Was George Wrong? Relapse Matter

When CCSVI was in its hayday, the believers would question the immune theory and trot out the suggestion that having relapses didn’t matter.

Perhaps not surprising it they had read the Work from The George Ebers Lab

Early relapses, onset of progression, and late outcome in multiple sclerosis. Scalfari A, Neuhaus A, Daumer M, Deluca GC, Muraro PA, Ebers GC. JAMA Neurol. 2013; 70:214-22

“Our results indicate dissociation between early inflammatory attacks and onset of the SP phase and further question the validity of relapse frequency as a surrogate marker for late disability”.

This new paperTomassini V, Fanelli F, Prosperini L, Cerqua R, Cavalla P, Pozzilli C. Predicting the profile of increasing disability in multiple sclerosis. Mult Scler. 2018 Aug 2:1352458518790397

BACKGROUND: Effective therapeutic strategies to preserve function and delay progression in multiple sclerosis (MS) require early recognition of individual disease trajectories.
OBJECTIVES: To determine the profiles of disability evolution, identify their early predictors and develop a risk score of increasing disability.
METHODS: We analysed demographic, clinical and magnetic resonance imaging (MRI) data from patients with relapsing MS, Expanded Disability Status Scale (EDSS) score of 3.0-4.0 and follow-up ≥ 2 years. Attaining EDSS = 6.0 defined increasing disability; relapses and/or MRI defined disease activity.
RESULTS: In total, 344 out of 542 (63.5%) patients reached EDSS ≥ 6.0; of these, 220 (64.0%) showed disease activity. In patients with activity, the number of relapses before reaching EDSS 3.0-4.0 predicted increasing disability; age > 45 at baseline predicted increasing disability without activity. Combining age and number of relapses increased the risk of and shortened the time to EDSS = 6.0.
CONCLUSION: Increasing disability is frequently associated with persistent activity. The high number of relapses identifies early those patients worsening in the presence of activity. Age predicts increasing disability in the absence of activity. The presence of both factors increases the risk of developing severe disability. As this study likely describes the transition to progression, our findings contribute to improving patient management and stratification in trials on progressive MS.

Score = 0, if the patient was ≤45 years and experienced ≤6 relapses before reaching an EDSS of 3.0–4.0;

Score = 1, if the patient was >45 years or, alternatively, experienced >6 relapses before reaching an EDSS of 3.0–4.0;

Score = 2, if the patient was >45 years and experienced >6 relapses before reaching an EDSS of 3.0–4.0.

To further evidence that relapses are not good, Don’t have them.

More effective treatments were associated with a better outlook

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  • Come on MD, the argument is always as follows:
    1. Relapse is a mix of traumatic CNS damage and immune response to it.
    2. Drugs dampen the immune response and thus ameliorate the perceived relapse.
    3. Background CNS trauma continues.

    Is there a natural history-with drugs study that proves their long term impact on MS?

    What is your definition of relapse? Pathological, not clinical.

    • People who unfortunately have died on natalizumab do not show CNS trauma, indeed I have heard of a case where there was fantastic remyelination, suggesting that if you can get inflammation under control repair can occur. Hence ProfGs concern that we are putting alot of resource in repair, when perhaps the best driver of repair is to get disease under control and let the natural repair mechanisms do their job

    • Natural History data…there is quite abit on CRAB drugs, but this is frankly not sufficiently informative enough as they are frankly not good enough. There is the long term follow up of the Cambridge alemtuzumab cohort.

  • If diet, mindfulness/meditation, stress management and exercise perform better than all/any of the DMD's is it possible/probable that if a px does not attend to the above they will have relapses and progression?
    Is it also correct when you look at the same insight from the direction that when a DMD is stopped there will be a change in disease progression that is often a worsening over time.
    If the triggers in diet such as gluten and dairy are not intelligently and correctly tested when ruling out MS in the dx process, such as a zonulin serum test and a trigger food elimination diet of at least 3 months preferably 6 months of both gluten and dairy then reintroduction to check for symptomatic changes, then is the dx of MS bogus if this is not part of the work up for finding a cause of symptoms and then the label of the outcome of the symptom package?
    There seems to be an elephant in the room 'again' if trigger foods and stress events are not assessed.
    CCSVI is real and the published papers are corrupted by the reductionism system and the lack of intelligent assessment by unbiased Pharma pawns, imo BTW.

    • Diet, meditation, stress management, excercise and CCSVI do not perform better than DMTs. That's called wishfull thinking, not science (you can't even manage IBS with these, not to mention MS!)

  • Rounded..the numbers are 75%..65%..55%
    This is only 15 years..given enough time
    all will turn progressive. The first compassionate
    care to get immunotherapy had enhancing lesions
    and IgG go way down..none of these DMT's can do this
    so not good treatments and not good use of funds on
    studies like this of "old" treatments. Money should
    be axon sprouting research as this patient had EDSS 8
    and that is only thing that will get him out of a chair.
    Going forward research needs to justify itself to be useful.


    • Money on sprouting..Maybe we have to ask why has the human central nervous system evolved to not sprout. I suspect because it has undesirable consequences

    • People who injured their legs/arms and didn't axon sprout probably
      didn't thrive..People who injured their CNS probably all died so
      evolution never had a chance to act.
      Maybe stem cells is away to help SCI patients but how do you
      get them to go to the right place and stay there.

  • Can CCSV not explain, for example, why more women have multiple sclerosis than men, and where would the relationship between Vitamin D and venous stenosis be within CCSV…

  • Why does this contradict with what we now know about MS? Relapses and microglia-related neurodegeneration are part of the same reaction but can evolve independently too.
    We have to move on from the idea that if we prevent effectively lesions and relapses there wont be progression. And I am sure that the idea will be considered obsolete soon.

  • "More effective treatments were associated with a better outlook"

    EDSS 6 was reached by:
    -66% of CRAB users (median follow up in years=6.6)
    -64% of patients under immunosuppressants (median follow up in years=6.3)
    -52% of tysabri recipients(median follow up in years=5.0)

    How much better is 52% compared to 66% when the former is from 1.6 years less follow up?

  • as someone with ms, I hear peoples frustration and anger, yet I don't see why this concepts so hard to follow

    if we have a relapse in the wrong (or right!?) place, it could lead to irreversible disability….

    if we have ongoing activity without relapses, the damage over time to the brain can eventually lead to a point where "the straw that breaks the camels back" will be an apt description….

    DMTS can prevent nasty lesions that might be the last one you could get away with.. or stopping accumulation of damage stops your brain shrinking and becoming helpless to deal with the inevitable aging process that everyone will go through….

    I don't hear anyone calming there are any guarantees with any of this time. they tend to be more anal in the detail then anyone…
    they present DMT x can prevent lesions by x % on average over x time.
    the risks of getting x are y… and so on, and so on.

    I don't believe anyone is saying there wont be progression by stopping relapses.. but there is a chance to reduce the progression. which is the whole point… we might all end up at a really bad place with our MS…or we may not… but to prevent wherever we will end up … by 5 to 10years. or even 1 or 2 years… that's the point…no?

  • "PPms patients dont have much relapses(if any)
    Are they better of reading this?"

    Good point..thanks for the reminder.
    tv actress Annette Funicello went
    21 years with PPMS This Canada news video
    goes into her CCSVI try(15:00) and other
    wacko therapies. Sad/hard to watch so much disability
    ..if it's all just from a simple EBV virus.

    here she is one year in on a talk show 1993

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