title: Autoimmune encephalitis: recent updates and emerging challenges.
abstract: The knowledge of immune dysregulation and autoimmunity in neurological disorders has expanded considerably in recent times. Recognition of clinical syndromes, reliable methods of diagnosis, and early targeted immunotherapy can lead to a favourable outcome in acute and subacute neurological disorders that may be associated with significant morbidity and mortality if left untreated. This review focuses on the rapidly expanding field of autoimmune encephalitis. We describe the differences between limbic encephalitis associated with antibodies targeting intracellular antigens, and neuronal surface antibody syndromes (NSAS) where the antigens are primarily receptors or synaptic proteins located on the neuronal cell surface. We chronologically highlight important developments in NSAS by focusing on voltage gated potassium channel complex-associated antibody mediated encephalitis, anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, and anti-dopamine 2 receptor antibody-associated basal ganglia encephalitis. Contentious issues such as the complexities of using serum antibodies as biomarkers, the initiation of central nervous system autoimmunity, and possible pathogenic mechanisms of these antibodies will be reviewed. The therapeutic challenges that clinicians face such as the timing of therapy and the role of second-line therapy will be discussed, with crucial concepts highlighted in the form of clinical vignettes. Future directions will involve the identification of novel antigens and methods to establish their pathogenicity, as well as evaluation of the most efficacious therapeutic strategies in patients with established NSAS.
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Locked Bag 4001, Westmead, Sydney, NSW 2145, Australia; Department of Neurology, Westmead Hospital, Westmead, Sydney, NSW, Australia.
authors.forename: Sudarshini
authors.initials: S
authors.lastname: Ramanathan
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Locked Bag 4001, Westmead, Sydney, NSW 2145, Australia; TY Nelson Department of Neurology and Neurosurgery, Children's Hospital at Westmead, Westmead, Sydney, NSW, Australia.
authors.forename: Shekeeb S
authors.initials: SS
authors.lastname: Mohammad
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Locked Bag 4001, Westmead, Sydney, NSW 2145, Australia.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brilot
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Locked Bag 4001, Westmead, Sydney, NSW 2145, Australia; TY Nelson Department of Neurology and Neurosurgery, Children's Hospital at Westmead, Westmead, Sydney, NSW, Australia. Electronic address: russell.dale@health.nsw.gov.au.
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
mesh_terms: D000818:Animals; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D001323:Autoantibodies / Q000276:immunology; D001927:Brain Diseases / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis; D005260:Female; D050031:Hashimoto Disease / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000639:trends*; D020363:Limbic Encephalitis / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D008297:Male
chemical_list: D001323:Autoantibodies
keywords: Anti-NMDAR encephalitis; Autoimmune encephalitis; Autoimmune epilepsy; Basal ganglia encephalitis; Limbic encephalitis; VGKC encephalitis