Central Nervous System Of Dogs Research Articles

Prognosis in meningoencephalitis of unknown origin in dogs: Risk factors associated with survival, clinical relapse, and long-term disability.

Meningoencephalitis of unknown origin (MUO) comprises a group of noninfectious inflammatory diseases affecting the central nervous system of dogs. Previous studies have reported individual risk factors for survival but prognostication for MUO remains challenging. Identify clinical prognostic variables in dogs with MUO. A retrospective study of 447 dogs presented to 2 UK referral hospitals and diagnosed with MUO. Medical records of dogs diagnosed with MUO were retrospectively reviewed. Multivariable logistic regression was used for the identification of risk factors for survival and Cox proportional hazards analysis for the identification of risk factors for clinical relapse. Eighty-two percent (366/447) of dogs with presumptive MUO survived to discharge and 63.5% (284/447) were alive at 6 months; 36% of the latter (103/284) had persistent neurological deficits. Breed (pugs; P = .03), epileptic seizures (P < .001), paresis (P < .001), and higher neurodisability scale (NDS) score (P < .001) at presentation were negatively associated with survival to 6 months. Dogs with persistent deficits had higher NDS scores on presentation (P = .001). Median follow-up time was 11 months (interquartile range [IQR], 1-24) and 50.6% (160/316) relapsed during treatment (median time to relapse, 7 months; IQR, 2-15). Incomplete resolution of the clinical signs during the 6 months after diagnosis (P < .001), higher NDS score (P < .001), and longer duration of the clinical signs (P < .001) were associated with relapse. Knowledge of risk factors associated with survival, incomplete recovery and clinical relapse in MUO can help guide monitoring and treatment and improve owner communications regarding prognosis for this debilitating disease.

Headache as initial presentation of human chronic necrotizing granulomatous meningoencephalitis: A rare case report

Chronic necrotizing granulomatous meningoencephalitis is an idiopathic inflammatory disease with possible autoimmune mediated delayed type hypersensitivity response. It commonly affects the central nervous system of dogs, and on rare occasions cats. However, this inflammatory disease has rarely been reported in humans. A 69-year-old woman presented with subacute intermittent sharp headaches. Brain MRI revealed multifocal enhancing lesions and edema as well as multifocal signal abnormality throughout the supratentorial and infratentorial parenchyma. Cerebrospinal fluid showed elevated opening pressure, pleocytosis, and elevated protein. MRA head, MRV head, cerebral angiogram, extensive serum and CSF work up for infectious and autoimmune etiologies were also unremarkable. Brain biopsy revealed necrotizing granulomatous inflammation with dystrophic calcification. High dose of methylprednisolone followed by a 6-week prednisone taper resolved her headache and the brain MRI abnormalities. This case demonstrates the response of necrotizing granulomatous meningoencephalitis in humans to steroids.

Immunohistochemical evaluation of fibrin/fibrinogen, d-dimers, and intravascular thrombosis in brains of dogs with meningoencephalitis of unknown origin

Granulomatous meningoencephalitis (GME) and necrotizing encephalitides (NE) are the most common immune-mediated inflammatory diseases of the central nervous system in dogs. Activation of the fibrinolytic system in multiple sclerosis, a similar immune-mediated disease affecting the central nervous system in humans, seems to be related to disease progression. The aim of this study was to identify fibrin/fibrinogen and D-dimer deposition, as well as presence of intravascular thrombosis (IVT) in brains of dogs with a diagnosis of GME or NE. Immunohistochemical studies using antibodies against fibrin/fibrinogen and D-dimers were performed. Statistical analyses were performed to determine whether there were differences in the presence and location of fibrin/fibrinogen, D-dimers deposits, and IVT between GME and NE. Samples from sixty-four dogs were included in the study: 32 with a diagnosis of GME and 32 with a diagnosis of NE. Fibrin/fibrinogen depositions were detected in all samples and d-dimers were detected in 43/64 samples. IVT was present in 29/64 samples, with a significantly higher score in samples from dogs with NE than in samples from dogs with GME (P = 0.001). These data support hemostatic system activation in both diseases, especially NE. This finding might be related to the origin of the necrotic lesions seen in NE, which could represent chronic ischemic lesions. Further studies are needed to investigate the association between vascular lesions and the histopathological differences between GME and NE and the hemostatic system as a potential therapeutic target.

Reduced cingulate gyrus volume in Cavalier King Charles Spaniels with syringomyelia and neuropathic pain revealed by voxel-based morphometry: a pilot study.

Pathomorphological alterations of the central nervous system in dogs, such as syringomyelia and Chiari-like malformation, can cause cranial and cervical hyperesthesia and neuropathic pain. The long-term activity of the pain network can induce functional alteration and eventually even morphological changes in the pain network. This may happen especially in the prefrontal and cingulate cortex, where atrophy of the gray matter (GM) was observed in humans with chronic pain, irrespective of the nature of the pain syndrome. We tested the hypothesis that Cavalier King Charles Spaniels (CKCS) with Chiari-like malformation and associated syringomyelia (SM) and pain show cerebral morphological differences compared to animals without signs of syringomyelia and pain. Volumetric datasets of 28 different brain structures were analyzed in a retrospective manner, including voxel-based morphometry, using magnetic resonance imaging data obtained from 41 dogs. Volumetric analyses revealed a decrease in GM volumes in the cingulate gyrus (CG) in CKCS with SM and chronic pain when normalized to brain volume. This finding was supported by voxel-based morphometry, which showed a cluster of significance within the CG. GM atrophy in the CG is associated with chronic pain and thus may serve as an objective readout parameter for the diagnosis or treatment of canine pain syndromes.

MicroRNA profiling of cerebrospinal fluid from dogs with steroid responsive meningitis-arteritis and meningoencephalitis of unknown origin.

Non-infectious inflammatory diseases of the central nervous system in dogs, such as steroid responsive meningitis-arteritis (SRMA) and meningoencephalitis of unknown origin (MUO), represent a common clinical challenge that needs extensive and multimodal work-up to reach a presumptive diagnosis. Both diseases are presumably caused by dysregulations of the immune system, but further research is needed in order to understand the molecular mechanisms behind each disease and to optimize treatment. By next-generation sequencing and subsequent quantitative real-time PCR (qPCR) verification, we designed a prospective case-control pilot study to analyze the small RNA profiles of cerebrospinal fluid from dogs suffering from MUO (N = 5), dogs suffering from SRMA (N = 8), and healthy dogs (N = 5) presented for elective euthanasia used as the Control group. Our results showed an overall enrichment in Y-RNA fragments across all samples, followed by microRNAs (miRNAs) and ribosomal RNAs as the major findings. Additional traces of short RNA reads mapped to long non-coding RNAs and protein-coding genes were also found. From the detected canine miRNAs, miR-21, miR-486, miR-148a, miR-99a, miR-191 and miR-92a were among the most abundant. Dogs with SRMA showed higher differences in miRNA abundance than dogs with MUO when compared to healthy dogs, and miR-142-3p was consistently detected as differentially upregulated in both diseases, although at a low concentration. Moreover, miR-405-5p and miR-503-5p showed different profiles between SRMA and MUO dogs. Subsequent qPCR analyses confirmed miR-142-5p, miR-191-5p and miR-92a-3p as significantly upregulated miRNAs in dogs with SRMA and/or MUO. Cerebrospinal fluid is a challenging biological material to use for profiling miRNAs due to the low content of circulating RNAs. Despite this, we could confirm several miRNAs being differentially abundant when comparing healthy dogs and dogs with MUO and SRMA, respectively. The results of this study indicate a potential role of miRNAs in the underlying molecular mechanisms of these diseases and establish the basis for further studies.

Development of a reliable clinical assessment tool for meningoencephalitis in dogs: The neurodisability scale

Meningoencephalitis of unknown origin (MUO) comprises a group of debilitating inflammatory diseases affecting the central nervous system of dogs. Currently, no validated clinical scale is available for the objective assessment of MUO severity. Design a neurodisability scale (NDS) to grade clinical severity and determine its reliability and whether or not the score at presentation correlates with outcome. One hundred dogs with MUO were included for retrospective review and 31 dogs were subsequently enrolled for prospective evaluation. Medical records were retrospectively reviewed for 100 dogs diagnosed with MUO to identify the most frequent neurological examination findings. The NDS was designed based on these results and evaluated for prospective and retrospective use in a new population of MUO patients (n = 31) by different groups of independent blinded assessors, including calculation of interobserver agreement and association with outcome. The most common clinical signs in MUO patients were used to inform categories for scoring in the NDS: seizure activity, ambulatory status, posture and cerebral, cerebellar, brainstem, and visual functions. The intraclass correlation coefficient (ICC) for prospective use of the NDS was 0.83 (95% confidence interval [CI], 0.68-0.91) indicating good agreement, and moderate agreement was found between prospective and retrospective assessors (ICC, 0.71; 95% CI, 0.56-0.83). No association was found between NDS score and long-term outcome. The NDS is a novel clinical measure for objective assessment of neurological dysfunction and showed good reliability when used prospectively in MUO patients but, in this small population, no association with outcome could be identified.

Headache as Initial Presentation of Human Chronic Necrotizing Granulomatous Meningoencephalitis

Objective Chronic necrotizing and granulomatous meningoencephalitis is an idiopathic inflammatory disease with possible autoimmune mediated delayed type hypersensitivity response. It commonly affects the central nervous system of dogs and cats. However, this inflammatory disease has rarely been described in humans. Background A 69-year-old right-handed woman presented with worsening subacute headaches that were intermittent, sharp and holocephalic in nature which worsened with coughing and/or laughing. Her initial neurological examination was unremarkable. MRI of the brain revealed multifocal enhancing lesions and edema as well as multifocal signal abnormality throughout the supratentorial and infratentorial parenchyma. Her cerebrospinal fluid showed elevated opening pressure, elevated nucleated cells, elevated protein and normal glucose. CSF cytology, gram stains and cultures were unremarkable. Possibility of sarcoidosis, mycobacterium and fungal etiologies were ruled out. Other work up included but not limited to MRA head, MRV head, diagnostic cerebral angiogram, extensive serum and CSF autoimmune labs were also unremarkable. She underwent a brain biopsy which showed necrotizing granulomatous inflammation with associated dystrophic calcification. Patient was started on high dose methylprednisolone followed by a 6-week prednisone taper. There was a complete resolution of her symptoms, as well as improvement in her follow up MRI brain over a six month period. Design/Methods N/A. Results N/A. Conclusions We describe what we believe would be the third reported case of necrotizing granulomatous meningitis of an unknown cause in humans. This case demonstrates the response of necrotizing granulomatous meningoencephalitis in humans to steroid therapy. Yet, further studies are necessary to determine symptomatology and pathogenesis, as well as the treatment in humans.

Inflammatory Disease Affecting the Central Nervous System in Dogs: A Retrospective Study in England (2010-2019).

The epidemiology of inflammatory diseases affecting the central nervous system (CNS) in dogs is largely unknown. We aimed to report the relative proportion of different causes of inflammatory disease affecting the CNS in dogs and identify predictors for infectious vs. immune-mediated conditions and predictors for the most common diseases affecting the brain and the spinal cord. This was a retrospective cohort study over a 10-year period in 2 referral institutions using multivariable and multinomial logistic regression for identification of risk factors. In total, 1,140 client-owned dogs diagnosed with inflammatory disease affecting the CNS were included. Fifteen different diagnoses were identified, with immune-mediated (83.6%) disease being more common than infectious conditions (16.4%). The most common immune-mediated conditions diagnosed were meningoencephalitis of unknown origin (47.5%) and steroid-responsive meningitis–arteritis (30.7%), and the most common infectious conditions were discospondylitis (9.3%) and otogenic intracranial infection (2.2%). Older age (p < 0.001, OR = 1.019, 95% CI: 1.014–1.024), higher body weight (p < 0.001, OR = 1.049, 95% CI: 1.025–1.074), male sex (p = 0.009, OR = 1.685, 95% CI: 1.141–2.488), longer duration of the clinical signs before presentation (p < 0.001, OR = 1.011, 95% CI: 1.006–1.017), progressive nature of the clinical signs (p < 0.001, OR = 2.295, 95% CI: 1.463–3.599), identification of a possibly associated preceding event (p = 0.0012, OR = 1.93, 95% CI: 1.159–3.213), and hyperesthesia on presentation (p < 0.001, OR = 2.303, 95% CI: 1.528–3.473) were associated with a diagnosis of infectious diseases. Our data shows that immune-mediated diseases are more common than infectious conditions as a cause for inflammatory CNS disease in dogs. The risk factors for the most common diagnoses were identified from signalment, history, and findings of the physical and neurological examinations to give valuable information that can guide clinicians with their investigations.

Canine Tick-Borne Encephalitis: Clinical Features, Survival Rate and Neurological Sequelae: A Retrospective Study of 54 Cases (1999-2016).

Tick-borne encephalitis (TBE) is one of the most important infectious diseases of the central nervous system in dogs from endemic areas. While in humans survival rate and long-term outcomes are well described, these data are lacking in veterinary literature. The aim of the present paper is to characterize the clinical aspects of TBE and to investigate fatality rate, long-term outcome and the long-term neurological sequelae in a population of dogs infected with TBE. We performed a retrospective analysis of 54 dogs diagnosed with TBE at the veterinary hospital of the University of Zurich between 1999 and 2016. Medical data such as signalment, clinical presentation, results of diagnostic procedures, treatment and outcome were collected and analyzed. Statistical analysis including a cox proportional hazard model using a backward stepwise regression approach was performed. In 62% of the TBE cases unspecific signs were described before the onset of neurological signs, resembling a biphasic appearance that is well known in human TBE. Case fatality rate was 33% and all dogs died within the first 4 months after diagnosis. Long-term neurological sequalae were detected in 17% of the TBE cases. For each day of clinical signs before hospital entry the odds of sequalae increased by a factor of 1.88 (CI 1.04–3.15). Older dogs and dogs presented with seizure activity had an increased hazard risk of death (Hazard ration = 1.2, p = 0.03; and 9.38, p = 0.001, respectively). In conclusion, despite TBE being a life-threatening disease with severe clinical signs, the survival rate in our study was 67%. However, long-term sequalae can be of concern especially in dogs with longer clinical course.

Heterogenous deposition of β-amyloid in the brain of aged dogs

Dogs have been used as animal models for human diseases in which there is beta-amyloid (Aβ) deposition in the central nervous system (CNS), such as Alzheimer's and cerebral amyloid angiopathy (CAA). However, many aspects of Aβ deposition in the CNS of dogs still remain unknown. This study aimed to evaluate the deposition of Aβ in different areas of the CNS of aged dogs from different breeds. Aβ was detected in the brains of aged dogs, forming either senile plaques in the neuropil of cortical gray matter or within the walls of parenchymal or leptomeningeal blood vessels. There was a positive correlation between aging and senile plaques or CAA. In dogs older than 8 years, there was no correlation between the area of Aβ plaques and age, with frontal, temporal, and occipital cortices being affected with approximately equal frequency. There was a positive correlation between Aβ deposition in vessel walls and age. Importantly, CAA was associated with the occurrence of microperivascular hemorrhages in the brains of aged dogs. In conclusion, this study demonstrated that Aβ deposition as plaques or within vessel walls are extremely heterogenous in dogs from different breeds and sizes. Although many features of this disease in dogs are similar to those observed in humans, the choice of dog breed and size as a model for human disease will substantially affect the pattern of Aβ deposition.

Steroid-responsive meningitis-arteritis in dogs in Germany: Are there epidemiological or clinical factors influencing recurrence rate?

Steroid-responsive meningitis arteritis (SRMA) is one of the most common inflammatory diseases of the central nervous system in dogs. The present study examined breed and sex predisposition factors based on the population of dogs in Germany as well as epidemiological and clinical factors regarding the relapse rate of SRMA. Data of 153 dogs with SRMA (SRMA) were analysed retrospectively in this multicentre study. It was investigated whether some dog breeds that suffer from SRMA were disproportionately more often (n ≥ 5) represented when compared to the total population of dogs in Germany. Furthermore it was examined which sex is affected more often. Data provided by "Verband für das deutsche Hundewesen" (VDH) and "Tasso e. V." was used as reference data of the total population. The following factors were investigated with regard to the occurrence of one or more relapses: signalment; body weight; age at first presentation; time period between last vaccination and onset of clinical signs; clinical signs and timepoint of the first SRMA manifestation; results of cerebrospinal fluid (CSF) analysis at first presentation (nucleated cell count and differentiation, protein concentration); immunglobulin A and C-reactive protein (CRP) concentrations in serum and CSF; immunosuppressive medication; follow-up data including response to therapy, occurrence of relapses and mortality including reasons, i. e. due to the disease, therapy or euthanasia. The breed had a statistically significant influence on the development of SRMA (p < 0.05). Beagles and Boxers were affected more often by SRMA than other breeds in relation to the total population in Germany. Relapses occurred in 29.4 % of the 153 dogs of this study. In contrast to the development of SRMA, in which male dogs have a significantly increased risk of developing SRMA (p < 0.05), female dogs are more likely to relapse (p = 0.02). Patients on prednisolone monotherapy had fewer relapses than those with prednisolone and azathioprine in combination (p < 0.05). Younger age (p = 0.071) und lower CRP concentrations (p = 0.081) at first presentation were tentatively associated with a higher incidence of relapses. The determined breed and sex predispositions support the diagnosis of SRMA arteritis and confirm previous observations. This study allows a more accurate explanation to owners about the risk of relapse.

Clinicopathological characteristics of histiocytic sarcoma affecting the central nervous system in dogs.

BackgroundHistiocytic sarcoma affecting the central nervous system (CNS HS) in dogs may present as primary or disseminated disease, often characterized by inflammation. Prognosis is poor, and imaging differentiation from other CNS tumors can be problematic.ObjectiveTo characterize the clinicopathological inflammatory features, breed predisposition, and survival in dogs with CNS HS.AnimalsOne hundred two dogs with HS, 62 dogs with meningioma.MethodsRetrospective case series. Records were reviewed for results of cerebrospinal fluid (CSF) analysis, CBC, treatment, and outcome data.ResultsPredisposition for CNS HS was seen in Bernese Mountain Dogs, Golden Retrievers, Rottweilers, Corgis, and Shetland Sheepdogs (P ≤ .001). Corgis and Shetland Sheepdogs had predominantly primary tumors; Rottweilers had exclusively disseminated tumors. Marked CSF inflammation was characteristic of primary rather than disseminated HS, and neoplastic cells were detected in CSF of 52% of affected dogs. Increased neutrophil to lymphocyte ratios were seen in all groups relative to controls (P <.008) but not among tumor subtypes. Definitive versus palliative treatment resulted in improved survival times (P < .001), but overall prognosis was poor.Conclusions and Clinical ImportanceClinicopathological differences between primary and disseminated HS suggest that tumor biological behavior and origin may be different. Corgis and Shetland Sheepdogs are predisposed to primary CNS HS, characterized by inflammatory CSF. High total nucleated cell count and the presence of neoplastic cells support the use of CSF analysis as a valuable diagnostic test. Prognosis for CNS HS is poor, but further evaluation of inflammatory mechanisms may provide novel therapeutic opportunities.

Astrocyte lesions in cerebral cortex and cerebellum of dogs with congenital ortosystemic shunting.

BackgroundCongenital portosystemic shunt (cPSS) is one of the most common congenital disorders diagnosed in dogs. Hepatic encephalopathy (HE) is a frequent complication in dogs with a cPSS and is a major cause of morbidity and mortality. Despite HE been a major cause of morbidity in dogs with a cPSS, little is known about the cellular changes that occur in the central nervous system of dogs with a cPSS.ObjectivesThe objective of this study was to characterise the histological changes in the cerebral cortex and cerebellum of dogs with cPSS with particular emphasis on astrocyte morphology.MethodsEight dogs with a confirmed cPSS were included in the study.ResultsSix dogs had substantial numbers of Alzheimer type II astrocytes and all cases had increased immunoreactivity for glial fibrillary acidic protein in the cerebral cortex, even if there were minimal other morphological changes.ConclusionsThis study demonstrates that dogs with a cPSS have marked cellular changes in the cerebral cortex and cerebellum. The cellular changes that occur in the cerebral cortex and cerebellum of dogs with spontaneously arising HE are similar to changes which occur in humans with HE, further validating dogs with a cPSS as a good model for human HE.

Cellular Distribution of Canonical and Putative Cannabinoid Receptors in Canine Cervical Dorsal Root Ganglia.

Growing evidence indicates cannabinoid receptors as potential therapeutic targets for chronic pain. Consequently, there is an increasing interest in developing cannabinoid receptor agonists for treating human and veterinary pain. To better understand the actions of a drug, it is of paramount importance to know the cellular distribution of its specific receptor(s). The distribution of canonical and putative cannabinoid receptors in the peripheral and central nervous system of dogs is still in its infancy. In order to help fill this anatomical gap, the present ex vivo study has been designed to identify the cellular sites of cannabinoid and cannabinoid-related receptors in canine spinal ganglia. In particular, the cellular distribution of the cannabinoid receptors type 1 and 2 (CB1 and CB2) and putative cannabinoid receptors G protein-coupled receptor 55 (GPR55), nuclear peroxisome proliferator-activated receptor alpha (PPARα), and transient receptor potential vanilloid type 1 (TRPV1) have been immunohistochemically investigated in the C6–C8 cervical ganglia of dogs. About 50% of the neuronal population displayed weak to moderate CB1 receptor and TRPV1 immunoreactivity, while all of them were CB2-positive and nearly 40% also expressed GPR55 immunolabeling. Schwann cells, blood vessel smooth muscle cells, and pericyte-like cells all expressed CB2 receptor immunoreactivity, endothelial cell being also PPARα-positive. All the satellite glial cells (SGCs) displayed bright GPR55 receptor immunoreactivity. In half of the study dogs, SGCs were also PPARα-positive, and limited to older dogs displayed TRPV1 immunoreactivity. The present study may represent a morphological substrate to consider in order to develop therapeutic strategies against chronic pain.

Pathological features of 78 metastatic or multicentric neoplasms involving the central nervous system in dogs

ABSTRACT: Secondary neoplasms affecting the central nervous system (CNS) may occur through blood flow or direct extension. This condition occurrence has increased both due to a longer life expectancy of dogs, as well as with the employment of chemotherapeutics, which may increase the survival period and, thus, the odds of the occurrence of metastasis. The aim of this study was to analyze the epidemiological features, such as the age, breed and sex of the animals affected, as well as the gross and microscopic findings of the metastasis from neoplasms involving the CNS of 78 dogs, and, based on the data, estimate the occurrence and frequency of the metastatic or multicentric neoplasms. Females (71.79%) were most affected than males, with an average age of 9.5-years-old and a median of 10-years-old. Most of the cases had a multifocal distribution (73.07%), and epithelial neoplasms (50%) were the most common. Telencephalon was the most affected neuroanatomical region (61.1%). Mammary neoplasms were the most frequent (47.44%), followed by hemangiosarcoma (19.23%), lymphoma (10.26%) and melanoma (6.41%). Less common neoplasms included osteosarcoma, histiocytic sarcoma and lung carcinoma (2.56%). Mammary neoplasms were mainly composed of anaplastic and micropapillary carcinomas, of which only multifocal microscopic lesions were observed.

Cerebral Candida albicans Infection in Two dogs

Background: Candida spp. are pleomorphic fungi that are commensal inhabitants of the oral, gastrointestinal, upper respiratory and urogenital mucosa of mammals. Candida albicans is described as the most important species. This opportunistic pathogen may produce local or systemic infections in dogs. Local infections have been reported in several tissues and systemic infection is rare in dogs with few reports in the literature describing this presentation. The aim of the present study was to report two cases of cerebral Candida albicans infection in dogs in Brazil.Case: Two cases of cerebral Candida albicans infection in dogs that showed nervous signs are described. In both cases, the brain showed marked asymmetry of the telencephalic hemispheres with multifocal to coalescing yellowish or reddish areas and a partial loss of distinction between gray and white matter. In Case 1, the mediastinal, tracheobronchial and mesenteric lymph nodes, as well as the right kidney and adrenal gland, showed altered architecture due to numerous whitish gray nodules. Histological lesions were characterized by granulomatous (case 1) or pyogranulomatous (case 2) necrotizing meningoencephalitis with intralesional fungal organisms. In case 1, similar granulomatous infiltrate with intralesional fungal organisms was also seen in the lymph nodes, kidney and adrenal gland. In case 2, there was evidence consistent with an underlying infection of canine distemper virus. Were observed lymphoplasmocytic interstitial pneumonia, lymphoid rarefaction in lymph nodes, and viral intracytoplasmic inclusion bodies in the epithelial cells of the stomach and vesical urothelium. In these two cases, the fungal organisms displayed three different morphological patterns. The first pattern was characterized by delicate tubular structures with thin parallel walls that were rarely septate and tended to undulate slightly, and measured approximately 4-20 µm (true hyphae). The second pattern was characterized by chains of elongated yeast, separated by constrictions at septal sites, and measured approximately 4-10 µm (pseudohyphae). The other morphological pattern, which was rarely observed, was characterized by round budding yeast cells that measured 3-4 µm in diameter and were often elongated by the germ tube. Sections were also stained using immunohistochemical antibodies against Candida albicans. The fungi revealed strong immunolabelling of the cytoplasm and wall for Candida albicans.Discussion: The diagnosis was based on the histomorphological and immunohistochemical characteristics of the agent, which were consistent with Candida albicans. In these two cases, immunocompromise appeared to have been an important factor in the progression of the infection. In case 1, the dog was senile and treated with corticosteroids, conditions that could effectively limit innate, humoral and cell-mediated immune response to infection. In case 2, the dog displayed cachexia and was infected by canine distemper virus, evidenced by the presence of viral inclusion bodies. The inflammatory reactions in both cases were characteristic of fungal infections, but were distinct due to differences in the infectious process. In case 1, there was a subacute to chronic progression; while in case 2 neutrophilic infiltrate predominated, suggesting an acute progression. The different morphological patterns of the fungi suggested a pleomorphic fungi and the immunohistochemistry allowed us to identify the infectious agent. In conclusion, opportunistic infections caused by Candida albicans should be considered when diagnosing diseases that affect the central nervous system of dogs, particularly in immunosuppressed animals.

Main lesions in the central nervous system of dogs due to Leishmania infantum infection

BackgroundCanine visceral leishmaniasis (CVL) is endemic in São Luís Maranhão/Brazil and it leads a varied clinical picture, including neurological signs.ResultsHistopathological evaluation showed that 14 dogs exhibited pathological alterations in at least one of the analyzed areas. Of these, mononuclear inflammatory reaction was the most frequent, although other lesions, such as hemorrhage, chromatolysis and gliosis were also observed. The presence of L. infantum amastigotes was confirmed in eight dogs, identified in four regions: telencephalon, hippocampus, thalamus and caudal colliculus, but only one presented neurological signs. Polymerase chain reaction results detected the DNA of the parasite in 11 samples from seven dogs. The positive areas were the telencephalon, thalamus, hippocampus, cerebellum, caudal and rostral colliculus.ConclusionThese results reveal that during canine visceral leishmaniasis, the central nervous system may display some alterations, without necessarily exhibiting clinical neurological manifestations. In addition, the L. infantum parasite has the ability to cross the blood brain barrier and penetrate the central nervous system.

Expression of canine distemper virus receptor nectin-4 in the central nervous system of dogs

Canine distemper virus (CDV) exhibits lymphotropic, epitheliotropic, and neurotropic nature, and causes a severe systemic infection in susceptible animals. Initially, signaling lymphocyte activation molecule (SLAM) expressed on immune cells has been identified as a crucial cellular receptor for CDV. Currently, nectin-4 expressed in epithelia has been shown to be another receptor for CDV. Our previous study demonstrated that neurons express nectin-4 and are infected with CDV. In this study, we investigated the distribution pattern of nectin-4 in various cell types in the canine central nervous system and showed its relation to CDV infection to further clarify the pathology of disease. Histopathological, immunohistochemical and immunofluorescent analyses were done using formalin-fixed paraffin-embedded tissues of CDV-infected dogs. Dual staining of nectin-4 and CDV antigen or nectin-4 and brain cell markers was performed. Nectin-4 was detected in ependymal cells, epithelia of choroid plexus, meningeal cells, neurons, granular cells, and Purkinje’s cells. CDV antigens were detected in these nectin-4-positive cells, further suggesting contribution of nectin-4 for the CDV neurovirulence. On the other hand, astrocytes did not express nectin-4, although they were frequently infected with CDV. Since astrocytes are negative for SLAM expression, they must express an unidentified CDV receptor, which also contributes to CDV neurovirulence.

Plasma and serum concentrations of cytarabine administered via continuous intravenous infusion to dogs with meningoencephalomyelitis of unknown etiology.

The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client-owned dogs received a CRI of CA at a dose of 25mg/m2 /h for 8h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12h after initiating the CRI. Plasma (n=13) and serum (n=11) cytarabine concentrations were measured by high-pressure liquid chromatography. The mean peak concentration (CMAX ) and area under the curve (AUC) after CRI administration were 1.70±0.66μg/mL and 11.39±3.37h·μg/mL, respectively, for dogs receiving cytarabine alone, 2.36±0.35μg/mL and 16.91+3.60h·μg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0μg/mL at both the 1- and 8-h time points. The steady-state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma.

A multiplex quantitative real-time polymerase chain reaction panel for detecting neurologic pathogens in dogs with meningoencephalitis.

Meningoencephalitis (ME) is a common inflammatory disorder of the central nervous system in dogs. Clinically, ME has both infectious and non-infectious causes. In the present study, a multiplex quantitative real-time polymerase chain reaction (mqPCR) panel was optimized for the detection of eight canine neurologic pathogens (Blastomyces dermatitidis, Cryptococcus spp., Neospora caninum, Borrelia burgdorferi, Bartonella spp., Toxoplasma gondii, Ehrlichia canis, and canine distemper virus [CDV]). The mqPCR panel was subsequently applied to 53 cerebrospinal fluid (CSF) samples collected from dogs with ME. The analytic sensitivity (i.e., limit of detection, expressed as molecules per 1 µL of recombinant vector) was 3.8 for CDV, 3.7 for Ehrlichia canis, 3.7 for Bartonella spp., 3.8 for Borrelia burgdorferi, 3.7 for Blastomyces dermatitidis, 3.7 for Cryptococcus spp., 38 for Neospora caninum, and 3.7 for Toxoplasma gondii. Among the tested CSF samples, seven (15%) were positive for the following pathogens in decreasing order of frequency: Cryptococcus spp. (3/7), Blastomyces dermatitidis (2/7), and Borrelia burgdorferi (2/7). In summary, use of an mqPCR panel with high analytic sensitivity as an initial screen for infectious agents in dogs with ME could facilitate the selection of early treatment strategies and improve outcomes.