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OBJECTIVE: To describe the long-term outcomes, overall survival, progression-free survival, and prognostic factors in dogs with necrotizing encephalitis (NE). ANIMALS: 37 client-owned dogs clinically diagnosed with NE. METHODS: All dogs underwent MRI and CSF analysis. Cox proportional hazards regression was used to examine factors related to the risk of relapse and death, including signalment, history, diagnostic investigation results, and treatments before the first relapse. RESULTS: The medians of the overall and progression-free survival times were 639 days (IQR, 342 to 1,482 days) and 233 days (IQR, 111 to 775 days), respectively. Overall survival was highly correlated with progression-free survival. Four dogs (11%) died or were euthanized within 3 months of diagnosis. Relapse within 6 months was associated with a shorter overall survival. However, no prognostic factors for overall survival were found. The category of patients with presenting clinical signs that lasted 29 days to 6 months (OR, 3.26; 95% CI, 1.35 to 7.90) was associated with a higher risk of relapse. Seizures were presented in 75.7% of dogs, with a recurrence rate of 100%. CLINICAL RELEVANCE: This report provides comprehensive follow-up information for dogs with NE, revealing a fair prognosis and low early mortality rate. Seizure is a very common clinical sign with a high recurrence rate.
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Idiopathic non-infectious meningoencephalomyelitis (NIME), which is thought to be an immune-mediated disease, is a common inflammatory disease in dogs. Meningoencephalomyelitis of unknown origin (MUO), a subgroup of NIME, consists of necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis, and granulomatous meningoencephalomyelitis. Recent studies have shown associations between disease development and dog leukocyte antigen (DLA) class II genes in NME in Pugs and in NIME in Greyhounds. This study focused on Chihuahuas, which have a high incidence of MUO and are one of the most common dog breeds in Japan. Because the development of MUO seems to be associated with DLA class II genes, we aimed to evaluate the association between DLA class II genes and MUO development in Chihuahuas. Blood samples were obtained from 22 Chihuahuas with MUO (MUO group) and 46 without neurological diseases (control). The allele sequences of three DLA class II loci were determined, and haplotypes were estimated from these data. In total, 23 haplotypes were detected. The frequency of one haplotype (DLA-DRB1*015:01--DQA1*006:01--DQB1*023:01) was significantly higher in the MUO group than in the control group (odds ratio, 7.11; 95% confidence interval, 1.37-36.81; P=0.0141). The results suggest that the development of MUO in Chihuahuas may be associated with DLA class II genes. Because the identified risk haplotypes differed from those of other breeds, the pathogenesis of NIME-related diseases may differ among dog breeds.
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Enfermedades de los Perros , Leucocitos , Perros , Animales , Haplotipos , Alelos , Japón/epidemiología , Enfermedades de los Perros/genéticaRESUMEN
Meningoencephalomyelitis of unknown origin (MUO) is a common disorder in dogs that results in mononuclear inflammation in the brain and/or spinal cord. MUO is presumed to be autoimmune but specific immunological aberrations have not been identified. This exploratory study aimed to evaluate T cell production of two cytokines commonly implicated in autoimmune disease, interferon-gamma (IFNg) and interleukin-17 (IL17). Peripheral blood mononuclear cells were obtained from 12 dogs with MUO and 10 healthy controls, stimulated to activate intracellular signaling pathways, and stained with a cluster of differentiation 4 (CD4), cluster of differentiation eight (CD8), IFNg, and IL17 antibodies prior to analysis by flow cytometry. Mean differences in absolute cell numbers are represented as MUO cases minus healthy controls, and 95% Cis are reported. Overall IFNg-producing lymphocytes (mean difference = 241.8 cells/ul, 95% CI = 65.6 to 418.1) and CD4+ IFNg-producing T-cells (mean difference = 188.4, 95% CI = 77.3 to 299.5) were fewer in MUO cases. Additionally, CD4+ IL17-producing T-cells were greater in MUO cases (mean difference -34.9, 95% CI = -50.54 to -19.17) and CD8+ IL17-producing T-cells were fewer in MUO cases (mean difference = 73.5, 95% CI = 6.8 to 140.1). These results support that immunological changes can be identified in peripheral blood cells of dogs with MUO and suggest that T-helper type 17 (Th17) cells may play a role in pathogenesis.
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Meningoencephalomyelitis of unknown origin (MUO) is a common disorder of dogs that results in significant morbidity and mortality. The ideal treatment regimen is not known but a second immunosuppressive agent is often utilized in combination with glucocorticoids to increase efficacy and reduce side effects. Recently, a benefit to using a cytosine arabinoside (CA) constant rate infusion (CRI) at the time of diagnosis has been demonstrated. Here, a retrospective study was performed to determine if administration of CA at the time of diagnosis would alter prognosis in dogs receiving cyclosporine and prednisone for treatment of MUO. Medical records of 51 client-owned dogs diagnosed with MUO at one institution were reviewed (2009-2019). All dogs were treated with cyclosporine and a tapering course of prednisone. Twenty-one dogs received a single initial 200 mg/m2 treatment with CA either as a CRI or subcutaneously. Significantly more patients in the CA treatment group were obtunded on presentation but all other baseline parameters were similar between groups. No differences in success (defined as sustained improvement on neurological exam with owner perceived good quality of life), relapse, or death were identified at 1-, 3-, 6-, 9-, 12-, 18-, or 36-month time points. These results do not support treatment with CA (either as a CRI or subcutaneously) at the time of diagnosis in dogs treated with cyclosporine and prednisone.
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Canine non-infectious inflammatory meningoencephalomyelitis is termed meningoencephalomyelitis of unknown origin (MUO) and may affect dogs of every breed at any age. Treatment with immunosuppressive medication, the survival time based on MRI, and cerebrospinal fluid (CSF) findings has been widely reported; however, these studies only included a small number of patients, or they are summaries from the literature. Therefore, the aim of this study was to compare the clinical presentation, diagnostic findings, treatment protocol and long-term survival time in many dogs diagnosed with MUO in one clinic with previously published studies. One hundred eighty-two dogs met the inclusion criteria. Age, sex, duration of clinical signs before diagnosis, presence of neurological signs, MRI and CSF analysis were similar to those in previous reports. Our study revealed that dogs with a brainstem lesion have a 60% lower chance of death before 1 year than dogs with multifocal brain lesions. A total of 55.56% of treated dogs survived for more than 1 year, and 10.55% survived for more than 5 years since diagnosis. The median survival time for all dogs was 540 days. Our findings support glucocorticosteroid monotherapy as a viable treatment option for dogs with MUO.
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Enfermedades de los Perros , Meningoencefalitis , Animales , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Europa (Continente) , Imagen por Resonancia Magnética/veterinaria , Meningoencefalitis/diagnóstico , Meningoencefalitis/tratamiento farmacológico , Meningoencefalitis/veterinariaRESUMEN
The objective of this study was to evaluate the pharmacokinetics of the standard cytarabine (Ara-C) protocol (50 mg/m2 subcutaneously every 12 hr for 2 days) used for dogs with neuroinflammatory disease and compare it to two more practical protocols (a single 200 mg/m2 subcutaneous dose and two 100 mg/m2 subcutaneous doses every 12 hr). Four client-owned dogs previously diagnosed with meningoencephalomyelitis of unknown origin were administered three distinct Ara-C protocols with a 21-day washout between each protocol. A complete blood count was performed seven days after each dosing protocol to assess for clinically relevant myelosuppression. No adverse events were observed. Plasma Ara-C concentrations were measured using a validated liquid chromatography coupled to tandem mass spectrometry assay. The mean maximal concentrations in this study were 4,230, 9,293, and 16,675 ng/ml for a single dose of 50, 100, and 200 mg/m2 , respectively. There was a linear relationship between dose and drug exposure. Drug exposure was similar regardless of the dosing protocol when the total dose was analyzed, with an area under the concentration versus time curve of 37,026, 38,465, and 32,510 ng × hr/ml for 50, 100, and 200 mg/m2 , respectively.
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Citarabina/farmacocinética , Citarabina/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Meningoencefalitis/veterinaria , Animales , Área Bajo la Curva , Citarabina/administración & dosificación , Enfermedades de los Perros/sangre , Perros , Relación Dosis-Respuesta a Droga , Femenino , Semivida , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Inyecciones Subcutáneas , Masculino , Meningoencefalitis/tratamiento farmacológicoRESUMEN
The potential of microRNAs (miRNAs) as biomarkers for canine meningoencephalomyelitis of unknown origin (MUO) was investigated by using quantitative real-time (qRT)-PCR to determine the expression of microRNA-21 (miR-21) and microRNA-181c (miR-181c) in the cerebrospinal fluid (CSF) of dogs. Dogs with MUO (n = 10) had higher levels of expression of miR-21 and miR-181c in the CSF than dogs with non-inflammatory neurological diseases (n = 8). There was a positive correlation between CSF cellularity and expression of miRNAs in the CSF, particularly for miR-21 in the MUO group.