Wednesday, 25 November 2015

ResearchSpeak: brain volume loss and disability progression

Do you want to know if you are losing brain volume? #BrainHealth #ResearchSpeak #MSBlog #MSResearch

"I am a big proponent of brain atrophy, or brain volume loss, as an integrator of end-organ damage in MS. Brain volume loss occurs in MS at a rate of between 2-7x the normal rate. Brain volume loss is linked to previous inflammatory activity and is a poor prognostic variable. In other words MSers with progressive brain volume loss do badly; brain volume loss is associated with cognitive impairment and physical disability progression. The analysis below from the fingolimod clinical studies shows that brain volume at baseline was predictive of brain volume loss over 2 years and was highly predictive of disability progression and reaching hard disability outcomes, for example needing to use a walking stick."

"I am not surprised by this data. Why? Disability progression must be linked to loss of axons and nerve cells and this is manifested in brain volume loss. The implications of this is that we need to use treatments to slow, or preferably normalise, brain atrophy rates. The good news is that emerging data suggests we can achieve this with current licensed DMTs. Unfortunately, we are not yet able to reliably implement brain atrophy measures into clinical practice at the individual patient level. This will change with emerging algorithms, or setting thresholds above what occurs as part of day to day variability that occurs as part of the measurement. These latter thresholds will get lower with multiple measurements that will be able to exclude day-to-day variability, particularly if they show a consistent trend over time. Our centre is in the process of testing brain atrophy measurements to see if we can start using them in clinical practice. Would you want your brain volume measured as part of your annual assessment?"

Epub: Jeffery et al. The relationship between the rate of brain volume loss during first 24 months and disability progression over 24 and 48 months in relapsing MS. J Neurol. 2015 Nov 14.

Background: Clinical evidence in patients with relapsing-remitting multiple sclerosis suggests an association between MRI outcome measures and disability progression (DP). 

Objective: Post hoc analysis to investigate the association and potential predictive value of brain volume loss (BVL) with long-term DP in FREEDOMS (Gilenya study). 

Methods: Patients were categorized into quartiles by SIENA-calculated percent brain volume change from baseline to month (M) 24. Patient characteristics at baseline were determined for each quartile, as were the proportions of patients at M24 and M48 reaching Expanded Disability Status Scale (EDSS) scores of ≥4.0 or ≥6.0 or DP confirmed at 3 months (CDP3) or 6 months (CDP6), and change in EDSS and Multiple Sclerosis Functional Composite. 

Results: MS disease activity and severity as well as brain volume at baseline were predictive of subsequent BVL over 24 months. The quartiles of patients with greater BVL at 24 months were at highest risk (odds ratio, p value) for reaching EDSS ≥4 (2.8, p = 0.001) or ≥6 (5.73, p = 0.0005) and experienced more DP at M24 (CDP3 2.13, p = 0.002; CDP6 2.17, p = 0.003) and M48 (CDP3 1.98, p = 0.006; CDP6 1.87, p = 0.018) compared to the quartile of patients with the least amount of BVL. 

Conclusions: These findings confirm the clinical relevance of early brain volume changes for long-term DP.

CoI: multiple


  1. Dear Prof G,

    Since my diagnosis I have learnt a great deal from this site. Thank you all.

    I would like to really learn how to read an MRI both for my care and other family members with MS. How could I do this? I don't understand the 4 shots above are these slightly different cross sections? Why does baseline look more like 12 months than 6 months?

    Btw, because of this site, I did ask about brain volume after my first annual MRI.

    1. Enjoy

      Tony Fonda

    2. Tony - what an excellent link you have provided - have saved it for future reference for my own MRIs and reports. Will also be sending it on to quite a few other people like me who want more understanding. Thank you.

      Aidan - if you haven't already found it, this article on this blog is also excellent, and provides really good explanations about the brain and MRIs in language normal people can understand

  2. At my last annual check, my neuro did not even do a clinical exam. While discovering my MRI with me, he told that he might have spotted a new lesion. It was a baseline MRI so no change in treatment. I know you want to perform annual check fast. But a clinical exam would have been better than the result of a rebasing MRI. In short, volume loss measure are not interesting without a clinical exam. Don't you think?

  3. Do chronic T1 hypointense lesions that we see on MRI's represent the dying of nerves and axons that lead to brain volume loss in RRMS?


      Tony F

  4. Didn't I read you were doubting the affects of alemtuzumab atrophy rates? Something about falsely thinking atrophy was back to normal when actually you thought it might be inflammation forming again? Thanks


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