Tuesday, 8 January 2013

Unrelated Blogger Comments Jan 2013

Sometimes you want to say something that is unrelated to the threads. This is a spot for You. Previous comments can be got at on the posts on the right of the main page.



53 comments:

  1. Need some advice on what seems to be 'depersonalization-derealization' (This is a term I just learned)

    The problem is: constantly feeling as if everything is happening in a dream

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    1. Depersonalisation is a rare psychiatric manifestation of MS. In general psychiatrists treat this symptom with SSRIs, or selective serotonin re-uptake inhibitors, for example paroxetine. If it is intermittent a sodium channel blocker would seem reasonable, based on the most likely pathogenesis of the condition, i.e. aberrant firing of demyelinated axons.

      Ströhle A, Kümpfel T, Sonntag A. Paroxetine for depersonalization associated with multiple sclerosis.Am J Psychiatry. 2000 Jan;157(1):150.

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  2. Since the discoverer of NGF passed away (Prof. Levi-Montalcini) I wondered what Team G thinks of her proverbial usage of NGF as eye drops. Is NGF tangible as a therapeutic? Is anyone doing something in that direction?

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    1. I was surprised that a protein can get from eye drops and into the eye but it appeas possible. Lambiase A et al. Proc Natl Acad Sci U S A. 2009 106(32): 13469–13474. There have been a few studies in EAE and MS such as
      Kalinowska-Łyszczarz A et al. J Neurol Sci. 2012;321:43-8.
      Colafrancesco V, Villoslada P. Arch Ital Biol. 2011;149:183-92

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    2. Mouse watch this space, will ya? Perhaps the eye is not only a window to the brain but the front door? I find it highly interesting what they find and not only for glaucoma. This lady, Montalcini said that her brain was better functioning at 100 than at 20 which got me thinking... .

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    3. Maybe she was a guinea pig for her ideas

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  3. Since I am at it - could this article on PubMed explain the link between high cholesterol/cardiovascular problems and neurodegeneration and if so how exactly? The question is of interest to me because way before I became diagnosed with MS I used to have regular blood checks for cholesterol which had been very high even than so perhaps there is a link after all.

    Title of Article - "Cross talk between the cardiovascular and nervous systems: neurotrophic effects of vascular endothelial growth factor (VEGF) and angiogenic effects of nerve growth factor (NGF)-implications in drug development."

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    1. You may be interested in Prof G post
      http://multiple-sclerosis-research.blogspot.co.uk/2012/12/cardiovascular-risk-in-ms.html Maybe he has been thinking about it.
      I think the article you mention is showing pleotrophy. i.e one cytokine can have many different effects)

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  4. A lot of us are waiting for BG12. From the trials, does it help with fatigue and improving old symptoms?

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    1. It does improve fatigue a lot. Not sure about the other symptoms though - it certainly won't make you walk faster once you lost the ablility to do so or make your imbalance go away. It seems to dampen new attacks a bit.

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  5. Has this been covered on the blog? How can somebody get PML while negative for JC virus?

    A case of natalizumab-associated progressive multifocal leukoencephalopathy with repeated negative CSF JC virus testing
    http://informahealthcare.com/doi/abs/10.3109/00207454.2012.760561

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    1. I can't see the article, but from looking at the abstract it looks like the negative test they are reporting is looking for JC virus DNA in the CSF. This isn't a new finding - we know that there are a proportion of people who have active JC virus in the brain (ie PML) in whom we don't find the DNA in the spinal fluid. There are a couple of reasons for this - the test may not be able to detect tiny amounts of DNA, and the virus is reproducing in the brain rather than the CSF, so levels in the CSF may be low.
      The test that we do on people who are receiving tysabri to look for evidence of previous infection is different - we do an antibody test looking for an immune response against the virus.
      An important thing to remember in medicine is that no test is 100% perfect though, much as we might wish it was!
      hope that helps

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    2. Yes, thank you so much

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    3. can we quantify this risk please?

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    4. With the new generation JCV PCR assays less than 10% of biopsy positive PML cases are JCV-PCR (DNA) neagtive in their CSF. This drops with repeated lumbar punctures; i.e. successive CSF analyses are likely to be positive. However, virtually all these cases with be JCV seropositive (previous JCV exposure). The chance of developing PML and being JCV seronegative is less than 1 in 11,000; this is a conservative estimate and the risk is probably much less than that. We also have to remember that the PCR test is designed to detect JCV; it is theoretically possible that other viruses from this family may cause a PML-like condition or the virus undergoes sufficient mutations to make the PCR-reaction unreliable.

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    5. many thanks.I was wondering if the 1/11,000 figure took this into consideration....

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    6. It is impirical based on responses to assays used to detect JC

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  6. May I ask you your opinion on this new therapeutic approach in autoimmune diseases targeting at Protection of Tregs, Suppression of Th1 and Th17 Cells by a physically modified (harmless) saline?

    "Revalesio RNS60 ameliorates dramatically EAE": http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0051869

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  7. I would like to know what your hopes are for neuro-protective therapies?

    I have PPMS. As far as I can tell my MS just gets worse which means the disease is very active. By protecting my nerves, you won't stop my disease. What thoughts do you have regarding what is driving progression and what can be done to stop that? What I'm trying to say is that protecting nerves does not mean you're stopping disease activity. How can one stop disease activity in PPMS?

    Also, let's say a neuro-protective drug actually stops nerve damage, forever. Will that mean the brain and spinal cord will automatically begin to repair itself without further prompting? Do you think that dead motor-nerves may just start re-growing? Have you ever seen evidence of this in your labs?

    Happy New Year, by the way.

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  8. Neuroprotective therapies are being increasingly tested and this year we will see a number of new studies will be initiated...Trust me I know this.

    Will they work I hope so, but we can not promise anything.

    If you search on education you will find posts about potential processes driving progression.

    Stopping disease activity I would say deal with inflammation, protein existing nerves and stimulate remyelination, but to stop disease you need to get at the cause.

    If you stop disease the nervous system with repair, this may be growing new connections but I am not sure about motor nerves regrowing...the CNS has mechanisms designed to stop this happening and even if they did it would take years I suspect.

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  9. Adverting posts are deleted, but some get through spam filter and have to be removed manually.

    Any carrying advertising post with a name gets reported to google as a spammer.

    Any post with link in it is invariably spam do not open.

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  10. Mouse I have a question for you: I've just read that the MS clinic I thinking of going for a yearly check has a software called Brain Voyager 2000 - does it ring bells with you? It is somehow important to say that I want my MRT pics scanned with this tool? Maybe it's the new one which can count lesions more effectively? What do ya think? Thanx.

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    1. It didn't ring bells but I am not an MRIer. Brain Voyager is a bit of software that allows for 2D 3D images to be created from your scanns, The software costs 5,000 euros for the programme, so it makes pretty pictures. Maybe Dr Klause die fledermaus can comment as he is n MRIer

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    2. Thanx Mouse. Can you ask Fledermaus to comment? I would then try to insist in the clinic to use it for my new scan (or maybe also the old ones). Would it make sense to compare the old ones with the new one to see if brain atrophy has occurred? that's my main objective.

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  11. Mouse Doc and Prof. G what are your research priorities for 2013? Any promises or predictions?

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  12. Can I suggest they try and survive; there are more budget cuts and redundancies to come! I wonder if they will be on the list!

    A concerned QM colleague!

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    1. Priorities for 2013.....survivng dealing with the REF2014

      Any promises ......No....I know better
      Any Predictions....Maybe but No....I know better

      Yep I'm probably on the list, Prof G no chance

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  13. What's the REF2014? Hope you survive it!

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    1. www.ref.ac.uk/

      New system for assessing research quality in UK universitoes

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    2. It was set up with the view of increasing research quality in UK universities those that score high get more cash those that score low get no cash. However this created a transfer market for scientists in Universities.

      The ones publishing in top journals are covetted. So universities want to keep certain people and get rid of others. So now we have a sack and hire culture. Sack the ones that do not fit the metric and then hire ones who do in the hope that you do well in the REF and get money.

      People with a good profile of seeming International star quality are poached/lured from one place to another or others use the offer of moving elsewhere as leverage to get more, so in effect the research becomes more expensive.

      This could be stopped by making the research outcome stay where it was done. With each REF the university heads work out how to play the game in their favour before the rules change. I heard on assessor say that they did a list , on the back of a fag packet, and then when thousands were spent doing the actual assessment they were pretty similar we already know who the top 5 will be. However people form these institutions help set the rules so it will advantage them

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    3. Interesting, the politicians where I live are talking very favourably about your system and want´s to start using the same over here...
      //Swedish Sara

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  14. I don't know if this is a Shania moment, but I saw it on the MSRC website. This week in Nature Immunology, Univ. of Washington shows Tip-dendritic cells spread the immune response from CD4+ to CD8+ T cells. May be a reason for slow burning lesions

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  15. A little light relief showing what really goes on in labs (not ours of course)!
    http://www.guardian.co.uk/science/blog/2013/jan/10/scientists-twitter-methods

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  16. If a virus causes MS, maybe bats, not mice, have the answers?

    Bats are pretty impressive critters. They are notorious for carrying viruses like Ebola and SARS, but somehow avoid getting these diseases themselves. They are the only mammal that can fly, and they live far longer than other mammals their size. What’s their secret? ...

    When researchers looked at bats’ immune response to the viruses they carry, they found something quite novel. When mammals, including humans, die from a virus, it is usually due to an extreme immune reaction called a cytokine storm. It’s the body’s attempt to save itself, but it can actually do the opposite. Bats, however, are missing the genes that trigger this reaction—they don’t experience a cytokine storm, allowing them to carry the viruses unharmed. Understanding how they do this may eventually allow researchers to create drugs that suppress cytokine storms in people or to develop gene therapies to prevent them.

    http://blogs.discovermagazine.com/80beats/?p=41984

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  17. What do you think of the potential of intrethecal methotrexate for progressive MS?

    https://www.ncbi.nlm.nih.gov/pubmed/20532907

    http://www.msrcny.org/sites/default/files/abstracts/attachments/ECTRIMS2011%20ITMTX%20in%20Cuprizone.pdf

    http://www.msrcny.org/sites/default/files/abstracts/attachments/js_Long%20Term%20MTX%20Poster%20Revised%2004-09-12%20for%20AAN.pdf

    http://www.wheelchairkamikaze.com/2013/01/a-potentially-effective-treatment-for.html

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    1. It may work, but we would need more definitive evidence. Intrathecal methotrexate is associated with some severe side effects, for example, diffuse damage to the white matter and it can cause severe cognitive problems. With the emerging DMTs being so effective at switching off inflammation why would you take a risk?

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    2. "With the emerging DMTs being so effective at switching off inflammation why would you take a risk?"

      So far as I know none of the emerging DMTs is available(or likely to be available soon) to people with progressive MS and methotrexate seems to be cheap enough to be on the table.

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  18. methrotrexate is an immunosuppressive drug that acts on dividing cells. It acts by inhibiting the metabolism of folic acid. Folic acid is needed for the synthesis of the nucleoside thymidine, required for DNA synthesis. Also, folate is needed for purine base synthesis, so all purine synthesis will be inhibited. Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylates, and proteins.

    So if the action is only on the immune arm,then we have seen that very powerful immunosuppressants can only target the gadolium enhancing lesion & relapsing element of progression.

    Maybe Prof G has different experience?

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  19. I guess you are familiar with the EBV Stress Hypothesis

    I think this is a quite good theory about why a relapse or even the initial relapse occurs.

    In short:

    somewhen you get infected with EBV. The Immunesystem is then trained to fight against EBV which has a specific gene squence on its outside.
    In most people nothing or not much happens.

    But MSers seem to react different to stress (in a medical / biological sense). If heat or psychological stress occurs, "Heat Stress Proteins" are formed. Even in the CNS.
    The Immunesystem then starts to attack these proteins (which use myelin as a kind of adjuvant) because they have the same gene sequence as EBV.

    This theory could explain the Uthoff phenomenon and doesn't dissent with the autoimmune hypothesis.


    http://www.ncbi.nlm.nih.gov/pubmed/12578854

    Heat Shock Protein 70: Roles in Multiple Sclerosis, María José Mansilla, Xavier Montalban, and Carmen Espejo

    Yes I have read

    http://multiple-sclerosis-research.blogspot.de/2012/01/research-msers-react-againist-myelin.html

    :D

    I know of a lot of MSers who were exposed to heat or stress before their fist relapse (including myself).

    Is there something fundamentally wrong with this theory? Because this theory is as old as 198x.

    Thanks!

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    1. Add: Simvastatin.

      http://www.sciencedirect.com/science/article/pii/S0009912010004261

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  20. Have you got a programme for the Research Day yet that we can see? Thanks

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  21. Yes we do have a programme, I check to see if it is ready for circulation

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  22. Just thought id put something here about Alice in wonderland syndrome as I think this was something I suffered from as a child repeatedly,not got anything to say about it just is it important are you aware of it.I think its to do with ebv.

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    1. The Alice-in-Wonderland syndrome or Lilliputian hallucinations, is a neurological condition that affects human visual perception. It could possibly occur in MS as it is due to cortical dysfunction of the occipital lobe of the brain. It could occur with EBV infection, but that would imply an infection of the brain. I would need to look into things.

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  23. This was what I was thinking it sounds like EBV had entered the brain,i used to suffer from hallucinations as well as distortions in the size of objects and a high temperature,the hallucinations were rarer but the temperatures and distortions in size especially before sleep were most common I grew out of it eventually.

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  24. I am on Natalizumab and am JC+. As I have been on the drug for almost four years I was discussing whether to continue with it with my neurologist.

    We talked over the statistical risks of PML, which I quoted as around 1 in 192. He said my risk was likely to be lower due to the length of time I had been on it and the window of maximum risk is around two years.

    Is there an expected decline in risk over time and why ? Is this expected decline being borne out by actual PML cases ? Is the number of people taking Tysabri for more than four years large enough to get decent data on the statistical risk ?

    Thanks

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    1. The declining risk after 2-3 years is selection bias. The group of MSers staying in Natalizumab longer than 24 months is being enriched for MSers that are JCV-ve. There is no evidence that the risk goes down with time. I have never said that nor has Biogen-Idec. In addition, the error bars around the estimates are large; not small enough to give you any confidence.

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    2. Thanks - that it was I had thought.

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  25. The HMRC has returned Prof. G's tax return after he apparently answered one of the questions incorrectly.

    In response to the question, Do you have anyone dependant on you? Prof G wrote: "2.1 million illegal immigrants, 1.1 million crackheads, 4.4 million unemployable Jeremy Kyle scroungers, 900,000 criminals in over 85 prisons plus 635 idiots in Parliament and the entire European Commission".

    The HMRC stated that the response Prof. G gave was unacceptable.

    Prof. G's response back to HMRC was "Who did I miss out?".

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    1. At least someone has a sense of humour; the truth is I am about to miss the Jan 31st deadline for my tax return. C'est la vie! I never seem to have much time for these sorts of things.

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