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  • does flair T2 hyperintense lesion on an mri report mean inflamation currently present ?
    if not how is inflamation present phrased in an mri report i.e would it be enhancing lesion ?
    whats the diffrence between enhancing lesion and hperintensity ? any info or feedback is apreciated 🙂 also is there any other research apart from the info on ms society you are aware of on alpha lipoic acid ?

  • I signed up to your blog email updates a while back.
    The postings by Professor Giovanonni are clear in terms of where they have come from.
    Who is the ‘MouseDoctor’; I guess there are several as this latest posting is from No 2.

      • ‘It’s a secret’
        Cloak and Dagger, I like it!

        What’s the significance of the name ‘mousedoctor’?
        It implies you are not a real doctor or a much smaller version, and that you squeak instead of speaking.

        Please excuse my impertinence!

  • Hi MD,

    Slightly random question and you may not know the answer : I’ve always carried an organ donor card, but now I’ve been diagnosed with MS will I still be allowed to donate my bits and pieces or are they deemed not healthy? I know that it’s my brain and spine that are taking a kicking and I’m in the process of sorting out where samples of them will go but what about other organs and my eyes and stuff?

  • Hi again,

    Relapsed 4 years after HSCT (with great effects).
    Checked my EBV levels and the IgG are still high. Does it mean that chemotherapy hasn’t cleaned them from the virus? What next steps to take – deplete B cells to keep MS away?


  • Please could you give your opinion on whether gabapentin has neuroprotective qualities? i have just come off amitriptaline following Prof G’s posts about anticholinergics. Gabapentin has been prescribed as an alternative means of symptom control but when i read your post about GABA drugs (i know that gabapentin is not one, despite the name) it wasnt clear to me whether gabapentin fell into the same camp as Baclofen in that is had neuroprotective qualities regardless of the mechanism

    Thank you

  • Citrulline Malate is a dietary supplement, that acts as a nitric oxide booster, and it is used to relieve fatigue (quite successfully it seems).

    There has been one study for C.M. and MS fatigue which was quite successful.

    However, nitric oxide has been implicated in the pathogenesis of MS (ProfG article).

    Do you think it would be safe to supplement with CM for fatigue relief?

  • What’s the current understanding of Natalizumab and the COVID risk? I assume this has changed since March because we know that COVID encephalitis is a thing now.

  • Do you have any theories on why Ocrelizumab may actually make patients worse? these cases are increasingly being reported on the facebook group. I know that the high percentage for which it works are likely to be the quieter ones and that there will always be a small percentage for which treatments are not effective but to actual make patients worse is another matter

    • Hi,

      Just to follow up on your question; that is my observation too!!! I have followed FB groups for Ocrevus and Rituxan, and like you state, there are scaringly many pwRMS who report significant worsening on Ocrevus, while the Rituxan group is filled with praise and joy. I’m not talking side effects as in infections etc., I’m talking deterioration of functioning!!!

      • One hypothesis may be that people failing on other drugs are the ones going on Ocrevus now. Rituxan folk may have been on it for longer and earlier in the disease course. Also lot of PPMS folk on ocrevus

  • Ampyra – dalfampridine – Writing from the states, and I believe not approved by NHS in England. This said, can you provide any overview of what data say about possible benefits/risks? I am a PPMS patient that has been diagnosed 20 years – SC lesions, on Ocrevus, exercise daily, healthy diet,, but disease impacting gait(EDSS of ~4; left food drop and hip flexor weakness, resulting in swing and hitching of gait). Hoping some benefit to my gait by using Ampyra. I understand you can not give individual medical advice but what do the data show in terms of % of positive effect? Why does NHS not approve? I assume limited efficacy and the high costs, even for generic. My health plan will cover it. Do potential benefits warrant a trial? I have watched the marketing videos by manufacturer and the gait improvements seem small. This said, I have heard of “super responders”.

  • Are there any updates you might be able to give on the risk profile/treatment of PML in Tysabri patients with Extended Interval Dosing? I’m reluctantly back on after 11 years, having failed on other DMDs. Thanks for any info 🙂

  • Hi Prof G,

    Some people already are questioning what your thoughts are on Ocrevus causing worsening function over time. I am interested in this as well, but I experienced worse balance on the 2nd day post infusion, which lasted for 2 weeks or so. I’m not sure it’s fully back to 100% of what it was before.

    From your experience, any idea why a patient might have such a reaction? Would this occur with each and every 6mthly infusion? Am I more at risk for “deterioration” due to the drug in the long run as other have mentioned?

    Best wishes,

  • Been overseas (below average hygiene condition, under extreme stress but lower MS risk country) for 6 months just before onset, then diagnosed at onset 3 months after relocated back to Australia, no more extreme stress and consistent environment factors. Would the moving back have an impact on disease progression giving no longer exposed to extreme stress and challenging living conditions? On Ocrevus since onset.

  • Dear Barts team,

    In 2001 there was a study about remyelinating Schwanncells. Obviously that didn’t work out. Can anyone of you please explain what didn’t work?

    With the knowhow of 2020, is it worth considering to have another look at Schwanncells for remyelination?

    Thanks and regards,

  • LONG COVID – any data concerning PwMS? Fatigue is bad enough with MS without something else adding a long term dose of it!

    The Covid Symptom Tracker App – used by around four million people in the UK – found 12% of people still had symptoms after 30 days. Its latest, unpublished data, suggests as many as one in 50 (2%) of all people infected have long-Covid symptoms after 90 days.
    Do you need severe Covid to get long Covid?
    It appears not.
    Half of people in a study in Dublin still had fatigue 10 weeks after being infected with coronavirus. A third were physically unable to return to work.
    Crucially, doctors found no link between the severity of the infection and fatigue.

  • If I remember correctly there was a study (maybe the OBOE) in actrims2020 on OCB in ocrelizumab patients saying that they did not disappear but that a change was observed both qualitatively and quantitatively. Can you please comment?

    What is your prediction about the head to head comparison between ocrelizumab and fenebrutinib study by Roche? Who is going to be the best in your opinion?

  • Hi MD & all,

    Lots and lots of questions….:)

    If you had to recommend to a patient, that was on maximum pregablin dose but still felt gnawing pain throughout the day in the legs and forearms and oddly the left neck muscle and the right side of head (specifically behind the ear!) – what additional help, support or meds would you suggest?

    If you also had severe muscle stiffness and spasms apart from Baclofen, which medication or advice would you give?

    If you have been on a treatment and coincidentally you are plagued with a infection that only by taking an antibiotic long-term, seems to quash the infection – what are you thoughts on is it the treatment causing the infection and how do you prove that? Or is it something else, which no one in UK seems to want to address. Especially when you ask your MS team the question – they confirm that ‘it isn’t something that they have come across!’ Anyone out there…who wants to help!?!

    Lastly, tee-hee (not really I have soooooo many questions regarding the disease!) – but I will stick to this as being the last urgent one! When someone is treated with a DMD – how do you monitor a patient? Is there a standard list of questions you ask regularly – or do you need physically to see how the patient is walking – gait assessment – flexibility – sensation test – numbness assessment. Infection rates etc? There doesn’t seem to be a standard procedure to measure or assess that can be done over the telephone and I totally understand the problems COVID is causing and the need to keep ALL parties safe – but may be this should be something that can be set-up so patients don’t feel that they have been left and not monitored correctly.

    Thanks for the platform to ask all these questions and looking forward to hearing more on Cladribine and what impact that will have on a person in general over the years.

    Take care and stay safe,

  • Dear Team G
    I am on Ocrevus since 3 years. I have just received the results of a blood test. According to this analysis my b cells are completely gone. Is this what is wanted? I thought that b cells should only partially disappear? Had my last inufsion in July. Unfortunately my neurologist is on holiday.
    Thanks a lot

  • Hi,
    My apologies if my English is not up to standard, as I’m not a native speaker.
    I’ve been doing some reading on serious infections, and/or adverse events linked to DMTs. It struck me that the papers I’ve read rarely define what qualifies as a ‘serious’ (or opportunistic) infection, or – to a lesser extent – an ‘adverse event’. I gather this is considered to be self-evident, but it seems to me there’s quite a difference if an infection is thought of as serious only if it requires hospitalization and/or emergency rooms visits (e.g. Warny et al., PLOS Medicine November 2018) or if other criteria, such as duration (e.g. chronic infections) or impact on patient autonomy, are used. Moreover, the infection or adverse event in question would also need to be diagnosed and reported in order to be taken into account. Here it would seem that there’s a certain amount of confirmation bias involved, in so far as, in the papers I read, there’s a tendency to limit the focus on previously reported or well-known adverse events or (serious) infections.
    Would you agree?

  • Good day.

    I see copious amounts of information on this blog, mostly about pathological processes driving MS progression but almost solely focused on errant immune system cells. Also multiple sclerosis is known as a multifactorial disease, and is many times referred to as such in the medical literature.

    My question is why doesn’t anyone here really discuss those other factors? Such issues as widespread mitochondrial dysfunction. Or the ongoing findings of previously unknown sophisticated and influential connections between gut microbiome and the brain.

    It seems that decades of researchers focusing mostly on B cells and T cells, and their constituents, hasn’t really produced much more than deeper questions and possibly, maybe somewhat of a probable chance of slowing disease progression… in some people. But then again, no one is really sure.

    • I can speak for myself, but I post on what sparks my attention. I have little to say on lifestyle diet alternative therapies, it is not it my remit to give advice. ProfG may do this. I post what is relevant to the research we are doing so that when our work arrives you may better understand it.
      Mitochondrial damage yep…our paper with Don Mahad was on mitochondria.i tend to do animal.studies in journals like science and nature and the media, but I don’t do cure of the week. Most of these studies go nowhere in relation to human disease and it takes hours to do these paperslsewhd properly because they need the context reported My view on microbiome is clear you can get `Its amazing and we are all made out of stardust e

    • Were you at my talk today online…it seems this paper is haunting me today…perhaps have a close look at the results rather than the abstract.

  • Furthermore, we detected that patients with a predominantly memory/balanced B cell phenotype had a lower EDSS score when compared to patients with predominantly naive peripheral B cells. This comes as a surprise, as memory B cells are thought to have a more proinflammatory phenotype (8), and their increase worsens the clinical activity of MS (17).

    Well so manny years listen the oposite 🙂

    Go figure

  • Hi
    I’ve been following this blog since my diagnosis last year. I find it very informative, though I admit lots of it is way over my head, but I do try to keep up.

    I’ve noted the strong suspicion that EBV or other virus is in some way driving MS, and I read re patients on antiviral fairing better in terms of disability progression, if post IRT like hsct one should stay on low dose of acyclovir indefinitely /beyond current (Variable) guidelines to try and suppress such virus as EBV / CMV /VZ

    • Yes and no. The article is about mortality only. I am sure the Swedish economists have priced into the equation what the costs of x number of mainly elderly people dying versus the other mainly hidden impacts of COVID-19, i.e. the effects on mental health, the longterm social determinants on health, education of children and the short and long term effects on the economy. There is a lot of deep thinking that has gone into their strategy that has yet to manifest itself.

      Dealing with COVID-19 is like a game of chess. A game of chess is divided into three distinct phases, (1) the Opening, (2) the Middlegame, and (3) the Endgame, each of which has its own strategies (although there are many strategies that apply equally to all three). Please remember we are still in the Opening. I think we need to wait for the Endgame before throwing stones at the Swedes. I personally think although they have lost the Opening on one metric they much yet be declared the winners after the Endgame 😉

      • 🙂

        Microglia good

        and bad

        Eating myelin debris makes microglia happy

        Objective: Traumatic brain injury (TBI) induces neuroinflammation and white matter injury (WMI). It is suggested
        that neuroinflammation, more particularly microglial activation, could promote WMI over time. Depending on its
        microenvironment, activated microglia can adopt either a pro-inflammatory (M1-like) or an antiinflammatory/
        immunoregulatory phenotype (M2-like). Our laboratory contributed to show (1) that TBI induces a
        mixed population of microglial phenotypes and (2) that this microglial activation precedes the demyelination,
        which results in myelin debris production. Several studies suggest that these myelin debris might in turn increase
        neuroinflammation by promoting M1-like phenotype, thus forming a vicious circle. However, other studies
        challenge this hypothesis. In this context, we evaluated the myelin debris effects on microglial polarization on
        primary culture of murine microglia.
        Material and methods: To mimic physiological conditions, microglia were incubated with mouse myelin debris
        (40 µg of proteins/ml) for 6 or 24 hours. LPS was used as a positive control of M1-like phenotype.
        To mimic the post-TBI inflammatory environment, microglia were co-incubated with pro- or anti-inflammatory
        stimuli (TNFa 50 ng/ml or IL-4 20 ng/ml, respectively) and myelin debris for 24 hours.
        Phenotypes were characterized by RT-qPCR, western blotting, immunofluorescence staining, and nitrite assay.
        Myelin debris phagocytosis was evaluated using cytochalasin D.
        Results: Under physiological conditions, myelin debris did not modify microglial phenotypes.
        Under pro-inflammatory conditions, myelin debris myelin debris not only decreased the M1-like phenotype, but
        also promoted the M2-like phenotype. Under anti-inflammatory conditions, myelin debris increased the M2-like
        phenotype. Phagocytosis inhibition reduced myelin debris effects.
        Conclusion: Our study shows that myelin debris do not induce a M1-like phenotypic shift, but on the contrary,
        identifies, for the first time, myelin debris as potential endogenous antiinflammatory components following TBI.
        Moreover, their beneficial effect is partly mediated by their phagocytosis by microglia. Future work will have to
        identify (1) which phagocytosis pathway(s) is(are) particularly involved, and/or (2) other mechanism(s) such as
        those triggered by myelin debris lipid components

  • As a tysabri user, I was pleased to be told I have reverted back from JC+ -> JC- after 1 year of being on the low end of positive.

    While this is good, I am a little confused as to How this happens? Does it mean I am actually negative or the level so low it’s non-detectable?

    My nurse suggested it could be related to me being on 6 weekly doses, but i don’t understand the correlation .


    • Wow this is interesting and I would love to see some a response on this, I had figured that like other virus’ JC would never leave our body once exposed, but perhaps the numbers can go low enough to be not detectable. I was diagnosed last year and my JC tither was 4+ and I was upset as it limited my drug choices. It would be good to know if this change going forward. I did find and article


      ‘seven of 109 patients (6.4%, 95%‐CI: 2.6%–12.8%) changed serostatus during the study, i.e., converted and reverted between negative and positive serostatus. No patient in our cohort converted from negative to positive anti‐JCV antibody status and remained consistently positive thereafter’

    • JC virus positive means antibody positive.

      Natalizumab allows cells to get into brain to clear the virus and I guess it clears the virus so may be the push that makes the B cells make antibody are gone

    • The study was done in mice in a model that has more similarities with relapsing MS than progressive MS and whilst it does not appear the effect was driven by immunosuppressive issues, we know that macrophages have to clean up debris to repair. Is tremelose the answer? Let’s wait until proper studies are done others say “his rise in dangerous C. difficile infections coincided with more and more of the sugar trehalose being added to foods”.

  • Is bladder pain an MS symptom?
    I have intermittent UTI’s and ongoing bladder pain. The local bowel and bladder service are more bladder maintenance than investigation, covering scanning for urine retention, advice on incontinence pads and catheters.
    I know we shouldn’t assume everything a pwMS has is caused by the MS and a urology appointment might be more appropriate in this case?

  • Finally Biogen come clean and drop the useless drug Anti-Lingo inspite their spin on the data of a parabolic efficacy. I remember barts getting very excited and getting shot down when I said it was just marketing exercise to recoup losses from the cost of the trial. Hey feel like prof G getting vindicated for doing a study 20 years ago (then sitting on it) in microgiala pathogen in MS and having the study results being confirmed 20 years later by a junior researcher. Just hope Biogen show the same honesty in their alzhimiers drug aducanmub.

  • Another stupid drug fails, that went to phase 3 on basis of 13 % showing improving. Pointless drug MD1003 and pointless trial.

    • Thanks for this In this report they have discovered a new type of immune cell that not only rescues damaged nerve cells from death, but partially reverses nerve fiber damage. The research team also identified a human immune cell line, with similar characteristics, that promotes nervous system repair……Sound great. A new neutrophil subset promotes CNS neuron survival and axon regeneration, Nature Immunology (2020). DOI: 10.1038/s41590-020-00813-0 , http://www.nature.com/articles/s41590-020-00813-0. They crush a nerve and the new neutrophils arrive and repair the damage.

      However, the main point here is that you hear “Neutrophil” and “mouse” and then I start to worry. Mousers have been working on EAE and they find neutrophils in the tissues. Indeed in some models we have worked with they make up 80% of the infiltrate into the brain. Therefore there is a move that says neutrophils are very important in MS. They shout hard and loud and the EAEers believe this and are happy to work with the mice and their neutrophils.

      However, if you look in a guinea pig, and a rat there is essentially not a neutrophil to be seen because it is well known that allergic reactions in mice are full of neutrophils. I have seen this. However look in MS and neutrophils are hard to be see. So are neutrophils important in MS? Where is the evidence? Or is is it that it is the Mousers who say it is important..

      This study is about Ly6G. LY6 also known as lymphocyte antigen 6 or urokinase-type plasminogen activator receptor (uPAR) is family of proteins that share a common structure but differ in their tissue expression patterns and function. A total of 35 human and 61 mouse Ly6 family members have been identified. So now we have a problem Ly6G does not seem to be present in humans. In mice the Ly6G neutrophils expressing Ly6G are thought to harbour suppressor cells and the neutrophils causing the repair are immature have low levels of Ly6G but express Arg1 and Nerve growth factor. There is a neutrophil cancer cell line that produces nerve growth factor, which other cells produce to promote nerve health. There are plenty of studies looking at gene expression in the CNS can they be found. They we can start to get our hopes up. Neutrophils remove debri as do other cells and you have to do this to repair.

      • Thanks so much for a prompt and detailed reply MD!
        Sorry to prove to be a signed up member of the layperson club, but I’ve read your reply as: don’t get excited coz with regards neutrophils – work is being done in mice (different to other wee beasties) Also due to neutrophils being hard to see in MS.
        This is when you’re so glad your colleagues are fellow scientists 🤣

        • You tell me but immature is age of the neutrophil, not the age of the producer of the neutrophils. They have a life span on about 5 days

  • This is a really really really good one

    High fat or ‘ketogenic’ diets could prevent, reverse heart failure

    Thus, these studies suggest that consumption of higher fat and lower carbohydrate diets may be a nutritional therapeutic intervention to treat heart failure,” McCommis said.

    Like ketogenic diet, prolonged fasting increases the cardiac reliance on fatty acid oxidation and reduces ketolytic flux despite increased cardiac ketone body delivery. The 24-hour fast reduced blood glucose levels, and strongly enhanced plasma concentrations of non-esterified fatty acids and ketone bodies.


  • So Imperial College London say antibody levels to COVID-19 have been dropping rapidly? So much for reinfection likely being a rare event.

      • I think the point is that we do not know. And no one should be making wishful thinking assertions at this stage.

        • We do know; read the literature (see Science article below) and follow the London COVID-19 data it is clear we are getting close to herd immunity and that is only with a seroprevalence rate of anti-SARS-CoV-2 antibodies of ~30%.

          Mateus J, Grifoni A, Tarke A, et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science. 2020;370(6512):89-94. doi:10.1126/science.abd3871

          Preexisting immune response to SARS-CoV-2: Robust T cell responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus occur in most individuals with coronavirus disease 2019 (COVID-19). Several studies have reported that some people who have not been exposed to SARS-CoV-2 have preexisting reactivity to SARS-CoV-2 sequences. The immunological mechanisms underlying this preexisting reactivity are not clear, but previous exposure to widely circulating common cold coronaviruses might be involved. Mateus et al. found that the preexisting reactivity against SARS-CoV-2 comes from memory T cells and that cross-reactive T cells can specifically recognize a SARS-CoV-2 epitope as well as the homologous epitope from a common cold coronavirus. These findings underline the importance of determining the impacts of preexisting immune memory in COVID-19 disease severity.

    • I disagree with your logic.
      Immunology 101 says you mount an immune response and get rid of the virus and then you stop your effort into making an immune response as it is not needed. Therefore you immune response will wane over time. For COVID-19 we know that the antibody response may only be high for a few weeks, we also know that if you are asymptomatic, possibly because you got a low load of virus, you make low levels of antibody and they disappear quickly. If you are old you have a weaker immune response and so there will be less antibodies.
      Now in March we went into lockdown so you get infected make an antibody response and in lockdown never see the virus again. Immunology 101 says the antibody levels will drop. The half-life of an antibody (time taken for half to disappear) may be in over of 2-4 weeks so every month the level drops by a half. So by June there is 3 half-lives and the level will drop to an eight of the original level. This what you would expect if re-infection was a rare event.
      If you are be re-infected then you would anticipate that you will make a new immune response and could even boost the level of antibodies. So if antibody levels are dropping re-infection is rare.
      In Kuwait they monitored 130,000 people and found about 50 with evidence of re-infection of which only 1 person was hospitalised, suggesting that re-infection was low. Similarly re-infection in a Mexican study of 100,000 people showed low re-infection rates.
      However immunology 101 says it doesn’t matter about being re-infected once you are immune because you will deal with the infection better than you did in the first place. This is called immunity. People will encounter SARS-CoV-2 again most people do OK second time round but there are a few cases where the person is hospitalized on the second exposure. In monkeys infected with SARS-CoV-2 the level of virus increased over 3-5 days after infection and then decreased to undetectable within 10 days. They had high levels of antibody and on re-exposure the animals got a temperature for a day but the virus was not detectable…This is immunity.

      • In the Colonial (Imperial) College study 6% of people had antibodies on the first screen and 4% on the second screen and the levels dropped by 30%. Hospital workers only dropped by 3%…Why?
        It is likely that they were re-exposed to the COVID-19 virus boosting their response. E.g first contact with alemtuzumab only about 60% of people make anti-drug antibodies with a level of about 400 on second exposure about 80% of people have antibodies within a month and have antibody levels of a few hundred thousand. In addition if the health care workers were exposed to more virus they would have had a stronger immune response…so the antibody levels may not drop as fast. However in London it was evident that the occurrence of antibodies was about 17% when it was only a few percent in the rest of the country. This showed that Londoners had been more exposed to the virus and if anyone has been on a Tube in London you know that you rammed together in an environment perfect for spreading infection.
        However do low antibody levels mean you can be re-infected. Sure it can but if you are fully immune who cares you get rid of the virus. If you need antibody you will make it within a few days second time around rather than a few weeks first time around. B cells that make antibodies divide a lot and have a shorter life than T cells. So whilst antibody levels may have dropped the T cell levels may not. Importantly as macrophages and T cells are important in getting rid of the virus , not having a big antibody response may not be important.
        We know that people who are asymptomatic may make a poor antibody response but they make a T cell response and remember about 80% of people are asymptomatic possibly because their innate (macrophages) give a great response as occurs in young people which we know repair MS well because their macrophages can clear damage and possibly because they have been exposed to viruses that protect against the SARS-COV2. For vaccine responses we are measuring response to essentially one antigen the receptor binding domain of spike because this protein is used for infection. Block it an no infection occurs. However T cells can recognise any of the 30 proteins in SARS-OV-2 to be able to recognise the cell is infected and get rid of it and it is clear that cold-causing coronaviruses produce cross-reactive T and B cell responses that may give partial of perhaps complete protection against COVID.

  • Some Covid Survivors Have Antibodies That Attack the Body, not Virus
    New research found ‘autoantibodies’ similar to those in lupus and rheumatoid arthritis patients. But patients may also benefit from treatments for those autoimmune diseases.

    To worry or not to worry?

    • Antibodies in covid are good and bad, I suspect if you are liberating damaged tissues the there is a risk of autoimmunity, on balance I suspect the nornal trajectory is non autoimmunity but that doesnt help if you are one where autoimmunity occurs, such as autoimmunity against alpha interferon

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