2 things:1.This is something I asked a little while ago but there was no answer, possibly because there isn't one.What happens if you are changing to oral meds (tecfidera) because it is now available and because it may be more effective at reducing relapse than injectables? Does this mean that there is quite a long period when you have no effective active cover? Should there be an overlap with interferon? Probaly can't be recommended either for lack of evidence.2. Is the research day full? I was waiting for the programme to be published before deciding.thank you
1. The problem has been the natalizumab switch say to fingolimod. A period of washout is required to expose sub-clinical PML, which allows break through of disease. The others don't have that PML risk and so I am not sure a wash-out is needed, the question is how quick does protection occur with tecfidera, I don't know maybe a Biogen rep could comment or maybe a doc even ProfG however this is pretty standard in the dose escalation scenario that people come of injectables.2. I don't know but I know it was pretty full last week with very few places free. There is a new format planned and some of the content was still being confirmed e.g stuff on physiotherapy and stuff. We have listened to the feedback for last time
What is the most efficacious new anti-spastic agent? What things should an MSers consider when being prescribed such drugs?
While I could say our new drug, that you will hear about soon, but I am biased and conflicted, I won't say this. However, many agents can be efficacious and the the best drug is the one or ones that work for you. The problem with most anti-spastic drugs is their side-effects, and there are choices of baclofen tizanidine dantrolene,botox etc etc some agents can get rid of spasticity but sometimes you need a stiff limb for support.I was at a UCLP meeting recent with the spasticity team and they were showing some examples of intrathecal baclofen, where the results were really impressive. This allowed them to wean the MSer off their other meds and the cogfog they have been in for years. This was amazing, The point is not that I am supporting intrathecal baclofen,I am not, the point I am making is that you have to talk to your neuro, spasticity, rehab team so that they can taylor the right treatmen.However you have to be aware of how they work and this will help understand the side effects
I keep thinking about MS could be seen as a series of events that result in a cascade of lesion accumulation. Where the CNS is not able to recover fully. The events trigger inflamation in the brain and or spinal cord. Events might include injury to head or spine, infection etc.. I asked three MSers today if they had a head injury or spine injury previous to this first MS symptom. I had a head injury six weeks prior to my first MS symptom (vertigo and very sensitive eyes). One MSer reported falling down stairs another MSer reported a fall on a winter sports trip leading to numbness. The third MSer reported no injury. So the initial trigger of the cascade for some MSers may be the injury. But I know MS may be latent and an event sets off this cascade.I know a few articles have touched on this but it would be interested if there was a bit more research into this.
In PPMS what would be the expected number of new lesions to have per year ? Also is it more common in PPMS to have a negative lumbar puncture ? If in PPMS your LP is negative for OCBs then is your PPMS les5 ys severe.I have been tested for PPMS for five years. No answers yet as dont't satisfy McDonald criteria.Thankyou
Hi Joanna, Val Stevenson ( Stevenson VL, Miller DH, Leary SM, Rovaris M, Barkhof F, Brochet B, Dousset V, Filippi M, Hintzen R, Montalban X, Polman CH, Rovira A, De Sa J, Thompson AJ. One year follow up study of primary and transitional progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 2000;68:713-18.) found that 43.6% PPMS developed 1 or more brain lesion over a one year period (so low). Almost 9/10 times it is expansion of existing lesions than formation of new lesions in PPMS.PPMSers have OCBs but less than in RRMS ~ 75% versus 85% and greater. In fact positivity is based on your ethnicity with >95% MSers being positive from the Western hemisphere. Brazilians have notoriously low OCB positivity. And around 50% OCB negative MSers become positive on average when repeated over a follow up of 4 years (therefore may be worth repeating). In general terms in RRMS the presence of OCBs has been linked to poorer prognosis reflecting establishment of autoimmune activity in MS. In the OLYMPUS study of rituximab in PPMS, the presence of IgM OCBs as opposed to IgG OCBs was linked to more active inflammatory disease. However, although IgM OCBs have been linked to poorer prognosis in RRMS, not in PPMS. So the answer on prognostic value of OCBs in PPMS is outstanding. The McDonald criteria are based around MRI evidence and therefore greater chance of diagnosing RRMS. PPMS is largely a clinical diagnosis with OCBs thrown in into the mix as a paraclinical measure. A consensus from MS clinicians should therefore help you.
Thankyou for your reply. I had radiation treatment for hodgkins lymphoma in 1990. L'hermittes 6 months later. MRI and LP were negative. L'hermittes cleared up. Fine until 2008 had a sort of CIS which I recovered from then year later foot drop began to develop. Seen 3 neuros with DX of delayed radiation myelopathy, CIS , possible PPMS or SPMS. 2 more LPs have been negative.
Active EBV can cause hodgkins lymphoma. Have you been tested for EBV?
bout onset progressive ms - does this exist? is it when you have an initial episode and then recover but then start a progressive path some time later (year +).Thanks
Yes it does, please refer to my blog in Feb - when does relapsing-remitting MS stop?
Hi again, Have you ever seen a patient who had radiation treatment for cancer in the neck area to then years later (15 years +) have lesions in only the area of the spinal cord that was irradiated and have MS. Thankyou
No I haven'tbut I don' t see patients
dear Profs. can you tell me more about cladribine vs alemtuzumab- from reading the clinical trials data it seems that alemtuzumab is much more efficacious than cladribine. Can you please tell me why you think they are the same? thanks
If you look at the phase II data with alemtuzumab the data is very impressive, but if we look at the phase III pivotal trial data then they appear much more similar in terms of effect on efficacy. Whilst one was placebo controlled and the other was against beta interferon, this makes it impossible to compare, without a head to head study. One is an infusion causing a few infusion problems the other is a pill. If you look at the actual relapse rate annualised per year and then if you look at NEDA it is very similar between the two, but where cladribine clearly benefits is that it does not induce the secondary autoimmunities of lemtrada and there it is much safer and so does not require the monthly monitoring. However cladribine failed its development, which was because of a perceived cancer risk that is not different from Lemtrada. However, rather than do more trials to make the regulators happy Merck Serono terminated the programme and flushed Movectro down the toilet, never to be seen again. Weird thing was they were already doing trials which did not support the cancer risk, so if they had waited a couple of years there may have been a different outcome. I think the decision to pull the plug was more financial than scientific as I have heard there wasn't much patent life in the drug, however that would have meant a toe in the highly effective DMT market for a few years and Gilenya is off patent in 2019. Maybe they felt they had lost the race with Gilenya, however I think they threw ProfG's new baby out with the bath water. Each drug has its merits the major one for Alemtuzumab is that it is in the here and now and can be prescribed
So is chemo the future of MS treatments?What's the point in messing around with all these experimental "new" mab treatments when there's a wealth of chemo agents out there which are here already, can do the same job, generally have greater potency in terms of lymphoablation, have better CNS access, have similar or better safety profiles, far lower cost, generally are induction therapies (so eliminate the adherence risks and improve QoL), and are already approved?As an MS'er, I find that incredibly frustrating. I know I've posted this sentiment before, but keen to understand the views of Team G on this...If lymphoablation is accepted to be the best new frontier of treatment (and the current pipeline suggests it is), then why is the MS world not bringing in the expert haemo's and oncologists who have been doing this for 50 years for leukemia and lymphoma, and why is there no lobbying to use their already-approved drugs, given that they're being used for exactly the same biological purpose in MS as in the cancer they're already approved for (lymphoablation)?Is it not complete and utter madness, spending hundreds of millions of pounds and wasting a decade or more on trials of drugs which have not only already passed safety/efficacy trials for the exact same biological purpose, but have already been in use for exactly the same purpose for years and years (sometimes decades)?If you're testing the safety and efficacy of anything else in the world, you wouldn't apply this approach. If you tried to apply this logic in any other field in the world, you'd lose your job for gross incompetence and ineffeciency (not aimed at you guys, just the system).When will common sense prevail over this red tape and commercially-driven political insanity?
Dear Matt You... like us, are starting to sound like a stuck record...You have become a HSCT evangelist that is clear, we have been banging on about the problems of development of treatments outside of pharma, but what is clear that what you may think is good for MS is not good for Pharma. You seem to want our approval for HSCT, we accept there is positive data but ask the same level of proof that we would ask for CCSVI, without it we would be listening say to a CCSVI evangelist that comes on the blog too.Pharma do not make money out of old treatments they make them out of new treatments. Neuros do not have the (guts) ability or money or time to develop one of these old chemo agents to a level that is acceptable to the regulators who are fed by the pharma hand. This is the system which has evolved in a way that excludes Neuros from doing much in the way positive action.This is frustrating for you and it is frustrating for me as our science may go nowhere because pharma are not interested. So what has to change. Well the system of licensing needs to change, the hurdles to get new treatments need to change and we have said until we are blue in the face that this needs a political solution and the lobbying needs to come from you and not us. People power made a different to how for example HIV is treated. There are loads of cheap safe drugs out there that could be useful but academic repurposing has not delivered anything but frustration but the red tape is the rules, it needs government to change these rules. So it is not incompetenceHowever why do we not do this (maybe we are) or that.....simple, time and resource, if people feel that haemos and oncos are the way forward you can lobby your MS Societies. They will respond to their members. Maybe they are actually doing this already but it is not the right time to may these plans public. It takes years of planning to get things off the ground.Maybe get the press on the case...they can make a story out of nothing so should be able to make one out of something There is the billl going through parliament as we rant
I think Matt makes a salient point regarding MS treatments and reliance on pharma for new treatments. Neuros need to be more proactive in the area of repurposing drugs. Pharma seems content with their control of the pipe line.
Haha sorry. I don't mean to be an evangelist. I do believe in it, clearly, but I just like to understand the for and against from different angles. This post does a good job of answering that from a Team G perspective!I go back to work next month so I'm sure these posts will be much less frequent! :)
"I think Matt makes a salient point regarding MS treatments and reliance on pharma for new treatments. Neuros need to be more proactive in the area of repurposing drugs. Pharma seems content with their control of the pipe line"We all agree but in fact the big problem is the regulators (funded by pharma) who put huge obstacles in the way of anybody trying to do this, as MD knows only too well.
Regarding the comparison between HSCT and CCSVI, I do not think this is valid. As the "HSCT Evangelist" Matt Perry has argued, this procedure is decades old and has been performed thousands of times for blood cancers. CCSVI, on the other hand, is a theory that was found to be lacking after rigorous trials. Also, since HSCT is just a more extreme method of ablation than the targeted alemtuzumab therapy, the question that needs to be answered - does HSCT provide better long term remission of disease activity compared to alemtuzumab. It would be interesting to get the perspective from an haematologist on lymphocyte re-population dynamics in autoimmunity.
Second question from me;What do you guys think about allogeneic transplantation. I've seen a lot of research recently about new ways to transplant allogeneic cells which can prevent Graft versus Host disease by manipulating the graft ex vivo. Dr Susan Ildstad I believe is working on this.As allo graft can replace the entire T and B cell populations (unlike an auto graft) with a new immune system from a donor who does not have a genetic susceptability to MS, presumably this represents the best theoretical chance of a permanent cure. If they overcome the safety issues associated with GvH through ex vivo graft manipulation, would that not be the absolute of all MS treatments?If so, why does this not have as much focus/investment for MS as it does for cancer? Feels like the capability is there already?
In cancer this is an instant and life and death decision making process, risk of dying and other complications from the procedure and risk of dying from the cancer. Simply put percieved and real danger and perhaps a sledge hammer too far...Graft verses host disease (So you have an autoimmune disease of the entire body is a ticking time bomb and if you prevent it then surely you completely prevent the graft from killing off the remaining immune cells you can't have it both ways as the mechanisms but let use see.The trial is ongoingTheir mechansim of action claimed is a facilitating cell however they are applying our view for immunological tolerance induction which is transient T cell depletion followed by intravenous immune tolerance tolerance induction. The depletion involves the the conditioning they recieve and then there is an intravenous antigen transfusion in the form of bone marrow transplant. To get optimal tolerance you need both the depletion and the tolerance. There are a few immuno-tolerance studies on going and in my opinion they will not work effectively or will more likely fail. so when they do remember this prediction. The MBP trial has gone down the pan already. People doing these studies don't want to listen and plough on regardless because they have no control on the depleting agent and no patentHowever this approach works in animals and works in humans and in EAE we can turn EAE off with a couple of injections and that it that no more relapsing disease. This is antigen specific so you not susceptible to to infections etc.It works after 1,2,3,4 (they go secondary progressive after that) attacks, the tolerance alone can work if done before disease starts but is simply not good enough after disease starts. We have had hundreds of success and very few failuresProblem is which antigen and which depletion tool, We believe we have answers to both of these, and both aspects have been tried and failed as individual treatments in animals and humans we have even tried the approach in MS..
I am intrigued by the statement that you have a good idea which antigen to try - is the antigen (antigens?) known in MS? It surely is known in EAE...
Definitely in EAE, not proven with anything like certainty in MS despite decades of trying, which I guess tells us something.
I guess this may tell us that autoimmune hypothesis is not correct. Alternatively, a complex antigen may be involved: di- or polyvalent recognition? E.g. myelin epitopes plus ion channels in close proximity ('unwrapping" the nodes of Ranvier)? An even more speculative idea: electric field-induced conformational changes in normal vs. faulty nerve conduction may expose usually hidden epitopes.
Which antigen?..You don't need to know!..they will be different between two individuals anyway
Incidentally, re Dr Ildstad, having read a bit more into it, I think what she is working on is stable mixed chimerism. Can't get my head around whether that would have a positive effect on MS or not really...
we shall see to report next year or so.
Team G, there was an article in the news yesterday about we have a 'mini brain' in the spinal cord and it's function is to help us keep our balance. The cluster of spinal neurons receives messages from touch sensors on the feet and adjusts our muscles to avoid slipping on ice for example. It would be interesting to see how MS effects the mini brain. It mentioned if we had a better understanding of this mini brain it could help developments of treatmments for diseases affecting balance and spinal cord injury.
While I'm very grateful for this blog, as an MSer I'm really only interested in what therapies might become a available in the next few years. There are often hints that the results of Team G's work will be published soon, but I'd like to get a better feel for when we may see the results e.g. In what month will the Charcot project results be published, when will we hear the results of the anti-spasticity trial, what other Team G work will be published this year?
I cant say we dont know the charcot has not yet been analysedso the paper has not been submitted the spasticity trial haz yet to start and we he not idea if and when papers will be accepted we like you need to wait. The clinical stuff often goes public at meetings like AAN in April or ECTRIMS in october. These days once a paper is accepted it can be online within a few weeks or less it used to take three to six months
ps we are wrting some cracking papers
Team G, I've been on the FACETs fatigue management programme. It has been very worth while as it is helping me identify when some symptoms occur and if these are related to fatigue. It is also helping me look at my MS in a much more holistic way that helps my MS with the DMT's. How food, sleep, stress to name a few effects my fatigue.
Mouse Doc I've got something important to ask: i am thinking about lobbying a bit for MS in some high places but need to have my aim formulated so that I can convince them to shine the spotlight on MS research.So what topic should I choose - simvastatin and repurposing of old drugs?or Charcot? or this initiative of yours BPA (but I need a summary of what it does and what the benefit is)Sorry, that it's so ominous but as of now I can't tell more. I don't know if my plan will achieve the desired effect but I will keep you updated - but you need to give me some concrete data of the most pressing issue - my intuition tells me that simvastatin and BPA could be summed up as one and I would pass it on.
Definitely the BPA (which includes simvastatin). The Charcot project is not a political issue.
MD2 - in case I achieve something (big IF) would any of you docs/profs be prepared to take part in a meeting, symposium etc to argue for your case?
yes definiately. The BPA includes repurposing and simvastatin stuff you dont know anything about and neuroprotective drugs the white knights etc send me and email if you want more info offline.
Thanks Mouse Doc - I just started thinking about how I formulate my plea and I need solid argumentation (short but sound) to say what it's about and if they agree to something what is the desired aim eg a meeting with XY or trying to get some big donors together - we need to have some clear objectives/prerogatives - I will try to drop you an email MouseDoc over the weekend - you'll see from the heading that's it's me.Thanks.
Definitely up for a meeting if needed.
Mouse Docs - I just found an organisation called CuresWithinReach which sounds similar to BPA - would it not make sense for you guys to contact those and somehow join efforts?
Thanks but we've beaten you to this already, we are in contact with them and awaiting a meeting dateOFF THEIR WEBSITE please forgive my use of the TROLL fontAll research must target an unsolved disease. IS MS REALLY UNSOLVED?Repurpose at least one human approved medical asset. OK SOUNDS GOODHave the potential to improve patient lives in 3-5 years, OK BUT CAN WE DO THIS FOR PROGRESSIVE MS THAT QUICKLY? Cost less than $250k, PINCH ME OR AM I DREAMING THAT IT CAN BE DONE FOR THIS AMOUNT?Be publishable in a peer-reviewed journal OK.
I would define MS as unsolved as in 'unsolved progressive part of MS' which is the part which counts frankly.the only thing i am also surprised is the costs - but they say project for a few years - i don't know how long it would take dr chataway to do the simvasatin trial phase three - perhaps they have a way to cut costs somehow? i hope you'll get feedback from them it's worth trying.
Prof G and Neuro Doc N I had severe phonophobia with a VI nerve palsy, I was hypervigilent. I was very stressed also at the time. I had a severe relapse from this and feel I should warn neurologists of this. It must be to do with the lesion being in the brain stem. I was having anxiety attacks and my hands were clenched as fists, my stomach was contracting, I think my teeth were chattering. Team G it's important that neurologists know a VI nerve palsy can be a very very nasty symptom.
Phonophobia is an anxiety disorder and can be very damaging to MSers. Relapses can be even more severe if they are triggered by a mixture of anxiety and stress.
The pons and medulla contain some of the most important structures in the brain, not to mention the control of breathing. MS plaques in these areas are taken seriously by neurologists and given steroids to reduce the morbidity from these relapses
Thanks Doc Gnanapavan. I would say that a VI nerve palsy needs to be treated quickly, none of the wait for two weeks and see how it is business. That's what happend to me and I had to wait many weeks to start steroids for my VI nerve palsy. It was a mistake that I had to wait for an MRI scan, I didn't know anything about neurology when this happened. Double vision in other conditions is seen as urgent such as a brain tumour or stroke. Why in MS do neurologists (from my experience) just treat a VI nerve palsy like a numb foot, with 'wait and see'. This is playing a risky game with MSers and their health. My VI nerve palsy was triggered by an ear infection, I have had a few different palsy's now and all have been ear infection related.
See post done on this paper
http://www.winnipegfreepress.com/breakingnews/Sufferers-feel-swindled-288496041.html?cx_navSource=d-top-storyon the flip side.........be careful of bogus claims
Yep buyer beware
Team G I wondered how does sugar effect MS? I know it's hard to cut out all sugar as there is sugar in fruit and even in bread. I find sweets and fizzy drinks act like a stimulant (not just the caffeine) and I find it hard to sleep if I have sweets or cakes late afternoon and evening. I know there was some research on having high amounts of salt in diet may lead to an increase in activity. I know that sugar may give an energy boost then a crash.My question I guess is does having a high sugar diet increase MS activity?
no idea ProfG?
Re: "My question I guess is does having a high sugar diet increase MS activity?"I have no idea; but can't think how sugar will affect immune function.
Thanks, I've decided to reduce my sugar substantially intake as it was pretty high and see how I get on. I noticed this paper was quite interesting. J Am Coll Cardiol. 2006 Aug 15;48(4):677-85. Epub 2006 Jul 24.The effects of diet on inflammation: emphasis on the metabolic syndrome.Giugliano D1, Ceriello A, Esposito K.Dietary patterns high in refined starches, sugar, and saturated and trans-fatty acids, poor in natural antioxidants and fiber from fruits, vegetables, and whole grains, and poor in omega-3 fatty acids may cause an activation of the innate immune system, most likely by an excessive production of proinflammatory cytokines associated with a reduced production of anti-inflammatory cytokines.Western dietary patterns warm up inflammation, while prudent dietary patterns cool it down.
I really hope someone can research into sugar and how it effects MS soon, I think it could give an idea how some mechanisms in MS work. I have been reading that Type 3 Diabeties is a proposed name for Alzheimers disease which results in resistance to insulin in the brain. There is some thought that a diet with high amounts of refined sugar may be major contributing factor or even the cause. Alzheimers can cause brain atrophy, along with other diseases/conditions and brain injury. There also seems to be thought among some nutritionists that a high sugar diet can suppress the immune system, hence causing vulnerability to infections, especially viral infections. This window of vulnerability can be up to five hours after eating the high sugar foodstuff. There's a big campain on at the moment for the general population, especially kids called Sugar Swaps highlighting changing high sugar cereals for sugar free cereals, changing snacks such as sweets for fruit.
A high suagr diet can lead to tooth decay and mouth and teeth infections. It would seem then dental care should be priority too for MSers. I don't want infections with my RRMS.
This seems to be the message I read about excess refined sugar and the immune system...Excess sugar meaning 75 grams or more of refined sugar eaten or drunk such as a can of fizzy drink and a cake or large fizzy drink. Can lead to a 40-50% drop in the ability of white blood cells to engulf bacteria for up to five hours. This wouldn't of overly bothered me before I got MS but now I have MS I want to avoid infections as much as I can.
I have seen on quite a few general websites about MS where the usual MS symptoms etc are listed that unexplained episodic lower back pain can be a symptom (i.e. there is no triggering over-exertion or identifiable physical cause such as disc problems or pinched nerves)Is there any data or studies on this?If this pain can be a symptom, what is MS doing that causes the pain? (e.g. is it muscle spasms/spasticity resulting from corrupted nerve transmissions, can it be a sign of current active inflammation even if no relapse as such is apparent?)If MS is the culprit, how can this pain be treated?
if your circuits get damaged then firing of then nerves that sense pain can trigger pain sensations in the brain and this can persist after the inflammation has died down. It is difficult to treat and can be a question of trial and error
Thanks MDThe pain "sensations" are very real even if it is just MS playing nasty games in my brain, and have been crippling several times recently i.e. have had to hang on to walls and furniture to stay standing up, and have been stuck to a chair several times because the stabbing pains were so severe if I tried to stand up (bad news if you need to go to the loo because of MS related bladder problems). The physio did find a couple of tight muscles and worked on them (hence my question about spasticity/spasms, but the relief I usually get from this didn't persist, and NSAIDs haven't helped either.I'd be interested to hear of anything other people may have found helpful (but don't suggest a nice hot bath - I can't do that because I also suffer from system shutdown when my core temperature rises, and I certainly don't want to get stuck in the bath!!!)Bloody MS - I do hope this isn't a sign of new disease activity, and another symptom coming to join my existing collection..........
profs,I came across the website of the XXXXX MS centre in New York. They are undertaking a repair trial and also claim that they may be close to announcing that target of the immune system. Are they a bona fide outfit? Are they doing interesting work?XXXXXXXThe repair trial is for mesenchymal stem cells, which so far in animals have had a modest immuno-modulatory effect the repair aspect has been more limited. There is a massive international effort on this aspect. The results of which will be reported soonThey claim that they have found an antibodies environmental antigen in 75% of people. lets see when it is publishedI am sure the centre is bone fida, but some of the scientists,I think were supporters of CCSVI.I have deleted the link as it is to a site requesting donations
XXXXX in New York raised money for their trials on Indiegogo (which is basically a Kickstarter clone).Just curious - do you guys see crowdfunding as a potential future avenue for any of your research in future? I see they raised nearly $320k for their Phase 1 study on MSCs, which is pretty impressive.I reckon you guys probably have a bigger following on here, and there are lots of studies you mention on here that people would like to see done (but where funding is an issue).Maybe this could be an interesting option to get some of your independent trials going (i.e. those that are not in the interests of pharma)...Maybe do one a year or something. Put a few options up, let people vote on which they'd be most interested in seeing done, and then ask the people to put their money where there mouth is. Ultimate patient power.I'm claiming 10% for the idea. You're welcome! :-)
Thanks for the Idea, it has already crossed our mind and the ProfGs have been thinking seriously about Charcot2, and I overheard some knights thinking about something else, so not sure you will get the ten percent. Maybe the idea of putting up a few options and putting money where the mouth is would be interesting. What percentage do you think is reasonable to charge for the administration? Just Giving takes 5% is that OK,what about 10%, Would it put you off donating when 10p in pound goes to pay the machine. However people donate to MS societies and they have big machine to support. What effect will crowd sourcing have of their ability to generate funds.Stem cells are a great hope, but CCSVI trialsdidnot really get going so are MSers up for crowd sourcing?Our requests for the help of a big benefactor has so far fallen on deaf ears:-).HoweverIf we look in the US and elsewhere a link to donation is par for the course on many websites, but this crowd sourcing route of funding is a relatively untested route of funding and it will be interesting how the MS research community view this
Crowd funding can work effectively but a lot of bits and bobs need to be built in (simple ask but strong narrative) and large investment in time. Also worth doing a test with a small discrete time-limited project. Ask for around £10,000-15,000. Make sure you networks are involved -initially you must have stakeholders action and backing (sharing, donating, blogging etc). Also use the mainstream media. Individual MS stories to focus on, will humanise and work well.There are non-profit crowd funding sites, with less admin costs. Also check out Virgin giving, I recollect less admin costs last time I used it. But all depends on if going for a local or international market. Re a benefactor, I don't know how you made the ask or to whom but probably worth revisiting with some specific targets, who have the dosh plusan emotional interest in MS. Lots of other ways to raise money but you may need someone who has the fundraising expertise (sorry but I'm having a relapse at the moment, otherwise I'd volunteer).
Also, I forgot ... Look at getting a charity involved that can receive the money for your projects as then you can - hopefully - claim gift aid in UK. Not something I've kept up as in last 5 years mainly working more on internet based fundraising and less on the actual law part but many ways of incorporating as a non profit these days (no idea how you do this as a research body or if you need this), that are not as difficult as getting full charity status in UK but mean your projects have more 'legitimacy'.
P.S. Regarding a big benefactor, I think you need to do a marketing job on it and tap into the emotions. I've not seen what youv'e done previously, but it feels like you need a bitesized deck (like your infographic at the bottom of the page), or maybe a short video, which gets across the terrible impact of the disease, the number of people affected, pitches your theory and why you think it's viral, and why pharma (or whoever) aren't funding it, and asks the question "what if we're right?" - and what the impact of that would be in human terms.In my experience, people invest in 2 things: 1) People, and 2) BIG, moving ideas.
Matt PerryWednesday, February 11, 2015 3:08:00 pmThe XXXXXX example suggests there is an appetite for it. I think what they do very well is tell the story. They've a very clear mission and all of their initiatives are stepping stones towards those goals (i.e. they have one team with a mission to identify the cause, one team with a focus on repair strategies, and one to understand progression, etc.).When you pitch it in that way, everything becomes more joined up and there's a sense of momentum and progression towards what people want, which inspires people to want to get involved. There's something in it for them. I think that's actually where XXXXX stand out, in that most research projects are focusing on a single experiment, so you end up with a random spattering of projects that are not joined up or part of the same overall story. XXXXX has very big, bold aims (in line with the BIG questions MS'ers want to see answered), and it's all joined up. And (unliike the MS societies) all the funding is going to causes that really matter to people - rather than studies to find out what MS'ers favourite colour is, or studies that are so underpowered that they're meaningless even when positive.Where I think this could work for you is in Charcot. In that arena, you guys are pushing the boundaries and everyone wants to know if there is a viral cause. So I think you'd get some good buy-in if you raised money for that. Set out your goal "We want to prove MS is caused by EBV" or whatever, an easy to digest background on what's gone before to indicate it is EBV, and then break down your mission into chunks with a timeline attached to it, and i think you'll genereate that sense of momentum that people will want to buy in to.I think a lot of MS'ers want to have that power and ownership of finding answers, and crave that involvement and early access to knowledge. There's definitely a sense of frustration with "the establishment" (in this case big pharma). You guys can tap into that and become the UKIP of MS! haha :)
One other thing I forgot also to say (bloody relapse) is that in fundraising, it is more about the donor then the project. I won't go into details but essentially a big mistake I've seen over the years in fundraising and marketing is ignoring this fact. An individual donor needs to know how they can help and that it is their help that will make the difference. There is a formula to writing an appeal (slightly different depending on if it is to a major donor, prospect or committed small donor), using nudge marketing techniques but always always it is about the donor. Not something always acknowledged openly in the charity world. Hopefully I will be back to normal soon and happy to give some advice when I do, if any use!
something analogous to the ALS "ice-bucket challenge" would help the funding along. Unfortunately, no one really knows what is driving neurodegeneration and how to target the process. $$$=cure? I applaud XXXXX in NYC for having the guts to raise funds and proceed.
Re Anonymous at 9.16am, 10.53am 7.50pm and your comments about crowd funding.There has been much discussion on this blog about re-purposing old drugs which are out of patent. A prime candidate for crowd funded research would be Low Dose Naltrexone. See the following for my suggestions for setting up a decent database to try and get some real data about LDN.http://multiple-sclerosis-research.blogspot.com/2014/12/time-to-changetime-to-repurpose.htmlThere is already a registered charity set up which is trying to raise funds for LDN research, so that could take care of one aspect of your suggestions. Bring in some MS clinical expertise and some statistical analysts to help set it up properly (the couple of existing self-reporting databases are very lacking in these aspects).Given the thousands of MSers around the world who are already using LDN, I suspect that some decent funds could be raised from them to actually make this happen, and while it would not be "Gold Standard" clinical trials there could still be useful and meaningful data collected for analysis.Note - I am nothing to do with the aforementioned charity - just an MSer for whom there aren't really any options because I'm not RR.
Re the ALS Ice bucket challengeHow about three legged races, over a timed 25 metre "run". Sounds boring? Well - have one person facing one way and the other person facing the other way - that should produce a few undignified and amusing spills. Maybe have a blind-folded version as well. And it would generate some understanding of what happens when MS stops your legs from doing what you tell them to.Funds raised could go to the Progressive MS Alliance as progressive MS is the one that's really missing out.
Fampridine.I am a bit wary about this drug as I read somewhere that it puts extra pressure on already damaged axons and that you may end up worse over time in taking it.Also does it reduce spasticity, or drop foot etc. If I was helped on one of those levels I would walk faster. I cant decide whether or not to ask for it. Thankyou
That is my concern about fampridine. Are you getting a short-term benefit that is actually detrimental in the long-term?
How might a potassium channel blocker such as fampridine be deleterious to axon survival? Is the increase in nerve conduction not beneficial?
It might not be in a demyelinated or damaged axon that is having to work harder anyway. It's not something that Biogen are willing to investigate I suspect.
This should be something a registry could see.
Mouse Doctor it was great to see you in Berkshire this afternoon - thanks for your talk but also a massive thanks to everyone involved in the blog and empowering us MSers through knowledge. It isn't always cuddly, re-assuring knowledge but I'm a face problems head-on type of person so really appreciate learning more.
Thanks for your kind words
Who said MS was not a profitable disease?http://www.propertymentorgroup.com/stock-alert-biogen-idec-inc-nasdaqbiib-eclipse-resources-corporation-nyseecr-aerovironment-nasdaqavav-vantage-drilling-company-nysemktvtg-cae-inc-nysecae/1270162/
A different bit of research to that of the MDs and Prof GAs many of us who follow this blog have had to go down that horrible path of getting told we or a partner or family member has MS, and then working out what to do next, I thought I'd post this here so that those of us who are MSers can contribute a little bit of our time to help with some other research (with not even a single mouse involved!).The School of Psychological Sciences at the University of Melbourne in Australia is conducting a survey to help with research towards "how to effectively help individuals adjust positively to MS". The survey is for people who have been formally diagnosed with MS and the following is from the info sheet on the survey being done:"What is this study about?This research aims to investigate the relationship between individuals’ personality, their understanding and beliefs about their multiple sclerosis, and their adjustment to multiple sclerosis including acceptance of multiple sclerosis and any feelings of depression or anxiety. This project has been approved by the Human Research Ethics CommitteeWhat will I be asked to do?If you agree to participate, you will be asked to complete a questionnaire on our secure website that asks about the factors outlined above. You will not be asked to provide any identifying information apart from your email address. The total time commitment required is not expected to exceed 40 minutes."I've completed the on-line survey and it actually took me quite a bit less than the 40 minute estimate. As far as I can see you do not need to be in Australia to complete the survey, because there was a question which asked which country I was from. I understand that the survey will be open for another couple of months until the required number of participants for statistical analysis is reached, so go for it guys and gals, and do your bit (drum roll - end of sales pitch..........)You can find more info on the following link, and the contact e-mail address of the person who is conducting the study (link should work if you copy and paste it as text into your browser)http://www.mstrials.org.au/do-illness-representations-mediate-relationship-between-personality-and-adjustment-multiple-sclerosi(PS – this post is NOT from the researcher in disguise – just a humble ol’ MSer trying to do their bit!!)
I have to say... I'm getting pretty depressed reading this blog.Each day I come here hoping to find some good news or hope, but it's never there.That makes me real sad :(
The aim of the blog is to present information and news both good and bad. If you want rose-tinted, there are plenty of other sites.Believe me, there is good news coming down the pipe.
"Believe me, there is good news coming down the pipe."May God bless you for these precious words.we are here waiting.....
Sometimes that light we see at the end of the tunnel is a train:-)
Half the problem is that when you do see a light at the end of the tunnel some b..st..d goes and orders more tunnel!!!But life would be a lot worse without the "Barts Express Daily Newspaper" - as the good MD2 notes - there're plenty of other "fluffy" sites out there for those who only want the rose-tinted or "low fat" versions........
"Sometimes that light we see at the end of the tunnel is a train:-)"As a regular user of the London Underground I usually take that as a good sign ;-)
Re "Believe me, there is good news coming down the pipe"Is the good news going to be for progressive forms of MS, is it for (same old, same old) Relapsing MS?
Team Gthe John Hopknis neurology team seem to be doing trials with the drug avastin on people with TM and NMO. The aim is to reduce damage from relapse and repair myelin. Avastin has been shown to improve/resolve lesion load on MRI too.Also they are doing a lot of research on stem cells for TM and injecting them directly into the lesion. Is this a different type of stem cell than the ones used in the MS trials.
NMO/TM is not MS but there is interesting blocking VEGF. There are so many stem cells types going into MSers they will be the same but to be honest I don't know the fine details
This might be a bizarre question, but what is the "new" prognosis of an MS'er.There's lots of data out there on the natural history (i.e. 10-15 years to SPMS, all of the stats re unemployment, time to wheelchair/walker, etc.).But in this era of drug therapies, what is the "new" expected prognosis - has it changed and is anyone working this up?
No idea we have had ten years of tysabri is that long enough
Does anyone know when the trial data for Raltegravir will appear? I thought it was scheduled for January/February 2015 or was that 2016?
when its published maybe 2016
This trial has slipped and slipped. I thought we'd hear something by this Easter. Why don't the two Prof Gs do something innovative - use this blog to publicise the initial results. Something on the lines of 'the trials results suggest that raltigravir had a marked effect / limited effect / no effect on preventing new lesions / mri activity'. Following the slow academic formula of having to get results published in academic journals is why MS research has been so slow.
The trial is finished, the data needs to be locked and then it can be analysed, as you would want the ProfGs to be be peeking before then. I do not thing he analysis will be finished before Q2 2015. Then the data will be written up and presented/published. as you have been told many times that many places embargo reporting of he result until the paper is published.At the moment altimetrics have not taken over publications as the unit of assessment and that is what we work to. However once accepted, then he papers can go on the web within few days in some journals
Patient.co.uk talks about Azathioprine (Imuran) being used for MS. Not a drug I've come across. Is it any good / plans to licence?
Its an old anti cancer drug, lets see if the italian docs can get it licensed;. I doubt it. Its abit better than beta interferon
It is very popular in other inflammatory disorders, often being used as a steroid sparing agent: neurosarcoid, myaesthenia gravis, CNS lupus, Behect's, stiff person, rheumatoid arthritis (a few that come to me). Its main SE's include those on the liver (abnormal LFTs) and bone marrow (low blood count) but has been used for donkey's years.
I think it would be helpful to have a discussion about the various neuroprotective trials underway. Phenytoin may be the first to report, the the various drugs being tested under SMART MS. Lets imagine that the results of Phenytoin are positive. What next? The trial was a Phase II looking at ON. Could they got straight to a Phase III for the whole nervous system? Who would fund such a trial? Aren't we facing the same issues as for the recent trial run by Dr Chattaway for Simvastin? We could be looking at lots of drugs tested in Phase II that will never find their way to market. Even if a drug was licensed e.g. Phentoin, we are looking at 2020 before it becomes available. Perhaps you can understand why we don't get over-excited. May be a kind GP would prescribe Phentoin if the Phase II results were very convincing. If not, I can see a situation where MSers will be buying drugs on the internet as they can't wait another 5-7 years.
I have been asking the same questions what if? and what's next?First thing you should all be doing is signing up to the PROXIMUS trial in MS, because if you guys don't want to do it in enough numbers the trial will be a non starter....Part of the sabbatical of ProfG was to get people in this study what are you waiting for the results of the phenytonin trial? The PROXIMUS trial uses the same class of drug as the phenytoin trialAs for phenytonin trial in MS it was actually all planned about 6 years ago in Yale, but it was bottled because of results from EAE. The group was new to EAE and somehow showed phenytonin was immunosuppressive and this stopped disease, so when you stop drug in EAE, disease almost always comes back, this came as shock and as disease came back with a bang and they ran a mile. This should have been expected, we see this all the time. This made the MS study with lamotrigine be extended for months. When drug was stopped inflammation brain swelling came back, but not with the bang. When drugs stops working the re-activation of disease could be quick, with our statin work it was within 2 days of stopping drug, which is the time it takes to be removed from the system. For some antibodies it takes a few weeks for EAE to come back. However is this expected experience in EAE going to stop the studies that you are suggesting? However if the phenytonin trial fails the answer will be "back to the drawing board"If positive another study, would this be a test case for the Evans re-purposing bill or maybe this is why Biogen spent $650 million buying a British company that makes sodium channel blockers....Although they were after a 1.7 blocker for pain, there will surely be others in the company vaults.
I've been reading about how the garments we wear may effect our health. I used to wear skinny jeans and still do wear jeggings (leggings that are more like jeans) and have been thinking how these could be effecting my MS. Skinny jeans can cause meralgia parethetics which is compression of the superficial nerves that gives/supply sensation to the lateral thighs. This compression over time can cause numbness, pain and tingling. I have already got painful legs. So i'm going to give up these tight fitting clothes for more looser trousers or ones with alot more stretch and see if that helps me.
I'm not giving up my skinny jeans, which have never caused my legs to go numb, compression or pain. Sorry to hear they've done this to you but the only reports I've found seem to be in individuals wearing a too small size, and it goes away after stopping. Anyway, apparently flares are back in fashion (yet again) so there you go:)
http://www.fool.com/investing/general/2015/02/14/3-biotech-stocks-i-love.aspxBiogen #2. Last paragraph says it all..........if you are going to be stuck with MS might as well make some $. Buy some stock. This is not an indictment of Biogen, they are doing their best in providing therapies for MS. As we all know MS is a chronic disease that strikes most in their 20s and 30s with no known cure. In other words a pharmaceutical company's jack pot.
http://www.huffingtonpost.com/jeffrey-sachs/the-drug-that-is-bankrupt_b_6692340.html?ncid=txtlnkusaolp00000592Why do drug companies charge much more than the cost to manufacture the drug? Pharma says it is to recoup the cost of development, R&D, clinical trials, etc. But as this article points out, the NIH funded much of the basic science in the drug development. The U.S. government seems to be willing to let pharma charge the exorbitant prices to keep corporations in the U.S. and reap the taxes and jobs created. It would seem that pharma and the government are in bed together. So if we say "let's fund academic research and bypass the greedy pharma corporations", it may be somewhat naive. But grass root fundraising or "crowdfunding", ice bucket challenge, etc. serves to keep the public engaged and to lobby for research $$.
Interesting I suggest people have a read. Can a repurposing programme ever get off the ground? Requires politics to happen and politics and maybe will stop it happening.
Team G I wonder can whiplash cause white matter lesions (such as in the neck) that look like MS? I have had whiplash twice now, first was 25 yeas ago from a car accident and more recently through an Epley treatment around two years ago. I did read a bit that fMRI might show these changes, another source mentions changes probably wouldn't show on MRI. Thank you.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2539006/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538999/Sorry I am not a radiographer and don't know what whiplash lesions look like
I have a question regarding "clinically silent" MS, sometimes found in people postmortem, although they showed no symptoms during life. Also the fact that siblings of people with MS are found to have lesions in some cases, but no (noticeable) symptoms. Is this more likely to be (a) because the lesions, as a matter of sheer luck, did not occur in a crucial area, (b) because the individual had more remyelination going on, or (c) for some reason, their brains adapted to the damage better?
Probably mostly (a) but it's possible (b) and (c) might play a role too. It also could be that some people handle the lesion better as their nerves are better able to withstand the inflammation, which I've been pondering for some time. There's probably a genetic study in this.
Might MS be less common in equatorial regions due to natural selection given the effect of heat related fatigue, not just the influence of vitamin D? I live in the far north of the UK; if I resided in equatorial Africa, I would simply no longer function. In terms of my mobility, from about 22 degrees ambient temperatue, I can only loll about the place.
MD I've contacted NICE about their guidelines and suggested that MS relapses are treated quickly. If one of my relapses a few years ago was treated quickly I am pretty sure I would be in a much better physical state today. I got to start oral steroids on the 32nd day of the eye symptom!! I was suffering from severe stress and anxiety at the time, including stress and anxiety from having the symptoms, I then had a nasty relapse triggered by stress and anxiety.
It is amazing that all we do with relapses is treat with steroids, there are hundreds of drugs in animals that are started just after onset and it they had to wait 32 days they would have got better and relapsed again in this time. Based on animal stuff the quicker you start treatment the less deficit accumulated. If you look at the graph I posted on optic neuritis this idea is supported in MS too. If the optic neuritis trial works then it gives a new idea of what to do with relapses over and above giving steroids
Hi MD, can you post the link to this post and also elaborate on what treatment work 'over and above giving steroids' thank you
http://multiple-sclerosis-research.blogspot.com/2015/01/remyelination-on-its-way.htmlhttp://multiple-sclerosis-research.blogspot.com/2015/02/remyelination-its-easy-in-animals-but.htmlThe trial we did was sodium channel blockage the results will be announced soon I am led to believe
Thanks MD. I am thinking of beginning a petition or campaign on raising the awareness (for neurologists, MS nurses, GP's etc) of how stress and anxiety can be so damaging for MSers. I really can't get over why research on stress and anxiety in MS in still in it's infancy.
I knew about stress levels impacting MS nearly 40 years ago. There are an awful lot of bloggers that are complaining that they've never been told. Has something changed?
Anon at 8.17pm - I agree with you - negative impacts of too much stress have been known about for years and years - and not just in relation to MS.Maybe the change is that potential negative impacts are so widely known and accepted that the neuros et al don't mention it as it is just assumed that such knowledge is in the "public domain" by now, but some people just need a hobbyhorse or a hook to hang a blame hat on! In my opinion there is no need for research on stress/anxiety in MS - the money would be far better spent on other more important and relevant research e.g. treatments for progressive MS. The time some people might be interested in using to start petitions or campaigns to "raise awareness" on an already well-known issue would probably be better spent reading a few of the zillions of self-help books available on de-stressing and relaxation techniques.
Sadly for me I was very very stressed when I had my first relapse. I didn't know I had MS at the time so didn't know stress and my symptoms were related, I had no idea. I told the neurologist I was very stressed and his reaction was 'he wrote down the words and changed the subject'. No concern shown, no questions asked about my severe stress, no warning about stress, no reaction from him. He just changed the subject!! I am unable to work for being too sick, I have many lesions in my brain and spine. My first relapse was such magnitude and if I experience another relapse of that magnitude I would be in a very poor state. I have discussed my experience with different doctors. One implied MSers are clutching at straws and looking for a reason for a relapse. He really has no idea. All my relapses have triggers other MSers might not have this experience. Infections, stress and anxiety so far are my triggers. It's fine if you are introduced to your MS in a much more subtle way and then get the chance to read about stress and MS on the web, then you have the knowledge, awareness and are warned. Take the MS Society Forum MSers are warning CISers to watch their stress levels. My campaign is for doctors and nurses to understand stress and anxiety in MS is very damaging. I meditate twice a day and do yoga so I have learn't the very very hard way. It's only when we tell them our experiences that things can change for the better.
There was no Web when I was diagnosed I was told for months that I was ill because I was neurotic, considering how many terrible things were happening to me and my family. I can't tell you how thrilled I was when I was given a diagnosis of a physical condition.The doctors knew then and they know now what stress does. However, they can't stop our relatives being seriously ill or events that we have no control ourselves.
My mother knew about stress in MS can cause problems and that was before year 2000. That was because my mothers friends partner has MS. Of course there may have been information on stress and MS in books, leaflets, magazines, newspapers at that time. But there doesn't seem to be much if any concern about stress in MS amongst neurologists and MS nurses. No neurologist or MS nurse warned me about infections can trigger relapses, same with stress and anxiety. I find that shocking too. As i've had quite a bit of damage done from infection triggered relapses. I had to find that out for myself by reading MS Society leaflets, this blog and on the web. I even spoke with some other MSers a while back, they had no idea infections can trigger relapses !!!
I can't see why you still need nurses and neurologists to tell you about stress. Stress will affect cancer, psoriasis, asthma, angina, diabetes, cardiac illnesses. There is more information available now than there has ever been. The time we spend with our MS specialists is precious and what can they do? Maybe a visit to the GP would help. Some things we have to do ourselves.
I'm not getting my message through. Anon at 8.05.00am What I am trying to say (shout out really) is that stress and anxiety is MS IS very very damaging. It is for Neurologists and Registrars and Psychiatrists and Doctors to know this. I told the registrar I was very very stressed and he did nothing, said nothing about stress, neither did his supervisor. They treated me non-urgently like 'severe stress' means nothing and it wasn't not of any importance. I promise you it is VERY damaging. I got to begin steroids on the 51st day of being sick!!! It was my first relapse and the symptoms made me feel stressed and anxious. I have written a list of the other 19 reasons why I was stressed and anxious during that relapse. Like I said before when you discover you have MS in a more gentle way then you read about stress being not good in MS. I didn't have this, then you are able make changes in your life, do things differently when you are warned. I don't need a GP visit. I did tell an experienced GP about stress and he said "sometimes we don't ask patients why they are stressed". Well all I can say to him is he needs to ask the patients questions.
Doctors and Nurses know that stress can have effects on MS, but stress means so many different things and are both physical and psychological
If doctors are being trained to know stress effects MS then why is their reaction to me telling them I was very stressed 'nothing'? The registrar just wrote down the words. His supervisor saw my examination sheet that states very stressed. It diidn't raise alarm bells for him too. Why did he not comment or even say stress is good for no one, there was no reaction. It was like I told him I had bananas yesterday for breakfast. Like it was nothing of importance. At that point I had been stressed for many weeks, it was chronic severe ongoing stress. If I was a neurologist, GP or nurse and I was examining a patient and I susected they had MS and they told me they were very stressed I would discuss stress for a few minutes. I would draw it to their attention that stress is no good for anyone and ask why they are stressed. I would point out that it is very important to get the stress under control. There may be something that the neurologist or doctor can suggest to help the situation.
Have you tried counselling? I can see by the tone of your posts you are quite angry. This is obviously stressing you and not good for your health. Doctors and nurses cannot change our personal circumstances. They can make a note, but it is up to you to find ways to relieve the stress in your life.
I've been seeing a neuropsychiatrist about my experience. I am a postgrad researcher anyway so I am wriitng about my experience, it might as well be documented. I am more sad than angry and I do stress reduction twice a day. You will never understand what happened to me and it sounds like your introduction to MS was much more gentle and you were able to learn about stress and MS before experiencing it. I was niave and I didn't get the best medical care. But thats life things happen.
Team G,For people in limbo with negative LPs would it be worthwhile to ask to be tested for the EBV If this was negative would that rule out MS ?Thanks
most people are positive
Team G, "We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation. In Epstein Barr cites research findings in their serum levels of Vitamin D3." Forgive me the question but what do you think about the low levels of Vitamin D3? She would have more implication for the conversion of CIS to MS than the virus itself Epstein Barr?
Something for the doctors-http://www.nytimes.com/2015/02/18/health/doctors-strive-to-do-less-harm-by-inattentive-care.html
Interesting that it mentions a survey asked patients ' Is it quiet in your room at night? (in hospital). It mentions what is really being asked is: Can you get a good night’s sleep without interruption?'. This was discussed by a few of us MSers on the post :http://multiple-sclerosis-research.blogspot.com/2014/12/does-sleep-deprivation-make-your-brain.html
Nope, that is impossible in my experience of being in a UK hospital. Constant interruptions all night, ugh.
Dear Docs/Prof, I had a truckload of (what seemed like) random symptoms last summer. I started having excrutiating migraines at work, light sensitivity, dizziness, severe back pain, vertigo faintness & numb chin & lips. Imaging was done & some unrelated observations were made but no lesions were evident. Months later, my nuerologist ordered an lumbar puncture & 4 tubes of CSF for analysis. I saw the list of tests that were ordered & was hopeful we could rule out some things & establish a baseline for others. I received a few of the test results & they seemed incomplete. It took me awhile but I finally realized one the reports missing the order for the Oligoconal Bands. I asked my Neuro about that test & she said that yes, she had ordered them, but that the hospital called & said they didn't do the OCBs; only the IgG Synthesis Rate because it is more sensitive. Then she told me that actually the hospital called & she okayed not doing the OCBs but the hospital ran them anyway & I'm fine. She is unable to produce a report re the OCBs so I feel like the lumbar puncture was a waste of time. I am seeking perspective & advice regarding having only an IgG Synthesis Rate (w/i range) & NO OCB lab work/report. Is the IgG Syn specific enough to rely on for NOT having MS at this time? Should I have another lumbar puncture done elsewhere? The recent events & squirely explanation motivated me to end our relationship.Thank you in advance for everything you do!
Dear H PhillipsWe can't give personal medical advice on the blog. The diagnosis of MS and related conditions is complex and requires a detailed history, examination and series of investigations. What I can say is that the detection of OCBs using isoelectric focusing with immunofixation is a more sensitive than the IgG index; the former is positive in ~85-98% of patients who fulfill criteria for clinically definite MS (CDMS). In comparison the IgG index is only raised in about of 70% of patients with CDMS.
H Phillips - you should get you Vitamin B12 levels checked - low or deficient B12 can mimic MS, and I learnt from my researches that checking B12 is supposed to be part of the standard blood tests done if MS is suspected (i.e. to rule out B12 deficiency as a cause of the neurological symptoms). Some countries are still working on very low bottom ends for their reference ranges for serum B12, but many experts now reckon that the lowest acceptable level of serum B12 should be 550pg/ml or 400pmol/L - which some countries do use as acceptable bottom levels. May also be worth getting your red blood cell magnesium checked as well, as low magnesium levels can also cause symptoms similar to those you have described.
Thank you Dr. G & Anonymous. I sincerely appreciate the information & recommendation. I'm hoping Johns Hopkins will take me as a referral & review the detailed history information, examination & investigations & if appropriate, order a new lumbar puncture & blood work with OCB analysis etc.
Team G, it would be interesting to know if Reynaulds Syndrome and related condition Acrocyanosis (but not the same) are quite common in MSers. I have Acrycianosis which is my left foot goes purple/bluish and very very cold when I am sitting down. When my foot is raised such as laying down the foot returns to normal colour and temperature. I think it's to do with insufficient blood flow and I wear thick socks with a thin layer of socks under them to keep feet warm, walk around often and massage the foot. This paper mentions Acrocyanosis in MS a bit.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105617/
Would love to see something on this as well. My wife was diagnosed with both MS and Reynauds. Both feet swell, turn purple/blue and get cold. We were told by her neurologist that the two were totally unrelated... It has often made me wonder more about how Neurologists rule out things like Antiphospholipid syndrome, which behaves similarly to MS, but seems to include symptoms very similar to Reynaud's syndrome as well.
Unrelated but just wanted to put out a nice positive post about my NHS neuro. I’ve seen him today and he let me harp on about NEDA and windows of opportunities. He listened while I pleaded my case and answered all my questions. He agreed to support me in whichever DMT choice I make. I’ve chose Lemtrada, not his first choice but he’s happy to go with it and respects my reasons. He really has restored my faith and given me some hope. After seeing several neuro's this one is totally on the level and the difference is remarkable.
Congrats. Mine didn't know what a B cell was. I shit thee not.
That is both staggering and disturbing.
Perhaps send him a link to this blog.
Profs.Tysabri in HIV therapies temporary blocking the pathways to "viral reservoirs" in the brain and gut during HART therapy.http://www.sciencedaily.com/releases/2015/02/150218123617.htmCould the same be useful in Charcot as well?
T-cells that are blocked by tysabri are not reservoirs of EBV, that would be b-cells. Anti-retrovirals supposedly inhibit HERVs. In HIV T-cells carry the virus therefore blocking with tysabri may prevent seeding into CNS
I have some doubts that afflict me a little about MS and I think should be the same for many patients, doctors and researchers. For example, with respect to the HSCT. Good in the process is resetting the immune system so that it heals why efficacy in clinical trials is not 100%? It would be the interaction of genes still "active" would prevent this process of recovering all or have any other "hidden factor"? ... I am very curious about the viral theory, HHV 6, HHV 5 and Epstein Barr, and the interaction of genetic factors ...And vitamin D3 would have something to "talk" in the MS process? ... Any doc to answer me? ...Thank you now!!
Re HSCT, here's a few theoretical reasons from Dr Perry (i'm not a doctor) for why it might not be 100% successful...1) Neither myeloablative nor non-myeloablative protocols wipe out ALL lymphocytes (just a substantial proportion). So, it may be that for some people, it is not strong enough and some of the memory cells/autoreactive lymphocytes survive. This makes sense when you look at the data for Alemtuzumab, where if you keep adding induction therapy after induction therapy (multiple doses), the success rate jumps substantially with each additional dose (hence in CARE-MS1 the NEDA rate is 39%, but it rises to 70-something percent when you include multiple doses). Equally, in Dr Burt's previous studiy, around 20% of patients having non-myelo HSCT relapsed. They were all treated with additional lymphoablation (either pulsed chemo "top up" treatment, or mabs), and if you include that data then 100% of them were in remission. Big caveat is that it was a small patient population. Similarly, Dr Freedman in Ottowa uses a very high intensity chemo protocol for his HSCT, and I believe he is at 100% remission for all his patients at 8 years and counting.2) It is conceivable that, for some, the disease is actually reactivated (i.e. the enivronmental trigger reoccurs).3) MS has two components; immune-mediated inflammation, and neurodegeneration. Prof G often talks on the blog of the rheumatoid arthritis example whereby, if you stop inflammation early, the end-organ degenerative process can be prevented from occuring. But if you leave it too late, then the degenerative process becomes decoupled from the inflammation and deteriorates independently (even if you then stop the inflammation). If you look at the patient cohorts in the majority of published HSCT studies, the majority of patients are high EDSS, highly active disease, refractory to drug therapies. So, for some, it's quite likely may have missed the window in which HSCT is most effective, and their neurodegenerative process has become "decoupled" from the inflammation which primes it (and which HSCT is effective at quashing).4) If Dr F's theory on therapeutic lag is correct, then stopping the inflammation now may mean that you have still primed some neurodegeneration which will occur (up to 2 years, maybe more) down the line. It may have stopped you from accruing more damage, but as a treatment it does not claim to be neuroprotective/reparative so it may be that you'll still experience a period of decline. This is actually a big problem with a lot of the HSCT studies out there - they only measure NEDA rates and most are only 3-5 years follow up. So if Dr F's therapeutic lag theory is true, it's likely that the "success" rate for stopping disease activity in HSCT is probably higher, but a proportion of patients experienc EDSS progression as a result of damage done prior, but may have a better/more stable outcome if followed for longer. i.e. HSCT hasn't failed.5) Chemo is neurotoxic. It can cause peripheral neuropathy, brain atrophy, and it aggravates the nerves in general. Moreso with stronger protocols, and moreso where there is extensive CNS injury already. So whilst the disease activity may be stopped, it's conceivable that there will be some injury (usually temporary - but can take 24 months to settle) from the chemo. This may conceivably be responsible for some "relapses" or "progression" failures, and is why (in my opinion) they need to track HSCT disability progression curves at patient level over the long term (and not just focus on the overall NEDA rates, which drops patients out of the stats if they have a 0.5 EDSS progression or a relapse) - to understand what impact HSCT has on overall long-term prognosis.That's my two-pence worth anyway. Hope that helps!
Matt,hope you don't mind me asking, did you have any treatment pre HSCT? Was your EDSS particularly high?many thanks - your input and experience is very interesting.
Matt Perry thank you for answering me. I am still "new" in this world of MS (I'm 29 years), my symptoms started last year and two months later was already closed and making treatment diagnosis. I started with Rebif 44th but could not stand the side effects and switched to Copaxone. So far everything is fine, but I've been curious about the research being done on the disease and even about what we can expect about the future ... What about vitamin D3 that back and a half I see an article being published about it, what you and the blog doctors think about (also discovered the blog recently and has not "managed to read all publications)?
Hey Anon2!II think a lot of MS'ers (myself included) take a high dose of Vit D3 just in case. As Prof G says, it's good for your bones anyway. And whilst there's no studies that prove any effect on MS as yet, it's cheap, safe, easy to take, no side effects and has other health benefits so it seems (to me) like a bit of a no-brainer.It's difficult because if you read everything on the net, you'll end up taking hundreds of supplements which are untested, but for me, there's enough circumstantial evidence and evidence of other health benefits (bone health) from D3 to make it worthwhile. Personal choice I guess.
Hi MD and MD2,I know you guys don't work on the basic science behind cognitive dysfunction but would you be able to point me in the direction of who is?I am extremely worried about the slow processing speeds / memory lapses etc. It freaks the hell out of me.Thanks...
Dear migiTrudi Pickin of Barts Health is speaking on this subject at our upcoming research day. If you're not attending the talk will be uploaded to the web afterwards.
Hey Team G.Hot off the press... New study from Moscow on HSCT, with the majority of the patient population being progressive. Interesting..!Note that these results come from a study using a BEAM-like regimen, rather than the Cyclophosphamide + Rituximab protocol they use there today (which itself is due to be published next year).http://www.ncbi.nlm.nih.gov/pubmed/25711670
Hey we know about this and it is in the in-box of prof G if he aims to comment
Sorry - just to flag that the reason I'm bringing this particular study to your attention is that over half of the patient cohort had progressive forms of the disease.
This is just an observation. For around 15 years (may be more) before my onset of MS I had a small patch of hair on the back of my head, top of neck area which is like afro hair. Very crinkly and curly looking and to touch. The rest of hair is much straighter. After my first relapse another afro hair patch appeared on a different area of my head. I have a few patches now and I've had several relapses. I looked into it a bit and it was suggested that these hair changes may have a neurological cause.
In the news today about drinking coffee may reduce risk of getting MS. I gave up coffee quite a few years ago as I'm sensitive to it, even decaffeinated.
I remember seeing a simple chart on here some time ago which mapped out all the DMT's for efficacy and risks at a glance. It may have been on a presentation slide by Prof G. I found it very useful at the time and thought it may be worth putting up as a sticky on here if you've still got it.
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