IgG and complement deposition and neuronal loss in cats and humans with epilepsy and voltage-gated potassium channel complex antibodies.
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.
From the Institute of Pathology and Forensic Veterinary Medicine, Department for Pathobiology (AK, PS), Clinic for Internal Medicine and Infectious Diseases (AP), Diagnostic Imaging (SK), Department for Companion Animals and Horses, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Neuroimmunology (JB), Center for Brain Research, Medical University of Vienna, Vienna, Austria; Austrian Agency for Health and Food Safety (ZB), Institute for Veterinary Disease Control, Mödling, Austria; Department of Clinical Neurology (AV, BL, TM), Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, England; Hospital Mara (CGB), Epilepsy Center Bethel, Bielefeld, Germany; Institute of Experimental Medicine (PH), Budapest, Hungary.
Andrea
A
Klang
Peter
P
Schmidt
Sibylle
S
Kneissl
Zoltán
Z
Bagó
Angela
A
Vincent
Bethan
B
Lang
Teresa
T
Moloney
Christian G
CG
Bien
Péter
P
Halász
Jan
J
Bauer
Akos
A
Pákozdy
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D002415:Cats; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D003165:Complement System Proteins / Q000378:metabolism*; D004827:Epilepsy / Q000097:blood* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D024642:Potassium Channels, Voltage-Gated / Q000097:blood*
D000927:Anticonvulsants; D001323:Autoantibodies; D007074:Immunoglobulin G; D024642:Potassium Channels, Voltage-Gated; D003165:Complement System Proteins