Thursday, 8 December 2011

Early cortical disease in MS

Lucchinetti et al. Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 2011;365:2188-97.

BACKGROUND: Cortical (the outside bit of the brain containing the nerve cell bodies) disease has emerged as a critical aspect of the pathogenesis of MS, being associated with disease progression and cognitive impairment. Most studies of cortical lesions have focused on autopsy findings in patients with long-standing, chronic, progressive MS, and the noninflammatory nature of these lesions has been emphasized. MRI studies indicate that cortical damage occurs early in the disease.

METHODS: The investigators evaluated the prevalence and character of demyelinating cortical lesions in MS'ers. Cortical tissues were obtained in passing during biopsy sampling of white-matter lesions. In most cases, biopsy was done with the use of stereotactic procedures to diagnose suspected tumors. MS'ers with sufficient cortex (138 of 563 patients screened) were evaluated for cortical demyelination.

RESULTS: Cortical demyelination was present in 53 patients (38%) (104 lesions and 222 tissue blocks) and was absent in 85 patients (121 tissue blocks). Twenty-five patients with cortical demyelination had definite multiple sclerosis (81% of 31 patients who underwent long-term follow-up), as did 33 patients without cortical demyelination (72% of 46 patients who underwent long-term follow-up). In representative tissues, 58 of 71 lesions (82%) showed T-cell infiltrates, and 32 of 78 lesions (41%) showed macrophage-associated demyelination. Meningeal inflammation was topographically associated with cortical demyelination in patients who had sufficient meningeal tissue for study.



Cortical lesions on MRI in MS

CONCLUSIONS: In this cohort of patients with early-stage MS, cortical demyelinating lesions were frequent, inflammatory, and strongly associated with meningeal inflammation.#

"This study supports MRI findings and what we know about cognitive impairment in early MS. 30-50% of subjects with CIS (first demyelinating event) have significant cognitive impairment. I am not sure that this study provides any new insights, except cortical lesions are not associated with Dawson's fingers; their morphology is very different to white matter lesions. Understanding gray matter cortical lesions is clearly very important and area of active research. "

Click here for a radio cast on this topic

However, this is not really a paradign shift as claimed on the radio, but is providing evidence that is supportive of things that we thought we knew already.

5 comments:

  1. Come to the MS research Day as Grey Matter (bits whrere nerve heads) pathology is one of our research topics.

    The expresso pathology of Dr Love was talking about the lesions in the white matter. We are planning further posts on heterogenieity (differences) and similarities on lesions, such as ones with a lot of immune cells and ones with few immune cells.

    We will also do one on Grey Matter Pathology as it is different as there is less damaged myelin to deal with.

    These different aspects need to be considered. In these early lesions there were T and B cells, in contrast to some other studies.

    At present we can still say that the oligodendrocyte appears to be the target for the problem.

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  2. MouseDoc, do you think that oligodendrocyte issues also feature in PPMS cases, or is the disability factor more a result of nerve death which means that new oligodendrocytes won't help because the nerves are now dead?

    Not sure if I'm making sense. English is not my first language.

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  3. Dear Anon 6:17
    Yes I think oligodendrocyte issue are the an important feature of PPMS cases.

    I think that some of the disability factor in PPMS, SPMS and RRMS is a result of nerve death. Unfortunately it does mean that new oligodendrocytes won't be of use for nerves that have been lost as there is nothing for the oligodendrocyte to repair.

    However, this nerve damaging process is an ongoing slow process that goes on throughout the course of MS, so if you give new oligodendrocytes to any MSer there are always nerves present that could benefit from repair.

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  4. Re- "...if you give new oligodendrocytes to any MSer there are always nerves present that could benefit from repair."

    My mom has been in a wheelchair for the last 7 years. Do you think that new oligodendrocytes could, even marginally, help even someone like her even though she's now disabled for so many years?

    I guess I just want some hopeful news is all. It all seems so bleak at the moment.

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  5. If there are nerves that need myelinating, which I am sure there will be then if we get myelin back on them it is going to be useful.

    The problem that we face is showing that we can make new oligodendrocytes and that they can them to do their job of repair. Those studies have not yet been done and shown to work.

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