Friday, 9 March 2012

Research: Inflammation in the brain on balance is a bad thing

Magraner et al.The relationship between inflammatory activity and brain atrophy in natalizumab treated patients.Eur J Radiol. 2012 Mar 3. [Epub ahead of print]

OBJECTIVE: To assess the evolution of brain atrophy and its relationship with inflammatory activity in RRMS patients treated with natalizumab.

METHODS: Eighteen RRMS patients were prospectively followed up for 18 months after starting natalizumab therapy. Patients were monitored monthly and assessed for signs of relapses, adverse events or disability increase. MRI scans were performed before starting natalizumab and every six months. Cross-sectional T2 lesion volume and the normalized brain volume at baseline and 18 months MRI scans, Longitudinal Percentage of Brain Volume Change was estimated Linkage between inflammatory activity and brain atrophy was studied.

RESULTS: Natalizumab reduced the relapse rate by 67% and cumulative lesion load by 87.5%. T2 lesion volume decreased from 1000 cubic mm, to 960 cubic mm (p=0.006) and brain volume decreased from 1.55×10(5) cubic mm to 1.42×10(5) cubic mm (p=0.025). Global Percentage of Brain Volume Change( from baseline to 18 months was -2.5%, predominantly during the first six months (0-6 months -1.7%; 6-12 months, -0.74%; ans 12-18months -0.50%). The number of relapses before treatment was correlated to the Percentage of Brain Volume Change during the first semester (p=0.003), while the number of basal MRI lesions or baseline T2 lesion load did not correlate with brain atrophy rate. During follow-up, nine patients had clinical or radiological inflammatory activity. Their Percentage of Brain Volume Change was significantly higher in the first semester (-2.3% to -1.1%, p=0.002).

CONCLUSIONS: Natalizumab reduced relapse rate and lesion load in MRI. Brain atrophy predominated in the first semester and was related to previous inflammatory activity.



Inhibiting the immune response from entering the brain reduces nerve damage and brain shrinkage caused by MS. So not much evidence for protective autoimmunity from this study and yet more evidence for a damaging influence of the immune system in MS.

15 comments:

  1. This is a non-scientific reaction, but I think it's an absurd idea to think that inflammation in the brain is doing good.

    Inflammation is bad in the lungs, the intestines, the joints, the skin, everywhere else. Why would the brain be different?

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  2. "Why would the brain be any different?"

    In my opinion I agree with you.

    However, inflammation is a process aimed of removing infections and then repairing the damage caused as a consequence of the former.

    So there is an element of inflammation being a good guy.

    Some people (perhaps just one person)who view the blog seem to think that this clear up job is all that the immune system does and it is a bystander of no importance...

    This study is yet further evidence that that view is too simplistic and not likely to be correct.

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  3. Don't put so much energy into arguments with the one person

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  4. I wonder who you are talking about? ;-)

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  5. Let me pose a simplistic question:
    What will happen to the dead oligos if you prevent the immune system from entering the brain and cleaning them up?

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  6. Too simplistic.

    If you prevent the immune system from entering the CNS...you do not have any microglia in the brain. This is a resident CNS cell and will probably be bad news as you have these cells in the CNS for a reason.

    Do oligodencrocytes die? if they do how do they die?

    If they die by apoptosis (die and and dissovled itself from within), this will be different if they die by necrosis (where the cell contents are liberated as the cell ruptures) . If they are from the whirte matter, there is a differnce compared to grey matter.

    The debris will be taken and digested by other cells in the nervous system, probably without too much immune consequnce.

    I am sure as ever you have your own answer.

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  7. There must be some interesting pathological specimens out there from people on potent immunosuppressives at the time of post-mortem.

    There are few reports on this aspect.

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  8. From the long discussed Barnett & Prineas study:

    "all normal appearing oligodendrocytes were replaced by apoptotic oligodendrocytes, that is, oligoden-
    drocytes with shrunken nuclei and annular or compact condensation of nuclear chromatin. Thirty percent of
    the affected cells showed commencing nuclear fragmentation (“nuclear body” formation) with approximately 10% showing condensed cytoplasm and round-
    ing up of the cell body, both features typically associated with apoptotic cell death."

    They die by apoptosis, no doubt about it, right?
    Theoretically, which process would need more time, the immune-assisted clearance of the dead cells, or their self dissolution (in case immunosuppressants are used)?

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  9. They die by apoptosis Right?

    Professional phagocytic cells will clear stuff up faster than non--professional cells, this is obvious Right?

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  10. We agreed, at last. Obvious is sometimes the question.

    Here is the next thought: Since a person under Tysabri has his dead cells removed in a slower pace, they could still be counted as existent brain mass, though, obviously, not working. So lower brain shrinkage may simply mean exactly that, that the dead cells are there and contribute to total brain mass because the professional garbage collectors are inhibited, not because Tysabri has some putative neuroprotective action.

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  11. If microglia are 'resident CNS cells' they should not be affected when we stop the immune system entering the brain. They are already in the brain. Wont they continue working as usual?

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  12. Anon 9:49

    Wont they continue working a usual

    Yes I think so. They will engulf dead cells

    Here is an idea Microglia have a very slow turn over, what if tysabri stopped their replacement it would take a year or two to
    to exhaust the supply of micoroglia
    Then maybe PML occurs.

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  13. I do not know of evidence that brain is stuffed full of dead cell debris due to tysabri making a false brain mass. So the argument appears floored

    Much more likely to be oedema (fluid cusing swelling) accounting for brain mass effect. Evidence for this exists.

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  14. Some ideas on PML/tysabri from Prof G -

    http://multiple-sclerosis-research.blogspot.com/2012/02/natalizumab-january-2012-pml-update.html?showComment=1328520456286#c438379865889537285

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