1. Distinctive seizure signature in the first video case-control study of a naturally-occurring feline autoimmune encephalitis model.
- Author
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Binks SNM, Crawford AH, Ives E, Davison LJ, Fower A, Fox H, Kaczmarska A, Woodhall M, Waters P, Handel AE, Irani SR, Quintana RG, Chowdhury FA, Eriksson SH, and Pakozdy A
- Abstract
Background and Objective: Autoimmune encephalitis (AE) is a form of brain inflammation where pathogenic autoantibodies bind surface proteins. In humans, AE is at least as common as infective encephalitis, and seizures are a prominent manifestation. The most common adult human AE is associated with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E). AE in non-human mammals is also recognised, notably the polar bear 'Knut', diagnosed with N-methyl D-aspartate receptor antibody encephalitis. LGI1-Ab-E is an emerging cause of spontaneously-arising AE in domestic cats. Our objective was to phenotype the seizure profile of feline LGI1-Ab-E and probe parallels to its human counterpart., Methods: We characterised seizures in naturally-occurring feline LGI1-Ab-E. Three veterinary and two human neurologists independently blind-rated 35 LGI1-antibody positive and negative feline seizure videos from 24 cats (16 LGI1-Ab-E positive, 8 negative). Data analysed included seizure frequency, semiologies and their co-occurrence, localisation, inter-rater agreement, and predictive factors., Results: The mean number of daily seizures at peak was significantly higher in LGI1-antibody positive compared to LGI1-antibody-negative cats (12.6 vs. 1.9/day, pcorr = 0.011). Semiologies statistically significantly enriched in LGI1-Ab-E observations included orofacial automatisms (88/120, 73 % vs. 26/55, 47 %, pcorr = 0.024), salivation (87/120, 73 % vs. 23/55, 42 %, pcorr = 0.004); and mydriasis (79/120, 66 % vs 19/55, 35 %, pcorr = 0.004), and almost exclusively seen in LGI1-Ab-E were circling (39/120, 33 % vs. 1/55, 2 %, pcorr=<0.001) and aggression (14/120, 12 % vs. 0/55, 0 %, non significant after correction). A temporal lobe onset was proposed in 67 % (80/120) of seropositive ratings, compared to 28 % (15/55) LGI1-Ab-E negative (p < 0.0001). Network analysis depicted complex and overlapping relationships between features, akin to the frequent and multifaceted seizures of human LGI1-Ab-E. Orofacial automatisms, mydriasis and temporal lobe localisation were predictive semiological features of feline LGI1-Ab-E., Significance: Feline LGI1-Ab-E represents a clinically distinctive seizure disorder. Our findings highlight the value of studying naturally-occurring, biologically representative animal models which closely mimic human diseases. This bidirectional translational approach confers benefits across species and unites human and veterinary neurology., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Binks has received an honorarium from Vetmeduni Wien and is named on a patent application entitled “Diagnostic Strategy to improve specificity of CASPR2 antibody detection” (TBA / BB Ref. JA94536P.GBA). Dr Handel has received research funding from UCB-Pharma. Dr Waters is a named inventor on patents for antibody assays and has received royalties. He has received honoraria from Biogen Idec, Mereo Biopharma, Retrogenix, UBC, Euroimmun AG, UCB, F. Hoffmann La-Roche, MIAC and Alexion; travel grants from the Guthy-Jackson Charitable Foundation; and research funding from Euroimmun AG. His work in the Autoimmune Neurology Diagnostic Laboratory is supported by the NHS Commissioning service for NMOSD. Professor Irani has received honoraria/research support from UCB, Argenx, Immunovant, MedImmun, Roche, Janssen, Cerebral therapeutics, ADC therapeutics, Brain, CSL Behring, and ONO Pharma, and receives licensed royalties on patent application WO/2010/046716 entitled 'Neurological Autoimmune Disorders', and has filed two other patents entitled “Diagnostic method and therapy” (WO2019211633 and US-2021-0071249-A1; PCT application WO202189788A1) and “Biomarkers” (PCT/GB2022/050614 and WO202189788A1). Dr Eriksson has received honoraria for educational activities from Eisai, Fidia, Lincoln and UCB pharma, nonrelevant for the current study. Dr Crawford, Dr Ives, Professor Davison, Mr Fower, Dr Fox, Dr Kaczmarska, Dr Woodhall, Dr Gutierrez Quintana, Dr Chowdhury, and Dr Pakozdy declare no competing interests., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2025
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