#ThinkSpeak: unrelated comments as a forum for change

The best way to treat your pet troll is to be kind and patient; at Barts-MS we like to think that we are both kind and patient. #ThinkSpeak

Do you use, and read, unrelated comments? This is a useful feature of our blog that we added many years ago to improve our offering. It is important to let the blog evolve over time, which explains why we have expanded our readership over the years. The idea of the unrelated comments is to ask questions and start a conversation about a topic that is unrelated to a specific post. Yesterday one commentator asked a string of questions. I will try and answer these over the next few days. Three of the questions are all related to alemtuzumab.

Prof G do you claim alemtuzumab to be curative in MS? 

Incorrect. I have never claimed alemtuzumab is a cure for MS. I have always taken the position that based on the autoimmune hypothesis that PIRTs (pulsed immune reconstitution therapies) of which alemtuzumab is one may offer a potential cure. This is the underlying therapeutic principle that underpins PIRTs; in addition to alemtuzumab cladribine and HSCT can also be classified as PIRTs. I have also discussed many times what a potential cure would look like in MS and we are not there yet in terms of follow-up. I have always maintained that this is a 15-20 year experiment

Could something cure MS even though no-one knows why MS happens?

Yes, something could cure MS even if no-one knows why MS happens. This is called an empirical observation and it has happened many times in medicine, particularly in relation to environmental exposures. We didn’t know how alcohol caused caused acute liver damage, but abstinence was the empirical cure. I don’t agree with the comment that ‘no-one knows why MS happens’. MS is a complex disease due to an interaction between genetic susceptibility and the environment. The main environmental factors are low vitamin D or low UV sun exposure, EBV and smoking. I am convinced that EBV is causal based on strong epidemiological data. We are working on a study design for an EBV vaccination study, that should answer the question whether or not  EBV is the cause of MS. What we don’t know is how EBV triggers or drives MS once someone develops the disease. We have many ongoing research projects that are looking into this. We have discussed most of these projects on the blog under the ‘Charcot Project‘ an initiative that brings all this research together. The Charcot Project is not one study but a many studies that look into the viral hypothesis of MS. 

Why do some patients who go onto alemtuzumab continue to progress?

This is has been discussed endlessly under the so called asynchronous progressive MS hypothesis and length-dependent axonopathy hypothesis. Unfortunately, progression is often primed by previous damage and switching off inflammation now with alemtuzumab is unable to repair the previous damage that has primed neurons and axons to die off over time. This is why we recommend early effective treatment to prevent damage. Another factor that plays out in so called ‘progressive disease’ is premature ageing. Life is a sexually-transmitted neurodegenerative disease. If we all live long-enough we will see the effects of ageing on the nervous system (poor memory, unsteadiness of gait, poor balance, reduced hearing, etc.). What protects us from age-related neurodegeneration is brain and cognitive reserve. Unfortunately, MS reduces both brain and cognitive reserve and brings ageing forward in time. Alemtuzumab like all other DMTs that have been licensed to treat MS have not been shown to impact on ageing of the nervous system. This is why some pwMS will continue to progress despite being rendered NEDA by alemtuzumab. Finally, the dreaded intrathecal plasma cell. One of the hypotheses that we are exploring is that the long-lived plasma cell, which makes immunoglobulin with the brain and spinal cord, may be responsible for delayed progression. We have shown that alemtuzumab does not impact on these cells and hence this is another reason why pwMS may continue to progress despite being treated with alemtuzumab. 

Our Pet Troll

I must point out that if this particular commentator had taken the time and effort to read the blog they would have had all their questions answered. This explains why we repeat ourselves. Most readers dip in and out of the blog and only read current posts, by repeating ourselves we hope the messages get through. We also need to curate the blog. Blogging software is not ideal for navigation. I have been working on creating a curation site with links to important posts to make it easier for you to find information and to help navigate the blog. This is part of evolving our site to make it more user-friendly; we really don’t want the blog to be stuck in time. 

CoI: multiple

28 thoughts on “#ThinkSpeak: unrelated comments as a forum for change”

    1. Dre can answer this, a new persona of Dre after the dummy was spat read the comments trump mentioned. Hes from Yorkshire born in Bradford if it is true what he says, we have to translate to ProfG .e.g. Smoke = London and as Yorkshireman Trumpster an opinionated idito would fit some of my relatives. My Uncle never left except for war and hated the south. He had a cherry tree that wouldnt grow it was probaboly southern Shite according to him. Get the picture of the rant from the man sat in room with flat cap on

    2. I should say opinionated bigot as I know it will upset some of our American readers to diss el presidentey, can't be an idito he got nearly half of the US electorate to vote for him

    3. "can't be an idito he got nearly half of the US electorate to vote for him"False logic. If a high proportion of the people who voted for Trump were idiots (I'm saying nothing), the possibility that Trump himself is in an idiot cannot be excluded by considering the numbers who voted for him alone.

    4. Yes, I am a Yorkshireman. Yes, I am comfortable with that. Yes, I am enlightened.My T2 Trainspotting riff on MS comment last night was pure genius and you're bang out of whack for not publishing it. It was Pulitzer worthy.Let me tell you something, my mate Trump hates NICE and with a passion. He wants it gone because it is anticompetitive and costs America extra. The special relationship will demand the neutering of NICE in return for capitalistic trade favours. I heard on Sky News in the gym this morning.Oh, well. Ta for the reply. Off to feed me whippet.

    5. So was having a meeting with an Indian lady in my NYC office, I asked her where she had spent her recent vacation; Yorkshire she replied. Frankly I was surprised my edss score momentarily peaked. Once I had recovered from the shock; she added 'I enjoyed it so much last year that I went again this year.'

    6. You made the assumption that we would get your trainspotting riff…the powers that be didn't and it sounded like a rant.As I said too cryptic

    7. Dear Aiden Whilst off topic as proud Yorkshireman….In a number of polls, Yorkshire is one of the best places to visit.e.g. Lonely planet it was number 3https://www.lonelyplanet.com/travel-tips-and-articles/lonely-planets-best-in-travel-2014-top-10-regions After all it is known as "Gods own County" 🙂

  1. The vaccine against EBV as a form of treatment/prevention of MS is an interesting idea, but how do you stop the vaccine starting the process that leads to MS. The vaccine would have to contain the same antigens from the EBV and in susceptible individuals could actually cause MS( if MS is a disease caused by immune reactions to antigens on EBV )

  2. Many thanks Prof G. As someone with RRMS, I can read the trial results of the various medications, but guidance from an expert who sees things at the coalface is way more valuable. I don't expect any neuro to push a particular drug, but it can be very helpful to hear real life experience e.g. in my practice I have 50 Alemtuzumab patients and 90% are doing very well and most still in work. This sort of real life observation is more helpful than a research paper with complex tables and standard deviations etc. As a 45 year old who had Alemtuzumab 7 years ago, I am glad to report that I have done extremely well. As my disease appears to be in remission, I am focussing on exercise. My next focus is to ensure I go into old age as well prepared as I can, given that MS took away some of my reserve. Thanks again.

  3. I think this pulling together of some of the key facts about Alemtuzumab is incredibly helpful. Clear and succinct it's a summary that I can point family and friends to without having to say look at X,Y&Z. As someone who is appalling IT illiterate I have been aware of not always being sure of accessing everything on the blog or doing effective searches, so it's reassuring too – that I've not missed vital understanding of how A works. I'd like to suggest that the team add to their monumental workload and do such summaries on a regular basisđź‘Ť

  4. I have a question re MRI's and NICE policy. I have been pushing my neurologist for an MRI as I have been on DMT's for a year and would like to know if I have progressed. If I have, then I would like to change to something else than Tecfidera. Now that I finally got an appointment letter for an MRI arranged – I noticed that it is only an MRI of the head. MS is a brain and spinal cord disease, so why not do an MRI of the spine as well?My questions are: Is it common practice to do an MRI of the head but not of the spinal cord? And since no lesions on the head does not mean no lesions on the spine, how else would one know if progression has occurred?I tend to present my neuro with the recommendations from NICE to remind him of the care that I should receive, but have not found anything yet as to how MRI's should be conducted. Any info would be greatly appreciated.

    1. Hi Anon. I am on Tec too and have a brain only MRI once each year. This is standard as far as I have been informed. I had no contrast which I was surprised about even though I discussed it with the two radiographers, they said it wasn't requested by my neuro.

    2. "more common"… sucks if you are in the less common category and there was evidence that tecfidera is not working but it wasn't picked up because it is less common?barts have also reported spine is narrower than the brain and therefore much less likely to be able to re-route once lesions appear.NHS makes decisions based on what is "more common". If you are satisfied with that great. If not, insist on a brain and spine MRI.

  5. Ok! Fingo-Alemtuzumab switch may be not the best way for JC pos MSer. What's your opinion about the potential fingo-OCR switch. (cause cladribine is offlabel)

  6. "Unfortunately, progression is often primed by previous damage and switching off inflammation now with alemtuzumab is unable to repair the previous damage that has primed neurons and axons to die off over time."Then how is there hope for this Think Hand campaign. Ifsomeone has lost legs surely the damage to hands can't be far behind.Seems doubtfull there is a window wide enough. But even if it'sonly the eye of a needle I understand it's worth tryingBut why is it even a question isn't there enough clinical history to know how long hands follow legs or is everyone's disease course drastically different.

    1. If you look at ocrelizumab trial data slowing of loss of leg function is 25% slowing of loss of hand function is 45% so there is time.

    2. But why is it even a question isn't there enough clinical history to know how long hands follow legs or is everyone's disease course drastically different.Every individual disease course is drastically different… (though apparently about 1 in 20 persons with MS don't even have MS lol)

  7. I would also like to know why I only have brain scans and not brain and spine? I have lesions on my spine which I know about from the first scan I ever had to diagnose MS.

    1. AnonymousSunday, January 29, 2017 8:52:00 pm – you should be having spine scans and you should get on your neuro's back about this. Sometimes it depends on the system and the country you are from, but there is ample evidence that you should be having brain and spine scans and insist on them. Ps. The public hospital my partner sometimes has the MRI in Aus for whatever reason schedules brine and spine on different days, which in my view is just silly and unnecessary (other places have done it all in one go). The public hospital sends the notification of spine/brain appointments separately, sometimes a month apart and they don't always specify on the notification which one it will be (their administration is really wonderful, clearly).

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