This study investigates structural changes in the hippocampus, fornix, and mammillary bodies in patients with mesial temporal sclerosis (MTS), examining their relationship to clinical characteristics and association with memory performance. We conducted a retrospective study involving 104 patients with unilateral MTS and 47 age-matched healthy controls. Automatic segmentation of MRI scans was performed to calculate volumes, and atrophy was assessed relative to average values in the control group. Volume differences between patients and controls as well as associations of circuit atrophy with clinical features and memory impairment were examined. In the left MTS group, all three structures showed significantly lower normalized volumes compared to healthy controls whereas atrophy was confined to the hippocampus and fornix in the right MTS group. No significant correlations were found between atrophy and disease duration or age at seizure onset for any structure, though age at MRI was significantly correlated with hippocampal atrophy. Volume reductions in each of the circuit endpoints (hippocampus and mammillary bodies) were correlated with the degree of atrophy in the bridging white matter structure, the fornix. Lastly, comparisons between subgroups with hippocampal atrophy only versus those with greater circuit damage revealed no significant differences in memory scores, age of onset, or duration. Our findings support the view that MTS involves network-level degeneration affecting multiple memory-related structures beyond the hippocampus. Unexpectedly, no significant associations were found between atrophy and clinical or memory measures, suggesting structural damage in this portion of the Papez circuit may be of limited clinical relevance in this population.
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