ABSTRACT
BACKGROUND: Different subregional patterns of hippocampal involvement have been observed in diverse multiple sclerosis (MS) phenotypes. OBJECTIVE: To evaluate the occurrence of regional hippocampal variations in clinically isolated syndrome (CIS) patients, their relationships with focal white matter (WM) lesions, and their prognostic implications. METHODS: Brain dual-echo and three-dimensional (3D) T1-weighted scans were acquired from 14 healthy controls and 36 CIS patients within 2 months from clinical onset and after 3, 12, and 24 months. Radial distance distribution was assessed using 3D parametric surface mesh models. A cognitive screening was also performed. RESULTS: Patients showed clusters of reduced radial distance in the Cornu Ammonis 1 from month 3, progressively extending to the subiculum, negatively correlated with ipsilateral T2 and T1 lesion volume. Increased radial distance appeared in the right dentate gyrus after 3 (p < 0.05), 12, and 24 (p < 0.001) months, and in the left one after 3 and 24 months (p < 0.001), positively correlated with lesional measures. Hippocampal volume variations were more pronounced in patients converting to MS after 24 months and did not correlate with cognitive performance. CONCLUSION: Regional hippocampal changes occur in CIS, are more pronounced in patients converting to MS, and are modulated by focal WM lesions.