Avances en el estudio de biomarcadores en el líquido cefalorraquídeo canino y su relevancia en las meningoencefalitis de origen desconocido

Resumen

Background: Inflammatory diseases of the central nervous system (CNS), in dogs, are difficult processes to diagnose due to the structure of this organ and the low percentage of cases observed in the clinic. Imaging tests and cerebrospinal fluid (CSF) analysis are essential for diagnosis. In dogs with meningoencephalitis of unknown etiology (MOU), definitive diagnosis of these animals is only possible postmortem, since magnetic resonance imaging (MRI) and CSF analysis are unable to provide a definitive diagnosis, nor to distinguish between the different subtypes of MOU. For this reason, a panel of 26 parameters was measured (total protein, creatinine, urea, calcium, phosphorus, UIBC, iron, ferritin, amylase, CK, ALT, LDH, cholesterol, triglycerides, ALP, GGT, AST, glucose, C-reactive protein, haptoglobin, ADA, TIOL, CUPRA, TEA, ACHE and BCHE) in CSF, to search for biomarkers, which help early diagnosis and distinction between subtypes, in animals suffering from this type of pathologies. Material and methods: The animals in this study were divided into: control group (group A), composed of animals with idiopathic epilepsy and problem group, which was subdivided into two: dogs with MOU (group B) and dogs with MOU treated with glucocorticoids (group C). MRI and routine CSF analysis were obtained in all of them, ruling out meningoencephalitis of infectious origin in the animals with MOU. CSF parameters were measured using an automatic biochemistry analyzer. To perform the comparative study between groups (control group, problem group and problem group with corticoids), the Kruskal-Wallis nonparametric test was applied, followed by Dunn's test for multiple comparisons. Results: After measurement of the 26 parameters it was observed that 19 could be detected in canine CSF (total proteins, creatinine, urea, calcium, phosphorus, ferritin, amylase, cholesterol, triglycerides, LDH, AST, GGT, glucose, CRP, ADA, CUPRA, TEA, ACHE and BCHE) showing some of them statistically significant alterations between groups, while in other parameters their measurement was not possible (UIBC, iron, CK, ALT, ALP, haptoglobin and TIOL). Discussion: The use of biomarkers for the early diagnosis of inflammatory diseases of the CNS is a trend in human medicine. These biomarkers have not only been used for early diagnosis, but also to provide a prognosis and even to monitor the effectiveness of certain treatments. In the case of MOU, so far there are no studies with relevant information that would be able to solve the major drawback of not being able to obtain a definitive diagnosis of these pathologies, other than postmortem. Nor that would help to stop the diagnosis of the different subtypes of these diseases from being made in a presumptive manner. The measurement of a panel of analytes has been useful, as different values in CSF parameters were observed between the control group and the problem group. These results could be useful as early markers of this pathology, helping to distinguish between the different subtypes of MOU and could even be useful for the prognosis of the disease and the follow-up of the animals under treatment. Conclusions: There are CSF analytes that vary in dogs with idiopathic epilepsy and dogs with MOU that could be used as biomarkers of these pathologies. In addition, other analytes are detectable in canine CSF, but do not vary in dogs with idiopathic epilepsy and dogs with MOU. Finally, other parameters could not be detected in the CSF of the dogs included in this study and their measurement using other more sensitive analytical techniques should be considered. The administration of glucocorticoids varies the results obtained in CSF, a fact that should be considered for the correct interpretation of these analytes in dogs treated with these drugs.