Autoimmune encephalitis as differential diagnosis of infectious encephalitis

Curr Opin Neurol. 2014 Jun;27(3):361-8. doi: 10.1097/WCO.0000000000000087.


Purpose of review: This review describes the main types of autoimmune encephalitis with special emphasis on those associated with antibodies against neuronal cell surface or synaptic proteins, and the differential diagnosis with infectious encephalitis.

Recent findings: There is a continuous expansion of the number of cell surface or synaptic proteins that are targets of autoimmunity. The most recently identified include the metabotropic glutamate receptor 5 (mGluR5), dipeptidyl-peptidase-like protein-6 (DPPX), and γ-aminobutyric acid-A receptor (GABAAR). In these and previously known types of autoimmune encephalitis [N-methyl-D-aspartate receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABABR), leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated protein-like 2 (CASPR2)], the prodromal symptoms or types of presentations often suggest a viral encephalitis. We review here clues that help in the differential diagnosis with infectious encephalitis. Moreover, recent investigations indicate that viral encephalitis (e.g., herpes simplex) can trigger synaptic autoimmunity. In all these disorders, immunotherapy is usually effective.

Summary: Autoimmune encephalitis comprises an expanding group of potentially treatable disorders that should be included in the differential diagnosis of any type of encephalitis.

Video abstract:,

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / diagnosis*
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / immunology
  • Autoantibodies / immunology
  • Brain / pathology*
  • Brain Diseases / diagnosis*
  • Brain Diseases / immunology
  • Diagnosis, Differential
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / immunology
  • Encephalitis / diagnosis*
  • Encephalitis / immunology
  • Encephalitis, Herpes Simplex / diagnosis
  • Encephalitis, Herpes Simplex / immunology
  • Hashimoto Disease / diagnosis*
  • Hashimoto Disease / immunology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Magnetic Resonance Imaging
  • Membrane Proteins / immunology
  • Nerve Tissue Proteins / immunology
  • Potassium Channels / immunology
  • Proteins / immunology
  • Receptor, Metabotropic Glutamate 5 / immunology
  • Receptors, GABA-A / immunology
  • Receptors, Glutamate / immunology
  • Tuberculosis, Central Nervous System / diagnosis*
  • Tuberculosis, Central Nervous System / immunology


  • Autoantibodies
  • CNTNAP2 protein, human
  • GRM5 protein, human
  • Intracellular Signaling Peptides and Proteins
  • LGI1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Potassium Channels
  • Proteins
  • Receptor, Metabotropic Glutamate 5
  • Receptors, GABA-A
  • Receptors, Glutamate
  • alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptor, human
  • DPP6 protein, human
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

Supplementary concepts

  • Hashimoto's encephalitis