Mechanisms of central brain atrophy in multiple sclerosis

Abstract

Background and objectivesThe measurement of longitudinal change in ventricular volume has been suggested as an accurate and reliable surrogate of central brain atrophy (CBA), potentially applicable to the everyday management of patient with multiple sclerosis (MS). To better understand mechanisms underlying central brain atrophy in RRMS patients we investigated the contribution of inflammatory activity in different lesion compartments to the enlargement of ventricular CSF volume. In addition, we investigated the role of the severity of lesional tissue damage in CBA progression.MethodsPre- and post-gadolinium 3D-T1, 3D fluid-attenuated inversion recovery (FLAIR) and diffusion tensor images were acquired from 50 patients with relapsing MS. Lesional activity between baseline and 48 months was analysed on FLAIR images using custom-build software, which independently 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 as a measure of central brain atrophy.ResultsDuring follow-up ventricles expanded on average by 12.6+/-13.7%. There was significant increase of total lesion volume, 69.3% of which was due to expansion of chronic lesions and 30.7%-to new (confluent and free-standing) lesional activity. There was high degree of correlation between volume of combined lesional activity and CBA (r2=0.67), which became considerably stronger when lesion volume was adjusted by the degree of tissue damage severity (r2=0.81). Linear regression analysis explained 90% of CBA variability and revealed that chronic lesion expansion was by far the largest contributor to ventricular enlargement (Standardized Coefficient Beta 0.68 (p<0.001) for expansion of chronic lesions compared to 0.29 (p=<0.001) for confluent lesions and 0.23 (p=0.001) for free-standing new lesions). Age and baseline ventricular volume also provided significant input to the model.DiscussionOur data suggest that central brain atrophy is almost entirely explained by the combination of the volume and severity of lesional tissue activity. Furthermore, the expansion of chronic lesions plays a central role in this process.