Autoimmune encephalitis: clinical spectrum and management

Abstract

Autoimmune encephalitis defines brain inflammation caused by a misdirected immune response against self-antigens expressed in the central nervous system. It comprises a heterogeneous group of disorders that are at least as common as infectious causes of encephalitis. The rapid and ongoing expansion of this field has been driven by the identification of several pathogenic autoantibodies that cause polysymptomatic neurological and neuropsychiatric diseases. These conditions often show highly distinctive cognitive, seizure and movement disorder phenotypes, making them clinically recognisable. Their early identification and treatment improve patient outcomes, and may aid rapid diagnosis of an underlying associated tumour. Here we summarise the well-known autoantibody-mediated encephalitis syndromes with neuronal cell-surface antigens. We focus on practical aspects of their diagnosis and treatment, offer our clinical experiences of managing such cases and highlight more basic neuroimmunological advances that will inform their future diagnosis and treatments.

Keywords: clinical neurology; epilepsy; immunology; limbic system; neuroimmunology.

Figure 1

Classic syndromes and characteristic features of neuronal autoantibodies. Listed in an estimated order of descending frequency. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; CASPR2, contact-associated protein 2; DPPX, dipeptidyl peptidase-like protein 6; GABA_A/BR, gamma aminobutyric acid; IgLON5, immunoglobulin-like cell-adhesion molecule 5; LGI1, leucine-rich glioma inactivated protein 1; NMDAR, N-methyl-D-aspartate receptor; MOG, myelin-oligodendrocyte glycoprotein.

Figure 2

Neuronal surface antibody detection methods. Current research and diagnostic methods expose the test sample to neuronal antigens which differ in the properties of the antigens. Cell-based assays aim largely to expose a single known antigen, by its expression in mammalian cells. Conversely, neurone-based assays and tissue-based assays expose multiple endogenous antigens, both those known to be targets of pathogenic antibodies and as yet unknown antigens. Additionally, the assays vary on whether the antigen was fixed before incubation with the patient sample (serum or cerebrospinal fluid) and whether the cell membrane is intact (‘live’). Live cell-based assays and live neurone-based assays neither fix the surface antigen nor permeabilise the membrane before exposure to the patient’s sample. By contrast, in fixed permeabilised cell-based assays and tissue-based assays, target antigens are potentially altered by fixation and cell membrane integrity is lost. Figure modified from Ramanathan et al. CBA, cell-based assay.