Autoimmune encephalitis with anti-leucine-rich glioma-inactivated 1 or anti-contactin-associated protein-like 2 antibodies (formerly called voltage-gated potassium channel-complex antibodies)

Curr Opin Neurol. 2017 Jun;30(3):302-309. doi: 10.1097/WCO.0000000000000444.

Abstract

Purpose of review: Twenty years since the discovery of voltage-gated potassium channel (VGKC)-related autoimmunity; it is currently known that the antibodies are not directed at the VGKC itself but to two closely associated proteins, anti-leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (Caspr2). Antibodies to LGI1 and Caspr2 give well-described clinical phenotypes. Anti-LGI1 encephalitis patients mostly have limbic symptoms, and anti-Caspr2 patients have variable syndromes with both central and peripheral symptoms. A large group of patients with heterogeneous symptoms are VGKC positive but do not have antibodies against LGI1 or Caspr2. The clinical relevance of VGKC positivity in these 'double-negative' patients is questionable. This review focusses on these three essentially different subgroups.

Recent findings: The clinical phenotypes of anti-LGI1 encephalitis and anti-Caspr2 encephalitis have been described in more detail including data on treatment and long-term follow-up. A specific human leukocyte antigen (HLA) association was found in nontumor anti-LGI1 encephalitis, but not clearly in those with tumors. There has been increasing interest in the VGKC patients without LGI1/Caspr2 antibodies questioning its relevance in clinical practice.

Summary: Anti-LGI1 encephalitis and anti-Caspr2 encephalitis are separate clinical entities. Early recognition and treatment is necessary and rewarding. The term VGKC-complex antibodies, lumping patients with anti-LGI1, anti-Caspr2 antibodies or lacking both, should be considered obsolete.

Publication types

  • Review

MeSH terms

  • Autoantibodies / analysis*
  • Encephalitis / immunology*
  • Encephalitis / physiopathology
  • Encephalitis / therapy
  • Hashimoto Disease / immunology*
  • Hashimoto Disease / physiopathology
  • Hashimoto Disease / therapy
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / immunology*
  • Nerve Tissue Proteins / immunology*
  • Potassium Channels, Voltage-Gated / immunology
  • Proteins / immunology*

Substances

  • Autoantibodies
  • CNTNAP2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • LGI1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Potassium Channels, Voltage-Gated
  • Proteins

Supplementary concepts

  • Hashimoto's encephalitis