Relationship between inflammatory lesions and cerebral atrophy in multiple sclerosis

Abstract

To investigate the temporal relationship between inflammation and cerebral atrophy in a longitudinal study of 19 patients with relapsing-remitting multiple sclerosis (RRMS) using serial monthly contrast enhanced MRI examinations and monthly measurements of brain fractional volume (BFV) for an average of 4 (range 2.4 to 10) years. In this retrospective study, all patients had an active MRI scan at entry with a minimum of two new contrast enhancing lesions (CEL) on baseline MRI examinations. Patients were followed for a minimum of 3 months during a baseline (pretreatment) phase and subsequently followed during treatment with recombinant interferon beta (IFN) and various other immunomodulatory agents. Pre- and post contrast axial images were obtained using 3-mm slice thickness and a gadolinium contrast dose of 0.1 mmol/kg. Monthly CEL were sequentially numbered on hardcopy films and monthly BFV was determined on precontrast T1W images using a semiautomated program. For BFV measurements, all T1W scans were registered to the entry examination, which served as a mask image. Cerebral atrophy was measured as percent brain fractional volume change (PBVC) compared to the entry baseline scan. The results demonstrate that cerebral atrophy paralleled that of contrast enhancing lesion accumulation. The correlation between cumulative CEL and PBVC ranged from R2 = 0.47 to 0.81. Immunomodulatory agents that effectively reduced CEL accumulation also slowed the rate of atrophy. The correlation between contrast enhancing lesions (CEL) and atrophy suggests that patients who are not responding to therapy with a decrease in CEL may also be at risk for developing increased atrophy.