Autoimmune Encephalitis: Current Knowledge on Subtypes, Disease Mechanisms and Treatment.

Abstract

Autoimmune Encephalitides (AE) comprises a group of diseases with antibodies against neuronal synaptic and cell surface antigens. Since the discovery of the most common subtype, NMethyl- D-Aspartate (NMDA) receptor encephalitis, an astonishing number of novel disease-causing antibodies have been described. This includes other glutamatergic and GABAergic receptor antibodies and antibodies against various other surface proteins. Many of these novel conditions present as limbic encephalitis with memory impairment, psychiatric features and epileptic seizures, often alongside subtype specific clinical features. Others present with a clinical disease course specific to the antibody. In contrast to the well-known paraneoplastic syndromes with antibodies directed against intracellular antigens (e.g. limbic encephalitis with Hu antibodies), autoimmune encephalitides are often highly responsive to immunotherapy, with a good outcome if diagnosed and treated early. Prognosis depends on aggressive immunotherapy, often with a combination of corticosteroids, intravenous immunoglobulin, plasma exchange or in some cases anti-CD20 therapy and cyclophosphamide. Other treatment regimens exist, and prognosis varies between disease subtypes and occurrence of underlying cancer. We review current knowledge on subtype-specific clinical presentation, disease mechanisms, diagnosis including pitfalls, treatment paradigms and outcome in autoimmune encephalitides, and provide suggestions for future research.