Autoimmune encephalitis with psychiatric features in adults: historical evolution and prospective challenge

Abstract

Our review aims to delineate the psychiatric spectrum of autoantibody-associated autoimmune encephalitis over time through its discoveries of antibodies. We searched in PubMed for appropriate articles depicting the first appearance and spectrum of psychiatric symptomatology in autoantibody-positive encephalitis for this narrative review. Memory impairment was first associated with autoantibodies against intracellular antigens such as anti-HuD antibodies in 1993. 8 years later, autoantibodies against cell membrane surface antigens such as voltage-gated potassium channels were described in conjunction with memory dysfunction. The spectrum of psychiatric syndromes was amplified between 1990 and 2020 to include disorientation, behavior, cognitive dysfunction, obsessive compulsive behavior and suicidality in encephalitis patients occurring together mainly with antibodies against surface antigens, less so against intracellular antigens. In general, we found no specific psychiatric symptoms underlying specific autoantibody-associated encephalitis. As fundamental data on this issue have not been systemically assessed to date, we cannot know whether our specific findings would remain from systematic studies, i.e., on the association between cerebrospinal fluid N-methyl-D-aspartate receptor antibodies in catatonia. The psychiatric symptomatology overlaps between psychiatric domains and occurs frequently in antibody-positive encephalitis. No specific psychiatric symptoms imply an underlying, specifically autoantibody-associated encephalitis. The psychiatric phenotypology associated with antibody-positive encephalitis has evolved tremendously recently, and this new evidence reveals its relevance for future diagnostic and treatment aspects of autoimmune encephalitis patients.