Introduction. Neurodegeneration is likely to be present from the earliest stages of multiple sclerosis (MS). MS responds poorly to disease-modifying treatments (DMTs) and leads to irreversible brain volume loss (BVL), which is a reliable predictor of future physical and cognitive disability. Our study aimed to discover the relationship between BVL, disease activity, and DMTs in a cohort of patients with MS.

Material and methods. A total of 147 patients fulfilled our inclusion criteria. Relevant demographic and clinical data (age, gender, time of MS onset, time of treatment initiation, DMT characteristics, Expanded Disability Status Scale (EDSS), number of relapses in the last two years prior to MRI examination) were correlated with MRI findings.

Results. Patients with progressive MS had significantly lower total brain and grey matter volumes (p = 0.003; p < 0.001), and higher EDSS scores (p < 0.001), compared to relapsing-remitting patients matched by disease duration and age. There was no association between MRI atrophy and MRI activity (c2 = 0.013, p = 0.910). Total EDSS negatively correlated with the whole brain (rs = −0.368, p < 0.001) and grey matter volumes (rs = −0.308, p < 0.001), but was not associated with the number of relapses in the last two years (p = 0.278). Delay in DMT negatively correlated with whole brain (rs = −0.387, p < 0.001) and grey matter volumes (rs = −0.377, p < 0.001). Treatment delay was connected with a higher risk for lower brain volume (b = −3.973, p < 0.001), and also predicted a higher EDSS score (b = 0.067, p < 0.001).

Conclusions. Brain volume loss is a major contributor to disability progression, independent of disease activity. Delay in DMT leads to higher BVL and increased disability. Brain atrophy assessment should be translated into daily clinical practice to monitor disease course and response to DMTs. The assessment of BVL itself should be considered a suitable marker for treatment escalation.