Paraneoplastic and non-paraneoplastic autoimmunity to neurons in the central nervous system.

Autoimmune central nervous system (CNS) inflammation occurs both in a paraneoplastic and non-paraneoplastic context. In a widening spectrum of clinical disorders, the underlying adaptive (auto) immune response targets neurons with a divergent role for cellular and humoral disease mechanisms: (1) in encephalitis associated with antibodies to intracellular neuronal antigens, neuronal antigen-specific CD8(+) T cells seemingly account for irreversible progressive neuronal cell death and neurological decline with poor response to immunotherapy. However, a pathogenic effect of humoral immune mechanisms is also debated. (2) In encephalitis associated with antibodies to synaptic and extrasynaptic neuronal cell surface antigens, potentially reversible antibody-mediated disturbance of synaptic transmission and neuronal excitability occurs in the absence of excessive neuronal damage and accounts for a good response to immunotherapy. However, a pathogenic effect of cellular immune mechanisms is also debated. We provide an overview of entities, clinical hallmarks, imaging features, characteristic laboratory, electrophysiological, cerebrospinal fluid and neuropathological findings, cellular and molecular disease mechanisms as well as therapeutic options in these two broad categories of inflammatory CNS disorders.