Saturday, 28 July 2012

Research: a case for combined neuroprotection and immunomodulation

Braley et al. Differences in Diffusion Tensor Imaging-Derived Metrics in the Corpus Callosum of Patients WithMultiple Sclerosis Without and With Gadolinium-Enhancing Cerebral Lesions. J Comput Assist Tomogr. 2012;36:410-415.
 

OBJECTIVE: To analyze differences in corpus callosum diffusion tensor imaging metrics among MSers with RRMS and SPMS with enhancing and nonenhancing cerebral lesions.

The corpus callosum is the white matter tract that connects the two cerebral hemispheres together.


Diffusion tensor imaging is MRI technique that assesses the integrity of white matter tracts, in other words how intact they are.
DTI image of the corpus callosum
RESULTS: The subjects with SPMS with enhancing lesions had significantly lower genu and body of the corpus callosum fractional anisotropy (FA) values than those with nonenhancing SPMS and significantly lower genu, body, and splenium FA values than those with RRMS. Regression models: Enhancement was associated with decreased genu FA (P = 0.014). Secondary progressive MS was associated with decreased genu (P = 0.002) and splenium FA (P < 0.001) and significantly increased mean diffusivity.



CONCLUSION: Patients with SPMS with enhancing lesions may be at increased risk for neuronal damage compared to nonenhancing SPMS and RRMS subtypes.


"Nothing really new here. MSers with more advanced disease and active lesions are more likely to have damage to the corpus callosum and the nerve fibres that connect the two halves of the brain. Best to try and stop this happening! How? Early aggressive treatment before your MS becomes secondary progressive. There is no point waiting for damage to occur before treating; this is why we have to lobby NICE to give you access to the emerging more effective treatments as early as possible."




16 comments:

  1. Prof G,

    Two questions:

    1. How best to lobby? The national MS organisations seem conservative and more concerned with a softly softly approach. Would you be interested in heading up a team of Neuros aligned with more outspoken patient groups? I can orchestrate a media campaign...

    2. On the issue of early treatment. The existing options above and beyond the first tier 4 seem to be effectively Campath (if you can get access to it) and Tysabri (at least these are the two heavy hitters). But it is too early to say, isn't it, that they will halt the transiton from RRMS to SPMS. Or is there evidence to the contrary? Which one do you think works best?

    The focus on dampening down inflammatory process has left neuroprotection in the sidelines, I think. I posted about Modafinil... and Minocycline shows some promise. Perhaps we need to be more agressive with combination therapy? Copaxone plus Minocycline has been shown in a small study to be 57% more effective than Copaxone alone.

    So I ask again - when you boldly (and correctly - praise to you!) - suggest early aggressive treatment what therapies do you think give you the best chance of neuroprotection in the long run?

    And if you are going to push the boat out why not full body irradiation and stem cell? Treat MS like a bad cancer...

    Also - can you as a Prof give drugs on a patient by patient basis... you have strong enough evidence of the viral link. Why can't you just prescribe HIV DMT drugs and see what happens? Or is that just a no - no?

    It seems that in the 60s Drs were allowed to be a little more experimental. Sure more patients died, but more saved in the long term.... controversial. But it seems that we are in a holding pattern. The evidence is there but the treatment lags behind. And every day we lose something more of our souls and selves.

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  2. Not sure about the need to lobby. As a doctor the patients interest must come first. You need to walk the talk - if early aggressive treatment offers the best chance start offering it to patients. The DMTs have been shown to be mildy effective at best + they are expensive. Head down to your oconology department and take a box of Campath 1H. Treat your next 30 newly diagnosed RRMS patients with this (give them the choice). Over 3-5 years our Trust will be saving money - cost of expensive DMT (every year) and cost of all the relapses they would have dealt with for those of DMTs.

    Be the change you want to see Prof G. Do what's best for your patients. If NICE get angry you can always blame the pony-tailed, heavy-metal, beer swigging colleague.

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  3. I think Prof G already does this...
    I'm a little disappointed that my GP thought it best not to 'open a can of worms' and explore DMTs during the 1990s and 2000s when although I was only having occasional mild 'episodes' maybe in hindsight I could have delayed the onset or severity of SP :-(
    My experience reflects the times, I think - there was little or nothing that could be done, so bury your head and hope it goes away...

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  4. BTW (to previous poster) you could join the MS Society's campaign network if you want to join forces with other people and organisations which already lobby to their best ability.

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  5. If NICE get angry you can always blame the pony-tailed, heavy-metal, beer swigging colleague.

    Character and assassination spring to mind......cheers mates :-(

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  6. Oh, I was just going to say that MD is probably a red wine conneisseur who likes Vivaldi :-) So who's right?

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  7. you just have to read the blog to get the musical tastes....

    As to tipple .....thats on the blog also.

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  8. Surely mice only drink water, or milk if they can get it??

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  9. "this is why we have to lobby NICE to give you access to the emerging more effective treatments as early as possible."

    That's easy. Convince NICE that first line DMTs are worthless and should not be prescribed. You don't have to try hard, the evidence against them are building up. Then tell NHS to spend money only on newer treatments. Every public health system would be happy with such a deal, provided that doctors could handle the lobbying from pharma industry against such a movement...

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  10. Re: "Convince NICE that first line DMTs are worthless and should not be prescribed. You don't have to try hard, the evidence against them are building up. Then tell NHS to spend money only on newer treatments. Every public health system would be happy with such a deal, provided that doctors could handle the lobbying from pharma industry against such a movement..."

    Good idea; but at the moment they want MSers to fail these first-line therapies before we can use the more aggressive ones.

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  11. Re: "Head down to your oconology department and take a box of Campath 1H. Treat your next 30 newly diagnosed RRMS patients with this (give them the choice). Over 3-5 years our Trust will be saving money - cost of expensive DMT (every year) and cost of all the relapses they would have dealt with for those of DMTs."

    I wish it was simple as this; even though Campath-1h is relatively inexpensive we still have to get the PCTs or Commissioners to pay. We do this by completing an IFR (individual funding request); these are typically turned down for unlicensed drugs or licensed drugs that have not been given a green-light by NICE.

    The way the NHS is configured prevents us using expensive drugs.

    Mouse Doctor thinks we should start using intravenous cladribine under the NHS. He has a point.

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  12. Re: "1. How best to lobby? The national MS organisations seem conservative and more concerned with a softly softly approach. Would you be interested in heading up a team of Neuros aligned with more outspoken patient groups? I can orchestrate a media campaign..."

    Yes, I am up for that! I can give you a list of liked-minded neurologists to start the campaign. The main problem is communicating the correct risk:benefit ratio to MSers. The one problem we face is that we all have conflicts or interest so most people will simply dismiss us as doing Pharma's bidding. One way to avoid is to include non-Pharma drugs or strategies in the lobbying, e.g. mitoxantrone, iv cladribine, autologous bone marrow transplantation.

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  13. Re: " On the issue of early treatment. The existing options above and beyond the first tier 4 seem to be effectively Campath (if you can get access to it) and Tysabri (at least these are the two heavy hitters). But it is too early to say, isn't it, that they will halt the transiton from RRMS to SPMS. Or is there evidence to the contrary? Which one do you think works best?"

    Alemtuzumab, Natalizumab, iv cladribine (off-license), rituximab (off-license), mitoxantrone & autlogous bone marrow transplantation. Apart from the latter I would consider all the others. Which is bes? I am not sure. They all have pros and cons and risk profiles that differ. Mitoxantrone is the one that is least favoured due to its toxicity profile and risk of leukaemia, but in some MSers this is all we have!

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  14. Re: "...you have strong enough evidence of the viral link. Why can't you just prescribe HIV DMT drugs and see what happens? Or is that just a no - no?"

    The evidence at the moment could be explained on association rather than causation. This is why we need evidence and that has to be collected in well-designed clinical trials. If we simply prescribed them we would be open to criticism and would be no better than the charlatans that peddle CCSVI treatments outside of clinical trials.

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  15. Re: "t seems that in the 60s Drs were allowed to be a little more experimental."

    That is correct. Many treatments emerged because if you had an idea you would have a go and if it worked you would try it again and gradually collect a case series. Only after this empirical or observational evidence would you do a properly designed trial. This is the nature of the modern era - risk adverse and litigious. Most clinicians don't want to take chances.

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