{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T05:27:46Z","timestamp":1783747666989,"version":"3.55.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":1313,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Necrotizing meningoencephalitis (NME) in the pug dogs is a fatal neuroinflammatory disease associated with rapid progression and poor response to conventional immunosuppressive therapy. Diagnosis is typically made after severe neurological abnormalities have manifested.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis\/Objective<\/jats:title>\n                    <jats:p>Pug dogs at genetic risk for NME might manifest neurological abnormalities before developing pathognomonic clinical signs of NME.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Thirty-six pug dogs less than 4\u2009years of age asymptomatic for NME.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective observational cohort study with germline genome-wide genotyping. Neurological examinations were performed 4\u2009weeks apart to document reproducible findings of central nervous system disease. Magnetic resonance imaging, cerebrospinal fluid analysis, and testing for infectious diseases were performed in all pugs with reproducible abnormalities detected on neurological examination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall risk allele frequency in this cohort was 40%; 5 (14%) dogs were high risk, 19 (53%) dogs were medium risk, and 12 (33%) dogs were low genetic risk for NME. Reproducible abnormalities detected on neurological examination were identified in 8\/24 (33%) genetically at-risk dogs and 0\/12 (0%) low risk dogs. Clinical abnormalities included multifocal spinal pain in 8\/8, reduced menace response in 5\/8, and lateralizing postural reaction deficits in 5\/8 pugs. There was a strong association between genotype risk and the presence of this clinical phenotype (P\u00a0=\u00a0.03).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Our findings suggest the presence of a novel early clinical phenotype of NME in apparently asymptomatic genetically at-risk pugs which might be used to plan early diagnostic and therapeutic clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.16444","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T05:54:19Z","timestamp":1653630859000},"page":"1382-1389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A potential early clinical phenotype of necrotizing meningoencephalitis in genetically at-risk pug dogs"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7443-2912","authenticated-orcid":false,"given":"Rebecca","family":"Windsor","sequence":"first","affiliation":[{"name":"Ethos Veterinary Health , Woburn, Massachusetts,","place":["USA"]},{"name":"Ethos Discovery (501c.3.) , San Diego, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1148-2589","authenticated-orcid":false,"given":"Samuel","family":"Stewart","sequence":"additional","affiliation":[{"name":"Ethos Veterinary Health , Woburn, Massachusetts,","place":["USA"]},{"name":"Ethos Discovery (501c.3.) , San Diego, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Ethos Veterinary Health , Woburn, Massachusetts,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Mosqueda","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute , Phoenix, Arizona,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazio","family":"Piras","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute , Phoenix, Arizona,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan M.","family":"Keller","sequence":"additional","affiliation":[{"name":"Microbiology, Immunology, University of California, Davis Department of Pathology, , Davis, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana","family":"Steinmetz","sequence":"additional","affiliation":[{"name":"Ethos Veterinary Health , Woburn, Massachusetts,","place":["USA"]},{"name":"Ethos 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