Case Report: Anti-GABAA Receptor Encephalitis in a Dog

Abstract

Autoantibodies against neurotransmitter receptors detected in cerebrospinal fluid (CSF) and serum are increasingly recognized in people with human autoimmune encephalitis causing severe neurological deficits, such as seizures and behavioral abnormalities. This case report describes the first encephalitis associated with antibodies against the γ-aminobutyric acid-A receptor (GABAAR) in a dog. A young male intact Cavalier King Charles Spaniel was presented with recent onset of initial multiple generalized tonic-clonic seizures progressing into a status epilepticus. Interictally, he showed alternating stupor and hyperexcitability, ataxia, pleurothotonus and circling behavior to the left side. Magnetic resonance imaging (MRI) of the brain showed breed-specific anatomical abnormalities. Standard CSF analysis was unremarkable. Despite treatment with multiple antiseizure medications (ASMs) seizures and behavior abnormalities sustained. Immunotherapy with dexamethasone was started on the fifth day after disease manifestation. This led to rapid improvement of clinical signs. An extensive antibody search in CSF and serum demonstrated a neuropil staining pattern on a tissue-based assay compatible with GABAAR antibodies. The diagnosis was confirmed by binding of serum and CSF antibodies to GABAAR transfected Human Embryonic Kidney cells. The serum titer was 1:320, the CSF titer 1:2. At the control visit 4.5 weeks after start of immunotherapy, the dog was clinically normal. The GABAAR antibody titer in serum had strongly decreased. The antibodies were no longer detectable in CSF. Based on clinical presentation and testing for GABAAR binding antibodies, this describes the first veterinary patient with an anti-GABAAR encephalitis with a good outcome following ASM and corticosteroid treatment.

Suspected pregnancy‐associated meningoencephalitis of unknown origin in a dog

“…There are a number of different immune‐mediated diseases associated with the peripartum period in human patients. These diseases may vary in their development and progression, which is likely due to the complex interplay between sex hormones and immunological modifications 7,10,23 . In veterinary medicine, a similar correlation has been suggested for immune‐mediated haemolytic anaemia and immune‐mediated polyarthritis 16,17 .…”

“…The underlying mechanism is not clear, but autoantibodies (anti‐centromere antibodies) with unknown effects on the neurons have been detected and seem to have an important role 24 . The identification of immunoglobulin G (IgG) antibodies against neural antigens in patients with autoimmune encephalitis has been developed in recent years 23,25 . Since commercial antibody testing has become available, the prevalence of these diseases has increased 13 .…”

“…A better understanding of these autoantibodies in dogs may lead to improved detection and classification of MUO in canine patients 26 . In order to assess the relevance of these antibodies in the canine population, a larger, prospective evaluation is warranted 23,26 …”

Investigation of the presence of specific neural antibodies in dogs with epilepsy or dyskinesia using murine and human assays

“…Recently, we described a 1‐year‐old male intact Cavalier King Charles Spaniel with GABAAR AB, serum titer 1:320, CSF titer 1:2 and a corresponding staining pattern on mouse brain. This dog recovered upon steroid treatment from its acutely emerging and progressive signs like tonic‐clonic epileptic seizures, episodic hyperexcitability alternating with episode of stupor, and intermittent circling behavior 22 …”

“…A further report refers to a cat with LE in association with deleted colorectal carcinoma (DCC, also known as netrin‐1 receptor) autoantibodies 18 . Reports on dogs are scarce 19‐22 . N ‐methyl‐ d ‐aspartate receptor (NMDAR) antibodies are suggested in the CSF of two dogs with meningoencephalitis of unknown etiology (MUE) and one dog with multifocal signs of neurologic disease and an abscessed maxillary tooth, and in the CSF of a polar bear ( Ursus maritimus ) that drowned because of epileptic seizures and NMDAR‐antibody (AB) mediated encephalitis 20,23 .…”