Table 1

Proposed classification concepts in autoimmune encephalitis

Anatomical classificationSerological classificationAetiological classification
  1. Limbic

  2. Cortical/subcortical

  3. Striatal

  4. Diencephalic

  5. Brainstem

  6. Cerebellar

  7. Encephalomyelitis

  8. Meningoencephalitis

  9. Combined

  1. Antibodies to intracellular antigens (classical onconeuronal antibodies).*

  2. Antibodies to surface antigens and other antigens with high clinical relevance (eg, NMDAR, AMPAR, LGI1, CASPR2, GABAR A/B, DPPX, glycine receptor, AQP4, MOG, GFAP†).

  3. Antibodies to surface antigens with low clinical relevance (eg, VGKC, VGCC).‡

  4. Seronegative autoimmune encephalitis.

  1. Idiopathic

  2. Paraneoplastic

  3. Postinfectious

  4. Iatrogenic (eg, in the setting of immune check point inhibitors or other immune-modulating agents).

  • *GAD65 antibody is directed against an intracellular antigen but in high titers, it mediates an autoimmune encephalitis phenotype similar to surface antibodies with high clinical relevance, and in low titers is usually clinically irrelevant to neurological symptoms.

  • †GFAP is a cytoplasmic antigen associated with intermediate filaments. Considered clinically relevant in patients presenting with typical radiological findings (perivascular radial enhancement).

  • ‡Clinical relevance of these antibodies varies according to presentation. Although they may not be clinically relevant in certain patients with typical autoimmune encephalitis, some of these antibodies have higher clinical relevance to other neurological presentations (eg, VGCC is likely relevant in patients with Lambert-Eaton myasthenic syndrome and acquired autoimmune ataxia).

  • AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor ; AQP4, aquaporin-4; CASPR2, Contactin-associated protein-like 2 ; DPPX, Dipeptidyl-peptidase-like protein 6 ; GABAR, Gamma-Amino butyric acid Receptor ; GFAP, glial fibrillary acidic protein; LGI1, Leucine-rich glioma inactivated ; MOG, Myelin oligodendrocyte glycoprotein ; VGCC, voltage-gated calcium channel; VGKC, voltage-gated potassium channel .