Encephalitis: intersections between infections and autoimmunity

Encephalitis is a serious condition accompanied by substantial morbidity. Although infections have long been recognized as causes, there has been growing appreciation of autoimmune aetiologies of encephalitis, most notably those associated with anti-neuronal antibodies.

This narrative review focuses on points of commonality among clinical features, pathophysiology, and management of infectious and autoimmune encephalitis, while also noting important distinctions.

I identified studies, comprising research articles and reviews, that provide data on the epidemiology of infectious versus autoimmune encephalitis, and on clinical features that either co-occur or distinguish between them. In addition, I reviewed management practices, preclinical data, and clinical trials on the treatment of infectious and autoimmune encephalitis.

I first discuss the clinical overlap between infectious and autoimmune causes of encephalitis, highlighting features and syndromes that can confound the diagnosis. I next turn to the pathogenic overlap between the two, exemplified by the development of autoimmune encephalitis with antibodies against the N-methyl-D-aspartate receptor following a bout of herpes simplex encephalitis. Finally, I discuss management of infectious and autoimmune encephalitis, focusing on current and future avenues of treatment.

Although our understanding of causes of infectious and autoimmune encephalitis has improved considerably over the past decade, diagnosis remains challenging given the clinical and pathophysiological overlap between the two. Large multicentre clinical trials are needed to evaluate treatments that target inflammation and potentially benefit both.