Should Brain Volume Loss Be Used as a Marker of Therapeutic Efficacy in MS?


Researchers aim to determine whether an annual brain volume loss rate of less than 0.4% is a valid marker to assess treatment response.

Brain volume loss may not be an adequate marker for determining the efficacy of a treatment in patients with multiple sclerosis (MS), according to a new study published in JAMA.

Prior research has indicated that brain volume loss (BVL) and brain lesion atrophy are associated with physical disability in patients with MS, and that disease-modifying therapies can reduce the rate of BVL. In the study, the researchers aimed to evaluate whether a BVL rate of less than 0.4% annually can be used as a valid marker to assess treatment efficacy.

For the study, a cohort of 140 patients who had either clinically isolated syndrome (CIS) or MS was enrolled from February 2011 through October 2015. All patients underwent a series of annual magnetic resonance imaging (MRI) scans, using 2 methods: Jacobian Integration (JI) and the Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL). The patients with CIS or with MS underwent 4 MRI scans at roughly 1 year intervals. Two groups of healthy participants underwent 2 MRI scans.

According to the findings, the BVL rates were higher in the first 5 years after MS onset, with a direct association with steroids and an inverse association with age at MS onset. The researchers indicated that the younger a patient is at MS onset, the faster the rate of gray matter volume loss.

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“Considering an expected loss of 0.5% to 1.35% per year, the poor repeatability of 2 separate imaging methods prevents their use at the individual levels,” the researchers wrote.

Based on the results, the researchers concluded that the proposed BVL threshold of less than 0.4% per year as a marker for therapeutic efficiency should be reconsidered. Further clarification is needed before promoting brain volume loss as a marker for therapeutic response in MS, the authors wrote.


Andorra M, Nakamura K, Lampert EJ, et al. Assessing biological and methodological aspects of brain volume loss in multiple sclerosis. JAMA Neurology. 2018. doi:10.1001/jamaneurol.2018.1596

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