Subcortical shape biomarkers reveal limbic and basal ganglia damage in anti-LGI1 encephalitis.

Introduction: Anti-LGI1 encephalitis is associated with disruptions in large-scale brain network functionality. Although hippocampal atrophy has been structurally characterized, the morphometric patterns of subcortical structures and their surface deformations remain poorly understood. We therefore investigated the shape abnormalities of subcortical structures and their morphological correlations in patients with anti-LGI1 encephalitis. Methods: This study included 31 patients diagnosed with anti-LGI1 encephalitis and 31 group-matched healthy controls. The mesh-based shape method was performed on the fifteen segmented subcortical structures for vertex-wise analyses. Permutation method based on general linear model was applied for statistical group comparison. Associations with disease severity and cognitive impairment were assessed in the patients. The volumetric representations of these subcortical structures were also estimated. Correlations between subcortical shape alterations and disease severity were explored. Results: Significant inward shape deformations were observed in the limbic system and basal ganglia in patients with anti-LGI1 encephalitis compared to healthy controls. Moreover, correlation analyses revealed that greater inward shape indices in the hippocampus and thalamus were associated with increased disease severity and poorer cognitive functioning, underscoring the pathological significance of these morphological alterations. Discussion: These findings indicate that precisely localized subcortical shape deformations are associated with disease severity and cognitive impairment, suggesting widespread damage of limbic system and basal ganglia in anti-LGI1 encephalitis.