Comparative Effects of Domain-Specific Human Monoclonal Antibodies Against LGI1 on Neuronal Excitability

Abstract

These findings indicate an epitope-specific pathophysiology of LGI1 autoantibodies. The pronounced neuronal hyperexcitability and SFA together with dropped slope of ramp-like depolarization after LRR-targeted interference suggest disruption of LGI1-dependent clustering of K⁺ channel complexes. Moreover, considering the effective triggering of action potentials at the distal AIS, the altered spatial distribution of K_v1.1 channel density may contribute to these effects through impairing neuronal control of action potential initiation and synaptic integration.