Patient characteristics and outcome associations in AMPA receptor encephalitis

J Neurol. 2019 Feb;266(2):450-460. doi: 10.1007/s00415-018-9153-8. Epub 2018 Dec 17.

Abstract

Antibody-mediated encephalitis defines a class of diseases wherein antibodies directed at cell-surface receptors are associated with behavioral and cognitive disturbances. One such recently described encephalitis is due to antibodies directed at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). This entity is exceptionally rare and its clinical phenotype incompletely described. We present findings from two cases of AMPAR encephalitis that exemplify variability in the disease spectrum, and summarize findings in published cases derived from a systematic literature review. When all patients are considered together, the presence of psychiatric symptoms at presentation portended a poor outcome and was associated with the presence of a tumor. Furthermore, we provide evidence to suggest that the topography of magnetic resonance imaging abnormalities in reported cases mirrors the distribution of AMPARs in the human brain. The potential for neurological improvement following immunomodulatory therapy together with the favorable outcome reported in most cases emphasizes the importance of testing for autoantibodies against neuronal cell-surface proteins, including AMPAR, in patients with clinical and neuroimaging findings suggestive of autoimmune encephalitis. Close attention to the clinical phenotype may inform the presence of malignancy and long-term prognosis.

Keywords: Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; Autoimmune encephalitis; Limbic encephalitis; Paraneoplastic encephalitis.

Publication types

  • Case Reports
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoimmune Diseases of the Nervous System* / diagnostic imaging
  • Autoimmune Diseases of the Nervous System* / immunology
  • Autoimmune Diseases of the Nervous System* / pathology
  • Autoimmune Diseases of the Nervous System* / physiopathology
  • Encephalitis* / diagnostic imaging
  • Encephalitis* / immunology
  • Encephalitis* / pathology
  • Encephalitis* / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Neuroimaging
  • Receptors, Glutamate / immunology*
  • Young Adult

Substances

  • Receptors, Glutamate
  • alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptor, human