Friday, 28 October 2011

Cortical lesions in MS

Sormani et al. Modeling the distribution of new MRI cortical lesions in multiple sclerosis longitudinal studies. PLoS One. 2011;6(10):e26712. Epub 2011 Oct 20.

OBJECTIVE: Recent studies have shown the relevance of the cerebral grey matter involvement in MS. The number of new cortical lesions (CLs), detected by specific MRI sequences, has the potential to become a new research outcome in longitudinal MS studies. 

AIM: To define the statistical model better describing the distribution of new CLs developed over 12 and 24 months in patients with RRMS.

METHODS: Four different models were tested on a group of 191 RRMS patients untreated or treated with 3 different disease modifying therapies. Sample size for clinical trials based on this new outcome measure were estimated by a bootstrap resampling technique.

RESULTS: The zero-inflated Poisson model gave the best fit for new CLs developed over 12 and 24 months both in each treatment group and in the whole RRMS patients group adjusting for treatment effect.

CONCLUSIONS: The sample size calculations based on the zero-inflated Poisson model indicate that randomized clinical trials using this new MRI marker as an outcome are feasible.

"Why is this study important? Because it focuses on an area of the disease that until recently has been hidden from view and which contributes a lot to the burden of the disease. We simply need therapies that protect the gray matter; gray matter is the part of the brain that use to think - it makes us who we are. MS disease in gray matter results in cognitive impairment and contributes to fatigue. By stopping gray matter pathology we may be able to protect MS'ers from developing cognitive impairment."

"Again progressive MS'ers seem to have been forgotten in this study. I will write to Professor Sormani to ask her if she has a data set to look at this issue in people with SP and PP MS."


  1. Do current treatments have any impact on protecting grey matter? What comes first, white matter or grey matter damage? Why can't inflammation be the cause of white matter and grey matter damage e.g. if you pointed a flame thrower at a brain it would damage white and grey matter.

  2. See this:

    "White Matter Hemodynamic Abnormalities precede Sub-cortical Gray Matter Changes in Multiple Sclerosis"

    The answer to your question is hypoperfusion, namely altered cerebral blood flow.

  3. And this:

    "Gray matter involvement in multiple sclerosis"

    "1) GM involvement and in particular cortical demyelination can be extensive in MS; 2) GM pathology may occur in part independently of WM lesion formation; 3) a primarily GM-related process may be the earliest manifestation of MS; 4) GM involvement is associated with physical disability, fatigue, and cognitive impairment in MS; and 5) GM disease might help explain the observed dissociation between markers of inflammatory demyelination (relapses, WM gadolinium enhancement, WM lesion burden) and disease progression."

  4. Re: "Do current treatments have any impact on protecting grey matter? What comes first, white matter or grey matter damage?"

    Almost certainly. Some of drugs delay brain atrophy, which includes gray matter. What is needed are studies that break-up the atrophy into white matter and gray matter fractions to be confident of the effect on gray matter. This new technique looks at focal lesions in the gray matter.

    There is a lot of new data that is emerging on the gray matter lesions that suggests it is different to white matter lesions. I must stress that there is no evidence at all the gray matter lesions are due to hypoperfusion. There is nothing wrong with the arterial blood supply to brain in MS; unlike disease such as vasculitis (inflammation of blood vessels) that causes blockages in the arteries.

  5. Prof G,

    Thanks. I asked Dr Coles this a couple of years ago and he thought that Campath (which I received) would have an effect on both types of lesions. I can't believe that we are unlucky enough to have two different diseases - just one disease which is complicated and destroys different elements of the CNS.

  6. In both grey and white matter lesions the common characteristic is damage to the oligodendrocytes and so is probably one disease, but it looks like there are at least two elements to the disease.

    This is because one aspect responds to immunosuppressive drugs, another aspect (progression) does not.

  7. Re "There is nothing wrong with the arterial blood supply to brain in MS;"

    Sure. Who said anything about impaired inflow? But what about outflow? Some posts below you posted a research by Zivadinov about decreased venous vasculature in the brain ("CCSVI:Pro-Data").

    So, the arteries are fine, the veins are not. The outcome is hypoperfusion and hypoxia. Extremely underestimated so far.

  8. Could you explain the purpose and results of this study a little. I couldn't follow

  9. For many years Neuros have been focusing on the white matter (bit of the brain that has the myelinated axons in them) of the brain. Because this was bit of the brain was thought to contain all the lesions of MS. Therefore all the MRI outcomes were focused on imaging the white matter.

    However when pathologists started staining for myelin rather than using a biochemical stain, it was realised that there were alot of demyelinated lesions in the grey matter (Bit of the brain that contains the nerve cell bodies). These had been missed because they contain few white blood cells compared to white matter lesions. Frankly I think this is pretty shocking because you can see these things with the naked eye. Dogma is a powerful thing to make you blinkered.

    Anyway it is possible that these grey matter lesions have a better correlation with behavioural effects of MS than white matter lesions and also they have been linked to progression. Furthermore it is thought that grey matter lesions may be more useful in assessing drug therapy than white matter lesions.

    Therefore it is important that we find MRI methods to detect these.

    This study looked differnt MRI sequences for maging the cortex of the brain the outside bit of the brain one of them was better than the others for imaging the lesions

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  11. Thank you. I still don't understand anything about the statistical modelling but it probably doesn't matter.

  12. Re "I still don't understand anything about the statistical modelling but it probably doesn't matter."

    The research aimed at finding out the amount of "randomness" in cortical lesion number and dispersion, so that the number of necessary samples for a viable research could be calculated. They find out that this number is within feasible trial sizes.

    Somebody correct me if i am wrong.

  13. Re "So I don't understand how issues with veins are responsible for hypoperfusion and hypoxia in the brain."

    Impaired outflow reduces blood speed and its ability to deliver the oxygen it carries. It is a chronic and low-grade hypoxia, incomparable to the catastrophic hypoxia of a stroke. That's why MS needs years to cause the damage that a stroke does in a minute.


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