND: Grey matter (GM) pathology in MS is associated with progressive long-term disability. Detection of GM abnormalities in early MS may therefore be valuable in understanding and predicting the long-term course. However, structural MRI measures such as volume loss have shown only modest abnormalities in early RRMS. This study therefore looked for evidence of abnormality in GM perfusion (blood flow), consistent with metabolic dysfunction, in early RRMS.

METHODS: 25 RRMSers with ≤5 years disease duration and 25 age-matched healthy controls underwent 3 Tesla MRI with a pseudo-continuous arterial spin labelling sequence to quantify GM perfusion and a volumetric T1-weighted sequence to measure GM volume. Neurological status was assessed in patients and neuropsychological evaluation undertaken in all subjects. Voxel-based analysis was used to compare regional GM perfusion and volume measures in MSers and controls.

RESULTS: There was reduced global GM perfusion in MSers versus controls (50.6±5.8 mL/100 g/min vs 54.4±7.6 mL/100 g/min, p=0.04). Voxel-based analysis revealed extensive regions of decreased cortical and deep GM perfusion in MSers. Reduced perfusion was associated with impaired memory scores. There was no reduction in global or regional analysis of GM volume in MSers versus controls.

CONCLUSIONS: The decrease in GM perfusion in the absence of volume loss is consistent with neuronal metabolic dysfunction in early RRMS. Future studies in larger cohorts and longitudinal follow-up are needed to investigate the functional and prognostic significance of the early GM perfusion deficits observed.

50 comments:

  1. Could this be connected to the previous post regarding the incidence of Migraine in MS sufferers.

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    Replies
    1. Re migraine and reduced perfusion. I don't think they are linked. Migraine aura is associated with a condition called spreading depression that is not linked to a perfusion deficit. The vascular hypothesis of migraine aura has also been discredited.

      The headache part involves lower structures that are quite a distance from the cortex of the brain.

      Good suggestion.

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    2. Can you comment at all about decreased jugular distensibility leading to cerebral venous hypertension in migraine patients? This is what I mean (link to Chung research): http://www.umbjournal.org/article/S0301-5629(09)01471-9/abstract

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    3. Yes i too would like to hear this.
      It seems the word 'Discredited' is used far to liberally lately on here for things that have only actually been discredited in the authors opinion?
      This surely discredits the scientific validity of this whole site?

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    4. http://www.umbjournal.org/article/S0301-5629(09)01471-9/abstract

      I suggest we wait and see if these findings are reproduced; it takes more than a swallow to make a summer. Science is all about reproducibility.

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    5. Yes indeed, lets ALL wait before making statements in theory that seem to give the impression of a categorical fact.

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    6. Search discredited it gives 8 posts of about 3,000 is hardly liberal use of the word :-)

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    7. Three of the eight have been in the last four months, I did say lately.
      Even one is too much when it gives an impression that could be misconstrued.

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  2. Prof. G I think you should start a "Save My Grey Matter Campaign" it sounds better than "Switch of the Shredder Campaign".

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    Replies
    1. What about the 'brain is time'?

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    2. Or 'Neuro Protect my Brain'?

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    3. I like them all. As you know this issue is close to my heart and giving it a slogan may help. I am participating in a bloggers session at ECTRIMS on brain atrophy. I am planning to talk to a infographic; having a name for the infographic would be helpful.

      I like the "Your brain is power: protect it!"

      More suggestions would be helpful. Thanks.

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  3. Or, DO NOT SHRED: Grey Matter matters

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  4. Rich MurraySaturday, September 21, 2013 6:23:00 pm

    POST SPAMMED

    Anonymous Saturday, September 21, 2013 8:57:00 pm
    They might be common but I never had one in my whole life... never smoked, never used aspartame or any other artificial sweetener.. so to me it seems like you are barking up the wrong tree.

    Delete

    ReplyDelete
    Replies
    1. Uh, Anonymous -- neither my post, gently proposing methanol as a reasonable candidate for the prime cause of MS, nor this one, can fairly be termed, "spam" --

      anyway, methanol also is provided by dark wines and liquors, wood and peat smoke, smoked fermented and spoiled foods, fresh tomatoes and black currants, unfresh vegetables juices fruits cut up and preserved wet at room temperature in sealed jars cans plastics, jellies jams marmalades, industries that involve solvents and heated wood and paper production, chemical medical and mortuary facilities -- do any of these ring a bell?

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    2. We have asked politely many many times and like fingers into a candy jar you cannot stop yourself. Whilst we cannot slap your wrist we can throw away the candy

      Delete
    3. Rich
      We don't care how infrequent the methanol posts appear, one is too many any will be dealt with the same way and spammed. We have asked you too many times to desist.

      Delete
  5. "Now that CCSVI has been discredited as a MS-specific entity"

    Please clarify, Are you stating CCSVI does not have anything to do with MS?
    Because if you are i want a copy of that for future reference.

    Or are you, by using the term "MS-specific entity" saying that CCSVI does exist not only in MS but in other neurological conditions?

    Question screen saved and dated, Please answer.

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    Replies
    1. If he been reading the Italian COSMO study there was essential no
      evidence of CCSVI.It is referenceson r

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    2. Re: "Please clarify, Are you stating CCSVI does not have anything to do with MS? Because if you are i want a copy of that for future reference."

      The data has been published in the scientific literature, summarised on this blog, presented and debated at many scientific conferences and incorporated into many national guidelines. There is no one reference, but a substantial body of work supporting this claim.

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    3. We recently hear that the trial in USA (Gary Siskin Albany) has been cancelled because there was not enough interest

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    4. I'm not asking about crooked studies, I'm asking for clarification on YOUR post....
      "Now that CCSVI has been discredited as a MS-specific entity"

      As this is not the house of commons I think I'm entitled to a straight answer so i will ask again.
      Are you, Prof. Gavin Giovannoni saying CCSVI has nothing to do with MS?
      Simple question,
      Please answer yes or no?

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    5. Nothing to do with MS. If it exists it is a non-specific finding and found in normal people and a large number of other conditions. A large number of studies suggest the condition does not exist; this is a philosophical argument about how we define diseases.

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    6. Am i not making my self clear?
      Again a politicians answer?
      I understand the context of the philosophical argument, so easy to use this context to excuse information that could be mistaken by some as factual.

      Just please answer the question without all the explanations.

      Do you Prof. Gavin Giovannoni Say CCSVI is part of the MS condition?

      Please Simply answer,
      YES IT IS,
      NO IT IS NOT,
      or
      I DO NOT KNOW.


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    7. What are you, a lawyer, Yam? He said no. Now STFU.

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    8. Are you dumb or something Andy?

      Get off the case.

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    9. If I did not know otherwise that AY is a real person could it be Jeremy Paxman on the blog :-)

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    10. I'm glad that I wasn't the only one who completely understood what Prof. G was saying, which, to put it in the most simplest of terms, is a big fat NO to Yam's question! But since Yam doesn't believe in the "crooked" studies, his inability to comprehend G's response was understandable.

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    11. MD we have met more than once, I'll take that as a compliment,
      Interesting that you see the comparison between the dynamics of Paxman trying to nail down a slippery member of parliament and me trying to get a simple straight one line answer from GG
      One which up to now is still being avoided.

      If dumbfounds me that no one else here can see the answer is a no with conditional future wriggle room.
      I'm not asking for every ones opinion of what GG says, i'm not here to argue.
      I'm asking for a straight one line answer to a straight one line question from the man himself.
      Simple.
      GG.
      YES
      NO
      I DON'T KNOW.

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    12. It is the nature of science to maintain wriggle room....we are trained to say maybe... perhaps....it is possible etc.

      I have just been rebuked by a referee for been too positive about the interpretation of some results.

      Why nail yourself to a mast when you can wait for the trial evidence to materialise and then make comment,.....,there is an increasing weight of evidence building up.

      Delete
    13. Will we having this debate over faecal transplantation in a few moths/years time?

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    14. Andy, You're being controlling and abusive.

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    15. En O, spells NO! CCSVI has nothing to do with MS; as defined by Zamboni it is found in normal people and people with a raft of other conditions. As of yet there is no clinico-pathological correlate therefore it cannot be defined as a disease in its own right.

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    16. This quote would seem to be appropriate regarding our vociferous proponents of CCSVI/Liberation therapy.

      ‘‘If a man is offered a fact which goes against his
      instincts, he will scrutinize it closely, and unless the
      evidence is overwhelming, he will refuse to believe
      it. If, on the other hand, he is offered something
      which affords a reason for acting in accordance to his
      instincts, he will accept it even on the slightest evidence.
      The origin of myths is explained in this way.’’
      Bertrand Russell
      (Roads to Freedom) 1970

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    17. Does NO mean nitric oxide? :-) Of is that a wriggle?

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    18. Thank you for more of the same in your final answer (and sarcasm MD, you really are wasted here)
      I guess by now i expect nothing more.
      As we ALL know Zamboni's work is only a small part of the full venous picture in MS as defined and reported by Dr. Franz Schelling.

      http://www.ms-info.net/ms_040504.pdf

      MD and MD2, Your replies regarding wait and see and Bertrand Russell's quote could easily be reflected back upon your own actions.
      Thinking about it why would any one expect any more from a group who have been happy to keep chasing their tails for over 50 years.

      I'll leave you for now with the Anonymous cheer leaders.
      Arguing with faceless posters is so 2010 and unlike the rest of the MS world a number of people have moved on in the past three years both in attitude and understanding.
      Keep relying on the poorly executed studies for your back up, It will all come out in the wash.
      http://www.youtube.com/watch?v=mS6DC2w5j5I

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    19. happy to keep chasing their tails for over 50 years........so that means we can should have retired about 5 years ago. Thanks for the link to Bob Dylan not even I am old enough to remember that one

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    20. Poorly executed studies for your back up.....it that what allows one to shift goalposts when data appears that does not appear with your world view.

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    21. Professor Mouse. I wouldn't bother engaging with these people any more. CCSVI has become a religion and when you have blind faith or a belief in something you become inflexible. Save your energy for more valuable endeavours.

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    22. http://www.ncbi.nlm.nih.gov/pubmed/24045400

      More on the same, but we wouldn't want to engage too much and waste anyone's time now would we ;-)

      Regards as always.

      Delete
    23. Anonymous Sept 27 9.23 am
      Entirely agree but we feel we have to engage in case anyone is tempted to try "liberation therapy" and end up with the only result being anorexia of the wallet.

      Delete
    24. "When the facts change, I change my mind. What do you do, sir?" John Maynard Keynes

      The facts certainly appear to have changed re CCSVI. What do you do Andy, keep on believing because so many studies telling me I'm wrong means I must be right?

      Delete
  6. This might be worth reading and responding to
    http://www.thisisms.com/forum/chronic-cerebrospinal-venous-insufficiency-ccsvi-f40/topic10680-7935.html#p215441
    It's Dr. Sclafani, an IR who treats jugular abnormalities, speaking about what's seen in the literature.

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    1. Is this guy a car boot salesman getting in an advert, otherwise why would there would be an email link termed "ccsviliberation"

      A post from a goalpost mover

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    2. Maybe direct us to a post by Dr Siskin who can give his own words what happened and not some reporters

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    3. Dr. Sclafani is the Cheif of Radiology at SUNY Downstate Medical Center in Brooklyn, NY. Two years ago a prominent American newspaper wrote an article about his department's failure to adequately shield infants from being exposed to dangerous levels of radiation from X-rays and CT scanners: http://www.nytimes.com/2011/02/28/health/28radiation.html?pagewanted=all&_r=1&
      Maybe Dr. Sclafani should pay more attention to what his techs are doing rather than spend his time posting at "This is MS".

      As for Dr. Siskin, this article's got some choice quotes from him: http://www.theglobeandmail.com/life/health-and-fitness/health/saskatchewan-trial-for-ms-liberation-therapy-cancelled-citing-lack-of-volunteers/article14209033/
      I feel bad for him. According to the article, over 3,000 people petitioned for this study to be funded, so why didn't they immediately sign up to participate in Siskin's study?

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    4. If they needed 200 people and canada was to supply 100 of them it all sounds very,very odd.

      I am sure there must be more to this story.

      Delete

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