Demystifying immune-mediated CNS disease

Small and toy breeds, like pugs, are predisposed to necrotizing forms of meningoencephalitis , suggesting some degree of genetic influence. (Image: Shutterstock.com)

Meningoencephalitis of unknown etiology (MUE) is a general term encompassing several immune-mediated central nervous system (CNS) diseases that are typically diagnosed after ruling out infectious causes. MUE accounts for up to 25% of all CNS disorders in canine patients.

A recent review by veterinarians at University of Illinois-Urbana summarized causes of MUE, which they admitted is “challenging to diagnose and manage.”1

Disease presentation

The three main MUE diseases discussed-granulomatous meningoencephalitis (GME), necrotizing leukoencephalitis (NLE) and necrotizing meningoencephalitis (NME)-are characterized based on histologic appearance and localization within the CNS. The median age at presentation is 5 years, and young females are generally overrepresented.

Small and toy breeds are predisposed to necrotizing forms of the disease, suggesting some degree of genetic influence. Previous names for NME and NLE were “pug dog encephalitis” and “Yorkie encephalitis,” respectively. In contrast, GME has been reported in a wide range of ages and breeds. Clinical signs typically depend on the disease's location within the cerebrum, cerebellum, brainstem and/or spinal cord, and seizures are especially common with NME.  

Thus far, researchers have failed to correlate any infectious pathogens with MUE, although several dogs have tested positive for Mycoplasma spp.2 In another study, fecal microbiome populations varied between dogs with MUE and normal controls.3

Diagnosis

Magnetic resonance imaging (MRI) is the gold standard antemortem diagnostic test for MUE, which cannot be differentiated from other neurologic diseases via patient examination or blood work. However, some MUE cases are normal on MRI but may have increased leukocyte percentages on cerebrospinal fluid (CSF) analysis. One study also used antemortem, MRI-guided biopsy of forebrain tissue to successfully characterize 14 of 17 MUE cases to a specific subtype; however, neurologic signs worsened for 29% of dogs afterward, indicating some risk associated with the procedure.4

Cortisol, thyroid hormone and creatine phosphokinase levels should be measured in all MUE cases to look for metabolic or systemic causes of neurologic disease; also, underlying infections with protozoal, viral, tickborne and fungal diseases should be ruled out before instituting treatment.

Treatment and prognosis

Immunosuppressive therapy using glucocorticoids dosed at 1 to 2 mg/kg/day is the current mainstay of MUE treatment. Studies suggest the first few months of treatment are the most critical for prognosis, and survival is longest for dogs showing a complete response to therapy without relapse.5-7 Prognosis is relatively poor for dogs presenting with decreased mentation, seizures and increased neutrophil percentage in CSF.8

Studies also showed that prognosis and median survival time (MST) were significantly shorter for dogs with multifocal disease (8 days) compared with those with focal disease (114 days), while dogs with spinal-only disease had the longest MST (669 days).9 CSF cell count and severity of MRI lesions did not affect overall survival time in most studies.

What to remember

MUE should be considered for young and middle-aged dogs presenting with neurologic signs, particularly small breeds such as the Pug and Yorkie. Diagnosis should rule out infectious, metabolic and neoplastic causes of disease before steroid therapy is initiated. Prognosis is generally guarded.

Dr. Stilwell provides freelance medical writing and aquatic veterinary consulting services through her business, Seastar Communications and Consulting. In addition to her DVM obtained from Auburn University, she holds a MS in fisheries and aquatic sciences and a PhD in veterinary medical sciences from the University of Florida.

References

Vitale S, Foss K. Immune-mediated central nervous system disease-current knowledge and recommendations. Top Compan Anim Med 2019;34:22-29.

Barber RM, Porter BF, Li Q, et al. Broadly reactive polymerase chain reaction for pathogen detection in canine granulomatous meningoencephalomyelitis and necrotizing meningoencephalitis. J Vet Intern Med 2012;26:962-968.

Jeffery ND, Barker AK, Alcott CJ, et al. The association of specific constituents of the fecal microbiota with immune-mediated brain disease in dogs. PLoS ONE 2017;12:e0170589.

Flegel T, Oevermann A, Oechtering G, et al. Diagnostic yield and adverse effects of MRI-guided free?hand brain biopsies through a mini-burr hole in dogs with encephalitis. J Vet Intern Med 2012;26:969-976.

Flegel T, Boettcher IC, Matiasek K, et al. Comparison of oral administration of lomustine and prednisolone or prednisolone alone as treatment for granulomatous meningoencephalomyelitis or necrotizing encephalitis in dogs. J Am Vet Med Assoc 2011;238:337-345.

Smith PM, Stalin CE, Shaw D, et al. Comparison of two regimens for the treatment of meningoencephalomyelitis of unknown etiology. J Vet Intern Med 2009;23:520-526.

Wong MA, Hopkins AL, Meeks JC, et al. Evaluation of treatment with a combination of azathioprine and prednisone in dogs with meningoencephalomyelitis of undetermined etiology: 40 cases (2000-2007). J Am Vet Med Assoc 2010;237:929-935.

Cornelis I, Volk HA, Van Ham L, et al. Prognostic factors for 1-week survival in dogs diagnosed with meningoencephalitis of unknown aetiology. Vet J 2016;214:91-95.

Muñana KR, Luttgen PJ. Prognostic factors for dogs with granulomatous meningoencephalomyelitis: 42 cases (1982-1996). J Am Vet Med Assoc 1998;212:1902-1906.