Case Report: Anti-GABA A 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 (GABA_AR) 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 GABA_AR antibodies. The diagnosis was confirmed by binding of serum and CSF antibodies to GABA_AR 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 GABA_AR antibody titer in serum had strongly decreased. The antibodies were no longer detectable in CSF. Based on clinical presentation and testing for GABA_AR binding antibodies, this describes the first veterinary patient with an anti-GABA_AR encephalitis with a good outcome following ASM and corticosteroid treatment.

Keywords: GABAA receptor encephalitis; autoimmune encephalitis; dog; epilepsy; seizures.

Figure 1

Antibody diagnostics. Immunofluorescence studies: diluted patient material is incubated with mouse brain sections or human embryonic kidney (HEK) cells transfected with the antigens of interest. Binding of patient antibodies to the respective matrix is visualized by a secondary anti-human/canine antibody coupled with an immunofluorescence dye resulting in a red signal. (A–C) Tissue-based assays, mouse cerebellum. (D) cell-based assay with HEK cells which were transfected with the γ-aminobutyric acid (GABA)-A receptor (GABA_AR) subunits α1β3 (all assays from Euroimmun, Lübeck, Germany). Molecular layer (ML), purkinje cell layer (Pu), granular cell layer (GL), white matter (WM). (A) Human antibodies against the GABA_AR. (B) Human antibodies against the GABA_BR. (C) The canine antibodies against the GABA_AR. Please note that the binding pattern is similar to (A) and not to (B). (D) The canine serum binds to GABA_AR transfected HEK cells. Nuclear counterstaining with Hoechst 33342 in blue. Bar in (A), valid also for (B,C): 100 μm. Bar in (D): 25 μm.