Meningoencephalomyelitis of Unknown Origin in Dogs:

Utility of S100B as a Diagnostic Biomarker

Abstract

Background: Meningoencephalomyelitis of unknown origin (MUO) is an immune-mediated, noninfectious inflammatory disease of the canine central nervous system (CNS). Despite its clinical importance, diagnosis remains presumptive, as definitive confirmation requires histopathology. Therefore, reliable biomarkers are required to improve diagnostic accuracy. Astrocytic S100B, which contributes to neuroinflammation and oxidative stress, may serve as a potential biomarker for MUO. This study aimed to evaluate S100B in dogs with MUO compared to healthy controls (HC) and those with idiopathic epilepsy (IE).

Materials, Methods & Results: This study included 43 client-owned dogs: 16 with MUO, 13 with IE, and 14 HC based on clinical records, cerebrospinal fluid (CSF) analysis, and magnetic resonance imaging (MRI) findings. Blood and CSF samples were collected on the day of MRI and S100B concentrations were measured. Nonparametric and inferential statistical analyses were performed. CSF and serum S100B levels were significantly higher in dogs with MUO than in HC or IE. S100B levels were not significant between HC and IE groups in either CSF or serum. A significant correlation was found between S100B levels in CSF and serum. Receiver operating characteristic curve analysis for MUO versus control indicated that a CSF S100B cutoff of 699.11 pg/mL yielded 85.7% sensitivity and 84.2% specificity, whereas 835.82 pg/mL provided 71.4% sensitivity and 100% specificity. For serum S100B, a cutoff of 782.39 pg/mL showed 100% sensitivity and 84.2% specificity, whereas 977.06 pg/mL had 85.7% sensitivity and 100% specificity. 

Discussion: Both CSF and serum S100B concentrations were significantly elevated in dogs with MUO compared with healthy and epileptic controls, supporting the involvement of S100B in the neuroinflammatory pathogenesis of the disease. This finding aligns with previous evidence from human neuroinflammatory conditions such as multiple sclerosis, suggesting a conserved mechanism of astrocytic activation and S100B overexpression during central nervous system inflammation. The strong correlation between CSF and serum S100B levels further demonstrates that peripheral S100B reflects intracranial pathology and blood-brain barrier disruption, providing a feasible and minimally invasive diagnostic approach. These results indicate that measuring S100B could improve diagnostic confidence when magnetic resonance imaging or cerebrospinal fluid analysis yields inconclusive results, reducing reliance on invasive procedures. Moreover, the availability of a serum-based assay may enhance its translational potential and feasibility within veterinary diagnostic applications. In addition, the absence of elevated S100B in idiopathic epilepsy emphasizes its diagnostic specificity for inflammatory rather than non-inflammatory neurological disorders, reinforcing its potential utility in differentiating neuroinflammation from seizure disorders without structural lesions. Although the study was limited by small sample size and the lack of other structural CNS disease controls, the consistent increase in both serum and CSF S100B provides compelling evidence that this astrocytic protein represents a promising diagnostic and possibly therapeutic biomarker for MUO. Future large-scale investigations incorporating disease severity, treatment monitoring, and other CNS pathologies are warranted to confirm its clinical applicability and explore the benefits of targeting S100B-mediated neuroinflammatory pathways.

Keywords: cerebrospinal fluid, dog, idiopathic epilepsy, meningoencephalomyelitis of unknown origin, S100B.