About the author

BartsMSBlog

68 comments

  • Question about the “flipping the pyramid” strategy.

    We know now that, statically, pwMS have better outcomes when high efficacy DMTs are taken early.

    But what about pwMS with current DMT and being NEDA-3 ? Do we have elements / facts to answer the following question : ‘what is the benefice / risk ratio for pwMS well controlled with their current DMT (NEDA3) to switch to a more aggressive DMT’ ?

    Thanks in advance!
    Best,

  • Question about the EBV hypothesis

    I know that Doctor G. think EBV infection could be the cause of MS. If so, how can we explain the big difference of pwMS’s percentage among western coutries ?

    Thanks !

    • “how can we explain the big difference of pwMS’s percentage among western coutries ?”

      Easy one it’s genetics or more exact CD8+ T cells that can’t control EBV .

      I had HSCT for MS my sister had HSCT for SAA. Not a coincidence.

      In MS autoreactive CD8+ cells attack brain and SAA they attack bone marrow.

      “CD8+ T cells were seen, which affirmed that EBNA-1 gene insertion had a strong influence on the function of CD8+ T cells in patients with SAA patients. CD8+ T cells are key pathogenic cells of SAA, and our study showed that EBV infection is likely to be a vital factor in the activation of CD8+ T cells, further damaging the bone marrow hematopoietic function in patients with SAA.”

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976969/

      Yes..totally ignore nonsense put here that hsct doesn’t work in progressive ms.

      • Thanks, Anono for your answer! Very interesting.

        So, if I understand well, it’s means that Americans are (in mean) genetically more predisposed (EBNA-1 gene insertion, etc.) than French to have their CD8+ T cells activated to EBV infection?

        But, if so, what is the origin of this genetic difference?! I mean, two centuries ago, white Americans and white Europeans were the same people.

        I also read (can’t find the numbers) that the American percentage of pwMS in the general population have increased a lot since 1960 (I mean more than the EU percentage in the same period). Someone can confirm that? If so, how can we explain this difference?

  • Hi!

    Thanks for providing us with this opportunity.

    Question #1:
    During the trials with cladribine, or from other experience databases, has there been observed any pattern for when relapses are most likely to occur during the 4 year treatment period?

    Question #2:
    Can the timing of when to re-treat with cladribine be determined by blood samples/ tests? If so, are we likely to see the label to be updated with such recommendations any time soon?

    Question #3:
    With DMTs like cladribine, alemtuzemab and rituximab, will vaccines have to be refreshed due to the drugs wiping out the cells forming memory of viruses?

    Question #4: Can infections, viral or bacterial, trigger MS attacks (not pseudo attacks)?

    Thanks!!

    • Question #1: During the trials with cladribine, or from other experience databases, has there been observed any pattern for when relapses are most likely to occur during the 4 year treatment period?

      No. About 10% of pwMS treated with cladribine breakthrough per annum.

    • Question #2: Can the timing of when to re-treat with cladribine be determined by blood samples/ tests? If so, are we likely to see the label to be updated with such recommendations any time soon?

      At the moment we don’t know, but we hypothesise that we may be able to use the memory B cell repopulation kinetics to decide.

    • Question #3: With DMTs like cladribine, alemtuzumab and rituximab, will vaccines have to be refreshed due to the drugs wiping out the cells forming memory of viruses?

      Cladribine, no. It does not deplete the T-cells that much. Similarly, there is no evidence that alemtuzumab culls the memory T cell responses. With myeloablative HSCT the routine is to revaccinate. In term of rituximab and other anti-CD20 therapies, we don’t know as it will depend on the duration of treatment. What we do know is that once you are on an anti-CD20 you respond very poorly to vaccines. In other words, you need to be vaccinated before starting treatment.

    • Question #4: Can infections, viral or bacterial, trigger MS attacks (not pseudo attacks)?

      Yes, this is well known. About a third of relapse are preceded by an infection.

      • I asked my UK consultant MS neuro about this in the last year or so and they said “there’s no evidence infections lead to an MS relapse” (not pseudo relapse).
        I know that you know the neuro that I mentioned Prof G, and I am as baffled as you probably are.

  • Please don’t roll your eyes. Please think about Gadolinium. Do you feel like Multiple Sclerosis patients are receiving too many cumulative doses and retaining this toxic heavy metal? I’ve received 9 doses in 7 years on CombiRx study. Is there any thought of studying people like myself who feel we have symptoms of toxic metal retention?

    • More research is needed. There is not enough evidence to say categorically that gadolinium-based contrast agents (GBCAs) are toxic. The older generation linear GBCAs carry a greater risk than the so-called macrocyclic or non-linear agents, and that there is a greater risk for certain patient populations. I think that in someone with normal kidney function the risks are low.

      The European Medicines Agency (EMA) has recommended restricting the use of some linear gadolinium-based contrast agents (GBCAs) and suspending the marketing authorizations of others, citing concerns about gadolinium deposition. But, the EMA said it supports the continued use of macrocyclic GBCAs. The EMA has also stated “there is currently no evidence that gadolinium deposition in the brain has caused any harm to patients. However, the EMA has recommended restrictions for some intravenous linear agents in order to prevent any risk that could potentially be associated with gadolinium brain deposition.”

      The EMA recommended suspending the marketing authorizations of GBCAs Magnevist (gadopentetate dimeglumine), Omniscan (gadodiamide) and OptiMark (gadoversetamide). The group cited the benefit-risk balance is no longer favourable for certain linear GBCAs. But, the EMA recognized certain linear GBCAs are still needed for liver imaging, so retained Primovist (Eovist in the U.S., gadoxetate disodium) and MultiHance (gadobenate dimeglumine).

      Not sure this helps.

      • I think what you’re saying is what I have heard as well. I don’t need you to agree with me or accept my thoughts as facts. As I told my neurologist, here are my symptoms, here is my hypothesis. If you see others with similar symptoms please think of me. Gadolinium is a Toxic Heavy Metal. Paramagnetic. Sourced in China. Makes Pharma a fortune. I have not seen the Safety studies. I don’t believe they exist. I reported my symptoms to the USA FDA. If I have retained Gad in my brain, bones, connective tissue, who can say it’s ok? Now gadolinium being found downstream from medical centers with MRI’S. It can’t be filtered out in wastewater treatment facilities. Gadolinium has become so routine. Had a workup for ankle mass and I refused it and had 4 people question me about why. I explained that Gadolinium Enhancement would not be definitive enough. A plain MRI adequate. The oncologist agreed with me. Please consider my concerns and the concerns of others like me. I’m willing to be wrong. Show me study that says “it’s safe”. I’m looking for quality/purity testing. Are there impurities like arsenic in gadolinium refinement? Do miners have ill effects? I don’t need you to answer. Just be aware.

        • I am aware that gadolinium is probably not inert and there reports by regulators perhaps neurofilament with overtake the need for gadolinium

        • We only use Gad for diagnostic scans and the re-baselining scan after starting a DMT. After that standard non-enhanced scans should be fine.

          • I was having Gad MRI scans for every annual and relapse related MRI scan, up until about 2 or 3 years ago. I questioned the safety of Gad with the radiographer about 6 years ago and they said it was perfectly safe and not to worry. I was not keen to have Gad at the time but they rested my concerns.

  • Hello,
    I have had my first attack in July of this year, it was so severe that I have almost lost control of the right side of the body. It took a week for an MRI for them to say that I had lésions both in brain and in my back. I got administered IV steroids the following week. It took me at least 2 months to come back together.
    There has been some residual damage left; my right fist still tingles, occasionally I have Hermitte sign and sometimes I have touch sensations in my right leg. Other than that, I feel fine.
    My neurologist has had me done many tests, blood work, lumbar puncture, jcv test etc and he has told me that the tests aren’t conclusive and while that might be so, based on my symptoms he still thinks that it is the MS that I have. He has sent me to do some more tests (anti something..) and to do a lot of vaccines and another MRI and he told me that I should think of the DMT to take. We did not go into specifics yet, but since I am JCV positive, Choices might be less obvious.
    ….sorry I talk too much
    Question: If my test are not conclusive, should I be going for medication asap or should I wait for him to confirm it 100 percent?
    He said, the longer I wait, more irreparable damage I’ll have. And it seems to me that he is not interested much in the first generation of medication.
    He does specialize in MS and has been practicing since 1993.

    I would an honest opinion please.

  • I have been diagnosed with SPMS since 2015, relapsing remitting 2013, and symptoms since 1995. I’ve never had any DMTs. My question is this in the past year I have developed consistently low lymphocyte counts (0.8) which seems counter intuitive, which have resulted in persistent, repeated UTIs. Is this ‘normal’ for someone with MS? I live in fear of picking up an antibiotic resistant infection.

    • I am not aware of untreated pwMS developing unexplained lymphopenia. It is likely to be due to another factor. UTIs tend to relate to local factors (ISC, a raised residual volume, bladder calculi etc.) and not lymphocyte counts.

  • I’ve had some DMF-users tell me that they went to half a dose (some with the consent of their neurologist), and felt noticeably less fatigue, had higher lymphocyte counts, and a stable RRMS. I fully understand the reluctance to endorse this as a general strategy, but is it conceivable that for some individuals half a dose DMF works as a successful DMT?

    • Is that half a tablet twice a day or one tablet once a day? DMF fumarate is taken twice a day so that drug remains in the body based on the earlier tests, but this may be different in some individuals.

      • they took 2×120 mg (the ‘starters’ dose), rather than the normal 2×240 mg – so it is not a stretch that the 2×240 mg is generally more effective (and therefore recommended as a rule), but that in some individuals, 2×120 mg is sufficient (and has less side-effects)?

        • Personally, I don’t buy this “one size fits all” approach. How can be 2x240mg equally effective (and have same rate of side effects) in person with 150 kg vs a person with 50 kg? One could be under and the other overmedicated.

  • If a person is already receiving regular rituxamab infusions but then develops MS like symptoms will it effect lumbar puncture oligoclonal band results, i.e produce a false negative result.

  • How close would you say we are from having neuroprotective and remyelinating agents?

    If not very close, are there any other possible developments in the short term (say, in the next 5 years) that you think should be a good reason for PwMS to be optimistic? Anything you’re really looking forward to and that might plausibly be a game changer?

    Thank you for all your brilliant, super illuminating work.

    • We have them already, they just need to be proven and universally used.

      I hope that our team will start to give people the option and let us get some real life data like we have with cladribine.

      If you live in the UK and are willing to take part in the trials that are on the cards then you may have neuroprotective and remyelination therapy on offer.

      These have been in the planning for a few years and are at an advanced stage. I can’t say more.

      • “I hope that our team will start to give people the option and let us get some real life data like we have with cladribine.”

        Eagerly waiting for your cladribine&OCB long term data!

          • Didn’t you (Or ProfK, don’t remember exactly) said somewhere on this blog that you already have LP samples collected from previous off-label clad usage, but you of course need to get new consent to use that in a new research proejct? I bet that majority of these patients will agree to extra tests on these existing samples…

          • Is this a formal study or just an off hand comment. I’m debatably eligible for cladribine treatment under nice, after a profoundly bad ms summer, but my consultant is a bit conservative so looking for observational type trials at other centres as a route of getting a second opinion…..

  • Are there any studies that have looked at post partum relapses after Lemtrada? Having had both rounds I’d love to have a child but the thought of a relapse terrifies me especially as I’m currently NEDA

    Thanks

  • The flue is a known trigger of ms relapse yet flu vaccine is not as effective on people taking ocrevus or similar meds. What is your position on prophylactic flu antivirals if flu epidemic hits your community? Yes/no and if so when to start (ie how do you define “exposure “).

  • Nervous system comtrol the immune system

    Eavesdropping on intimate ‘crosstalk’: Communication between immune and nervous systems in vaccination

    A stunning and unexpected twist in the research was discovering that responses by the immune system are regulated by neurons responsible for sending pain signals. If these neurons are compromised, Tracey and his team additionally found that inflammation becomes pervasive, leading to inflammatory disorders.

    https://medicalxpress.com/news/2019-12-eavesdropping-intimate-crosstalk-immune-nervous.html

    • Look in progressive EAE. The number one dysregulated pathway is the Cholesterol Pathway, look at Alzheimers Disease the number one dysregulated pathway is the Cholosterol pathway. So after discovering that Cholesterol pathway genes are dysregulated in motor neuron disease and the Eureka moment, the authors should have done a reading moment…Do statins cure MS….No, will they cure Motor Neuron Disease….No. Is it interesting sure it is.

    • Yes, but if I told you, I’ld have to kill you:-)

      For most of my life it was plain flour , pinch of salt, eggs milk and abit of water, more recently I have been weighing starting with 100 g of plain.flour, pinch of.salt.two eggs mix and add about 120-140ml of milk..

      The key is a hot.oven and hot fat/oil get it hot.fill the tin and don’t open the oven. I prefer the Yorkshire to sink when you take it out of the oven after 10-15mins rather than over.cook to get a crisp Yorkshire that doesn’t sink.

  • I started Ocrelizumab as part of a clinical trial a few years ago. When I started it stated to wait 6 month for a pregnancy, in the latest consent form now it states 12 months. Can anyone explain me this change? If its half life is 26 days and anyway doesn’t cross the placenta for the first three months (or so I read in a study) what would be the risk for the fetus after 6 months? Thanks for any answers

    • The trial was based around the US usage, and in USA and Australia, you only have to wait for 6 months from last dose before attempted conception, but in Europe the wait is twelve months as they are being more cautious, because you are wrong about it not crossing the placenta. Some babies from CD20-treated mums are born without any B cells because ocrelizumab and other IgG1 antibodies do cross the placenta. The 600mg dose is overkill for most people and with the half life of about a month it will be depleting for many months as a 10-20mg dose depletes virtually all peripheral blood B cells. So you can see that half is there after one month, a quarter after 2 months, so you can see at 6 months there is still enough antibody to deplete in most people. This can get across the placenta. Now you (the foetus) do not start to produce B cells until about 9 weeks (in the fotal liver) and you do not have a spleen until about 3 months gestation. Therefore there are no foetal B cells to target until about 9 months after the last dose. These could lose B cells. However, if babies are breast fed, they will get maternal antibodies even abfter birth and get protection from infections, so despite the potential for depletion, to date affected infants have I believe done OK.

      Based on the unpublished phase II data CD19 depletion ranged lasted on average 72 (18 months) weeks (range 27 [6-7 months] – 175 weeks [3 years] and as we know the memory cells are depleted for many months longer than the CD19 suggests that there is perhaps enough time to have a drug-administration free pregnancy. This is why it is important that the phase II trial data is properly aired.

  • Norway
    Rich country

    Anne Hege Aamodt, head of the Norwegian Neurological Association, refers to the recent decision by the Resolution Forum, which means that two of the treatment options MS doctors have had available are removed from the list of alternatives that doctors can put on new patients.

    She explains that there is concern in the professional community that the Decision Forum decided that the use of natalizumab (Tysabri) and fingolimod (Gilenya) on new patients should be stopped from December 1, 2019 due to price.

    https://www.dagensmedisin.no/artikler/2019/12/23/nevrologileder–legene-instrueres/?fbclid=IwAR3Hae6APnGHshMpHbzOK_0H7OM4OHpu4glQab5FPUjv2BAeRhx7mcbboDs

By BartsMSBlog

Translate

Categories

Recent Posts

Recent Comments

Archives