Mechanisms of central brain atrophy in multiple sclerosis

Background: Change in ventricular volume has been suggested as surrogate measure of central brain atrophy (CBA) applicable to the everyday management of multiple sclerosis (MS) patients. Objectives: We investigated the contribution of inflammatory activity (including the severity of lesional tissue damage) to CBA. Methods: Fifty patients with relapsing-remitting multiple sclerosis (RRMS) were enrolled. Lesional activity during 4 years of follow-up was analysed using custom-build software, which segmented expanding part of the chronic lesions, new confluent lesions and new free-standing lesions. The degree of lesional tissue damage was assessed by change in mean diffusivity (MD). Volumetric change of lateral ventricles was used to measure CBA. Results: During follow-up, ventricles expanded on average by 12.6% +/- 13.7% (mean +/- SD). There was a significant increase of total lesion volume, 69.3% of which was due to expansion of chronic lesions. Correlation between volume of combined lesional activity and CBA (r(2) = 0.67) increased when lesion volume was adjusted by the degree of tissue damage severity (r(2) = 0.81). Regression analysis explained 90% of CBA variability, revealing that chronic lesion expansion was by far the largest contributor to ventricular enlargement. Discussion: CBA is almost entirely explained by the combination of the volume and severity of lesional activity. The expansion of chronic lesions plays a central role in this process.