Brain atrophy and magnetization transfer ratio following methylprednisolone in multiple sclerosis: short-term changes and long-term implications

Abstract

The short-term effect of corticosteroids on MRI measures of multiple sclerosis (MS) is not well understood and may have a significant impact when using these quantitative measures to evaluate disease activity and changes following other therapeutic interventions. To determine the impact of a course of intravenous methylprednisolone (IVMP) on quantitative measures of disease activity and tissue injury in MS patients. We prospectively measured brain parenchymal fraction (BPF), magnetization transfer ratio (MTR, lesional and whole brain), and lesion volumes on nine weekly brain MRI studies in ten MS patients receiving a course of IVMP. A group of nine MS patients not receiving IVMP served as controls. In comparison to untreated controls, BPF declined over the eight weeks following IVMP treatment (P <0.02). BPF decline was most prominent in patients with secondary progressive MS (SPMS, P <0.03), and was not seen in relapsing-remitting (RR) MS patients. Short-term change in BPF correlated with baseline BPF (r =0.62, P =0.05) and short-term change in lesional MTR (r = -0.55, P =0.03), but not with change in enhancing lesion volume. Short-term change in lesional MTR inversely correlated with baseline lesional and whole brain MTR (r = -0.79, P =0.04 for both). There was no significant difference between treated and control patients in measures of MTR or T2, T1 or enhancing lesion volumes. Patients with SPMS showed a greater decline in BPF following IVMP than RRMS patients. A correlation between changes in BPF and MTR suggest that these changes are secondary to altered water content within MS lesions. Differential response to a standardized therapeutic intervention in RRMS and SPMS suggests that responses to therapy may differ due to a fundamental pathologic difference between early and late stage MS.