Steroid-responsive myelitis in dogs - comparison with steroid-responsive meningitis-arteritis

Background: Myelitis is the inflammation of the spinal cord parenchyma alone, whereas meningitis is the inflammation of the meninges. Steroid-responsive meningitis-arteritis (SRMA) is a meningomyelitis in which the major lesions involve the meninges, not the spinal cord parenchyma, and respond well to glucocorticoid treatment. However, myelitis in dogs has rarely been reported, and myelitis with a good response to glucocorticoid treatment without relapse has not been reported. This report describes 5 cases of steroid-responsive myelitis (SRM) in dogs. Cases: Case 1. A 8-year-old intact female Cocker Spaniel presented with progressive nonambulatory paraplegia. Whole spinal parenchymal lesions were identified using magnetic resonance imaging (MRI) scan. Mononuclear pleocytosis with increased total protein levels was the only abnormal finding on cerebrospinal fluid (CSF) analysis. Prednisolone (PDS) was administered followed by dose tapering according to therapeutic response. Cyclosporine was administered until the termination of PDS. Since then, no recurrence of neurological symptoms has been observed. Follow-up MRI and CSF analysis revealed resolution of previously observed abnormal findings. Case 2. A 2-year-old intact female Maltese presented with non-progressive paraparesis. A spinal parenchymal lesion in the lumbosacral region was observed on MRI. PDS was administered and slowly tapered at approximately 3-week intervals. No recurrence of neurological symptoms was observed after the treatment. Case 3. A 6-year-old intact female Miniature Pinscher presented with neck pain, along with leukocytosis and neutrophilia. Cervical spinal parenchyma lesions were revealed through MRI. Increased total protein concentration with mixed cell pleocytosis was observed on CSF analysis. Immunomodulatory therapy, similar to that in case 2, was initiated. A second MRI and CSF analysis revealed an improvement in the previously observed abnormalities. Case 4. A 2-year-old, intact female Toy Poodle presented with acute paraplegia and back pain. Lesions were observed in the spinal parenchyma at the T12-L3 levels on MRI. The treatment was conducted as in case 2. During treatment, neurological symptoms, including paraplegia and back pain, were not observed. Follow-up MRI revealed improvement in the spinal lesion. Case 5. A 6-month-old, castrated male Standard Poodle presented with progressive paraparesis. On MRI, lesions were observed in the T11-T13 regions. Immunomodulation therapy, similar to that in case 2, was initiated. No recurrence of neurological symptoms was observed after treatment initiation Discussion: SRM is similar to SRMA in terms of good steroid-responsiveness and noninfectious inflammation etiology; however, it does not exactly satisfy the diagnostic criteria for SRMA, nor does it progress similarly. The characteristics of SRM that do not satisfy the diagnostic criteria of SRMA include the absence of fever, C-reactive protein elevation, hyperglobulinemia, and relapse, and the presence of spinal parenchymal lesions without parenchymal or meningeal enhancement on MRI. It is also a seemingly different from spinal cord-only meningoencephalomyelitis of unknown origin due to its better treatment response and prognosis. However, the dogs in the present report with SRM satisfied the diagnostic criteria for transverse myelitis in human patients. Therefore, SRM, including good steroid responsiveness and good prognosis without relapse, may represent a novel type of meningomyelitis.

Infecção por Gurltia paralysans em gatos domésticos no Estado de Pernambuco, Brasil / Gurltia paralysans infection in domestic cats in the State of Pernambuco, Brazil

Background: The Gurltia paralysans nematode was initially described in Chile and for many years it was believed that thedisease caused by this parasite was restricted to this country. However, in Argentina, Uruguay and more recently in Brazil,among other countries, cases of Gurltiosis have been described in both domestic and wild cats. This disease is chronic anddebilitating due to the progressive paralysis developed. This study aimed to describe the clinical, epidemiological and pathological aspects of G. paralysans infection in domestic cats of the Agreste region of the state of Pernambuco, Northeast Brazil.Case: Clinical, epidemiological and pathological aspects of G. paralysans infection in domestic cats in the rural area oftwo Agreste municipalities in the state of Pernambuco, Brazil, are described. Seven farms were visited, in which 11 maleand female affected felines were evaluated. Among these, euthanasia was performed in four cases, at the owners requestand due to the advanced stage of the disease. Clinical signs began with ataxia of the pelvic limbs and evolved to jumpingdifficulty, lateral falls, muscle atrophy, pelvic limb scarring, and paralysis at the most severe stage of the disease, whichdeveloped in a one-year period, approximately. According to the owners, the affected cats died between six months andone year after the initial clinical signs. At necropsy, there were segments of the spinal cord with extensive reddish areasin the dura, between T7 and S2, corresponding to varices. These were characterized by numerous congestive, dilatedand tortuous blood vessels observed in the dorsal plane, but more pronounced in the ventral plane of the meninges. Inthe bladder, multifocal areas of hemorrhage were observed. Histologically, vascular lesions in veins and venules of theleptomeninges were characterized by venous varices with thrombosis, fibrosis and intravascular parasites associated withmoderate...(AU)

Infecção por Gurltia paralysans em gatos domésticos no Estado de Pernambuco, Brasil / Gurltia paralysans infection in domestic cats in the State of Pernambuco, Brazil

Background: The Gurltia paralysans nematode was initially described in Chile and for many years it was believed that thedisease caused by this parasite was restricted to this country. However, in Argentina, Uruguay and more recently in Brazil,among other countries, cases of Gurltiosis have been described in both domestic and wild cats. This disease is chronic anddebilitating due to the progressive paralysis developed. This study aimed to describe the clinical, epidemiological and pathological aspects of G. paralysans infection in domestic cats of the Agreste region of the state of Pernambuco, Northeast Brazil.Case: Clinical, epidemiological and pathological aspects of G. paralysans infection in domestic cats in the rural area oftwo Agreste municipalities in the state of Pernambuco, Brazil, are described. Seven farms were visited, in which 11 maleand female affected felines were evaluated. Among these, euthanasia was performed in four cases, at the owners’ requestand due to the advanced stage of the disease. Clinical signs began with ataxia of the pelvic limbs and evolved to jumpingdifficulty, lateral falls, muscle atrophy, pelvic limb scarring, and paralysis at the most severe stage of the disease, whichdeveloped in a one-year period, approximately. According to the owners, the affected cats died between six months andone year after the initial clinical signs. At necropsy, there were segments of the spinal cord with extensive reddish areasin the dura, between T7 and S2, corresponding to varices. These were characterized by numerous congestive, dilatedand tortuous blood vessels observed in the dorsal plane, but more pronounced in the ventral plane of the meninges. Inthe bladder, multifocal areas of hemorrhage were observed. Histologically, vascular lesions in veins and venules of theleptomeninges were characterized by venous varices with thrombosis, fibrosis and intravascular parasites associated withmoderate...

TRANSPLANTE DE CÉLULAS-TRONCO MESENQUIMAIS ALOGÊNICAS EM CÃES COM MENINGOENCEFALOMIELITE DE ORIGEM DESCONHECIDA

A meningoencefalomielite de origem desconhecida (MUO) canina é uma doença neuroinflamatória de provável origem imunomediada, altamente debilitante, que apresenta prognostico desfavorável e falha terapêutica com o uso de imunossupressores. As células-tronco mesenquimais (MSCs) são promissoras para o tratamento de doenças neuroimunes, porém, diferentes fontes podem apresentar variações no potencial imunomodulador e neuroprotetor. In vitro, avaliamos a expressão gênica de BDNF, GDNF, HGF, IDO, IL-10 e PTGES2 e o perfil secretório de IL-2, IL-6, IL-8, IL-10, GM-CSF e MCP-1 de MSCs caninas derivadas do tecido adiposo (Ad-MSCs) e placenta (PMSCs) após estimulação única com INF- e combinada com INF- com TNF-. In vivo, avaliamos a resposta terapêutica ao transplante de Ad-MSCs alogênicas em cães com MUO que apresentaram falha terapêutica ao tratamento imunossupressor. Grupo PAC: 12 cães com MUO tratados com o protocolo imunossupressor de citarabina (ara-C) e prednisona. Grupo cMSC: Cinco cães que apresentaram falha terapêutica tratados com dois transplantes de 2,5x106 Ad-MSCs pela via intratecal (IT) (totalizando seis transplantes) ou intravenosa (IV) (totalizando três transplantes), com intervalo de 40 dias. Avaliamos a recuperação funcional, redução das lesões inflamatórias por ressonância magnética (RM) e líquido cefalorraquidiano (LCR). In vitro, observamos aumento significativo na expressão de BDNF, GDNF, HGF e IDO pelas Ad-MSCs após as estimulações, e na expressão de IDO pelas PMSCs após a estimulação combinada. Houve tendência a maior expressão de IL-10 nas células estimuladas de ambas fontes. Houve aumento significativo na secreção de IL-6 pelas Ad-MSCs e de IL-8 pelas PMSCs após estimulação. In vivo, houve tendência a melhora funcional e dos parâmetros inflamatórios no LCR em ambos grupos, indicando efeitos positivos. No grupo cMSC, a maioria dos cães teve remissão parcial e eventos adversos leves foram observados em 4/6 animais após transplantes IT, sendo ausentes pela via IV. Todos os cães do grupo PAC desenvolveram efeitos adversos. Não houve diferenças significativas nas variáveis de hemograma e bioquímica dentro e entre os grupos. O transplante de Ad-MSCs alogênicas em cães com MUO demonstrou efeitos benéficos

Canine meningoencephalomyelitis of unknown origin (MUO) is an immune-mediated neuroinflammatory disease, highly debilitating, with poor prognosis and therapeutic failure. Mesenchymal stem cells (MSCs) are promising for the treatment of neuroimmune diseases. Different sources may present differences in the immunomodulatory/neuroprotective potential. In vitro, we evaluated the gene expression of BDNF, GDNF, HGF, IDO, IL-10 and PTGES2 and the secretory profile of IL-2, IL-6, IL-18, IL-10, GM-CSF and MCP- 1 of canine MSCs derived from adipose tissue (Ad-MSCs) and placenta (PMSCs) after priming with the pro-inflammatory cytokines INF- alone and combined INF- and TNF-. In vivo, we evaluated the clinical response to allogeneic Ad-MSCs transplantation in dogs with MUO. PAC group: 12 dogs treated with immunosuppressant cytarabine (ara-C) and prednisone. cMSC group: 5 dogs of PAC group with therapeutic failure were treated with 2.5x106/kg Ad-MSCs by intrathecal (IT) (n = 6) or intravenous (IV) (n = 3) delivery routes (40 days of interval). Functional recovery and the reduction of inflammatory lesions by magnetic resonance imaging (MR) and cerebrospinal fluid (CSF) were evaluated. In vitro, there was significant increase of BDNF, GDNF, HGF and IDO expression by Ad-MSCs after priming and expression of IDO after combined priming by PMSCs. Ad-MSCs had a significant increase in the secretion of IL-6 and PMSCs of IL-8 after priming. In vivo, a trend towards functional improvement was observed in both groups after treatment. In the cMSC group, most dogs had partial remission and mild adverse events were observed in 4/6 animals after IT transplantations, being absent by IV. Clinical and laboratory variables showed no statistical differences. Allogeneic Ad-MSCs transplantation demonstrated beneficial effects in dogs with MUO.

DETERMINAÇÃO DE BIOMARCADORES NO SANGUE E FLUIDO CEREBROESPINHAL DE CÃES COM AFECÇÃO DO SISTEMA NERVOSO CENTRAL

Lesões encefálicas podem causar debilitações severas em humanos, gerando a necessidade de formas de monitoramento não invasiva que possam servir como método auxiliar no monitoramento, e como fatores prognósticos de curto e longo prazo nestes pacientes. Dentre estes métodos a mensuração de biomarcadores no soro e/ou líquido cerebroespinhal (LCE), a exemplo da Enolase Neuronal Especifica (NSE), da Proteína Ácida Fibrilar Glial (GFAP) e do Lactato, apresentam resultados promissores. Na medicina veterinária, pesquisas similares utilizando os mesmos biomarcadores foram realizadas em cães com afecções do sistema nervoso central, porém, há escassez de dados relacionando-os resultados a aplicabilidade destes na prática clínica como fatores prognósticos. Desta forma doenças de curso agudo e progressivo a exemplo as meningoencefalites infecciosas, e doenças que podem se tornar crônicas, a exemplo das meningoencefalites de causa desconhecida (MOD), o monitoramente em curto e longo prazo usualmente se baseia em avaliações periódicas para realização do exame neurológico; esta avaliação per se pode conter algo de subjetivo o que enfraquece a possibilidade de inferências mais acuradas sobre prognóstico, principalmente em longo prazo. Assim sendo, na busca por um método auxiliar para o monitoramento e que possa servir como fator prognóstico de afecções neurológicas em cães, o objetivo deste estudo foi avaliar se existe correlação entre as mensurações dos biomarcadores citados em amostras de LCE e sangue de cães com doença do sistema nervoso central, e investigar a aplicabilidade destes como fator prognóstico. Para isso foram realizados dois estudos: o primeiro caracterizou-se como transversal prospectivo, no qual foram utilizados 21 cães com afecções do sistema nervoso central. Utilizando-se de amostras de LCE e sangue obtidas no mesmo momento, para a mensuração do lactato no LCE e no plasma imediatamente após a coleta, e para a posterior mensuração da NSE e GFAP foi utilizado amostras de LCE e soro, armazenadas a - 80 o C. Para quantificação da NSE e GFAP foi utilizado o método de ELISA. A avaliação estatística descritiva dos dados foi realizada por meio de média e mediana, e para avaliar a correlação entre os resultados foi utilizado o coeficiente spearman. O resultados obtidos foram os seguintes, respectivamente: NSE do LCE e soro com mediana de 127,23 ng/ml e 76.63 ng/ml; GFAP no LCE e no soro com mediana de 0,67 ng/ml e 0 ng/ml; lactato no LCE e no plasma com mediana de 2,2 mmol/L e 3,10 mmol/L. Somente a NSE e o lactato apresentaram correlação entre os valores do LCE e do soro, sendo 0,60 (p=0,009) e 0,56 (p=0,059), respectivamente. Por questões éticas não se realizou a colheita de LCE de cães saudáveis e, portanto, admitiu-se para fins de controle os resultados obtido em outros estudos, em que os pesquisadores mensuraram a NSE e GFAP no LCE e soro, e lactato no LCE e plasma de cães saudáves. Nesse estudo concului-se que a NSE, GFAP e o lactato estavam aumentados e que valores elevados de NSE estão associados a condições graves e, portanto, podem ser utilizadas como exame complementar na avaliação e monitoramento de cães com afecções sistema nervoso central. No segundo estudo foram analisados retrospectivamente os dados de 25 cães, os quais foram distribuídos em dois grupos, um denominado de grupo meningoencefalite (GM) composto por animais com diagnóstico de MOD e outro designado de grupo controle (GC) composto por 5 animais saudáveis. Foram utilizadas amostras de LCE e soro. As amostras do GM foram obtidas no momento do diagnóstico e armazenadas a -80oC para posterior mensuração dos biomarcadores NSE e GFAP por meio de teste de ELISA. Para as inferências a respeito da sobrevida (prognóstico em longo prazo) utilizou-se o teste estatístico de Kaplan Meyer com o objetivo de se definir a média do tempo de sobrevida em dias dos cães do GM, e a curva característica de operação do receptor (ROC) para determinar o melhor ponto de corte dos biomarcadores em função da média de sobrevida. As mensurações de NSE do GM em amostras de LCE e soro apresentaram valores maiores do que o GC, enquanto a GFAP foi expressa apenas nas amostras de LCE. A média de sobrevida do GM foi de 62 dias, o ponto de corte e a acurácia dos biomarcadores para prever o óbito e piora clínica antes da média de sobrevida foram: LCE-NSE 84,53 ng/ml (85%); soro-NSE 113,47 ng/ml (67,5%); LCE-GFAP 6,93 ng/ml (30%). Não houve correlação entre as amostras de LCE e soro dos biomarcadores. Portanto, conclui-se que os valores de NSE no LCE e soro podem ser utilizados como fator prognóstico de longo prazo para cães com MOD.

Brain injuries can cause severe debilitations in humans, generating the need for non-invasive forms of monitoring that can serve as an auxiliary method in monitoring, and as short and long-term prognostic factors in these patients. Among these methods, the measurement of biomarkers in serum and/or cerebrospinal fluid (CSF), such as Specific Neuronal Enolase (NSE), Glial Fibrillar Acid Protein (GFAP), and Lactate, show promising results. In veterinary medicine, similar research using the same biomarkers has been carried out in dogs with central nervous system disorders, however, there is a lack of data relating the results to their applicability in clinical practice as prognostic factors. Thus, diseases of acute and progressive course, such as infectious meningoencephalitis, and diseases that can become chronic, such as meningoencephalitis of unknown origin (MUO), the short- and long-term monitoring is usually based on periodic evaluations to perform the neurological exam; this assessment per se may contain something subjective, which weakens the possibility of more accurate inferences about prognosis, especially in the long term. Therefore, in the search for an auxiliary method for monitoring that can serve as a prognostic factor for neurological disorders in dogs, the objective of this study was to evaluate whether there is a correlation between the measurements of the biomarkers mentioned in samples of CSF and blood of dogs with disease central nervous system, and to investigate their applicability as a prognostic factor. For this, two studies were carried out: the first was characterized as a prospective cross-section, in which 21 dogs with central nervous system disorders were used. Using CSF and blood samples obtained at the same time, for the measurement of lactate in the CSF and the plasma immediately after collection, and for the subsequent measurement of the NSE and GFAP, samples of CSF and serum, stored at -80 o C. The ELISA method was used to quantify NSE and GFAP. The descriptive statistical evaluation of the data was performed using means and medians, and to assess the correlation between the results, the spearman coefficient was used. The results obtained were as follows, respectively: NSE of CSF and serum with a median of 127.23 ng/ml and 76.63 ng/ml; GFAP in CSF and serum with a median of 0.67 ng/ml and 0 ng/ml; lactate in CSF and plasma with a median of 2.2 mmol/L and 3.10 mmol/L. Only the NSE and the lactate showed the correlation between the values of the CSF and the serum, being 0.60 (p = 0.009) and 0.56 (p = 0.059), respectively. For ethical reasons, CSF was not collected from healthy dogs and, therefore, the results obtained in other studies was admitted for control purposes, in which the researchers measured the NSE and GFAP in the CSF and serum, and lactate in the CSF and plasma of healthy dogs. In this study, it is suggested that NSE, GFAP, and lactate were increased and that high values of NSE are associated with severe conditions and, therefore, can be used as a complementary exam in the evaluation and monitoring of dogs with central nervous system diseases. In the second study, data from 25 dogs were retrospectively analyzed, which were divided into two groups, one called the meningoencephalitis group (MG) composed of animals diagnosed with MUO and the other designated as a control group (CG) composed of 5 healthy animals. Samples of CSF and serum were used. MG samples were obtained at the time of diagnosis and stored at -80oC for later measurement of the NSE and GFAP biomarkers using an ELISA test. For inferences about survival (long-term prognosis), the Kaplan Meyer statistical test was used to define the average survival time in days of the MG dogs, and the characteristic operation curve of the recipient (ROC) to determine the best cut-off point for biomarkers as a function of mean survival. Measurements of NSE of MG in CSF and serum samples showed higher values than the CG, while GFAP was expressed only in CSF samples. The mean survival of the MG was 62 days, the cutoff point and the accuracy of the biomarkers to predict death and clinical worsening before the average survival was: CSF-NSE 84.53 ng/ml (85%); serum-NSE 113.47 ng/ml (67.5%); CSF-GFAP 6.93 ng/ml (30%). There was no correlation between the samples of CSF and serum from biomarkers. Therefore, it is concluded that the NSE values in the LCE and serum can be used as a long-term prognostic factor for dogs with MUO. Key words: Central Nervous System, Central Nervous System Diseases, Central Nervous System Infections, Encephalitis, Meningoencephalitis, Myelitis, Specific Neuron Enolase, Glial Fibrillary Acid Protein, L-Lactate Dehydrogenase, Prognosis.

Parasite meningomyelitis in cats in Uruguay / Meningomielites parasitária em gatos no Uruguai

Two outbreaks of progressive hind limb paresis in cats (Felis catus) caused by parasitic meningomyelitis in Uruguay are reported. The case studies occurred in 2008 and 2009 respectively, in the rural areas of Fray Bentos (33º 07' 40.39" S) and were characterized by hindquarter paralysis. This paralysis was progressive and had a chronic progression of approximately 12 months until the death or euthanasia of the animals. Clinical symptoms started with ataxia of the hindquarters with lateral side-to-side swaying and culminated in total paralysis. Two animals were sent for necropsy in 2009. The main histopathological findings were severe myelitis in the lumbar spinal cord with perivascular cuffing and white matter necrosis, severe nonsuppurative meningitis with thrombi in subarachnoid blood vessels, and intravascular presence of multiple adult parasites. From the morphological characteristics of the parasites and location in the leptomeninges, the parasite was identified as the nematode Gurltia paralysans.(AU)

São relatados dois surtos de paralisia progressiva dos membros posteriores em gatos (Felis catus), causada por meningomielite parasitária no Uruguai. Os estudos de casos ocorreram entre os anos 2008 e 2009, respectivamente, nas zonas rurais de Fray Bentos (33º 07' 40,39" S) e foram caracterizados por paralisia dos membros posteriores. Esta paralisia era progressiva e tinha evolução crônica de aproximadamente 12 meses, até que os animais vinham a óbito ou eram eutanasiados. Os sintomas clínicos começaram com ataxia dos membros posteriores, com movimentos laterais, terminado em paralisia total. Em 2009, dois animais foram encaminhados para necropsia. Os achados histopatológicos foram caracterizados por severa mielite na medula espinhal lombar com manguitos perivasculares linfocitarios e necrose da substância branca, severa meningite não supurativa com trombos nos vasos sanguíneos subaracnóideos, e presença intravascular de múltiplos parasitos adultos. De acordo com as características morfológicas dos parasitos e localização nas leptomeninges, este foi identificado como um nematóide da espécie Gurltia paralysans.(AU)