Progressive decline in fractional anisotropy on serial DTI examinations of the corpus callosum: A putative marker of disease activity and progression in SPMS

Introduction: Clinical trials of secondary progressive multiple sclerosis (SPMS) is lacking reliable biomarkers or outcome measures that reflect tissue injury incurred within a 1-to 2-year observation period. Diffusion tensor imaging (DTI) is sensitive in detecting acute brain tissue damage. We monitored SPMS patients over 12 months for diffusion changes within the corpus callosum (CC). Methods: Bimonthly MRI examinations over a 1-year period were performed on 11 SPMS patients. The protocol included postcontrast T1-weighted images and DTI. Based on the appearance of T1 enhancing lesion(s) during the study period, the patients were divided into enhancing (five patients) and nonenhancing (six patients) groups. Fractional anisotropy (FA) and mean diffusivity (MD) of the genu, body, and splenium of the CC were measured and temporal changes in mean FA and MD were evaluated for each group as well as between groups. Immunology data from peripheral blood mononuclear cells were also collected on a monthly basis. Results: The enhancing group showed significant, progressive decrease in FA in body (p=0.012) and splenium (p=0.033) of CC, and significantly higher lymphotoxin-β levels. No significant FA changes were seen in the nonenhancing group. Moreover, the FA decline in the enhancing group deviated significantly from the nonenhancing group, which remained essentially stable. Although MD increased slightly in both groups, there was no significant difference between the two groups. Conclusion: Based on the MR and immunology findings, the results of our study suggest that DTI undergo more rapid and longitudinal changes in SPMS patients with inflammatory activity.