Changes in brain volume loss vary as multiple sclerosis (MS) progresses, according to results published in JAMA Neurology.

In addition, different imaging methods used to assess changes in brain volume have limited reproducibility. These results suggest that the proposed brain volume loss of <0.4% per year as a marker of therapeutic efficacy should be reconsidered.

The study included participants with clinically isolated syndrome or MS (n=140). Participants underwent a series of annual magnetic resonance imaging (MRI) scans. MRIs from 2 cohorts of healthy controls were used to evaluate short-term repeatability of MRI measurements (n=34) and annual brain volume loss (n=20). The researchers measured goodness of fit for different models of how brain volume loss changed throughout MS disease course. They used correlations of the changes in the brain using Functional Magnetic Resonance Imaging of the Brain Software Library (FSL) and Jacobian Integration (JI) to measure compatibility of imaging methods.

Participants with clinically isolated syndrome or MS underwent 4 MRIs with a median interscan period of 264 days. The 2 control cohorts underwent 2 MRIs with a median interscan period of 24.5 and 384.5 days for the short-term and long-term MRI follow-up, respectively.

In participants with clinically isolated syndrome and MS, brain volume loss rates were higher during the first 5 years after MS onset (correlations [R2]=0.65 for whole-brain volume change and R2=0.52 for gray matter volume change). The researchers found that brain volume loss had a direct association with steroids (β=0.280; P=.02) and an inverse association with age at MS onset, particularly in the first 5 years (β=0.015; P=.047).

The researchers found that the results for whole-brain volume loss were reproducible using FSL and JI. JI produced more precise, less biased estimates for brain volume loss for specific brain regions compared with FSL.

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The correlation between whole-brain volume loss using JI and FSL was high (R2=.92), but the same correlations were poor for specific brain regions.

“These findings may have implications for the therapeutic decision-making process, because when the dynamics of [brain volume loss] are considered, a fixed cutoff (eg, <0.4%28) may underestimate the therapeutic response in the first 5 years and overestimate the therapeutic response thereafter. Thus, different targets may be necessary at different stages of MS,” the researchers wrote.


Andorra M, Nakamura K, Lampert EJ, et al. Assessing biological and methodological aspects of brain volume loss in multiple sclerosis [published online July 2, 2018]. JAMA Neurol. doi:10.1001/jamaneurol.2018.1596