Sunday, 1 March 2015

Unrelated Blogger comments-March 2015

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172 comments:

  1. http://www.telegraph.co.uk/news/science/science-news/11442985/Miracle-st...

    Is there any truth in this ? A Professor Basil Sharrack in Sheffield appears to have remarkable results.

    I thought Stem Cells may at best reboot the immune system to stop MS.But not repair nerve damage. But some of these patients have been in wheel chairs for 10 years so they must have had some nerve damage

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    1. UGH.....lets give the journalist a good verbal kicking..irresponsible reporting as ever. We reported on this paper

      http://www.ncbi.nlm.nih.gov/pubmed/25602998

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    2. To be fair, I think the professor reluctantly used the word "miraculous".

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    3. "Some of the results we have seen have bee miraculous".....I don't think the reporter coerced the prof.

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  2. http://www.telegraph.co.uk/news/science/science-news/11442985/Miracle-stem-cell-therapy-reverses-multiple-sclerosis.html

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  3. Questions for the MRI gurus - I understand that Gad contrast shows if there is current active inflammation in relation to brain lesions, but does it show if spinal lesions are active or not? If it doesn't and there is no active inflammation relating to brain lesions, but symptoms are still slowly worsening, what does this mean? How should this influence/affect decisions a patient may need to make in relation to taking or not taking a DMT? In asking these questions I'm sort of assuming (maybe incorrectly?) that no current active inflammation and no increase in lesion numbers over a year or two indicates NEDA (at least at this point in time). It would be great if you could answer, as I'm sure other bloggers probably have similar questions.

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    1. Hi there has been no change on my MRI for 5 years yet foot drop has developed slowly over that period. Not enough evidence on MRI for MS dx and negative LP. I reckon I have had a CIS and due to that inflammation some nerve damage has slowly developed over time. Things have been static now for a year so I am hoping all the damage that is going to happen has already happened. My CIS happened in 2008 and I recovered well, then foot drop sarted to develop in 2010.

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    2. I have had a positive diagnosis, but M\my understanding is that in some cases it won't always show enhanced lesions, but there are 'smoldering' lesions...not necessarily enhanced by the gad..but still there, Not every lesion will enhance, either - at least according to three different neurologists I've consulted with.

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  4. Gad contrast will show up enhancement/activity in the brain and spine, as long as they run a post contrast T1-weighted scan of both.

    MRI activity is not a particularly strong indicator of disability/progression. Some have high lesion load and low disability, and some have low lesion load and high disability. It's a bit like battleships - if a lesion by chance hits one of your battleships (important nerve pathways) it will manifest as disability. If the lesion lands in a less prominent area of the brain, the impact may be more subtle/harder to notice.

    For that reason NEDA includes clinical relapse and EDSS progression as well as MRI activity, and ideally at some point in the not-too-distant future, will include brain atrophy as well which, unlike MRI, is a decent correlate with disability.

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    1. Anon 12.02 again - thanks Matt for the explanation. I know about the issues around lesions load/location and disability - but I do like your battleship analogy.
      Gad used for last MRI showed no enhancement of anything, but there were maybe a couple more tiny lesions in the cerebellar region, and one spinal lesion more defined. Apart from that, MRI-wise things have basically been stable since the first MRI a couple of years back and it appears that most of the damage and disability accumulated over several years prior to diagnosis (no defined relapses either before or since), although there has been some increase in mobility and fatigue problems in the last couple of years.

      If anyone has some thoughts on "How should this influence/affect decisions a patient may need to make in relation to taking or not taking a DMT?" it would be good to hear them - neuro appointment is in a few weeks and there's never the time to properly discuss these issues, but you are still expected to make decisions about what to do next. What is Team G's standard protocol/guidelines in such a situation?

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    2. When new MS lesions are big enough to show on MR, it is highly likely that they will have enhanced around the time of their appearance until 4 to 8 weeks after, then the enhancement usually disappears. So an MRI scan is only a snapshot in time - if you were to have one with contrast an often as once a year it would only show as enhancing those lesions that appeared in the 4 to 8 weeks in the run up to the scan. So if you have new lesions, that's a sign of disease activity - these lesions will have enhanced at some stage if they had been caught. There are however lesions that are likely too small to be detected by standard MRI and will neither show up as white dots nor will ever have shown enhancement.... and then there are grey matter lesions which are almost impossible to see on the majority of scanners used clinically around the world. There is therefore more going on under the surface than can be detected. New lesions, however, between two scans are a definite sign of active disease.

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  5. MD I know I raised it with you about caffeine or coffee can cure EAE, can't remember which one.

    "Caffeine intake has been associated with a reduced risk of Parkinson's and Alzheimer's diseases, and our study shows that coffee intake may also protect against MS, supporting the idea that the drug may have protective effects for the brain," said study author Ellen Mowry, MD, MCR, with Johns Hopkins University School of Medicine in Baltimore and a member of the American Academy of Neurology.

    "Caffeine should be studied for its impact on relapses and long-term disability in MS as well," said Mowry.

    Drinking coffee may be associated with a lower risk of developing multiple sclerosis (MS), according to a study released today that will be presented at the American Academy of Neurology's 67th Annual Meeting in Washington, DC, April 18 to 25, 2015.

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    1. I was drinking around three cups of tea a day when I first became unwell with MS. I don't drink tea now (or coffee) , I drink fennel tea and mint tea. I used to drink echinacea tea also but gave up when I read it is not recommended for those with MS as it may increase activity.

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    2. Docs, is there any truth in coffee being good for MS or is that immaterial?

      Potentially it could help with fatigue, no?

      Of course urination frequency and BP might increase but if it might help MS...

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    3. There is evidence that caffeine is a neuroprotective agent so could be useful in MS. I'll have to install a coffee machine for the meeces ;-)

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    4. I am sensitive to caffeine and when I drink coffee, tea, hot chocolate, eat chocolate or caffeine loaded drinks it increases my anxiety. When I get anxious my MS gets worse, so I would need to be cautious about taking caffeine.

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    5. The news that I read about this study discusses caffeine being the neuroprotective agent, but also mentions coffee. There seems to be a debate if coffee contains more caffeine than tea. I suppose that depends on how long the tea is brewed for, quality of tea and amount used. I'm sure I read an article that discussed decaffeinated coffee still has some neuroproctective properties, so that would imply it's something in the coffee and not necessarily just the caffeine. I will try and locate that article.

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    6. Neurochem Int. 2012 Apr;60(5):466-74. doi: 10.1016/j.neuint.2012.02.004. Epub 2012 Feb 15.
      Caffeinated coffee, decaffeinated coffee, and the phenolic phytochemical chlorogenic acid up-regulate NQO1 expression and prevent H₂O₂-induced apoptosis in primary cortical neurons.
      Kim J1, Lee S, Shim J, Kim HW, Kim J, Jang YJ, Yang H, Park J, Choi SH, Yoon JH, Lee KW, Lee HJ.

      Abstract
      Neurodegenerative disorders are strongly associated with oxidative stress, which is induced by reactive oxygen species including hydrogen peroxide (H₂O₂). Epidemiological studies have suggested that coffee may be neuroprotective, but the molecular mechanisms underlying this effect have not been clarified. In this study, we investigated the protective effects of caffeinated coffee, decaffeinated coffee, and the phenolic phytochemical chlorogenic acid (5-O-caffeoylquinic acid), which is present in both caffeinated and decaffeinated coffee, against oxidative neuronal death. H₂O₂-induced apoptotic nuclear condensation in neuronal cells was strongly inhibited by pretreatment with caffeinated coffee, decaffeinated coffee, or chlorogenic acid. Pretreatment with caffeinated coffee, decaffeinated coffee, or chlorogenic acid inhibited the H₂O₂-induced down-regulation of anti-apoptotic proteins Bcl-2 and Bcl-X(L) while blocking H₂O₂-induced pro-apoptotic cleavage of caspase-3 and pro-poly(ADP-ribose) polymerase. We also found that caffeinated coffee, decaffeinated coffee, and chlorogenic acid induced the expression of NADPH:quinine oxidoreductase 1 (NQO1) in neuronal cells, suggesting that these substances protect neurons from H₂O₂-induced apoptosis by up-regulation of this antioxidant enzyme. The neuroprotective efficacy of caffeinated coffee was similar to that of decaffeinated coffee, indicating that active compounds present in both caffeinated and decaffeinated coffee, such as chlorogenic acid, may drive the effects.

      Will read more about Mowry's study when I can.

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  6. Thanks Matt Perry for the comprehensive answer :)

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  7. Not seen this before... thoughts?
    http://www.eurekalert.org/pub_releases/2015-03/wuso-nti022715.php

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    1. May contribute to the variability of MS, why some patients present as PPMS and others with RRMS recover more quickly than others. It would be interesting to look at TREM expression in PPMS, SPMS and RRMS.

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  8. Docs what do you think about this study, about drug MIS 146? : http://multiplesclerosisnewstoday.com/2015/02/13/experimental-spms-drug-from-innate-therapeutics-shows-success-in-early-trials/

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    1. The headline says drug shows success in SPMS but the link is really a post about recruiting to the trial.
      Without published data it mat be hogwash. The drug aims to target the microglial response and we think that this may be importan in progression

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  9. Out of all the medications available, which are the ones showing most promise for stopping progressive forms of MS, and which are the ones that look most likely to slow down the non-imflammatory degenerative processes?

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    1. Of those available none are really a8imed at progression

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    2. None as yet but watch this space. There is definitely going to be progress on this which hopefully will rapidly be taken up clinically and combined with effective control of relapses could definitely be a game changer for MS. I wish i could say more but we are gagged at the moment.

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    3. MD2 is back in pub stripper mode. Down to his / her thong and teasing us. We've waited too long for good news. Either give us the full frontal or put your clothes back on.

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    4. Thanks MD & MD2 - I thought some of the indications were, now that there is more data/information accumulating over time, that some meds (even older ones) were showing some promise with progressive MS. I'm thinking of Prof G's Therapeutic Lag Theory here - i.e. where initial trial results have been disappointing with Progressive forms of MS, but now that more time has passed with post trial data collection there were starting to be some pointers that some drugs may still have benefits in slowing progression, but not in the first couple of years of treatment.

      Sorry MD 2 - I acknowledge that the majority of MS diagnoses are RRMS, but I'm not really interested in "effective control of relapses". If you don't have relapses it's all a bit pointless, and the RRMS crowd have plenty of options currently, while the Progressive minority don't have any.

      Maybe there isn't an answer, but in a sense my question still stands - which is asking which of the current drugs looks like it/they may have some benefits for progressive MS.

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    5. Anon 9.02 Full frontal in next month or so. Waxed in preparation ;-)

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    6. If I stuck a £50 note in your g-string would you spill the beans? Sorry for the stripper analogies, but the tension is killing me (I had a premonition that 2015 would be a good year). Team G is like a London buses, you stand there waiting and nothing arrives and then three come along together (I'm talking good research results).

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    7. I really really wish I could spill the beans but I'd be dead meat if I did so you're 50 quid is safe for now ;-)
      In the next month or so all will be revealed. Take it from me, 2015 is definitely a good year.

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    8. MD2 - final offer. £100, bottle of champagne AND you don't have to remove your nipple tassles. We can meet in a pub near to your lab. No need to invite Big Mouse.

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    9. A very tempting offer but I regretfully have to decline. Honestly, I wish I could tell you and it's as frustrating for us that we can't say anything but at least we're another day closer. Beers are on me when the results come out at a pub of your choosing.

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    10. another day closer ? to standing in the sunshine , give us a break

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  10. Docs and what do you think about this study, about MD-1003, it appears that the aim is to treat PPMS and SPMS...: http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=109110#.VPcxeNLF_kU

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    1. We'll have to see what the results are before we can comment.

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  11. Anti-Muscarinic Adjunct Therapy Accelerates Functional Human Oligodendrocyte Repair
    http://www.jneurosci.org/content/35/8/3676.short?sid=35d8de58-7f3a-4eb7-a755-87cb47470a18
    Well again pretty popular class of drugs suspected in remyelination. Is there any data could be pulled from detailed registers?

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    1. Yep muscarinic receptors seems to be a common theme.

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  12. MD2,

    Do you think any meds or therapies will be developed for cognitive dysfunction?

    I read the exercise post and how it helps with processing speed, as well as the post about cognitive reserve.

    But do you think we have something to look forward to in terms of stopping the cognitive decline?

    Scared.

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    1. Research on neuroprotective agents that should address this this is well underway. Team G are probably at the forefront of this. Also first clinical trial to report soon.

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    2. Thank you MD2. Please do your best to find something, and hopefully fast.

      I don't want to rush you but I (and other cognitive-MSers) are quickly running out of time.

      I don't want to become a walking zombie and will try whatever it takes to prevent it from getting worse.

      Hugs.

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  13. Docs did you see this article about this possible genetic risk found in a family in which 05 brothers have MS? http://medicalxpress.com/news/2015-03-strong-genetic-factor-ms-family.html

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  14. Team G
    I've been reading about exercising our nervous system in regards to the fine motor skills. The fine motor skills being involved with the smaller movements of the wrists, hands, fingers, feet and toes. These fine motor skills are continuously developing and need maintaining (for the general population) so the ideal is to take part in fifteen minutes of task/s that use these skills each day. Such as writing with a pen instead of only using the computer, drawing, sewing, crafts, playing an instrument, cooking such as chopping vegetables and probably many more examples. I just thought it was interesting with regards to my MS.

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  15. Dear Team G, I keep coming across patients with MS and they report having trauma to the head or spine before their first MS symptom. Be it a car accident, fall, severe head bang are a few examples. This could mean two things perhaps 1) the trauma caused/triggered inflammation that the CNS was unable to recover from. 2) the patient had latent MS and the trauma brings the first MS symptom out.
    I understand that there can be increased vulnerability to infection after a trauma, escpecially head trauma. This could be an added factor.

    It's a bit similar to the post that was done recently on patients with psoriasis and RA given etanercept. Was the MS latent in the patients or did the drug trigger demylination?
    http://multiple-sclerosis-research.blogspot.com/2015/02/causing-ms-by-blockade-of-tnf.html

    Any thoughts??? thanks

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    1. Hi , I have read that inflammation to the nervous system through a trauma can expose the nerves which may later develop neurodegeneration. This neirodegeneration will "Look Like" progressive MS. In my case I had radiation treatment for cancer. Suffered inflammation at the time of radiation with symptom of l'hermittes. 20 years later neurodegenertion. Was first dx with PPMS then later changed to delayed radiation myleopathy..

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    2. I do feel there is a connection with trauma and MS.

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    3. I think if any thing would be the way you stress out on it ,when in my teens was hit hard with hammer when in my 40,s fell broke neck 1234 with no problems after wards, 20 years later dx with pp and don't feel like a person that has stress ful problems

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  16. Your below blog post criticizes poor reporting on HSCT

    http://multiple-sclerosis-research.blogspot.com/2015/03/miracle-stem-cells.html

    However, you use the Daily Mail report from 2006 regarding Tony Johntone (golfer) in many presentations. In 2006 alemtuzumab was still in trials and no the effectiveness of this drug was still an unknown.Do you feel there is a little bit of double standards in criticizing a poorly worded reporting regarding HSCT(a treatment that you as a group obviously don't believe in) vs quoting an article that is reporting alemtuzumab as giving him a 'miraculous' recovery'

    To me that is double standards.

    2nd question - you call HSCT the ultimate induction therapy, can you explain with some detail your logic to not explore this avenue further but to continue with drugs and your EBV theory? You are prepared to push for drugs that cost the NHS £56,000 a year, but HSCT costs £30,000 a year? Do you just believe that HSCT won't work?If it is a better alternative to the DMD's isn't it your duty as doctors to try and get the best for your patients? Why can't you collate what now has to be considered the large amount of data available on HSCT, work with the neurology community and then NICE to get it approved AS WELL as continuing to work on your EBV theory and other treatments? You always talk about patient power, but it was most cerntainly neurology power that got alemtuzumab approved as a first line therapy.

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    1. What's the drug you refer to.... Cladribine?

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    2. Yes it does criticize poor reporting because that is what it is poor reporting that is misleading. I the report was using that language and was reporting about any treatment including lemrada then I would be happy to criticise that too.

      Not sure I was using the Daily Mail from 2006...I wasn't blogging in 2006...and not reading the Mail. I do not understand why you would think we do not believe in HSCT...It is the most extreme form of immune rebooting so if you think Alemtuzumab can work then surely HSCT can work too. Maybe ProfG was writing about a golfer, its not my style

      He is a free to say what he wants, we do not yet do things by committee. Does he give the belief that every thing has gone back to normal?

      Next it is not my theory of EBV, it is profGs baby and yep ProfG was happy that Alemtuzumab got a first line licence and if HSCT was given a first line license he would be happy if you had choice.

      Why haven't people paid too much attention to HSCT. I think the percieved adverse events. But these have been minimised admittedly.

      The people doing the work with HSCT need to get it to a stage where the regulators approve, I have enough to do. Then people may use it. The cost is immaterial if the procedure is not approved I can give you a name of a drug that costs a few quid and works as well as lemtrada and probably HSCT. Furthermore I know the cost to the NHS for Lemtrada is more than £56K. That is only the drug cost but there are 8 infusions to pay for, anti-virals for a month, methyl predniselone to stop the infusion reactions, blood tests once a month, urine tests every 6, then there is the cost of dealing with 20-50% autoimmunities and some of these are not trivial, 3% surgical removal of thyroid etc, etc, etc.:-).

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    3. Name of drug is irrelevant unless it gets licensed...which the system will ensure never happens. If Lemtrada gets a third line in the US, will HSCT be forth line, because one needs to ask will it be adopted without regulatory approval or will it get approval and will there be a double standard in this process.

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    4. P.S. This approach works in mice so I dont need to waste my time repeating it

      http://www.jleukbio.org/content/72/4/609/T6.expansion.html

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  17. This looks promising... Thoughts?
    http://www.healthline.com/health-news/bladder-drug-re-grows-myelin-could-ease-ms-symptoms-030915#4

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  18. MD - Prof G is the one who has used the article regarding the golfer and alemtuzumab, which to me is just as poorly written as the HSCT one above. When you say, " I have enough to do" I was referring to Clinicians, as opposed to researchers. I feel that as a doctor who treats patients it's part of the job to ensure that my patients get the best treatment available. Not to push their own agenda. We have three year data HSCT Vs alemtuzumab, if you as a researcher analysis the results can you not review the data and then state which has the better results? The write up that stated alemtuzumab was as effective as HSCT recently was challenged by Matt and others and then not answered. I think you should to the same for alemtuzumab vs nataluzumab - patients care about this data and want it analysed in an unbiased way - you guys could easily do this but you often seem to put a slant on the things you write, which is misleading.

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  19. MD do you have any idea of the percentage of MSers that are tested EBV positive? I was tested over a year ago and was negative. I didn't have an LP as the MRI results gave me my RRMS diagnosis. thanks.

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  20. Have there been any studies on how vitamin C effects MS? or is there already general knowledge about it? I've looked into it a but and can not see anything about it.

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  21. I too have always tested negative for EBV and am also fortunately negative for JCv since have been on Tysabri for past 3 years. I believe a virus is the trigger for MS in susceptible individuals just not yet convinced it is EBV

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    1. Team G are there two blood tests for EBV? One to test if the EBV is currently active and the other to test is the patient has ever had EBV?

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  22. http://www.ncbi.nlm.nih.gov/pubmed/25710567
    Too much as well as too little of the sunshine vitamin may be associated with cardiovascular risk

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    1. Thanks for posting that.

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    2. interesting but being Viamin D sufficient is associated with lowest risk

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  23. I know steroids have their use in MS however there is some correlation with steroid use and brain atrophy, is that correct?
    http://www.ncbi.nlm.nih.gov/pubmed/15882880
    This article is some year old now.

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  24. I would like to ask my doctor for the blood test to see if I have ever had EBV. Which test should I ask for? I have been in MS limbo for a while and if my test was negative then maybe I can put the MS possibility to bed for good. My GP is really unsure and I said that I would try and find out the test that I need.
    Thanks

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  25. Im curious about post alemtuzumab treatment options. would rituximab/ocrelizumab be a treament option post infusion if alemtuzumab doesnt do what it says on the tin? I know the states are using ritux as a f/u infusion to try prevent secondary autoimmunity but all that immunomodulation seems like playing with fire to me? many thanks

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  26. Fasting might reboot the immune system. Is that correct? I wouldn't try this though at the moment as I'm getting on underweight so would need to put on some weight, (which I am trying to do).
    http://www.medicalnewstoday.com/articles/277860.php

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    1. This report relates I believe to a report (http://www.cell.com/cell-stem-cell/abstract/S1934-5909(14)00151-9). Will it reboot the system. I suspect there are many muslim and other MSers who fast, I wonder if their MS reboots and goes away...I suspect I know the answer.

      http://www.mssociety.org.uk/sites/default/files/Documents/Essentials/Fasting-and-MS-factsheet-Jul-12.pdf

      Islamic fasting and MS
      http://www.ncbi.nlm.nih.gov/pubmed/24655543

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    2. Thanks MD. There's also this

      http://www.sciencedaily.com/releases/2015/02/150216131146.htm
      Anti-inflammatory mechanism of dieting and fasting revealed
      Date:
      February 16, 2015
      Source:
      Yale University
      Summary:
      Researchers have found that a compound produced by the body when dieting or fasting can block a part of the immune system involved in several inflammatory disorders such as type 2 diabetes, atherosclerosis, and Alzheimer's disease.

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    3. This paper by Yale is interesting as when we eat there is some inflammation in the body. If we eat little and often then that could mean there is constant imflammation. So then perhaps it is better to eat three or two large meals a day with no eating inbetween and not before bed. Some foods may produce more imflammation than others such as milk and red meat.

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    4. Thanks for commenting, MD

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  27. "In nerve cells that have lost myelin, MD1003 may increase energy production by activating what is known as the krebs cycle. It could also activate enzymes that help to increase the production of new myelin. In a pilot study of 23 people with primary and secondary progressive MS, up to 90% of the participants showed clinical improvement over time. This provides hope that the treatment will be successful, but larger studies are needed both to assure that MD1003 is effective, and for regulatory approval. Following positive Phase III clinical trials the medication may be made available for prescribing and use by people with MS."
    Phase III in one study is already complete, another phase III will be completed at the end of 2015. Exciting, in that by increasing energy production via TCA cycle (Krebs cycle) in axons, that myelin production may be increased. This is more evidence supporting the link between maintaining mitochondrial function and promoting remyelination. http://multiplesclerosisnewstoday.com/2015/03/13/two-progressive-ms-phase-iii-trials-to-be-presented-at-aan-annual-meeting/

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    1. So we have to wait until the data is presented at the AAN, it looks like this is a meeting for progressive MSers. I guess the company producing MD1003 is not publically traded as they would be releasing the trial results just as Novartis released their in December about their trial in progressive MS, which I also believe will be presented at the AAN too.

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  28. Thanks for posting Anon 1.23 - interesting. Profs, would you be able to comment on this study? Thank you, I would really appreciate it.

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  29. Could I please ask a question which will no doubt seem very basic? All this research going on into progressive MS is exciting, but the MS-Smart trials seem to specify secondary progressive MS. If drugs are found to be effective for SPMS, will they also be useful for PPMS?

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  30. Do MSers suffer from cortisol deficiency? I am reading conflicting information.
    Also progesteron deficiency and increased estrogens.

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    1. Also MS associated with insulin resistance?
      Nutrition. 2014 Mar;30(3):268-73. doi: 10.1016/j.nut.2013.08.001.
      Disability in patients with multiple sclerosis: influence of insulin resistance, adiposity, and oxidative stress.
      Oliveira SR1, Simão AN2, Kallaur AP1, de Almeida ER3, Morimoto HK3, Lopes J1, Dichi I4, Kaimen-Maciel DR4, Reiche EM3.
      CONCLUSION:

      This is the first study to demonstrate an increase IR prevalence and the association between IR and adiposity with disability assessed by EDSS in patients with MS. IR seems to be associated with chronic inflammatory process and oxidative stress in patients with MS. More studies are warranted to elucidate the mechanisms by which IR and adiposity could contribute to the progression and disability in patients with MS.

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  31. Several MSers I have met and others also, are convinced they have never been infected by EBV. Michael Pender’s comment in this blog Feb 11, 2014 may be helpful to review:

    “With regard to your comment about there being EBV-negative people with MS, this is by no means certain. Some people with MS may be negative for one type of anti-EBV antibody but positive for another type. The careful study by Pakpoor and colleagues in 2013 (Multiple Sclerosis Journal 19:162-166) concluded that, when looking at studies where two independent methods are used and therefore are likely to be the most robust, EBV appears to be present in 100% of MS patients.

    The one study on children with MS where only 86% of patients were EBV-seropositive compared to 64% of matched controls (Banwell and colleagues [2007] Lancet Neurology 6:773-781) stands in contrast to the study of Pohl and colleagues in 2006 (Neurology 67:2063-2065) who found that 99% of children with MS are EBV-seropositive compared to only 72% of healthy children.”

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    1. Then it would seem the wise and obvious thing to do is for all MSers to get tested for all anti-EBV antibody. I have my blood tests for Tecfidera coming up in a few weeks time, I wonder if I can request this testing too?

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  32. Article on the BBC news website today about lack of sleep and sleep debt.
    http://www.bbc.co.uk/news/health-31869053
    Studies have already shown that shift work can rapidly put healthy people into a pre-diabetic state.
    The action of throwing the body clock out of sync is thought to disrupt the natural rhythm of hormones in the body, leading to a host of health problems.

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    1. maybe search through the blog there was a recent post on a paper on shift work and MS risk

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  33. When I was very unwell with a bad relapse I got severe constipation, fissures and hemoroids, it was very painful. My whole body would stiffen up when I needed a number 2. I tried different diets, more then lesss fiber, more liquid I didn't try laxatives which I should of. The thing I found that helped me the most was to sit on the toilet in the squattiing position. I did this by raising my feet on a very sturdy box. This then raises the knees. I've looked into it a bit and the most natural position for going to number 2 is the squatting position. This is because our inners go relaxed in this position meaning the poop can pass down easier.
    This toilet position is recommended for those with Chrohns disease, bowel problems to name a few.
    Constipation was discussed briefly on this blog in 2012.
    http://multiple-sclerosis-research.blogspot.com/2012/03/research-outcome-measures-for.html

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    1. I don't have the problem myself, but I caught the end of a feature on TV about this. The doctor said it was about the position of the bowel. I think you're right, it's worth a try.

      Delete
  34. The Guardian is today reporting research about links between salt and autoimmune diseases:

    http://www.theguardian.com/lifeandstyle/2015/mar/15/salt-worse-than-thought-link-to-autoimmune-disease

    I leave it there for it to be shot down in flames (living with a scientist, I am naturally sceptical of all science reporting in newspapers)

    ReplyDelete
    Replies
    1. Thanks I will post on the MS study that I missed. This follows on from some studies in EAE, I originally though we would have to take the story with a pinch of salt, as I have seen other studies that do not repeat the observations and likewise other studies do no repeat the the observations. Maybe time to cut salt abit more reading needed

      Delete
    2. I raised the subject of salt intake and an increase in MS activity with my registered dietitian some months ago. His response was there is no proof of salt (or an increased level of) being bad for us and I shouldn't make conclusions from reading one study. hmm

      Delete
    3. There's also this that mentions the study and another study about salt and autoimmune diseases.
      http://news.sciencemag.org/biology/2013/03/salty-food-may-be-culprit-autoimmune-diseases

      Delete
    4. As I've said before, the Nature paper showing high salt diet linked to autoimmunity had the high salt mice ingesting 176 mg of salt per day in their food and 60 mg per day in their water (based on the average food and water consumption per day of the mouse strain used here and assuming a body weight of around 25 grammes). Scaling up for average body weight in a human (let's say 70 kg) this would mean a person would have to eat around half a kilo of salt per day to replicate the mouse study, which I suspect would be toxic long before any proposed autoimmnity would be apparent.
      I did post this comment on the paper on the Nature website but it seems to have been deleted. I'm surprised the referees didn't pick this up.

      Delete
    5. Yep just checking MD2s facts.

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1397713 (Food & Drink intake of mouse). Food intake of a mouse 4.4g/day and fluid = 6ml of fluid a day. 1% salt in water = 1g in 100ml and 4% in food = 4g in 100g of food. This is 236 mg/day in 25g mouse = 236mg/25g = 9.44g/kg so 660g for a human. Half a Kg of salt a day.

      Even doing a factor of ten 60g of salt which is 4 times a recommended limit of 15g/day and twice the 35g/day found in some papers.

      There was no dose response done in the nature paper, or repetition of the result reported. Give 18g of salt in water and if makes humans vomit.....Poor old mices can't vomit (Did you know that mice and rats can't vomit?). It is interesting the mice were not so stressed that there disease did not get better, but with a control group only getting a limp tail it would be hard to show. I guess we will have to see if it repeats....I have already seen someone else's data showing 180 degree different result...will they ever get that published?

      Delete
    6. We commented on the study reported in the guardian in sept 2014
      http://multiple-sclerosis-research.blogspot.com/2014/09/too-much-salt-appears-to-be-bad.html

      Yep get it here first folks:-)

      Delete
  35. Prof G and N Doc N, I have been in touch with NICE about treatment guidelines for MSers. I informed them I suffered from an extremely bad relapse triggered by sleep deprevation, stress and severe anxiety (inc from phonophobia). They said they were very sorry to hear my experience but it would go on record for the decision makers reviewing the next NICE treatment guidelines for MS relapses. As MS relapses are treated as non-urgent typically.
    Having particular symptoms can be very stressful and cause anxiety for example double vision and other eye symptoms and they are connected to very important parts of the brain. If I was involved in the recommendations I would put forward urgently that eye symptoms are treated quickly to help save nerves and help the relapse resolve quicker. Perhaps other symptoms such as a numb foot would be fine at staying wait and see, no hurry to help recovery.
    My MS nurse said that relapses triggered by stress are common but neurologists and nurses don't want to alarm MSers about this. Another MS nurse said to me that anxiety is probably the most common as a relapse trigger.
    So that really makes me think MSers that have experienced a relapse triggered by stress or/and anxiety could help others by also writing to NICE just like I have. I informed NICE about the survey Prof G did about stress and MS. That 68% of MSers reported a relapse triggered by stress. They said that well thought out research like that does help making decisions on guidelines for treating relapses. When MSers get stressed or anxious I expect this increases inflammation by triggering new lesions.
    I guess the current gidelines stem from studies of stress and MS have not resulted in confirm conclusions.
    I feel that the current guidlines for treating MS relapses are not offering the best for MSers.

    ReplyDelete
    Replies
    1. Time is of the essence when someone is stressed for what ever reason. I wouldn't make an animal wait for treatment if I knew they were suffering from stress from symptoms.

      Delete
  36. MD,

    Everytime I saw your white knight posts it gave me hope that you guys were close to finding a cure or really effective treatment.

    Can you give more detail as to how the knight was slain? :( i actually really liked the white knight posts

    ReplyDelete
    Replies
    1. Apathy and money...people dont care enough about you. :-(

      Delete
    2. That's always nice to hear.

      Can you give more details about what you were trying to accomplish?

      Delete
    3. Also on a completely other note.... if money is an issue and you have such a good plan....

      why don't you try and speak with celebrities to raise awareness and get some funding?

      I'm being serious - I am sure for ex. Sharon Osbourne would donate if it meant it could help her son.

      But we need details if we are to try and help...

      Delete
    4. Also JK Rowling as her mother suffered from MS.

      Delete
    5. She gave a lot of money to the MS society a while back though disappointingly only to be spent in Scotland.

      Delete
    6. Sour grapes here Mousedoctor2, so what your implying is if they come up with something, they will keep it to themselves. I'm sure most people with MS wouldn't care if the cure came from Timbuktu.

      Delete
    7. All good points the question is how to contact such people they have teams of people making sure that the average Joe Smo does not get anywhere near them.....ProfG was keen to get to speak with JKR but his stalking was no use as he was not sure how to find her.

      Sharon O must be worth a few bob after the Money Supermarket Ad. check out the twerking on Youtube
      How about that we could get sponsored by Ozzy Osborne. We tried to get an Iron Maiden studentship once.

      The ProfGs would also love the contacts too, but I guess so would every MS researcher. I am sure they get bombarded. But if you are reading Sharon (I forgive you for dissing Bruce Dickinson) or Jack or JK drop us an email...please

      Delete
    8. AnonymousThursday, March 19, 2015 8:25:00 am
      A little I must admit, the condition that the money was only to be spent in Scotland seems wrong to me and as you probably appreciate the funding climate is tough in the UK these days. It also caused a rift in the UK MS society.The wider you spread the cash the better the chance of making a breakthrough in my opinion. Agree, if the Martians came up with a cure that'd be fine with me.

      Delete
    9. So let's talk numbers and facts:

      1. it seems to me that your idea is sound academically and medically and the reason you're down is because of lack of funding,

      is that correct? So you didn't crash because of a false hypothesis but because of money, right?

      2. HOW MUCH money would you need to realistically drive forward what you want to do and suceed?

      Delete
    10. Twitter may be your answer on how to reach celebrities in a more direct way. Although I guess you've probably thought of that.

      Delete
    11. Dear Jims Thanks or the idea...I'll pass it on

      Dear Anon 11:07
      1. Thanks for the kind support I am sure the knights will appreciate this
      2. A few £ million..but plan B could be cheaper than Plan A

      Delete
    12. If you get a hold of jack ask him why he chose to shell out a lot of money on stem cell transplant, that is unproven, rather than go the DMT route

      Delete
  37. With regard to today's white knights post - I'm glad the white knights have been mortally wounded. Fed up to the back teeth with all this "carry on jousting" rubbish. It looks like it is poorly thought through ideas / theories that are the issue. The funding / approving authorities must be rejecting them as they don't stack up. What's needed is less of the mad-professor approach and instead looking at all the results / data / knowledge which Team G has and come up with an original / plausible idea which can be taken forward. Most of the successful teams are known for one thing (Cambridge - alemtuzumab, Professor Hauser - B cells, Professor Pender EBV). Team G has taken the jack-of-all trades approach. Look at what you are really good at and pursue this rather that the blunderbuss approach of putting your fingers in too many pies.

    ReplyDelete
    Replies
    1. so are you saying ProfC and genetics at cambridge is a waste of time or remyelination for that matter

      Delete
    2. Prof C is my hero. What I'm saying is that Team G seems to have bad luck with some of its work e.g. Oral cladribine. The white knights posts don't seem to go anywhere e.g. the proposals get rejected. There's been a lot of work around cannaboids without any success. I wish you guys luck. But I think you have so many projects on the go that it might be better to focus on a smaller number. Quality rather than quantity. On the plus side I have faith in MD2.

      Delete
    3. " It looks like it is poorly thought through ideas / theories that are the issue."
      You couldn't be wider of the mark. We have several plausible ideas which are being taken forward with excellent results. If you limit yourself to one area there is a chance that you will miss out on other potentially important discoveries, our cannabis work would be a case in point. As I'm sure you're aware the majority of great scientific discoveries come from inspired look and see pure research rather than applied. Perhaps we should prepare a list of the varied areas we've been involved with in the MS field over the years and highlight the progress each has made?

      Delete
    4. Sativex is cannabinoid and a licenced drug for MS. The fact that GW pharma want to charge too much for it so that NICE will never approve it, is not our fault and is not with our control either.

      P.S. You know what we do because we talk about it and give you access to comment on it.

      Delete
    5. PPS to answer the first comment.... yes I am a mad professor very mad indeed...fuming in fact

      Delete
  38. I hope your post of today doesn't mean you're giving up on the blog. It is so important as it gives you the facts straight. It's the only place I look for what's going on in the MS world. I don't want the 'happy/clappy' 2 month's out of date stuff on the various MS charities websites. I know you get trolls and negative grumblies, but this is so worthwhile and important to the majority of MSers. Please- don't stop believing (now that 'll be in your head all day!)

    ReplyDelete
    Replies
    1. Don't worry Lexie, we'll never give up on you guys or the blog. We've got plenty of other really great stuff coming down the pipe so we can bear a few frustrations.

      Delete
    2. Dont stop Believing

      How about

      When you have desire there's gonna be a flame
      When you have a flame someone's gonna get burnt
      Just because you burn does mean you have to die
      You gotta get up again and try

      Delete
    3. I second that Lexie

      Delete
    4. Never took you for a Pink fan MD! ;-)

      Just because you burn doesn't mean you have to die

      Keep on keepin' on.

      Delete
    5. If you don’t try at anything, you can’t fail...............................

      RIP chivalric brothers

      Delete
    6. heard it on a plane a few days ago though it was apt
      Ps how did you know it was pink closet fan

      Delete
  39. I think researchers looking at arthritis have uncovered what smoldering activation of the innate immune system is caused by.

    Here is an article that seems to explain a lot about inflammation both acute and chronic. I think these mechanisms could be driving progression in MS:

    http://arthritis-research.com/content/16/6/504

    ReplyDelete
    Replies
    1. This was in the news a lot just before christmas will it work for MS,I bet it will get tried will it stop progression I amnot so convincedif it has a different mechanism for that driving immune attacks..but I keep an open mind.

      Delete
  40. Anyone have garlic, leeks and onions in their diet daily/often for their anti-viral and antibacterial properties ? Though some sources say these foods boost the immune system and i'm not sure that's a good idea with MS.

    ReplyDelete
    Replies
    1. These have compounds of allicin, sulfur, quercetin and prostaglandin which are antiviral and antibacterial.

      Delete
    2. Personally I think that onions, leeks and garlic are very tasty and healthy. (Although I tend to prefer leeks and garlic as onions make me fart for Britain.) And so many things boost the immune system - anything with vitamin C in it, sunlight, perhaps even laughter. So if one needs to avoid boosting the immune system with MS, one would need to remain in the dark, be miserable, and eat things devoid of nutritional goodness - perhaps cardboard. Just my opinion (I'm not a medic).

      Delete
    3. On the BBC website today 1,000 year old onion and garlic remedy kills MRSA.
      http://www.bbc.co.uk/news/health-32124642

      Delete
  41. Is there a more current trials or more up to date information?
    Last I find is July 2012
    Modafinil and Progression

    ReplyDelete
  42. Will you be sharing what White Knights actually was? Please do - even if it's hit the rocks it would be good to know what it was...

    ReplyDelete
  43. Docs and blog readers I have some doubts about some issues, you could help me solve them through their answers? I would like to know about vitamin B3 (niacin or nicotinamide), would have some applicability in effect for MS? http://jama.jamanetwork.com/article.aspx?articleID=1983668

    And Coenzyme Q10 and L-carnitine could help how to symptom fatigue and promote neuroprotection? Now grateful for the attention!

    ReplyDelete
    Replies
    1. As part of the MS-SMART we were commissioned to look at nicotinamide and there was other data which I am not in a position to talk about.

      Delete
    2. Md - do you work for the security services? I've never come across someone so secretive. I suspect you worked on the original enigma machines for the Germans (hence your knowledge of their language). Can we rename the blog 'a blog that will not divulge any information about MS research'?

      Delete
    3. How about ' a blog that divulges information on MS research when that information is available'. Indulge MD, he really has your best interests at heart. Personally I'll be spilling at the research day tomorrow.

      Delete
    4. If I were to tell you about someone else's work before they say something I think you would under stand that they would not be too happy.

      If I spill the beans will the beans actually happen, do I actually know what the beans are? and if I spill the beanz and they don't materialise, then there could be people who could get egg on their faces. As it stands its only me, as the chronicler who loses face and the chance of a freebie to ECTRIMS.

      As to German......maybe I am German:-), after all we are Anglo-Saxons (Angles-German Saxons-Germans)
      P.S. Research is when you dont know the answer.......I believe I know the answer.

      Delete
    5. I respect your right to keep schtum. I won't pester Herr Mouse any further. As I learned from Fawlty Towers - don't mention the war. You are the research equivalent of Donald Rumsfeld "there are known knowns". I know you have signed the Official Secrets Act so cannot divulge anything. I was going to come to the research day, but the thought of you doing the dance of the seven veils with your sidekick MD2 and the refusing to answer any questions (what are the 39 steps?) has put me off. More off booking is the thought of Prof G showing off his tan and banging on about how many air-miles he has clocked up. I hope the day goes well.

      Delete
    6. Shame. I was going to tell you everything you wanted to know.

      Delete
  44. Hum ok, thank MD, but you just did not respond as L-Carnitine and Coenzyma Q10 ... What about glatiramer acetate acts on B cells, which could be related to infection with EBV virus?

    ReplyDelete
    Replies
    1. A theoretical possibility without sufficient evidence but they are nutriceuticals so the chance of this being investigated properly is in my opinion minimal. I didn't realise that carnitine is a growth factor for mealworms, there are some studies with Q10 http://www.ncbi.nlm.nih.gov/pubmed/23659338 and more recently http://www.ncbi.nlm.nih.gov/pubmed/25603363
      .
      Does glaterimer act on B cells...it works on everything doesn't it if you read the literature (yes this is tongue in cheek) so it is a possibility

      Delete
    2. P.S. it did nothing interesting from our point ofview

      Delete
  45. Team G, have there been any reportings of MSers who have been on Tecfidera and they have no reduction in lymphocytes? thanks

    ReplyDelete
  46. I would like to know about the studies of the EBV and MS, these studies are still following?

    ReplyDelete
  47. Docs high doses of corticosteroids used in pulse therapy when the patient is in outbreak can cause severe hair loss as a side effect?

    ReplyDelete
    Replies
    1. I took five days of oral steroids (prednisolone) for relapse two years ago, five tablets a day and had very severe hair loss. My bedroom carpet was covered in hair. I was concerned at the time I had something else wrong with me, it caused me great anxiety so not good in my condition. Then I read side effects of steroids on the web and hair loss can be a side effect.

      Delete
    2. Oh and it did grow back. It took around six months before my hair was back to normal thickness.

      Delete
  48. How did the research day go? When will the videos be online?

    ReplyDelete
  49. http://www.msra.org.au/australian-researchers-develop-new-anti-inflammatory-molecule-could-help--ms

    ReplyDelete
  50. Replies
    1. Blocking cytokine release over the long term is likely to be disastrous.

      Delete
    2. Yeah really sorry that I had to miss the research day in the end. I was looking forward to meeting you both, and selling HSCT Evangelist t-shirts on the door!! :)
      I did drop an email to say I couldn't make it. Unfortunately I got the lurgy and had to spend a couple of nights in hospital under observation as I was running a temperature so high I could poach eggs on my forehead! (anything over 38c and they bring me in to play it safe as my immune system isn't back to full strength yet). Was gutted to have to miss it - hopefully will be at the next one!

      Delete
    3. Sorry to hear that Matt. Hope you're feeling better now.

      Delete
  51. Hello, Do many MSers have a history of being nervous and anxious people before their diagnosis? I say this because I have been this most of my life. I feel more in control now about my nervousness and anxiety through relaxation techniques. My GP said to me a few years back that it seems some anxious people do seem to go on to develop MS.
    I know some medical professionals say anxiety is common in MS and not only about having a diagnosis of MS can make us anxious. I discussed this with my MS nurse and she said MS patients are not typically anxious and anxiety is something that needs to be investigated/treated/reduced.

    ReplyDelete
    Replies
    1. I would say that I have tended to be an anxious person most of my life, though I am less so now. Receiving a diagnosis of PPMS and studying Buddhism have reduced my controlling & clinging tendencies. So I don't see the anxiety as an MS symptom. Also - I know and have known many anxious people over the years, and none of them have MS. Anxiety tends to be encouraged in our society, for many reasons that I will not start harping on about here...

      Delete
    2. Apparently us Welsh according to a study all over the news today are more neurotic/anxious than the rest of the UK. Interestingly up in the north of Scotland, with the highest rates of MS, neuroticism/anxiety is at its lowest. Go figure ;-)

      Delete
    3. Neuroticim is a much wider umbrella term than anxiety. Neurocis covers many traits that includes anger, depression, anxiety, vulnerability and lonliness, worry, moodiness, fear and frustration.
      I have read that MSers tend to be more of a less agressive nature and this may be due to having increased estrogens and less testosterone. Both men and women.

      Delete
    4. I'm going to keep an open mind. A hospital doctor said to me recently anxiety often triggers MS relapses. My MS nurse said to me before Christmas that relapses triggered by anxiety are very common. When I go on forums I do see it crop up fairly often about anxiety making MS symptoms worse.

      Delete
    5. MouseDoctor2 - interesting. But I am from as far north in Scotland as you can go (born & bred with ancestry), and I have known many anxious Shetlanders. Perhaps we are less likely to admit being anxious and try not to show it - a sort of stiff upper lip thing. I have also known many anxious English people, Germans, cats... One of my family's dogs, bless her, was quite anxious at times. I find that I am anxious when thinking of what the garage are going to charge me for making my old banger MOT ready. Or when I'm running out of quality, loose leaf tea. If I don't have an excellent cup of tea in the morning, I become very aggressive.

      Delete
  52. Apparently, according to a study that's all over the news today, us Welsh have the highest rates of neurosis/anxiety in the UK yet those in the highlands of Scotland, with the highest rates of MS in the UK have the lowest rates of neurosis/anxiety. Go figure ;-)

    ReplyDelete
  53. I'm glad MD has stopped comments on the neurorestoration blog. Anon was really making me fed up harping on and on about MD2 giving false hope, being facetious blah blah blah- stop reading the blog if all you want to do is get at people who are trying to help and maybe lighten it up from time to time. MS is bad enough without us all sitting around contemplating how awful life is and expecting a miracle around the corner. If you've read the blog you know that most of the work the MDs do is not going to be a drug for sale tomorrow but possibly in 10 years time. If no one puts in the work today, there's not going to be a drug in the future

    ReplyDelete
    Replies
    1. Such lovely words of wisdom - much needed these days.

      My personal wish would be for MS research time frame to fasten from 10 years for big trials to 5 years and for minor discoveries from 5 years to 2-3 years.

      I've been long enough on this blog to see progress being made - eg in 2010 stopping progression was still in its infancy and there was no mention of remyelination (no serious one) - no it's a given.

      We RRMS don't need to inject and there is a wide range of options - taking vitamins or supplementation is not frowed upon anymore and we begin to understand the biomarkers so much better as we do with the atrophy - I'm sure that the MRI still holds some big surprises as does OCT.

      Once there is at least ONE reliable drug stopping or significantly slowing progression we will be able to have our lives back and the vampire which is called 'wheelchair' will be stuff of the past.

      I'm waiting for that day and keep my champagne in the freezer for now ............. HURRY UP MICE!

      Delete
    2. if we can't recruit to PROXIMUS we will have to try something else but the plan is that it takes 18 month rather than 5 years

      Delete
    3. I agree that the PROXIMUS trial is hugely important if we're going to translate the very promising experimental results into something that could be very important for progressive MS.

      Delete
  54. Just watching Andrew Marr. Ian Duncan Smith talking about saving taxpayers money by cutting benefits. The trouble with MS is we pay our taxes for years and then SPMS comes along and you turn into a scrounger overnight. They're even talking about cutting the little bit extra we receive for having made NI contributions. I'd love to be cured, but it just isn't going to happen.

    ReplyDelete
    Replies
    1. Never say never.

      We know how to save the taxpayer a lot of money but shame it ain't going to happen without a miracle....I live in hope.

      Delete
    2. Mousedoctor, just had a really posh looking blue booklet shoved through my letterbox. Not a mention of the NHS, I'd start retraining if I was you.

      Delete
    3. I don't work in the NHS..but I suspect not much on the educational system either...maybe vote for the little blue book and there will be no NHS.

      I see you've changed channels from the neurorestoration post:-)

      Delete
    4. I think you may have mistaken me for someone else, haven't read the neurorestoration post.

      Delete
    5. My mistake...you have a like-minded soul.

      Delete
  55. A thought regarding recruitment to the proximus trial. It has occurred to me that many progressive MSers may largely have contact with an MS nurse rather than a neurologist, especially if you're slightly further away from the big centres. Perhaps you need to reach out to the wider MS nurse community (and thus patient community) to raise awareness of the trial? Also, the MS society has a list of open trials on their website but I can't see the proximus trial there - maybe another avenue to recruit people? How many participants are you looking for in total? It would be such a shame if this trial didn't get off the ground!

    ReplyDelete
  56. And Docs you must be knowing that australians are also investigating about the Epstein Barr Virus and MShttp://multiplesclerosisnewstoday.com/2015/03/31/ms-research-australia-funds-project-on-ms-and-epstein-barr-virus/

    ReplyDelete
    Replies
    1. Anon 1:45:00

      You must be new to the blog. Take a look at this: http://multiple-sclerosis-research.blogspot.com/2014/02/guest-post-professor-michael-pender.html

      Delete

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