IgG and complement deposition and neuronal loss in cats and humans with epilepsy and voltage-gated potassium channel complex antibodies

J Neuropathol Exp Neurol. 2014 May;73(5):403-13. doi: 10.1097/NEN.0000000000000063.

Abstract

Voltage-gated potassium channel complex (VGKC-complex) antibody (Ab) encephalitis is a well-recognized form of limbic encephalitis in humans, usually occurring in the absence of an underlying tumor. The patients have a subacute onset of seizures, magnetic resonance imaging findings suggestive of hippocampal inflammation, and high serum titers of Abs against proteins of the VGKC-complex, particularly leucine-rich, glioma-inactivated 1 (LGI1). Most patients are diagnosed promptly and recover substantially with immunotherapies; consequently, neuropathological data are limited. We have recently shown that feline complex partial cluster seizures with orofacial involvement (FEPSO) in cats can also be associated with Abs against VGKC-complexes/LGI1. Here we examined the brains of cats with FEPSO and compared the neuropathological findings with those in a human with VGKC-complex-Ab limbic encephalitis. Similar to humans, cats with VGKC-complex-Ab and FEPSO have hippocampal lesions with only moderate T-cell infiltrates but with marked IgG infiltration and complement C9neo deposition on hippocampal neurons, associated with neuronal loss. These findings provide further evidence that FEPSO is a feline form of VGKC-complex-Ab limbic encephalitis and provide a model for increasing understanding of the human disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Autoantibodies / biosynthesis
  • Autoantibodies / blood*
  • Cats
  • Cell Count / methods
  • Cell Death / physiology
  • Complement System Proteins / metabolism*
  • Epilepsy / blood*
  • Epilepsy / pathology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Immunoglobulin G / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / pathology
  • Potassium Channels, Voltage-Gated / blood*

Substances

  • Anticonvulsants
  • Autoantibodies
  • Immunoglobulin G
  • Potassium Channels, Voltage-Gated
  • Complement System Proteins