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.

Clinical Features and Early Recognition of 242 Cases of Autoimmune Encephalitis

“…A prospective study of the reliability of the ACES score is necessary. The study by Hansen et al ( 35 ) showed that there are various manifestations of psychiatric symptoms in AE. Given that the behavior is a broad term, it is important to develop a better scoring system that includes different aspects of psychiatric symptoms.…”

Autoimmune Encephalitis Presenting as Dystonia-Parkinsonism

“…1 Patients with autoimmune encephalitis may also have psychologic features such as anxiety, depression, mood dysfunction, and hallucinations. 7 Imaging findings for autoimmune encephalitis are variable and can range from none at all to a markedly abnormal examination with symptoms including cranial neuropathies, dystonia, chorea, psychosis, or seizures. 6 Signal changes may affect the white matter, cortex, deep gray nuclei, and brain stem.…”

More than just anti-NMDAR: the many facets of autoimmune encephalitis

“…9,10 Although psychiatric symptomatology can occur with any antibody-positive encephalitis, it is more frequent in presentations associated with autoantibodies targeting extracellular antigens. 11…”

“…These antibodies most likely act through T-cell mechanisms and are associated with psychosis. 11,21,22 antibodies are very strongly associated with breast cancer in women. These antibodies target intracellular proteins important for recycling synaptic vesicles.…”