Clinical Features and Molecular Mechanisms Underlying Autoantibody-Mediated Seizures

Abstract The last two decades have seen the discovery of a plethora of cell-surface autoantibodies causally implicated in clinically distinctive central nervous system (CNS) diseases. These autoantibody-mediated neurological disorders frequently present with multifocal neurological and psychiatric symptoms with both focal and generalized seizures as a core feature. This chapter describes the clinical spectrum of autoantibody-mediated CNS disorders, focusing on autoantibodies which target the extracellular domains of cell-surface antigens, including NMDAR and LGI1. In addition, the preclinical immune mechanisms underlying the genesis and propagation of these conditions are explored, and the chapter reviews how these autoantibodies directly modulate neuronal and circuit functions to explain the observed clinical features.