title: 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).
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: aDepartment of Neurology, Erasmus University Medical Center, Rotterdam bDepartment of Neurology, Haga Hospital, The Hague, the Netherlands.
authors.forename: Anna E M
authors.initials: AEM
authors.lastname: Bastiaansen
authors.forename: Agnes
authors.initials: A
authors.lastname: van Sonderen
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Titulaer
mesh_terms: D001323:Autoantibodies / Q000032:analysis*; D004660:Encephalitis / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D050031:Hashimoto Disease / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology; D011506:Proteins / Q000276:immunology*
chemical_list: D001323:Autoantibodies; C403049:CNTNAP2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins