Brain MRI Longitudinal Volumetric Characteristics Associated with Outcomes of CASPR2-Autoimmune Limbic Encephalitis

Autoimmune encephalitis is a heterogeneous neurologic disorder with inflammation of the brain mediated by autoantibodies against neuronal antigens. Within its subtypes, CASPR2-Autoimmune Limbic Encephalitis (CASPR2-ALE) stands out because of its varied clinical manifestations that slowly progress in time. This study investigates structural brain changes of patients with CASPR2-ALE by applying advanced segmentation algorithms to multi-centric 3D T1-weighted MRIs of patients with CASPR2-ALE. The five algorithms assessed in the study were FreeSurfer, FastSurfer, SPM, Joint Label Fusion (JLF), and nnUNET. Manual segmentations represented the 'gold standard,' and each algorithm's performance was assessed by the following metrics: Dice Coefficient, Hausdorff Distance, Average Symmetric Surface Distance, and Volume Similarity. Longitudinal volumetric analyses showed progressive hippocampal inflammation followed by atrophy that was correlated with disease progression, while cross-sectional analyses underlined volume differences between anti-CASPR2 associated phenotypes. Clinical correlations further demonstrated the relationship between measured volumes, mesiotemporal hyperintensities, and disease-specific symptoms. The study emphasizes the importance of accurate brain segmentation algorithms in longitudinal studies of CASPR2-ALE and identifies FreeSurfer as the most reliable algorithm for such assessments. These findings underscore the unique neuroimaging characteristics of CASPR2-ALE: these findings not only widen our knowledge of disease dynamics but also pave the way for more accurate diagnoses and better-targeted treatments.