Will the real MS stand up again


Uher T, Krasensky J, Malpas C, Bergsland N, Dwyer MG, Kubala Havrdova E, Vaneckova M, Horakova D, Zivadinov R, Kalincik T. Evolution of Brain Volume Loss Rates in Early Stages of Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2021 Mar 16;8(3):e979.

Objective: To describe the dynamics of brain volume loss (BVL) at different stages of relapsing-remitting multiple sclerosis (RRMS), to describe the association between BVL and clinical measures, and to investigate an effect of treatment escalation on the rate of BVL.

Methods: Together, 1903 patients predominantly with RRMS from the Avonex-Steroids-Azathioprine cohort (N = 166), the study of early IFN-β1a treatment cohort (N = 180), and the quantitative MRI cohort (N = 1,557) with ≥2 MRI scans and ≥1-year of follow-up were included. Brain MRI scans (N = 7,203) were performed using a single 1.5-T machine. Relationships between age or disease duration and global and tissue-specific BVL rates were analyzed using mixed models.

Results: Age was not associated with the rate of BVL (β = -0.003; Cohen f2 = 0.0005; adjusted p = 0.39). Although disease duration was associated with the rate of BVL, its effect on the BVL rate was minimal (β = -0.012; Cohen f2 = 0.004; adjusted p = 4 × 10-5). Analysis of association between tissue-specific brain volume changes and age (β = -0.019 to -0.011; adjusted p = 0.028-1.00) or disease duration (β = -0.028 to -0.008; adjusted p = 0.16-0.96) confirmed these results. Although increase in the relapse rate (β = 0.10; adjusted p = 9 × 10-9), Expanded Disability Status Scale (EDSS; β = 0.17; adjusted p = 8 × 10-5), and EDSS change (β = 0.15; adjusted p = 2 × 10-5) were associated with accelerated rate of BVL, their effect on the rate of BVL was minimal (all Cohen f2 ≤ 0.007). In 94 patients who escalated therapy, the rate of BVL decreased following treatment escalation by 0.29% (β = -0.29; Cohen f2 = 0.133; p = 5.5 × 10-8).

Conclusions: The rate of BVL is relatively stable throughout the course of RRMS. The accelerated BVL is weakly associated with concurrent higher disease activity, and timely escalation to high-efficacy immunotherapy helps decrease the rate of BVL.

This idea of brain volume loss being relatively constant throughout your MS history is not a new one, but I just wish that people would start doing studies on the higher efficacy agents used as first line, rather than getting the constant trickle of CRAB studies. This will show the need to add treatments to deal with the smouldering lesions.some people think it is the real MS….it certainly is the MS that is not being effectively dealt with

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  • Do you think Natalizumab is a good drug to stop smouldering lesions ? I have been taking Natalizumab for 5 years and it has been my first and only drug since I was diagnosed with MS 5 years ago. I have been taking it for about a year with an extended interval of 6 weeks between each infusion.
    Thank you MouseDoctor

  • All the study’s into brain volume loss seam to be in patients with secondary progressive ms. Which is great as it identifies what works and what doesn’t

    When treatments are found to significantly slow brain volume loss, will they be prescribed to patients with RRMS and PPMS?

    Hopefully a phase 3 can be done on lipoid acid soon enough, crazy that it’s taken so long as it seams to be the best treatment found to slow brain volume loss as you know. Organic flax seed oil from Amazon for example, £5 – bargain and natural.


    • I think you might have alpha lipoic acid (which had some promising clinical trial results for BVL) mixed up with alpha linolenic acid – which is the Omega-3 in flax. I thought the exact same thing when I first heard of ALA. I am a fan of both ALA’s 🙂

  • I’m switching from tecfidera to ocrevus because I’ve had cognitive changes (memory, focus, attention span) in the last year and so I’m worried about smoldering MS. (I’m not sure I’ve had a relapse.) Will the ocrevus help?

  • Is it/should it be a standard procedure to measure BVL in pwMS?
    I have 3 MRI’s spread over almost 2 years and they never mentioned anything about BVL to me.
    Conclusion is that my brain is normal and i have a stable spinal form of PPMS.
    This raises the same question about spinal cord volume loss.

    • BVL has to be be calculated and is not standard…they may not mentionit because they haven’t measured it

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