Cubed

How do we colour in each block of this cube?

Making a decision about which DMT to prescribe, or preferably to help your patients make a decision, many of my colleagues mix up their priorities. For example, some mix-up baseline prognostic profiling and disease activity, and then some of them throw disease-stage or disability progression into the mix. I think this occurs because these factors are somewhat related, but only tell part of the story.

Disease activity (DA) – Disease activity (DA) really refers to the here-and-now and what has happened in the last 12-24 months. DA does affect prognostic profiling (PP), but it is only one component of PP.

DA refers to recent focal inflammatory activity and hence is defined as relapses in the last 2 years and focal MRI activity, i.e. new or enlarging T2 lesions and Gd-enhancing lesions, in the last 12 months. More recently raised at Barts-MS we have also incorporated raised CSF neurofilament levels in the last 12 months.

In the UK/NHS we have 4 categories of DA:

  1. Inactive
  2. Active
  3. Highly-active
  4. Rapidly evolving severe

Inactive MS – If you have had no relapses in the last 24 months, and serial MRI studies covering this period show no new lesions, then your MS is defined as being inactive. This does not mean your MS is necessarily stable. I have said that you could have worsening disability as part of the progressive phase of the disease without focal inflammatory activity. If you have so-called inactive MS you need to be monitored, as inactive MS may reactivate and you could then become eligible for treatment.

Active MS – Most neurologists require evidence of disease activity in the last 24 months, with most accepting a 12-month window if there is MRI support. Our current criteria for active MS incorporates MRI into the definition, which allows us to treat so-called high-risk patients with CIS.

Highly-active MS – These are MSers with unchanged or increased relapse rate, or ongoing severe relapses compared with the previous year, despite treatment with beta interferon, or another so-called first-line DMT. Another category refers to treatment-naive MSers with two attacks in a 12 month period with MRI evidence of activity during this period.

Rapidly-evolving severe MS – Rapidly-evolving severe MS (RES) is defined as two disabling attacks in a 12 month period with MRI evidence of activity during this period.

Prognostic Profiling (PP) – Prognostic profiling (PP) really refers to baseline factors that have been linked to poor prognosis. Although several of DA metrics are associated with a poor prognosis they are a small part of the prognostic profiling metrics I personally use. The following is a list of 24 prognostic factors I tend to use in clinical practice. In general, if you have four or less you fall into the good prognostic category, five to eight the intermediate prognostic category and if nine or more the poor prognostic category.

  1. Age of onset (<40 vs. >40 years) (1)
  2. Sex (F vs. M) (1)
  3. Sites: unifocal vs. multifocal onset (1)
  4. System:
    1. Motor:  no vs. yes (1)
    2. Cerebellar: no vs. yes (1)
    3. Bladder: no vs. yes (1)
    4. Cognition
      1. Impairment: no vs.  yes (1)
      2. Learner: yes vs. no (1)
  5. Recovery: complete vs. partial or no recovery from initial relapses (1)
  6. Relapse rate: low/ ≤ 2 vs. high / >2 in the first 2 year (1)
  7. Early disability: EDSS < 3.0 vs. EDSS ≥ 3.0 within 5 years (1)
  8. MRI
    1. Baseline lesion load: low / <9 T2 vs. ≥ 9 T2 lesions (1)
    2. Active: no Gd-enhancing vs. Gd-enhancing lesions (1)
    3. Posterior fossa lesions: no vs. yes (1)
    4. Spinal cord lesions: no vs. yes (1)
    5. Brain atrophy: no vs. yes (1)
  9. CSF
    1. OCBs (oligoclonal IgG bands): no vs. yes (1)
    2. Raised neurofilament levels: no vs. yes  (1)
  10. Vitamin D levels: low vs. normal (1)
  11. Smoker: no vs. yes (1)
  12. Comorbidities
    1. diabetes/prediabetes: no vs. yes (1)
    2. Hypertension: no vs. yes (1)
    3. Hypercholesterolaemia: no vs. yes (1)
    4. obesity: no vs. yes (1)

      Total Score out of 24

Disease Stage (DS) – Disease stage (DS) simply refers to the amount of damage accumulated, i.e. how disabled you are. We tend to overlap this with disease descriptors early in the disease course, simply to help deal with treatment guidelines and to set the scene for changing our worldview of MS; i.e. away from a neurological/clinical perspective to a biological perspective (pathology). If we changed our worldview of MS we would almost certainly want to treat MS in the asymptomatic stage to prevent disability. Please note that we still live in an EDSS-centric world and hence the EDSS is used by most people to define disability.

In an ideal world, we would include other metrics, in particular, cognition, to define MS-related disability and include end-organ damage markers (brain volume loss) or other metrics that measure reserve capacity. The latter is critical in defining the resilience of your nervous system to deal with insults in the future including physiological or normal ageing.  

The following is my classification system of DS:

  1. Radiologically isolated syndrome (RIS) with no apparent disability (EDSS = 0)
  2. Clinically isolated syndrome (CIS) with no apparent disability (EDSS = 0)
  3. MS with no apparent disability (EDSS = 0)
  4. MS with mild physical disability (EDSS=1.0-3.0)
  5. MS with moderate physical disability (EDSS=3.5-5.5)
  6. MS with severe physical disability (EDSS=6.0-6.5)
  7. Advanced MS with profound physical disability(EDSS >=7.0)

Although DS may affect treatment decisions we need to get away for the idea that to be treated effectively, i.e. with highly-effective treatments, you need to be disabled. Our current philosophy is to treat early to prevent disability.

In the following slideshow, I try and put all these factors together in a 3D graph. Please note that the grey cubes represent an evidence-free zone and DMTs are typically not used in MSers with these attributes. We are trying to change this with our #TreatEarly, #BrainHealth, #PreventMS and #ThinkHand campaigns.

The colour scheme to denote the level of DMT by risk category is an estimate. I have included this to try an illustrate the complexity of decision making that is involved in selecting DMTs when considering only three factors. This gets even much more complex when you start to incorporate personal factors.

I predict this post will be very controversial. So let me know your thoughts.

CoI: multiple

46 thoughts on “Cubed”

  1. 1) I am assuming from the Graf JCV- natalizumab is classified as moderate risk?

    (Highly active, no apparent & mid disability is yellow, yet prescribed Tysabri under the NICE guidelines)

    2) What is the point of the prognosis axis if we are all exposed to smouldering MS regardless of brain inflammation status (i.e. activity level)?

    3) Where does Very High Risk Therapy (i.e. HSCT) fit in this diagram?

    Tony

    Reply

    1. I simply refer to the agents as tier 1, 2 and 3 to cover how they are used in the NHS. The tiering is again somewhat related to risk, but not exactly. Built into tiering is cost-effectiveness which is how NICE approve agents.

      Reply

      1. Thanks for answering 1) and addressing 3) elsewhere.

        But what about the very important question 2) ?

      2. Qu 2: What is the point of the prognosis axis if we are all exposed to smouldering MS regardless of brain inflammation status (i.e. activity level)?

        There is a hypothesis if you treat MS early and effectively you prevent the substrate for smouldering MS. This is something we want to test in the #AttackMS study. Smouldering MS is complex and depends on many factors, some of which need more study. At the moment it is best to work on the hypothesis that ‘prevention is better than cure’.

      3. But we know that pretty much all patients on highly effective DMTs covert to SPMS in due time, regardless of prognosis factor or risk strata.

        If the outcome is inevitably SPMS, shouldn’t most (/all) patients be considered to have a poor prognosis?

        I know that I am pressing on a very difficult point here, but one that must underscore any treatment decision algorithm in my view.

        Tony

      4. Re: If the outcome is inevitably SPMS, shouldn’t most (/all) patients be considered to have a poor prognosis?

        This position is based on natural history, pre-DMT, data. We don’t know if this applies to treated cohorts of MSers. Who knows a proportion of MSers treated early and effectively with high-efficacy DMTs who a rendered NEDA-5 may never develop SPMS. This is an experiment that is currently running.

      6. Re: Have we forgotten already the work of Bielekova et al. ?

        This is based on trial cohorts using EDSS as an outcome and also short-term outcomes (2-3 years). These patients were not necessarily treated early and to a target.

      7. Thanks again Gavin.

        On a separate note, I am now reading Geneuro’s latest annual report. I am somehow concerned that their partner Servier pulled out before the ANGEL-MS results were even published. CFO says change of strategy (not sure I follow him here as Servier has made no announcements regarding this matter).

        Now a quick search on ClinicalTrials.gov shows that GeNeuro is not designing or recruiting for any trials yet: https://clinicaltrials.gov/ct2/results?term=geneuro&Search=Apply&recrs=b&recrs=a&recrs=f&recrs=d&age_v=&gndr=&type=&rslt=

        I was hopping to see trials of BVL add-ons or other therapeutic alliances with the likes of Biogen… their cash position is not solid enough to allow them to run those trials solo.

        Are the major pharma group doing much in terms of HERV-W at all?

      8. No Pharma company outside of Geneuro, to the best of my knowledge, is interested in HERVs in MS. If any are reading this please get hold of me.

      9. Qu 3: Where does Very High-Risk Therapy (i.e. HSCT) fit in this diagram?

        Again isn’t what is a high-risk therapy in the eye of the beholder? Some MSers would think HSCT is relatively low-risk and want it 1st-line (me included) and others will never take on the risks associated with HSCT. Whereas others may find the risks too high for a specific stage of their life; for example, a young woman may not want to take on the infertility risks and this may be irrelevant to an older woman. For a father with a young family who does not have adequate life insurance, staying alive at least until his family are financially secure, may be an important determinant in terms of risk. The mortality of HSCT is probably in the region of 0.5% (1 in 200) with some units quoting figures of up to 2% (1 in 50).

      10. I did thank you for “addressing 3) elsewhere.”

        But thanks again for clarifying your point.

        Tony

      11. “Who knows a proportion of MSers treated early and effectively with high-efficacy DMTs who a rendered NEDA-5 may never develop SPMS”

        The conjecture is straight forward here then: None of the current DMTs nor the ones in the pipline (Geneuro, etc…) achieve NEDA-5 (not sure about HSCT, but I hear your very well when you expose the risks).

        Then most (/all) patients ought to be considered to have a poor prognosis by this same logic.

      12. “Who knows a proportion of MSers treated early and effectively with high-efficacy DMTs who a rendered NEDA-5 may never develop SPMS. This is an experiment that is currently running.”
        Experiment.??…like the ones Dr. Mengele did..?
        All those patients will be in wheelchairs unless given hsct…Monitoring brain volume will tell you the reality.

      13. There are people on fingolimod, DMF, natalizumab, cladribine, ocrelizumab or alemtuzumab who are NEDA and ‘normal’ brain annual brain volume loss. You don’t need to be treated with HSCT to achieve this aim. On the flipside, there are MSers treated with HSCT who have acclerated brain volume loss. It is not as simple as treating everyone with HSCT.

      14. “There are people on fingolimod, DMF, natalizumab, cladribine, ocrelizumab or alemtuzumab who are NEDA and ‘normal’ brain annual brain volume loss.”

        Are there data confirming what you say? Because we have some data for HSCT and alem., and even in the second normal BVL does not apply for the whole amount of patients treated. Are you referring to daily clinical practice where neuros see an MRI and say “yup, normal”?

      15. “There are people on fingolimod, DMF, natalizumab, cladribine, ocrelizumab or alemtuzumab who are NEDA and ‘normal’ brain annual brain volume loss.”

        In natalizumab/DMF would be cures..yet we all know they aren’t…the question is how long “normal” brain loss. Studies..?

        People who get abnormal brain loss from hsct most likely ones who had brain smoldered away on ineffective DMT’s and
        then no “reserve” to cope with
        secondary progressive or hsct. Hsct at first diagnosis would have cured them and saved them from progressive disease that years of DMT smouldering primed the brain for. Most likely hsct shut off inflammation but already damaged parts
        of brain continue to atrophy.

        Do you really not understand the damage these DMT’s do ???…Wow look no lesions/relapses…never mind brain is slowly wasted away.

      16. Again, it has to be said that hsct is not a one size fits all therapy. The biggest need is to identify effective neuroprotectants that can be used as an add-on to all these therapies. It is a source of much personal frustration that we are still way behind on this, for a variety of reasons.

  2. Please note the colour coding in this 3D graph is based on my personal perspective and will differ depending on which HCP you see. I am even suggesting we consider DMTs in some RISers. This is not the consensus view; in fact, RIS is not MS hence not covered by treatment guidelines and hence won’t be covered by payers.

    Reply

    1. “Again, it has to be said that hsct is not a one size fits all therapy. ”

      Huh…Actually it is the only therapy that completely stops brain inflammation.
      If DMT’s cut all inflammation there’d be no need for nueroprotectants.
      Their need only proves only how ineffective DMT’s are.

      It can not make ms worse than it is. All it can do is speed up brain loss but
      would happen anyway….i.e. Brain cells on the edge of cliff get pushed off from chemo.
      But they were too damaged anyway from years of smolderiing ineffective DMT’s.

      Reply

      1. Anon you are beginning to sound like an HSCT zealot (believing in something without thinking). HSCT is just a rebranding of BMT and a guise for high-dose, or very high-dose, chemotherapy and nothing else. High-dose chemotherapy has been tried in MS before, many times and with mixed results. It is a sledgehammer and what we need are set of molecular tweezers. HSCT is not for everyone and is definitely not the longterm solution to MS.

        HSCT is just another IRT and with time MS reactivates; sadly I suspect in the majority of MSers. Is it better than alemtuzumab? Not sure we have that answer yet as there have been no head-2-head studies. Can I suggest we wait for the completion of the trial?

      2. “Anon you are beginning to sound like an HSCT zealot ‘

        Instead of crying zealot and waiting around forever for trials you might actually learn by doing tests to
        see why some fail/respond…like an actual scientist..as
        opposed to a wanna/be graphic designer w/tubes’n cubes.

        Why did C.Wyatt have such response and then fail..?
        “‘I managed to walk more than ten miles…I hadn’t been able to do that for years” “..suddenly she could thread a needle, so she sewed on buttons” but then”At six months her walking began to get worse:”
        https://www.dailymail.co.uk/news/article-6533923/How-two-BBC-stars-took-different-paths-dealing-MS.html

        For every hsct spms who stops progression for 10 years there is a rr who relapses at 10 years. Hsct is at least on/off
        it doesn’t smolder you for a decade and give you spms.
        [youtube=https://www.youtube.com/watch?v=iiuUPAZvPNg&w=640&h=360]
        http://themscure.blogspot.com/

        “Can I suggest we wait for the completion of the trial?”
        Sorry can’t wait just told of new brain lesion and am progressive..so no rituximab. So hsct is my only treatment option now.

        Besides no-one can get ahold of alem. now anyway. Apparently Burt referred to it as liquid HIV since he thought immune reconstitution is better under hsct.
        How come my post has links and such and yours are
        mostly just colored tubes’n cubes.’n pyramids
        with non-existant treatments labeled “nueroprotectants”

      3. “HSCT is just another IRT and with time MS reactivates; sadly I suspect in the majority of MSers. Is it better than alemtuzumab?”

        Quit it you are attacking a legit therapy as being outside the norm….what norm…taking ineffective drugs that cost $$$.

        18 years no progression…maybe he was only one in the trial..I don’t know.

        Justin Sears: I had HSCT with Dr, Burt in 2001, I was # 26 to have this for MS.

        “Wow! 2001. Justin Sears how have the last 18 years been?”

        Justin Sears: I’ve been ok. HSCT helped a lot and stopped any progression, but MS is still a pain in my backside, especially the whole heat intolerance thing.

        Justin Sears: I am grateful every day that I had HSCT, things were horrible before I had it, and now it’s not as bad. Still evil, just not as bad… I was SPMS going in to HSCT, edss was about 6, I was a mess, and yes, tbi was part of my hsct.

        https://www.chicagotribune.com/news/ct-xpm-2002-06-04-0206040150-story.html?fbclid=IwAR1wbYGKzmm1BW-T4fZUsMpRfx-_A7s2-NutQUdVScHpw9REzaeYf8IvorA

      4. “HSCT is just another IRT and with time MS reactivates; sadly I suspect in the majority of MSers. ”

        Again. Data.
        (for RRMS. we know from trials that half times returns to SPMS, yet 50% is still not that bad)

      5. Data = 46% NEDA at 5 years = minority
        Mortality = 2.8% = high

        Muraro et al. Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. JAMA Neurol. 2017 Apr 1;74(4):459-469.

        IMPORTANCE: Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies.

        OBJECTIVE: To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort.

        DESIGN, SETTING, AND PARTICIPANTS: Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015.

        EXPOSURES: Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen.

        MAIN OUTCOMES AND MEASURES: The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models.

        RESULTS: Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95).

        CONCLUSIONS AND RELEVANCE: In this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results support the rationale for further randomized clinical trials of AHSCT for the treatment of MS.

      6. I asked for RRMS.

        “Seventy-eight percent (218 of 281) of patients had progressive forms of MS. ”

        I already said that for progressive MS about 50% is the average success number, still better than 0%.

        Mortality for the years 1995-2006, myelo-protocol?

        We have been here before, please.

      8. 50% yeah…it’s not bad…there’s no alternative.

        2012 Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

        Lesson 6 Several cohort studies and registry reports have demonstrated that HSCT can result in the cessation of progressive accumulation of disabilities and long-term stability of the EDSS in patients with SP-MS, without the need for ongoing disease-modifying agents. Approximately 45 % of patients have a stable EDSS score at 5 to 7 years after HSCT

        The duration of stability in objective disability measures has been remarkable and appears to represent a marked change in outcome when compared to historical and concurrent MS populations. However, caution should be exercised in interpreting these results as the progression-free survival is lower in studies with longer follow-up [50, 52].
        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557353/

      9. “Again. Data.
        (for RRMS. we know from trials that half times returns to SPMS, yet 50% is still not that bad)”
        50% wasn’t good enough for someone who had it done in Russia for ppms and failed treatment…suicide got him not the chemo.
        The center claims 65-75%ppms rate which
        is outrageous. Have only come across 6 or
        7 on facebook who have been progression free for 4-5 years. Outliers exist though
        one ppms went from 5.5 to 4 from 100 ft.
        walk to 3 miles..was 63 y/o too.

      10. “Data = 46% NEDA at 5 years = minority
        Mortality = 2.8% = high”

        The mortality rate isn’t going to scare most.
        Saw one woman died before she could evengive hsct a try. She was not even high edss but died while she was fundraising to go…she never made it there.

      11. “50% wasn’t good enough for someone who had it done in Russia for ppms and failed treatment…suicide got him not the chemo.”

        Imagine if there was a one and only drug for cancer cure eih 50% success, but it wasn’t offer to patients, That would be called scandal.
        But if you go bankrapt and at the wrong 50%, well you are, at least for the moment, really desperate.

        “The center claims 65-75%ppms rate which
        is outrageous. Have only come across 6 or
        7 on facebook who have been progression free for 4-5 years. ”

        The centers’ claims can be either lies or based on one year results. We must see the data, and the data repeatedly have around this percent 50% or a little less (starting from the first trial in the 90s).
        There are very few treated patients that are PMS been treated 4-5-6 years ago to find them, so there isn’t much to see there, again look at the -not few- studies.

        The problem is that new trials do not want to treat them, so only privately these PMS patients will have their chances. Such a shame really.

  3. I’m probably being really daft, but do you define somewhere in here what DMTs you regard as high, medium & low risk?
    (Really interesting read btw – thank you)

    Reply

    1. I think the risk of DMTs is in the eye of the beholder. For example, some MSers consider natalizumab to be low-risk if they are JCV-ve MSers, but relatively high-risk in JCV+ve MSers. Ocrelizumab is considered low-risk by some MSers and high-risk by others. Similarly, alemtuzumab and HSCT are considered by some MSers low-risk relative to them having MS. This is why working in an environment where all DMTs are 1st-line and the decision to treat with DMT x, y or z is between the MSer and their HCP.

      Reply

  4. Fiddling, Fiddling, Fiddling,

    Prof G,

    Once again you are fiddling while Rome burns.

    I have several issues with the cube:

    – you may get a letter from the lawyers of Ernő Rubik;

    – you need to be Stephen Hawkins to understand what the hell is going on;

    – you are a frustrated graphic designer. First we had the tube map and now the cube! How much time are you spending on these distractions? Your time would be better spent seeing patients and writing up study findings.

    Things need to be simplified. Neuro: following your diagnosis what do you want? Patient: not to become disabled or more disabled. Neuro: to achieve this I would recommend the following treatment. There are the risks if you take this treatment and the risks if you don’t….. neuros need to start behaving like other specialisms and use their knowledge / experience to guide patients (strongly guide) rather than ducking their responsibilities and handing patients complicated graphics or apps.

    Reply

    1. A picture is worth a thousand words. Not sure about being a graphic designer; we have a designer in our group for those sorts of activities.

      Reply

      1. “Fiddling, Fiddling, Fiddling, ….. = Thinking, Thinking, Thinking …
        “0, 0, 0,.. = 0, 0, 0…”
        Not a virologist or immunologist….it’s way out of your box….

      2. Wow, many of these comments are way out of line. The man is simply proposing a treatment model. I also think Prof G has made he’s thoughts on HSCT clear in a number of other posts (advocating for first line therapy). I think people are venting at the wrong person. Perhaps start screaming at the pharmaceutical companies who don’t release the raw data associated with their drugs. Perhaps scream at the HSCT clinics who are not measuring and reporting outcomes in a robust and reliable manner.

    3. you are a frustrated graphic designer. First we had the tube map and now the cube!
      😅 That’s really funny! 🤣

      Reply

    4. “Fiddling, Fiddling, Fiddling,
      Prof G,
      Once again you are fiddling while Rome burns.”
      Hcst is only thing that seems to stop progression and instill normal brain loss rate.
      But it doesn’t work for everyone and sometimes ms comes back.
      Here is Barry Goudy, whom was one of the trial’s first phase II MS patients transplanted in 2003. His disease remains in remission today, +16 years later. Any neurologist that says HSCT doesn’t last very long is clueless…it’s been updated to 2 years ago no progression…… https://youtu.be/Y8SAgUB5hQs
      Justin Seears had HSCT with Dr, Burt in 2001, he was # 26 to have this for MS.
      EDSS 6 after 3 years MS…now walks miles and stopped progression but he still has heat intolerance…
      https://www.chicagotribune.com/news/ct-xpm-2002-06-04-0206040150-story.html?fbclid=IwAR2VxI6pSwL6-PuYe_r1ocDUGpq5iKaRg4_j3SGSG5atRmbNW8nVbAPdPk0

      Reply

  5. I think the way you’ve put this together invaluable. Though you are clear it is your view and will not meet with universal endorsement, I’d like to see it routinely used in pretty much all neurologist training, seminars, meetings etc to engender very useful debate. Further still, I’d like it to be considered by NICE etc as to a very useful tool to inform the approval parameters of DMTs.
    In saying this I’m not ignoring the points made by Tony, but am of the view that the treatment guidelines can and should be open to regular review and revision.

    Reply

  6. My thoughts is that, even as a physician, this cube gives me a headache. Somebody with epilepsy will surely have a seizure.

    Also, call me insane but if one actually attacked a root cause of MS (EBV controlled memory B-cells with the possible trigger of latent HERV DNA affecting microglia, oligodendrocytes, neurons and myelin function) instead of downstream reactions (B or T cells) there would be no need for the partially effective immunosuppressants whether your first diagnosed or a progressive patient.

    Dare to dream of a real solution, instead of a bandaid solution currently given by immunosuppressant only approach!

    PS. The “horse is out of the barn” and the smouldering MS is an issue for the majority of MS patients so #TreatEarly is not an option.

    Reply

    2. “so #TreatEarly is not an option.”
      It is of no consequence as there are no DMT’s that stop ms from smoldering.
      Hsct is the only one one out there and even that’s not 100%.

      Reply

  7. Great post although a bit confusing. I would have been in the low risk area at diagnosis, but my neuro firmly believed in hit it with all you can. 14 years later I am thankful and stable.

    Reply

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