Is gadolinium enhancement predictive of the development of brain atrophy in multiple sclerosis? A review of the literature

Background and Purpose. Several studies have demonstrated that brain atrophy can be detected over relatively short intervals from the earliest stages of multiple sclerosis (MS). Reviewing the published data, the authors highlight some hypothetical pathological mechanisms proposed as determinants of brain atrophy. Methods. Using the terms multiple sclerosis, MRI (magnetic resonance imaging), and brain atrophy, 181 citations were identified. The authors considered only studies with prospective designs with natural-course MS patients and/or placebo-treated patients of therapeutic trials, in which patients under-went baseline and follow-up scans with a T1-weighted gadolinium diethylenetriamine penta-acetic acid sequence (0.1 mmol/kg body weight), and correlation analyses between Gd enhancement activity and brain atrophy progression. Results. Five hundred thirty-two patients of 5 natural history studies and 5 therapeutic trial studies participated in the review process. The main observation was that in patients with a relapsing-remitting (RR) disease course, there was a correlation between Gd enhancement activity and brain atrophy progression. This correlation was not influenced by any other demographic and clinical additional data considered in the review process. Conclusions. Examination of the pathological mechanisms proposed in the reviewed studies led the authors to believe that inflammation is only in part responsible for the development of brain atrophy. This conclusion may have an implication for the strategies of tissue protection advocated in the early stages of the RR course and strengthen recent evidence indicating that anti-inflammatory immunomodulatory agents and immunosuppressive treatments, which predominantly act against the inflammatory component of disease activity, may not have similar effects on progressive tissue loss, either in RR or progressive MS.