Meningoencephalitis of unknown origin (MUO) in dogs under veterinary referral care in England (2017-2021): a multicentre case control study

Yeonsoo Choi¹Dan Gerard O'Neill²Edward Ives³Thomas Robert Harcourt-Brown¹Bruno Lopes^3,4Lisa Alves⁵Thomas Cardy⁶Marco Ruggeri⁷Anna Tauro^7,8Giunio Bruto Cherubini^10,9Mark Lowrie¹¹Louisa Saunders^12,13Nicolas Granger¹²Maria Stefaniuk¹⁴Rodolfo Capello^14,15Raquel Trevail¹⁶Sophie Adamantos¹⁷Rita Goncalves¹⁸Steven De Decker¹⁹Angela Fadda^1*

• ¹Bristol Veterinary School, University of Bristol, Langford Vets Small Animal Referral Hospital, Langford, United Kingdom
• ²The Royal Veterinary College Department of Pathobiology and Population Sciences, Hatfield, United Kingdom
• ³Anderson Moores Veterinary Specialists, Winchester, United Kingdom
• ⁴Southfields Veterinary Specialists, Basildon, United Kingdom
• ⁵University of Cambridge Department of Veterinary Medicine, Cambridge, United Kingdom
• ⁶Cave Veterinary Specialists Ltd, Wellington, United Kingdom
• ⁷ChesterGates Veterinary Referrals, Chester, United Kingdom
• ⁸Access Specialty Animal Hospital, Pasadena, United States
• ⁹Dick White Referrals Ltd, Six Mile Bottom, United Kingdom
• ¹⁰Universita degli studi di Pisa Dipartimento di Scienze Veterinarie, Pisa, Italy
• ¹¹Movement Referrals: Independent Veterinary Specialists, Uttoxeter, United Kingdom
• ¹²Bristol Vet Specialists, Bristol, United Kingdom
• ¹³Shepton Veterinary Group Ltd, Shepton Mallet, United Kingdom
• ¹⁴North Downs Specialist Referrals, Bletchingley, United Kingdom
• ¹⁵South East Vet Referrals, Sevenoaks, United Kingdom
• ¹⁶Southern Counties Veterinary Specialists, Ringwood, United Kingdom
• ¹⁷Paragon Veterinary Referrals, Wakefield, United Kingdom
• ¹⁸University of Liverpool School of Veterinary Science, Neston, United Kingdom
• ¹⁹Royal Veterinary College, London, United Kingdom

Background: A considerable body of published research on meningoencephalitis of unknown origin (MUO) exists; however, certain fundamental aspects relating to the epidemiology remain poorly characterised. These include frequency of MUO diagnosis at referral level, reliable demographic risk factors, and extent to which proposed diagnostic criteria are applied in referral clinical settings. Methods: Based on 1121 MUO cases (01 January 2017 to 31 December 2021) treated at 13 referral centres in England and 750,000 control dogs from the VetCompass Programme, this study investigated a range of demographic risk factors using multivariable logistic regression analysis. Additionally, we report on clinical methods used for diagnosis. Results: MUO represented 2.21% (95% CI: 2.08 – 2.34) of new neurological referrals (1121/50721). Clinical diagnosis included both magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis in 1026 (91.5%) cases. Of these, 961 (89.3%) showed results indicative of MUO in both MRI and CSF. Abnormal MRI but normal CSF were found in 55 cases (5.4%), while normal MRI and abnormal CSF were found in 36 cases (3.5%). Both normal MRI and normal CSF were reported in 19 cases (1.5%). Screening for infectious disease was carried out in 1037 (92.5%) of cases. The diagnosis of MUO peaked at 4 years (median 4.33, IQR 2.50–6.92, range 0.30–15.00) and declined after age 10. Welsh Springer Spaniel (OR 23.76, 95% CI 10.37–54.43), Maltese (OR 20.53, 95% CI 14.53–29.01), Papillon (OR 17.48, 95% CI 7.66–39.91), Boston Terrier (OR 17.31, 95% CI 11.17–26.82), and French Bulldog (OR 9.14, 95% CI 7.14–11.71) had the highest MUO odds compared to crossbreed dogs. Brachycephalic breeds had 2.56 times higher odds (95% CI 2.23–2.95) than mesocephalic breeds. Dogs ≥15kg had lower odds than those <10kg. Conclusion: This study provides the largest referral-based analysis of MUO cases to date, offering updated insights into breed predispositions and clinical diagnosis. This characterisation of the demographic factors adds valuable context for future research design, particularly in breed-focused investigations and risk stratification. By documenting current diagnostic practices used by referral specialists, this work lays the foundation for greater consistency in case recognition and offers practical guidance for structuring future MUO clinical trials.