MAGNETIC RESONANCE IMAGING FEATURES AND OUTCOME FOR SOLITARY CENTRAL NERVOUS SYSTEM COCCIDIOIDES GRANULOMAS IN 11 DOGS AND CATS.

Little published information is available to guide therapy for canine and feline patients with Coccidioides infections involving the central nervous system (CNS). The purpose of this cross-sectional retrospective study was to describe magnetic resonance imaging (MRI) features and outcome for a group of dogs and cats with solitary CNS Coccidiodes granulomas. Nine canine and two feline cases met inclusion criteria; four diagnosed and treated with surgery and fluconazole and seven diagnosed by serology or cytology and treated medically. Three cases had left Coccidioides endemic areas long before developing neurological disease. The MRI lesions shared many features with neoplastic masses. The extra-axial granulomas often had a lack of a distinct border between the mass and neural parenchyma. Four cases were extra-axial and seven were intra-axial, but distinguishing between extra-axial and intra-axial locations was sometimes challenging. The surgical cases had good outcomes and histology allowed definitive diagnosis. Medically managed patients also had generally good outcomes, with resolution of clinical signs in most cases. Findings indicated that distinction between neoplasia and focal Coccidioides granulomas based on MRI features is likely to be imprecise. Demonstration of the organism by cytology or histology is required for definitive diagnosis. The role of surgery for improving the outcome of brain or spinal coccidioidomycosis granulomas warrants further study.

Neurological trypanosomiasis in quinapyramine sulfate-treated horses--a breach of the blood-brain barrier?

Trypanosoma evansi infection typically produces wasting disease, but it can also develop into a neurological or meningoencephalitis form in equids. Trypanosomiasis in horses was treated with quinapyramine sulfate, and all the 14 infected animals were recovered clinically. After clinical recovery, four animals developed a neurological form of the disease at various intervals. Two of these animals treated with diminazene aceturate recovered temporarily. Repeated attempts failed to find the parasite in the blood or the cerebrospinal fluid (CSF), but all of the animals were positive in enzyme-linked immunosorbent assay. The calculation of the antibody index (AI) in the serum and the CSF and polymerase chain reaction (PCR) analysis of the CSF and brain tissue were carried out to confirm the neuro-infection. We found PCR and AI analyses of the CSF to be useful tools in the diagnosis of the neurological form of trypanosomiasis when the organism cannot be found in the blood or CSF. The increased albumin quotient is indicative of barrier leakage due to neuroinflammation. The biochemical changes in the CSF due to nervous system trypanosomiasis include increases in the albumin quotient, total protein, and urea nitrogen. It seems to be the first report on relapse of the nervous form of trypanosomiasis in equids even after quinapyramine treatment in endemic areas.

Detection and characterization of a divergent avian reovirus strain from a broiler chicken with central nervous system disease.

Avian orthoreoviruses have been associated with a variety of diseases in chickens, including tenosynovitis, runting-stunting syndrome, hepatitis, myocarditis, osteoporosis, respiratory diseases, and central nervous system disease. The primary objective of our study was the molecular characterization of an avian reovirus strain, T1781, which was isolated from a broiler chicken with a central nervous system disorder in Hungary during 2012. The complete genome sequence was determined using a traditional sequencing method after cell culture adaptation of the strain. Sequence and phylogenetic analyses showed that T1781 shared only moderate nucleic acid sequence identity in several genes to previously analyzed reovirus strains from chickens, and each gene formed separate branches in the corresponding phylogenetic trees. The maximum nucleotide sequence identities of strain T1781 genes to reference avian reovirus strains ranged from 79 % to 90 %. Collectively, our analyses indicated that T1781 is a divergent chicken reovirus strain. The genetic background of this and other avian reoviruses associated with various disease manifestations needs further investigation.

Serial MRI and CSF analysis in a dog treated with intrathecal amphotericin B for protothecosis.

A 3 yr old female spayed English setter mixed-breed dog presented with diarrhea, weight loss, side stepping to the right, and a right head tilt. Rectal and cerebrospinal fluid cytology and culture confirmed a diagnosis of Prototheca zopfii. MRI of the brain showed inflammation of the brain and meninges, ventriculomegaly, and syringomyelia. Treatment with prednisone, itraconazole, and amphotericin B lipid complex administered intrathecally yielded transient improvement. Progressive brainstem signs were noted, and a repeat MRI and cerebrospinal fluid analysis documented persistent disease. This is the first description of the MRI findings and treatment with intrathecal amphoteracin B lipid complex for protothecosis of the central nervous system. Protothecosis should be considered in dogs with chronic diarrhea and compatible MRI findings.

Henneguya torpedo sp. nov. (Myxozoa), a parasite from the nervous system of the Amazonian teleost Brachyhypopomus pinnicaudatus (Hypopomidae).

A new species of Myxosporea, Henneguya torpedo sp. nov., is described from the brain and spinal cord of the Amazonian teleostean fish Brachyhypopomus pinnicaudatus collected from the Peixe Boi River, State of Park, Brazil. The spores were surrounded by a thick hyaline sheath that is homogeneous and electron translucent and consists of 2 layers of different densities. The total spore length is 48.62 +/- 0.51 microm (mean +/- SE), the ellipsoidal spore body length is 28.53 +/- 0.36 microm, the body width is 7.25 +/- 0.31 microm and the body thickness is 3.06 +/- 0.26 microm. Each of the 2 equal-sized valves presented a tapering tail (19.64 +/- 0.44 microm in length). The 2 equal-sized thin and smooth valves surrounded 2 equal-sized and elongated ellipsoidal polar capsules (6.41 +/- 0.26 x 1.84 +/- 0.19 microm) that contained 5 to 6 (rarely 7) polar filament coils. The binucleated sporoplasm contained numerous spherical sporoplasmosomes (-260 x -280 nm) with a laterally eccentric-dense structure containing a half-crescent section. The sporoplasmosomes are surrounded by a hyaline homogenous sheath. Based on the data obtained by light and electron microscopy and on the host specificity, the spores differed from the previously described Henneguya spp., mainly in the presence of a sheath surrounding the spores, the spore shape and size and the number and arrangement of the polar filament coils. Therefore, from this description we propose the establishment of a new species, which we have named Henneguya torpedo sp. nov.

Clinical signs, imaging features, neuropathology, and outcome in cats and dogs with central nervous system cryptococcosis from California.

BACKGROUND: Cryptococcus spp. is a fungal pathogen with a predilection for the central nervous system (CNS). OBJECTIVES: To compare the clinical, advanced imaging, and neuropathologic findings in dogs and cats with CNS cryptococcosis, and to evaluate outcome of treatment in these animals. ANIMALS: Twenty-six cats and 21 dogs with CNS cryptococcosis. METHODS: Medical records were reviewed for clinical findings and results of CNS imaging. Archived cerebrospinal fluid and CNS tissue specimens were reviewed for pathology. Findings in cats were compared with those in dogs and the effects of variables on survival were determined by survival curve analysis. RESULTS: When present, pain was localized to the cervical region in dogs and was generalized or localized to the thoracolumbar spine or pelvic limbs in cats. Magnetic resonance imaging (MRI) findings were variable but correlated with CNS histopathological findings of meningitis, meningitis with gelatinous pseudocyst formation, and granulomatous mass lesions. Peripherally enhancing brain lesions were seen only in cats. Histopathologically, the inflammatory response was milder in cats compared with dogs. Remissions of ≥1 year occurred in 32% of treated animals. Altered mentation was associated with negative outcome. Glucocorticoid use after diagnosis was associated with improved survival in the first 10 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Lesions seen on MRI reflected neuropathological findings and were similar to those reported in human patients. The immune response to infection may differ between cats and dogs, or relate to the infecting cryptococcal species. Long-term (>6 month median survival time) survival may be possible in animals surviving ≥4 days after diagnosis.

Pathogenesis and immunopathology of systemic and nervous canine distemper.

Canine distemper is a worldwide occurring infectious disease of dogs, caused by a morbillivirus, closely related to measles and rinderpest virus. The natural host range comprises predominantly carnivores. Canine distemper virus (CDV), an enveloped, negative-sense RNA virus, infects different cell types, including epithelial, mesenchymal, neuroendocrine and hematopoietic cells of various organs and tissues. CDV infection of dogs is characterized by a systemic and/or nervous clinical course and viral persistence in selected organs including the central nervous system (CNS) and lymphoid tissue. Main manifestations include respiratory and gastrointestinal signs, immunosuppression and demyelinating leukoencephalomyelitis (DL). Impaired immune function, associated with depletion of lymphoid organs, consists of a viremia-associated loss of lymphocytes, especially of CD4+ T cells, due to lymphoid cell apoptosis in the early phase. After clearance of the virus from the peripheral blood an assumed diminished antigen presentation and altered lymphocyte maturation cause an ongoing immunosuppression despite repopulation of lymphoid organs. The early phase of DL is a sequel of a direct virus-mediated damage and infiltrating CD8+ cytotoxic T cells associated with an up-regulation of pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha and IL-12 and a lacking response of immunomodulatory cytokines such as IL-10 and transforming growth factor (TGF)-beta. A CD4+-mediated delayed type hypersensitivity and cytotoxic CD8+ T cells contribute to myelin loss in the chronic phase. Additionally, up-regulation of interferon-gamma and IL-1 may occur in advanced lesions. Moreover, an altered balance between matrix metalloproteinases and their inhibitors seems to play a pivotal role for the pathogenesis of DL. Summarized, DL represents a biphasic disease process consisting of an initial direct virus-mediated process and immune-mediated plaque progression. Immunosuppression is due to early virus-mediated lymphocytolysis followed by still poorly understood mechanisms affecting antigen presentation and lymphocyte maturation.

Cryptococcus gattii with bimorphic colony types in a dog in western Oregon: additional evidence for expansion of the Vancouver Island outbreak.

Cryptococcus gattii was isolated from a 1.5-year-old dog with systemic cryptococcosis in Oregon. The dog had no link to Vancouver Island or British Columbia, Canada. Samples from a nasal swab and from a granulomatous mass within the cranial cavity were pooled for culture. Colonies on Sabouraud dextrose agar were mucoid and exhibited bimorphic morphology, melanin-pigmented and unpigmented. Pigmented colonies were encapsulated budding spherical yeast, whereas unpigmented colonies were of unencapsulated ovoid budding yeast. In addition to defective melanin production, the unpigmented colony type exhibited defective mating. Genetic analysis by high-resolution multilocus sequence typing revealed that the 2 isolates are genetically identical at 8 unlinked loci tested and that the 2 isolates are both the VGIIa Vancouver Island major genotype. Findings are consistent with expansion of the Vancouver Island outbreak onto the mainland Pacific Northwest region of the United States.

Comparison of medical and/or surgical management of 23 cats with intracranial empyema or abscessation.

OBJECTIVES: Feline intracranial abscessation or empyema is infrequently reported in the veterinary literature. To date, the largest study is based on a population of 19 cats with otogenic infection. The aim of this study was to review a larger population of cats with intracranial empyema from multiple aetiologies and document their signalment, imaging findings, treatment protocols (including medical and/or surgical management) and to compare outcomes. METHODS: Cases presenting to a single referral centre over a 10 year period with compatible history, neurological signs and imaging findings consistent with intracranial abscessation and empyema were reviewed retrospectively. RESULTS: Twenty-three cats met the inclusion criteria. Advanced imaging (CT and/or MRI) was performed in 22/23 cats; one case was diagnosed via ultrasound. Ten cases underwent medical and surgical management combined, 10 underwent solely medical management and three were euthanased at the time of diagnosis. Short-term outcome showed that 90% of surgically managed and 80% of medically managed cats were alive at 48 h post-diagnosis. Long-term survival showed that surgically managed cases and medically managed cases had a median survival time of 730 days (range 1-3802 days) and 183 days (range 1-1216 days), respectively. No statistical significance in short- or long-term survival ( P >0.05) was found between medically and surgically managed groups. CONCLUSIONS AND RELEVANCE: Feline intracranial abscessation and empyema are uncommon conditions that have historically been treated with combined surgical and medical management. This study documents that, in some cases, intracranial abscessation and empyema can also be successfully treated with medical management alone.

Clinicopathologic and diagnostic imaging characteristics of systemic aspergillosis in 30 dogs.

BACKGROUND: Systemic aspergillosis is a serious disease of dogs for which the clinical characteristics are poorly described. OBJECTIVE: To describe the clinical and diagnostic imaging characteristics of dogs with systemic aspergillosis. ANIMALS: Thirty dogs with systemic aspergillosis. METHODS: Retrospective case review. Medical records were reviewed for signalment, clinical features, and results of clinicopathologic testing and diagnostic imaging. Diagnosis was confirmed by culture of Aspergillus terreus (n = 13), Aspergillus deflectus (n = 11), or other Aspergillus spp. (n = 6). RESULTS: Compared with the background hospital population, German Shepherd dogs and female dogs were overrepresented (odds ratio [OR] 43, 95% confidence interval [CI] 20-91, P < .0001, and OR 2.9, 95% CI 1.2-6.7, P= .02), respectively, with 20 of the 30 dogs being German Shepherd dogs and 77% (23 of 30) of the dogs being female. The median age was 4.5 years (range 2-8 years). Anemia, leukocytosis, hyperglobulinemia, azotemia, hypercalcemia, and hypoalbuminemia were present in 8, 21, 12, 9, 8, and 6 dogs, respectively. Diskospondylitis, osteomyelitis and thoracic lymphadenomegaly were present in 16, 10, and 5 dogs, respectively. Sonographic findings were enlarged hypoechoic lymph nodes (n = 12), mottled and irregular kidneys with or without masses (n = 12), pyelectasia, and an aggregate of echogenic material in the renal pelvis (n = 9). Thirteen dogs were treated with antifungal drugs, with survival times ranging from 0 to 25 months after diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic aspergillosis typically involves young to middle-age female German Shepherd dogs, and there are characteristic abdominal ultrasound findings with the disease process. Infection with A. deflectus was as common as A. terreus, and in rare cases, long-term survival was associated with antifungal therapy.

4-hydroxy-2-nonenal as a marker of the oxidative stress in brains of dogs with canine distemper / 4-hidroxi-2-nonenal como marcador de estresse oxidativo no cérebro de cães com cinomose

Canine Distemper is a disease caused by Canine morbillivirus (CM), a pantropic virus that can affect the central nervous system (CNS), causing demyelination. However, the pathogenesis of this lesion remains to be clarified. Brain samples of 14 naturally infected dogs by CM were analyzed to evaluate the presence of oxidative stress and demyelination. RT-PCR assay was performed to confirm a diagnosis of canine distemper in the brain, immunohistochemistry anti-CM was used to localize the viral proteins in the tissue, and anti-4-hydroxy-2-nonenal (4-HNE) was a marker of a product of lipid peroxidation. The results showed the presence of viral proteins in the demyelinated area with the presence of 4-HNE. Our results suggest that the CM virus infection causes oxidative stress leading to lipid peroxidation, which causes tissue damage and demyelination. In conclusion, oxidative stress plays a significant role in canine distemper pathogenesis in the CNS.(AU)

A cinomose canina é uma doença causada pelo Morbilivírus canino (CM), um vírus pantrópico que pode afetar o sistema nervoso central (SNC), causando desmielinização. No entanto, a patogênese dessa lesão não está totalmente esclarecida. RT-PCR e imuno-histoquímica foram realizadas para confirmação do diagnóstico de cinomose em amostras de encéfalo de 14 cães naturalmente infectados. Após confirmação, foi realizada uma avaliação do estresse oxidativo por imuno-histoquímica com uso de anti-4-hidroxi-nonenal (4HNE) como marcador de produtos resultantes da peroxidação lipídica. Os resultados sugerem que a infecção pelo CM causa estresse oxidativo no tecido, levando a peroxidação lipídica, a qual causa danos ao tecido, culminando com desmielinização. Conclui-se que o estresse oxidativo tem papel importante na patogênese da cinomose canina no sistema nervoso central.(AU)

Parelaphostrongylus tenuis Cerebrospinal Nematodiasis in a Horse with Cervical Scoliosis and Meningomyelitis.

There are reports of horses with acute onset acquired cervical scoliosis and cutaneous analgesia. The underlying dorsal gray column myelitis that produces these neurologic signs has been only presumptively attributed to migration of Parelaphostrongylus tenuis within the spinal cord. Despite previous confirmation brain by polymerase chain reaction testing, of P. tenuis within the brain of horses by polymerase chain reaction testing, genetic testing has failed to definitively identify the presence of this parasite in cases of equine myelitis. This case report provides molecular confirmation via polymerase chain reaction of P. tenuis within the cervical spinal cord of a horse with scoliosis and cutaneous analgesia.

Glial response in the central nervous system of cats with feline infectious peritonitis.

OBJECTIVES: The aim of the study was to evaluate central nervous system (CNS) lesions in non-effusive and effusive cases of feline infectious peritonitis (FIP) regarding aspects related to astrocytic and microglial reactions. METHODS: Five necropsied cats that were naturally infected with FIP virus, confirmed by reverse transcriptase polymerase chain reaction and immunohistochemistry, with different intensities of CNS lesions, were studied. Brain and cerebellum were evaluated by light microscopy and immunohistochemistry for glial fibrillary acidic protein (GFAP) and vimentin to assess astrocytic morphology, and lectin histochemistry for Ricinus communis agglutinin-I (RCA-I) to detect microglia was performed to evaluate the glial response in the CNS of cats with FIP. RESULTS: An important astrocytic response in many areas of the CNS of all cats, including the periventricular areas of lateral ventricles and fourth ventricle, the molecular layer of the cerebellum and cerebral cortex, was visualized. This astrocytic reactivity was associated with areas of granulomatous or pyogranulomatous vasculitis/perivasculitis in most cases, and it was characterized by multifocal to coalescing astrocytosis and astrogliosis with an increase in the expression of intermediate filaments, such as GFAP. However, astrocytes exhibited strong vimentin expression in neuroparenchyma with severe inflammatory and necrotic changes, but GFAP expression was mild or absent in these cases. A microglial response was present only in severe lesions, and RCA-I expression was detected primarily in gitter cells and resting microglia. CONCLUSIONS AND RELEVANCE: The present study indicates a strong astrocytic response, including the presence of many less differentiated vimentin-positive astrocytes and gitter cells positive for RCA-1 in severe lesions in the CNS of cats with FIP.

Development of a sensitive and quantitative diagnostic assay for fish nervous necrosis virus based on two-target real-time PCR.

The aim of the present work was to develop two new independent SYBR Green I-based real-time PCR assays for both detection and quantification of betanodavirus, an RNA virus that infects several species of marine teleost fish causing massive mortalities in larvae and juveniles. The assays utilized two pairs of primers targeting highly conserved regions of both the RNA molecules forming the betanodavirus genome: RNA1 encoding the RNA-dependent RNA polymerase (RdRP) and RNA2 encoding the coat protein (CP). The specificity of amplifications was monitored by the melting analysis and agarose gel electrophoresis of the amplified products. The applicability of these assays was confirmed with 21 betanodavirus strains, covering all the four main clades. In addition, a BLAST (NCBI) search with the primer sequences showed no genomic cross-reactivity with other viruses. The new assays were able to quantify concentrations of betanodavirus genes ranging from 10(1) to 10(8) copies per reaction. The intra-assay coefficients of variation (CV) of threshold cycle (Ct) values of the assays were 1.5% and 1.4% for CP and RdRP RNAs, respectively. The inter-assay CVs of Ct values were 2.3% and 2.4% for CP and RdRP RNAs, respectively. Moreover, regression analysis showed a significant correlation (R2>0.97) between genome number, as determined by real-time PCR assays and the corresponding virus titer expressed as TCID50/ml of two different betanodavirus strains propagated in cell culture. The two assays were compared with a previously established one-step RT-PCR assay and with the classical virus isolation test and found to be more sensitive. In conclusion, the developed real-time RT-PCR assays are a reliable, specific and sensitive tool for the quantitative diagnosis of betanodavirus.

Canine neural angiostrongylosis: a case-control study in Sydney dogs.

OBJECTIVE: To determine the risk factors for canine neural angiostrongylosis in dogs domiciled in Sydney, Australia; geographic location, age, sex, neuter status, weight and breed were assessed. PROCEDURE: Case and matched-control dogs were selected from three veterinary clinics in Sydney. Conditional logistic regression was used to identify factors associated with disease status. A scan statistic was used to identify disease clusters. RESULTS: Age (young dogs) and neuter status (entire dogs) were independent risk factors for neural angiostrongylosis diagnosis, and diagnoses predominantly occurred during autumn, with some evidence of spatial clustering. CONCLUSIONS: Veterinarians in endemic areas should be aware of these risk factors when presented with suspect canine neural angiostrongylosis cases and also should consider advising clients of preventive treatment. Potential human health risks should be further investigated, because urban dog populations might represent a useful sentinel species for disease in humans.

Central nervous system mucormycosis caused by Cunninghamella bertholletiae in a bottlenose dolphin (Tursiops truncatus).

In May 2012, an adult, male bottlenose dolphin (Tursiops truncatus) was found stranded and dead on the Spanish Mediterranean coast. At necropsy, several areas of malacia were macroscopically observed in the periventricular parenchyma of the cerebrum. Microscopically a severe, diffuse, pyogranulomatous, and necrotizing meningoencephalomyelitis was associated with numerous intralesional highly pleomorphic fungal structures. After culture, the fungus, Cunninghamella bertholletiae, was identified by culture and PCR. To our knowledge, this is the first reported case of central nervous system mucormycosis due to Cunninghamella bertholletiae in a cetacean.

Biomarkers for neural injury and infection in small animals.

Cross-sectional imaging techniques have facilitated diagnosis of central nervous system (CNS) diseases. However, there is still frequently a lack of definition of the cause of neurologic lesions, because tissue sampling from the pathologic site is often difficult and there are few clinical diagnostic tools to assist diagnosis. Biomarkers can assist in understanding the cause, diagnosis, severity, and prognosis for neural injury. Integration of conventional testing and new diagnostic techniques will overcome shortcomings in understanding infectious diseases of the CNS. Diagnostic tests may be limited by poor positive and negative predictive values, which must be recognized when interpreting test results.

Genetic analysis of vibriosis and viral nervous necrosis resistance in Atlantic cod (Gadus morhua L.) using a cure model.

The aim of this study was to investigate whether observed time-until-death of Atlantic cod (Gadus morhua L.) juveniles in separate challenge tests with Vibrio anguillarum (causes vibriosis) and nodavirus [causes viral nervous necrosis (VNN)] are due to differences in susceptibility (whether at risk or not) or increased endurance (individual hazard, given that the animal is susceptible) using a cure mixture (CURE) model with Gibbs sampling. Observed time-until-death, prepared as sequential binary records, were analyzed with the CURE model and results were compared with cross-sectional threshold (SIMPLE) and an ordinary longitudinal survival score (NAÏVE) model (i.e., assuming that all animals are susceptible). Overall mortality at the end of the test was 86 and 71% for vibriosis and VNN, respectively. But the CURE model estimated 92 and 82% of the population to be susceptible to vibriosis and VNN, respectively. Hence, a substantial fraction among the survivors were considered to be susceptible but with high endurance. The underlying heritability of susceptibility was moderate for vibriosis (0.33) and extremely high for VNN (0.91), somewhat greater compared with classical SIMPLE model (0.19 and 0.76 for vibriosis and VNN, respectively), analyzing end survival as a cross-sectional binary trait. Estimates of the underlying heritability were low for single test-day scores of both endurance (0.02 and 0.15 for vibriosis and VNN, respectively) in the CURE model and for the NAÏVE model (0.02 and 0.18 for vibriosis and VNN, respectively). Based on the CURE model, the genetic correlation between susceptibility and endurance was low to moderately positive and significantly different from unity (P < 0.01) for both vibriosis (0.13) and VNN (0.47). Estimated breeding values from the SIMPLE and NAÏVE models showed moderate to high correlations (0.41 to 0.96) with EBV for susceptibility and endurance in the CURE model. The analyses indicate that susceptibility and endurance are apparently distinct genetic traits. Still, the genetic variation estimated in the SIMPLE and NAÏVE models seems to a large extent to be controlled by susceptibility and an efficient genetic selection for reduced susceptibility to vibriosis and VNN is therefore likely feasible even when using classical (noncure) models. Earlier termination of the challenge test or back truncation of survival data is not recommended as this likely shifts the focus of selection towards endurance rather than susceptibility.