Relationship between inflammatory lesions and cerebral atrophy in multiple sclerosis

Objective: 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. Methods: 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 β (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. Results: 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. Conclusions: 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.