Focused Workshops

Abstract

The initial trigger leading to the immune tolerance breakdown is still unknown in most autoimmune encephalitites associated with antibodies targeting neuronal surface antigens. Nevertheless, prodromal symptoms compatible with mild infections are not infrequent, suggesting that some common and benign microbiological agents could act as triggers of the autoimmune reaction. Conversely, herpes simplex virus (HSV) encephalitis is now a well-characterized trigger of autoimmune encephalitis, and is particularly related to the development of anti- NMDAR antibodies, though other specificities have also been reported. Serological studies as well as an animal model further support the association between HSV and anti-NMDAR encephalitis, but the underlying pathogenesis is still obscure. However, a genetic predisposition involving the Toll-like receptor 3-pathway might exist at least in a subset of patients. In addition to HSV, anti-NMDAR and other autoimmune encephalitis have also been associated with other infections, chiefly Japanese encephalitis and HIV, but new epidemic and pandemic diseases such as COVID-19 are raising concern as potential triggers of autoimmune encephalitis. On the contrary, despite the recent description of anti-neural antibodies against different targets in some patients, solid evidence regarding the autoimmune pathogenesis is still lacking for several historically reported post-infectious neurological diseases, such as Sydenham chorea and von Economo's encephalitis lethargica. Interestingly, type 1 narcolepsy constitutes a good example of neurological autoimmunity triggered by infection in genetic susceptible subjects that might provide some clues for future research in autoimmune encephalitis.