Saturday, 29 December 2012

Research vessels at the centre of the lesion

Epub: Gaitán et al. Initial investigation of the blood-brain barrier in MS lesions at 7 tesla. Mult Scler. 2012 Dec 17.

BACKGROUND: We previously described two dynamics of contrast enhancement in scans of active multiple sclerosis lesions: Medium-sized, early lesions enhance centrifugally, whereas larger, slightly older lesions enhance centripetally. Due to technical limitations, our previous study did not characterize lesions < 5 mm in diameter, cortical enhancement, and anatomical structures within lesions.

OBJECTIVE: The objective of this paper is to obtain initial observations of these important aspects of lesion development on a 7 tesla scanner at high spatial resolution. 

METHODS: We scanned eight patients, acquiring precontrast T2*-weighted scans, T1-weighted scans before and after contrast, and high-resolution dynamic contrast-enhanced scans during and up to 30 min after contrast. 

RESULTS: We detected 15 enhancing lesions, obtaining dynamic data in 10: Five lesions < 4 mm enhanced centrifugally (initial central enhancement expanded outward), and five lesions > 4 mm enhanced centripetally (initial peripheral enhancement gradually filled the lesion). A leukocortical lesion (lesion spanning the grey and white matter) initially showed enhancement in its white matter portion, which gradually spread into the cortex. Seventy-three percent of lesions were clearly perivenular.

CONCLUSION: Most active lesions are perivenular, and the smallest lesions enhance centrifugally. This supports the idea that lesions grow outward from a central vein.



Well more data indicating that the lesions expand from around vessels. This is consistent with the histology, but it does not necessaily say what the trigger is and may not centre on the vasculature but may be just outside this. The MRI does not have the resolution for this 4mm could be 40-400 cells thick  and we know that gadolium (the tracer) is entering the brain from the vasculature but as it expands from it does point to a central role in lesion formation.

13 comments:

  1. Cyndi, I hope you contact me directly re methanol made by ADH1 enzyme into formaldehyde inside cells of inner walls of blood vessels at base of brain, the "perivascular loci" of MS and Alzheimer's...

    rmforall.blogspot dot com

    ReplyDelete
  2. very interesting, HOPE for a CURE!!!

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  3. mmm Very interesting, as is the option to comment on this one. A 'Honey Trap ??? well we'll see.

    As I've said before, modern imaging techniques will reveal the true extent to which vascular abnormalities play a role in the developement of MS lesions, I also believe the findings will revolutionise the treatment of Alzheimer's in the coming years.

    The call for a quick answer by using inferior poorly designed trials is premature at best and a smoke screen at worst.
    I've also said before there is no time scale to which research should be held to, it's robust Science that will win the day and the part in which 'Google Trends' play in this is frankly Childish.

    Also the Upright MRI will, (despite your "dissing" as a sales pitch study)come into play, as it will be a invaluable tool with which to see the effects of weight bearing, gravity etc has on compromised blood flow.

    I do appreciate the fact that the people on the pro vasular side of this are now slowly being trated with a little more respect and that is to be welcomed.
    Let the robust studies continue.

    Regards as always.


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  4. These data clearly neutralize the EBV hypothesis. Unless, you can explain how the EBV-infected B-cells manage to cause such symmetrical, perivenular damage, while flowing inside the bloodstream and in the absence of other lesions in the neighbourhood.

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    Replies
    1. Nobody said b-cells themselves cause the damage

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    2. Yes, I agree from histology it is clear that the majority of the cells in these lesions are macrophages

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    3. Anon, we seem to have a bigger problem agreeing in what a typical MS lesion looks like. However, if you have a clear picture of the way that lesions form under the viral hypothesis, i would be interested to hear it.

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  5. Rmforall said "may I"

    No you may not!

    In the spirit of Christmas I left the advertising post from Cyndi but Rich please do not start your crusade on here again, it wastes your and our time.
    Your posts will end up in Spam if it revolves around methanol and Monte as we have asked you countless times in the past.

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  6. Its only about 150 years from another research, done by E.Rindfleich in Germany. He said:
    "If one looks carefully at freshly altered parts of the white matter ... one perceives already with the naked eye a red point or line in the middle of each individual focus,.. the lumen of a small vessel engorged with blood ... All this leads us to search for the primary cause of the disease in an alteration of individual vessels and their ramifications; All vessels running inside the foci, but also those which traverse the immediately surrounding but still intact parenchyma are in a state characteristic of chronic inflammation."

    Its so exiting that new MRI studies come to same conclusion :) We are going back to veins.

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  7. rmforallTuesday, January 01, 2013 10:36:00 PM
    said

    http://en.wikipedia.org/wiki/Eduard_von_Rindfleisch

    Georg Eduard von Rindfleisch (December 15, 1836 – 1908) was a German pathologist. He was born in Köthen and died in Würzburg.

    He was one of the first proposers of a vascular theory for multiple sclerosis after noticing in 1863 that the inflammation-associated lesions were distributed around veins.[1] This work was the ground layer for the later Tracy Putnam work in the vascular theory of MS.

    1. Lassmann H (1999-10-29). "The pathology of multiple sclerosis and its evolution". Philos Trans R Soc Lond B Biol Sci. 354 (1390): 1635–40. doi:10.1098/rstb.1999.0508.
    PMC 1692680.
    PMID 10603616.

    [ See also:
    305. Compston A, Confavreux C, Lassmann H, McDonald I, Miller D, Noseworthy J, et al. McAlpine’s Multiple Sclerosis. Fourth Edition. 4 ed. London: Churchill Livingston - Elsevier.; 2005.

    "Then you try and sneak in your crusade" and your posts get deleted.

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  8. Well, I'm comforted this moment in my old age of 70 that you and I have become friends, despite ourselves, despite each other, that's the delight and mystery of life, for, surely, our destiny is to collaborate deeply for mutual benefit and the profound service of the unlimited evolution of everyone...

    Rich

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  9. sir, at your service, the properly decrusaded section:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1692680/

    Philos Trans R Soc Lond B Biol Sci. 1999 October 29; 354(1390): 1635–1640.
    PMCID: PMC1692680
    The pathology of multiple sclerosis and its evolution.
    H Lassmann
    Department of Neuroimmunology, University of Vienna, Austria. hans.lassmann@univie.ac.at

    ABSTRACT

    The pathology of multiple sclerosis (MS) was defined more than a century ago as a chronic inflammatory process which is associated with widespread primary demyelination and glial scarring.
    In this short review we discuss controversial issues on
    (i) the relationship between inflammation and demyelination,
    (ii) the various possible mechanisms of myelin destruction,
    and (iii) axonal involvement in this disease.
    We suggest that the disease process of MS is more complex that previously believed.

    FULL TEXT
    The Full Text of this article is available as a PDF (293K).

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1692680/pdf/10603616.pdf
    free full text

    ReplyDelete

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