Background Autoimmune mechanisms represent a novel category for causes of seizures and epilepsies in humans, and LGI1‐antibody associated limbic encephalitis occurs in cats. Hypothesis/Objectives To investigate the presence of neural antibodies in dogs with epilepsy or dyskinesia of unknown cause using human and murine assays modified for use in dogs. Animals Fifty‐eight dogs with epilepsy of unknown cause or suspected dyskinesia and 57 control dogs. Methods Serum and CSF samples were collected prospectively as part of the diagnostic work‐up. Clinical data including onset and seizure/episode type were retrieved from the medical records. Screening for neural antibodies was done with cell‐based assays transfected with human genes for typical autoimmune encephalitis antigens and tissue‐based immunofluorescence assays on mouse hippocampus slices in serum and CSF samples from affected dogs and controls. The commercial human und murine assays were modified with canine‐specific secondary antibody. Positive controls were from human samples. Results The commercial assays used in this study did not provide unequivocal evidence for presence of neural antibodies in dogs including one dog with histopathologically proven limbic encephalitis. Low titer IgLON5 antibodies were present in serum from one dog from the epilepsy/dyskinesia group and in one dog from the control group. Conclusion and Clinical Importance Specific neural antibodies were not detected using mouse and human target antigens in dogs with epilepsy and dyskinesia of unknown origin. These findings emphasize the need for canine‐specific assays and the importance of control groups.

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