Cognitive Deficits in Anti-LGI1 Encephalitis Are Linked to Immunotherapy-Resistant White Matter Network Changes
Stephan Krohn, Leonie Müller‐Jensen, Joseph Kuchling, Amy Romanello, Katharina Wurdack, Sophia Rekers, Thorsten Bartsch, Frank Leypoldt, Friedemann Paul, Christoph J. Ploner, Harald Prüß, Carsten Finke
Abstract
BACKGROUND AND OBJECTIVES: Cognitive deficits represent a major long-term complication of anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E). Although severely affecting patient outcomes, the structural brain changes underlying these deficits remain poorly understood. In this study, we hypothesized a link between white matter (WM) networks and cognitive outcomes in LGI1-E. METHODS: In this cross-sectional study, we combined clinical assessments, comprehensive neuropsychological testing, diffusion tensor MRI, probabilistic WM tractography, and computational network analysis in patients with LGI1-E referred to Charité-Universitätsmedizin Berlin. Healthy individuals were recruited as control participants and matched to patients for age and sex with logistic regression propensity scores. RESULTS: = 0.017). DISCUSSION: Although traditionally viewed as a form of limbic encephalitis, our study characterizes LGI1-E as a "network disorder" that affects the whole brain. Structural reorganization of WM networks was linked to long-term and multidomain cognitive impairment, which was not prevented by immunotherapy. These findings highlight the need for closer monitoring and improved treatment strategies to mitigate long-term cognitive impairment in LGI1-E.