{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:24:18Z","timestamp":1787984658666,"version":"build-2784847793"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>\n                    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 \u03b3-aminobutyric acid-A receptor (GABA\n                    <jats:sub>A<\/jats:sub>\n                    R) 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\n                    <jats:sub>A<\/jats:sub>\n                    R antibodies. The diagnosis was confirmed by binding of serum and CSF antibodies to GABA\n                    <jats:sub>A<\/jats:sub>\n                    R 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\n                    <jats:sub>A<\/jats:sub>\n                    R antibody titer in serum had strongly decreased. The antibodies were no longer detectable in CSF. Based on clinical presentation and testing for GABA\n                    <jats:sub>A<\/jats:sub>\n                    R binding antibodies, this describes the first veterinary patient with an anti-GABA\n                    <jats:sub>A<\/jats:sub>\n                    R encephalitis with a good outcome following ASM and corticosteroid treatment.\n                  <\/jats:p>","DOI":"10.3389\/fvets.2022.886711","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T04:49:19Z","timestamp":1655959759000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Case Report: Anti-GABAA Receptor Encephalitis in a Dog"],"prefix":"10.3389","volume":"9","author":[{"given":"Enrice I.","family":"Huenerfauth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian G.","family":"Bien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Bien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger A.","family":"Volk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Meyerhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"134","DOI":"10.5698\/1535-7511.17.3.134","article-title":"\u201cAutoimmune epilepsy\u201d: encephalitis with autoantibodies for epileptologists","volume":"17","author":"Bien","year":"2017","journal-title":"Epilepsy Curr."},{"key":"B2","doi-asserted-by":"publisher","first-page":"100539","DOI":"10.1016\/j.tcam.2021.100539","article-title":"Clinical presentation, diagnostic findings, and long-term survival time in 182 dogs with meningoencephalitis of unknown origin from central europe that were administered glucocorticosteroid monotherapy","volume":"44","author":"Pau\u0161ov\u00e1","year":"2021","journal-title":"Top Companion Anim Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1136\/vr.101431","article-title":"Meningoencephalitis of unknown origin: investigation of prognostic factors and outcome using a standard treatment protocol","volume":"172","author":"Lowrie","year":"2013","journal-title":"Vet Rec."},{"key":"B4","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1097\/WCO.0b013e3283446f05","article-title":"Autoimmune epilepsies","volume":"24","author":"Irani","year":"2011","journal-title":"Curr Opin Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"596","DOI":"10.3389\/fneur.2019.00596","article-title":"Clinical features, treatment, and outcomes among chinese children with anti-methyl-D-aspartate receptor (anti-NMDAR) encephalitis","volume":"10","author":"Zhang","year":"2019","journal-title":"Front Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/S1474-4422(13)70299-0","article-title":"Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies","volume":"13","author":"Petit-Pedrol","year":"2014","journal-title":"Lancet Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e20210012","DOI":"10.1101\/2021.01.28.428602","article-title":"Encephalitis patient-derived monoclonal GABAA receptor antibodies cause epileptic seizures","volume":"218","author":"Kreye","year":"2021","journal-title":"J Exp Med"},{"key":"B8","first-page":"86","article-title":"Encephalitis associated with autoantibodies binding to \u03b3-aminobutyric acid-A, \u03b3-aminobutyric acid-B and glycine receptors: immunopathogenic mechanisms and clinical characteristics","volume":"3","author":"Quek","year":"2016","journal-title":"Neurol-Neuroimmunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e1916337118","DOI":"10.1073\/pnas.1916337118","article-title":"Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABA(A) receptor encephalitis","volume":"118","author":"Br\u00e4ndle","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e554","DOI":"10.1212\/NXI.0000000000000554","article-title":"Encephalitis, severe seizures, and multifocal brain lesions: Recognizing autoimmunity to the GABA(A) receptor","volume":"6","author":"Lancaster","year":"2019","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B11","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1002\/ana.25131","article-title":"Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis","volume":"83","author":"Dubey","year":"2018","journal-title":"Ann Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1038\/s41577-021-00543-w","article-title":"Autoantibodies in neurological disease","volume":"21","author":"Pr\u00fcss","year":"2021","journal-title":"Nat Rev Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"819945","DOI":"10.3389\/fvets.2021.819945","article-title":"Inflammatory disease affecting the central nervous system in dogs: a retrospective study in England (2010\u20132019)","volume":"8","author":"Gon\u00e7alves","year":"2022","journal-title":"Front Vet Sci"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1212\/WNL.0000000000003713","article-title":"Investigations in GABA(A) receptor antibody-associated encephalitis","volume":"88","author":"Spatola","year":"2017","journal-title":"Neurology."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1212\/WNL.0000000000001326","article-title":"Antibodies to GABAA receptor \u03b11 and \u03b32 subunits: clinical and serologic characterization","volume":"84","author":"Pettingill","year":"2015","journal-title":"Neurology."},{"key":"B16","doi-asserted-by":"publisher","first-page":"8151","DOI":"10.1523\/JNEUROSCI.4415-13.2014","article-title":"Identification and characterization of GABA(A) receptor autoantibodies in autoimmune encephalitis","volume":"34","author":"Ohkawa","year":"2014","journal-title":"J Neurosci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1111\/jvim.15616","article-title":"Presence of cerebrospinal fluid antibodies associated with autoimmune encephalitis of humans in dogs with neurologic disease","volume":"33","author":"Stafford","year":"2019","journal-title":"J Vet Intern Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/ng0501-46","article-title":"First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene","volume":"28","author":"Baulac","year":"2001","journal-title":"Nat Genet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e552","DOI":"10.1212\/NXI.0000000000000552","article-title":"GABA(A) receptor autoimmunity: a multicenter experience","volume":"6","author":"O'Connor","year":"2019","journal-title":"Neurol Neuroimmunol Neuroinflamm."},{"key":"B20","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3389\/fvets.2018.00171","article-title":"Morphogenesis of Canine Chiari malformation and secondary syringomyelia: disorders of cerebrospinal fluid circulation","volume":"5","author":"Knowler","year":"2018","journal-title":"Front Vet Sci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1111\/j.1740-8261.1999.tb00884.x","article-title":"Reversible magnetic resonance imaging abnormalities in dogs following seizures","volume":"40","author":"Mellema","year":"1999","journal-title":"Vet Radiol Ultrasound."},{"key":"B22","doi-asserted-by":"publisher","first-page":"12805","DOI":"10.1038\/srep12805","article-title":"Anti-NMDA receptor encephalitis in the polar bear (Ursus maritimus) knut","volume":"5","author":"Pr\u00fcss","year":"2015","journal-title":"Sci Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1038\/s41380-017-0011-3","article-title":"Uncoupling the widespread occurrence of anti-NMDAR1 autoantibodies from neuropsychiatric disease in a novel autoimmune model","volume":"24","author":"Pan","year":"2019","journal-title":"Mol Psychiatry."},{"key":"B24","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1111\/jvim.12026","article-title":"Suspected limbic encephalitis and seizure in cats associated with voltage-gated potassium channel (VGKC) complex antibody","volume":"27","author":"Pakozdy","year":"2013","journal-title":"J Vet Intern Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1111\/jvim.15492","article-title":"Deleted in colorectal cancer (netrin-1 receptor) antibodies and limbic encephalitis in a cat with hippocampal necrosis","volume":"33","author":"Hasegawa","year":"2019","journal-title":"J Vet Intern Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1038\/s41582-018-0074-z","article-title":"A cross-species approach to disorders affecting brain and behaviour","volume":"14","author":"Devinsky","year":"2018","journal-title":"Nat Rev Neurol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1292\/jvms.66.295","article-title":"Prevalence of autoantibody in cerebrospinal fluids from dogs with various CNS diseases","volume":"66","author":"Matsuki","year":"2004","journal-title":"J Vet Med Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"403","DOI":"10.3389\/fneur.2020.00403","article-title":"Clinical characteristics of anti-GABA-B receptor encephalitis","volume":"11","author":"Zhu","year":"2020","journal-title":"Front Neurol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S1474-4422(15)00401-9","article-title":"A clinical approach to diagnosis of autoimmune encephalitis","volume":"15","author":"Graus","year":"2016","journal-title":"Lancet Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.tvjl.2018.06.001","article-title":"review of treatment options for behavioural manifestations of clinical anxiety as a comorbidity in dogs with idiopathic epilepsy","volume":"238","author":"Watson","year":"2018","journal-title":"Vet J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e0192182","DOI":"10.1371\/journal.pone.0192182","article-title":"Cognitive dysfunction in naturally occurring canine idiopathic epilepsy","volume":"13","author":"Packer","year":"2018","journal-title":"PLoS ONE"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1111\/jvim.15552","article-title":"Behavioral and clinical signs of Chiari-like malformation-associated pain and syringomyelia in Cavalier King Charles spaniels","volume":"33","author":"Rusbridge","year":"2019","journal-title":"J Vet Intern Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s12917-017-1077-5","article-title":"Cavalier King Charles Spaniels with Chiari-like malformation and Syringomyelia have increased variability of spatio-temporal gait characteristics","volume":"13","author":"Olsen","year":"2017","journal-title":"BMC Vet Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S1474-4422(09)70324-2","article-title":"Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen","volume":"9","author":"Lancaster","year":"2010","journal-title":"Lancet Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"843","DOI":"10.2169\/internalmedicine.3652-19","article-title":"Autoimmune encephalitis associated with anti-gamma-aminobutyric acid B receptor antibodies mimicking syncope","volume":"59","author":"Kitazaki","year":"2020","journal-title":"Intern Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1016\/S1474-4422(08)70224-2","article-title":"Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies","volume":"7","author":"Dalmau","year":"2008","journal-title":"Lancet Neurol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S1474-4422(12)70310-1","article-title":"Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study","volume":"12","author":"Titulaer","year":"2013","journal-title":"Lancet Neurol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"131","DOI":"10.2214\/ajr.152.1.131","article-title":"Dyke award. Gd-DTPA-enhanced MR imaging of experimental bacterial meningitis: evaluation and comparison with CT","volume":"152","author":"Mathews","year":"1989","journal-title":"Am J Roentgenol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1111\/j.1740-8261.1996.tb01254.x","article-title":"Magnetic Resonance Imaging in the diagnosis of focal granulomatous meningoencephalitis in two dogs","volume":"37","author":"Lobetti","year":"1996","journal-title":"Vet Radiol Ultrasound."},{"key":"B40","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/j.1939-165X.2006.tb00138.x","article-title":"Cerebrospinal fluid analysis and magnetic resonance imaging in the diagnosis of neurologic disease in dogs: a retrospective study","volume":"35","author":"Bohn","year":"2006","journal-title":"Vet Clin Pathol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/j.1740-8261.2005.00003.x","article-title":"Magnetic resonance imaging findings in 25 dogs with inflammatory cerebrospinal fluid","volume":"46","author":"Lamb","year":"2005","journal-title":"Vet Radiol Ultrasound."},{"key":"B42","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.tvjl.2009.03.031","article-title":"Clinical findings and treatment of non-infectious meningoencephalomyelitis in dogs: a systematic review of 457 published cases from 1962 to 2008","volume":"184","author":"Granger","year":"2010","journal-title":"Vet J."},{"key":"B43","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/S2215-0366(17)30330-9","article-title":"Functional connectivity of large-scale brain networks in patients with anti-NMDA receptor encephalitis: an observational study","volume":"4","author":"Peer","year":"2017","journal-title":"Lancet Psychiatry."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e457","DOI":"10.1212\/NXI.0000000000000457","article-title":"Diagnosing MRI-negative autoimmune diseases","volume":"5","year":"2018","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B45","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1002\/ana.23932","article-title":"Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis","volume":"74","author":"Finke","year":"2013","journal-title":"Ann Neurol."},{"key":"B46","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/B978-0-12-057550-3.50072-7","article-title":"Metabolism of immunoglobulins","volume-title":"Progress in Immunology.","author":"Waldmann","year":"1971"},{"key":"B47","doi-asserted-by":"publisher","first-page":"12696","DOI":"10.1038\/s41598-020-69618-3","article-title":"Pre-existing canine anti-IgG antibodies: implications for immunotherapy, immunogenicity testing and immunoassay analysis","volume":"10","author":"Bergman","year":"2020","journal-title":"Sci Rep."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1093\/clinchem\/37.7.1153","article-title":"Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain","volume":"37","author":"Reiber","year":"1991","journal-title":"Clin Chem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13317-019-0124-6","article-title":"Associations between HLA and autoimmune neurological diseases with autoantibodies","volume":"11","author":"Mu\u00f1iz-Castrillo","year":"2020","journal-title":"Autoimmun Highlights."},{"key":"B50","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.rvsc.2008.10.002","article-title":"Heritability and transmission analysis of necrotizing meningoencephalitis in the Pug","volume":"86","author":"Greer","year":"2009","journal-title":"Res Vet Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1111\/j.1939-1676.2004.tb02605.x","article-title":"Inheritance of occipital bone hypoplasia (Chiari type I malformation) in Cavalier King Charles Spaniels","volume":"18","author":"Rusbridge","year":"2004","journal-title":"J Vet Intern Med."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.886711\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T04:49:51Z","timestamp":1655959791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.886711\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,23]]},"references-count":51,"alternative-id":["10.3389\/fvets.2022.886711"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2022.886711","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,23]]},"article-number":"886711"}}